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Proton Pump Inhibitor

Rabeprazole suppresses gastric acid secretion by inhibiting the gastric H⁺/K⁺-ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, Rabeprazole has been characterized as a gastric proton-pump inhibitor.

Active Duodenal Ulcer and Active Benign Gastric Ulcer: The recommended oral dose for both bioactive duodenal ulcer and active benign gastric ulcer is 20 mg to be taken once daily in the morning. Most patients with active duodenal ulcer heal within four weeks. However, a few patients may require an additional four weeks of therapy to achieve healing. Most patients with active benign gastric ulcer heal within six weeks. However, again a few patients may require an additional six weeks of therapy to achieve healing.

Erosive or Ulcerative Gastro-Esophageal Reflux Disease (GERD): The recommended oral dose for this condition is 20 mg to be taken once daily for four to eight weeks.

Gastro-Esophageal Reflux Disease Long-term Management (GERD Maintenance): For long-term management, a maintenance dose of rabeprazole sodium 20 mg or 10 mg once daily can be used depending upon patient response.

Symptomatic treatment of moderate to very severe Gastro-Esophageal Reflux Disease (symptomatic GERD): 10 mg once daily in patients without oesophagitis. If symptom control has not been achieved during four weeks, the patient should be further investigated. Once symptoms have resolved, subsequent symptom control can be achieved using an on-demand regimen taking 10 mg once daily when needed.

Treatment of GERD in pediatric patients 1 to 11 years of age (Less than 15 kg): 5 mg once daily for 12 weeks with the option to increase to 10 mg if inadequate response.

Treatment of GERD in pediatric patients 1 to 11 years of age (15 kg or more): 10 mg once daily for 12 weeks. 

Zollinger-Ellison Syndrome: The recommended adult starting dose is 60 mg once a day. The dose may be titrated upwards to 120 mg/day based on individual patient needs. Single daily doses up to 100 mg/day may be given. 120 mg dose may require divided doses, 60 mg twice daily. Treatment should continue for as long as clinically indicated.

Eradication of H. pylori: Patients with H. pylori infection should be treated with eradication therapy. The following combination given for 7 days is recommended. Rabeprazole sodium 20 mg twice daily, clarithromycin 500 mg twice daily and amoxicillin 1g twice daily.

For indications requiring once-daily treatment Rabeprazole tablets should be taken in the morning, before eating; and although neither the time of day nor food intake was shown to have any effect on rabeprazole sodium activity, this regimen will facilitate treatment compliance. Patients should be cautioned that the Rabeprazole tablets should not be chewed or crushed, but should be swallowed whole.

In general, Rabeprazole is well-tolerated in both short-term and long-term studies. Rabeprazole may sometimes cause headache, diarrhoea, abdominal pain, vomiting, constipation, dry mouth, increased or decreased appetite, muscle pain, drowsiness, dizziness.

Hypersensitivity to the active substance or to any of the excipients. Rabeprazole is contra-indicated in pregnancy and during breastfeeding.

• Symptomatic response to therapy with Rabeprazole does not preclude the presence of gastric or oesophageal malignancy, therefore the possibility of malignancy should be excluded prior to commencing treatment with Rabeprazole 20 mg Gastro-resistant Tablets.
• Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance.
• Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10–40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care and they should have an adequate intake of vitamin D and calcium.
• A risk of cross-hypersensitivity reactions with other proton pump inhibitor or substituted benzimidazoles cannot be excluded.
• Patients should be cautioned that Rabeprazole gastro-resistant tablets should not be chewed or crushed, but should be swallowed whole.
• There have been post marketing reports of blood dyscrasias (thrombocytopenia and neutropenia). In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole.
• Hepatic enzyme abnormalities have been seen in clinical trials and have also been reported since market authorisation. In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole.
• No evidence of significant drug related safety problems was seen in a study of patients with mild to moderate hepatic impairment versus normal age and sex matched controls. However because there are no clinical data on the use of rabeprazole in the treatment of patients with severe hepatic dysfunction the prescriber is advised to exercise caution when treatment with Rabeprazole 20mg Gastro-resistant. Tablets is first initiated in such patients.
• Co-administration of atazanavir with Rabeprazole is not recommended.
• Treatment with proton pump inhibitors, including rabeprazole, may possibly increase the risk of gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile.

Hypomagnesaemia: Severe hypomagnesaemia has been reported in patients treated with PPIs like rabeprazole for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

Influence on vitamin B12 absorption: Rabeprazole sodium, as all acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or a- chlorhydria. This should be considered in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if respective clinical symptoms are observed.

Subacute cutaneous lupus erythematosus (SCLE): Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping Rabeprazole. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.

Interference with laboratory tests: Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, Rabeprazole 20mg Gastro-resistant Tablets treatment should be stopped for at least 5 days before CgA measurements. If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.

Respite produces a profound and long-lasting inhibition of gastric acid secretion. An interaction with a compound whose absorption is pH dependent may occur. Co-administration of rabeprazole sodium with ketoconazole or itraconazole may result in a significant decrease in antifungal plasma levels. Therefore individual patients may need to be monitored to determine if a dosage adjustment is necessary when ketoconazole or itraconazole are taken concomitantly with Respite. No interaction with liquid antacids was observed. The absorption of atazanavir is pH-dependent. Therefore PPIs, including rabeprazole, should not be co-administered with atazanavir.

US FDA pregnancy category 'C'. Studies have been performed in animals and have revealed no evidence of impaired fertility or harm to the fetus due to Rabeprazole. There are however, no adequate and well-controlled studies in pregnant women. Rabeprazole is likely to be excreted in human milk, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Renal and hepatic impairment: No dosage adjustment is necessary for patients with renal or hepatic impairment.

Pediatric populations: Rabeprazole is not recommended for use in children due to a lack of data on safety and efficacy.

The maximum established exposure has not exceeded 60 mg twice daily, or 160 mg once daily. Effects are  generally minimal, representative of the known adverse event profile and reversible without further medical intervention. No specific antidote is known. Rabeprazole is extensively protein bound and is, therefore, not dialysable. As in any case of overdose, treatment should be symptomatic and general supportive measures should be utilised.

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

Motility Stimulants, Motility stimulants/Dopamine antagonist, Prokinetic drugs

Domperidone is a dopamine antagonist that principally blocks the dopamine receptors located in the ChemoreceptorTrigger Zone (CTZ) and stomach. Its gastroprokinetic action is based on its blocking effect of dopamine receptors that have an influence on the motility of the gastrointestinal tract. Due to its weak penetration across the blood-brain barrier, Domperidone has almost no effect on the dopaminergic receptors in the brain, therefore, excluding psychotropic and neurologic side effects. Domperidone restores normal motility and tone of the upper gastrointestinal tract, facilitates gastric emptying, enhances antral and duodenal peristalsis and regulates contraction of the pylorus. Domperidone also increases esophageal peristalsis and lower esophageal sphincter pressure, and thus prevents regurgitation of gastric content.

Domperidone should be taken 15-30 minutes before meals and, if necessary, before retiring.

The usual recommended oral dose of Domperidone is as follows:

• Adults: 10-20 mg (1-2 tablet or 10-20 ml suspension), every 6-8 hours daily. The maximum dose of Domperidone is 80 mg daily.
• Children: 2-4 ml suspension/10 kg body weight or 0.4-0.8 ml paediatric drops/10 kg body weight, every 6-8 hours daily.

In dyspeptic symptom:

• Adults: 10-20 mg (1-2 tablet or 10-20 ml suspension), every 6-8 hours daily.
• Children: 0.2-0.4 mg/kg (2-4 ml suspension/10 kg or 0.4-0.8 ml paediatric drops/10 kg) body weight, every 6-8 hours daily.

In acute and sub-acute conditions (mainly in acute nausea and vomiting):

• Adults: 20 mg (2 tablets or 20 ml suspension), every 6-8 hours daily
• Children: 0.2-0.4 mg/kg (2-4 ml suspension/10 kg or 0.4-0.8 ml paediatric drops/10 kg) body weight, every 6-8 hours daily. (In acute nausea and vomiting maximum period of treatment is 12 weeks).

By rectum in suppositories:

• Adults (including elderly): 30-60 mg every 4-8 hours.
• Children: The maximum daily dose rectally in children's is 30 mg for those weighting 10 to 25 kg. The dose may be divided throughout day if necessary.
• The maximum period of treatment is 12 weeks.

Domperidone may produce hyperprolactinemia (1.3%).This may result in galactorrhea, breast enlargement, and soreness and reduced libido. Dry mouth (1%), thirst, headache (1.2%), nervousness, drowsiness (0.4%), diarrhea (0.2%), skin rash and itching (0.1%) may occur during treatment with domperidone. Extra-pyramidal reactions are seen in 0.05% of patients in clinical studies.

Domperidone is contraindicated to patients having known hypersensitivity to this drug and in the case of neonates. Domperidone should not be used whenever gastrointestinal stimulation might be dangerous i.e., gastrointestinal hemorrhage, mechanical obstruction or perforation. Also contraindicated in patients with prolactin releasing pituitary tumor (prolactinoma).

Domperidone should be used with absolute caution in the case of children because there may be an increased risk of extra-pyramidal reactions in young children because of an incompletely developed blood-brain barrier. Since domperidone is highly metabolized in liver, it should be used with caution in patient with hepatic impairment.

Domperidone may reduce the risk of hypoprolactemic effect of bromocriptine. The action of Domperidone on Gl function may be antagonized by antimuscarinics and opoid analgesics. Care should be exercised when domperidone is administered in combination with MAO (monoamine oxidase) inhibitors.

The safety of domperidone has not been proven and it is therefore not recommended during pregnancy. Animal studies have not demonstrated the teratogenic effect in the fetus. Domperidone may precipitate galactorrhea and improve post-natal lactation. It is secreted in breast milk but in very small quantities insufficient to be considered harmful.

There are no reported cases of overdose.

Store below 30°C, Protected from light & moisture. Keep out of children's reach.

Motility Stimulants, Motility stimulants/Dopamine antagonist, Prokinetic drugs

Domperidone is a dopamine antagonist that principally blocks the dopamine receptors located in the ChemoreceptorTrigger Zone (CTZ) and stomach. Its gastroprokinetic action is based on its blocking effect of dopamine receptors that have an influence on the motility of the gastrointestinal tract. Due to its weak penetration across the blood-brain barrier, Domperidone has almost no effect on the dopaminergic receptors in the brain, therefore, excluding psychotropic and neurologic side effects. Domperidone restores normal motility and tone of the upper gastrointestinal tract, facilitates gastric emptying, enhances antral and duodenal peristalsis and regulates contraction of the pylorus. Domperidone also increases esophageal peristalsis and lower esophageal sphincter pressure, and thus prevents regurgitation of gastric content.

Domperidone should be taken 15-30 minutes before meals and, if necessary, before retiring.

The usual recommended oral dose of Domperidone is as follows:

• Adults: 10-20 mg (1-2 tablet or 10-20 ml suspension), every 6-8 hours daily. The maximum dose of Domperidone is 80 mg daily.
• Children: 2-4 ml suspension/10 kg body weight or 0.4-0.8 ml paediatric drops/10 kg body weight, every 6-8 hours daily.

In dyspeptic symptom:

• Adults: 10-20 mg (1-2 tablet or 10-20 ml suspension), every 6-8 hours daily.
• Children: 0.2-0.4 mg/kg (2-4 ml suspension/10 kg or 0.4-0.8 ml paediatric drops/10 kg) body weight, every 6-8 hours daily.

In acute and sub-acute conditions (mainly in acute nausea and vomiting):

• Adults: 20 mg (2 tablets or 20 ml suspension), every 6-8 hours daily
• Children: 0.2-0.4 mg/kg (2-4 ml suspension/10 kg or 0.4-0.8 ml paediatric drops/10 kg) body weight, every 6-8 hours daily. (In acute nausea and vomiting maximum period of treatment is 12 weeks).

By rectum in suppositories:

• Adults (including elderly): 30-60 mg every 4-8 hours.
• Children: The maximum daily dose rectally in children's is 30 mg for those weighting 10 to 25 kg. The dose may be divided throughout day if necessary.
• The maximum period of treatment is 12 weeks.

Domperidone may produce hyperprolactinemia (1.3%).This may result in galactorrhea, breast enlargement, and soreness and reduced libido. Dry mouth (1%), thirst, headache (1.2%), nervousness, drowsiness (0.4%), diarrhea (0.2%), skin rash and itching (0.1%) may occur during treatment with domperidone. Extra-pyramidal reactions are seen in 0.05% of patients in clinical studies.

Domperidone is contraindicated to patients having known hypersensitivity to this drug and in the case of neonates. Domperidone should not be used whenever gastrointestinal stimulation might be dangerous i.e., gastrointestinal hemorrhage, mechanical obstruction or perforation. Also contraindicated in patients with prolactin releasing pituitary tumor (prolactinoma).

Domperidone should be used with absolute caution in the case of children because there may be an increased risk of extra-pyramidal reactions in young children because of an incompletely developed blood-brain barrier. Since domperidone is highly metabolized in liver, it should be used with caution in patient with hepatic impairment.

Domperidone may reduce the risk of hypoprolactemic effect of bromocriptine. The action of Domperidone on Gl function may be antagonized by antimuscarinics and opoid analgesics. Care should be exercised when domperidone is administered in combination with MAO (monoamine oxidase) inhibitors.

The safety of domperidone has not been proven and it is therefore not recommended during pregnancy. Animal studies have not demonstrated the teratogenic effect in the fetus. Domperidone may precipitate galactorrhea and improve post-natal lactation. It is secreted in breast milk but in very small quantities insufficient to be considered harmful.

There are no reported cases of overdose.

Store below 30°C, Protected from light & moisture. Keep out of children's reach.

Tiemonium Methylsulphate is an antispasmodic drug that reduces muscles spasm of the intestine, biliary system, bladder and uterus. It is used in symptomatic treatment of pain related to functional disorders of the digestive tract and biliary system. It is also indicated for the treatment of spasm and pain in urological and gynaecological diseases.

Anticholinergics

Tiemonium Methylsulphate a competitive antagonist of Acetylcholine, Histamine and strengthens of calcium bond with membrane phospholipids and proteins. Thus inhibits intracellular contractile protein of visceral cell which causes inhibition of visceral spasm and pain.

Tablet/Syrup-

• Adult: usual dose is 2-6 tablets or 3-9 teaspoonfuls syrup daily in divided doses.
• Children: 3 ml/kg or 6 mg/kg body weight daily in divided doses.

Injection: 1 Tiemonium Methylsulphate Injection 3 times daily, through Intravenous route slowly or Intramuscular route.

Suppository: 20 mg Tiemonium Methylsulphate suppository two or three times daily, through rectal route.

Tiemonium Methylsulphate may have the risk of hypotension & tachycardia in certain individuals.

It should not be used in urethroprostatic disorder involving a risk of urine retension. It is contraindicated in patient with having risk of angle closure glaucoma.

Caution should be taken during treatment of patients with disorders of the prostate. Caution should also be taken in case of chronic bronchitis, coronary insufficiency, ambient hyperthermia, renal & hepatic insufficiency. The risks of visual disturbances can make it dangerous to drive or use machines.

Tiemonium methylsulphate tablet should not be used with other drugs without prior consult of a registered physician to avoid possible drug interaction.

The results of animal studies of Tiemonium Methylsulphate did not reveal any teratogenic effects; no deformities have been reported up till now with normal use. In absence of sufficient data, prudence should be the rule for nursing mothers although no problems have been reported with normal use.

Paediatric use: safety and effectiveness of Tiemonium methylsulphate in paediatric patients have not been established.

Geriatric use: Efficacy and safety were maintained with increasing age.

There is not available data regarding the overdose of Tiemonium methylsulphate tablet.

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

Parenteral anti-coagulants

Enoxaparin Sodium is a low molecular weight heparin with a high anti-Xa activity and low anti-lla or antithrombin activity. At doses required for the various indications, Enoxaparin Sodium does not increase bleeding time. At preventive doses, Enoxaparin Sodium causes no notable modification of activated Partial Thromboplastin Time (aPTT). It neither influences platelet aggregation nor binding of fibrinogen to platelets. Enoxaparin Sodium is primarily metabolised in the liver.

Treatment of deep vein thrombosis, with or without pulmonary embolism: Subcutaneously 100 anti-Xa lU/kg twice daily for 10 days or Subcutaneously 150 anti-Xa lU/kq once daily for 10 days. Oral anticoagulant therapy should be initiated when appropriate and Enoxaparin Sodium treatment should be continued until a therapeutic anticoaqulant effect has been achieved.

Treatment of unstable angina and non-Q-wave myocardial infarction, administered concurrently with aspirin: Subcutaneously 100 anti-Xa lU/kg twice daily for 2- 8 days. Should be administered concurrently with oral aspirin (100 to 325 mg once daily). Treatment with Enoxaparin Sodium in these patients should be prescribed fora minimum of 2 days and continued until clinical stabilization.

Prevention of thrombus formation in extra corporeal circulation during hemodialysis: Recommended dose is 100 anti-Xa lU/kg. For patients with a high risk of hemorrhage, the dose should be reduced to 50 anti-Xa lU/kg for double vascular access or 75 anti-Xa lU/kg for single vascular access. During hemodialysis, Enoxaparin Sodium should be introduced into the arterial line of the circuit at the beqinninq of the dialysis session.

Prophylaxis of venous thromboembolic disease in surgical patients:

• Patients undergoing general surgery with a moderate risk of thromboembolism (e.g. abdominal surgery): Subcutaneously 2000 anti-Xa IU (0.2 ml) or 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 2 hours before the surgical procedure.
• Patients undergoing orthopedic surgery with a high risk of thromboembolism: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 12 hours before the surgical procedure. Longer treatment duration may be appropriate in some patients like continued therapy with 4000 anti-Xa IU once daily for 3 weeks following the initial therapy has been proven to be beneficial in orthopaedic surqery.

Prophylaxis of venous thromboembolic disease in medical patients: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 6- 14 days.

Haemorrhage (bleeding), Thrombocytopenia, elevations of serum aminotransferase. Pain, bluish marks at injection sites to skin rash at injection sites. Cases of neuraxial hematomas with the concurrent use of Enoxaparin and spinal/epidural anesthesia or spinal puncture have resulted in varying degrees of neurologic injuries.

Patients with known hypersensitivity to Enoxaparin Sodium, heparin or other low molecular weight heparins. Patients with active major bleeding and conditions with a high risk of uncontrolled hemorrhage including recent hemorrhagic stroke.

Enoxaparin Sodium should be injected by deep subcutaneous route in prophylactic and curative treatment and by intravascular route during hemodialysis. Do not administer by the intramuscular route. Enoxaparin Sodium should be used with caution in conditions with increased potential for bleeding, such as impaired hemostasis, history of peptic ulcer, recent ischemic stroke, uncontrolled severe arterial hypertension, diabetic retinopathy and recent neuro- or ophthalmologic surgery, concomitant use of medications affecting hemostasis. It is recommended that the platelet counts be measured before the initiation of the treatment and regularly thereafter during treatment.

It is recommended that agents which affect hemostasis should be discontinued prior to Enoxaparin Sodium therapy unless strictly indicated. These agents include medications such as: acetylsalicylic acid (and derivatives), NSAIDs (including ketorolac), ticlopidine,clopidogrel,dextran 40,glucocorticoids, thrombolytics and anticoagulants, other antiplatelet aggregation agents including glycoprotein llb/llla antagonists. If the combination is indicated, should be used with careful clinical and laboratory monitoring.

Pregnancy category B. In humans, there is no evidence that Enoxaparin Sodium crosses the placental barrier. As there are no adequate and well-controlled studies in pregnant women, Enoxaparin Sodium should be used during pregnancy only if clearly needed. Pregnant women with mechanical prosthetic heart valves may be at a higher risk for thromboembolism.

It is not known whether Enoxaparin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue Enoxaparin, taking into account the importance of Enoxaparin to the mother and the known benefits of nursing.

Dose in Elderly Patients: No dosage adjustment is necessary, unless kidney function is impaired.

Dose in Renal Impairment: Although no dosage adjustment is recommended in patients with moderate (creatinine clearance: 30-50 ml/min) and mild (creatinine clearance: 50 80 ml/min) renal impairment, all such patients should be observed carefully for signs and symptoms of bleeding. For patients with severe (creatinine clearance <30 ml/min) renal impairment, following dosage adjustments are recommended: Prophylactic dose ranges: 2000 antiXa IU once daily; Therapeutic dose ranges: 100 anti-Xa lU/kg once daily.

Dose in Hepatic Impairment: Caution should be used in hepatically impaired patients.

Accidental overdosage following administration of Enoxaparin may lead to hemorrhagic complications. Injected Enoxaparin may be largely neutralized by the slow i.v. injection of protamine sulfate (1% solution) The dose of protamine sulfate should be equal to the dose of Enoxaparin injected: 1 mg protamine sulfate should be administered to neutralize 1 mg Enoxaparin.

Store in a cool and dry place, protect from light and moisture. Do not store above 25°C. Do not store in a refrigerator or freezer. Keep out of the reach of children

Parenteral anti-coagulants

Enoxaparin Sodium is a low molecular weight heparin with a high anti-Xa activity and low anti-lla or antithrombin activity. At doses required for the various indications, Enoxaparin Sodium does not increase bleeding time. At preventive doses, Enoxaparin Sodium causes no notable modification of activated Partial Thromboplastin Time (aPTT). It neither influences platelet aggregation nor binding of fibrinogen to platelets. Enoxaparin Sodium is primarily metabolised in the liver.

Treatment of deep vein thrombosis, with or without pulmonary embolism: Subcutaneously 100 anti-Xa lU/kg twice daily for 10 days or Subcutaneously 150 anti-Xa lU/kq once daily for 10 days. Oral anticoagulant therapy should be initiated when appropriate and Enoxaparin Sodium treatment should be continued until a therapeutic anticoaqulant effect has been achieved.

Treatment of unstable angina and non-Q-wave myocardial infarction, administered concurrently with aspirin: Subcutaneously 100 anti-Xa lU/kg twice daily for 2- 8 days. Should be administered concurrently with oral aspirin (100 to 325 mg once daily). Treatment with Enoxaparin Sodium in these patients should be prescribed fora minimum of 2 days and continued until clinical stabilization.

Prevention of thrombus formation in extra corporeal circulation during hemodialysis: Recommended dose is 100 anti-Xa lU/kg. For patients with a high risk of hemorrhage, the dose should be reduced to 50 anti-Xa lU/kg for double vascular access or 75 anti-Xa lU/kg for single vascular access. During hemodialysis, Enoxaparin Sodium should be introduced into the arterial line of the circuit at the beqinninq of the dialysis session.

Prophylaxis of venous thromboembolic disease in surgical patients:

• Patients undergoing general surgery with a moderate risk of thromboembolism (e.g. abdominal surgery): Subcutaneously 2000 anti-Xa IU (0.2 ml) or 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 2 hours before the surgical procedure.
• Patients undergoing orthopedic surgery with a high risk of thromboembolism: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 12 hours before the surgical procedure. Longer treatment duration may be appropriate in some patients like continued therapy with 4000 anti-Xa IU once daily for 3 weeks following the initial therapy has been proven to be beneficial in orthopaedic surqery.

Prophylaxis of venous thromboembolic disease in medical patients: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 6- 14 days.

Haemorrhage (bleeding), Thrombocytopenia, elevations of serum aminotransferase. Pain, bluish marks at injection sites to skin rash at injection sites. Cases of neuraxial hematomas with the concurrent use of Enoxaparin and spinal/epidural anesthesia or spinal puncture have resulted in varying degrees of neurologic injuries.

Patients with known hypersensitivity to Enoxaparin Sodium, heparin or other low molecular weight heparins. Patients with active major bleeding and conditions with a high risk of uncontrolled hemorrhage including recent hemorrhagic stroke.

Enoxaparin Sodium should be injected by deep subcutaneous route in prophylactic and curative treatment and by intravascular route during hemodialysis. Do not administer by the intramuscular route. Enoxaparin Sodium should be used with caution in conditions with increased potential for bleeding, such as impaired hemostasis, history of peptic ulcer, recent ischemic stroke, uncontrolled severe arterial hypertension, diabetic retinopathy and recent neuro- or ophthalmologic surgery, concomitant use of medications affecting hemostasis. It is recommended that the platelet counts be measured before the initiation of the treatment and regularly thereafter during treatment.

It is recommended that agents which affect hemostasis should be discontinued prior to Enoxaparin Sodium therapy unless strictly indicated. These agents include medications such as: acetylsalicylic acid (and derivatives), NSAIDs (including ketorolac), ticlopidine,clopidogrel,dextran 40,glucocorticoids, thrombolytics and anticoagulants, other antiplatelet aggregation agents including glycoprotein llb/llla antagonists. If the combination is indicated, should be used with careful clinical and laboratory monitoring.

Pregnancy category B. In humans, there is no evidence that Enoxaparin Sodium crosses the placental barrier. As there are no adequate and well-controlled studies in pregnant women, Enoxaparin Sodium should be used during pregnancy only if clearly needed. Pregnant women with mechanical prosthetic heart valves may be at a higher risk for thromboembolism.

It is not known whether Enoxaparin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue Enoxaparin, taking into account the importance of Enoxaparin to the mother and the known benefits of nursing.

Dose in Elderly Patients: No dosage adjustment is necessary, unless kidney function is impaired.

Dose in Renal Impairment: Although no dosage adjustment is recommended in patients with moderate (creatinine clearance: 30-50 ml/min) and mild (creatinine clearance: 50 80 ml/min) renal impairment, all such patients should be observed carefully for signs and symptoms of bleeding. For patients with severe (creatinine clearance <30 ml/min) renal impairment, following dosage adjustments are recommended: Prophylactic dose ranges: 2000 antiXa IU once daily; Therapeutic dose ranges: 100 anti-Xa lU/kg once daily.

Dose in Hepatic Impairment: Caution should be used in hepatically impaired patients.

Accidental overdosage following administration of Enoxaparin may lead to hemorrhagic complications. Injected Enoxaparin may be largely neutralized by the slow i.v. injection of protamine sulfate (1% solution) The dose of protamine sulfate should be equal to the dose of Enoxaparin injected: 1 mg protamine sulfate should be administered to neutralize 1 mg Enoxaparin.

Store in a cool and dry place, protect from light and moisture. Do not store above 25°C. Do not store in a refrigerator or freezer. Keep out of the reach of children

Parenteral anti-coagulants

Enoxaparin Sodium is a low molecular weight heparin with a high anti-Xa activity and low anti-lla or antithrombin activity. At doses required for the various indications, Enoxaparin Sodium does not increase bleeding time. At preventive doses, Enoxaparin Sodium causes no notable modification of activated Partial Thromboplastin Time (aPTT). It neither influences platelet aggregation nor binding of fibrinogen to platelets. Enoxaparin Sodium is primarily metabolised in the liver.

Treatment of deep vein thrombosis, with or without pulmonary embolism: Subcutaneously 100 anti-Xa lU/kg twice daily for 10 days or Subcutaneously 150 anti-Xa lU/kq once daily for 10 days. Oral anticoagulant therapy should be initiated when appropriate and Enoxaparin Sodium treatment should be continued until a therapeutic anticoaqulant effect has been achieved.

Treatment of unstable angina and non-Q-wave myocardial infarction, administered concurrently with aspirin: Subcutaneously 100 anti-Xa lU/kg twice daily for 2- 8 days. Should be administered concurrently with oral aspirin (100 to 325 mg once daily). Treatment with Enoxaparin Sodium in these patients should be prescribed fora minimum of 2 days and continued until clinical stabilization.

Prevention of thrombus formation in extra corporeal circulation during hemodialysis: Recommended dose is 100 anti-Xa lU/kg. For patients with a high risk of hemorrhage, the dose should be reduced to 50 anti-Xa lU/kg for double vascular access or 75 anti-Xa lU/kg for single vascular access. During hemodialysis, Enoxaparin Sodium should be introduced into the arterial line of the circuit at the beqinninq of the dialysis session.

Prophylaxis of venous thromboembolic disease in surgical patients:

• Patients undergoing general surgery with a moderate risk of thromboembolism (e.g. abdominal surgery): Subcutaneously 2000 anti-Xa IU (0.2 ml) or 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 2 hours before the surgical procedure.
• Patients undergoing orthopedic surgery with a high risk of thromboembolism: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 12 hours before the surgical procedure. Longer treatment duration may be appropriate in some patients like continued therapy with 4000 anti-Xa IU once daily for 3 weeks following the initial therapy has been proven to be beneficial in orthopaedic surqery.

Prophylaxis of venous thromboembolic disease in medical patients: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 6- 14 days.

Haemorrhage (bleeding), Thrombocytopenia, elevations of serum aminotransferase. Pain, bluish marks at injection sites to skin rash at injection sites. Cases of neuraxial hematomas with the concurrent use of Enoxaparin and spinal/epidural anesthesia or spinal puncture have resulted in varying degrees of neurologic injuries.

Patients with known hypersensitivity to Enoxaparin Sodium, heparin or other low molecular weight heparins. Patients with active major bleeding and conditions with a high risk of uncontrolled hemorrhage including recent hemorrhagic stroke.

Enoxaparin Sodium should be injected by deep subcutaneous route in prophylactic and curative treatment and by intravascular route during hemodialysis. Do not administer by the intramuscular route. Enoxaparin Sodium should be used with caution in conditions with increased potential for bleeding, such as impaired hemostasis, history of peptic ulcer, recent ischemic stroke, uncontrolled severe arterial hypertension, diabetic retinopathy and recent neuro- or ophthalmologic surgery, concomitant use of medications affecting hemostasis. It is recommended that the platelet counts be measured before the initiation of the treatment and regularly thereafter during treatment.

It is recommended that agents which affect hemostasis should be discontinued prior to Enoxaparin Sodium therapy unless strictly indicated. These agents include medications such as: acetylsalicylic acid (and derivatives), NSAIDs (including ketorolac), ticlopidine,clopidogrel,dextran 40,glucocorticoids, thrombolytics and anticoagulants, other antiplatelet aggregation agents including glycoprotein llb/llla antagonists. If the combination is indicated, should be used with careful clinical and laboratory monitoring.

Pregnancy category B. In humans, there is no evidence that Enoxaparin Sodium crosses the placental barrier. As there are no adequate and well-controlled studies in pregnant women, Enoxaparin Sodium should be used during pregnancy only if clearly needed. Pregnant women with mechanical prosthetic heart valves may be at a higher risk for thromboembolism.

It is not known whether Enoxaparin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue Enoxaparin, taking into account the importance of Enoxaparin to the mother and the known benefits of nursing.

Dose in Elderly Patients: No dosage adjustment is necessary, unless kidney function is impaired.

Dose in Renal Impairment: Although no dosage adjustment is recommended in patients with moderate (creatinine clearance: 30-50 ml/min) and mild (creatinine clearance: 50 80 ml/min) renal impairment, all such patients should be observed carefully for signs and symptoms of bleeding. For patients with severe (creatinine clearance <30 ml/min) renal impairment, following dosage adjustments are recommended: Prophylactic dose ranges: 2000 antiXa IU once daily; Therapeutic dose ranges: 100 anti-Xa lU/kg once daily.

Dose in Hepatic Impairment: Caution should be used in hepatically impaired patients.

Accidental overdosage following administration of Enoxaparin may lead to hemorrhagic complications. Injected Enoxaparin may be largely neutralized by the slow i.v. injection of protamine sulfate (1% solution) The dose of protamine sulfate should be equal to the dose of Enoxaparin injected: 1 mg protamine sulfate should be administered to neutralize 1 mg Enoxaparin.

Store in a cool and dry place, protect from light and moisture. Do not store above 25°C. Do not store in a refrigerator or freezer. Keep out of the reach of children

Parenteral anti-coagulants

Enoxaparin Sodium is a low molecular weight heparin with a high anti-Xa activity and low anti-lla or antithrombin activity. At doses required for the various indications, Enoxaparin Sodium does not increase bleeding time. At preventive doses, Enoxaparin Sodium causes no notable modification of activated Partial Thromboplastin Time (aPTT). It neither influences platelet aggregation nor binding of fibrinogen to platelets. Enoxaparin Sodium is primarily metabolised in the liver.

Treatment of deep vein thrombosis, with or without pulmonary embolism: Subcutaneously 100 anti-Xa lU/kg twice daily for 10 days or Subcutaneously 150 anti-Xa lU/kq once daily for 10 days. Oral anticoagulant therapy should be initiated when appropriate and Enoxaparin Sodium treatment should be continued until a therapeutic anticoaqulant effect has been achieved.

Treatment of unstable angina and non-Q-wave myocardial infarction, administered concurrently with aspirin: Subcutaneously 100 anti-Xa lU/kg twice daily for 2- 8 days. Should be administered concurrently with oral aspirin (100 to 325 mg once daily). Treatment with Enoxaparin Sodium in these patients should be prescribed fora minimum of 2 days and continued until clinical stabilization.

Prevention of thrombus formation in extra corporeal circulation during hemodialysis: Recommended dose is 100 anti-Xa lU/kg. For patients with a high risk of hemorrhage, the dose should be reduced to 50 anti-Xa lU/kg for double vascular access or 75 anti-Xa lU/kg for single vascular access. During hemodialysis, Enoxaparin Sodium should be introduced into the arterial line of the circuit at the beqinninq of the dialysis session.

Prophylaxis of venous thromboembolic disease in surgical patients:

• Patients undergoing general surgery with a moderate risk of thromboembolism (e.g. abdominal surgery): Subcutaneously 2000 anti-Xa IU (0.2 ml) or 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 2 hours before the surgical procedure.
• Patients undergoing orthopedic surgery with a high risk of thromboembolism: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 7 to 10 days. The first injection should be given 12 hours before the surgical procedure. Longer treatment duration may be appropriate in some patients like continued therapy with 4000 anti-Xa IU once daily for 3 weeks following the initial therapy has been proven to be beneficial in orthopaedic surqery.

Prophylaxis of venous thromboembolic disease in medical patients: Subcutaneously 4000 anti-Xa IU (0.4 ml) once daily for 6- 14 days.

Haemorrhage (bleeding), Thrombocytopenia, elevations of serum aminotransferase. Pain, bluish marks at injection sites to skin rash at injection sites. Cases of neuraxial hematomas with the concurrent use of Enoxaparin and spinal/epidural anesthesia or spinal puncture have resulted in varying degrees of neurologic injuries.

Patients with known hypersensitivity to Enoxaparin Sodium, heparin or other low molecular weight heparins. Patients with active major bleeding and conditions with a high risk of uncontrolled hemorrhage including recent hemorrhagic stroke.

Enoxaparin Sodium should be injected by deep subcutaneous route in prophylactic and curative treatment and by intravascular route during hemodialysis. Do not administer by the intramuscular route. Enoxaparin Sodium should be used with caution in conditions with increased potential for bleeding, such as impaired hemostasis, history of peptic ulcer, recent ischemic stroke, uncontrolled severe arterial hypertension, diabetic retinopathy and recent neuro- or ophthalmologic surgery, concomitant use of medications affecting hemostasis. It is recommended that the platelet counts be measured before the initiation of the treatment and regularly thereafter during treatment.

It is recommended that agents which affect hemostasis should be discontinued prior to Enoxaparin Sodium therapy unless strictly indicated. These agents include medications such as: acetylsalicylic acid (and derivatives), NSAIDs (including ketorolac), ticlopidine,clopidogrel,dextran 40,glucocorticoids, thrombolytics and anticoagulants, other antiplatelet aggregation agents including glycoprotein llb/llla antagonists. If the combination is indicated, should be used with careful clinical and laboratory monitoring.

Pregnancy category B. In humans, there is no evidence that Enoxaparin Sodium crosses the placental barrier. As there are no adequate and well-controlled studies in pregnant women, Enoxaparin Sodium should be used during pregnancy only if clearly needed. Pregnant women with mechanical prosthetic heart valves may be at a higher risk for thromboembolism.

It is not known whether Enoxaparin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue Enoxaparin, taking into account the importance of Enoxaparin to the mother and the known benefits of nursing.

Dose in Elderly Patients: No dosage adjustment is necessary, unless kidney function is impaired.

Dose in Renal Impairment: Although no dosage adjustment is recommended in patients with moderate (creatinine clearance: 30-50 ml/min) and mild (creatinine clearance: 50 80 ml/min) renal impairment, all such patients should be observed carefully for signs and symptoms of bleeding. For patients with severe (creatinine clearance <30 ml/min) renal impairment, following dosage adjustments are recommended: Prophylactic dose ranges: 2000 antiXa IU once daily; Therapeutic dose ranges: 100 anti-Xa lU/kg once daily.

Dose in Hepatic Impairment: Caution should be used in hepatically impaired patients.

Accidental overdosage following administration of Enoxaparin may lead to hemorrhagic complications. Injected Enoxaparin may be largely neutralized by the slow i.v. injection of protamine sulfate (1% solution) The dose of protamine sulfate should be equal to the dose of Enoxaparin injected: 1 mg protamine sulfate should be administered to neutralize 1 mg Enoxaparin.

Store in a cool and dry place, protect from light and moisture. Do not store above 25°C. Do not store in a refrigerator or freezer. Keep out of the reach of children

For the short-term treatment of postoperative pain in adults. The decision to prescribe a selective cyclooxygenase-2 (COX-2) inhibitor should be based on an assessment of the individual patient's overall risks

Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Parecoxib is a prodrug of valdecoxib. Valdecoxib is a selective COX-2 inhibitor within the clinical dose range. Cyclooxygenase is responsible for generation of prostaglandins. Two isoforms, COX-1 and COX-2, have been identified. COX-2 is the isoform of the enzyme that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. COX-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function, and central nervous system functions (fever induction, pain perception and cognitive function). It may also play a role in ulcer healing. COX-2 has been identified in tissue around gastric ulcers in man but its relevance to ulcer healing has not been established.

The difference in antiplatelet activity between some COX-1 inhibiting NSAIDs and COX-2 selective inhibitors may be of clinical significance in patients at risk of thrombo-embolic reactions. COX-2 selective inhibitors reduce the formation of systemic (and therefore possibly endothelial) prostacyclin without affecting platelet thromboxane. The clinical relevance of these observations has not been established.

Adult: The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. As the cardiovascular risk of COX-2 specific inhibitors may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. There is limited clinical experience with Parecoxib treatment beyond three days.

Elderly: No dose adjustment is generally necessary in elderly patients (≥65 years). However, for elderly patients weighing less than 50 kg, treatment should be initiated with half the usual recommended dose of Parecoxib and reduce the maximum daily dose to 40 mg.

Children: The safety and efficacy of parecoxib in children under 18 years old have not been established. No data are available. Therefore, parecoxib is not recommended in these patients.

The IV bolus injection may be given rapidly and directly into a vein or into an existing IV line. The IM injection should be given slowly and deeply into the muscle. For instructions on reconstitution of the medicinal product before administration. Precipitation may occur when Parecoxib is combined in solution with other medicinal products and therefore Parecoxib must not be mixed with any other medicinal product, either during reconstitution or injection. In those patients where the same IV line is to be used to inject another medicinal product, the line must be adequately flushed prior to and after Parecoxib injection with a solution of known compatibility.

Commonside effects are-

• Change in your blood pressure (up or down)
• You may get back pain
• Ankles, legs and feet may swell (fluid retention)
• You may feel numb- your skin may lose sensitivity to pain and touch
• You may get vomiting, stomach ache, indigestion, constipation, bloating and wind
• Tests may show abnormal kidney function
• You may feel agitated or find it hard to sleep
• Dizziness
• There is a risk of anaemia- changes in red blood cells after an operation that may cause fatigue and breathlessness
• You may get a sore throat or difficulty breathing (shortness of breath)
• Your skin may be itchy
• You may pass less urine than usual.
• Dry socket (inflammation and pain after a tooth extraction)
• Increased sweating
• Low levels of potassium in blood test results.

Hypersensitivity to the active substance or to any of the excipients.

Parecoxib has been studied in dental, orthopaedic, gynaecologic (principally hysterectomy) and coronary artery bypass graft surgery. There is limited experience in other types of surgery, for example gastrointestinal or urological surgery. Modes of administration other than IV or IM (e.g. intra-articular, intrathecal) have not been studied and should not be used. Because of the possibility for increaed adverse reactions at higher doses of parecoxib, other COX-2 inhibitors and NSAIDs, patients treated with parecoxib should be reviewed following dose increase and, in the absence of an increase in efficacy, other therapeutic options should be considered. There is limited clinical experience with Parecoxib treatment beyond three days. If, during treatment, patients deteriorate in any of the organ system functions described below, appropriate measures should be taken and discontinuation of parecoxib therapy should be considered.

Parecoxib is suspected to cause serious birth defects when administered during the last trimester of pregnancy because as with other medicinal products known to inhibit prostaglandin, it may cause premature closure of the ductus arteriosus or uterine inertia. NSAID use during the second or third trimester of pregnancy may cause foetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation and are usually reversible. Pregnant women on NSAIDs should be closely monitored for amniotic fluid volume. Parecoxib is contraindicated in the third trimester of pregnancy.

Administration of a single dose of parecoxib to lactating women following caesarean section resulted in the transfer of a relatively small amount of parecoxib and its active metabolite valdecoxib into human milk, and this resulted in a low relative dose for the infant (approximately 1% of the weight-adjusted maternal dose). Parecoxib must not be administered to women who breast-feed.

Reporting of overdose with parecoxib has been associated with adverse reactions which have also been described with recommended doses of parecoxib. In case of overdose, patients should be managed by symptomatic and supportive care. Valdecoxib is not removed by haemodialysis. Diuresis or alkalisation of urine may not be useful due to high protein binding of valdecoxib.

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

Pramipexole is indicated for the treatment of-

• Parkinson's disease used alone or as an adjunct to levodopa with dopa-decarboxylase inhibitor
• Moderate to severe restless legs syndrome

Antiparkinson drugs

The exact mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown at this time. It is thought, however, that the ability of pramipexole to cause stimulation of the dopamine receptors in the striatum of the brain, a region that receives a vast array of neurological input and is responsible for a wide variety of functions, may be involved. Studies performed in animals show that pramipexole influences striatal neuronal transmission rates following activation of dopamine receptors. Pramipexole is considered a non-ergot dopamine agonist that shows specificity and strong activity at the D2 subfamily of dopamine receptors in vitro, binding selectively and dopamine D2 receptors and showing a preference for the dopamine D3 receptor subtype rather than other subtypes. The clinical significance of this binding specificity is unknown.

The recommended dose of Pramipexole is as follows-

Parkinson's disease:

• Initial dose: 88 micrograms 3 times daily, dose doubled every 5-7 days if tolerated to 350 micrograms 3 times daily; further increased if necessary by 180 micrograms 3 times daily at weekly intervals
• Maximum dose: 3.3 mg daily in 3 divided doses. During pramipexole dose titration and maintenance Levodopa dose should be reduced.

Restless legs syndrome:

• Initial dose: 88 micrograms once daily 2-3 hours before bedtime, dose doubled every 4-7 days if necessary to 350 micrograms daily.
• Maximum dose: 540 micrograms daily.

Use in children: Pramipexole is not recommended for children below 18 years of age.

The common side effects are dizziness, dyskinesia, nausea, hypotension, abnormal dreams, confusion, constipation, delusion, hallucinations, headache, hyperkinesia, increased eating (binge eating, hyperphagia), insomnia, libido disorders, nausea, peripheral oedema, paranoia, pathological gambling, hypersexuality and other abnormal behaviour, somnolence, weight increase, sudden onset of sleep, pruritus and rash and other hypersensitivity.

Pramipexole is contraindicated in patients with known Hypersensitivity to the active substance or to any of the excipients.

Caution should be taken in patients with psychotic disorder, ophthalmologic monitoring is recommended at regular intervals, severe cardiovascular disease and renal impairment.

Pramipexole is the only dopamine agonist not appreciably metabolized by the P450 system which minimizes about possible drug-drug interactions. Cimetidine and amantadine may reduce the renal clearance of pramipexole. Sedating medicinal products or alcohol in combination with pramipexole may cause additive effects.

The effect of pramipexole on pregnancy and lactation has not been investigated in humans so it should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Pramipexole inhibits secretion of prolactin in humans. The excretion of pramipexole into breast milk has not been studied in women so it should not be used during breast-feeding. However, if its use is unavoidable then breast-feeding should be discontinued.

There is no clinical experience with massive overdose. Symptoms of overdose are nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension. There is no established antidote. If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated. Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.

Store in a cool and dry place. Protect from light.

Pramipexole is indicated for the treatment of-

• Parkinson's disease used alone or as an adjunct to levodopa with dopa-decarboxylase inhibitor
• Moderate to severe restless legs syndrome

Antiparkinson drugs

The exact mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown at this time. It is thought, however, that the ability of pramipexole to cause stimulation of the dopamine receptors in the striatum of the brain, a region that receives a vast array of neurological input and is responsible for a wide variety of functions, may be involved. Studies performed in animals show that pramipexole influences striatal neuronal transmission rates following activation of dopamine receptors. Pramipexole is considered a non-ergot dopamine agonist that shows specificity and strong activity at the D2 subfamily of dopamine receptors in vitro, binding selectively and dopamine D2 receptors and showing a preference for the dopamine D3 receptor subtype rather than other subtypes. The clinical significance of this binding specificity is unknown.

The recommended dose of Pramipexole is as follows-

Parkinson's disease:

• Initial dose: 88 micrograms 3 times daily, dose doubled every 5-7 days if tolerated to 350 micrograms 3 times daily; further increased if necessary by 180 micrograms 3 times daily at weekly intervals
• Maximum dose: 3.3 mg daily in 3 divided doses. During pramipexole dose titration and maintenance Levodopa dose should be reduced.

Restless legs syndrome:

• Initial dose: 88 micrograms once daily 2-3 hours before bedtime, dose doubled every 4-7 days if necessary to 350 micrograms daily.
• Maximum dose: 540 micrograms daily.

Use in children: Pramipexole is not recommended for children below 18 years of age.

The common side effects are dizziness, dyskinesia, nausea, hypotension, abnormal dreams, confusion, constipation, delusion, hallucinations, headache, hyperkinesia, increased eating (binge eating, hyperphagia), insomnia, libido disorders, nausea, peripheral oedema, paranoia, pathological gambling, hypersexuality and other abnormal behaviour, somnolence, weight increase, sudden onset of sleep, pruritus and rash and other hypersensitivity.

Pramipexole is contraindicated in patients with known Hypersensitivity to the active substance or to any of the excipients.

Caution should be taken in patients with psychotic disorder, ophthalmologic monitoring is recommended at regular intervals, severe cardiovascular disease and renal impairment.

Pramipexole is the only dopamine agonist not appreciably metabolized by the P450 system which minimizes about possible drug-drug interactions. Cimetidine and amantadine may reduce the renal clearance of pramipexole. Sedating medicinal products or alcohol in combination with pramipexole may cause additive effects.

The effect of pramipexole on pregnancy and lactation has not been investigated in humans so it should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Pramipexole inhibits secretion of prolactin in humans. The excretion of pramipexole into breast milk has not been studied in women so it should not be used during breast-feeding. However, if its use is unavoidable then breast-feeding should be discontinued.

There is no clinical experience with massive overdose. Symptoms of overdose are nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension. There is no established antidote. If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated. Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.

Store in a cool and dry place. Protect from light.

Trihexyphenidyl Hydrochloride is indicated as an adjunct treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic & idiopathic). Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as dibenzoxazepines, phenothiazines, thioxanthenes & butyrophenones.

Antiparkinson drugs

Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M1 subtype. In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally. Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum. Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated.

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether Trihexyphenidyl may best be given before or after meals should be determined by the way the patient reacts.

Idiopathic Parkinsonism: 1 mg of Trihexyphenidyl may be administered the first day. The dose may then be increased by 2mg increments at intervals of three to five days.

Drug-Induced Parkinsonism: Commence therapy with a single 1 mg dose increase the total daily dosage to 5-15 mg range if the extrapyramidal manifestations are not controlled.

Concomitant Use with Levodopa: When Trihexyphenidyl is used concomitantly with levodopa, the usual dose is 3-6 mg daily.

Minor side effects such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness. Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Potential side effects are constipation, drowsiness, urinary hesitancy or retention, pupil dilation, increased intraocular tension, vomiting and headache.

Contraindicated in patients with hypersensitivity to Trihexyphenidyl HCI or to any of the tablet or elixir ingredients. Trihexyphenidyl is also contraindicated in patients with narrow angle glaucoma. Blindness after long-term use due to narrow angle glaucoma has been reported.

Patients with cardiac, liver, or kidney disorders, or with hypertensioon, should closely be monitored. Since Trihexyphenidyl HCI has parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy. Trihexyphenidyl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson’s disease. Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided.

Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with Trihexyphenidyl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with Trihexyphenidyl may cause increased sedative effects. It may be contraindicated in patients taking monoamine oxidase inhibitors & tricycllic antidepressants.

Pregnancy Category C. It is not known whether the drug is excreted in human milk and therefore Trihexyphenidyl should only be used if the expected benefit to the mother outweighs the potential risk to the infant.

Overdosage with Trihexyphenidyl produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Signs & symptoms are: dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of mouth, pharynx, nose and bronchi, foul smelling breath, tachycardia etc. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations etc. The condition can progress to stupor, coma, paralysis, cardiac, respiratory arrest and death.

Do not store above 30°C. Keep away from light and out of the reach of children.

Trihexyphenidyl Hydrochloride is indicated as an adjunct treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic & idiopathic). Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as dibenzoxazepines, phenothiazines, thioxanthenes & butyrophenones.

Antiparkinson drugs

Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M1 subtype. In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally. Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum. Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated.

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether Trihexyphenidyl may best be given before or after meals should be determined by the way the patient reacts.

Idiopathic Parkinsonism: 1 mg of Trihexyphenidyl may be administered the first day. The dose may then be increased by 2mg increments at intervals of three to five days.

Drug-Induced Parkinsonism: Commence therapy with a single 1 mg dose increase the total daily dosage to 5-15 mg range if the extrapyramidal manifestations are not controlled.

Concomitant Use with Levodopa: When Trihexyphenidyl is used concomitantly with levodopa, the usual dose is 3-6 mg daily.

Minor side effects such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness. Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Potential side effects are constipation, drowsiness, urinary hesitancy or retention, pupil dilation, increased intraocular tension, vomiting and headache.

Contraindicated in patients with hypersensitivity to Trihexyphenidyl HCI or to any of the tablet or elixir ingredients. Trihexyphenidyl is also contraindicated in patients with narrow angle glaucoma. Blindness after long-term use due to narrow angle glaucoma has been reported.

Patients with cardiac, liver, or kidney disorders, or with hypertensioon, should closely be monitored. Since Trihexyphenidyl HCI has parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy. Trihexyphenidyl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson’s disease. Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided.

Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with Trihexyphenidyl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with Trihexyphenidyl may cause increased sedative effects. It may be contraindicated in patients taking monoamine oxidase inhibitors & tricycllic antidepressants.

Pregnancy Category C. It is not known whether the drug is excreted in human milk and therefore Trihexyphenidyl should only be used if the expected benefit to the mother outweighs the potential risk to the infant.

Overdosage with Trihexyphenidyl produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Signs & symptoms are: dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of mouth, pharynx, nose and bronchi, foul smelling breath, tachycardia etc. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations etc. The condition can progress to stupor, coma, paralysis, cardiac, respiratory arrest and death.

Do not store above 30°C. Keep away from light and out of the reach of children.

Antiparkinson drugs

If 100/10 mg tablet is used: Dosage may be initiated with one tablet three or four times a day. Titration upward may be required in some patients to achieve optimum dosage of carbidopa. The dosage may be increased by one tablet every day or every other day until a total of eight tablets (two tablets q.d.s.) is reached.

For patients starting with 250/25 mg tablet: The initial dose is one half taken once or twice daily. However, this may not provide the optimal amount of Carbidopa needed by many patients. If necessary, add one-half every day or every other day until optimal response is reached. The suggested starting dosage for most patients taking more than 1500 mg of Levodopa a day is one tablet of 250/25 mg three or four times a day.

Maintenance dose: Therapy should be individualized and adjusted according to the desired therapeutic response. When more levodopa is requried, 250/25 mg tablet should be substituted at a dosage of one tablet three or four times a day. If necessary, the dosage of 250/25 mg tablet may be increased by half to one tablet every other day to a maximum of eight tablets a day. Experience with a total daily dosage greater than 200 mg Carbidopa is limited.

Adverse effects that occur frequently in patients receiving Carbidopa-Levodopa are those due to the central neuropharmacologic activity of dopamine. These reactions usually can be diminished by dosage reduction. The most common adverse effects are dyskinesias including choreiform, dystonic, and other involuntary movements and nausea.

• Body as a whole: syncope, chest pain, anorexia.
• Cardiovascular: palpitation, orthostatic effects including hypotensive episodes, hypertension, phlebitis.
• Gastrointestinal: vomiting, gastrointestinal bleeding, development of duodenal ulcer, diarrhoea, dark saliva.
• Haemotologic: leukopenia, haemolytic and non-haemolytic anaemia, thrombocytopenia, agranulocytosis.
• Hypersensitivity: angioedema, urticaria, pruritus, Henoch-Schonlein purpura.
• Nervous System: dizziness, somnolence, paresthesia, delusions, hallucinations and paranoid ideation, depression with or without development of suicidal tendencies, dementia, dream abnormalities, agitation, confusion, increased libido.
• Respiratory: dyspnea.
• Skin: alopecia, rash, dark sweat.
• Urogenital: dark urine.

Carbidopa-Levodopa tablet is contraindicated in patients with hypersensitivity to Carbidopa and Levodopa, and in patients with narrow-angle glaucoma. Since Levodopa may activate a malignant melanoma, Carbidopa-Levodopa should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.

Carbidopa-Levodopa is not recommended for the treatment of medicine-induced extrapyramidal reactions. Carbidopa Levodopa may be given to patients already taking Levodopa alone; however, the Levodopa must be discontinued at least 12 hours before Carbidopa-Levodopa started. Dyskinesias may occur in patients previously treated with Levodopa alone because Carbidopa permits more Levodopa to reach the brain and, thus, more dopamine to be formed. The occurrence of dyskinesias may require dosage reduction. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Patients with past or current psychoses should be treated with caution. Carbidopa-Levodopa should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or a history of peptic ulcer disease or of convulsions.

Care should be exercised to patients with a history of myocardial infarction who have atriai, nodal, or ventricular arrhythmia. In such patients, cardiac function should be monitored with particular care during the period of initial dosage administration and titration. Patients with chronic wide-angle glaucoma may be treated cautiously with Carbidopa-Levodopa, provided the intraocular pressure is weli controlled and the patient monitored carefully for changes in intraocular pressure during therapy.

Symptomatic postural hypotension has occurred when Carbidopa-Levodopa is added to the treatment of a patient receiving antihypertensive medicines. Therefore, when therapy with CarbidopaLevodopa is started, dosage adjustment of the antihypertensive medicine may be required. There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and Carbidopa-Levodopa. Studies demonstrate a decrease in the bioavailability of Carbidopa and/or Levodopa when it is ingested with ferrous sulphate or ferrous gluconate. Dopamine-2 receptor antagonists (e.g., phenothiazines, butyrophenones and risperidone) and isoniazid may reduce the therapeutic effects of Levodopa. In addition, the beneficial effects of Levodopa in Parkinson's disease have been reported to be reversed by phenytoin and papaverine. Patients taking these medicines with Carbidopa-Levodopa should be carefully observed for loss of therapeutic response. Concomitant therapy with selegiline and Carbidopa-Levodopa may be associated with severe orthostatic hypotension not attributable to Carbidopa-Levodopa alone.

Although the effects of CarbidopaLevodopa on human pregnancy are unknown both Levodopa and combinations of Carbidopa and Levodopa have caused visceral and skeletal malformations in rabbits. Therefore, use of CarbidopaLevodopa in women of childbearing potential requires that the anticipated benefits of the medicine be weighed against possible hazards should pregnancy occur. It is not known whether Carbidopa is excreted in human milk. Because many medicines are excreted in human milk and because of the potential for serious adverse reactions in infants, a decision should be made whether to discontinue nursing or to discontinue the use of Carbidopa-Levodopa, taking into account the importance of the medicine to the mother.

Use in children: Safety and effectiveness of Carbidopa-Levodopa in infants and children have not been established, and its use in patients below the age of 18 years is not recommended.

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

Trihexyphenidyl Hydrochloride is indicated as an adjunct treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic & idiopathic). Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as dibenzoxazepines, phenothiazines, thioxanthenes & butyrophenones.

Antiparkinson drugs

Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M1 subtype. In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally. Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum. Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated.

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether Trihexyphenidyl may best be given before or after meals should be determined by the way the patient reacts.

Idiopathic Parkinsonism: 1 mg of Trihexyphenidyl may be administered the first day. The dose may then be increased by 2mg increments at intervals of three to five days.

Drug-Induced Parkinsonism: Commence therapy with a single 1 mg dose increase the total daily dosage to 5-15 mg range if the extrapyramidal manifestations are not controlled.

Concomitant Use with Levodopa: When Trihexyphenidyl is used concomitantly with levodopa, the usual dose is 3-6 mg daily.

Minor side effects such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness. Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Potential side effects are constipation, drowsiness, urinary hesitancy or retention, pupil dilation, increased intraocular tension, vomiting and headache.

Contraindicated in patients with hypersensitivity to Trihexyphenidyl HCI or to any of the tablet or elixir ingredients. Trihexyphenidyl is also contraindicated in patients with narrow angle glaucoma. Blindness after long-term use due to narrow angle glaucoma has been reported.

Patients with cardiac, liver, or kidney disorders, or with hypertensioon, should closely be monitored. Since Trihexyphenidyl HCI has parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy. Trihexyphenidyl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson’s disease. Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided.

Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with Trihexyphenidyl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with Trihexyphenidyl may cause increased sedative effects. It may be contraindicated in patients taking monoamine oxidase inhibitors & tricycllic antidepressants.

Pregnancy Category C. It is not known whether the drug is excreted in human milk and therefore Trihexyphenidyl should only be used if the expected benefit to the mother outweighs the potential risk to the infant.

Overdosage with Trihexyphenidyl produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Signs & symptoms are: dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of mouth, pharynx, nose and bronchi, foul smelling breath, tachycardia etc. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations etc. The condition can progress to stupor, coma, paralysis, cardiac, respiratory arrest and death.

Do not store above 30°C. Keep away from light and out of the reach of children.

Trihexyphenidyl Hydrochloride is indicated as an adjunct treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic & idiopathic). Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as dibenzoxazepines, phenothiazines, thioxanthenes & butyrophenones.

Antiparkinson drugs

Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M1 subtype. In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally. Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum. Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated.

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether Trihexyphenidyl may best be given before or after meals should be determined by the way the patient reacts.

Idiopathic Parkinsonism: 1 mg of Trihexyphenidyl may be administered the first day. The dose may then be increased by 2mg increments at intervals of three to five days.

Drug-Induced Parkinsonism: Commence therapy with a single 1 mg dose increase the total daily dosage to 5-15 mg range if the extrapyramidal manifestations are not controlled.

Concomitant Use with Levodopa: When Trihexyphenidyl is used concomitantly with levodopa, the usual dose is 3-6 mg daily.

Minor side effects such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness. Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Potential side effects are constipation, drowsiness, urinary hesitancy or retention, pupil dilation, increased intraocular tension, vomiting and headache.

Contraindicated in patients with hypersensitivity to Trihexyphenidyl HCI or to any of the tablet or elixir ingredients. Trihexyphenidyl is also contraindicated in patients with narrow angle glaucoma. Blindness after long-term use due to narrow angle glaucoma has been reported.

Patients with cardiac, liver, or kidney disorders, or with hypertensioon, should closely be monitored. Since Trihexyphenidyl HCI has parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy. Trihexyphenidyl is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson’s disease. Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms; therefore, abrupt withdrawal should be avoided.

Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with Trihexyphenidyl, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with Trihexyphenidyl may cause increased sedative effects. It may be contraindicated in patients taking monoamine oxidase inhibitors & tricycllic antidepressants.

Pregnancy Category C. It is not known whether the drug is excreted in human milk and therefore Trihexyphenidyl should only be used if the expected benefit to the mother outweighs the potential risk to the infant.

Overdosage with Trihexyphenidyl produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Signs & symptoms are: dilated and sluggish pupils, warm, dry skin, facial flushing, decreased secretions of mouth, pharynx, nose and bronchi, foul smelling breath, tachycardia etc. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations etc. The condition can progress to stupor, coma, paralysis, cardiac, respiratory arrest and death.

Do not store above 30°C. Keep away from light and out of the reach of children.

4-Quinolone preparations

Sparfloxacin is a synthetic, broad-spectrum antibacterial agent from the difluoroquinolone family. It has been reported to be more active in vitro than ciprofloxacin against some organisms, including staphylococci and Mycobacteria, and has a much longer plasma half-life (16 hours).

Sparfloxacin inhibits the supercoiling activity of DNA gyrase which is an enzyme essential for DNA replication thus promoting the breakage of DNA structures. It has activity against S. pneumoniae, S. aureus, H. influenzae, K. pneumoniae, M. catarrhalis and Mycobacterium spp.

In patients with normal renal function the recommended daily dose is two tablets of Sparfloxacin 200 mg on first day as a loading dose, thereafter take one tablet of Sparfloxacin 200 mg every 24 hours for a total of 10 days of therapy.

The recommended daily dose of Sparfloxacin in patients with renal impairment (Creatinine clearance < 30 ml/min) is two tablets of 200 mg taken on the first day as a loading dose. Thereafter, should be taken one tablet of 200 mg every 48 hours for total of 9 days of therapy.

Sparfloxacin can be taken with or without food.

Most of the adverse events were mild to moderate in severity and transient in nature. The most frequently reported events among the Sparfloxacin treated patients with the recommended dosage are: diarrhea, nausea, headache, dyspepsia, dizziness, insomnia, abdominal pain and QTc interval prolongation.

Sparfloxacin is contraindicated for individuals with a history of hypersensifivity and in achilles tend in its following the use of fluoroquinolone and in pregnancy and lactation. Sparfloxacin is contraindicated in patients with known QTc prolongation or in patients being treated concomitantly with medications known to produce an increase in the QTc interval and/or torsade depointes.

It should be used with caution in renal diseases, gastric ulcers and with concomitant use of NSAIDs. In renal failure of third degree severity (creatinine clearance < 30 ml/min) dosage modification is recommended 400 mg on 1st day, 200 mg on 2nd and 3rd day followed by 200 mg every 48 hours. Because fluoroquinolones have been associated with tendon rupture, Sparfloxacin should be discontinued at the first sign of tendon pain. Exposure to UV radiation during treatment should be avoided.

On concomitant use with Quinidine, Sotalol, Erythromycin, Astemizole, Terfenadine, vinca alkaloids there is increased risk of arrhythmia. Salts, oxides and hydroxides of Magnesium, Aluminium and Calcium decrease absorption of Sparfloxacin.

There are no adequate and well controlled studies in pregnant women. Sparfloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in children: Safety and effectiveness have not been established in patients below the age of 18 years.

Store at temperature below 30° C.

Albendazole is indicated in single and mixed infestations of-

• Hookworm (Ancylostoma, Necator)
• Roundworm (Ascaris)
• Threadworm (Enterobius)
• Whipworm (Trichuris)
• Strongyloides
• Tapeworm
• Opisthorchi
• Hydatid.

Anthelmintic

Albendazole is a broad spectrum anthelmintic. Albendazole exhibits vermicidal, ovicidal and larvicidal activities. The drug is thought to exert its anthelmintic effect by blocking glucose uptake in the susceptible helminths, thereby depleting the energy level until it becomes inadequate for survival. Immobilization is followed by the parasite. These events may be a consequence of the binding and subsequent inhibition of parasite tubulin polymerization by Albendazole and its metabolites, although the drug also binds to human tubulin. Albendazole is extensively metabolized, probably in the liver. Albendazole is poorly absorbed from the gastrointestinal tract but rapidly undergoes extensive first-pass metabolism. The principal metabolite albendazole sulphoxide has anthelmintic activity and a plasma half-life of about 8.5 hrs. It is excreted in the urine together with other metabolites.

Adults & children over 2 years:

• 400 mg (1 tablet or 10 ml suspension) as a single dose in cases of Enterobius vermicularis, Trichuris trichiura, Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus.
• In cases of strongyloidiasis or taeniasis, 400 mg (1 tablet or 10 ml suspension) daily should be given for 3 consecutive days. If the patient is not cured on follow-up after three weeks, a second course of treatment is indicated. 

Children of 1-2 years: Recommended dose is a single dose of 200 mg (5 ml suspension).

Children under 1 year: Not recommended.

In Hydatid disease (Echinococcosis):

• Albendazole is given by mouth with meals in a dose of 400 mg twice daily for 28 days for patients weighing over 60 kg.
• A dose of 15 mg/kg body weight daily in two divided doses (to a maximum total daily dose of 800 mg) is used for patients weighing less than 60 kg.
• For cystic echinococcosis, the 28 days course may be repeated after 14 days without treatment, to a total of 3 treatment cycles.
• For alveolar echinococcosis, cycles of 28 days of treatment followed by 14 days without treatment, may need to continue for months or years.
• In giardiasis, 400 mg (1 tablet or 10 ml suspension) once daily for five days is used.

Gastrointestinal disturbances, headache, dizziness, changes in liver enzymes, rarely reversible alopecia; rash, fever, blood disorders including leucopenia and pancytopenia reported; allergic shock if cyst leakage; convulsion and meningism in cerebral disease.

Neonates: Albendazole is not normally used in neonates.

Children: Reduction of the dose from 400 mg to 200 mg may be indicated in children weighing less than 10 kg but there are no grounds for a general reduction in dosage to children.

Pregnant woman: Albendazole should not be given during pregnancy or women thought to be pregnant. No information is available on placental transfer.

Concurrent disease: There is no evidence to suggest that dose should be altered in renal, hepatic or cardiac failure.

Blood counts and liver function tests before treatment and twice during each cycle; breastfeeding; exclude pregnancy before starting treatment. Albendazole should only be used in the treatment of Echinococcosis if there is constant medical supervision with regular monitoring of serum-transaminase concentrations and of leucocyte and platelet counts

No interaction involving Albendazole, either pharmacodynamic or pharmacokinetic, has been reported.

US FDA Pregnancy category of Albendazole is C. So, Albendazole should be avoided in pregnancy and lactation unless the potential benefits to the other outweigh the possible risks to the fetus.

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

Paroxetine  is indicated in:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Panic Disorder
• Social Anxiety Disorder
• Generalized Anxiety Disorder
• Posttraumatic Stress Disorder.

SSRIs & related anti-depressant drugs

The efficacy of Paroxetine is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5 HT). Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic, alpha1, alpha2, beta adrenergic, dopamine (D2), 5-HT1, 5 HT2 and histamine (H1)-receptors; antagonism of muscarinic, histaminergic and alpha1-adrenergic receptors has been associated with various anticholinergic, sedative and cardiovascular effects for other psychotropic drugs. Because the relative potencies of paroxetine’s major metabolites are at most 1/50 of the parent compound, they are essentially inactive.

Major Depressive Disorder:

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dose is 20 mg/day. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Systematic evaluation of the efficacy of Paroxetine hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg.

Obsessive Compulsive Disorder (OCD):

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended dose of Paroxetine in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10 mg/day increments. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Panic Disorder:

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The target dose of Paroxetine in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week. The maximum dosage should not exceed 60 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Social Anxiety Disorder (SAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Generalized Anxiety Disorder (GAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Posttraumatic Stress Disorder (PTSD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day. Dose changes, if indicated, should occur in 10 mg/day increments and at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Major depressive disorder: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance and other male genital disorders.

Obsessive compulsive disorder: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence and abnormal ejaculation.

Panic disorder: Asthenia, sweating, decreased appetite, decreased libido , tremor, abnormal ejaculation, female genital disorders and impotence.

Social anxiety disorder: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, decreased libido, yawn, abnormal ejaculation, female genital disorders and impotence.

Generalised anxiety disorder: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, decreased libido, somnolence, tremor, sweating and abnormal
ejaculation.

Post-traumatic stress disorder: Asthenia, sweating nausea, dry mouth, diarrhoea, decreased appetite, somnolence, decreased libido, abnormal ejaculation, female genital disorders and impotence.

Concomitant use in patients taking either monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated. This is contraindicated in patients with a hypersensitivity to Paroxetine.

Cardiac conditions: Paroxetine does not produce clinically significant changes in blood pressure, heart rate and ECG. Nevertheless, as with all psychoactive drugs, caution is advised when treating patients with cardiac conditions.

Epilepsy: As with other antidepressants, Paroxetine should be used with caution in-patients with epilepsy.

Seizures: Overall, the incidence of seizures is < 0.1% in patients treated with Paroxetine. Paroxetine should be discontinued in any patient who develops seizures.

ECT: There is little clinical experience of concurrent administration of Paroxetine with ECT.

Ability to drive/use machines: Clinical experience has shown that therapy with Paroxetine is not associated with impairment of cognitive or psychomotor function. However, as with all psychoactive drugs, patients should be cautioned about their ability to drive a car and operate machinery.

Discontinuation of Treatment with Paroxetine: Recent clinical trials supporting the various approved indications of Paroxetine employed a taper phase regimen, rather than an abrupt discontinuation of treatment. The taper phase regimen used in GAD and PTSD clinical trials involved an incremental decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, patients were continued on this dose for 1 week before treatment was stopped.

Food/antacids: The absorption and pharmacokinetics of Paroxetine are not affected by food or antacids.

Tryptophan: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and Tryptophan may occur, resulting in a ‘serotonin syndrome’ suggested by a combination of agitation, restlessness and gastrointestinal symptoms including diarrhoea. 

Drug metabolizing enzyme inducers /inhibitors: The metabolism and pharmacokinetics of Paroxetine may be affected by drugs, which induce or inhibit hepatic drug metabolizing enzymes. When Paroxetine is to be coadministered with a known drug metabolizing inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment of Paroxetine is considered necessary when it is to be co-administered with known drug metabolizing enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect (tolerabilityand efficacy).

Alcohol: Although Paroxetine does not increase the impairment of mental and motor skill caused by alcohol, the concomitant use of Paroxetine and alcohol in depressed patients is not advised.

Haloperidol/amylobarbitone/oxazepam: Experience in a limited number of healthy subjects has shown that Paroxetine did not increase the sedation and drowsiness associated with haloperidol, amylobarbitone or oxazepam when given in combination.

MAOls: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and monoamine oxidase (MAO) inhibitors may occur.

Lithium: Since there is little clinical experience, and there have been reports of interaction of lithium with other 5-HT re-uptake inhibitors, the concurrent administration of Paroxetine and lithium should be undertaken with caution.

Lithium levels should be monitored. Phenytoin / anticonvulsants: Co-administration of Paroxetine and phenytoin is associated with decreased plasma concentrations of Paroxetine and increased adverse experiences. Co-administration of Paroxetine with other anticonvulsants may also be associated with an increased incidence of adverse experiences.

Warfarin: Preliminary data suggest that there may be a pharmacodynamic interaction between Paroxetine and warfarin, which may result in increased bleeding in the presence of unaltered prothrombin times. Paroxetine should therefore be administered with great caution to patients receiving oral anticoagulants.

This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery: The effect of Paroxetine on labor and delivery in humans is unknown.

Nursing Mothers: Like many other drugs, Paroxetine is secreted in human milk, and caution should be exercised when Paroxetine hydrochloride is administered to a nursing woman.

Dosage for Elderly or Debilitated, and Patients with Severe Renal or Hepatic Impairment: The recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day.

Keep out of the reach of children. Store at a cool and dry place. Protect from light and moisture.

Paroxetine  is indicated in:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Panic Disorder
• Social Anxiety Disorder
• Generalized Anxiety Disorder
• Posttraumatic Stress Disorder.

SSRIs & related anti-depressant drugs

The efficacy of Paroxetine is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5 HT). Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic, alpha1, alpha2, beta adrenergic, dopamine (D2), 5-HT1, 5 HT2 and histamine (H1)-receptors; antagonism of muscarinic, histaminergic and alpha1-adrenergic receptors has been associated with various anticholinergic, sedative and cardiovascular effects for other psychotropic drugs. Because the relative potencies of paroxetine’s major metabolites are at most 1/50 of the parent compound, they are essentially inactive.

Major Depressive Disorder:

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dose is 20 mg/day. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Systematic evaluation of the efficacy of Paroxetine hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg.

Obsessive Compulsive Disorder (OCD):

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended dose of Paroxetine in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10 mg/day increments. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Panic Disorder:

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The target dose of Paroxetine in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week. The maximum dosage should not exceed 60 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Social Anxiety Disorder (SAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Generalized Anxiety Disorder (GAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Posttraumatic Stress Disorder (PTSD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day. Dose changes, if indicated, should occur in 10 mg/day increments and at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Major depressive disorder: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance and other male genital disorders.

Obsessive compulsive disorder: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence and abnormal ejaculation.

Panic disorder: Asthenia, sweating, decreased appetite, decreased libido , tremor, abnormal ejaculation, female genital disorders and impotence.

Social anxiety disorder: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, decreased libido, yawn, abnormal ejaculation, female genital disorders and impotence.

Generalised anxiety disorder: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, decreased libido, somnolence, tremor, sweating and abnormal
ejaculation.

Post-traumatic stress disorder: Asthenia, sweating nausea, dry mouth, diarrhoea, decreased appetite, somnolence, decreased libido, abnormal ejaculation, female genital disorders and impotence.

Concomitant use in patients taking either monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated. This is contraindicated in patients with a hypersensitivity to Paroxetine.

Cardiac conditions: Paroxetine does not produce clinically significant changes in blood pressure, heart rate and ECG. Nevertheless, as with all psychoactive drugs, caution is advised when treating patients with cardiac conditions.

Epilepsy: As with other antidepressants, Paroxetine should be used with caution in-patients with epilepsy.

Seizures: Overall, the incidence of seizures is < 0.1% in patients treated with Paroxetine. Paroxetine should be discontinued in any patient who develops seizures.

ECT: There is little clinical experience of concurrent administration of Paroxetine with ECT.

Ability to drive/use machines: Clinical experience has shown that therapy with Paroxetine is not associated with impairment of cognitive or psychomotor function. However, as with all psychoactive drugs, patients should be cautioned about their ability to drive a car and operate machinery.

Discontinuation of Treatment with Paroxetine: Recent clinical trials supporting the various approved indications of Paroxetine employed a taper phase regimen, rather than an abrupt discontinuation of treatment. The taper phase regimen used in GAD and PTSD clinical trials involved an incremental decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, patients were continued on this dose for 1 week before treatment was stopped.

Food/antacids: The absorption and pharmacokinetics of Paroxetine are not affected by food or antacids.

Tryptophan: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and Tryptophan may occur, resulting in a ‘serotonin syndrome’ suggested by a combination of agitation, restlessness and gastrointestinal symptoms including diarrhoea. 

Drug metabolizing enzyme inducers /inhibitors: The metabolism and pharmacokinetics of Paroxetine may be affected by drugs, which induce or inhibit hepatic drug metabolizing enzymes. When Paroxetine is to be coadministered with a known drug metabolizing inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment of Paroxetine is considered necessary when it is to be co-administered with known drug metabolizing enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect (tolerabilityand efficacy).

Alcohol: Although Paroxetine does not increase the impairment of mental and motor skill caused by alcohol, the concomitant use of Paroxetine and alcohol in depressed patients is not advised.

Haloperidol/amylobarbitone/oxazepam: Experience in a limited number of healthy subjects has shown that Paroxetine did not increase the sedation and drowsiness associated with haloperidol, amylobarbitone or oxazepam when given in combination.

MAOls: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and monoamine oxidase (MAO) inhibitors may occur.

Lithium: Since there is little clinical experience, and there have been reports of interaction of lithium with other 5-HT re-uptake inhibitors, the concurrent administration of Paroxetine and lithium should be undertaken with caution.

Lithium levels should be monitored. Phenytoin / anticonvulsants: Co-administration of Paroxetine and phenytoin is associated with decreased plasma concentrations of Paroxetine and increased adverse experiences. Co-administration of Paroxetine with other anticonvulsants may also be associated with an increased incidence of adverse experiences.

Warfarin: Preliminary data suggest that there may be a pharmacodynamic interaction between Paroxetine and warfarin, which may result in increased bleeding in the presence of unaltered prothrombin times. Paroxetine should therefore be administered with great caution to patients receiving oral anticoagulants.

This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery: The effect of Paroxetine on labor and delivery in humans is unknown.

Nursing Mothers: Like many other drugs, Paroxetine is secreted in human milk, and caution should be exercised when Paroxetine hydrochloride is administered to a nursing woman.

Dosage for Elderly or Debilitated, and Patients with Severe Renal or Hepatic Impairment: The recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day.

Keep out of the reach of children. Store at a cool and dry place. Protect from light and moisture.