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Theophylline is indicated for the-

• Control of acute asthma.
• Management of chronic asthma (For both Symptomatic and prophylactic treatment).
• For controlling nocturnal asthma and early morning wheezing.
• Management of chronic obstructive lung disease (Chronic bronchitis and emphysema) and acute exacerbation of chronic obstructive lung disease.
• Control of apnea of pre-maturity.

Bronchodilator, Theophylline & related drugs

Theophylline is a bronchodilator, structurally classified as a Methylxanthine. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation and suppression of the response of the airways to stimuli. Theophylline also increases the force of contraction of diaphragmatic muscles. The half-life of Theophylline is influenced by a number of known variables. In adult nonsmokers with uncomplicated asthma the half-life ranges from 3 to 9 hours

The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Most of the sustained release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic
metabolism of theophylline. The recommended maintenance dose within accepted therapeutic range is as follows :

• 16 years or older: 10 mg/Kg/day (Do not exceed 900 mg/day)
• 12 years-15 years: 13 mg/Kg/day
• 9-11 years: 16 mg/Kg/day
• 1 year-8 years: 24-24 mg/Kg/day
• 6 months-1 year: 12-18 mg/Kg/day
• 1-6 months: 10 mg/Kg/day.

Generally side effects are rare at normal dosage. It may include gastrointestinal discomfort, headache, nausea, insomnia and hypotension. CNS stimulation and diuresis may also occur, especially in children.

Theophylline is contraindicated in patients with hypersensitivity to Theophylline or any other component of the product.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Theophylline should not be used concurrently with other preparations containing xanthine derivatives. The clearance of theophylline is increased by barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone and it may therefore be necessary to increase dosage. On the other hand, the clearance of the drug is reduced by allopurinol, cimetidine, ciprofloxacin, corticosteroids, erythromycin, frusemide, isoprenaline, oral contraceptive and thiabendazole and a reduced dosage may therefore be needed to avoid side effects. Theophylline can potentiate hypokalemia resulting from beta-2-agonist therapy, steroids, diuretics and hypoxia, so serum potassium levels should be monitored in such instances.

It is not known whether Theophylline can cause foetal harm when administered to pregnant woman. Xanthines should be given to a pregnant woman only if clearly needed. Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Pediatrics use: The clearance of Theophylline is very low in neonates. Careful attention to dosage selection and monitoring of serum Theophylline concentrations are required in pediatric patients.

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

Theophylline is indicated for the-

• Control of acute asthma.
• Management of chronic asthma (For both Symptomatic and prophylactic treatment).
• For controlling nocturnal asthma and early morning wheezing.
• Management of chronic obstructive lung disease (Chronic bronchitis and emphysema) and acute exacerbation of chronic obstructive lung disease.
• Control of apnea of pre-maturity.

Bronchodilator, Theophylline & related drugs

Theophylline is a bronchodilator, structurally classified as a Methylxanthine. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation and suppression of the response of the airways to stimuli. Theophylline also increases the force of contraction of diaphragmatic muscles. The half-life of Theophylline is influenced by a number of known variables. In adult nonsmokers with uncomplicated asthma the half-life ranges from 3 to 9 hours

The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Most of the sustained release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic
metabolism of theophylline. The recommended maintenance dose within accepted therapeutic range is as follows :

• 16 years or older: 10 mg/Kg/day (Do not exceed 900 mg/day)
• 12 years-15 years: 13 mg/Kg/day
• 9-11 years: 16 mg/Kg/day
• 1 year-8 years: 24-24 mg/Kg/day
• 6 months-1 year: 12-18 mg/Kg/day
• 1-6 months: 10 mg/Kg/day.

Generally side effects are rare at normal dosage. It may include gastrointestinal discomfort, headache, nausea, insomnia and hypotension. CNS stimulation and diuresis may also occur, especially in children.

Theophylline is contraindicated in patients with hypersensitivity to Theophylline or any other component of the product.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Theophylline should not be used concurrently with other preparations containing xanthine derivatives. The clearance of theophylline is increased by barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone and it may therefore be necessary to increase dosage. On the other hand, the clearance of the drug is reduced by allopurinol, cimetidine, ciprofloxacin, corticosteroids, erythromycin, frusemide, isoprenaline, oral contraceptive and thiabendazole and a reduced dosage may therefore be needed to avoid side effects. Theophylline can potentiate hypokalemia resulting from beta-2-agonist therapy, steroids, diuretics and hypoxia, so serum potassium levels should be monitored in such instances.

It is not known whether Theophylline can cause foetal harm when administered to pregnant woman. Xanthines should be given to a pregnant woman only if clearly needed. Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Pediatrics use: The clearance of Theophylline is very low in neonates. Careful attention to dosage selection and monitoring of serum Theophylline concentrations are required in pediatric patients.

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

Theophylline is indicated for the-

• Control of acute asthma.
• Management of chronic asthma (For both Symptomatic and prophylactic treatment).
• For controlling nocturnal asthma and early morning wheezing.
• Management of chronic obstructive lung disease (Chronic bronchitis and emphysema) and acute exacerbation of chronic obstructive lung disease.
• Control of apnea of pre-maturity.

Bronchodilator, Theophylline & related drugs

Theophylline is a bronchodilator, structurally classified as a Methylxanthine. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation and suppression of the response of the airways to stimuli. Theophylline also increases the force of contraction of diaphragmatic muscles. The half-life of Theophylline is influenced by a number of known variables. In adult nonsmokers with uncomplicated asthma the half-life ranges from 3 to 9 hours

The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Most of the sustained release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic
metabolism of theophylline. The recommended maintenance dose within accepted therapeutic range is as follows :

• 16 years or older: 10 mg/Kg/day (Do not exceed 900 mg/day)
• 12 years-15 years: 13 mg/Kg/day
• 9-11 years: 16 mg/Kg/day
• 1 year-8 years: 24-24 mg/Kg/day
• 6 months-1 year: 12-18 mg/Kg/day
• 1-6 months: 10 mg/Kg/day.

Generally side effects are rare at normal dosage. It may include gastrointestinal discomfort, headache, nausea, insomnia and hypotension. CNS stimulation and diuresis may also occur, especially in children.

Theophylline is contraindicated in patients with hypersensitivity to Theophylline or any other component of the product.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Theophylline should not be used concurrently with other preparations containing xanthine derivatives. The clearance of theophylline is increased by barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone and it may therefore be necessary to increase dosage. On the other hand, the clearance of the drug is reduced by allopurinol, cimetidine, ciprofloxacin, corticosteroids, erythromycin, frusemide, isoprenaline, oral contraceptive and thiabendazole and a reduced dosage may therefore be needed to avoid side effects. Theophylline can potentiate hypokalemia resulting from beta-2-agonist therapy, steroids, diuretics and hypoxia, so serum potassium levels should be monitored in such instances.

It is not known whether Theophylline can cause foetal harm when administered to pregnant woman. Xanthines should be given to a pregnant woman only if clearly needed. Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Pediatrics use: The clearance of Theophylline is very low in neonates. Careful attention to dosage selection and monitoring of serum Theophylline concentrations are required in pediatric patients.

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

Theophylline is indicated for the-

• Control of acute asthma.
• Management of chronic asthma (For both Symptomatic and prophylactic treatment).
• For controlling nocturnal asthma and early morning wheezing.
• Management of chronic obstructive lung disease (Chronic bronchitis and emphysema) and acute exacerbation of chronic obstructive lung disease.
• Control of apnea of pre-maturity.

Bronchodilator, Theophylline & related drugs

Theophylline is a bronchodilator, structurally classified as a Methylxanthine. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation and suppression of the response of the airways to stimuli. Theophylline also increases the force of contraction of diaphragmatic muscles. The half-life of Theophylline is influenced by a number of known variables. In adult nonsmokers with uncomplicated asthma the half-life ranges from 3 to 9 hours

The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Most of the sustained release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic
metabolism of theophylline. The recommended maintenance dose within accepted therapeutic range is as follows :

• 16 years or older: 10 mg/Kg/day (Do not exceed 900 mg/day)
• 12 years-15 years: 13 mg/Kg/day
• 9-11 years: 16 mg/Kg/day
• 1 year-8 years: 24-24 mg/Kg/day
• 6 months-1 year: 12-18 mg/Kg/day
• 1-6 months: 10 mg/Kg/day.

Generally side effects are rare at normal dosage. It may include gastrointestinal discomfort, headache, nausea, insomnia and hypotension. CNS stimulation and diuresis may also occur, especially in children.

Theophylline is contraindicated in patients with hypersensitivity to Theophylline or any other component of the product.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Theophylline should not be used concurrently with other preparations containing xanthine derivatives. The clearance of theophylline is increased by barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone and it may therefore be necessary to increase dosage. On the other hand, the clearance of the drug is reduced by allopurinol, cimetidine, ciprofloxacin, corticosteroids, erythromycin, frusemide, isoprenaline, oral contraceptive and thiabendazole and a reduced dosage may therefore be needed to avoid side effects. Theophylline can potentiate hypokalemia resulting from beta-2-agonist therapy, steroids, diuretics and hypoxia, so serum potassium levels should be monitored in such instances.

It is not known whether Theophylline can cause foetal harm when administered to pregnant woman. Xanthines should be given to a pregnant woman only if clearly needed. Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Pediatrics use: The clearance of Theophylline is very low in neonates. Careful attention to dosage selection and monitoring of serum Theophylline concentrations are required in pediatric patients.

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

Theophylline is indicated for the-

• Control of acute asthma.
• Management of chronic asthma (For both Symptomatic and prophylactic treatment).
• For controlling nocturnal asthma and early morning wheezing.
• Management of chronic obstructive lung disease (Chronic bronchitis and emphysema) and acute exacerbation of chronic obstructive lung disease.
• Control of apnea of pre-maturity.

Bronchodilator, Theophylline & related drugs

Theophylline is a bronchodilator, structurally classified as a Methylxanthine. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation and suppression of the response of the airways to stimuli. Theophylline also increases the force of contraction of diaphragmatic muscles. The half-life of Theophylline is influenced by a number of known variables. In adult nonsmokers with uncomplicated asthma the half-life ranges from 3 to 9 hours

The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Most of the sustained release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic
metabolism of theophylline. The recommended maintenance dose within accepted therapeutic range is as follows :

• 16 years or older: 10 mg/Kg/day (Do not exceed 900 mg/day)
• 12 years-15 years: 13 mg/Kg/day
• 9-11 years: 16 mg/Kg/day
• 1 year-8 years: 24-24 mg/Kg/day
• 6 months-1 year: 12-18 mg/Kg/day
• 1-6 months: 10 mg/Kg/day.

Generally side effects are rare at normal dosage. It may include gastrointestinal discomfort, headache, nausea, insomnia and hypotension. CNS stimulation and diuresis may also occur, especially in children.

Theophylline is contraindicated in patients with hypersensitivity to Theophylline or any other component of the product.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Theophylline should not be used concurrently with other preparations containing xanthine derivatives. The clearance of theophylline is increased by barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone and it may therefore be necessary to increase dosage. On the other hand, the clearance of the drug is reduced by allopurinol, cimetidine, ciprofloxacin, corticosteroids, erythromycin, frusemide, isoprenaline, oral contraceptive and thiabendazole and a reduced dosage may therefore be needed to avoid side effects. Theophylline can potentiate hypokalemia resulting from beta-2-agonist therapy, steroids, diuretics and hypoxia, so serum potassium levels should be monitored in such instances.

It is not known whether Theophylline can cause foetal harm when administered to pregnant woman. Xanthines should be given to a pregnant woman only if clearly needed. Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Pediatrics use: The clearance of Theophylline is very low in neonates. Careful attention to dosage selection and monitoring of serum Theophylline concentrations are required in pediatric patients.

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

Theophylline is indicated for the-

• Control of acute asthma.
• Management of chronic asthma (For both Symptomatic and prophylactic treatment).
• For controlling nocturnal asthma and early morning wheezing.
• Management of chronic obstructive lung disease (Chronic bronchitis and emphysema) and acute exacerbation of chronic obstructive lung disease.
• Control of apnea of pre-maturity.

Bronchodilator, Theophylline & related drugs

Theophylline is a bronchodilator, structurally classified as a Methylxanthine. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation and suppression of the response of the airways to stimuli. Theophylline also increases the force of contraction of diaphragmatic muscles. The half-life of Theophylline is influenced by a number of known variables. In adult nonsmokers with uncomplicated asthma the half-life ranges from 3 to 9 hours

The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects. Most of the sustained release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic
metabolism of theophylline. The recommended maintenance dose within accepted therapeutic range is as follows :

• 16 years or older: 10 mg/Kg/day (Do not exceed 900 mg/day)
• 12 years-15 years: 13 mg/Kg/day
• 9-11 years: 16 mg/Kg/day
• 1 year-8 years: 24-24 mg/Kg/day
• 6 months-1 year: 12-18 mg/Kg/day
• 1-6 months: 10 mg/Kg/day.

Generally side effects are rare at normal dosage. It may include gastrointestinal discomfort, headache, nausea, insomnia and hypotension. CNS stimulation and diuresis may also occur, especially in children.

Theophylline is contraindicated in patients with hypersensitivity to Theophylline or any other component of the product.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Theophylline should not be used concurrently with other preparations containing xanthine derivatives. The clearance of theophylline is increased by barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone and it may therefore be necessary to increase dosage. On the other hand, the clearance of the drug is reduced by allopurinol, cimetidine, ciprofloxacin, corticosteroids, erythromycin, frusemide, isoprenaline, oral contraceptive and thiabendazole and a reduced dosage may therefore be needed to avoid side effects. Theophylline can potentiate hypokalemia resulting from beta-2-agonist therapy, steroids, diuretics and hypoxia, so serum potassium levels should be monitored in such instances.

It is not known whether Theophylline can cause foetal harm when administered to pregnant woman. Xanthines should be given to a pregnant woman only if clearly needed. Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Pediatrics use: The clearance of Theophylline is very low in neonates. Careful attention to dosage selection and monitoring of serum Theophylline concentrations are required in pediatric patients.

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

Vitamin-B preparations

Thiamine, in the form of thiamine pyrophosphate, is the coenzyme for decarboxylation of α-ketoglutaric acid. Thiamine deficiency affects the peripheral nervous system, the gastrointestinal tract, and the cardiovascular system. This vitamin is necessary for the optimal growth of infants and children. Thiamine is not stored in the body, and is regularly lost from tissues during short periods of deficiency. In order to maintain normal health, an adequate amount of thiamine is required every day. Deficiency of thiamine leads to fatigue, anorexia, gastrointestinal disturbance, tachycardia, irritability and neurological symptoms. Beriberi, a disease due to vitamin B1 deficiency, is common in alcoholics, in pregnant women receiving an inadequate diet, and in people with malabsorption syndrome, prolonged diarrhoea and hepatic disease.

Thiamine is well absorbed from the gastrointestinal tract and widely distributed throughout the body. Thiamine is rapidly absorbed from the upper small intestine. Thiamine is not stored in the body to any appreciable extent. Excess ingested thiamine appears in urine as intact thiamine or as pyrimidine, which arises from degradation of the thiamine molecule. The plasma half life of thiamine is 24 hours.

Prophylaxis: 3 to 10 mg daily.
Mild chronic deficiency: 10 to 25 mg daily.
Severe deficiency: 200 to 300 mg daily.

Vitamin B1 does not have adverse effects when given orally, but in a few fatal cases anaphylactic reactions have occurred after intravenous administration of large doses (400 mg) in sensitive patients, especially children, and in one case following an intramuscular dose of 125 mg. The risk of such reactions increases with repeated administration of the drug by parenteral route. Transient mild soreness may occur at the site of intramuscular administration

There is no absolute contraindication but the risk of anaphylaxis is increased by repeated parenteral administration. Mild allergic phenomena, such as sneezing or mild asthma are warning signs that further may give rise to anaphylactic shock. To avoid this possibility it is advisable to start a second course of injection with a dose considerably lower than that previously used. Because of the above, vitamin B1 injection should not be given intravenously except in the case of comatose patients. Once thiamine deficiency is corrected there is no need for parenteral administration or for the administration of amounts in excess of daily requirement.

No hazardous drug interactions have been reported. Vitamin B1 acts synergistically with other vitamins of the B-complex group and its potential for causing adverse effects is considerably reduced.

The drug may be given safely to neonates, children, pregnant and lactating women and elderly patients.

Thiamine injection should be protected from light and moisture.

Vitamin-B preparations

Thiamine, in the form of thiamine pyrophosphate, is the coenzyme for decarboxylation of α-ketoglutaric acid. Thiamine deficiency affects the peripheral nervous system, the gastrointestinal tract, and the cardiovascular system. This vitamin is necessary for the optimal growth of infants and children. Thiamine is not stored in the body, and is regularly lost from tissues during short periods of deficiency. In order to maintain normal health, an adequate amount of thiamine is required every day. Deficiency of thiamine leads to fatigue, anorexia, gastrointestinal disturbance, tachycardia, irritability and neurological symptoms. Beriberi, a disease due to vitamin B1 deficiency, is common in alcoholics, in pregnant women receiving an inadequate diet, and in people with malabsorption syndrome, prolonged diarrhoea and hepatic disease.

Thiamine is well absorbed from the gastrointestinal tract and widely distributed throughout the body. Thiamine is rapidly absorbed from the upper small intestine. Thiamine is not stored in the body to any appreciable extent. Excess ingested thiamine appears in urine as intact thiamine or as pyrimidine, which arises from degradation of the thiamine molecule. The plasma half life of thiamine is 24 hours.

Prophylaxis: 3 to 10 mg daily.
Mild chronic deficiency: 10 to 25 mg daily.
Severe deficiency: 200 to 300 mg daily.

Vitamin B1 does not have adverse effects when given orally, but in a few fatal cases anaphylactic reactions have occurred after intravenous administration of large doses (400 mg) in sensitive patients, especially children, and in one case following an intramuscular dose of 125 mg. The risk of such reactions increases with repeated administration of the drug by parenteral route. Transient mild soreness may occur at the site of intramuscular administration

There is no absolute contraindication but the risk of anaphylaxis is increased by repeated parenteral administration. Mild allergic phenomena, such as sneezing or mild asthma are warning signs that further may give rise to anaphylactic shock. To avoid this possibility it is advisable to start a second course of injection with a dose considerably lower than that previously used. Because of the above, vitamin B1 injection should not be given intravenously except in the case of comatose patients. Once thiamine deficiency is corrected there is no need for parenteral administration or for the administration of amounts in excess of daily requirement.

No hazardous drug interactions have been reported. Vitamin B1 acts synergistically with other vitamins of the B-complex group and its potential for causing adverse effects is considerably reduced.

The drug may be given safely to neonates, children, pregnant and lactating women and elderly patients.

Thiamine injection should be protected from light and moisture.

Vitamin-B preparations

Thiamine, in the form of thiamine pyrophosphate, is the coenzyme for decarboxylation of α-ketoglutaric acid. Thiamine deficiency affects the peripheral nervous system, the gastrointestinal tract, and the cardiovascular system. This vitamin is necessary for the optimal growth of infants and children. Thiamine is not stored in the body, and is regularly lost from tissues during short periods of deficiency. In order to maintain normal health, an adequate amount of thiamine is required every day. Deficiency of thiamine leads to fatigue, anorexia, gastrointestinal disturbance, tachycardia, irritability and neurological symptoms. Beriberi, a disease due to vitamin B1 deficiency, is common in alcoholics, in pregnant women receiving an inadequate diet, and in people with malabsorption syndrome, prolonged diarrhoea and hepatic disease.

Thiamine is well absorbed from the gastrointestinal tract and widely distributed throughout the body. Thiamine is rapidly absorbed from the upper small intestine. Thiamine is not stored in the body to any appreciable extent. Excess ingested thiamine appears in urine as intact thiamine or as pyrimidine, which arises from degradation of the thiamine molecule. The plasma half life of thiamine is 24 hours.

Prophylaxis: 3 to 10 mg daily.
Mild chronic deficiency: 10 to 25 mg daily.
Severe deficiency: 200 to 300 mg daily.

Vitamin B1 does not have adverse effects when given orally, but in a few fatal cases anaphylactic reactions have occurred after intravenous administration of large doses (400 mg) in sensitive patients, especially children, and in one case following an intramuscular dose of 125 mg. The risk of such reactions increases with repeated administration of the drug by parenteral route. Transient mild soreness may occur at the site of intramuscular administration

There is no absolute contraindication but the risk of anaphylaxis is increased by repeated parenteral administration. Mild allergic phenomena, such as sneezing or mild asthma are warning signs that further may give rise to anaphylactic shock. To avoid this possibility it is advisable to start a second course of injection with a dose considerably lower than that previously used. Because of the above, vitamin B1 injection should not be given intravenously except in the case of comatose patients. Once thiamine deficiency is corrected there is no need for parenteral administration or for the administration of amounts in excess of daily requirement.

No hazardous drug interactions have been reported. Vitamin B1 acts synergistically with other vitamins of the B-complex group and its potential for causing adverse effects is considerably reduced.

The drug may be given safely to neonates, children, pregnant and lactating women and elderly patients.

Thiamine injection should be protected from light and moisture.

Chlorthalidone is indicated in the management of hypertension. Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis and corticosteroid and estrogen therapy.

Thiazide diuretics & related drugs

Chlorthalidone is a thiazide-type Diuretic- Antihypertensive, used for the treatment of hypertension. It may be used alone or in association with other antihypertensive agents. Chlortalidone is also indicated for adjunctive therapy of edema associated with: renal disease; congestive heart failure of mild to moderate degree (functional class II, Ill), when glomerular filtration rate is greater than 30 ml/min; ascites due to cirrhosis of the liver in stable patients; estrogen therapy; corticosteroid therapy.

Chlorthalidone inhibits the reabsorption of sodium and chloride in the distal renal tubule thus promoting water loss. The higher urine volume increases potassium loss. Little information is available on the absorption of the drug. Its long elimination half-life and clinical experience place it as a long-acting thiazide derivative. The longer-acting agents appear to cause increased potassium loss.

Although a mild diuretic, its combination with loop diuretics is particularly potent because the latter presents much more sodium chloride to the distal tubule.

The blood pressure lowering effects are initially due to volume reduction but the persisting effect includes other undetermined mechanisms that reduce peripheral resistance. A high salt intake reverses its antihypertensive effect.

The major portion of an absorbed dose of Chlorthalidone is excreted by the kidneys with an elimination half life averaging 50 hours. Metabolism and hepatic excretion into the bile constitute a minor way of elimination. Within 120 hours, about 70% of the dose is excreted in the urine and in the feces, mainly in an unchanged form.

Therapy should be initiated with the lowest possible dose, and be titrated thereafter to gain maximum therapeutic benefit while keeping side effects to a minimum (e.g. determine the minimum effective maintenance dose for each patient). A single dose daily or every other day is given in the morning with food is recommended.

Hypertension: Usual adult dose is 25 to 50 mg daily. The clinically useful dosage range is 12.5 to 50 mg daily. Doses greater than 50 mg per day increase metabolic complications and are rarely of therapeutic benefit. For a given dose, the full effect is reached after 3 to 4 weeks. If the decrease in blood pressure obtained using doses of 25 or 50 mg/day proves inadequate, combined treatment with other antihypertensive drugs (such as beta-blockers and ACE inhibitors) is recommended. When adding an ACE inhibitor, Chlorthalidone is to be reduced or discontinued.

Edema of Specific Origin: The lowest effective dose is to be identified by titration. Maintenance doses should not exceed 50 mg/day and should be administered over limited periods only. The dosage should be individually adapted to the clinical picture and patient response. For long-term therapy, the lowest possible dosage sufficient to maintain an optimal effect should be employed; this applies particularly to elderly patients.

The therapeutic effect of Chlorthalidone occurs even without salt restriction and is well sustained during continued use.

The elderly: This is a suitable drug for treating hypertension in the elderly, in particular systolic hypertension. Dose of 50 mg daily, or less, should be used to avoid hypovolemia and hypokalemia.

Electrolytes and Metabolic Disorders: Frequent: mainly at higher doses, hypokalemia, hyperuricemia and rise in blood lipids. Occasional: hyponatremia, hypomagnesemia and hyperglycemia. Rare: hypercalcemia, glycosuria, worsening of diabetic metabolic state and gout.

Isolated cases: hypochloremic alkalosis.

Dermatology: Occasional: urticaria and other forms of skin rash. Rare: photosensitization.

Liver: Rare: Intrahepatic cholestasis or jaundice.

Cardiovascular: Occasional: postural hypotension, which may be aggravated by alcohol, anesthetics or sedatives. Rare: cardiac arrhythmias.

CNS: Occasional: dizziness, slow mentation and decreased reaction time.

Anuria, severe renal failure (creatinine clearance lower than 30 mL/min), severe hepatic failure, refractory hypokalemia or conditions involving enhanced potassium loss, hyponatremia, hypercalcemia, symptomatic hyperuricemia (history of gout or uric acid calculi). Hypersensitivity or suspected hypersensitivity to Chlorthalidone and other sulfonamide derivatives or their excipients.

Should be used with caution in patients with renal disease or with impaired hepatic function. Because of the possibility of progression of renal damage, periodic determination of the BUN and serum creatinine are indicated. Should there be an elevation of either parameter, treatment should be discontinued. Like thiazides, Chlorthalidone may lose its diuretic efficacy when glomerular filtration rate drops below 30 mL/min, a point at which treatment with loop diuretics may be more appropriate.

Electrolytes: As with thiazide diuretics, kaluresis induced by Chlorthalidone is dose dependent, and there is inter-individual variability in magnitude. With 25 mg/day, serum potassium concentration decreases average 0.5 mmol/L. If chronic treatment is contemplated, serum potassium concentrations should be determined initially, and then 3 to 4 weeks later. If thereafter, potassium balance is not disturbed further, concentrations should be assessed every 4 to 6 months. Conditions that may alter potassium balance include: vomiting, diarrhea, malnutrition, change in renal function (e.g. nephrosis), liver cirrhosis, hyperaldosteronism, or concomitant use of corticosteroids or ACTH. Titrated co-administration of an oral potassium salt (e.g. KCI) may be considered in patients: receiving digitalis; exhibiting signs of coronary heart disease, unless they are also receiving an ACE inhibitor; on high doses of a beta-adrenergic agonist; whose plasma potassium concentrations are less than 3.0 mmol/L.

Renal impairment: Chlorthalidone dosage should be reduced in moderate renal failure - every 24 or 48 h - and should not be used in advanced renal failure.

Liver disease: There is a risk of precipitating hepatic encephalopathy in patients with liver cirrhosis and ascites.

Use in pregnancy: It is better to avoid Chlorthalidone as it crosses the placenta.

Use in Lactation: In lactating mother, significant amount of Chlorthalidone enter breast milk; like other long-acting thiazides, it can suppress lactation. Chlorthalidone should not be prescribed for lactating mother.

Other interactions: Patients with Special Diseases and Conditions in patients with impaired hepatic function or progressive liver disease, caution should be exercised since even minor alterations in fluid and electrolyte balance or of serum ammonia may precipitate hepatic coma. Treatment with thiazide diuretics should be initiated cautiously in postsympathectomy patients since the antihypertensive effects may be enhanced. A cautious dosage schedule should be adopted in patients with severe coronary or cerebral ateriosderosis.

Drug Interactions-
Antihypertensive Agents: Diuretics potentiate the action of curare derivatives and antihypertensive agents (e.g. guanethidine, methyldopa, beta-blockers, vasodilators, calcium antagonists, ACE inhibitors).

Digitalis: Thiazide-induced hypokalemia or hypomagnesemia may increase the likelihood of digitalis-induced cardiac arrhythmias (see also Precautions).

Corticosteroids: The hypokalemic effects of diuretics may be increased by corticosteroids, ACTH and amphotericin. Insulin and Oral Antidiabetic Agents: It may be necessary to adjust the dosage of insulin or oral antidiabetic agents in response to changes in glucose tolerance that Chlorthalidone may produce.

NSAIDs: Concomitant administration of certain NSAIDs (e.g. indomethacin) may weaken the diuretic and antihypertensive activity of thiazides, and there have been isolated reports of a deterioration of renal function in predisposed patients.

Curare Derivatives and Ganglionic Blocking Agents: Thiazides may increase responsiveness to curare derivatives and ganglionic blocking agents.

Allopurinol: Co-administration of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Amantadine: Co-administration of thiazide diuretics may increase the risk of adverse effects from amantadine.

Antineoplastic Agents (e.g. cyclophosphamide, methotrexate): Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance the myelo suppressive effects. Anticholinergics (e.g. atropine, biperiden): The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents, apparently due to a decrease in gastrointestinal motility and rate of gastric emptying.

Cholestyramine: Absorption of thiazide diuretics is decreased by cholestyramine, therefore a decrease in pharmacological effect may be expected.

Vitamin D: Concomitant use of thiazide diuretics may decrease urinary excretion of calcium, and co-administration of Vitamin D may potentiate the increase in serum calcium.

Cyclosporin: Concomitant treatment with diuretics may increase the risk of hyperuricemia and gout-type complications.

Calcium Salts: Concomitant use of thiazide-type diuretics may cause hypercalcemia by increasing tubular calcium reabsorption.

Diazoxide: Thiazide diuretics may enhance the hyperglycemic effect of diazoxide.

Pregnancy: Chlorthalidone, like other diuretics, can cause placental hypoperfusion. Since they do not prevent or alter the course of EPH (edema, proteinuria, hypertension) preeclampsia, these drugs must not be used to treat hypertension in pregnant women. The use of Chlorthalidone for other indications (e.g. heart disease) in pregnancy should be avoided, particularly in the first trimester, unless the potential benefits outweigh the possible risks (e.g. when there are no safer altenatives).

Lactation: Chlorthalidone appears in breast milk, attaining concentrations of approximately 4% of maternal blood levels. Therefore use in nursing mothers should be avoided.

Symptoms of acute overdosage include nausea, weakness, dizziness, and disturbances of electrolyte balance. The oral LD 50 of the drug in the mouse and the rat is more than 25,000 mg/kg body weight. The minimum lethal dose (MLD) in humans has not been established. There is no specific antidote, but gastric lavage is recommended, followed by supportive treatment. Where necessary, this may include intravenous dextrose-saline with potassium, administered with caution.

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

Chlorthalidone is indicated in the management of hypertension. Chlorthalidone is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis and corticosteroid and estrogen therapy.

Thiazide diuretics & related drugs

Chlorthalidone is a thiazide-type Diuretic- Antihypertensive, used for the treatment of hypertension. It may be used alone or in association with other antihypertensive agents. Chlortalidone is also indicated for adjunctive therapy of edema associated with: renal disease; congestive heart failure of mild to moderate degree (functional class II, Ill), when glomerular filtration rate is greater than 30 ml/min; ascites due to cirrhosis of the liver in stable patients; estrogen therapy; corticosteroid therapy.

Chlorthalidone inhibits the reabsorption of sodium and chloride in the distal renal tubule thus promoting water loss. The higher urine volume increases potassium loss. Little information is available on the absorption of the drug. Its long elimination half-life and clinical experience place it as a long-acting thiazide derivative. The longer-acting agents appear to cause increased potassium loss.

Although a mild diuretic, its combination with loop diuretics is particularly potent because the latter presents much more sodium chloride to the distal tubule.

The blood pressure lowering effects are initially due to volume reduction but the persisting effect includes other undetermined mechanisms that reduce peripheral resistance. A high salt intake reverses its antihypertensive effect.

The major portion of an absorbed dose of Chlorthalidone is excreted by the kidneys with an elimination half life averaging 50 hours. Metabolism and hepatic excretion into the bile constitute a minor way of elimination. Within 120 hours, about 70% of the dose is excreted in the urine and in the feces, mainly in an unchanged form.

Therapy should be initiated with the lowest possible dose, and be titrated thereafter to gain maximum therapeutic benefit while keeping side effects to a minimum (e.g. determine the minimum effective maintenance dose for each patient). A single dose daily or every other day is given in the morning with food is recommended.

Hypertension: Usual adult dose is 25 to 50 mg daily. The clinically useful dosage range is 12.5 to 50 mg daily. Doses greater than 50 mg per day increase metabolic complications and are rarely of therapeutic benefit. For a given dose, the full effect is reached after 3 to 4 weeks. If the decrease in blood pressure obtained using doses of 25 or 50 mg/day proves inadequate, combined treatment with other antihypertensive drugs (such as beta-blockers and ACE inhibitors) is recommended. When adding an ACE inhibitor, Chlorthalidone is to be reduced or discontinued.

Edema of Specific Origin: The lowest effective dose is to be identified by titration. Maintenance doses should not exceed 50 mg/day and should be administered over limited periods only. The dosage should be individually adapted to the clinical picture and patient response. For long-term therapy, the lowest possible dosage sufficient to maintain an optimal effect should be employed; this applies particularly to elderly patients.

The therapeutic effect of Chlorthalidone occurs even without salt restriction and is well sustained during continued use.

The elderly: This is a suitable drug for treating hypertension in the elderly, in particular systolic hypertension. Dose of 50 mg daily, or less, should be used to avoid hypovolemia and hypokalemia.

Electrolytes and Metabolic Disorders: Frequent: mainly at higher doses, hypokalemia, hyperuricemia and rise in blood lipids. Occasional: hyponatremia, hypomagnesemia and hyperglycemia. Rare: hypercalcemia, glycosuria, worsening of diabetic metabolic state and gout.

Isolated cases: hypochloremic alkalosis.

Dermatology: Occasional: urticaria and other forms of skin rash. Rare: photosensitization.

Liver: Rare: Intrahepatic cholestasis or jaundice.

Cardiovascular: Occasional: postural hypotension, which may be aggravated by alcohol, anesthetics or sedatives. Rare: cardiac arrhythmias.

CNS: Occasional: dizziness, slow mentation and decreased reaction time.

Anuria, severe renal failure (creatinine clearance lower than 30 mL/min), severe hepatic failure, refractory hypokalemia or conditions involving enhanced potassium loss, hyponatremia, hypercalcemia, symptomatic hyperuricemia (history of gout or uric acid calculi). Hypersensitivity or suspected hypersensitivity to Chlorthalidone and other sulfonamide derivatives or their excipients.

Should be used with caution in patients with renal disease or with impaired hepatic function. Because of the possibility of progression of renal damage, periodic determination of the BUN and serum creatinine are indicated. Should there be an elevation of either parameter, treatment should be discontinued. Like thiazides, Chlorthalidone may lose its diuretic efficacy when glomerular filtration rate drops below 30 mL/min, a point at which treatment with loop diuretics may be more appropriate.

Electrolytes: As with thiazide diuretics, kaluresis induced by Chlorthalidone is dose dependent, and there is inter-individual variability in magnitude. With 25 mg/day, serum potassium concentration decreases average 0.5 mmol/L. If chronic treatment is contemplated, serum potassium concentrations should be determined initially, and then 3 to 4 weeks later. If thereafter, potassium balance is not disturbed further, concentrations should be assessed every 4 to 6 months. Conditions that may alter potassium balance include: vomiting, diarrhea, malnutrition, change in renal function (e.g. nephrosis), liver cirrhosis, hyperaldosteronism, or concomitant use of corticosteroids or ACTH. Titrated co-administration of an oral potassium salt (e.g. KCI) may be considered in patients: receiving digitalis; exhibiting signs of coronary heart disease, unless they are also receiving an ACE inhibitor; on high doses of a beta-adrenergic agonist; whose plasma potassium concentrations are less than 3.0 mmol/L.

Renal impairment: Chlorthalidone dosage should be reduced in moderate renal failure - every 24 or 48 h - and should not be used in advanced renal failure.

Liver disease: There is a risk of precipitating hepatic encephalopathy in patients with liver cirrhosis and ascites.

Use in pregnancy: It is better to avoid Chlorthalidone as it crosses the placenta.

Use in Lactation: In lactating mother, significant amount of Chlorthalidone enter breast milk; like other long-acting thiazides, it can suppress lactation. Chlorthalidone should not be prescribed for lactating mother.

Other interactions: Patients with Special Diseases and Conditions in patients with impaired hepatic function or progressive liver disease, caution should be exercised since even minor alterations in fluid and electrolyte balance or of serum ammonia may precipitate hepatic coma. Treatment with thiazide diuretics should be initiated cautiously in postsympathectomy patients since the antihypertensive effects may be enhanced. A cautious dosage schedule should be adopted in patients with severe coronary or cerebral ateriosderosis.

Drug Interactions-
Antihypertensive Agents: Diuretics potentiate the action of curare derivatives and antihypertensive agents (e.g. guanethidine, methyldopa, beta-blockers, vasodilators, calcium antagonists, ACE inhibitors).

Digitalis: Thiazide-induced hypokalemia or hypomagnesemia may increase the likelihood of digitalis-induced cardiac arrhythmias (see also Precautions).

Corticosteroids: The hypokalemic effects of diuretics may be increased by corticosteroids, ACTH and amphotericin. Insulin and Oral Antidiabetic Agents: It may be necessary to adjust the dosage of insulin or oral antidiabetic agents in response to changes in glucose tolerance that Chlorthalidone may produce.

NSAIDs: Concomitant administration of certain NSAIDs (e.g. indomethacin) may weaken the diuretic and antihypertensive activity of thiazides, and there have been isolated reports of a deterioration of renal function in predisposed patients.

Curare Derivatives and Ganglionic Blocking Agents: Thiazides may increase responsiveness to curare derivatives and ganglionic blocking agents.

Allopurinol: Co-administration of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Amantadine: Co-administration of thiazide diuretics may increase the risk of adverse effects from amantadine.

Antineoplastic Agents (e.g. cyclophosphamide, methotrexate): Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance the myelo suppressive effects. Anticholinergics (e.g. atropine, biperiden): The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents, apparently due to a decrease in gastrointestinal motility and rate of gastric emptying.

Cholestyramine: Absorption of thiazide diuretics is decreased by cholestyramine, therefore a decrease in pharmacological effect may be expected.

Vitamin D: Concomitant use of thiazide diuretics may decrease urinary excretion of calcium, and co-administration of Vitamin D may potentiate the increase in serum calcium.

Cyclosporin: Concomitant treatment with diuretics may increase the risk of hyperuricemia and gout-type complications.

Calcium Salts: Concomitant use of thiazide-type diuretics may cause hypercalcemia by increasing tubular calcium reabsorption.

Diazoxide: Thiazide diuretics may enhance the hyperglycemic effect of diazoxide.

Pregnancy: Chlorthalidone, like other diuretics, can cause placental hypoperfusion. Since they do not prevent or alter the course of EPH (edema, proteinuria, hypertension) preeclampsia, these drugs must not be used to treat hypertension in pregnant women. The use of Chlorthalidone for other indications (e.g. heart disease) in pregnancy should be avoided, particularly in the first trimester, unless the potential benefits outweigh the possible risks (e.g. when there are no safer altenatives).

Lactation: Chlorthalidone appears in breast milk, attaining concentrations of approximately 4% of maternal blood levels. Therefore use in nursing mothers should be avoided.

Symptoms of acute overdosage include nausea, weakness, dizziness, and disturbances of electrolyte balance. The oral LD 50 of the drug in the mouse and the rat is more than 25,000 mg/kg body weight. The minimum lethal dose (MLD) in humans has not been established. There is no specific antidote, but gastric lavage is recommended, followed by supportive treatment. Where necessary, this may include intravenous dextrose-saline with potassium, administered with caution.

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

General (Intravenous) anesthetics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia

Thiopental binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Thiopental Injection is administered intravenously normally as a 2.5% w/v solution. On occasions it may be administered as a 5% w/v solution (500 mg in 10 ml). The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution.

Premedication: Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Ideally, the peak effect of these medications should be reached shortly before the time of induction.

Test dose: It is advisable to inject a small "test" dose of 25 mg to 75 mg of Thiopental Sodium for Injection to assess tolerance or unusual sensitivity to Thiopental Sodium for Injection, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Thiopental Sodium for Injection, (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much.

Use in anaesthesia: Normal dosage for the induction of anesthesia is 100 mg to 150 mg injected over 10 to 15 seconds. If necessary, a repeat dose of 100 mg to 150 mg may be given after one minute. No fixed dosage recommendations for the intravenous injection can be given, since the dosage will need to be carefully adjusted according to the patient's response. Factors such as age, sex, and weight of the patient should be taken into consideration. Thiopental Sodium reaches effective concentrations in the brain within 30 seconds and anesthesia is normally produced within one minute of an intravenous dose.

• Adult: 100 mg to 150 mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 100 mg to 150 mg may be given after one minute. The intravenous injection should be given slowly and the amount given titrated against the patient's response to minimize the risk of respiratory depression or the possibility of over dosage. The average dose for an adult of 70 kg is roughly 200 mg to 300 mg (8 mls to 12 mls of a 2.5% w/v solution) with a maximum of 500 mg.
• Children: 2 mg/kg to 7 mg/kg bodyweight, intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 2 mg/kg to 7 mg/kg may be given after one minute. The dose is 2 mg/kg to 7 mg/kg based on the patient's response. The dose for children should not exceed 7 mg/kg.
• Elderly: Smaller adult doses are advisable.

Use in convulsive states: 75 mg to 125 mg (3 mls to 5 mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsion following the use of a local anesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Hypersensitivity reactions have been reported. Other adverse reactions to thiopental sodium include the followings: respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, hypotension, tachycardia, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic reactions have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema.

Absolute Contraindication:

• Absence of suitable veins for intravenous administration
• Hypersensitivity (allergy) to barbiturates
• Variegate porphyria (South African) or acute intermittent porphyria
• Status asthmaticus

Relative Contraindication:

• Severe cardiovascular disease
• Hypotension or shock
• Conditions in which the hypnotic effect may be prolonged or potentiated, eg, excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis

A person competent in anesthesia management should be in constant attendance and adequate facilities for support of respiration and circulation should be available when Thiopental Sodium for injection is being used. Thiopental Sodium for Injection should be administered with caution to patients with preexisting hypotension or in conditions where the hypnotic effect may be prolonged or intensified, such as in the presence of liver disease and renal disease.

This product may be habit forming. Keep resuscitative and endotracheal intubation equipment and oxygen readily available. Maintain patency of the airway at all times. Only persons qualified in the use of anesthetics should administer this drug. Avoid extravasations or intra-arterial injection.

Possible increase in difficulty in producing anaesthesia in patients taking alcohol or CNS depressants. Additive action with other CNS depressants including sedatives, hypnotics, nitrous oxide or alcohol. Increased hypotension and excitatory effects with phenothiazine antipsychotics. Increased hypnotic effect with antipsychotic. Decreased requirement of thiopental sodium with metoclopramide, sulfisoxazole, aspirin, meprobamate, probenecid and other highly protein bound drugs.

Pregnancy Category C. Animal reproduction studies have not been conducted with Thiopental. It is also not known whether Thiopental can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Thiopental should be given to a pregnant woman only if clearly needed. Thiopental sodium readily crosses the placental barrier and small amounts may appear in the milk of nursing mothers following administration of large doses.

Overdosage may occur from too rapid or repeated administration. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnoea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the agent should be discontinued.

Store at controlled room temperature of 15° C to 30° C. Solutions should be freshly prepared and used immediately. Any portion of the contents remaining should be discarded.

General (Intravenous) anesthetics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia

Thiopental binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Thiopental Injection is administered intravenously normally as a 2.5% w/v solution. On occasions it may be administered as a 5% w/v solution (500 mg in 10 ml). The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution.

Premedication: Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Ideally, the peak effect of these medications should be reached shortly before the time of induction.

Test dose: It is advisable to inject a small "test" dose of 25 mg to 75 mg of Thiopental Sodium for Injection to assess tolerance or unusual sensitivity to Thiopental Sodium for Injection, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Thiopental Sodium for Injection, (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much.

Use in anaesthesia: Normal dosage for the induction of anesthesia is 100 mg to 150 mg injected over 10 to 15 seconds. If necessary, a repeat dose of 100 mg to 150 mg may be given after one minute. No fixed dosage recommendations for the intravenous injection can be given, since the dosage will need to be carefully adjusted according to the patient's response. Factors such as age, sex, and weight of the patient should be taken into consideration. Thiopental Sodium reaches effective concentrations in the brain within 30 seconds and anesthesia is normally produced within one minute of an intravenous dose.

• Adult: 100 mg to 150 mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 100 mg to 150 mg may be given after one minute. The intravenous injection should be given slowly and the amount given titrated against the patient's response to minimize the risk of respiratory depression or the possibility of over dosage. The average dose for an adult of 70 kg is roughly 200 mg to 300 mg (8 mls to 12 mls of a 2.5% w/v solution) with a maximum of 500 mg.
• Children: 2 mg/kg to 7 mg/kg bodyweight, intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 2 mg/kg to 7 mg/kg may be given after one minute. The dose is 2 mg/kg to 7 mg/kg based on the patient's response. The dose for children should not exceed 7 mg/kg.
• Elderly: Smaller adult doses are advisable.

Use in convulsive states: 75 mg to 125 mg (3 mls to 5 mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsion following the use of a local anesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Hypersensitivity reactions have been reported. Other adverse reactions to thiopental sodium include the followings: respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, hypotension, tachycardia, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic reactions have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema.

Absolute Contraindication:

• Absence of suitable veins for intravenous administration
• Hypersensitivity (allergy) to barbiturates
• Variegate porphyria (South African) or acute intermittent porphyria
• Status asthmaticus

Relative Contraindication:

• Severe cardiovascular disease
• Hypotension or shock
• Conditions in which the hypnotic effect may be prolonged or potentiated, eg, excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis

A person competent in anesthesia management should be in constant attendance and adequate facilities for support of respiration and circulation should be available when Thiopental Sodium for injection is being used. Thiopental Sodium for Injection should be administered with caution to patients with preexisting hypotension or in conditions where the hypnotic effect may be prolonged or intensified, such as in the presence of liver disease and renal disease.

This product may be habit forming. Keep resuscitative and endotracheal intubation equipment and oxygen readily available. Maintain patency of the airway at all times. Only persons qualified in the use of anesthetics should administer this drug. Avoid extravasations or intra-arterial injection.

Possible increase in difficulty in producing anaesthesia in patients taking alcohol or CNS depressants. Additive action with other CNS depressants including sedatives, hypnotics, nitrous oxide or alcohol. Increased hypotension and excitatory effects with phenothiazine antipsychotics. Increased hypnotic effect with antipsychotic. Decreased requirement of thiopental sodium with metoclopramide, sulfisoxazole, aspirin, meprobamate, probenecid and other highly protein bound drugs.

Pregnancy Category C. Animal reproduction studies have not been conducted with Thiopental. It is also not known whether Thiopental can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Thiopental should be given to a pregnant woman only if clearly needed. Thiopental sodium readily crosses the placental barrier and small amounts may appear in the milk of nursing mothers following administration of large doses.

Overdosage may occur from too rapid or repeated administration. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnoea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the agent should be discontinued.

Store at controlled room temperature of 15° C to 30° C. Solutions should be freshly prepared and used immediately. Any portion of the contents remaining should be discarded.

General (Intravenous) anesthetics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia

Thiopental binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Thiopental Injection is administered intravenously normally as a 2.5% w/v solution. On occasions it may be administered as a 5% w/v solution (500 mg in 10 ml). The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution.

Premedication: Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Ideally, the peak effect of these medications should be reached shortly before the time of induction.

Test dose: It is advisable to inject a small "test" dose of 25 mg to 75 mg of Thiopental Sodium for Injection to assess tolerance or unusual sensitivity to Thiopental Sodium for Injection, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Thiopental Sodium for Injection, (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much.

Use in anaesthesia: Normal dosage for the induction of anesthesia is 100 mg to 150 mg injected over 10 to 15 seconds. If necessary, a repeat dose of 100 mg to 150 mg may be given after one minute. No fixed dosage recommendations for the intravenous injection can be given, since the dosage will need to be carefully adjusted according to the patient's response. Factors such as age, sex, and weight of the patient should be taken into consideration. Thiopental Sodium reaches effective concentrations in the brain within 30 seconds and anesthesia is normally produced within one minute of an intravenous dose.

• Adult: 100 mg to 150 mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 100 mg to 150 mg may be given after one minute. The intravenous injection should be given slowly and the amount given titrated against the patient's response to minimize the risk of respiratory depression or the possibility of over dosage. The average dose for an adult of 70 kg is roughly 200 mg to 300 mg (8 mls to 12 mls of a 2.5% w/v solution) with a maximum of 500 mg.
• Children: 2 mg/kg to 7 mg/kg bodyweight, intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 2 mg/kg to 7 mg/kg may be given after one minute. The dose is 2 mg/kg to 7 mg/kg based on the patient's response. The dose for children should not exceed 7 mg/kg.
• Elderly: Smaller adult doses are advisable.

Use in convulsive states: 75 mg to 125 mg (3 mls to 5 mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsion following the use of a local anesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Hypersensitivity reactions have been reported. Other adverse reactions to thiopental sodium include the followings: respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, hypotension, tachycardia, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic reactions have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema.

Absolute Contraindication:

• Absence of suitable veins for intravenous administration
• Hypersensitivity (allergy) to barbiturates
• Variegate porphyria (South African) or acute intermittent porphyria
• Status asthmaticus

Relative Contraindication:

• Severe cardiovascular disease
• Hypotension or shock
• Conditions in which the hypnotic effect may be prolonged or potentiated, eg, excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis

A person competent in anesthesia management should be in constant attendance and adequate facilities for support of respiration and circulation should be available when Thiopental Sodium for injection is being used. Thiopental Sodium for Injection should be administered with caution to patients with preexisting hypotension or in conditions where the hypnotic effect may be prolonged or intensified, such as in the presence of liver disease and renal disease.

This product may be habit forming. Keep resuscitative and endotracheal intubation equipment and oxygen readily available. Maintain patency of the airway at all times. Only persons qualified in the use of anesthetics should administer this drug. Avoid extravasations or intra-arterial injection.

Possible increase in difficulty in producing anaesthesia in patients taking alcohol or CNS depressants. Additive action with other CNS depressants including sedatives, hypnotics, nitrous oxide or alcohol. Increased hypotension and excitatory effects with phenothiazine antipsychotics. Increased hypnotic effect with antipsychotic. Decreased requirement of thiopental sodium with metoclopramide, sulfisoxazole, aspirin, meprobamate, probenecid and other highly protein bound drugs.

Pregnancy Category C. Animal reproduction studies have not been conducted with Thiopental. It is also not known whether Thiopental can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Thiopental should be given to a pregnant woman only if clearly needed. Thiopental sodium readily crosses the placental barrier and small amounts may appear in the milk of nursing mothers following administration of large doses.

Overdosage may occur from too rapid or repeated administration. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnoea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the agent should be discontinued.

Store at controlled room temperature of 15° C to 30° C. Solutions should be freshly prepared and used immediately. Any portion of the contents remaining should be discarded.

General (Intravenous) anesthetics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia

Thiopental binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Thiopental Injection is administered intravenously normally as a 2.5% w/v solution. On occasions it may be administered as a 5% w/v solution (500 mg in 10 ml). The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution.

Premedication: Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Ideally, the peak effect of these medications should be reached shortly before the time of induction.

Test dose: It is advisable to inject a small "test" dose of 25 mg to 75 mg of Thiopental Sodium for Injection to assess tolerance or unusual sensitivity to Thiopental Sodium for Injection, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Thiopental Sodium for Injection, (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much.

Use in anaesthesia: Normal dosage for the induction of anesthesia is 100 mg to 150 mg injected over 10 to 15 seconds. If necessary, a repeat dose of 100 mg to 150 mg may be given after one minute. No fixed dosage recommendations for the intravenous injection can be given, since the dosage will need to be carefully adjusted according to the patient's response. Factors such as age, sex, and weight of the patient should be taken into consideration. Thiopental Sodium reaches effective concentrations in the brain within 30 seconds and anesthesia is normally produced within one minute of an intravenous dose.

• Adult: 100 mg to 150 mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 100 mg to 150 mg may be given after one minute. The intravenous injection should be given slowly and the amount given titrated against the patient's response to minimize the risk of respiratory depression or the possibility of over dosage. The average dose for an adult of 70 kg is roughly 200 mg to 300 mg (8 mls to 12 mls of a 2.5% w/v solution) with a maximum of 500 mg.
• Children: 2 mg/kg to 7 mg/kg bodyweight, intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 2 mg/kg to 7 mg/kg may be given after one minute. The dose is 2 mg/kg to 7 mg/kg based on the patient's response. The dose for children should not exceed 7 mg/kg.
• Elderly: Smaller adult doses are advisable.

Use in convulsive states: 75 mg to 125 mg (3 mls to 5 mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsion following the use of a local anesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Hypersensitivity reactions have been reported. Other adverse reactions to thiopental sodium include the followings: respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, hypotension, tachycardia, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic reactions have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema.

Absolute Contraindication:

• Absence of suitable veins for intravenous administration
• Hypersensitivity (allergy) to barbiturates
• Variegate porphyria (South African) or acute intermittent porphyria
• Status asthmaticus

Relative Contraindication:

• Severe cardiovascular disease
• Hypotension or shock
• Conditions in which the hypnotic effect may be prolonged or potentiated, eg, excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis

A person competent in anesthesia management should be in constant attendance and adequate facilities for support of respiration and circulation should be available when Thiopental Sodium for injection is being used. Thiopental Sodium for Injection should be administered with caution to patients with preexisting hypotension or in conditions where the hypnotic effect may be prolonged or intensified, such as in the presence of liver disease and renal disease.

This product may be habit forming. Keep resuscitative and endotracheal intubation equipment and oxygen readily available. Maintain patency of the airway at all times. Only persons qualified in the use of anesthetics should administer this drug. Avoid extravasations or intra-arterial injection.

Possible increase in difficulty in producing anaesthesia in patients taking alcohol or CNS depressants. Additive action with other CNS depressants including sedatives, hypnotics, nitrous oxide or alcohol. Increased hypotension and excitatory effects with phenothiazine antipsychotics. Increased hypnotic effect with antipsychotic. Decreased requirement of thiopental sodium with metoclopramide, sulfisoxazole, aspirin, meprobamate, probenecid and other highly protein bound drugs.

Pregnancy Category C. Animal reproduction studies have not been conducted with Thiopental. It is also not known whether Thiopental can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Thiopental should be given to a pregnant woman only if clearly needed. Thiopental sodium readily crosses the placental barrier and small amounts may appear in the milk of nursing mothers following administration of large doses.

Overdosage may occur from too rapid or repeated administration. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnoea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the agent should be discontinued.

Store at controlled room temperature of 15° C to 30° C. Solutions should be freshly prepared and used immediately. Any portion of the contents remaining should be discarded.

Vitamin-B preparations

Thiamine, in the form of thiamine pyrophosphate, is the coenzyme for decarboxylation of α-ketoglutaric acid. Thiamine deficiency affects the peripheral nervous system, the gastrointestinal tract, and the cardiovascular system. This vitamin is necessary for the optimal growth of infants and children. Thiamine is not stored in the body, and is regularly lost from tissues during short periods of deficiency. In order to maintain normal health, an adequate amount of thiamine is required every day. Deficiency of thiamine leads to fatigue, anorexia, gastrointestinal disturbance, tachycardia, irritability and neurological symptoms. Beriberi, a disease due to vitamin B1 deficiency, is common in alcoholics, in pregnant women receiving an inadequate diet, and in people with malabsorption syndrome, prolonged diarrhoea and hepatic disease.

Thiamine is well absorbed from the gastrointestinal tract and widely distributed throughout the body. Thiamine is rapidly absorbed from the upper small intestine. Thiamine is not stored in the body to any appreciable extent. Excess ingested thiamine appears in urine as intact thiamine or as pyrimidine, which arises from degradation of the thiamine molecule. The plasma half life of thiamine is 24 hours.

Prophylaxis: 3 to 10 mg daily.
Mild chronic deficiency: 10 to 25 mg daily.
Severe deficiency: 200 to 300 mg daily.

Vitamin B1 does not have adverse effects when given orally, but in a few fatal cases anaphylactic reactions have occurred after intravenous administration of large doses (400 mg) in sensitive patients, especially children, and in one case following an intramuscular dose of 125 mg. The risk of such reactions increases with repeated administration of the drug by parenteral route. Transient mild soreness may occur at the site of intramuscular administration

There is no absolute contraindication but the risk of anaphylaxis is increased by repeated parenteral administration. Mild allergic phenomena, such as sneezing or mild asthma are warning signs that further may give rise to anaphylactic shock. To avoid this possibility it is advisable to start a second course of injection with a dose considerably lower than that previously used. Because of the above, vitamin B1 injection should not be given intravenously except in the case of comatose patients. Once thiamine deficiency is corrected there is no need for parenteral administration or for the administration of amounts in excess of daily requirement.

No hazardous drug interactions have been reported. Vitamin B1 acts synergistically with other vitamins of the B-complex group and its potential for causing adverse effects is considerably reduced.

The drug may be given safely to neonates, children, pregnant and lactating women and elderly patients.

Thiamine injection should be protected from light and moisture.

Sodium Thiosulfate is indicated for sequential use with sodium nitrite for treatment of acute cyanide poisoning that is judged to be life threatening. Use with caution if the diagnosis of cyanide poisoning is uncertain.

Antidote preparations

Sodium thiosulfate acts as an antidote in the treatment of cyanide poisoning. It acts as a sulphur-donating substrate for the enzyme rhodanese, thus speeding up the conversion of cyanide to thiocyanide, which is relatively non toxic. It is often used in combination with sodium nitrite but may be used alone in less severe poisoning.

Adult: To be given after 300 mg of sodium nitrite has been admin over 5-20 min: 12.5 g of sodium thiosulfate (50 ml of a 25% solution or 25 ml of a 50% solution) given over 10 min. Methaemoglobin concentration should not exceed 30-40%. If symptoms of cyanide toxicity recur, the doses of nitrite and thiosulfate may be repeated after 30 min at half the initial doses.

Child: To be given after 4-10 mg/kg of sodium nitrite (max: 300 mg) has been admin: 400 mg/kg of sodium thiosulfate, as a 25 or 50% solution (max: 12.5 g). Methaemoglobin concentration should not exceed 30-40%. If symptoms of cyanide toxicity recur, the doses of nitrite and thiosulfate may be repeated after 30 min at half the initial doses.

Osmotic disturbances. Oral: catharsis (at high doses).

Sodium thiosulfate drug product may contain trace impurities of sodium sulfite. The presence of a trace amount of sulfites in this product should not deter administration of the drug for treatment of emergency situations, even if the patient is sulfite-sensitive.

Formal drug interaction studies have not been conducted with Sodium Thiosulfate.

Pregnancy Category C. There are no adequate and well controlled studies in pregnant women. Sodium Thiosulfate Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether sodium thiosulfate is excreted in human milk. Because Sodium Thiosulfate Injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following Sodium Thiosulfate Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of sodium thiosulfate.

Pediatric Use: There are case reports in the medical literature of sodium nitrite in conjunction with sodium thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of sodium thiosulfate in the pediatric population.

Geriatric Use: Sodium thiosulfate is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

There is limited information about the effects of large doses of sodium thiosulfate in humans. Oral administration of 3 g sodium thiosulfate per day for 1-2 weeks in humans resulted in reductions in room air arterial oxygen saturation to as low as 75%, which was due to a rightward shift in the oxygen hemoglobin dissociation curve. The subjects returned to baseline oxygen saturations 1 week after discontinuation of sodium thiosulfate. A single intravenous administration of 20 mL of 10% sodium thiosulfate reportedly did not change oxygen saturations.

Store at controlled room temperature between 20°C and 25°C. Protect from direct light. Do not freeze.

Sodium Thiosulfate is indicated for sequential use with sodium nitrite for treatment of acute cyanide poisoning that is judged to be life threatening. Use with caution if the diagnosis of cyanide poisoning is uncertain.

Antidote preparations

Sodium thiosulfate acts as an antidote in the treatment of cyanide poisoning. It acts as a sulphur-donating substrate for the enzyme rhodanese, thus speeding up the conversion of cyanide to thiocyanide, which is relatively non toxic. It is often used in combination with sodium nitrite but may be used alone in less severe poisoning.

Adult: To be given after 300 mg of sodium nitrite has been admin over 5-20 min: 12.5 g of sodium thiosulfate (50 ml of a 25% solution or 25 ml of a 50% solution) given over 10 min. Methaemoglobin concentration should not exceed 30-40%. If symptoms of cyanide toxicity recur, the doses of nitrite and thiosulfate may be repeated after 30 min at half the initial doses.

Child: To be given after 4-10 mg/kg of sodium nitrite (max: 300 mg) has been admin: 400 mg/kg of sodium thiosulfate, as a 25 or 50% solution (max: 12.5 g). Methaemoglobin concentration should not exceed 30-40%. If symptoms of cyanide toxicity recur, the doses of nitrite and thiosulfate may be repeated after 30 min at half the initial doses.

Osmotic disturbances. Oral: catharsis (at high doses).

Sodium thiosulfate drug product may contain trace impurities of sodium sulfite. The presence of a trace amount of sulfites in this product should not deter administration of the drug for treatment of emergency situations, even if the patient is sulfite-sensitive.

Formal drug interaction studies have not been conducted with Sodium Thiosulfate.

Pregnancy Category C. There are no adequate and well controlled studies in pregnant women. Sodium Thiosulfate Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether sodium thiosulfate is excreted in human milk. Because Sodium Thiosulfate Injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following Sodium Thiosulfate Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of sodium thiosulfate.

Pediatric Use: There are case reports in the medical literature of sodium nitrite in conjunction with sodium thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of sodium thiosulfate in the pediatric population.

Geriatric Use: Sodium thiosulfate is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

There is limited information about the effects of large doses of sodium thiosulfate in humans. Oral administration of 3 g sodium thiosulfate per day for 1-2 weeks in humans resulted in reductions in room air arterial oxygen saturation to as low as 75%, which was due to a rightward shift in the oxygen hemoglobin dissociation curve. The subjects returned to baseline oxygen saturations 1 week after discontinuation of sodium thiosulfate. A single intravenous administration of 20 mL of 10% sodium thiosulfate reportedly did not change oxygen saturations.

Store at controlled room temperature between 20°C and 25°C. Protect from direct light. Do not freeze.

General (Intravenous) anesthetics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia

Thiopental binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Thiopental Injection is administered intravenously normally as a 2.5% w/v solution. On occasions it may be administered as a 5% w/v solution (500 mg in 10 ml). The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution.

Premedication: Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Ideally, the peak effect of these medications should be reached shortly before the time of induction.

Test dose: It is advisable to inject a small "test" dose of 25 mg to 75 mg of Thiopental Sodium for Injection to assess tolerance or unusual sensitivity to Thiopental Sodium for Injection, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Thiopental Sodium for Injection, (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much.

Use in anaesthesia: Normal dosage for the induction of anesthesia is 100 mg to 150 mg injected over 10 to 15 seconds. If necessary, a repeat dose of 100 mg to 150 mg may be given after one minute. No fixed dosage recommendations for the intravenous injection can be given, since the dosage will need to be carefully adjusted according to the patient's response. Factors such as age, sex, and weight of the patient should be taken into consideration. Thiopental Sodium reaches effective concentrations in the brain within 30 seconds and anesthesia is normally produced within one minute of an intravenous dose.

• Adult: 100 mg to 150 mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 100 mg to 150 mg may be given after one minute. The intravenous injection should be given slowly and the amount given titrated against the patient's response to minimize the risk of respiratory depression or the possibility of over dosage. The average dose for an adult of 70 kg is roughly 200 mg to 300 mg (8 mls to 12 mls of a 2.5% w/v solution) with a maximum of 500 mg.
• Children: 2 mg/kg to 7 mg/kg bodyweight, intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 2 mg/kg to 7 mg/kg may be given after one minute. The dose is 2 mg/kg to 7 mg/kg based on the patient's response. The dose for children should not exceed 7 mg/kg.
• Elderly: Smaller adult doses are advisable.

Use in convulsive states: 75 mg to 125 mg (3 mls to 5 mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsion following the use of a local anesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Hypersensitivity reactions have been reported. Other adverse reactions to thiopental sodium include the followings: respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, hypotension, tachycardia, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic reactions have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema.

Absolute Contraindication:

• Absence of suitable veins for intravenous administration
• Hypersensitivity (allergy) to barbiturates
• Variegate porphyria (South African) or acute intermittent porphyria
• Status asthmaticus

Relative Contraindication:

• Severe cardiovascular disease
• Hypotension or shock
• Conditions in which the hypnotic effect may be prolonged or potentiated, eg, excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis

A person competent in anesthesia management should be in constant attendance and adequate facilities for support of respiration and circulation should be available when Thiopental Sodium for injection is being used. Thiopental Sodium for Injection should be administered with caution to patients with preexisting hypotension or in conditions where the hypnotic effect may be prolonged or intensified, such as in the presence of liver disease and renal disease.

This product may be habit forming. Keep resuscitative and endotracheal intubation equipment and oxygen readily available. Maintain patency of the airway at all times. Only persons qualified in the use of anesthetics should administer this drug. Avoid extravasations or intra-arterial injection.

Possible increase in difficulty in producing anaesthesia in patients taking alcohol or CNS depressants. Additive action with other CNS depressants including sedatives, hypnotics, nitrous oxide or alcohol. Increased hypotension and excitatory effects with phenothiazine antipsychotics. Increased hypnotic effect with antipsychotic. Decreased requirement of thiopental sodium with metoclopramide, sulfisoxazole, aspirin, meprobamate, probenecid and other highly protein bound drugs.

Pregnancy Category C. Animal reproduction studies have not been conducted with Thiopental. It is also not known whether Thiopental can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Thiopental should be given to a pregnant woman only if clearly needed. Thiopental sodium readily crosses the placental barrier and small amounts may appear in the milk of nursing mothers following administration of large doses.

Overdosage may occur from too rapid or repeated administration. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnoea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the agent should be discontinued.

Store at controlled room temperature of 15° C to 30° C. Solutions should be freshly prepared and used immediately. Any portion of the contents remaining should be discarded.

General (Intravenous) anesthetics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia

Thiopental binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

Thiopental Injection is administered intravenously normally as a 2.5% w/v solution. On occasions it may be administered as a 5% w/v solution (500 mg in 10 ml). The intravenous injection preparation should be used after reconstitution of the sterile powder with Water for Injections, usually to produce a 2.5% w/v solution.

Premedication: Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Ideally, the peak effect of these medications should be reached shortly before the time of induction.

Test dose: It is advisable to inject a small "test" dose of 25 mg to 75 mg of Thiopental Sodium for Injection to assess tolerance or unusual sensitivity to Thiopental Sodium for Injection, and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Thiopental Sodium for Injection, (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much.

Use in anaesthesia: Normal dosage for the induction of anesthesia is 100 mg to 150 mg injected over 10 to 15 seconds. If necessary, a repeat dose of 100 mg to 150 mg may be given after one minute. No fixed dosage recommendations for the intravenous injection can be given, since the dosage will need to be carefully adjusted according to the patient's response. Factors such as age, sex, and weight of the patient should be taken into consideration. Thiopental Sodium reaches effective concentrations in the brain within 30 seconds and anesthesia is normally produced within one minute of an intravenous dose.

• Adult: 100 mg to 150 mg intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 100 mg to 150 mg may be given after one minute. The intravenous injection should be given slowly and the amount given titrated against the patient's response to minimize the risk of respiratory depression or the possibility of over dosage. The average dose for an adult of 70 kg is roughly 200 mg to 300 mg (8 mls to 12 mls of a 2.5% w/v solution) with a maximum of 500 mg.
• Children: 2 mg/kg to 7 mg/kg bodyweight, intravenously over 10 to 15 seconds, normally as a 2.5% w/v solution. A repeat dose of 2 mg/kg to 7 mg/kg may be given after one minute. The dose is 2 mg/kg to 7 mg/kg based on the patient's response. The dose for children should not exceed 7 mg/kg.
• Elderly: Smaller adult doses are advisable.

Use in convulsive states: 75 mg to 125 mg (3 mls to 5 mls of a 2.5% w/v solution) should be given as soon as possible after the convulsion begins. Further doses may be required to control convulsion following the use of a local anesthetic. Other regimens, such as the use of intravenous or rectal diazepam, may be used to control convulsive states.

Hypersensitivity reactions have been reported. Other adverse reactions to thiopental sodium include the followings: respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, hypotension, tachycardia, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic reactions have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema.

Absolute Contraindication:

• Absence of suitable veins for intravenous administration
• Hypersensitivity (allergy) to barbiturates
• Variegate porphyria (South African) or acute intermittent porphyria
• Status asthmaticus

Relative Contraindication:

• Severe cardiovascular disease
• Hypotension or shock
• Conditions in which the hypnotic effect may be prolonged or potentiated, eg, excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis

A person competent in anesthesia management should be in constant attendance and adequate facilities for support of respiration and circulation should be available when Thiopental Sodium for injection is being used. Thiopental Sodium for Injection should be administered with caution to patients with preexisting hypotension or in conditions where the hypnotic effect may be prolonged or intensified, such as in the presence of liver disease and renal disease.

This product may be habit forming. Keep resuscitative and endotracheal intubation equipment and oxygen readily available. Maintain patency of the airway at all times. Only persons qualified in the use of anesthetics should administer this drug. Avoid extravasations or intra-arterial injection.

Possible increase in difficulty in producing anaesthesia in patients taking alcohol or CNS depressants. Additive action with other CNS depressants including sedatives, hypnotics, nitrous oxide or alcohol. Increased hypotension and excitatory effects with phenothiazine antipsychotics. Increased hypnotic effect with antipsychotic. Decreased requirement of thiopental sodium with metoclopramide, sulfisoxazole, aspirin, meprobamate, probenecid and other highly protein bound drugs.

Pregnancy Category C. Animal reproduction studies have not been conducted with Thiopental. It is also not known whether Thiopental can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Thiopental should be given to a pregnant woman only if clearly needed. Thiopental sodium readily crosses the placental barrier and small amounts may appear in the milk of nursing mothers following administration of large doses.

Overdosage may occur from too rapid or repeated administration. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnoea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the agent should be discontinued.

Store at controlled room temperature of 15° C to 30° C. Solutions should be freshly prepared and used immediately. Any portion of the contents remaining should be discarded.