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It is indicated for the relief of symptoms associated with seasonal & perennial allergic rhinitis. It is also indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria and allergen induced asthma.

Sedating Anti-histamine

Cetirizine Hydrochloride is a potent H1 receptor antagonist without any significant anticholinergic and antiserotonic effects. At pharmacologically active dose levels, it has almost no drowsiness effect and does not cause behavioral changes. It inhibits the histamine-mediated early phase of the allergic reaction and also reduces the migration of inflammatory cells and the release of mediators associated with the late phase of the allergic reaction.

Pharmacokinetics: Cetirizine 10 mg achieves peak plasma concentrations of 257 mcg/L within one hour of administration (980 mcg/L in children). Food does not affect the extent of absorption, but it may slightly reduce the rate. Peak blood levels 0.3 micrograms/ml are reached between thirty & sixty minutes after administration of 10 mg dose of Cetirizine. Its plasma half-life is approximately 11 hours. Absorption is very consistent from one subject to the next. Its renal clearance is 30 ml/minute and the excretion half-life is approximately nine hours.

Adults and Children 6 years and older: 1 tablet or 2 teaspoonfuls daily (or 1 teaspoonful twice daily).

Children 2-6 years: 1 teaspoonful once daily or 1/2 teaspoonful twice daily.

Children 6 months to 2 years : 1/2 teaspoonful once daily. The dose in children 12-23 months of age can be increased to a maximum dose as 1/2 teaspoonful every 12 hours.

The most common side effects that occurred more frequently on Cetirizine is somnolence.

It is contraindicated in patients with a history of hypersensitivity to Cetirizine or hydroxyzine.

Caution should be exercised when driving a car or operating a heavy machinery.

No clinically significant drug interactions have been found with Theophylline, Azithromycin, Pseudoephedrine, Ketoconazole or Erythromycin and with other drugs.

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

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

It is indicated for the relief of symptoms associated with seasonal & perennial allergic rhinitis. It is also indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria and allergen induced asthma.

Sedating Anti-histamine

Cetirizine Hydrochloride is a potent H1 receptor antagonist without any significant anticholinergic and antiserotonic effects. At pharmacologically active dose levels, it has almost no drowsiness effect and does not cause behavioral changes. It inhibits the histamine-mediated early phase of the allergic reaction and also reduces the migration of inflammatory cells and the release of mediators associated with the late phase of the allergic reaction.

Pharmacokinetics: Cetirizine 10 mg achieves peak plasma concentrations of 257 mcg/L within one hour of administration (980 mcg/L in children). Food does not affect the extent of absorption, but it may slightly reduce the rate. Peak blood levels 0.3 micrograms/ml are reached between thirty & sixty minutes after administration of 10 mg dose of Cetirizine. Its plasma half-life is approximately 11 hours. Absorption is very consistent from one subject to the next. Its renal clearance is 30 ml/minute and the excretion half-life is approximately nine hours.

Adults and Children 6 years and older: 1 tablet or 2 teaspoonfuls daily (or 1 teaspoonful twice daily).

Children 2-6 years: 1 teaspoonful once daily or 1/2 teaspoonful twice daily.

Children 6 months to 2 years : 1/2 teaspoonful once daily. The dose in children 12-23 months of age can be increased to a maximum dose as 1/2 teaspoonful every 12 hours.

The most common side effects that occurred more frequently on Cetirizine is somnolence.

It is contraindicated in patients with a history of hypersensitivity to Cetirizine or hydroxyzine.

Caution should be exercised when driving a car or operating a heavy machinery.

No clinically significant drug interactions have been found with Theophylline, Azithromycin, Pseudoephedrine, Ketoconazole or Erythromycin and with other drugs.

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

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

Paracetamol is indicated for fever, common cold and influenza, headache, toothache, earache, bodyache, myalgia, neuralgia, dysmenorrhoea, sprains, colic pain, back pain, post-operative pain, postpartum pain, inflammatory pain and post vaccination pain in children. It is also indicated for rheumatic & osteoarthritic pain and stiffness of joints.

Non opioid analgesics

Paracetamol has analgesic and antipyretic properties with weak anti-inflammatory activity. Paracetamol (Acetaminophen) is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Paracetamol is a para aminophenol derivative, has analgesic and antipyretic properties with weak anti-inflammatory activity. Paracetamol is one of the most widely used, safest and fast acting analgesic. It is well tolerated and free from various side effects of aspirin.

Tablet:

• Adult: 1-2 tablets every 4 to 6 hours up to a maximum of 4 gm (8 tablets) daily.
• Children (6-12 years): ½ to 1 tablet 3 to 4 times daily. For long term treatment it is wise not to exceed the dose beyond 2.6 gm/day.

Extended Release Tablet:

• Adults & Children over 12 years: Two tablets, swallowed whole, every 6 to 8 hours (maximum of 6 tablets in any 24 hours).The tablet must not be crushed.

Syrup/Suspension:

• Children under 3 months: 10 mg/kg body weight (reduce to 5 mg/kg if jaundiced) 3 to 4 times daily.
• 3 months to below 1 year: ½ to 1 teaspoonful 3 to 4 times daily.
• 1-5 years: 1 -2 teaspoonful 3 to 4 times daily.
• 6-12 years: 2-A teaspoonful 3 to 4 times daily.
• Adults: 4-8 teaspoonful 3 to 4 times daily.

Suppository:

• Children 3-12 months: 60-120 mg,4 times daily.
• Children 1-5 years: 125-250 mg 4 times daily.
• Children 6-12 years: 250-500 mg 4 times daily.
• Adults & children over 12 years: 0.5-1 gm 4 times daily.

Paediatric Drop:

• Children Upto 3 months: 0.5 ml (40 mg)
• 4 to 11 months: 1.0 ml (80 mg)
• 7 to 2 years: 1.5 ml (120 mg). Do not exceed more than 5 dose daily for a maximum of 5 days.

Paracetamol tablet with actizorb technology: It dissolves up to five times faster than standard Paracetamol tablets. It is a fast acting and safe analgesic with marked antipyretic property. It is specially suitable for patients who, for any reason, can not tolerate aspirin or other analgesics.

• Adults and children (aged 12 years and over): Take 1 to 2 Tablets every four to six hours as needed. Do not take more than 8 caplets in 24 hours.
• Children (7 to 11 years): Take ½-1 Tablet every four to six hours as needed. Do not take more than 4 caplets in 24 hours. Not recommended in children under 7 years.

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

It is contraindicated in known hypersensitivity to Paracetamol.

Paracetamol should be given with caution to patients with impaired kidney or liver function. Paracetamol should be given with care to patients taking other drugs that affect the liver.

Patients who have taken barbiturates, tricyclic antidepressants and alcohol may show diminished ability to metabolise large doses of Paracetamol. Alcohol can increase the hepatotoxicity of Paracetamol overdosage. Chronic ingestion of anticonvulsants or oral steroid contraceptives induce liver enzymes and may prevent attainment of therapeutic Paracetamol levels by increasing first-pass metabolism or clearance.

Pregnancy category B according to USFDA. This drug should be used during pregnancy only if clearly needed

Symptoms of Paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12-48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur.

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

Salbutamol is indicated as a bronchodilator for use in-

• Asthma
• Chronic Bronchitis
• Emphysema and
• Other conditions associated with airways obstruction.

Short-acting selective & β2-adrenoceptor stimulants

Salbutamol is a synthetic sympathomimetic agent with predominant beta-2 adrenergic activity. Salbutamol produces bronchodilatation through stimulation of beta-2-adrenergic receptors in bronchial smooth muscles, thereby causing relaxation of bronchial muscle fibers. This action is manifested by an improvement in pulmonary function as demonstrated by spirometric measurements.

Salbutamol tablet or syrup-
Children:

• 2-6 years: 2.5 ml syrup, 3-4 times daily
• 6-12 years: 5 ml syrup, 3-4 times daily
• Over 12 years: 5-10 ml syrup, 3-4 times daily (2-4 mg tablet, 3-4 times daily)

Adults: 2-4 mg tablet, 3-4 times daily. Maximum single dose is 8 mg tablet.

Salbutamol Respirator Solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

Method-1 (Intermittent Administration):

• Adults (and the elderly): 0.5 ml-1.0 ml salbutamol up to four times a day. Up to 40mg per day can be given under strict medical direction in the hospital. 0.5-1 ml solution should be diluted to final volume of 2-4 ml with sterile normal saline solution. It will take time about 10 minutes.
• Salbutamol respiratory solution may be used undiluted for intermittent administration. For this 2.0 ml of the solution is placed in the nebulizer and the patient allowed to inhale until bronchodilation is achieved. This usually takes 3-5 minutes.
• Children under 12 years of age: 0.5 ml of the solution diluted to 2.0-4.0 ml with normal saline. Some children may however require higher doses of up to 1.0 ml of the solution. Intermittent treatment may be repeated four times a day.

Method-2 (Continuous administration): 1-2 ml solution is diluted to make up to 100 ml with normal saline solution. The diluted solution is administered by a suitable nebulizer devise. When there is risk of anoxia through hypoventilation, oxygen should be added to the inspired air.

Salbutamol nebulizer solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

• Adults & Elderly: 2.5 mg to 5 mg Salbutamol up to 4 times a day. Up to 40 mg/day may be given under strict medical direction in the hospital.
• Children under 12 years: 2.5 mg up to 4 times a day. A higher dose up to 5 mg four times a day may be used if required.

Salbutamol injection:
Adults:

• Salbutamol I.V. infusion solution is used to prepare a solution for continuous intravenous infusion. It should not be injected undiluted. A suitable solution for infusion may be prepared by diluting 5 mL of Salbutamol I.V. infusion solution (1000 mcg/mL) in 500 mL of a chosen i.v. solution to provide a salbutamol concentration of 10 mcg/mL.
• The only recommended diluents are Sodium Chloride Injection, or Sodium Chloride and Dextrose Injection.
• Infusion rates providing 3 to 20 micrograms salbutamol/minute (0.3 to 2ml/minute of the above infusion solution) are usually adequate. Infusion rates can be started at 5 mcg of salbutamol/min., and can be increased to 10 mcg/min., and 20 mcg/min. at 15 - 30 minute intervals, if necessary.
• As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discoloration and leakage prior to administration.
• All unused admixtures of Salbutamol infusion solution with infusion fluids should be discarded 24 hours after preparation.

Children and Adolescents (<18 years of age): The dosage of Salbutamol infusion solution in the pediatric age group has not been established. At present, there are insufficient data to recommend a dosage regimen for children.

Salbutamol Inhalation Capsule:

• Adults: For the relief of bronchospasm and for managing intermittent episodes of asthma, one or two inhalation capsule may be administered as a single dose. The usual recommended dosage of Salbutamol inhalation capsule for inhalation for adults for maintenance or prophylactic therapy is the contents of one 200 microgram capsule every 4 to 6 hours using a device. In some patients, the contents of two 200 microgram capsules inhaled every 4 to 6 hours may be required. Large doses or more frequent administration is not recommended. The use of salbutamol powder for inhalation can be continued as medically indicated to control recurring/intermittent episodes of bronchospasm.
• Children: One Salbutamol inhalation capsule is the recommended dose for relief of acute bronchospasm in the maintenance of episodic asthma or before exercise of children 4 years of age and older. One inhalation should be administered for three or four times a day for routine maintenance or prophylactic therapy. This dosage may be increased to inhalation of two inhalation capsule, if necessary. The bronchodilator effect of each administration of inhaled Salbutamol inhalation capsule lasts for at least four hours. Such patients should be warned not to increase the dose of inhaler, but should seek medical advice immediately.

Excercise-induced Asthma:

• Adults: 400 microgram
• Child: 200 microgram, 15-30 minutes prior to any physical exertion.

Salbutamol may cause fine tremor of skeletal muscles (particularly the hands), palpitations and muscle cramps. Tachycardia, tenseness, headaches and peripheral vasodilatation have been reported after large doses.

Salbutamol should be used with caution in patients with hyperthyroidism, cardiovascular disease, occlusive vascular disorders, hypertension and aneurysms. Hypokalaemia associated with high doses of Salbutamol may result in increased susceptibility to digitalis-induced cardiac arrhythmia. Tachyphylaxis with resistance may occur with prolonged use of high dosage. Care is necessary when treating patients with diabetes mellitus or closed angle glaucoma, and in those receiving antihypertensive therapy.

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, 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.

The symptoms with overdosage are angina, headache, nausea, vomiting, tremor etc. The preferred antidote for overdosage with Salbutamol is a cardio-selective beta-blocking agent but beta-blocking drugs should be used with caution in patients with a history of bronchospasm.

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

Salbutamol is indicated as a bronchodilator for use in-

• Asthma
• Chronic Bronchitis
• Emphysema and
• Other conditions associated with airways obstruction.

Short-acting selective & β2-adrenoceptor stimulants

Salbutamol is a synthetic sympathomimetic agent with predominant beta-2 adrenergic activity. Salbutamol produces bronchodilatation through stimulation of beta-2-adrenergic receptors in bronchial smooth muscles, thereby causing relaxation of bronchial muscle fibers. This action is manifested by an improvement in pulmonary function as demonstrated by spirometric measurements.

Salbutamol tablet or syrup-
Children:

• 2-6 years: 2.5 ml syrup, 3-4 times daily
• 6-12 years: 5 ml syrup, 3-4 times daily
• Over 12 years: 5-10 ml syrup, 3-4 times daily (2-4 mg tablet, 3-4 times daily)

Adults: 2-4 mg tablet, 3-4 times daily. Maximum single dose is 8 mg tablet.

Salbutamol Respirator Solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

Method-1 (Intermittent Administration):

• Adults (and the elderly): 0.5 ml-1.0 ml salbutamol up to four times a day. Up to 40mg per day can be given under strict medical direction in the hospital. 0.5-1 ml solution should be diluted to final volume of 2-4 ml with sterile normal saline solution. It will take time about 10 minutes.
• Salbutamol respiratory solution may be used undiluted for intermittent administration. For this 2.0 ml of the solution is placed in the nebulizer and the patient allowed to inhale until bronchodilation is achieved. This usually takes 3-5 minutes.
• Children under 12 years of age: 0.5 ml of the solution diluted to 2.0-4.0 ml with normal saline. Some children may however require higher doses of up to 1.0 ml of the solution. Intermittent treatment may be repeated four times a day.

Method-2 (Continuous administration): 1-2 ml solution is diluted to make up to 100 ml with normal saline solution. The diluted solution is administered by a suitable nebulizer devise. When there is risk of anoxia through hypoventilation, oxygen should be added to the inspired air.

Salbutamol nebulizer solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

• Adults & Elderly: 2.5 mg to 5 mg Salbutamol up to 4 times a day. Up to 40 mg/day may be given under strict medical direction in the hospital.
• Children under 12 years: 2.5 mg up to 4 times a day. A higher dose up to 5 mg four times a day may be used if required.

Salbutamol injection:
Adults:

• Salbutamol I.V. infusion solution is used to prepare a solution for continuous intravenous infusion. It should not be injected undiluted. A suitable solution for infusion may be prepared by diluting 5 mL of Salbutamol I.V. infusion solution (1000 mcg/mL) in 500 mL of a chosen i.v. solution to provide a salbutamol concentration of 10 mcg/mL.
• The only recommended diluents are Sodium Chloride Injection, or Sodium Chloride and Dextrose Injection.
• Infusion rates providing 3 to 20 micrograms salbutamol/minute (0.3 to 2ml/minute of the above infusion solution) are usually adequate. Infusion rates can be started at 5 mcg of salbutamol/min., and can be increased to 10 mcg/min., and 20 mcg/min. at 15 - 30 minute intervals, if necessary.
• As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discoloration and leakage prior to administration.
• All unused admixtures of Salbutamol infusion solution with infusion fluids should be discarded 24 hours after preparation.

Children and Adolescents (<18 years of age): The dosage of Salbutamol infusion solution in the pediatric age group has not been established. At present, there are insufficient data to recommend a dosage regimen for children.

Salbutamol Inhalation Capsule:

• Adults: For the relief of bronchospasm and for managing intermittent episodes of asthma, one or two inhalation capsule may be administered as a single dose. The usual recommended dosage of Salbutamol inhalation capsule for inhalation for adults for maintenance or prophylactic therapy is the contents of one 200 microgram capsule every 4 to 6 hours using a device. In some patients, the contents of two 200 microgram capsules inhaled every 4 to 6 hours may be required. Large doses or more frequent administration is not recommended. The use of salbutamol powder for inhalation can be continued as medically indicated to control recurring/intermittent episodes of bronchospasm.
• Children: One Salbutamol inhalation capsule is the recommended dose for relief of acute bronchospasm in the maintenance of episodic asthma or before exercise of children 4 years of age and older. One inhalation should be administered for three or four times a day for routine maintenance or prophylactic therapy. This dosage may be increased to inhalation of two inhalation capsule, if necessary. The bronchodilator effect of each administration of inhaled Salbutamol inhalation capsule lasts for at least four hours. Such patients should be warned not to increase the dose of inhaler, but should seek medical advice immediately.

Excercise-induced Asthma:

• Adults: 400 microgram
• Child: 200 microgram, 15-30 minutes prior to any physical exertion.

Salbutamol may cause fine tremor of skeletal muscles (particularly the hands), palpitations and muscle cramps. Tachycardia, tenseness, headaches and peripheral vasodilatation have been reported after large doses.

Salbutamol should be used with caution in patients with hyperthyroidism, cardiovascular disease, occlusive vascular disorders, hypertension and aneurysms. Hypokalaemia associated with high doses of Salbutamol may result in increased susceptibility to digitalis-induced cardiac arrhythmia. Tachyphylaxis with resistance may occur with prolonged use of high dosage. Care is necessary when treating patients with diabetes mellitus or closed angle glaucoma, and in those receiving antihypertensive therapy.

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, 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.

The symptoms with overdosage are angina, headache, nausea, vomiting, tremor etc. The preferred antidote for overdosage with Salbutamol is a cardio-selective beta-blocking agent but beta-blocking drugs should be used with caution in patients with a history of bronchospasm.

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

Pioglitazone & Metformin combination is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of Pioglitazone and Metformin or whose diabetes is not adequately controlled with Metformin alone or for those patients who have initially responded to Pioglitazone and require additional glycemic control.

Combination Oral hypoglycemic preparations

Pioglitazone depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulindependent glucose disposal and decreased hepatic glucose output. Pioglitazone is a potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPARg). Activation of PPARg nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.

Metformin hydrochloride improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia.

General: The use of antihyperglycemic therapy in the management of type 2 diabetes should be individualized on the basis of effectiveness and tolerability while not exceeding the maximum recommended daily dose of Pioglitazone 45 mg and Metformin 2550 mg.

Dosage Recommendations: Selecting the starting dose of Pioglitazone & Metformin should be based on the patient's current regimen of Pioglitazone and/or Metformin. Pioglitazone & Metformin should be given in divided daily doses with meals to reduce the gastrointestinal side effects associated with Metformin.

Starting dose for patients inadequately controlled on Metformin monotherapy Based on the usual starting dose of Pioglitazone (15-30 mg daily), Pioglitazone & Metformin may be initiated at either the 15 mg/500 mg or 15 mg/850 mg tablet strength once or twice daily, and gradually titrated after assessing adequacy of therapeutic response. Starting dose for patients who initially responded to Pioglitazone monotherapy and require additional glycemic control

Based on the usual starting doses of Metformin (500 mg twice daily or 850 mg daily), Pioglitazone & Metformin may be initiated at either the 15 mg/500 mg twice daily or 15 mg/850 mg tablet strength once daily, and gradually titrated after assessing adequacy of therapeutic response.

Starting dose for patients switching from combination therapy of Pioglitazone plus Metformin as separate tablets Pioglitazone & Metformin may be initiated with either the 15 mg/500 mg or 15 mg/850 mg tablet strengths based on the dose of Pioglitazone and Metformin already being taken.

Maximum Recommended Dose: Pioglitazone & Metformin tablets are available as a 15 mg Pioglitazone plus 500 mg Metformin or a 15 mg Pioglitazone plus 850 mg Metformin formulation for oral administration. The maximum recommended dose for Pioglitazone is 45 mg daily. The maximum recommended daily dose for Metformin is 2550 mg in adults. Special Patient Populations: The initial and maintenance dosing of combination of Pioglitazone and Metformin should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of combination of Pioglitazone and Metformin. Monitoring of renal function is necessary to aid in prevention of Metformin associated lactic acidosis, particularly in the elderly. Therapy with combination of Pioglitazone and Metformin should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serumtransaminase levels (ALT greater than 2.5 times the upper limit of normal) at start of therapy. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with combination of Pioglitazone and Metformin and periodically thereafter

Generally this combined preparation is well tolerated. However, the most common side effects are upper respiratory tract infection, diarrhea, peripheral edema and headache, respectively. These are mild in severity.

Contraindicated in patients with:

• Renal disease or renal dysfunction (e.g. as suggested by serum creatinine levels >1.5 mg/dl in male, >1.4 mg/dl in females or abnormal creatinine clearance), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction and septicemia.
• Known hypersensitivity to Pioglitazone, Metformin or any other component of this combination.
• Acute or chronic metabolic acidosis including diabetic ketoacidosis with or without coma.

Pioglitazone exerts its antihyperglycemic effect only in the presence of insulin. Therefore, Pioglitazone should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Pioglitazone should be used with caution in combination especially with insulin, hepatic insufficiency and heart diseases.

Metformin is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus patients with serum creatinine levels above the upper limit of normal for their age should not receive this combination.

May impair vit B12 absorption. Increased plasma levels with strong CYP2C8 inhibitors (e.g. gemfibrozil). Decreased plasma levels with CYP2C8 inducers (e.g. rifampicin). Reduced metabolism with cationic drugs eliminated by renal tubular secretion.

Pregnancy: There are no adequate and well-controlled studies in pregnant women with this combination or its individual components. So, it should only be used if the potential benefit justifies the potential risk to the fetus.

Nursing mother: It is not known whether Pioglitazone and/or Metformin are secreted in human milk. Because many drugs are excreted in human milk, this combination should not be administered to a breastfeeding woman.

The initial and maintenance dose of Pioglitazone & Metformin should be carefully selected in patients with advanced age due to the potential for decreased renal function in these populations. Monitoring of renal function is necessary to aid in prevention of Metformin associated lactic acidosis, particularly in the elderly. Pioglitazone & Metformin should not be initiated if the patients exhibit clinical evidence of active liver disease. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with combination of Pioglitazone and Metformin and periodically thereafter.

In the event of Overdosage, appropriate supportive treatment should be initiated according to patient's clinical signs and symptoms.

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

Pioglitazone & Metformin combination is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes who are already treated with a combination of Pioglitazone and Metformin or whose diabetes is not adequately controlled with Metformin alone or for those patients who have initially responded to Pioglitazone and require additional glycemic control.

Combination Oral hypoglycemic preparations

Pioglitazone depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulindependent glucose disposal and decreased hepatic glucose output. Pioglitazone is a potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPARg). Activation of PPARg nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism.

Metformin hydrochloride improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia.

General: The use of antihyperglycemic therapy in the management of type 2 diabetes should be individualized on the basis of effectiveness and tolerability while not exceeding the maximum recommended daily dose of Pioglitazone 45 mg and Metformin 2550 mg.

Dosage Recommendations: Selecting the starting dose of Pioglitazone & Metformin should be based on the patient's current regimen of Pioglitazone and/or Metformin. Pioglitazone & Metformin should be given in divided daily doses with meals to reduce the gastrointestinal side effects associated with Metformin.

Starting dose for patients inadequately controlled on Metformin monotherapy Based on the usual starting dose of Pioglitazone (15-30 mg daily), Pioglitazone & Metformin may be initiated at either the 15 mg/500 mg or 15 mg/850 mg tablet strength once or twice daily, and gradually titrated after assessing adequacy of therapeutic response. Starting dose for patients who initially responded to Pioglitazone monotherapy and require additional glycemic control

Based on the usual starting doses of Metformin (500 mg twice daily or 850 mg daily), Pioglitazone & Metformin may be initiated at either the 15 mg/500 mg twice daily or 15 mg/850 mg tablet strength once daily, and gradually titrated after assessing adequacy of therapeutic response.

Starting dose for patients switching from combination therapy of Pioglitazone plus Metformin as separate tablets Pioglitazone & Metformin may be initiated with either the 15 mg/500 mg or 15 mg/850 mg tablet strengths based on the dose of Pioglitazone and Metformin already being taken.

Maximum Recommended Dose: Pioglitazone & Metformin tablets are available as a 15 mg Pioglitazone plus 500 mg Metformin or a 15 mg Pioglitazone plus 850 mg Metformin formulation for oral administration. The maximum recommended dose for Pioglitazone is 45 mg daily. The maximum recommended daily dose for Metformin is 2550 mg in adults. Special Patient Populations: The initial and maintenance dosing of combination of Pioglitazone and Metformin should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of combination of Pioglitazone and Metformin. Monitoring of renal function is necessary to aid in prevention of Metformin associated lactic acidosis, particularly in the elderly. Therapy with combination of Pioglitazone and Metformin should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serumtransaminase levels (ALT greater than 2.5 times the upper limit of normal) at start of therapy. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with combination of Pioglitazone and Metformin and periodically thereafter

Generally this combined preparation is well tolerated. However, the most common side effects are upper respiratory tract infection, diarrhea, peripheral edema and headache, respectively. These are mild in severity.

Contraindicated in patients with:

• Renal disease or renal dysfunction (e.g. as suggested by serum creatinine levels >1.5 mg/dl in male, >1.4 mg/dl in females or abnormal creatinine clearance), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction and septicemia.
• Known hypersensitivity to Pioglitazone, Metformin or any other component of this combination.
• Acute or chronic metabolic acidosis including diabetic ketoacidosis with or without coma.

Pioglitazone exerts its antihyperglycemic effect only in the presence of insulin. Therefore, Pioglitazone should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Pioglitazone should be used with caution in combination especially with insulin, hepatic insufficiency and heart diseases.

Metformin is known to be substantially excreted by the kidney and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus patients with serum creatinine levels above the upper limit of normal for their age should not receive this combination.

May impair vit B12 absorption. Increased plasma levels with strong CYP2C8 inhibitors (e.g. gemfibrozil). Decreased plasma levels with CYP2C8 inducers (e.g. rifampicin). Reduced metabolism with cationic drugs eliminated by renal tubular secretion.

Pregnancy: There are no adequate and well-controlled studies in pregnant women with this combination or its individual components. So, it should only be used if the potential benefit justifies the potential risk to the fetus.

Nursing mother: It is not known whether Pioglitazone and/or Metformin are secreted in human milk. Because many drugs are excreted in human milk, this combination should not be administered to a breastfeeding woman.

The initial and maintenance dose of Pioglitazone & Metformin should be carefully selected in patients with advanced age due to the potential for decreased renal function in these populations. Monitoring of renal function is necessary to aid in prevention of Metformin associated lactic acidosis, particularly in the elderly. Pioglitazone & Metformin should not be initiated if the patients exhibit clinical evidence of active liver disease. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with combination of Pioglitazone and Metformin and periodically thereafter.

In the event of Overdosage, appropriate supportive treatment should be initiated according to patient's clinical signs and symptoms.

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

Pioglitazone is indicated as an adjunct to diet and exercise to improve glycaemic control in patients with type II diabetes (NIDDM). Pioglitazone is indicated for monotherapy and also indicated for use in combination with sulphonylurea, Metformin or Insulin when diet and exercise plus the single agent does not result in adequate glycaemic control.

Thiazolidinedione Group

Pioglitazone is a preparation of Pioglitazone which is a member of the newest class of oral antidiabetic agent called thiazolidinediones. It depends on the presence of Insulin for its mechanism of action. Pioglitazone decreases Insulin resistance in the periphery and in the liver, resulting in increased Insulin dependent glucose disposal and decreased hepatic glucose output. It also improves abnormality in lipid metabolism by activating peroxisome proliferator activated receptor gamma (PPAR-γ).

Pioglitazone can be taken once daily without regard to meals. The management of antidiabetic therapy should be individualized. Pioglitazone monotherapy may be initiated at 15 mg or 30 mg once daily dosages in patients not adequately controlled with diet and exercise alone. For patients who respond inadequately to the initial dose of Pioglitazone, the dose can be increased up to 45 mg once daily. For patients not responding adequately to monotherapy, combination therapy should be considered.

Maximum recommended daily dose of Pioglitazone should not exceed 45 mg since doses higher than 45 mg have not been studied in placebo controlled clinical studies. Besides, no placebo controlled clinical studies of more than 30 mg once daily have been conducted in combination therapy.

The overall incidence and types of adverse events reported in placebo controlled clinical trials of Pioglitazone monotherapy at doses of 7.5 mg, 15 mg, 30 mg or 45 mg once daily are upper respiratory tract infection (13.2%), headache (9.1%), sinusitis (6.3%), myalgia (5.4%), tooth disorder (5.3%), and pharyngitis (5.1%).

Pioglitazone is contraindicated in patients with known hypersensitivity to any of its components.

Pioglitazone exerts its antihyperglycaemic effect only in the presence of Insulin. Therefore, it should not be used in Type 1 diabetes or for the treatment of diabetic ketoacidosis. Pioglitazone should be used with caution in case of combination antidiabetic therapy and hepatic insufficiency. Liver enzyme should be monitored regularly.

Administration of thiazolidinediones with an oral contraceptive containing ethinyl oestradiol and norethindrone reduces the plasma concentration of both hormones by approximately 30% which could result in loss of contraception.

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

Lactation: It is not known whether Pioglitazone is secreted in human milk. As many drugs are excreted in human milk, it should not be administered to a lactating women.

Store at 25° C.

Pioglitazone is indicated as an adjunct to diet and exercise to improve glycaemic control in patients with type II diabetes (NIDDM). Pioglitazone is indicated for monotherapy and also indicated for use in combination with sulphonylurea, Metformin or Insulin when diet and exercise plus the single agent does not result in adequate glycaemic control.

Thiazolidinedione Group

Pioglitazone is a preparation of Pioglitazone which is a member of the newest class of oral antidiabetic agent called thiazolidinediones. It depends on the presence of Insulin for its mechanism of action. Pioglitazone decreases Insulin resistance in the periphery and in the liver, resulting in increased Insulin dependent glucose disposal and decreased hepatic glucose output. It also improves abnormality in lipid metabolism by activating peroxisome proliferator activated receptor gamma (PPAR-γ).

Pioglitazone can be taken once daily without regard to meals. The management of antidiabetic therapy should be individualized. Pioglitazone monotherapy may be initiated at 15 mg or 30 mg once daily dosages in patients not adequately controlled with diet and exercise alone. For patients who respond inadequately to the initial dose of Pioglitazone, the dose can be increased up to 45 mg once daily. For patients not responding adequately to monotherapy, combination therapy should be considered.

Maximum recommended daily dose of Pioglitazone should not exceed 45 mg since doses higher than 45 mg have not been studied in placebo controlled clinical studies. Besides, no placebo controlled clinical studies of more than 30 mg once daily have been conducted in combination therapy.

The overall incidence and types of adverse events reported in placebo controlled clinical trials of Pioglitazone monotherapy at doses of 7.5 mg, 15 mg, 30 mg or 45 mg once daily are upper respiratory tract infection (13.2%), headache (9.1%), sinusitis (6.3%), myalgia (5.4%), tooth disorder (5.3%), and pharyngitis (5.1%).

Pioglitazone is contraindicated in patients with known hypersensitivity to any of its components.

Pioglitazone exerts its antihyperglycaemic effect only in the presence of Insulin. Therefore, it should not be used in Type 1 diabetes or for the treatment of diabetic ketoacidosis. Pioglitazone should be used with caution in case of combination antidiabetic therapy and hepatic insufficiency. Liver enzyme should be monitored regularly.

Administration of thiazolidinediones with an oral contraceptive containing ethinyl oestradiol and norethindrone reduces the plasma concentration of both hormones by approximately 30% which could result in loss of contraception.

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

Lactation: It is not known whether Pioglitazone is secreted in human milk. As many drugs are excreted in human milk, it should not be administered to a lactating women.

Store at 25° C.

Rapid Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Always use your insulin and adjust your dose exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure. Eat a meal or snack containing carbohydrates within 30 minutes of the injection to avoid low blood sugar. Do not change your insulin unless your doctor tells you to. If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin.

Low blood sugar (hypoglycaemia) is a very common side effect. It may affect more than 1 in 10 people.

Signs of low blood sugar: Cold sweat; cool pale skin; headache; rapid heartbeat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This insulin can be used during pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important for the health of your baby. There are no restrictions on treatment with this insulin during breast-feeding.

Use in children and adolescents: Can be used in children and adolescents.

Use in special patient groups: If you have reduced kidney or liver function, or if you are above 65 years of age, you need to check your blood sugar more regularly and discuss changes in your insulin dose with your doctor.

Store in a refrigerator at 2°C-8°C. Keep away from the cooling element. Do not freeze.

Rapid Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Always use your insulin and adjust your dose exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure. Eat a meal or snack containing carbohydrates within 30 minutes of the injection to avoid low blood sugar. Do not change your insulin unless your doctor tells you to. If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin.

Low blood sugar (hypoglycaemia) is a very common side effect. It may affect more than 1 in 10 people.

Signs of low blood sugar: Cold sweat; cool pale skin; headache; rapid heartbeat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This insulin can be used during pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important for the health of your baby. There are no restrictions on treatment with this insulin during breast-feeding.

Use in children and adolescents: Can be used in children and adolescents.

Use in special patient groups: If you have reduced kidney or liver function, or if you are above 65 years of age, you need to check your blood sugar more regularly and discuss changes in your insulin dose with your doctor.

Store in a refrigerator at 2°C-8°C. Keep away from the cooling element. Do not freeze.

Rapid Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Always use your insulin and adjust your dose exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure. Eat a meal or snack containing carbohydrates within 30 minutes of the injection to avoid low blood sugar. Do not change your insulin unless your doctor tells you to. If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin.

Low blood sugar (hypoglycaemia) is a very common side effect. It may affect more than 1 in 10 people.

Signs of low blood sugar: Cold sweat; cool pale skin; headache; rapid heartbeat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This insulin can be used during pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important for the health of your baby. There are no restrictions on treatment with this insulin during breast-feeding.

Use in children and adolescents: Can be used in children and adolescents.

Use in special patient groups: If you have reduced kidney or liver function, or if you are above 65 years of age, you need to check your blood sugar more regularly and discuss changes in your insulin dose with your doctor.

Store in a refrigerator at 2°C-8°C. Keep away from the cooling element. Do not freeze.

Rapid Acting Insulin

The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Insulatard is a long-acting insulin. Onset of action is within 1½ hours, reaches a maximum effect within 4-12 hours and the entire time of duration is approximately 24 hours.

Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulins is therefore affected by significant intra- and inter-individual variation

Always use your insulin and adjust your dose exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure. Eat a meal or snack containing carbohydrates within 30 minutes of the injection to avoid low blood sugar. Do not change your insulin unless your doctor tells you to. If your doctor has switched you from one type or brand of insulin to another, your dose may have to be adjusted by your doctor.

For subcutaneous use. Insulatard is usually administered subcutaneously in the thigh. If convenient, the abdominal wall, the gluteal region or the deltoid region may also be used. Subcutaneous injection into the thigh results in a slower and less variable absorption compared to the other injection sites. Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.

Keep the needle under the skin for at least 6 seconds to make sure the entire dose is injected. Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy. Insulin suspensions are never to be administered intravenously. Insulatard is accompanied by a package leaflet with detailed instruction for use to be followed. The vials are for use with insulin syringes with corresponding unit scale. When two types of insulin are mixed, draw the amount of fast-acting insulin first, followed by the amount of long-acting insulin.

Low blood sugar (hypoglycaemia) is a very common side effect. It may affect more than 1 in 10 people.

Signs of low blood sugar: Cold sweat; cool pale skin; headache; rapid heartbeat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This insulin can be used during pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important for the health of your baby. There are no restrictions on treatment with this insulin during breast-feeding.

Use in children and adolescents: Can be used in children and adolescents.

Use in special patient groups: If you have reduced kidney or liver function, or if you are above 65 years of age, you need to check your blood sugar more regularly and discuss changes in your insulin dose with your doctor.

Store in a refrigerator at 2°C-8°C. Keep away from the cooling element. Do not freeze.

Anti-diarrhoeal Antimicrobial drugs, Sulphonamides & Trimethoprim

Cotrimoxazole having broad spectrum bactericidal activity against a wide range of gram-positive & gram-negative bacteria and some protozoa. Co-trimoxazole containing Trimethoprim and Sulphamethoxazole in a 1:5 combination exerts its bactericidal action by the sequential blockade of two bacterial enzyme systems in the biosynthesis of folinic acid in the microorganism.

Cotrimoxazole double strength tablet: Over 12 years

• For mild to moderate infections: 1 tablet twice daily.
• For severe infections: 1.5 tablets twice daily.
• Long term therapy (>14 days): 0.5 tablet twice daily.
• Gonorrhoea: 2 tablets every 12 hours for two days or 2.5 tablets followed by a further dose of 2.5 tablets after 8 hours.

Cotrimoxazole tablet: over 12 years

• For mild to moderate infections: 2 tablets twice daily.
• For severe infections: 2 tablets thrice daily.
• Long term therapy: (>14 days): 1 tablet twice daily.

Cotrimoxazole suspension: Under 12 years

• 6-12 years: 2 teaspoonful twice daily.
• 6 month-5 years: 1 teaspoonful twice daily.
• 6 weeks-6 months: 0.5 teaspoonful twice daily.

The side effects like crystalluria, allergic reactions, haemolysis, thrombocytopenia, neutropenia, agranulocytosis etc. have been reported rarely with Sulphamethoxazole-Trimethoprim combination. Other side effects are less serious in nature such as malaise, headache, nausea and vomiting. These are normally transient and do not require withdrawal of treatment.

Prolonged full dose treatment with sulfamethoxazole-trimethoprim combination is associated with the risk of macrocytic anaemia due to the drug’s interference in the conversion of Folic acid into Folinic acid. If this occurs, it can be reversed by giving Folinic acid. Care should be taken when giving this combination to diabetic patients receiving sulphonylurea drug for possible potentiation of action of sulphonylurea.

Pregnancy and during the nursing period, because sulphonamides pass the placenta and are excreted in the breast milk and may cause kernicterus.

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

Anti-diarrhoeal Antimicrobial drugs, Sulphonamides & Trimethoprim

Cotrimoxazole having broad spectrum bactericidal activity against a wide range of gram-positive & gram-negative bacteria and some protozoa. Co-trimoxazole containing Trimethoprim and Sulphamethoxazole in a 1:5 combination exerts its bactericidal action by the sequential blockade of two bacterial enzyme systems in the biosynthesis of folinic acid in the microorganism.

Cotrimoxazole double strength tablet: Over 12 years

• For mild to moderate infections: 1 tablet twice daily.
• For severe infections: 1.5 tablets twice daily.
• Long term therapy (>14 days): 0.5 tablet twice daily.
• Gonorrhoea: 2 tablets every 12 hours for two days or 2.5 tablets followed by a further dose of 2.5 tablets after 8 hours.

Cotrimoxazole tablet: over 12 years

• For mild to moderate infections: 2 tablets twice daily.
• For severe infections: 2 tablets thrice daily.
• Long term therapy: (>14 days): 1 tablet twice daily.

Cotrimoxazole suspension: Under 12 years

• 6-12 years: 2 teaspoonful twice daily.
• 6 month-5 years: 1 teaspoonful twice daily.
• 6 weeks-6 months: 0.5 teaspoonful twice daily.

The side effects like crystalluria, allergic reactions, haemolysis, thrombocytopenia, neutropenia, agranulocytosis etc. have been reported rarely with Sulphamethoxazole-Trimethoprim combination. Other side effects are less serious in nature such as malaise, headache, nausea and vomiting. These are normally transient and do not require withdrawal of treatment.

Prolonged full dose treatment with sulfamethoxazole-trimethoprim combination is associated with the risk of macrocytic anaemia due to the drug’s interference in the conversion of Folic acid into Folinic acid. If this occurs, it can be reversed by giving Folinic acid. Care should be taken when giving this combination to diabetic patients receiving sulphonylurea drug for possible potentiation of action of sulphonylurea.

Pregnancy and during the nursing period, because sulphonamides pass the placenta and are excreted in the breast milk and may cause kernicterus.

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

Osmotic purgatives

Lactulose is a synthetic disaccharide. Lactulose is metabolized in the colon by the saccharolytic bacteria, producing low molecular weight organic acids (mainly lactic acid), which lowers the pH of the colon contents, promote the retention of water by an osmotic effect; thus increasing peristaltic activity. Lactulose is minimally absorbed; therefore, the pharmacokinetics of the absorbed material are not relevant to the principal therapeutic action.

In constipation ( chronic constipation):

• Adults: Initially 3-6 tea-spoons daily, In long-term therapy 1½-6 tea-spoons daily
• Children up to 14 years: Initially 3 tea-spoons daily, In long-term therapy 1-2 tea-spoons daily
• Infants and toddlers: Initially 1-2 tea-spoons daily, In long-term therapy 1 tea-spoon daily

In damaged intestinal flora:

• Adults: 1-2 tea-spoons daily
• Children: 1 tea-spoon daily

For reduction of blood ammonia level:

• Hyper-ammoniemia in hepatopathy: a maximum of 18-30 tea-spoons daily.
• In portal systemic encephalopathy: hourly doses of 6-9 tea-spoons of Lactulose solution may be used to induce the rapid laxation. When the laxative effect has been achieved, the dose may then be reduced.

Occasionally flatulence, cramp and abdominal discomfort can occur at the beginning of treatment; this is rapidly eliminated by reducing the dose. Overdose can result in diarrhoea. In abuse, loss of electrolytes (primarily potassium).

Hypersensitivity to either galactose and or lactose; galactose-free diet, gastro-cardial symptom complex, suspected intestinal obstruction.

Lactulose should be administered with care to patients who are intolerant to lactulose. The dose used in the treatment of (pre) coma hepaticum is usually much higher and may need to be taken into consideration for diabetics.

There is no significant drug interactions with lactulose. The glycosidic effect of cardiac glycosides can be intensified by potassium deficiency in abuse.

US FDA Pregnancy Category of Lactulose is B. Studies show that Lactulose has no adverse effects. Decisions regarding use during pregnancy and lactation must be made by registered physician.

There have been no reports of accidental overdosage. In the event of acute overdosage it is expected that diarrhoea and abdominal cramps would be the major symptoms.

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

Bisoprolol is indicated in-

• Hypertension
• Angina
• Moderate to severe heart failure

Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit.

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

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min) as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction

Bisoprolol, like any medication, may have some side effects. It is important that you keep your doctor informed of all side effects especially if you experience one of the following for several days. The most common side effects, whether or not caused by Bisoprolol, are: headache, fatigue, urinary tract infection, rhinitis or sinusitis (inflammation in the nose), diarrhea, dizziness, peripheral edema (swelling of the ankles), joint pain, cough, insomnia (trouble sleeping), nausea (feeling like vomiting), and sore throat. You must seek medical attention immediately if you experience an allergic reaction with symptoms of rash, itching, swelling, dizziness or trouble breathing.

Medicines affect different people in different ways. Just because side effects have occurred in other patients does not mean you will get them. Discuss how you feel on Bisoprolol with your doctor or pharmacist. Do not stop or restart Bisoprolol on your own.

In patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension and sinus bradycardia.

Monitoring of renal, hepatic and hematopoietic function should be performed at regular intervals during long-term treatment with bisoprolol.

Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. Bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If use of bisoprolol fumarate is considered essential, then mothers should stop nursing.

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

Bisoprolol is indicated in-

• Hypertension
• Angina
• Moderate to severe heart failure

Bisoprolol is not recommended for the emergency treatment of hypertensive crises.

Anti adrenergic agent (Beta blockers), Beta-adrenoceptor blocking drugs, Beta-blockers

Bisoprolol Hemifumarate is the most selective ß1 blocker. It displays highest level of affinity for the ß1 receptor than any other beta-blocker available up to now. Selectively blocks ß1 adrenergic receptor in the heart and vascular smooth muscle and reduces heart rate and cardiac output resulting in decrease of arterial hypertension. Lipid metabolism can be adversely affected by ß-blockers, in patients with non-ß1 selective ß1-blocker, but Bisoprolol does not cause any change in the cholesterol fraction including the cardioprotective HDL-cholesterol, in long-term therapy.

Adult: In the treatment of mild to moderate hypertension, Bisoprolol fumarate must be individualized to the needs of the patient. The usual starting dose is 5 mg once daily either added to a diuretic or alone. If the response to 5 mg is inadequate, the dose may be increased to 10 mg and then, if necessary, to 20 mg once daily. An appropriate interval for dose titration is 2 weeks. Increasing the dose beyond 20 mg once daily produces only a small incremental benefit.

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

Patients With Renal or Hepatic Impairment: In patients with hepatic impairment (hepatitis or cirrhosis) or renal dysfunction (creatinine clearance less than 40 mL/min) as in other patients, the initial daily dose should be 5 mg. Because of the possibility of accumulation, caution must be used in dose titration. Since limited data suggest that bisoprolol fumarate is not dialysable, drug replacement is not necessary in patients undergoing dialysis.

Geriatrics: In the elderly, it is not usually necessary to adjust the dose, unless there is also significant renal or hepatic dysfunction

Bisoprolol, like any medication, may have some side effects. It is important that you keep your doctor informed of all side effects especially if you experience one of the following for several days. The most common side effects, whether or not caused by Bisoprolol, are: headache, fatigue, urinary tract infection, rhinitis or sinusitis (inflammation in the nose), diarrhea, dizziness, peripheral edema (swelling of the ankles), joint pain, cough, insomnia (trouble sleeping), nausea (feeling like vomiting), and sore throat. You must seek medical attention immediately if you experience an allergic reaction with symptoms of rash, itching, swelling, dizziness or trouble breathing.

Medicines affect different people in different ways. Just because side effects have occurred in other patients does not mean you will get them. Discuss how you feel on Bisoprolol with your doctor or pharmacist. Do not stop or restart Bisoprolol on your own.

In patients with cardiogenic shock, overt heart failure, second or third degree A-V block, right ventricular failure secondary to pulmonary hypertension and sinus bradycardia.

Monitoring of renal, hepatic and hematopoietic function should be performed at regular intervals during long-term treatment with bisoprolol.

Other β-blocking Agents: Bisoprolol fumarate should not be combined with other β-blocking agents.

Catecholamine-Depleting Drugs: Patients receiving catecholamine-depleting drugs, such as reserpine or guanethidine, should be monitored closely because the added β-adrenergic blocking action of bisoprolol fumarate may produce excessive reduction of sympathetic activity.

Centrally Active Antihypertensive Agents: β-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. If the two drugs are coadministered, the β-blocker should be withdrawn several days before discontinuing clonidine. If replacing clonidine by β-blocker therapy, the introduction of β-blockers should be delayed for several days after clonidine administration has stopped (see also prescribing information for clonidine).

Antiarrhythmic Agents: Bisoprolol fumarate should be used with care when myocardial depressants or inhibitors of A-V conduction, such as certain calcium antagonists (particularly of the phenyl alkylamine (verapamil) and benzothiazepine (diltiazem) classes), or antiarrhythmic agents, such as disopyramide, are used concurrently.

Calcium Channel Blockers: Combined use of β-blockers and calcium channel blockers with negative inotropic effects can lead to prolongation of S-A and A-V conduction, particularly in patients with impaired ventricular function or conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure.

Pregnancy: Bisoprolol fumarate was not teratogenic in rats at doses up to 150 mg/kg/day, which is 375 times the maximum recommended human daily dose. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body-weight gain) at 150 mg/kg/day. Bisoprolol fumarate was not teratogenic in rabbits at doses up to 12.5 mg/kg/day, which is 31 times the maximum recommended human daily dose, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. There are no studies in pregnant women. Bisoprolol fumarate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Small amounts of bisoprolol fumarate (<2% of the dose) have been detected in the milk of lactating rats. It is not known whether this drug is excreted in human milk. If use of bisoprolol fumarate is considered essential, then mothers should stop nursing.

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

Calcium-channel blockers

Amlodipine is a dihydropyridine calcium-channel blocker, with a long duration of action, used for the treatment of hypertension and angina pectoris. Amlodipine influences the myocardial cells, the cells within the specialized conducting system of the heart, and the cells of vascular smooth muscle. Administration of Amlodipine results primarily in vasodilation, with reduced peripheral resistance, blood pressure and afterload, increased coronary blood flow and a reflex increase in coronary heart rate. This in turn results in an increase in myocardial oxygen supply and cardiac output.

Hypertension: Usual dose is 5 mg once daily. The maximum dose is 10 mg once daily. Elderly patients with hepatic insufficiency may be started on 2.5 mg once daily; this dose may also be used when adding Amlodipine to other antihypertensive therapy.

Angina (Chronic stable or Vasospastic): 5 to 10 mg, using the lower dose for elderly and in patients with hepatic insufficiency. Most patients require 10 mg.

Administrations: May be taken without regard to meals.

The most common adverse effects of amlodipine are associated with vasodilatory action, such as dizziness, flushing, headache, hypotension and peripheral edema. Gastrointestinal disturbances, increased micturition frequency, lethargy, eye pain and mental depression may also occur. A paradoxical increase in ischaemic chest pain may occur at the start of the treatment and in a few patients excessive fall in blood pressure has led to cerebral or myocardial ischaemia or transient blindness. Rashes, fever and abnormalities in liver function due to hypersensitivity reaction of Amlodipine may occur.

Hypersensitivity to dihydropyridine derivatives. Pregnant woman.

Precaution should be taken in patients with hepatic impairment and during pregnancy and breast feeding.

Drug Interactions-

• Potentially hazardous interactions: Little or no data are available in patients with markedly impaired cardiac left ventricular function; however, as with other calcium antagonist drugs, the combination of Amlodipine and p-blockers should be avoided in such patients.

Other Significant Interactions-

• Digoxin: Absence of any interaction between Amlodipine and Digoxin in healthy volunteers has been documented in a controlled clinical study.
• Cimetidine: An unpublished clinical study indicated no interaction between, Amlodipine and Cimetidine in healthy volunteers.
• Warfarin: An unpublished clinical study in healthy volunteers indicates that Amlodipine did not significantly alter the effect of Warfarin on prothrombin time.
• Food: Food does not alter the rate or extent of absorption of Amlodipine.

Pregnancy Category C. There are no adequate and well-controlled studies of Amlodipine in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while Amlodipine is administered.

Children with hypertension from 6 years to 17 years of age: 2.5 mg once daily as a starting dose, up-titrated to 5 mg once daily if blood pressure goal is not achieved after 4 weeks. Doses in excess of 5 mg daily have not been studied in pediatric patients.

Children under 6 years old:  The effect of amlodipine on blood pressure in patients less than 6 years of age is not known.

Elderly: Amlodipine used at similar doses in elderly or younger patients is equally well tolerated. Normal dosage regimens are recommended in the elderly, but increase of the dosage should take place with care.

Renal impairment: Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment, therefore the normal dosage is recommended. Amlodipine is not dialysable.

Hepatic impairment: Dosage recommendations have not been established in patients with mild to moderate hepatic impairment; therefore dose selection should be cautions and should start at the lower end of the dosing range. The pharmacokinetics of Amlodipine have not been studied in severe hepatic impairment. Amlodipine should be initiated at the lowest dose (2.5 mg once daily) and titrated slowly in patients with severe hepatic impairment.

Symptoms: Available data suggest that large overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported.

Management: Clinically significant hypotension due to amlodipine overdosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. 

A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours after administration of amlodipine 10 mg has been shown to reduce the absorption rate of amlodipine. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit.

Keep all medicines out of reach of children. Store in a cool & dry place, protected from light.

This is indicated in-

• Patients with essential hypertension
• Patients with angina pectoris & hypertension as co-existing diseases
• ln post Ml patients
• ln patients with refractory angina pectoris where nitrate therapy has failed.

Combined antihypertensive preparations

This is a fixed-dose combination of Amlodipine and Atenolol. Amlodipine is a dihydropyridine calcium antagonist that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle; it has a greater effect on vascular smooth muscle than on cardiac muscle. Amlodipine is a peripheral vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Amlodipine reduces tone, decreases coronary vasoreactivity and lowers cardiac demand by reducing afterload.

Atenolol is a cardioselective beta-blocker. The cardio-selectivity is dose-related. Atenolol causes a reduction in blood pressure by lowering cardiac output, decreasing the plasma renin activity and sympathetic outflow from CNS. Atenolol also causes a reduction in myocardial oxygen demand by virtue of its negative inotropic and negative chronotropic effects.

The recommended dosage is Amlodipine and Atenolol 5/25 mg tablet once daily. If necessary, the dosage may be increased to 5/25 mg two tablets daily or as advised by the physicians. The dosage however should be individualized.

The combination of Amlodipine and Atenolol is well tolerated. Overall side-effects include
fatigue, headache, edema, nausea, drowsiness, anxiety and depression.

Hypersensitivity to either component, sinus bradycardia, second and higher degrees of heart block, cardiogenic shock, hypotension, congestive heart failure, poor left ventricular function.

Bronchospasm: The combination should be used with caution in patients with airway obstruction.

Renal impairment: The combination can be used in patients with renal impairment. However, caution may be necessary if the creatinine clearance is less than 30 ml/min because of possible reduction in the excretion of unchanged Atenolol.

Hepatic impairment: Caution may be necessary in the use of the combination in patients with severe liver damage because of prolongation of the elimination half-life of Amlodipine.

Drug withdrawal: Since coronary heart disease may exist without being recognized, patients should be warned against stopping the drug suddenly. Any discontinuation should be gradual and under observation.

Disopyramide: Atenolol reduces the clearance of disopyramide by 20%. Additive negative inotropic effects on the heart may be produced.

Ampicillin: at doses of 1 gm and above may reduce Atenolol levels.

Oral antidiabetics and insulin: Beta-blockers may decrease tissue sensitivity to insulin and inhibit insulin secretion e.g. in response to oral antidiabetics. Atenolol has less potential for these actions.

The combination should be used during pregnancy only if the expected benefit outweighs the potential fetal risk. The combination should not be used by nursing mothers. If its use is considered necessary, breast-feeding should be stopped.

Though not documented, hypotension and less frequently congestive cardiac failure may occur in cases of overdosage. Unabsorbed drugs may be removed by gastric lavage or administration of activated charcoal. Symptomatic treatment is suggested.

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