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Zoledronic Acid is indicated in:

• Hypercalcaemia of malignancy, 
• Bone metastases associated with solid tumours, Osteolytic lesions associated with multiple myeloma, 
• Corticosteroid-induced osteoporosis, Increase bone mass in men with osteoporosis, Osteoporosis in postmenopausal women
• Paget's disease of bone
• Prophylaxis of postmenopausal osteoporosis

Bisphosphonate preparations

Zoledronic acid belongs to the class of nitrogen-containing bisphosphonates and acts primarily on bone. It is an inhibitor of osteoclast-mediated bone resorption. The action of bisphosphonates on bone is based on their high affinity for mineralized bone. Intravenously administered Zoledronic acid is rapidly distributed to bone. The main molecular target of Zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthase, but this does not exclude other mechanisms. Clinical studies in tumour-induced hypercalcemia demonstrated that the effect of Zoledronic acid is characterized by decreases in serum calcium and urinary calcium excretion. In addition to its inhibitory activity against bone resorption, Zoledronic acid also possesses anti-tumour activity, anti-angiogenic activity, anti-pain activity, cytostatic and pro-apoptotic activity on tumour cells and synergistic cytostatic effect with other anti-cancer drugs. There was no accumulation of the active substance in plasma after multiple doses given every 28 days. Zoledronic acid is not metabolized and is excreted unchanged via the kidney.

Hypercalcemia of malignancy: The maximum recommended dose of Zoledronic Acid in hypercalcemia of malignancy (serum calcium 12 mg/dl or 3.0 mmol/l) is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion. Dose adjustment of Zoledronic Acid is not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment. Re-treatment with Zoledronic Acid may be considered if serum calcium does not return to normal after initial treatment. It is recommended that a minimum of 7 days elapse before re-treatment, to allow for full response to the initial dose. 

Multiple myeloma and bone metastases of solid tumors: The recommended dose of Zoledronic Acid in patients with multiple myeloma and metastatic bone lesions from solid tumors is 4 mg infused every 3-4 weeks. Patients should also be administered an oral calcium supplement of 500 mg and 400 IU of Vitamin-D daily.

Prior to administration, the required amount of concentrate from one vial must be further diluted with 100 ml of calcium-free infusion solution (0.9% w/v sodium chloride solution or 5% w/v glucose solution). The duration of infusion must not be less than 15 minutes. After addition of the solution to the infusion media, the infusion solution should be used as soon as possible. If storage of the infusion solution is necessary, hold at 2-8º C for not more than 24 hours. If refrigerated, the solution must be allowed to reach room temperature before administration.

Zoledronic Acid must not be mixed with calcium or other divalent cation-containing infusion solutions, such as Lactated Ringer's solution, and should be administered as a single intravenous solution in a line separate from all other drugs.

The post-dose side-effects are headache, nausea, anorexia, fatigue, osteonecrosis of jaw, anemia, bone pain, constipation, fever, vomiting, flu-like syndrome, hypocalcemia, myalgia, arthralgia and hypophosphataemia.

The drug is contraindicated if patients have hypersensitivity to the active substance or to any of the excipients or to any bisphosphonates; severe renal impairment (Creatinine clearance <30 ml/min); pregnancy and lactation.

Patients must be appropriately hydrated prior to administration of Zoledronic Acid. This is especially important in the elderly and for patients receiving diuretic therapy. Adequate hydration can be achieved by the patient drinking two glasses of fluid (such as water) before and after the infusion. Serum levels of calcium, phosphate, magnesium and potassium, as well as serum creatinine should be carefully monitored after initiating Zoledronic Acid therapy. If hypocalcemia, hypophosphatemia or hypomagnesemia occurs, short-term supplemental therapy may be necessary. Moreover, careful renal function monitoring should be considered.

In clinical studies, Zoledronic acid has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without interactions. Caution is advised when Zoledronic acid are administered with aminoglycosides, since these agents may have an additive effect to lower serum calcium level for prolonged periods. In multiple myeloma patients, the risk of renal dysfunction may be increased when Zoledronic acid is used in combination with thalidomide. Concomitant use of loop diuretics with Zoledronic acid increases the risk of hypocalcemia. Caution is indicated when Zoledronic acid is used with other potentially nephrotoxic drugs.

Zoledronic acid is contraindicated during pregnancy and in breast-feeding women. It is also not recommended for use in children and adolescents below 18 years of age.

Patients with renal impairment: The use of Zoledronic Acid is not recommended in patients with severe renal impairment (Creatinine clearance <30 ml/min). No dose adjustment is necessary in patients with creatinine clearance >60 ml/min. Based on creatinine clearance the following dose should be used in patient with impaired renal function:

• CrCl > 60 ml/min: 4 mg (5 ml)
• CrCl 50-60 ml/min: 3.5 mg (4.4 ml)
• CrCl 40-49 ml/min: 3.3 mg (4.1 ml)
• CrCl 30-39 ml/min: 3 mg (3.8 ml)

Clinical experience with acute over dosage is limited. Over dosage may cause hypocalcemia, hypophosphatemia, and hypomagnesemia. In such case, reduction in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate and magnesium sulfate respectively.

Dilute the required amount in 100 mL of NaCl 0.9% or dextrose 5%.

Store below 30° C prior to opening. Protect from moisture and light. Zoledronic Acid must be kept out of the reach and sight of children.

Ibandronic acid is indicated for the treatment of postmenopausal osteoporosis, to reduce the risk of fractures.

Treatment of Osteoporosis: Osteoporosis may be confirmed by the finding of low bone mass (T-score <-2.0 SD) and the presence or history of osteoporotic fracture, or a low bone mass (T-score <-2.5 SD) in the absence of documented pre-existing osteoporotic fracture.

Bisphosphonate preparations

The pharmacodynamic action of ibandronic acid is inhibition of bone resorption. In vivo, ibandronic acid prevents experimentally induced bone destruction caused by cessation of gonadal function, retinoids, tumors or tumor extracts. In young (fast growing) rats, the endogenous bone resorption is also inhibited, leading to increased bone mass compared with untreated animals. Animal models confirm that ibandronic acid is a highly potent inhibitor of osteoclastic activity. In growing rats, there was no evidence of impaired mineralization even at doses greater than 5,000 times the dose required for osteoporosis treatment. The high potency and therapeutic margin of ibandronic acid allows for more flexible dosing regimens and intermittent treatment with long drug-free intervals at comparatively low doses.

Ibandronic acid is a highly potent bisphosphonate belonging to the nitrogen-containing group of bisphosphonates, which act on bone tissue and specifically inhibit osteoclast activity, It does not interfere with osteoclast recruitment. The selective action of ibandronic acid on bone tissue is based on the high affinity of this compound for hydroxyapatite, which represents the mineral matrix of the bone. Ibandronic acid reduces bone resorption, with no direct effect on bone formation. In postmenopausal women, it reduces the elevated rate of bone turnover towards premenopausal levels, leading to a progressive net gain in bone mass. Daily or intermittent administration of ibandronic acid results in reduced bone resorption as reflected in reduced levels of serum and urinary biochemical markers of bone turnover, increased BMD and a decreased incidence of fractures.

The recommended dose of Ibandronic acid for treatment is one 150 mg film-coated tablet once a month. The tablet should preferably be taken on the same date each month. Ibandronic acid should be taken 60 minutes before the first food or drink (other than water) of the day or any other oral medication or supplementation (including calcium):

• Tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the patient is sitting or standing in an upright position. Patients should not lie down for 60 minutes after taking Ibandronic acid.
• Plain water is the only drink that should be taken with Ibandronic acid. Please note that some mineral waters may have a higher concentration of calcium and therefore should not be used.
• Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration. Patients should receive supplemental calcium or vitamin D if dietary intake is inadequate. In case a once-monthly dose is missed, patients should be instructed to take one Ibandronic Acid 150 mg tablet the morning after the tablet is remembered unless the time to the next scheduled dose is within 7 days. Patients should then return to taking their dose once a month on their originally scheduled date. If the next scheduled dose is within 7 days, patients should wait until their next dose and then continue taking one tablet once a month as originally scheduled. Patients should not take two 150 mg tablets within the same week.

The main side effects of ibandronic acid are dyspepsia, nausea, diarrhea, abdominal pain, muscle aches, headaches, dizziness.

Ibandronic Acid is contraindicated in patients with known hypersensitivity to ibandronic acid or to any of the excipients. Ibandronic Acid is contraindicated in patients with uncorrected hypocalcemia. As with all bisphosphonates indicated in the treatment of osteoporosis, pre-existing hypocalcemia needs to be corrected before initiating therapy with Ibandronic Acid. As with several bisphosphonates, Ibandronic Acid is contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia. Ibandronic Acid is contraindicated in patients who are unable to stand or sit upright for at least 60 minutes.

Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Ibandronic Acid therapy. Adequate intake of calcium and vitamin D is important in all patients. Orally administered bisphosphonates may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when Ibandronic Acid is given to patients with active upper gastrointestinal problems (e.g. known Barrett’s esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis or ulcers). Adverse experiences such as esophagitis, esophageal ulcers and esophageal erosions, in some cases severe and requiring hospitalization, rarely with bleeding or followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. The risk of severe esophageal adverse experiences appears to be greater in patients who do not comply with the dosing instruction and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Patients should pay particular attention and be able to comply with the dosing instructions.

Physicians should be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue Ibandronic Acid and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn. While no increased risk was observed in controlled clinical trials there have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications. Since NSAIDs and bisphosphonates are both associated with gastrointestinal irritation, caution should be taken during concomitant medication with Ibandronic Acid. Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis of the jaw include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment.

It is likely that calcium supplements, antacids and some oral medications containing multivalent cations (such as aluminium, magnesium, iron) are likely to interfere with the absorption of Ibandronic Acid. Therefore, patients must wait 60 minutes after taking Ibandronic Acid before taking other oral medications. Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (estrogen). No interaction was observed when co-administered with melphalan/prednisolone in patients with multiple myeloma. In healthy male volunteers and postmenopausal women, i.v. ranitidine caused an increase in ibandronic acid bioavailability of about 20 %, probably as a result of reduced gastric acidity. However, since this increase is within the normal range of the bioavailability of ibandronic acid, no dosage adjustment is required when Ibandronic Acid is administered with H2-antagonists or other drugs which increase gastric pH.

In relation to disposition, no drug interactions of clinical significance are considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats. Furthermore, plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other drugs. Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. The secretory pathway appears not to include known acidic or basic transport systems involved in the excretion of other drugs. In a one-year study in postmenopausal women with osteoporosis (BM16549). the incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking Ibandronic Acid 2.5 mg daily or 150mg once monthly. Of over 1500 patients enrolled in study BM 16549 comparing monthly with daily dosing regimens of ibandronic acid, 14% of patients used histamine (H2) blockers or proton pump inhibitors. Among these patients, the incidence of upper gastrointestinal events in the patients treated with Ibandronic Acid 150 mg once monthly was similar to that in patients treated with Ibandronic Acid 2.5 mg daily.

Pregnancy: Ibandronic Acid should not be used during pregnancy. There was no evidence for a direct fetal toxic or teratogenic effect of ibandronic acid in daily orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class. They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome). Specific studies for the monthly regimen have not been performed. There is no clinical experience with Ibandronic Acid in pregnant women.

Nursing Mothers: Ibandronic Acid should not be used during lactation. In lactating rats treated with 0.08 mg/kg/day IV. ibandronic acid, the highest concentration of ibandronic acid in breast milk was 8.1 ng/ml and was seen in the first 2 hours after i.v. administration. After 24 hours, the concentration in milk and plasma was similar, and corresponded to about 5 % of the concentration measured after 2 hours.

No specific information is available on the treatment of overdosage with ibandronic acid. However, oral overdosage may result in upper gastrointestinal adverse events, such as upset stomach, heartburn, esophagitis, gastritis, or ulcer. Milk or antacids should be given to bind ibandronic acid. Owing to the risk of esophageal irritation, vomiting should not be induced and the patient should remain fully upright.

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

This is indicated in oral contraception.

Oral Contraceptive preparations

This is a combined oral contraceptive tablet containing the synthetic progestogen, drospirenone and the synthetic estrogen, ethinylestradiol. The contraceptive effect of this tablet is based on the interaction of various factors, the most important of which are seen as the inhibition of ovulation and the changes in cervical secretion. When this tablet is taken according to instructions, the egg cells are prevented from maturing to the point at which they can be fertilized, the cervical mucus remains thick so as to constitute a barrier to sperm and the endometrium is rendered unreceptive to implantation. As well as protection against pregnancy, estrogen/progestogen combinations have several positive properties which, next to the negative properties, can be useful in deciding on the method of birth control. The cycle is more regular and the menstruation is often less painful and bleeding is lighter.

Drospirenone has antimineralocorticoid activity, counteracting estrogen related sodium retention. In combination with ethinylestradiol, drospirenone displays a favourable lipid profile with an increase in high-density lipoprotein HDL. Drospirenone exerts antiandrogenic activity and does not counteract the ethinylestradiol-related sex hormone binding globulin (SHBG) increase which is useful for binding and inactivating the endogenous androgens. Drospirenone is devoid of any androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. This in combination with the antimineralocorticoid and antiandrogenic properties, gives drospirenone a biochemical and pharmacological profile closely resembling the natural hormone progesterone.

When and how to take the tablets: The this tablet pack contains 21 tablets. On the pack, each tablet is marked with the day of the week on which it is to be taken. Take your tablet at about the same time each day, with some water if necessary. Follow the direction of the arrows until all 21 tablets have been taken. During the next 7 days don't take any tablet. A period should begin during these 7 days (the withdrawal bleed), unusually it will start on day 2-3 after the last this tablettablet. Start taking your next pack on the 8th day even if your period continues. This means that you will always start new packs on the same day of the week and also that you have your withdrawal bleed on about the same days each month.

Starting your first pack of this tablet: When no hormonal contraceptive has been used in the past month. Start taking this tablet on the first day of your cycle, i.e. the first day of menstrual bleeding. Take a tablet marked with that day of the week. For example, if your period starts on a Sunday, take a tablet marked Sunday. Then follow thedaysin order. You may also start on days 2-5 of your cycle, but in that case make sure you also use an additional contraceptive method (barrier method) for the first 7 days of tablet-taking in the first cycle.

When changing form another combined Pill: You can start taking this tablet the day after you have the last tablet from your present Pill pack (this means no tablet-free break). If your present Pill pack also contains inactive tablets you can start this tablet on the day after taking the first active tablet (if you are not sure which this is, ask your doctor or pharmacist). You can also start later, but never later than the day following the tablet free break of your present Pill (or the day after the last inactive tablet of your present Pill).

When changing from progestogen-only Pill (Mini Pill): You can stop taking the mini pill any day and start taking this tablet the next day, at the same time. But make sure you also use an additional-contraceptive method (a barrier method) for the first 7 days of tablet-taking when having intercourse.

When changing from an Injectable or Implant: Start using this tablet when your next injection is due or on the day that your implant is removed. But make sure you also use an additional contraceptive method (a barrier method) for the first 7 days of tablet-taking when having intercourse.

After having a baby: If you have just had a baby, your doctor may tell you to wait until after your first normal period before you start taking this tablet. Sometimes it is possible to start sooner. Your doctor will advise you. If you are breast-feeding and want to take this tablet you should discuss this first with your doctor.

After a miscarriage or an abortion: Your doctor will advise you.

If too many this tablet tablets are taken (overdose): There have been no reports of serious harmful effects from taking too many this tablet tablets at one time. If you have taken several tablets at a time, you may have nausea, vomiting or vaginal bleeding. If you discover that a child has taken this tablet ask your doctor for advice.

When you want to stop taking this tablet: You can stop taking this tablet at any time you want. If you do not want to become pregnant, ask your doctor about other methods of birth control. If you stop taking this tablet because you want to get pregnant, it is generally recommended that you wait until you have had a natural period before trying to conceive.

If you forget to take tablets

• If you are less than 12 hours late in taking a tablet, the reliability of the Pill is maintained. Take the tablet as soon as you remember and take the next tablets at the usual times.
• If you are more than 12 hours late in taking any tablet, the reliability of the Pill may be reduced. The more consecutive tablets you have missed, the higher the risk that the contraceptive efficacy is decreased. There is a particularly high risk of becoming pregnant if you miss tablets at the beginning or at the end of the pack. Therefore, you should follow the rules given below.

More than one tablet forgotten in a pack: Ask your doctor for advice.

• 1 tablet missed in week 1: Take the missed tablet as soon as your remember (even if this means taking two tablets at the same time) and take the next tablets at the usual time. Use extra contraceptive precautions (barrier method) for the next 7 days. If you had sexual intercourse in the week before missing the tablets, there is a possibility of becoming pregnant. So tell your doctor immediately.
• 1 tablet missed in week 2: Take the missed tablet as soon as you remember (even if this means taking two tablets at the same time) and take the next tablets at the usual time. The reliability of the Pill is maintained. You need not use extra contraceptive precautions.
• 1 tablet missed in week 3: You may choose either of the following options, without the need for extra contraceptive precautions.

Take the missed tablet as soon as you remember (even if this means taking two tablets at the same time) and take the next tablets at the usual time. Start the next pack as soon as the current pack is finished so that no gap is left between packs. You may not have a withdrawal bleed until the end of the second pack but you may have spotting or breakthrough bleeding on tablet-taking days. Or

Stop taking tablets from your current pack, have a tablet-free break of 7 days or less (also count the day you missed your tablet) and continue with the next pack. When, following this method, you can always start your next pack on the same day of the week as you usually do.

If you have forgotten tablets in a pack and you do not have the expected period in the first normal tablet-free break, you may be pregnant. Consult your doctor before you start with the next pack.

you vomit: If you vomit within 3 to 4 hours after taking your this tablet tablet, the active ingredients may not have been completely absorbed. This is like missing a tablet. Therefore, follow the advice for missed tablets.

you want to delay your period: you can delay your period if you start with your next pack of this tablet immediately after finishing your current pack. You can continue with this pack for as long as you wish, until this pack is empty. When you wish your period to begin, just stop tablet taking. While using the second pack you may have some breakthrough bleeding or spotting on tablet-taking days. Start with your next pack after the usual 7 days tablet free break.

you want to change the starting day of your period: If you take your tablets as directed, you will have your period on about the same day every 4 weeks. If you want to change this, just shorten, (never lengthen) the next tablet- free break. For example, if your period usually starts on a Friday and in future you want it to start on Tuesday (3 days earlier) you should now start your next pack 3 days sooner than you usually do. If you make your tablet-free break very short (e.g. 3 days or less) you may not have bleeding during the break. You may have some breakthrough bleeding or spotting during the use of the next pack.

you have unexpected bleeding: With all Pills, for the first few months, you can have irregular vaginal bleeding (spotting or breakthrough bleeding) between your periods. You may need to use sanitary protection, but continue to take your tablets as normal. Irregular vaginal bleeding usually stops once your body has adjusted to the Pill (usually after about 3 tablet-taking cycles). If it continues, becomes heavy or starts again, tell your doctor.

you have missed a period: If you have taken all of your tablets at the right time and you have not vomited or used other medicines then you are very unlikely to be pregnant. Continue to take this tablet as usual.

If you miss your period twice in row, you may be pregnant. Tell your doctor immediately. Do not start the next pack of this tablet until your doctor has checked you are not pregnant.

Like other contraceptives some undesirable effects may have seen with this tablet, these include venous and arterial thromboembolic disorders. The following undesirable effects have been reported in users of COCs and whether this association is causal has not been confirmed: Nausea, abdominal pain, Vomiting, diarrhoea, Weight increased, Fluid retention, Headache, Migraine, Depressed mood, mood altered, Breast pain, breast tenderness, Libido decreased, Breast hypertrophy, Rash, urticaria. In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.

Preparations containing estrogen/progestogen combinations should not be used in the presence of any of the conditions listed below. If any of the conditions appear for the first time during their use, the product should be stopped immediately.

• Thrombosis (venous or arterial) present or in history (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular accident)
• Presence or history of prodromi of a thrombosis (e.g.transient ischaemic attack, angina pectoris)
• Presence or history of migraine with focal neurological symptoms
• Diabetes mellitus with vascular involvement
• Disturbed lipometabolism
• The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication
• Pancreatitis or a history thereof if associated with severe hypertriglyceridemia
• Presence or history of severe hepatic disease as long as liver function values have not returned to normal
• Severe renal insufficiency or acute renal failure
• Presence or history of liver tumours (benign or malignant)
• Known or suspected malignant conditions of the genital organs or the breasts, if sex steroid-influenced
• Undiagnosed vaginal bleeding
• Known or suspected pregnancy
• Hypersensitivity to any of the components of this tablet.

The clinical and epidemiological evidence for estrogen/progestogen combinations like this tablet is predominantly based on experience with COCs in general. Therefore, the following warnings related to the use of COCs apply also to the use of this tablet. Also, increased risk of arterial, venous thrombotic and thromboembolic diseases such as myocardial infarction, deep venous thrombosis, pulmonary embolism and of cerebrovascular accidents. These events occur rarely.

• Cervical cancer
• Hypertriglyceridemia
• Blood pressure
• Jaundice
• Erythematosus
• Haemolytic uraemic syndrome
• Sydenham's chorea
• Herpes gestationis
• Otosclerosis-related hearing loss.
• Hereditary angioedema
• Acute or chronic disturbances of liver or kidney
• Crohn's disease and ulcerative colitis
• Chloasma

The Pill and other Medicines: Some medicines may stop the Pill from working properly. These include medicines used for the treatment of epilepsy (e.g. primidone, phenyton, barbiturates) and tuberculosis (e.g. rifampicin); and antibiotics (e.g. ampilicllin, tetracyclines, griseofulvin); for some other infectious diseases. Always tell the doctor, who prescribes the Pill, which medicines you are already using. Also tell other doctor/dentist who prescribes another medicine (or the dispensing pharmacist) that you use this tablet. They can tell you if you need to take additional contraceptive precautions and if so, for how long.

The Pill and Ability to Drive: There are no observed effects.

The Pill and Breastfeeding: This tablet is generally not recommended for use during breast feeding. If you wish to take the Pill while breastfeeding, please seek the advice of your doctor.

The Pill and Pregnancy: This tablet must not be used by women who are pregnant or who think they may be pregnant.

Store below 30°C. Store all drugs properly and keep them out of reach of children.

Drospirenone is indicated for oral contraception.

Oral Contraceptive preparations

Drospirenone is a Progestin-only pill which is a synthetic form of progesterone. The hormonal component of Drospi inhibit ovulation by Suppressing gonadotropin release, Secondary mechanisms, which may contribute to the effectiveness of Drospi as a contraceptive, include changes in the cervical mucus (which increase the difficulty of sperm penetration) and changes in the endometrium (which reduce the likelihood of implantation). Drospirenone has antimineralocorticoid activity, counteracting oestrogen related sodium retention. Drospirenone exerts antiandrogenic activity.

Drospirenone (white active and light pink inert tablets) is swallowed whole once a day. Take one tablet daily for 28 consecutive days; one white active tablet daily during the first 24 days and one light pink inert tablet daily during the 4 following days. Tablets must be taken every day at about the same time of the day so that the interval between two tablets is always 24 hours.

The following clinically significant Side Effects are described elsewhere in other sections of the labeling:

• Hyperkalemia
• Bleeding Irregularities and Amenorrhea
• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Before you take Drospirenone, do not take this medicine and tell your doctor if you are already taking the following medicines: efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, products containing St. John's wort. Take special care while taking Drospirenone Hyperkalemia Thromboembolic Disorders, Bone Loss, Liver Disease Ectopic Pregnancy, Risk of Hyperglycemia in Patients with Diabetes, Bleeding Irregularities, and Amenorrhea, Depression.

Drugs or herbal products that induce certain enzymes (for example, CYP3A4) may decrease the effectiveness of Drospirenone or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with Drospirenone.

Store below 30°C and dry place. Keep away from light. Keep out of the reach of children.

Drospirenone is indicated for oral contraception.

Oral Contraceptive preparations

Drospirenone is a Progestin-only pill which is a synthetic form of progesterone. The hormonal component of Drospi inhibit ovulation by Suppressing gonadotropin release, Secondary mechanisms, which may contribute to the effectiveness of Drospi as a contraceptive, include changes in the cervical mucus (which increase the difficulty of sperm penetration) and changes in the endometrium (which reduce the likelihood of implantation). Drospirenone has antimineralocorticoid activity, counteracting oestrogen related sodium retention. Drospirenone exerts antiandrogenic activity.

Drospirenone (white active and light pink inert tablets) is swallowed whole once a day. Take one tablet daily for 28 consecutive days; one white active tablet daily during the first 24 days and one light pink inert tablet daily during the 4 following days. Tablets must be taken every day at about the same time of the day so that the interval between two tablets is always 24 hours.

The following clinically significant Side Effects are described elsewhere in other sections of the labeling:

• Hyperkalemia
• Bleeding Irregularities and Amenorrhea
• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Before you take Drospirenone, do not take this medicine and tell your doctor if you are already taking the following medicines: efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, products containing St. John's wort. Take special care while taking Drospirenone Hyperkalemia Thromboembolic Disorders, Bone Loss, Liver Disease Ectopic Pregnancy, Risk of Hyperglycemia in Patients with Diabetes, Bleeding Irregularities, and Amenorrhea, Depression.

Drugs or herbal products that induce certain enzymes (for example, CYP3A4) may decrease the effectiveness of Drospirenone or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with Drospirenone.

Store below 30°C and dry place. Keep away from light. Keep out of the reach of children.

Anticholinergics

Drotaverine has antispasmodic effect mediated via inhibition of phosphodiesterase-IV, specific for smooth muscle. It has a rapid and direct action on the smooth muscle. It acts to correct cyclic AMP and Ca imbalance at the spastic site, thereby relieving smooth muscle spasm and pain.

Oral-

• Adults: 1 to 2 tablets, 3 times daily
• Children (over 6 years): 1/2 to 1 tablet, 1-2 times daily.
• Children (1-6 years): 1/4 to 1/2 tablet, 1-2 times daily.

Injection-

• Adults: 1 to 2 ampoules, intramuscularly or subcutaneously, 1-3 times daily.
• For the management of acute stone colics: 1 or 2 ampoules by slow intravenous injection.

The common side effects are headache, dizziness, rhinitis, sinusitis, gastrointestinal upset, nausea, pharyngitis, edema and fatigue.

Drotaverine is contraindicated in patients with known hypersensitivity to the products and its constituents.

Caution should be taken for patients suffering from liver and kidney disease.

May attenuate the action of levodopa. Concurrent use of analgesics, antimuscarinics or benzodiazepines. Additive beneficial effect with concurrent use of analgesics, antimuscarinics or benzodiazepines.

As with most drugs, the use of Drotaverine Hydrochloride should be avoided during pregnancy and lactation unless essential.

Anticholinergics

Drotaverine has antispasmodic effect mediated via inhibition of phosphodiesterase-IV, specific for smooth muscle. It has a rapid and direct action on the smooth muscle. It acts to correct cyclic AMP and Ca imbalance at the spastic site, thereby relieving smooth muscle spasm and pain.

Oral-

• Adults: 1 to 2 tablets, 3 times daily
• Children (over 6 years): 1/2 to 1 tablet, 1-2 times daily.
• Children (1-6 years): 1/4 to 1/2 tablet, 1-2 times daily.

Injection-

• Adults: 1 to 2 ampoules, intramuscularly or subcutaneously, 1-3 times daily.
• For the management of acute stone colics: 1 or 2 ampoules by slow intravenous injection.

The common side effects are headache, dizziness, rhinitis, sinusitis, gastrointestinal upset, nausea, pharyngitis, edema and fatigue.

Drotaverine is contraindicated in patients with known hypersensitivity to the products and its constituents.

Caution should be taken for patients suffering from liver and kidney disease.

May attenuate the action of levodopa. Concurrent use of analgesics, antimuscarinics or benzodiazepines. Additive beneficial effect with concurrent use of analgesics, antimuscarinics or benzodiazepines.

As with most drugs, the use of Drotaverine Hydrochloride should be avoided during pregnancy and lactation unless essential.

Antacids

This is the mixture of non-systemic acid neutralizing substances and antiflatulent. This preparation offers reliability as well as long action. Aluminium Hydroxide and Magnesium Hydroxide induce the relief of ulcer by neutralizing gastric acid secreted from parietal cells of the stomach. The clinical use of simethicone is based on its antifoam properties. Simethicone spreads on the surface of aqueous liquids, forming a film of low surface tension and causing collapse of foam bubbles. Simethicone repeatedly allows mucous surrounded gas bubbles in the GI tract to coalesce and be expelled.

This is used in the treatment of flatulence and meteorism for the elimination of gas, air or foam from the gastro-intestinal tract prior to radiography and for the relief of abdominal distension and dyspepsia.

Simethicone is physiologically inert; it does not appeared to be absorbed from the GI tract to interfere with gastric secretion or absorption of nutrients. Following oral administration, the drug is excreted unchanged in the feces.

Tablet: 1-2 tablets 1-3 hours after meal and at bed time or as directed by the physician.

Suspension: 1-2 teaspoonful 1-3 hours after meal and at bedtime or as directed by the physician.

Gastrointestinal side effects are uncommon. Occasionally, if excessive amount is consumed, diarrhea, constipation or regurgitation may occur.

This should not be administered in patients with renal failure or hypophosphataemia or in those who are severely debilitated. It is also contraindicated in alkalosis and hypermagnesaemia, where abdominal distention may be due to partial or complete intestinal obstruction.

This should be used with caution in patients with kidney disease.

All antacids may increase or decrease the rate and/or extent of absorption of concomitantly administered oral drugs. Antacids decrease the bioavailability of theophyline, tetracycline, quinolone antibiotics, isoniazide, ketoconazole, ethambutol, some antimuscarinic drugs, benzodiazepines, phenothiazines, ranitidine, indomethacine, nitrofurantoin, fluoride, phosphate, propanolol, atenolol, digoxins, vitamins etc. Antacids increase the bioavailability of some drugs; e.g. sulphonamides, levodopa, valproic acid, enteric coated aspirin etc.

It is advised to avoid antacid preparations in the first trimester of pregnancy.

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

Antacids

This is the mixture of non-systemic acid neutralizing substances and antiflatulent. This preparation offers reliability as well as long action. Aluminium Hydroxide and Magnesium Hydroxide induce the relief of ulcer by neutralizing gastric acid secreted from parietal cells of the stomach. The clinical use of simethicone is based on its antifoam properties. Simethicone spreads on the surface of aqueous liquids, forming a film of low surface tension and causing collapse of foam bubbles. Simethicone repeatedly allows mucous surrounded gas bubbles in the GI tract to coalesce and be expelled.

This is used in the treatment of flatulence and meteorism for the elimination of gas, air or foam from the gastro-intestinal tract prior to radiography and for the relief of abdominal distension and dyspepsia.

Simethicone is physiologically inert; it does not appeared to be absorbed from the GI tract to interfere with gastric secretion or absorption of nutrients. Following oral administration, the drug is excreted unchanged in the feces.

Tablet: 1-2 tablets 1-3 hours after meal and at bed time or as directed by the physician.

Suspension: 1-2 teaspoonful 1-3 hours after meal and at bedtime or as directed by the physician.

Gastrointestinal side effects are uncommon. Occasionally, if excessive amount is consumed, diarrhea, constipation or regurgitation may occur.

This should not be administered in patients with renal failure or hypophosphataemia or in those who are severely debilitated. It is also contraindicated in alkalosis and hypermagnesaemia, where abdominal distention may be due to partial or complete intestinal obstruction.

This should be used with caution in patients with kidney disease.

All antacids may increase or decrease the rate and/or extent of absorption of concomitantly administered oral drugs. Antacids decrease the bioavailability of theophyline, tetracycline, quinolone antibiotics, isoniazide, ketoconazole, ethambutol, some antimuscarinic drugs, benzodiazepines, phenothiazines, ranitidine, indomethacine, nitrofurantoin, fluoride, phosphate, propanolol, atenolol, digoxins, vitamins etc. Antacids increase the bioavailability of some drugs; e.g. sulphonamides, levodopa, valproic acid, enteric coated aspirin etc.

It is advised to avoid antacid preparations in the first trimester of pregnancy.

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

First generation Cephalosporins

Cefadroxil inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis and arresting cell wall assembly resulting in bacterial cell death.

Adult:

• Pharyngitis and Tonsillitis: 1 g per day in one or two divided doses.
• Urinary Tract Infections: 1 or 2 g per day in one or two divided doses.
• Skin and Skin Structure Infections: 1 g per day in one or two divided doses.

Children: 30 mg/kg daily in divided doses every 12 hours.

It may be taken with meals or on empty stomach. Administration with food may be helpful in diminishing potential gastrointestinal complaints.

Generally Cefadroxil is well tolerated. However, the most commonly reported side effects are gastrointestinal disturbances and hypersensitivity phenomena.

Cefadroxil is contraindicated in patients with a history of hypersensitivity to Cefadroxil or any of the ingredients of it.

Use of this antibiotic may cause pseudomembranous colitis; so caution should be taken during diagnosis in patients who develop diarrhea in association with Cefadroxil therapy.

There is no significant drug interaction with other drugs.

US FDA pregnancy category of Cefadroxil is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Cefadroxil have been shown to be excreted in human milk. So, caution should be exercised when Cefadroxil is administered during lactation.

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

First generation Cephalosporins

Cefadroxil inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis and arresting cell wall assembly resulting in bacterial cell death.

Adult:

• Pharyngitis and Tonsillitis: 1 g per day in one or two divided doses.
• Urinary Tract Infections: 1 or 2 g per day in one or two divided doses.
• Skin and Skin Structure Infections: 1 g per day in one or two divided doses.

Children: 30 mg/kg daily in divided doses every 12 hours.

It may be taken with meals or on empty stomach. Administration with food may be helpful in diminishing potential gastrointestinal complaints.

Generally Cefadroxil is well tolerated. However, the most commonly reported side effects are gastrointestinal disturbances and hypersensitivity phenomena.

Cefadroxil is contraindicated in patients with a history of hypersensitivity to Cefadroxil or any of the ingredients of it.

Use of this antibiotic may cause pseudomembranous colitis; so caution should be taken during diagnosis in patients who develop diarrhea in association with Cefadroxil therapy.

There is no significant drug interaction with other drugs.

US FDA pregnancy category of Cefadroxil is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Cefadroxil have been shown to be excreted in human milk. So, caution should be exercised when Cefadroxil is administered during lactation.

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

First generation Cephalosporins

Cefadroxil inhibits bacterial cell wall synthesis by binding to 1 or more of the penicillin-binding proteins (PBPs) which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis and arresting cell wall assembly resulting in bacterial cell death.

Adult:

• Pharyngitis and Tonsillitis: 1 g per day in one or two divided doses.
• Urinary Tract Infections: 1 or 2 g per day in one or two divided doses.
• Skin and Skin Structure Infections: 1 g per day in one or two divided doses.

Children: 30 mg/kg daily in divided doses every 12 hours.

It may be taken with meals or on empty stomach. Administration with food may be helpful in diminishing potential gastrointestinal complaints.

Generally Cefadroxil is well tolerated. However, the most commonly reported side effects are gastrointestinal disturbances and hypersensitivity phenomena.

Cefadroxil is contraindicated in patients with a history of hypersensitivity to Cefadroxil or any of the ingredients of it.

Use of this antibiotic may cause pseudomembranous colitis; so caution should be taken during diagnosis in patients who develop diarrhea in association with Cefadroxil therapy.

There is no significant drug interaction with other drugs.

US FDA pregnancy category of Cefadroxil is B. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Cefadroxil have been shown to be excreted in human milk. So, caution should be exercised when Cefadroxil is administered during lactation.

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

Fluorouracil is indicated alone or in combination for- 

• Carcinoma of the colon or rectum
• Carcinoma of the stomach and exocrine pancreas
• Carcinoma of the liver
• Carcinoma of the breast
• Carcinoma of the bladder
• Carcinoma of the lung
• Epithelial ovarian carcinoma
• Cervical carcinoma.

Fluorouracil is inactive as such in mammalian cells but is converted into the active 5-fluorodeoxyuridine monophosphate (FdUMP) by a variety of different metabolic pathways. The drug works by inhibiting the enzyme thymidylate kinase which results in reduced formation of thymidine and thus of DNA. The active metabolite FdUMP appears to form a stable complex with the folate cofactor N-5, 10-methylene tetrahydrofolate which inactivates thymidylate kinase. Fluorouracil as FdUMP is also incorporated into RNA which results in fluorination of RNA. The effect of fluorouracil on living cells is limited mainly to those in the proliferative phase but while cells in the G2 and S phase are most affected there may be effects at any stage of the cell cycle.

Intravenous 5-fluorouracil can be delivered by rapid intravenous bolus injection or slow infusion. The vial contents can rapidly be injected directly into a peripheral vein, the commonest schedules being: 12-13.5 mg/Kg (500 mg/m2) daily for 5 days repeated at 4-weekly intervals. Slow intravenous infusion requires the drug, to be diluted in 500 ml of dextrose 5% solution, then infused over 2-3 hr on 5 successive days.

For palliative management of cancer: Initial Dose: 12 mg/kg intravenously once daily for 4 successive days. Maximum Dose: 800 mg/day. If no toxicity is observed, 6 mg/kg may be administered on the 6th, 8th, 10th, and 12th day (No therapy is given on days 5, 7, 9, or 11). Discontinue at the end of day 12, even with no apparent toxicity.

Poor risk patients and those who are not in an adequate nutritional state: Initial Dose: 6 mg/kg/day for 3 days. Maximum Dose: 400 mg/day. If no toxicity is observed, 3 mg/kg may be administered on days 5, 7, and 9 (No therapy is to be administered on days 4, 6, or 8). Discontinue at the end of day 9, even with no apparent toxicity.

Maintenance therapy: In instances where toxicity has not been a problem, it is recommended that therapy be continued using either of the following schedules:

• Repeat the dosage of the first course every 30 days after the last day of the previous course, or
• When the toxic signs resulting from the initial course of therapy have subsided, administer a maintenance dose of 10 to 15 mg/kg/week as a single dose. Maximum Dose: 1g/week .The reaction by the patient to the previous course of therapy should be taken into account and the dosage should be adjusted accordingly.

Usual adult dose for cervical cancer: In combination with cisplatin 1 gm/m2 IV on day 1. The cycle is repeated every 21 days.

Usual pediatric dose for malignant disease: The manufacturer has reported that the safety and effectiveness of fluorouracil have not been established in children. However, the drug has been used in children following adult guidelines.

Intra-arterial infusion: Fluorouracil has also been given by intra-arterial infusion for adult in doses of 5 to 7.5 mg/kg body weight is dissolved in 20-100 ml of 5% Dextrose solution and administered 10-20 days by using an infusion pump.

Combination with radiation: Usual adult daily dose of 5-10 mg/kg body weight is given in combination with radiation according to systemic administration method or intra-arterial infusion method.

Combination with other anticancer drugs: Fluorouracil is used alone or in combination in the adjuvant treatment of breast and gastro-intestinal cancer, and palliation of inoperable malignant neoplasms, especially those of the gastro-intestinal tract, breast, head and neck, liver, genito-urinary system, and pancreas. It is also used with cyclophosphamide and methotrexate in the combination chemotherapy of breast cancer. A usual adult dose of 5 to 10 mg/kg body weight daily is given in combination with other anticancer drugs every day or intermittently once to twice a week by systemic administration method or intra-arterial infusion method.

Potentially life-threatening effects: Severe effects from 5-fluorouracil are related to the dosage and duration of therapy.

Cardiac effects: Occasional case reports associating 5-fluorouracil therapy with 'ischemic cardiac events' evidence against the autoimmune phenomenon is the fact that in several cases cardiotoxicity occurred within several hours of the first dose.

Hematological effects: Potentially lethal effects caused by severe hematological toxicity may develop within the first 10 days of treatment being instituted but generally resolves within 3 weeks. At the recommended dose and schedule it is rather uncommon for hematological toxicity to be severe. Any ontribute to severe effects from 5-fluorouracil on the blood-forming cells. Thus extensive prior irradiation or the concomitant use of cytotoxic drugs tend to exacerbate the severity of the hematological side effects of 5-fluorouracil.

Neurological effects: Effects on the central nervous system have been occasionally reported and cerebral ataxia is dose-dependent with an incidence of between 3.1 and 7%. Acute cerebellar syndromes and myelopathy have been described following intrathecal 5-fluorouracil. Neurological syndromes may occur rarely after carotid artery perfusion in head and neck cancer. Other effects Allergic reaction (including difficulty in breathing, closing of the throat, swelling of the lips, tongue, or face, or hives), decreased bone marrow function and blood problems (extreme fatigue, easy bruising or bleeding, black, bloody or tarry stools, or fever, chills, or signs of infection), hand-foot syndrome (tingling, pain, redness, swelling or tenderness of the hands and feet), severe vomiting, diarrhoea, frequent bowel movements or watery stools, or sores in the mouth or throat, or stomach pain or heartburn or black, bloody or tarry stools. Other less serious side effects may include mild to moderate nausea, vomiting or loss of appetite, balance problems, confusion, rash and itching, or temporary hair loss. Conjunctivitis, both acute and chronic can proceed to tear duct stenosis and ectropion following prolonged administration. Very chronic administration, extending beyond 3 months, of low dosage has been associated with low systemic toxicity but includes the possibility of painful and tender hands and feet associated with erythema of the extremities.

It is contraindicated in patients that are severely debilitated or in patients with bone marrow suppression due to either radiotherapy or chemotherapy. It is likewise contraindicated in pregnant or breastfeeding women. It should also be avoided in patients that do not have malignant illnesses.

5-fluorouracil is highly toxic drug with a narrow margin of safety. Therefore patients should be carefully supervised, since therapeutic response is unlikely to occur without some evidence of toxicity. Daily dose should not exceed 1 gram. Treatment should be discontinued promptly when one of the following signs of toxicity appears: Leucopenia (WBC under 3500/mm3). Thrombocytopenia (platelet under 100000/mm3). Stomatitis ( the first small ulceration at the inner margin of the lips is a signal for stopping treatment). Severe diarrhoea (frequent bowel movements and watery stools). Gastro-intestinal ulceration and bleeding.

Pre-treatment with cimetidine for 4 weeks led to increased plasma concentrations of fluorouracil following intravenous and oral administration in 6 patients. The effect was probably due to a combination of hepatic enzyme inhibition and reduced hepatic blood flow.

Fluorouracil is contraindicated throughout pregnancy. The literature pertaining to pregnancy and cytotoxic drugs is necessarily limited but it appears in general that risk of teratogenesis diminishes with the advancement of pregnancy. Therefore most cytotoxic drugs are absolutely contraindicated in the first trimester and 5-fluorouracil, used in the first trimester has been reported to cause multiple congenital abnormalities. There are many case reports, however, of pregnancy being conducted successfully with combination chemotherapy being given to the mother during the second and third trimesters. Because of the age of the population and the natural history of the tumors treated, most of the data on long-term follow-up pertain to therapy for leukemias. More data need to be accrued on the subsequent development of neonates before it is certain that any of these compounds are free of late effects.

It is not known whether fluorouracil is excreted in human milk. Because fluorouracil inhibits DNA, RNA and protein synthesis, mothers should not nurse while receiving this drug.

Neonates: No dosage recommendations are made for neonates.

Children: Safety and effectiveness in children have not been established.

The elderly: No special precautions are required, doses being adjusted for the patient's weight and height.

Cases of deliberate overdose are unknown but excessive toxicity because of the hematological effects as described above. There is no specific antidote to 5-fluorouracil toxicity; treatment consists in supportive care. In addition to the hematological toxicity other toxicities will occur with overdose. Sign and symptoms are qualitatively similar to the side effects. Treatment should be performed promptly and appropriate drugs are given to control symptoms of overdose.

5-Fluorouracil is a cytotoxic anticancer drug and, caution should be exercised in handling 5-Fluorouracil. Special, trained personnel should reconstitute the drug. Preparation requires a room reserved for this purpose. The work surface should be covered with disposable plastic-backed absorbent paper. Smoking, eating and drinking are prohibited in the room. The handling staff must have a set of appropriate equipment, particularly long-sleeved coats, protective masks, caps, protective goggles, sterile disposable gloves, worktop protection sheets and waste collection containers and bags. If 5-Fluorouracil solution contacts the skin, wash the skin immediately and thoroughly with soap and water. Following topical exposure, events have included tingling, burning and redness. If 5-Fluorouracil contacts mucous membranes, the membranes should be flashed thoroughly with water. Pregnant women must be warned and avoid handling cytotoxic agents. All broken containers must be treated with the same precautions and regarded as contaminated waste. Contaminated waste is to be disposed of by incineration in rigid containers labeled for this purpose or must be destroyed as per the government rules.

Store the vial in original carton not exceeding 25℃. Do not refrigerate. Protect from light.

Cough suppressant

Butamirate Citrate acts directly on the brain's cough center to suppress cough. Butamirate Citrate is safe and non-sedating which is neither chemically nor pharmacologically related to opium alkaloids. Butamirate Citrate is rapidly and completely absorbed after oral administration. Maximum concentration is reached within 9 hours with the sustained-release tablet. This is extremely protein-bound and plasma elimination half-life is about 13 hours. The active metabolites of Butamirate Citrate have also antitussive action.

Use in adult:

• Butamirate Citrate 50 mg tablet: 2-3 tablets daily.
• Butamirate Citrate syrup: 15 ml 4 times daily.

Use in children & adolescents:
Butamirate Citrate 50 mg tablet:

• Adolescent over 12 years old: 1-2 tablets daily.

Butamirate Citrate syrup:

• Children (3-6 yrs): 5 ml 3 times daily.
• Children (6-12 yrs): 10 ml 3 times daily.
• Adolescent: 15 ml 3 times daily.

Butamirate Citrate pediatric drops:

• Children ( 2 months- 1 yrs): 0.50 ml 4 times daily.
• Children (1-3 yrs): 0.75 ml 4 times daily.

Tolerance of Butamirate Citrate is good.Adverse reactions such as rash,nausea,diarrhoea and vertigo have been observed in a few rare cases,resolving after dose reduction or treatment withdrawal.

Hypersensitivity to the active ingredient.

Butamirate Citrate suppresses the cough reflex and therefore the concomitant use with expectorants should be avoided, since it may lead to mucus retention in the airways, which increases the risk of bronchospasm and respiratory infections. If the cough persists for more than 7 days (more than 3 days in children younger than12 years of age) doctor must be consulted.

Concomitant use with expectorants should be avoided.

Butamirate Citrate should not be used during the first trimester of pregnancy. During the remainder of pregnancy, it can be used if indicated by a physician but with caution. As a general rule, for safety reasons, in the absence of data on elimination of the active substance in breast milk, the benefits of Butamirate Citrate administration during breast feeding should be carefully weighed against the risks.

Accidental overdose with Butamirate Citrate can cause the following symptoms: drowsiness, nausea, vomiting, diarrhoea, loss of balance and hypotension. Standard emergency procedures should be followed: activated charcoal, saline laxatives and standard cardio-respiratory resuscitation.

Keep away from light and moisture, store below 30°C. Keep all the medicines out of the reach of children.

It is used as a lubricant to relieve irritation and discomfort due to dryness of the eye or due to exposure to wind or sun.

Carboxymethylcellulose binds to the surface of corneal epithelial cells via its glucopyranose subunits binding to glucose receptors GLUT-1. The residence time of carboxymethylcellulose bound to corneal cells is approximately 2 hours as indicated by a short-term binding assay. Binding of carboxymethylcellulose to the matrix proteins stimulated corneal epithelial cell attachment, migration, and re-epithelialization of corneal wounds.

This eye drop contains Carboxymethylcellulose Sodium similar to normal tears which acts as an ocular lubricant. It provides a lubricating and hydrating protective shield on the ocular surface.

Instill 1 drop in the affected eye(s) 4 times a day or as needed.

Burning, Eye Irritation or Pruritus, Visual disturbance, Ocular discharge were reported with this eye drop.

This eye drop is contraindicated in patients with known hypersensitivity to any ingredient of the product.

Concomitant ocular medication should be administered 15 minutes prior to the instillation of this eye drop.

Not known.

Safe use during pregnancy and lactation has not been established.

Pediatric use: This eye drop should not be used in infants and small children under 3 years.

Geriatric use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

The drug is to be used within 30 days after the first opening. Store at temperature not exceeding 30°C in a dry place. Protect from light. The bottle is to be closed strongly immediately after use. Keep away from the reach of children.

Proton Pump Inhibitor

Dexlansoprazole delayed-release capsule is a Proton Pump Inhibitor (PPI) which suppresses gastric acid secretion by specific inhibition of the (H⁺/K⁺)-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Dexlansoprazole blocks the final step of acid production. It is the R-enantiomer of lansoprazole (A racemic mixture of the R- and S-enantiomers). Dexlansoprazole is supplied as a Dual Delayed Release (DDR) formulation in a capsule for oral administration. This capsule contains a mixture of two types of enteric coated granules with different pH-dependent dissolution profiles. The dual delayed release formulation in dexlansoprazole, plasma concentration-time profile with two distinct peaks; the first peak occurs 1 to 2 hours after administration, followed by a second peak within 4 to 5 hours. After oral administration, mean C_max and AUC value of Dexlansoprazole increased approximately dose proportionally. Dexlansoprazole is extensively metabolized in the liver and excreated by urine.

Dexlansoprazole dosing recommendations-

• Maintenance of Healed erosive esophagitis and relief of heartburn: 30 mg Once daily
• Symptomatic Non-Erosive GERD: 30 mg Once daily for 4 weeks
• Healing of erosive esophagitis: 60 mg Once daily for up to 8 weeks

Dexlansoprazole can be taken without regard to food. It should be swallowed whole.

Alternatively, Dexlansoprazole capsules can be administered as follows:

• Open capsule
• Sprinkle intact granules on one tablespoon
• Swallow immediately.

Granules should not be chewed.

If a capsule is missed at its usual time, it should be taken as soon as possible. But if it is too close to the time of the next dose, only the prescribed dose should be taken at the appointed time. A double dose should not be taken.

Common side effects: Diarrhea, abdominal pain, nausea, vomiting & flatulence.

Dexlansoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation.

Gastric Malignancy, Clostridium difficile Associated Diarrhea, Bone fracture, Hypomagnesemia, and concomitant use of Dexlansoprazole with Methotrexate.

With medicine: Atazanavir, Warfarin, Tacrolimus, Clopidogrel & Methotrexate. With food & others: No data available.

Pregnancy Category B. There is no adequate and well-controlled studies with Dexlansoprazole in pregnant women. There is no adequate and well-controlled studies with Dexlansoprazole in Lactating mother.

Use in children & adolescents: Safety and effectiveness of Dexlansoprazole in patients below 12 years age have not been established.

Geriatric use: No dose adjustment is necessary for elderly patients.

Renal impairment: No dose adjustment of Dexlansoprazole is necessary for patients with renal
impairment.

Hepatic impairment: No dose adjustment for Dexlansoprazole is necessary for patients with mild hepatic impairment. A maximum daily dose of Dexlansoprazole 30 mg should be considered for patients with moderate hepatic impairment.

There have been no reports of a significant overdose of Dexlansoprazole. Multiple doses of Dexlansoprazole 120 mg and a single dose of Dexlansoprazole 300 mg did not result in death or other severe adverse events.

Store below 30°C temperature & in a dry place, protected from light. Keep all medicines out of reach of children.

Proton Pump Inhibitor

Dexlansoprazole delayed-release capsule is a Proton Pump Inhibitor (PPI) which suppresses gastric acid secretion by specific inhibition of the (H⁺/K⁺)-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Dexlansoprazole blocks the final step of acid production. It is the R-enantiomer of lansoprazole (A racemic mixture of the R- and S-enantiomers). Dexlansoprazole is supplied as a Dual Delayed Release (DDR) formulation in a capsule for oral administration. This capsule contains a mixture of two types of enteric coated granules with different pH-dependent dissolution profiles. The dual delayed release formulation in dexlansoprazole, plasma concentration-time profile with two distinct peaks; the first peak occurs 1 to 2 hours after administration, followed by a second peak within 4 to 5 hours. After oral administration, mean C_max and AUC value of Dexlansoprazole increased approximately dose proportionally. Dexlansoprazole is extensively metabolized in the liver and excreated by urine.

Dexlansoprazole dosing recommendations-

• Maintenance of Healed erosive esophagitis and relief of heartburn: 30 mg Once daily
• Symptomatic Non-Erosive GERD: 30 mg Once daily for 4 weeks
• Healing of erosive esophagitis: 60 mg Once daily for up to 8 weeks

Dexlansoprazole can be taken without regard to food. It should be swallowed whole.

Alternatively, Dexlansoprazole capsules can be administered as follows:

• Open capsule
• Sprinkle intact granules on one tablespoon
• Swallow immediately.

Granules should not be chewed.

If a capsule is missed at its usual time, it should be taken as soon as possible. But if it is too close to the time of the next dose, only the prescribed dose should be taken at the appointed time. A double dose should not be taken.

Common side effects: Diarrhea, abdominal pain, nausea, vomiting & flatulence.

Dexlansoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation.

Gastric Malignancy, Clostridium difficile Associated Diarrhea, Bone fracture, Hypomagnesemia, and concomitant use of Dexlansoprazole with Methotrexate.

With medicine: Atazanavir, Warfarin, Tacrolimus, Clopidogrel & Methotrexate. With food & others: No data available.

Pregnancy Category B. There is no adequate and well-controlled studies with Dexlansoprazole in pregnant women. There is no adequate and well-controlled studies with Dexlansoprazole in Lactating mother.

Use in children & adolescents: Safety and effectiveness of Dexlansoprazole in patients below 12 years age have not been established.

Geriatric use: No dose adjustment is necessary for elderly patients.

Renal impairment: No dose adjustment of Dexlansoprazole is necessary for patients with renal
impairment.

Hepatic impairment: No dose adjustment for Dexlansoprazole is necessary for patients with mild hepatic impairment. A maximum daily dose of Dexlansoprazole 30 mg should be considered for patients with moderate hepatic impairment.

There have been no reports of a significant overdose of Dexlansoprazole. Multiple doses of Dexlansoprazole 120 mg and a single dose of Dexlansoprazole 300 mg did not result in death or other severe adverse events.

Store below 30°C temperature & in a dry place, protected from light. Keep all medicines out of reach of children.

Indicated in acne vulgaris.

Benzoyl peroxide, Azelaic acid & other preparations

Clindamycin is a semi-synthetic derivative of lincomycin. It inhibits bacterial protein synthesis by reversibly binding to the 50S ribosomal subunits thus blocking the transpeptidation or translocation reactions of susceptible organisms.

Benzoyl peroxide has mild keratolytic effect and antimicrobial activity which is attributed to its potent oxidizing activity. Clindamycin and Benzoyl peroxide are both active against Propionibacterium acnes, an organism associated with acne vulgaris.

Apply to the affected areas once or twice daily (morning and evening) after the skin is gently washed and patted dry.

Application site pain, Application site exfoliation, Application site irritation, Erythema, Burning, Pruritus, Sunburn, Scaling, Drynes, Colitis, Peelin.

Hypersensitivity to Clindamycin, lincomycin, benzoyl peroxide, or any component of the formulation; history of regional enteritis, ulcerative colitis, pseudomembranous colitis or antibiotic-associated colitis.

Avoid contact with mouth, eyes, lips & mucous membranes; abraded or eczematous skin. May discolor hair & dyed fabrics. Pregnancy & lactation.

May enhance the action of neuromuscular blocking agents (e.g. atracurium). May antagonise the effects of parasympathomimetics. May competitively inhibit the effects of macrolides, ketolides, streptogramins, linezolid and chloramphenicol. Increased coagulation tests (prothrombin time/INR) and/or bleeding with vit K antagonists (e.g. warfarin, acenocoumarol, fluindione). PABA sunscreens may transiently discolour fabric.

Pregnancy Category- C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Lactation: Excretion in milk is unknown/ not recommended

Refer to individual product recommendations. Some combination products require reconstitution at the time of dispensing by dissolving the Clindamycin powder with purified water, add the solution to the Benzoyl peroxide gel provided and stir until the gel appears homogenous.

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.

Ledipasvir and Sofosbuvir combination is indicated for the treatment of chronic hepatitis C (CHC) genotype 1, 4 & 6 infection in adults.

Hepatic viral infections (Hepatitis C)

It is a fixed-dose combination tablet containing Ledipasvir and Sofosbuvir for oral administration. Ledipasvir is an HCV NS5A inhibitor and Sofosbuvir is a nucleotide analog inhibitor of HCV NS5B polymerase.

Recommended dosage: One tablet (90 mg of Ledipasvir and 400 mg of Sofosbuvir) taken orally once daily with or without food

Recommended treatment duration:

• Treatment-naive with or without cirrhosis: 12 weeks
• Treatment-experienced without cirrhosis: 12 weeks
• Treatment-experienced with cirrhosis: 24 weeks

A dose recommendation cannot be made for patients with severe renal impairment or end stage renal disease.

The most common adverse reactions with treatment with Ledipasvir and Sofosbuvir combination for 8, 12, or 24 weeks are fatigue and headache.

This combination is contraindicated in patients with Known hypersensitivity to Ledipasvir, Sofosbuvir or any other ingredient in the product.

Bradycardia with Amiodarone coadministration: Serious symptomatic bradycardia may occur in patients taking Amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of Amiodarone with Ledipasvir and Sofosbuvir combination is not recommended. In patients without viable treatment options, cardiac monitoring is recommended.

Use with other drugs containing sofosbuvir, is not recommended

Pregnancy Category B. There are no adequate and well-controlled studies with Ledipasvir and Sofosbuvir in pregnant women. Because animal reproduction studies are not always predictive of human response, this should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether Ledipasvir and Sofosbuvir and its metabolites are present in human breast milk.

Pediatric Use: Safety and effectiveness of Ledipasvir and Sofosbuvir have not been established in pediatric patients.

Geriatric Use: No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. No dosage adjustment of Ledipasvir and Sofosbuvir is warranted in geriatric patients.

No specific antidote is available for overdose

Keep out of the reach of children. Keep in a cool & dry place. Protect from light.