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Desogestrel is used to provide contraceptive efficacy in women who want to prevent pregnancy. Desogestrel has proved to be highly efficacious as a contraceptive pill and is an alternative for women who have a weak tolerance levels for the estrogen hormones or who are lactating or breast feeding.

Oral Contraceptive preparations

One tablet at the same time each day, taken continuously without a break. Tablets should be taken within 3 hours of the same time each day.

When and how to take the tablets: Each strip of Desogestrel contains 28 tablets. Arrows are printed on the front side of the strip, between the tablets. If you turn the strip over, next to each tablet is printed the day of the week each tablet should be taken. Take your tablet at about the same time each day. Swallow each tablet whole with water. Each time you start a new strip of Desogestrel; take a tablet in the top row. For example if you start on Wednesday, you should take the tablet from the top row marked that particular day. You should continue to take one tablet a day until the strip is empty, always follow the direction indicated by the arrows. In this way you can easily check whether you have taken your daily tablet. You may have some bleeding during the use of Desogestrel but you must continue to take your tablets as normal. When a strip is empty, you must start with a new pack of Desogestrel on the next day without interruption and without waiting for a bleed. You can stop taking Desogestrel whenever you want. From the day you stop, you are no longer protected against pregnancy.

Starting first pack of Desogestrel: If you are not using hormonal contraception at present (or in the past month) wait for your period to begin. On the first day of your period take the first Desogestrel tablet. If you take your first tablet on days 2 to 5 of your period use an additional barrier method of contraception for the first 7 days of tablet taking.

When change from a combined pill: Start Desogestrel on the day after the last active tablet of the combined pill; in this case additional contraceptive precautions are not necessary.

When change from a mini-pill, injection, implant or hormonal IUD: Switch on any day from another mini pill. Start Desogestrel the day an implant or IUD is removed or the day your next injection would be due, additional contraceptive precau-tions are not necessary.

If you have a baby or abortion: Start immediately after first trimester abortion, additional contraceptive precautions are not necessary. After delivery or second trimester abortion, start before periods return. If more then 21 days have elapsed, pregnancy must be ruled out and an additional barrier method of contraception should be used for the first 7 days.

If you forget to take one or more tablets

• If you are more than 12 hours late: Take a tablet as soon as you remember and take the next one at the usual time. This may mean taking two tablets in one day. This is not harmful. (If you have forgotten more than one tablet you don't need to take the earlier missed ones). You are not protected against pregnancy. Continue to take your tablets as usual but you must also use an extra method, such as a condom, for the next seven days. If you are more than 12 hours late taking your tablet and have had sex it is safe to use emergency contraception.
• If you are less than 12 hours late: Take the tablet as soon as you remember, and take the next tablet at the usual time. The contraceptive action of Desogestrel is maintained. If you missed one or more tablets in the first week of tablet intake and had intercourse in the week before missing the tablets, there is a possibility of becoming pregnant. The more consecutive tablets you have missed, the higher the risk that the contraceptive efficacy is decreased.

If you vomit or use medical charcoal: If you vomit or use medical charcoal within 3 - 4 hours after taking your Desogestrel tablet, the active ingredient may not have been completely absorbed. Follow the advice for missed tablets.

Common: irregular bleeding, amenorrhoea, headache, weight gain, breast pain, nausea, acne, mood changes, decreased libido. Less common: Vaginitis, dysmenorrhoea, ovarian cysts, vomiting, alopecia, fatigue, difficulty wearing contact lenses. Rare: Rash, urticaria, erythema nodosum.

Known or suspected pregnancy, active venous thromboembolic disorder, presence or history of severe hepatic disease with current abnormal liver function tests, progestogen dependent tumors, undiagnosed vaginal bleeding, hypersensitivity to ingredients.

Epidemiological studies have associated the use of combined OCs with an increased incidence of venous thromboembolism (VTE, deep venous thrombosis and pulmonary embolism). It is unclear whether desogestrel used alone carries the same risk. Discontinue in the event of a thrombosis. Consider stopping prior to long term immobilization due to surgery or illness. Benefit/risk assessment should be made in women with liver cancer. Caution patients with a history of thromboembolic disorders. Patients with diabetes should be carefully monitored. Effects on bone density are unknown.

Enzyme-inducing drugs may result in increased clearance and lead to breakthrough bleeding and contraceptive failure. This may be seen with hydantoins, barbiturates, primidone, carbamazepine, rifampicin, oxcarbazepine, rifabutin, felbamate, ritonavir, griseofulvin and products containing St John's Wort. Reduced absorption of etonogestrel may be seen with medical charcoal.

Not recommended for use during pregnancy. Desogestrel does not affect the production or quality of breast milk. Small amounts of the metabolite etonogestrel are excreted with the milk. Long term follow-up data are not available, however 7 month data do not indicate a risk to the nursing infant

No serious deleterious effects have been reported from an overdose. Other symptoms may include nausea, vomiting and in young girls, slight vaginal bleeding. Treatment should be symptomatic.

Store at room temperature (below 30°C). Do not use it after the expiry date stated on the package.

Proton Pump Inhibitor

Omeprazole, a substituted benzimidazole, is an inhibitor of gastric acid secretion. It inhibits gastric acid secretion by blocking hydrogen-potassium-adenosine triphosphatase (H⁺/K⁺ ATPase) enzyme system in the gastric parietal cell. After oral administration, the onset of the antisecretory effect occurs within one hour, with the maximum effect occurring within two hours and inhibition of secretion lasts up to 72 hours. When the drug is discontinued, secretory activity returns gradually, over 3 to 5 days.

Oral-

• Benign gastric and duodenal ulcer: 20 mg once daily for 4 weeks in duodenal ulceration, 8 weeks in gastric ulceration; in severe or recurrent cases, dose to be increased to 40 mg daily; maintenance dose for recurrent duodenal ulcer, 20 mg once daily; in prevention of relapse in duodenal ulcer, 10-20 mg daily.
• NSAID-associated duodenal or gastric ulcer: 20 mg once daily for 4 weeks, continued for further 4 weeks, if not fully healed. 20 mg once daily is used as prophylaxis in patients with a history of NSAID-associated duodenal or gastric ulcers.
• Gastro-esophageal reflux disease: 20 mg once daily for 4 weeks, continued for further 4-8 weeks, if not fully healed; 40 mg once daily has been given for 8 weeks in gastro-esophageal reflux disease, refractory to other treatment; maintenance dose is 20 mg once daily.
• Long-term management of acid reflux disease: 10-20 mg daily.
• Acid-related dyspepsia: 10-20 mg once daily for 2-4 weeks.
• Prophylaxis of acid aspiration: 40 mg on the preceding evening, then 40 mg 2-6 hours before surgery.
• Zollinger-Ellison syndrome: Initially 60 mg once daily; usual range 20-120 mg daily (If daily dose is more than 80 mg, 2 divided dose should be used).
• Helicobacter pylori eradication regimen in peptic ulcer disease: Omeprazole is recommended at a dose of 20 mg twice daily in association with antimicrobial agents as detailed below: Amoxicillin 500 mg and Metronidazole 400 mg both three times a day for one week, or Clarithromycin 250 mg and Metronidazole 400 mg both twice a day for one week, or Amoxicillin 1 g and Clarithromycin 500 mg both twice a day for one week.
• Paeditaric use in severe ulcerating reflux esophagitis (Child>1 year): If body-weight 10-20 kg, 10-20 -mg once daily for 4-12 weeks; if body-weight over 20 kg, 20-40 mg once daily for 4-12 weeks.

IV Injection-

• Prophylaxis of acid aspiration: Omeprazole 40 mg to be given slowly (over a period of 5 minutes) as an intravenous injection, one hour before surgery.
• Duodenal ulcer, gastric ulcer or reflux oesophagitis: In patients with duodenal ulcer, gastric ulcer or reflux oesophagitis where oral medication is inappropriate, Omeprazole IV 40 mg once daily is recommended.
• Zollinger- Ellison syndrome (ZES): In patients with Zollinger-Ellison Syndrome the recommended initial dose of Omeprazole given intravenously is 60 mg daily. Higher daily doses may be required and the dose should be adjusted individually. When doses exceed 60 mg daily, the dose should be divided & given twice daily.

Direction for use of IV Injection: Omeprazole lyophilized powder and water for injection is for intravenous administration only and must not be given by any other route. Omeprazole IV injection should be given as a slow intravenous injection. The solution for IV injection is obtained by adding 10 ml water for injection to the vial containing powder. After reconstitution the injection should be given slowly over a period of at least 2 to 5 minutes at a maximum rate of 4 ml/minute. Use only freshly prepared solution. The solution should be used within 4 hours of reconstitution.

Direction for use of IV Infusion: Omeprazole IV infusion should be given as an intravenous infusion over a period of 20-30 minutes or more. The contents of one vial must be dissolved in 100 ml saline for infusion or 100 ml 5% Dextrose for infusion. The solution should be used within 12 hours when Omeprazole is dissolved in saline and within 6 hours when dissolved in 5% Dextrose. The reconstituted solution should not be mixed or co-administered in the same infusion set with any other drug.

Omeprazole is generally well tolerated. Nausea, abdominal colic, paresthesia, dizziness and headache have been stated to be generally mild and transient and not requiring a reduction in dosage.

Omeprazole is contraindicated in patients with known hypersensitivity to any of the components of the formulation.

When gastric ulcer is suspected, the possibility of gastric malignancy should be excluded before treatment with Omeprazole is instituted, as treatment may alleviate the symptoms and delay diagnosis.

Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin. So, reduction of warfarin or phenytoin dose may be necessary when Omeprazole is added to the treatment. There is no evidence of an interaction of Omeprazole with theophylline, propranolol or antacids.

US FDA pregnancy category of Omeprazole is C. However, results from three prospective epidemiological studies indicate no adverse effects of Omeprazole on pregnancy or on the health of the fetus/newborn child. There is no information available on the passage of Omeprazole into breast milk or its effects on the neonate. Breast-feeding should, therefore, be discontinued, if the use of Omeprazole is considered essential.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Proton Pump Inhibitor

Omeprazole, a substituted benzimidazole, is an inhibitor of gastric acid secretion. It inhibits gastric acid secretion by blocking hydrogen-potassium-adenosine triphosphatase (H⁺/K⁺ ATPase) enzyme system in the gastric parietal cell. After oral administration, the onset of the antisecretory effect occurs within one hour, with the maximum effect occurring within two hours and inhibition of secretion lasts up to 72 hours. When the drug is discontinued, secretory activity returns gradually, over 3 to 5 days.

Oral-

• Benign gastric and duodenal ulcer: 20 mg once daily for 4 weeks in duodenal ulceration, 8 weeks in gastric ulceration; in severe or recurrent cases, dose to be increased to 40 mg daily; maintenance dose for recurrent duodenal ulcer, 20 mg once daily; in prevention of relapse in duodenal ulcer, 10-20 mg daily.
• NSAID-associated duodenal or gastric ulcer: 20 mg once daily for 4 weeks, continued for further 4 weeks, if not fully healed. 20 mg once daily is used as prophylaxis in patients with a history of NSAID-associated duodenal or gastric ulcers.
• Gastro-esophageal reflux disease: 20 mg once daily for 4 weeks, continued for further 4-8 weeks, if not fully healed; 40 mg once daily has been given for 8 weeks in gastro-esophageal reflux disease, refractory to other treatment; maintenance dose is 20 mg once daily.
• Long-term management of acid reflux disease: 10-20 mg daily.
• Acid-related dyspepsia: 10-20 mg once daily for 2-4 weeks.
• Prophylaxis of acid aspiration: 40 mg on the preceding evening, then 40 mg 2-6 hours before surgery.
• Zollinger-Ellison syndrome: Initially 60 mg once daily; usual range 20-120 mg daily (If daily dose is more than 80 mg, 2 divided dose should be used).
• Helicobacter pylori eradication regimen in peptic ulcer disease: Omeprazole is recommended at a dose of 20 mg twice daily in association with antimicrobial agents as detailed below: Amoxicillin 500 mg and Metronidazole 400 mg both three times a day for one week, or Clarithromycin 250 mg and Metronidazole 400 mg both twice a day for one week, or Amoxicillin 1 g and Clarithromycin 500 mg both twice a day for one week.
• Paeditaric use in severe ulcerating reflux esophagitis (Child>1 year): If body-weight 10-20 kg, 10-20 -mg once daily for 4-12 weeks; if body-weight over 20 kg, 20-40 mg once daily for 4-12 weeks.

IV Injection-

• Prophylaxis of acid aspiration: Omeprazole 40 mg to be given slowly (over a period of 5 minutes) as an intravenous injection, one hour before surgery.
• Duodenal ulcer, gastric ulcer or reflux oesophagitis: In patients with duodenal ulcer, gastric ulcer or reflux oesophagitis where oral medication is inappropriate, Omeprazole IV 40 mg once daily is recommended.
• Zollinger- Ellison syndrome (ZES): In patients with Zollinger-Ellison Syndrome the recommended initial dose of Omeprazole given intravenously is 60 mg daily. Higher daily doses may be required and the dose should be adjusted individually. When doses exceed 60 mg daily, the dose should be divided & given twice daily.

Direction for use of IV Injection: Omeprazole lyophilized powder and water for injection is for intravenous administration only and must not be given by any other route. Omeprazole IV injection should be given as a slow intravenous injection. The solution for IV injection is obtained by adding 10 ml water for injection to the vial containing powder. After reconstitution the injection should be given slowly over a period of at least 2 to 5 minutes at a maximum rate of 4 ml/minute. Use only freshly prepared solution. The solution should be used within 4 hours of reconstitution.

Direction for use of IV Infusion: Omeprazole IV infusion should be given as an intravenous infusion over a period of 20-30 minutes or more. The contents of one vial must be dissolved in 100 ml saline for infusion or 100 ml 5% Dextrose for infusion. The solution should be used within 12 hours when Omeprazole is dissolved in saline and within 6 hours when dissolved in 5% Dextrose. The reconstituted solution should not be mixed or co-administered in the same infusion set with any other drug.

Omeprazole is generally well tolerated. Nausea, abdominal colic, paresthesia, dizziness and headache have been stated to be generally mild and transient and not requiring a reduction in dosage.

Omeprazole is contraindicated in patients with known hypersensitivity to any of the components of the formulation.

When gastric ulcer is suspected, the possibility of gastric malignancy should be excluded before treatment with Omeprazole is instituted, as treatment may alleviate the symptoms and delay diagnosis.

Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin. So, reduction of warfarin or phenytoin dose may be necessary when Omeprazole is added to the treatment. There is no evidence of an interaction of Omeprazole with theophylline, propranolol or antacids.

US FDA pregnancy category of Omeprazole is C. However, results from three prospective epidemiological studies indicate no adverse effects of Omeprazole on pregnancy or on the health of the fetus/newborn child. There is no information available on the passage of Omeprazole into breast milk or its effects on the neonate. Breast-feeding should, therefore, be discontinued, if the use of Omeprazole is considered essential.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Proton Pump Inhibitor

Omeprazole, a substituted benzimidazole, is an inhibitor of gastric acid secretion. It inhibits gastric acid secretion by blocking hydrogen-potassium-adenosine triphosphatase (H⁺/K⁺ ATPase) enzyme system in the gastric parietal cell. After oral administration, the onset of the antisecretory effect occurs within one hour, with the maximum effect occurring within two hours and inhibition of secretion lasts up to 72 hours. When the drug is discontinued, secretory activity returns gradually, over 3 to 5 days.

Oral-

• Benign gastric and duodenal ulcer: 20 mg once daily for 4 weeks in duodenal ulceration, 8 weeks in gastric ulceration; in severe or recurrent cases, dose to be increased to 40 mg daily; maintenance dose for recurrent duodenal ulcer, 20 mg once daily; in prevention of relapse in duodenal ulcer, 10-20 mg daily.
• NSAID-associated duodenal or gastric ulcer: 20 mg once daily for 4 weeks, continued for further 4 weeks, if not fully healed. 20 mg once daily is used as prophylaxis in patients with a history of NSAID-associated duodenal or gastric ulcers.
• Gastro-esophageal reflux disease: 20 mg once daily for 4 weeks, continued for further 4-8 weeks, if not fully healed; 40 mg once daily has been given for 8 weeks in gastro-esophageal reflux disease, refractory to other treatment; maintenance dose is 20 mg once daily.
• Long-term management of acid reflux disease: 10-20 mg daily.
• Acid-related dyspepsia: 10-20 mg once daily for 2-4 weeks.
• Prophylaxis of acid aspiration: 40 mg on the preceding evening, then 40 mg 2-6 hours before surgery.
• Zollinger-Ellison syndrome: Initially 60 mg once daily; usual range 20-120 mg daily (If daily dose is more than 80 mg, 2 divided dose should be used).
• Helicobacter pylori eradication regimen in peptic ulcer disease: Omeprazole is recommended at a dose of 20 mg twice daily in association with antimicrobial agents as detailed below: Amoxicillin 500 mg and Metronidazole 400 mg both three times a day for one week, or Clarithromycin 250 mg and Metronidazole 400 mg both twice a day for one week, or Amoxicillin 1 g and Clarithromycin 500 mg both twice a day for one week.
• Paeditaric use in severe ulcerating reflux esophagitis (Child>1 year): If body-weight 10-20 kg, 10-20 -mg once daily for 4-12 weeks; if body-weight over 20 kg, 20-40 mg once daily for 4-12 weeks.

IV Injection-

• Prophylaxis of acid aspiration: Omeprazole 40 mg to be given slowly (over a period of 5 minutes) as an intravenous injection, one hour before surgery.
• Duodenal ulcer, gastric ulcer or reflux oesophagitis: In patients with duodenal ulcer, gastric ulcer or reflux oesophagitis where oral medication is inappropriate, Omeprazole IV 40 mg once daily is recommended.
• Zollinger- Ellison syndrome (ZES): In patients with Zollinger-Ellison Syndrome the recommended initial dose of Omeprazole given intravenously is 60 mg daily. Higher daily doses may be required and the dose should be adjusted individually. When doses exceed 60 mg daily, the dose should be divided & given twice daily.

Direction for use of IV Injection: Omeprazole lyophilized powder and water for injection is for intravenous administration only and must not be given by any other route. Omeprazole IV injection should be given as a slow intravenous injection. The solution for IV injection is obtained by adding 10 ml water for injection to the vial containing powder. After reconstitution the injection should be given slowly over a period of at least 2 to 5 minutes at a maximum rate of 4 ml/minute. Use only freshly prepared solution. The solution should be used within 4 hours of reconstitution.

Direction for use of IV Infusion: Omeprazole IV infusion should be given as an intravenous infusion over a period of 20-30 minutes or more. The contents of one vial must be dissolved in 100 ml saline for infusion or 100 ml 5% Dextrose for infusion. The solution should be used within 12 hours when Omeprazole is dissolved in saline and within 6 hours when dissolved in 5% Dextrose. The reconstituted solution should not be mixed or co-administered in the same infusion set with any other drug.

Omeprazole is generally well tolerated. Nausea, abdominal colic, paresthesia, dizziness and headache have been stated to be generally mild and transient and not requiring a reduction in dosage.

Omeprazole is contraindicated in patients with known hypersensitivity to any of the components of the formulation.

When gastric ulcer is suspected, the possibility of gastric malignancy should be excluded before treatment with Omeprazole is instituted, as treatment may alleviate the symptoms and delay diagnosis.

Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin. So, reduction of warfarin or phenytoin dose may be necessary when Omeprazole is added to the treatment. There is no evidence of an interaction of Omeprazole with theophylline, propranolol or antacids.

US FDA pregnancy category of Omeprazole is C. However, results from three prospective epidemiological studies indicate no adverse effects of Omeprazole on pregnancy or on the health of the fetus/newborn child. There is no information available on the passage of Omeprazole into breast milk or its effects on the neonate. Breast-feeding should, therefore, be discontinued, if the use of Omeprazole is considered essential.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Propylthiouracil is indicated:

• in patients with Graves' disease with hyperthyroidism or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment option
• to ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy in patients who are intolerant of methimazole

Thyroid drugs & hormone

Propylthiouracil inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. The drug does not inactivate existing thyroxine and triiodothyronine that are stored in the thyroid or circulating in the blood, nor does it interfere with the effectiveness of thyroid hormones given by mouth or by injection. Propylthiouracil inhibits the conversion of thyroxine to triiodothyronine in peripheral tissues and may therefore be an effective treatment for thyroid storm. Propylthiouracil is readily absorbed and is extensively metabolized. Approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours.

Adults: The initial dose is 300 mg daily. In patients with severe hyperthyroidism, very large goiters, or both, the initial dose may be increased to 400 mg daily; an occasional patient will require 600 to 900 mg daily initially. The usual maintenance dose is 100 to 150 mg daily.

Pediatric Patients: Propylthiouracil is generally not recommended for use in the pediatric patient population except in rare instances in which other alternative therapies are not appropriate options. Studies evaluating appropriate dosing regimen have not been conducted in the pediatric population although general practice would suggest initiation of therapy in patients 6 years or older at a dosage of 50 mg daily with careful upward titration based on clinical response and evaluation of TSH and free T4 levels. Although cases of severe liver injury have been reported with doses as low as 50 mg/day, most cases were associated with doses of 300 mg/day and higher.

The most common side effects of Propylthiouracil include:

• nausea
• muscle pain
• vomiting
• headache
• upper stomach pain or tenderness
• sleepiness
• joint pain
• nerve pain
• itching or tingling
• swelling (edema)
• loss or change in taste
• dizziness
• loss of hair
• enlarged salivary glands or enlarged lymph node

Propylthiouracil is contraindicated in patients who have demonstrated hypersensitivity to the drug or any of the other product components.

Patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, light colored stools, dark urine, right upper quadrant pain, etc.), particularly in the first six months of therapy. When these symptoms occur, measurement should be made of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT/AST levels). Patients who receive propylthiouracil should be under close surveillance and should be counseled regarding the necessity of immediately reporting any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. In such cases, white blood cell and differential counts should be obtained to determine whether agranulocytosis has developed. Particular care should be exercised with patients who are receiving concomitant drugs known to be associated with agranulocytosis.

Anticoagulants (oral): Due to the potential inhibition of vitamin K activity by propylthiouracil, the activity of oral anticoagulants (e.g., warfarin) may be increased; additional monitoring of PT/INR should be considered, especially before surgical procedures.

Beta-adrenergic blocking agents: Hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. A reduced dose of beta-adrenergic blockers may be needed when a hyperthyroid patient becomes euthyroid.

Digitalis glycosides: Serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; a reduced dose of digitalis glycosides may be needed.

Theophylline: Theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.

Pregnancy Category D. There are cases of liver injury, including liver failure and death, in women treated with propylthiouracil during pregnancy. Two reports of in utero exposure with liver failure and death of a newborn have been reported. If propylthiouracil is used during pregnancy, or if the patient becomes pregnant while taking propylthiouracil, the patient should be warned of the rare potential hazard to the mother and fetus of liver damage. Propylthiouracil crosses the placenta and can cause fetal goiter and cretinism when administered to a pregnant woman. After the first trimester of pregnancy, the use of an alternative antithyroid medication may be advisable.

Nursing Mothers: Propylthiouracil is present in breast milk to a small extent and therefore likely results in clinically insignificant doses to the nursing infant. In one study, nine lactating women were administered 400 mg of propylthiouracil by mouth. The mean amount of propylthiouracil excreted during 4 hours after drug administration was 0.025% of the administered dose.

Pediatric Use: Postmarketing reports of severe liver injury including hepatic failure requiring liver transplantation or resulting in death have been reported in the pediatric population. No such reports have been observed with methimazole. As such, propylthiouracil is not recommended for use in the pediatric population except in rare instances in which methimazole is not well-tolerated and surgery or radioactive iodine therapy are not appropriate. When used in children, parents and patients should be informed of the risk of liver failure. If patients taking propylthiouracil develop tiredness, nausea, anorexia, fever, pharyngitis, or malaise, propylthiouracil should be discontinued immediately by the patient, a physician should be contacted, and a white blood cell count, liver function tests, and transaminase levels obtained.

Geriatric Patients: Clinical studies of propylthiouracil did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Symptoms: Nausea, vomiting, epigastric distress, headache, fever, arthralgia, pruritus, edema, and pancytopenia. Agranulocytosis is the most serious effect. Rarely, exfoliative dermatitis, hepatitis, neuropathies or CNS stimulation or depression may occur. No information is available on the following: LD 50 ; concentration of propylthiouracil in biologic fluids associated with toxicity and/or death; the amount of drug in a single dose usually associated with symptoms of overdosage; or the amount of propylthiouracil in a single dose likely to be life-threatening.

Treatment: To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient. In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s medical status.

Store at controlled room temperature 15°-30°C

Paclitaxel is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment.

All patients should be premedicated prior to Paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel.

First-line treatment of ovarian cancer: Although alternative medication regimens for paclitaxel are under investigation at present, a combination therapy of paclitaxel and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for paclitaxel treatment: 175 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.

Second-line treatment of ovarian cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.

Adjuvant chemotherapy in breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.

First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), paclitaxel should be administered 24 hours after doxorubicin. The recommended dose of paclitaxel is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of paclitaxel is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Paclitaxel infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Second-line chemotherapy of breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.

Advanced non-small-cell lung cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.

Treatment of AIDS-related KS: The recommended dose of paclitaxel is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.

Dose adjustment: Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Paclitaxel should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after paclitaxel is given.

Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Paclitaxel should be given before cisplatin when used in combination.

Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving paclitaxel after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately.

Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).

Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.

Paclitaxel clearance is not affected by cimetidine premedication.

Cisplatin: Administration of paclitaxel after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in paclitaxel clearance. Patients treated with paclitaxel and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.

Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when paclitaxel and doxorubicin are given closer in time, paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours).

Active substances metabolized in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).

Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with paclitaxel.

Pediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Preparation for Intravenous Infusion: Paclitaxel Injection must be diluted prior to infusion. Paclitaxel should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/ml. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (below 30°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Pantoprazole is indicated where suppression of acid secretion has therapeutic benefit; i.e 

• Peptic ulcer diseases
• Gastroesophageal reflux diseases
• Ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs)
• Eradication of Helicobacter pylori (in combination with antibiotics)
• Zollinger-Ellison Syndrome

Proton Pump Inhibitor

Pantoprazole is a proton pump inhibitor that suppresses the final step in gastric acid production by covalently binding to the H⁺/K⁺ATPase enzyme system at the surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus that persists longer than 24 hours.

Oral:

• Benign gastric ulcer: 40 mg daily in the morning for 4 weeks, continued for further 4 weeks, if not fully healed.
• Gastro-esophageal reflux disease: 20-40 mg daily in the morning for 4 weeks, continued for further 4 weeks, if not fully healed; maintenance dose is 20 mg daily, which may be increased to 40 mg daily.
• Duodenal ulcer: 40 mg daily in the morning for 2 weeks, continued for further 2 weeks if not fully healed.
• Duodenal ulcer associated with Helicobacter pylori: Pantoprazole is recommended at a dose of 40 mg twice daily in association with antimicrobial agents as detailed below: Amoxycillin 1 g and Clarithromycin 500 mg both twice daily for one week, or Clarithromycin 250 mg and Metronidazole 400 mg both twice daily for one week.
• Prophylaxis of NSAID-associated gastric or duodenal ulcer: 20 mg daily for those require long-term NSAID treatment.
• Zollinger-Ellison Syndrome: Initially 80 mg once daily adjusted according to response (elderly max. 40 mg daily); daily doses above 80 mg given in 2 divided doses.

IV Injection:

• Duodenal ulcer and gastric ulcer: 40 mg once daily for 7-10 days
• Gastroesophageal reflux disease associated with a history of erosive esophagitis: 40 mg once daily for 7-10 days
• Prevention of rebleeding in peptic ulcer: IV 80 mg, followed by 8 mg/hour infusion for 72 hours
• Prophylaxis of acid aspiration: 80 mg IV every 12 h for 24 h, followed by 40mg every 12 hour
• Long-term management of Zollinger-Ellison Syndrome and other pathological hypersecretory conditions: 80 mg IV every 12 hours, may increase to 80 mg every 8 hours if needed, may titrate to higher doses depending on acid output.

Pantoprazole is well tolerated in both short-term and long-term treatment. Headache and diarrhea are the common side effects and rarely included side effects are abdominal pain, flatulence, rash, insomnia and hyperglycemia.

Pantoprazole is contraindicated in patients with known hypersensitivity to any of the components of the formulation.

Patients should be cautioned that Pantoprazole tablet should not be split, chewed or crushed. Long-term therapy of Pantoprazole may lead to malabsorption of cyanocobalamin (Vitamin B12) or may increase the risk of osteoporosis related disorders.

No significant drug interactions have been observed in clinical studies.

US FDA Pregnancy Category of Pantoprazole is B. There are, however, no adequate and well-controlled studies in pregnant woman. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Pantoprazole has been shown to be excreted in human milk. So, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

There are no known symptoms of overdosage in humans. Since Pantoprazole is highly protein bound, it is not readily dialyzable. Apart from symptomatic and supportive management, no specific therapy is recommended.

Direction for use of IV injection: Pantoprazole lyophilized powder and 0.9% Sodium Chloride Injection is for intravenous administration only and must not be given by any other route. Pantoprazole IV injection should be given as a slow intravenous injection. The solution for IV injection is obtained by adding 10 ml 0.9% Sodium Chloride Injection to the vial containing powder. After reconstitution the injection should be given slowly over a period of at least 2 to 5 minutes. Use only freshly prepared solution. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours.

Direction for use of IV infusion: Pantoprazole IV infusion should be given as an intravenous infusion over a period of approximately 15 minutes. Pantoprazole IV infusion should be reconstituted with 10 ml of 0.9% Sodium Chloride Injection and further diluted (admixed) with 0.9% Sodium Chloride Injection or 5% Dextrose or Lactated Ringer's Injection to a final volume of 100 ml. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours prior to further dilution. The admixed solution may be stored at room temperature (up to 30° C) and must be used within 24 hours from the time of initial reconstitution.

Keep in a dry place, away from light and heat. Keep out of the reach of children.

Pantoprazole is indicated where suppression of acid secretion has therapeutic benefit; i.e 

• Peptic ulcer diseases
• Gastroesophageal reflux diseases
• Ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs)
• Eradication of Helicobacter pylori (in combination with antibiotics)
• Zollinger-Ellison Syndrome

Proton Pump Inhibitor

Pantoprazole is a proton pump inhibitor that suppresses the final step in gastric acid production by covalently binding to the H⁺/K⁺ATPase enzyme system at the surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus that persists longer than 24 hours.

Oral:

• Benign gastric ulcer: 40 mg daily in the morning for 4 weeks, continued for further 4 weeks, if not fully healed.
• Gastro-esophageal reflux disease: 20-40 mg daily in the morning for 4 weeks, continued for further 4 weeks, if not fully healed; maintenance dose is 20 mg daily, which may be increased to 40 mg daily.
• Duodenal ulcer: 40 mg daily in the morning for 2 weeks, continued for further 2 weeks if not fully healed.
• Duodenal ulcer associated with Helicobacter pylori: Pantoprazole is recommended at a dose of 40 mg twice daily in association with antimicrobial agents as detailed below: Amoxycillin 1 g and Clarithromycin 500 mg both twice daily for one week, or Clarithromycin 250 mg and Metronidazole 400 mg both twice daily for one week.
• Prophylaxis of NSAID-associated gastric or duodenal ulcer: 20 mg daily for those require long-term NSAID treatment.
• Zollinger-Ellison Syndrome: Initially 80 mg once daily adjusted according to response (elderly max. 40 mg daily); daily doses above 80 mg given in 2 divided doses.

IV Injection:

• Duodenal ulcer and gastric ulcer: 40 mg once daily for 7-10 days
• Gastroesophageal reflux disease associated with a history of erosive esophagitis: 40 mg once daily for 7-10 days
• Prevention of rebleeding in peptic ulcer: IV 80 mg, followed by 8 mg/hour infusion for 72 hours
• Prophylaxis of acid aspiration: 80 mg IV every 12 h for 24 h, followed by 40mg every 12 hour
• Long-term management of Zollinger-Ellison Syndrome and other pathological hypersecretory conditions: 80 mg IV every 12 hours, may increase to 80 mg every 8 hours if needed, may titrate to higher doses depending on acid output.

Pantoprazole is well tolerated in both short-term and long-term treatment. Headache and diarrhea are the common side effects and rarely included side effects are abdominal pain, flatulence, rash, insomnia and hyperglycemia.

Pantoprazole is contraindicated in patients with known hypersensitivity to any of the components of the formulation.

Patients should be cautioned that Pantoprazole tablet should not be split, chewed or crushed. Long-term therapy of Pantoprazole may lead to malabsorption of cyanocobalamin (Vitamin B12) or may increase the risk of osteoporosis related disorders.

No significant drug interactions have been observed in clinical studies.

US FDA Pregnancy Category of Pantoprazole is B. There are, however, no adequate and well-controlled studies in pregnant woman. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Pantoprazole has been shown to be excreted in human milk. So, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

There are no known symptoms of overdosage in humans. Since Pantoprazole is highly protein bound, it is not readily dialyzable. Apart from symptomatic and supportive management, no specific therapy is recommended.

Direction for use of IV injection: Pantoprazole lyophilized powder and 0.9% Sodium Chloride Injection is for intravenous administration only and must not be given by any other route. Pantoprazole IV injection should be given as a slow intravenous injection. The solution for IV injection is obtained by adding 10 ml 0.9% Sodium Chloride Injection to the vial containing powder. After reconstitution the injection should be given slowly over a period of at least 2 to 5 minutes. Use only freshly prepared solution. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours.

Direction for use of IV infusion: Pantoprazole IV infusion should be given as an intravenous infusion over a period of approximately 15 minutes. Pantoprazole IV infusion should be reconstituted with 10 ml of 0.9% Sodium Chloride Injection and further diluted (admixed) with 0.9% Sodium Chloride Injection or 5% Dextrose or Lactated Ringer's Injection to a final volume of 100 ml. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours prior to further dilution. The admixed solution may be stored at room temperature (up to 30° C) and must be used within 24 hours from the time of initial reconstitution.

Keep in a dry place, away from light and heat. Keep out of the reach of children.

The is indicated in the following condition-

• Headache
• Migraine
• Toothache
• Neuralgia
• Feverishness
• Period pain
• Sore throat
• Backache
• Help to reduce the temperature
• Aches and pain of colds and flu

Non opioid analgesics

This is a combination of Paracetamol and Caffeine. Paracetamol has analgesic and antipyretic properties with weak anti-inflammatory activity. Caffeine is an alkaloid which is a theophylline-like xanthine derivative. By intermolecular association with Paracetamol, Caffeine increases the solubility and transmembrane permeation of Paracetamol. In addition, Caffeine increases the pain threshold and tolerance of pain. Caffeine has also an intrinsic power to raise vessel tone in the brain, which provides another benefit to treat migraine and headache.

Adult dose: 1-2 tablets every 4-6 hours. Maximum dose: 8 tablets daily.
Child dose: Not recommended for children below 12 years.

Side effects of paracetamol are usually mild, though haematological reactions including thrombocytopenia, leukopenia, pancytopenia, neutropenia, and agranulocytosis have been reported. Pancreatitis, skin rashes, and other allergic reactions occur occasionally.

Paracetamol is contraindicated in patients with severe renal function impairment and hepatic disease (Viral Hepatitis). Known hypersensitivity to paracetamol or caffeine.

Paracetamol & Caffeine should be given cautiously in the following cases: In patients with hepatic or renal failure, in patients taking other hepatotoxic medication. Prolonged use of the drug without consulting a physician should be avoided.

May reduce serum levels with anticonvulsants (e.g. phenytoin, barbiturates, carbamazepine). May enhance the anticoagulant effect of warfarin and other coumarins with prolonged use. Accelerated absorption with metoclopramide and domperidone. May increase serum levels with probenecid. May increase serum levels of chloramphenicol. May reduce absorption with colestyramine within 1 hr of admin. May cause severe hypothermia with phenothiazine.

Pregnant mothers should consult with doctors before taking Paracetamol & Caffeine. Paracetamol & Caffeine can be taken whilst breast feeding.

Symptoms of Paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 40 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur.

Store in a cool and dry place, protect from light and moisture.Keep all medicines out of the reach of the children.

Potassium channel blockers

Amiodarone Hydrochloride is used to correct abnormal rhythms of the heart. Amiodarone is considered a "broad spectrum" antiarrhythmic medication. The most important electrical effects of the drug includes : a delay in the rate at which the heart’s electrical system "recharges" after the heart contracts (repolarisation); a prolongation in the electrical phase during which the heart’s muscle cells are electrically stimulated (action potential); a slowing of the speed of electrical conduction (how fast each individual impulse is conducted through the heart’s electrical system); a reduction in the rapidity of firing of the normal generator of electrical impulses in the heart (the heart’s pacemaker); and a slowing of conduction through various specialised electrical pathways (called accessory pathways). In addition to being an antiarrhythmic medication, Amiodarone also causes blood vessels to dilate. Because of this effect it also may be of benefit in patients with  congestive heart failure. This effect can result in drop of blood pressure.

Tablet: 200 mg 3 times daily for 1 week reduced to 200 mg twice daily or the minimum required to control arrhythmia. Amiodarone is usually given in several daily doses to minimize stomach upset which is seen more frequently with higher doses. For this same reason, it is also recommended that Amiodarone should be taken with meals.

Injection: The recommended starting dose is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:

• Initial Load: 150 mg per 100 mL (in D5W or Normal Saline) infused over 10 minutes
• Followed by: 1 mg/min for 6 hours
• Followed by: 0.5 mg/min thereafter

In the event of breakthrough episodes of VF or hemodynamically unstable VT: Repeat the Initial Load described above as needed (infused over 10 minutes). Increase the rate of maintenance infusion to achieve effective arrhythmia suppression.

The most severe side effects of Amiodarone therapy are related to the lungs. These reactions can be fatal. Patients should report any symptoms of cough, fever, or painful breathing. Although quite rare, fatal liver toxicity may occur with Amiodarone therapy. Reversible corneal microdeposits (sometimes with night glare), rarely impaired vision due to optic neuritis; peripheral neuropathy and myopathy (usually reversible on withdrawal); bradycardia and conduction disturbances; phototoxicity and rarely persistent skin discolouration; hypothyroidism, hyperthyroidism; raised serum transaminases; jaundice, hepatitis and cirrhosis are reported. Other rare complaints are nausea, vomiting, metallic taste, tremor, sweating, vertigo, headache, sleeplessness, fatigue, alopecia, benign raised intracranial pressure, ataxia, rashes, vasculitis, renal involvement, thrombocytopenia, haemolytic or aplastic anaemia. In some cases, dose of Amiodarone may be reduced. In other cases, Amiodarone therapy may need to be stopped.

Amiodarone is contraindicated in patients with cardiogenic shock; severe sinus-node dysfunction, causing marked sinus bradycardia; second- or third degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker). Amiodarone is contraindicated in patients with a known hypersensitivity to the drug or to any of its components, including iodine.

Amiodarone may interact with b blockers such as Atenolol, Propranolol, Metoprolol, or certain calcium channel blockers, such as Verapamil or Diltiazem, resulting in an excessively slow heart rate. Amiodarone increases the blood levels of Digoxin when the two drugs are given together. Flecainide blood concentrations increase by more than 50% with Amiodarone. Procainamide and Quinidine concentrations increase by 30-50% during the first week of Amiodarone therapy. Amiodarone also can interact with tricyclic antidepressants (TCA). Amiodarone interacts with Warfarin and increases the risk of bleeding. Amiodarone inhibits the metabolism of Dextromethorphan.

In general, Amiodarone should not be administered during pregnancy because there have been reports of hypo or hyperthyroidism in infants from oral Amiodarone use during pregnancy. If Amiodarone use is considered essential, however, the patient should be warned of the risk to the foetus. The safe use of Amiodarone in lactating women has not been established.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Potassium channel blockers

Amiodarone Hydrochloride is used to correct abnormal rhythms of the heart. Amiodarone is considered a "broad spectrum" antiarrhythmic medication. The most important electrical effects of the drug includes : a delay in the rate at which the heart’s electrical system "recharges" after the heart contracts (repolarisation); a prolongation in the electrical phase during which the heart’s muscle cells are electrically stimulated (action potential); a slowing of the speed of electrical conduction (how fast each individual impulse is conducted through the heart’s electrical system); a reduction in the rapidity of firing of the normal generator of electrical impulses in the heart (the heart’s pacemaker); and a slowing of conduction through various specialised electrical pathways (called accessory pathways). In addition to being an antiarrhythmic medication, Amiodarone also causes blood vessels to dilate. Because of this effect it also may be of benefit in patients with  congestive heart failure. This effect can result in drop of blood pressure.

Tablet: 200 mg 3 times daily for 1 week reduced to 200 mg twice daily or the minimum required to control arrhythmia. Amiodarone is usually given in several daily doses to minimize stomach upset which is seen more frequently with higher doses. For this same reason, it is also recommended that Amiodarone should be taken with meals.

Injection: The recommended starting dose is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:

• Initial Load: 150 mg per 100 mL (in D5W or Normal Saline) infused over 10 minutes
• Followed by: 1 mg/min for 6 hours
• Followed by: 0.5 mg/min thereafter

In the event of breakthrough episodes of VF or hemodynamically unstable VT: Repeat the Initial Load described above as needed (infused over 10 minutes). Increase the rate of maintenance infusion to achieve effective arrhythmia suppression.

The most severe side effects of Amiodarone therapy are related to the lungs. These reactions can be fatal. Patients should report any symptoms of cough, fever, or painful breathing. Although quite rare, fatal liver toxicity may occur with Amiodarone therapy. Reversible corneal microdeposits (sometimes with night glare), rarely impaired vision due to optic neuritis; peripheral neuropathy and myopathy (usually reversible on withdrawal); bradycardia and conduction disturbances; phototoxicity and rarely persistent skin discolouration; hypothyroidism, hyperthyroidism; raised serum transaminases; jaundice, hepatitis and cirrhosis are reported. Other rare complaints are nausea, vomiting, metallic taste, tremor, sweating, vertigo, headache, sleeplessness, fatigue, alopecia, benign raised intracranial pressure, ataxia, rashes, vasculitis, renal involvement, thrombocytopenia, haemolytic or aplastic anaemia. In some cases, dose of Amiodarone may be reduced. In other cases, Amiodarone therapy may need to be stopped.

Amiodarone is contraindicated in patients with cardiogenic shock; severe sinus-node dysfunction, causing marked sinus bradycardia; second- or third degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker). Amiodarone is contraindicated in patients with a known hypersensitivity to the drug or to any of its components, including iodine.

Amiodarone may interact with b blockers such as Atenolol, Propranolol, Metoprolol, or certain calcium channel blockers, such as Verapamil or Diltiazem, resulting in an excessively slow heart rate. Amiodarone increases the blood levels of Digoxin when the two drugs are given together. Flecainide blood concentrations increase by more than 50% with Amiodarone. Procainamide and Quinidine concentrations increase by 30-50% during the first week of Amiodarone therapy. Amiodarone also can interact with tricyclic antidepressants (TCA). Amiodarone interacts with Warfarin and increases the risk of bleeding. Amiodarone inhibits the metabolism of Dextromethorphan.

In general, Amiodarone should not be administered during pregnancy because there have been reports of hypo or hyperthyroidism in infants from oral Amiodarone use during pregnancy. If Amiodarone use is considered essential, however, the patient should be warned of the risk to the foetus. The safe use of Amiodarone in lactating women has not been established.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Vitamin B1, B6 & B12 is indicated for the treatment of vitamin B1, B6 & B12 deficiency syndrome. It is also indicated for the supportive treatment of neuritis & non-inflammatory diseases of the nerves, e.g.- Diabetic neuropathy, Peripheral neuralgin, Lumbago, Myalgia, Optic neuritis, Sciatica, Facial neuralgia, Intercostal neuralgia, Spinal pain.

Specific combined vitamin preparations

Vitamin B1 converts carbohydrates, fatty acids and amino acids into energy, promotes healthy nerves, improves mood, strengthens the heart. Vitamin B6 forms RBCs, helps cells to make proteins, manufactures neurotransmitters e.g. serotonin and releases stored forms of energy, helps to prevent CVS diseases and stroke, helps to lift depression and eases insomnia. Vitamin B12 is essential for cell replication and important for RBC production, prevents anemia, helps to prevent depression, reduces nerve pain, numbness, tingling and lowers the risk of heart diseases.

The vitamin ingredients are absorbed well in per oral reception. It is widely distributed to most tissues and appears in breast milk. Within the cell, thiamine is mostly present as diphosphate. Thiamine is not stored to any appreciable extent in the body and amounts in excess of the body’s requirements are excreted in the urine as unchanged thiamine or as metabolites. Pyridoxine, pyridoxal and pyridoxamine are readily absorbed from the GIT following oral administration and are converted to the active forms of pyridoxal phosphate an pyridoxamine phosphate. They are stored mainly in liver where there is oxidation to 4-pyridoxic acid and other inactive metabolites, which are excreted in urine. As the dose increases, proportionally greater amounts are excreted unchanged in the urine.

Tablet: 1-3 Tablets per day or as advised by the physician.

Injection:

• In severe (acute) cases: 1 injection daily until the acute symptoms subside or taken as advised by the physician.
• In mild cases: 1 injection 2-3 times per week. Ampoules are preferably injected intramuscularly.

Use in children: There is no information on the use of this drug in children.

Generally well tolerated but allergic reactions may be observed in few cases.

Vitamin B1, Vitamin B6 and Vitamin B12 is contraindicated in patients on levodopa therapy, and in patients with hypersensitivity to any of the ingredients of the preparation.

Cyanocobalamin should not be given in patients with subacute degeneration of the spinal cord. Cyanocobalamin is not suitable form of vitamin B12 for the treatment of optic neuropathies associated with raised plasma concentrations of cyanocobalamin.

No drug interaction has been reported yet.

Oral tablet form is recommended but due to the presence of benzyl alcohol, injection is not recommended during pregnancy & lactation.

No overdosage symptoms are to be expected in the recommended dosage. If there is known overdose then treatment is symptomatic & supportive.

Keep out of reach of children. Store in a cool (below 25°C temperature) and dry place, protected from light.

Vitamin B1, B6 & B12 is indicated for the treatment of vitamin B1, B6 & B12 deficiency syndrome. It is also indicated for the supportive treatment of neuritis & non-inflammatory diseases of the nerves, e.g.- Diabetic neuropathy, Peripheral neuralgin, Lumbago, Myalgia, Optic neuritis, Sciatica, Facial neuralgia, Intercostal neuralgia, Spinal pain.

Specific combined vitamin preparations

Vitamin B1 converts carbohydrates, fatty acids and amino acids into energy, promotes healthy nerves, improves mood, strengthens the heart. Vitamin B6 forms RBCs, helps cells to make proteins, manufactures neurotransmitters e.g. serotonin and releases stored forms of energy, helps to prevent CVS diseases and stroke, helps to lift depression and eases insomnia. Vitamin B12 is essential for cell replication and important for RBC production, prevents anemia, helps to prevent depression, reduces nerve pain, numbness, tingling and lowers the risk of heart diseases.

The vitamin ingredients are absorbed well in per oral reception. It is widely distributed to most tissues and appears in breast milk. Within the cell, thiamine is mostly present as diphosphate. Thiamine is not stored to any appreciable extent in the body and amounts in excess of the body’s requirements are excreted in the urine as unchanged thiamine or as metabolites. Pyridoxine, pyridoxal and pyridoxamine are readily absorbed from the GIT following oral administration and are converted to the active forms of pyridoxal phosphate an pyridoxamine phosphate. They are stored mainly in liver where there is oxidation to 4-pyridoxic acid and other inactive metabolites, which are excreted in urine. As the dose increases, proportionally greater amounts are excreted unchanged in the urine.

Tablet: 1-3 Tablets per day or as advised by the physician.

Injection:

• In severe (acute) cases: 1 injection daily until the acute symptoms subside or taken as advised by the physician.
• In mild cases: 1 injection 2-3 times per week. Ampoules are preferably injected intramuscularly.

Use in children: There is no information on the use of this drug in children.

Generally well tolerated but allergic reactions may be observed in few cases.

Vitamin B1, Vitamin B6 and Vitamin B12 is contraindicated in patients on levodopa therapy, and in patients with hypersensitivity to any of the ingredients of the preparation.

Cyanocobalamin should not be given in patients with subacute degeneration of the spinal cord. Cyanocobalamin is not suitable form of vitamin B12 for the treatment of optic neuropathies associated with raised plasma concentrations of cyanocobalamin.

No drug interaction has been reported yet.

Oral tablet form is recommended but due to the presence of benzyl alcohol, injection is not recommended during pregnancy & lactation.

No overdosage symptoms are to be expected in the recommended dosage. If there is known overdose then treatment is symptomatic & supportive.

Keep out of reach of children. Store in a cool (below 25°C temperature) and dry place, protected from light.

Benzylpenicillin & Phenoxymethyl penicillin

Phenoxymethyl penicillin or penicillin V is acid-stable and is absorbed from the upper part of the small intestine. Of different forms of Phenoxymethyl penicillin, the potassium salt of Phenoxymethyl penicillin is best absorbed. This may be given with meals but maximum absorption is achieved when drug is administered orally at least 1 hour before or 2 hours after the meal. Phenoxymethyl penicillin offers a very convenient means of treating Grampositive infections. Phenoxymethyl penicillin has the distinct advantage over penicillin G in resistance to inactivation by gastric acid.

The dosage of Phenoxymethyl penicillin should be determined according to the sensitivity of the causative micro-organism and the severity of the infection, and adjusted to the clinical response of the patient.

Adults: 250-500 mg 6 hourly

Children (above 1 year):

• 125-250 mg 6 hourly
• 125 mg/5 ml powder for suspension: 1-2 teaspoonful (5-10 ml) 6 hourly
• 250 mg/5 ml powder for suspension: ½-1 teaspoonful (2.5-5 ml) 6 hourly

Infants (below 1 year):

• 62.5-125 mg 6 hourly.
• 125 mg/5 ml powder for suspension: ½-1 teaspoonful (2.5-5 ml) 6 hourly, or as prescribed by the physician.

Phenoxymethyl penicillin is best taken with an empty stomach, preferably at least 1 hour before or 2 hour after meal.

Phenoxymethyl Penicillin is best taken on an empty stomach, preferably one hour before meals. The tablets are swallowed without chewing with sufficient amounts of liquid. Before each use of this syrup, the bottle has to be shaken vigorously.

Occasionally, hypersensitivity reactions involving the skin (e.g. urticaria, morbilliform or scarlatiniform rashes, pruritus), eosinophilia or more serious allergic reactions, e.g. drug fever, vasculitis, serum sickness or interstitial nephritis, may develop. Anaphylactic or anaphylactoid reactions accompanied by, e.g- angioneurotic oedema, oedema of the larynx, bronchial spasm and shock may occur.

In the event of signs pointing to anaphylactic/anaphylactoid reactions, the treatment must be terminated immediately. In occasional instances, there may be skin rashes or inflammation of mucous membranes, especially in the region of the mouth (stomatitis); dryness of the mouth and disorders of taste may rarely occur.

The occurrence of severe bullous skin reactions- usually involving the mucosae- has been reported in isolated cases (Stevens-Johnson syndrome, Lyell's syndrome). Gastrointestinal disturbances with, e.g., nausea, vomiting, abdominal pain, loose stools, or diarrhoea may develop.

Diarrhoea may sometimes be a symptom of enterocolitis which may, in some cases, be haemorrhagic. A particular form of enterocolitis that can occur with antibiotics is pseudomembranous colitis (in most cases due to Clostridium diffcile). This must be considered in patients in whom severe, persistent diarrhoea occurs during treatment or in the initial weeks thereafter. Even if pseudomembranous colitis is only suspected, administration of Phenoxymethyl penicillin must be halted immediately. This type of colitis requires immediate and appropriate treatment by a physician. Drugs that inhibit intestinal peristalsis must not be taken in such cases. In isolated cases, particularly after high doses and prolonged administration, changes in blood picture such as reduction in the number of white blood cells (e.g.,leucopenia, granulocytopenia, agranulocytosis), erythrocytes (e.g., due to haemolytic anaemia), thrombocytes, or pancytopenia and myelosuppression may occur. During treatment for spirochaetal infections, Herxheimer's reaction characterized by the occurrence or worsening of general symptoms such as fever, chills, headache, and joint pains may develop. In isolated cases, drug-induced aseptic meningitis may occur.

In extremely rare cases, transient discolouration of the teeth may be seen during treatment with Phenoxymethyl penicillin. Administration of antibiotics, especially if prolonged, may lead to the proliferation of resistant micro organisms.

Beta-lactams predispose the patient to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness, movement disorders), particularly in case of overdose or renal impairment.

Phenoxymethyl Penicillin must not be administered in patients with hypersensitivity to penicillins or any of the excipients of this. Phenoxymethyl Penicillin must not be used to treat patients with severe gastrointestinal disorders accompanied by vomiting and diarrhea.

The possibility of cross-allergy between cephalosporins and penicillins must be considered. When treating patients with heart diseases or serious electrolyte disturbances of other origin, the potassium content of Phenoxymethyl Penicillin may have to be considered. Beta-lactams predispose the patient to encephalopathy risk (which may include convulsions, confusion, impairment of consciousness, movement disorders), particularly in case of overdose or renal impairment.

Administration of antibiotics, especially if prolonged, may lead to the proliferation of resistant micro-organisms. The patient's condition must therefore be checked at regular intervals. If a secondary infection occurs, appropriate measures must be taken. In patients with diabetes mellitus, the sugar content of Phenoxymethyl Penicillin syrup must be taken into consideration.

There is no indication of impaired ability to drive, or to operate machinery. Beta-lactams predispose the patient to encephalopathy risk. In the case of adverse reactions such as encephalopathy (which may include convulsions, confusion, impairment of consciousness, movement disorders), the patient should not operate machines or drive a vehicle.

Food: Concurrent intake of food leads to a reduction in the rate of absorption. Therefore, Phenoxymethyl penicillin is best taken on an empty stomach, preferably one hour before meals, in order to reach the highest possible rate of absorption.

Drug interactions: Concomitant administration of penicillins may lead to increased levels of methotrexate in serum and potentiate its toxic effects. Monitoring of methotrexate serum levels is therefore necessary.

If diarrhoea occurs as a consequence of treatment with Phenoxymethyl penicillin, the absorption of other orally administered drugs may be disturbed and their effcacy may consequently be impaired. If penicillins are combined with bacteriostatic chemotherapeutics or antibiotics (e.g., tetracyclines, chloramphenicol), the activity of penicillins may be attenuated or abolished. Concurrent administration of probenecid inhibits the renal excretion of penicillins. Concurrent use of indomethacin, phenylbutazone, salicylates or sulfinpyrazone may cause elevated and prolonged serum levels of phenoxymethylpenicillin.

Administration of penicillins may cause a transient reduction in plasma concentrations of oestrogens and gestagens. The effectiveness of oral contraceptives is therefore uncertain.

The absorption of Phenoxymethyl penicillin may be reduced where intestinal sterilization with aminoglycosides (e.g. neomycin) has just been performed or is still in progress. Combined use of penicillins and oral anticoagulants (e.g. warfarin) may prolong prothrombin time/INR.

Interference with laboratory and diagnostic tests: Non-enzymatic urine glucose determinations and tests for urobilinogen may give false-positive results.

Phenoxymethylpenicillin crosses the placenta. Given the appropriate indication, this may be used at any time throughout pregnancy. Phenoxymethylpenicillin passes into the breast milk in small amounts. This may be used during lactation; however, diarrhoea and yeast colonization of mucous membranes may occur in the infant.

The toxicity of phenoxymethylpenicillin is low, and it has a broad therapeutic range. When a multiple therapeutic dose is taken orally once only, phenoxymethylpenicillin has no acute toxicity. There is a risk of encephalopathy in cases of administration of beta-lactam antibiotics, particularly in case of overdose or renal impairment. Special measures in the event of overdosage, other than discontinuation of the medication, are not required. Elimination of phenoxymethylpenicillin can be accomplished through haemodialysis.

Store in a cool and dry place, protect from light.

Paclitaxel is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment.

All patients should be premedicated prior to Paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel.

First-line treatment of ovarian cancer: Although alternative medication regimens for paclitaxel are under investigation at present, a combination therapy of paclitaxel and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for paclitaxel treatment: 175 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.

Second-line treatment of ovarian cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.

Adjuvant chemotherapy in breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.

First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), paclitaxel should be administered 24 hours after doxorubicin. The recommended dose of paclitaxel is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of paclitaxel is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Paclitaxel infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Second-line chemotherapy of breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.

Advanced non-small-cell lung cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.

Treatment of AIDS-related KS: The recommended dose of paclitaxel is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.

Dose adjustment: Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Paclitaxel should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after paclitaxel is given.

Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Paclitaxel should be given before cisplatin when used in combination.

Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving paclitaxel after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately.

Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).

Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.

Paclitaxel clearance is not affected by cimetidine premedication.

Cisplatin: Administration of paclitaxel after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in paclitaxel clearance. Patients treated with paclitaxel and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.

Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when paclitaxel and doxorubicin are given closer in time, paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours).

Active substances metabolized in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).

Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with paclitaxel.

Pediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Preparation for Intravenous Infusion: Paclitaxel Injection must be diluted prior to infusion. Paclitaxel should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/ml. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (below 30°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Paclitaxel is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment.

All patients should be premedicated prior to Paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel.

First-line treatment of ovarian cancer: Although alternative medication regimens for paclitaxel are under investigation at present, a combination therapy of paclitaxel and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for paclitaxel treatment: 175 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.

Second-line treatment of ovarian cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.

Adjuvant chemotherapy in breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.

First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), paclitaxel should be administered 24 hours after doxorubicin. The recommended dose of paclitaxel is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of paclitaxel is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Paclitaxel infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Second-line chemotherapy of breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.

Advanced non-small-cell lung cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.

Treatment of AIDS-related KS: The recommended dose of paclitaxel is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.

Dose adjustment: Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Paclitaxel should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after paclitaxel is given.

Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Paclitaxel should be given before cisplatin when used in combination.

Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving paclitaxel after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately.

Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).

Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.

Paclitaxel clearance is not affected by cimetidine premedication.

Cisplatin: Administration of paclitaxel after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in paclitaxel clearance. Patients treated with paclitaxel and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.

Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when paclitaxel and doxorubicin are given closer in time, paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours).

Active substances metabolized in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).

Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with paclitaxel.

Pediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Preparation for Intravenous Infusion: Paclitaxel Injection must be diluted prior to infusion. Paclitaxel should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/ml. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (below 30°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Paclitaxel is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment.

All patients should be premedicated prior to Paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel.

First-line treatment of ovarian cancer: Although alternative medication regimens for paclitaxel are under investigation at present, a combination therapy of paclitaxel and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for paclitaxel treatment: 175 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.

Second-line treatment of ovarian cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.

Adjuvant chemotherapy in breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.

First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), paclitaxel should be administered 24 hours after doxorubicin. The recommended dose of paclitaxel is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of paclitaxel is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Paclitaxel infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Second-line chemotherapy of breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.

Advanced non-small-cell lung cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.

Treatment of AIDS-related KS: The recommended dose of paclitaxel is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.

Dose adjustment: Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Paclitaxel should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after paclitaxel is given.

Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Paclitaxel should be given before cisplatin when used in combination.

Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving paclitaxel after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately.

Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).

Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.

Paclitaxel clearance is not affected by cimetidine premedication.

Cisplatin: Administration of paclitaxel after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in paclitaxel clearance. Patients treated with paclitaxel and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.

Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when paclitaxel and doxorubicin are given closer in time, paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours).

Active substances metabolized in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).

Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with paclitaxel.

Pediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Preparation for Intravenous Infusion: Paclitaxel Injection must be diluted prior to infusion. Paclitaxel should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/ml. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (below 30°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Paclitaxel is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment.

All patients should be premedicated prior to Paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel.

First-line treatment of ovarian cancer: Although alternative medication regimens for paclitaxel are under investigation at present, a combination therapy of paclitaxel and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for paclitaxel treatment: 175 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.

Second-line treatment of ovarian cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.

Adjuvant chemotherapy in breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.

First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), paclitaxel should be administered 24 hours after doxorubicin. The recommended dose of paclitaxel is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of paclitaxel is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Paclitaxel infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Second-line chemotherapy of breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.

Advanced non-small-cell lung cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.

Treatment of AIDS-related KS: The recommended dose of paclitaxel is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.

Dose adjustment: Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Paclitaxel should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after paclitaxel is given.

Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Paclitaxel should be given before cisplatin when used in combination.

Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving paclitaxel after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately.

Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).

Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.

Paclitaxel clearance is not affected by cimetidine premedication.

Cisplatin: Administration of paclitaxel after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in paclitaxel clearance. Patients treated with paclitaxel and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.

Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when paclitaxel and doxorubicin are given closer in time, paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours).

Active substances metabolized in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).

Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with paclitaxel.

Pediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Preparation for Intravenous Infusion: Paclitaxel Injection must be diluted prior to infusion. Paclitaxel should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/ml. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (below 30°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Paclitaxel is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment.

All patients should be premedicated prior to Paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel.

First-line treatment of ovarian cancer: Although alternative medication regimens for paclitaxel are under investigation at present, a combination therapy of paclitaxel and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for paclitaxel treatment: 175 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.

Second-line treatment of ovarian cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.

Adjuvant chemotherapy in breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.

First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), paclitaxel should be administered 24 hours after doxorubicin. The recommended dose of paclitaxel is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of paclitaxel is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Paclitaxel infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Second-line chemotherapy of breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.

Advanced non-small-cell lung cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.

Treatment of AIDS-related KS: The recommended dose of paclitaxel is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.

Dose adjustment: Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Paclitaxel should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after paclitaxel is given.

Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Paclitaxel should be given before cisplatin when used in combination.

Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving paclitaxel after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately.

Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).

Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.

Paclitaxel clearance is not affected by cimetidine premedication.

Cisplatin: Administration of paclitaxel after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in paclitaxel clearance. Patients treated with paclitaxel and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.

Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when paclitaxel and doxorubicin are given closer in time, paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours).

Active substances metabolized in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).

Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with paclitaxel.

Pediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Preparation for Intravenous Infusion: Paclitaxel Injection must be diluted prior to infusion. Paclitaxel should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/ml. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (below 30°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.

Paclitaxel is a novel anti-microtubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or “bundles” of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. Following intravenous administration of Paclitaxel, paclitaxel plasma concentrations declined in a biphasic manner. The initial rapid decline represents distribution to the peripheral compartment and elimination of the drug. The later phase is due, in part, to a relatively slow efflux of paclitaxel from the peripheral compartment.

All patients should be premedicated prior to Paclitaxel administration in order to prevent severe hypersensitivity reactions. Such premedication may consist of dexamethasone 20 mg PO administered approximately 12 and 6 hours before Paclitaxel, diphenhydramine (or its equivalent) 50 mg IV 30 to 60 minutes prior to Paclitaxel, and cimetidine (300 mg) or ranitidine (50 mg) IV 30 to 60 minutes before Paclitaxel.

First-line treatment of ovarian cancer: Although alternative medication regimens for paclitaxel are under investigation at present, a combination therapy of paclitaxel and cisplatin is recommended. Depending on the duration of infusion, two different dosages are recommended for paclitaxel treatment: 175 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of three hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals, or 135 mg/m2 of paclitaxel is administered as an intravenous infusion over a period of 24 hours followed thereafter by 75 mg/m2 of cisplatin and the therapy is repeated at 3-week intervals.

Second-line treatment of ovarian cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours, with a 3-week interval between courses.

Adjuvant chemotherapy in breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours every 3 weeks for four courses, following AC therapy.

First-line chemotherapy of breast carcinoma: When used in combination with doxorubicin (50 mg/m2), paclitaxel should be administered 24 hours after doxorubicin. The recommended dose of paclitaxel is 220 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. When used in combination with trastuzumab, the recommended dose of paclitaxel is 175 mg/m2 administered intravenously over a period of 3 hours, with a 3-week interval between courses. Paclitaxel infusion may be started the day following the first dose of trastuzumab or immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Second-line chemotherapy of breast carcinoma: The recommended dose of paclitaxel is 175 mg/m2 administered over a period of 3 hours, with a 3-week interval between courses.

Advanced non-small-cell lung cancer: The recommended dose of paclitaxel is 175 mg/m2 administered over 3 hours followed by 80 mg/m2 of cisplatin, with a 3-week interval between courses.

Treatment of AIDS-related KS: The recommended dose of paclitaxel is 100 mg/m2 administered as a 3-hour intravenous infusion every two weeks.

Dose adjustment: Subsequent doses of paclitaxel should be administered according to individual patient tolerance. Paclitaxel should not be re-administered until the neutrophil count is >1.5 x 109/1 (>1 x 109/1 for KS patients) and the platelet count is >100 x 109/1 (>75 x 109/1 for KS patients).

Common: Low blood counts leading to increased risk for infection, anemia and/or bleeding, hair loss, arthralgias and myalgias, pain in the joints and muscles, peripheral neuropathy, nausea, vomiting (usually mild), diarrhea, Mouth sores, hypersensitivity reaction, fever, facial flushing, chills, shortness of breath, or hives after paclitaxel is given.

Rare: swelling of the feet or ankles (edema), liver problems, low blood pressure, darkening of the skin where previous radiation treatment has been given.

Paclitaxel should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Since significant hypersensitivity reactions may occur, appropriate supportive equipment should be available. Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration during drug administration. Paclitaxel should be given before cisplatin when used in combination.

Significant hypersensitivity reactions, as characterised by dyspnoea and hypotension requiring treatment, angioedema, and generalised urticaria have occurred in <1% of patients receiving paclitaxel after adequate premedication. Fatal hypersensitivity reactions have occurred in patients despite premedication. These reactions are probably histamine-mediated. In the case of severe hypersensitivity reactions, paclitaxel infusion should be discontinued immediately.

Bone marrow suppression, primarily neutropenia, is the dose-limiting toxicity. Neutrophil nadirs occurred at a median of 11 days. Frequent monitoring of blood counts should be instituted. Patients should not be retreated until the neutrophil count is ≥1.5 x 109/1 (≥1 x 109/1 for KS patients) and the platelets recover to ≥100 x 109/1 (≥75 x 109/1 for KS patients).

Severe cardiac conduction abnormalities have been reported rarely with single agent paclitaxel. If patients develop significant conduction abnormalities during paclitaxel administration, appropriate therapy should be administered and continuous cardiac monitoring should be performed during subsequent therapy with paclitaxel.

Paclitaxel clearance is not affected by cimetidine premedication.

Cisplatin: Administration of paclitaxel after cisplatin treatment leads to greater myelosuppression and about a 20% decrease in paclitaxel clearance. Patients treated with paclitaxel and cisplatin may have an increased risk of renal failure as compared to cisplatin alone in gynecological cancers.

Doxorubicin: Since the elimination of doxorubicin and its active metabolites can be reduced when paclitaxel and doxorubicin are given closer in time, paclitaxel for initial treatment of metastatic breast cancer should be administered 24 hours after doxorubicin. Sequence effects characterized by more profound neutropenic and stomatitis episodes have been observed with combination use of paclitaxel and doxorubicin when paclitaxel was administered before doxorubicin and using longer than recommended infusion times (paclitaxel administered over 24 hours; doxorubicin over 48 hours).

Active substances metabolized in the liver: The metabolism of paclitaxel is catalysed, in part, by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Therefore, in the absence of a PK drug-drug interaction study, caution should be exercised when administering paclitaxel concomitantly with medicines known to inhibit either CYP2C8 or CYP3A4 (e.g. ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, clopidogrel, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) because toxicity of paclitaxel may be increased due to higher paclitaxel exposure. Administering paclitaxel concomitantly with medicines known to induce either CYP2C8 or CYP3A4 (e.g. rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) is not recommended because efficacy may be compromised because of lower paclitaxel exposures.

Pregnancy Category D. There is no adequate data from the use of paclitaxel in pregnant women, however as with other cytotoxic medicinal products, paclitaxel may cause foetal harm when administered to pregnant women. Paclitaxel is contraindicated during lactation.

Patients who experience severe neutropenia: (neutrophil count <0.5 x 109/1 for a minimum of 7 days) or severe peripheral neuropathy, should receive a dose reduction of 20% for subsequent courses (25% for KS patients).

Patients with hepatic impairment: Inadequate data are available to recommend dosage alterations in patients with mild to moderate hepatic impairments. Patients with severe hepatic impairment must not be treated with paclitaxel.

Pediatric use: Paclitaxel is not recommended for use in children below 18 years due to lack of data on safety and efficacy

There is no known antidote for paclitaxel overdose. In case of overdose, the patient should be closely monitored. Treatment should be directed at the primary anticipated toxicities, which consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in paediatric patients may be associated with acute ethanol toxicity.

Preparation for Intravenous Infusion: Paclitaxel Injection must be diluted prior to infusion. Paclitaxel should be diluted in 0.9% Sodium Chloride Injection, USP; 5% Dextrose Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection, USP; or 5% Dextrose in Ringer’s Injection to a final concentration of 0.3 to 1.2 mg/ml. The solutions are physically and chemically stable for up to 27 hours at ambient temperature (below 30°C) and room lighting conditions. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children. Use only freshly prepared solution.