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Short-acting selective & β2-adrenoceptor stimulants

Salbutamol is a selective β2-adrenoceptor agonist. At therapeutic doses, it acts on the β2-adrenoceptors of bronchial smooth muscle, with little or no action on the β1-adrenoceptors of cardiac muscle. Salbutamol provides short-acting (4-6 hours) bronchodilatation with a fast onset (within 5 minutes) in reversible airway obstruction. It also has an anti-inflammatory effect on mast cells causing inhibition of release of bronchoconstrictor mediators including histamine, neutrophil chemotactive factor (NCF) and prostaglandin D2.

Administer Salbutamol Inhaler by oral inhalation only. Shake Salbutamol Inhaler well before each spray.

For relief of acute episodes of bronchospasm:

• Adults: 1 or 2 puffs as necessary. The maximum dose is up to 8 puffs in 24 hours.
• Children: Half the adult dose.

To prevent allergen-or exercise-induced bronchospasm:

• Adults: 2 puffs 15 minutes prior to exercise or exposure to the allergen. The maximum dose is 2 puffs, up to 4 times a day.
• Children: Half the adult dose.

Chronic therapy:

• Adults: Up to 200 mcg (2 puffs) four times daily.
• Children: Up to 200 mcg (2 puffs) four times daily.

Using an Inhaler seems simple, but most patients do not know how to use it in the right way. If the Inhaler is used in the wrong way, less medicine can reach the lungs. Correct and regular use of the Inhaler will prevent or lessen the severity of asthma attacks.

Following simple steps can help to use Inhaler effectively (According to "National Asthma Guidelines for Medical Practitioners" published by Asthma Association):

1. Take off the cap.
2. Shake the inhaler (at least six times) vigorously before each use.
3. If the inhaler is new or if it has not been used for a week or more, shake it well and release one puff into the air to make sure that it works.
4. Breathe out as full as comfortably possible & hold the inhaler upright.
5. Place the actuator into mouth between the teeth and close lips around the mouthpiece.
6. While breathing deeply and slowly through the mouth, press down firmly add fully on the canister to release medicine.
7. Remove the inhaler from mouth. Continue holding breath for at least for 10 seconds or as long as it is comfortable.
8. If doctor has prescribed more than one inhalation per treatment, wait 1 minute between puffs (inhalations). Shake the inhaler well and repeat steps 4 to 7.
9. After use, replace the cap on the mouthpiece. After each treatment, rinse mouth with water.
10. Check your technique in front of a mirror from time to time, if you see a white mist during the inhalation, you may not have closed your lips properly around mouthpiece, or you may not be breathing in as you press the can. This indicates failure of technique. If this happens, repeat the procedure from step 4 carefully.

Instructions for Cleaning Inhaler: Clean your Inhaler at least once a week. Remove canister and rinse the plastic actuator and cap in warm water but do not put the metal canister into water. Dry the actuator and cap thoroughly and gently replace the metal canister into the actuator with a twisting motion. Put the cap on the mouthpiece.

Salbutamol is generally well tolerated. Few side effects have been observed during inhalation. There are tremors, anxiety, muscle cramps, headache, palpitation, a compensatory small increase in heart rate, cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles), tachycardia may occur in some patients. Mouth and throat irritation may occur with inhaled salbutamol

Salbutamol inhaler is contraindicated in patients with a history of hypersensitivity to salbutamol or any other components of Salbutamol inhaler.

Paradoxical Bronchospasm: Inhaled salbutamol sulfate can produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs, the Salbutamol inhaler should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm when associated with inhaled formulations; frequently occurs with the first use of a new canister.

Cardiovascular Effects: Salbutamol inhaler, like all other β2-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients such as changes in pulse rate or blood pressure. If such effects occur, Salbutamol inhaler may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiograms (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression. The clinical relevance of these findings is unknown. Therefore, Salbutamol inhaler, like all other sympathomimetic amines, should be used with caution in patients with underlying cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Immediate Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur after administration of salbutamol sulfate inhalation aerosol, as demonstrated by cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Discontinue Salbutamol inhaler if immediate hypersensitivity reactions occur.

Coexisting Conditions: Salbutamol inhaler, like other sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines. Large doses of intravenous salbutamol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

Salbutamol and non-selective beta-blocking drugs such as propranolol should generally not be prescribed together. Potentially serious hypokalaemia may result from β2-agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids, diuretics, and by hypoxia. It is recommended that serum potassium levels are monitored in such situations.

Pregnancy Category C. There are no adequate and well-controlled studies of Salbutamol inhaler or salbutamol sulfate in pregnant women. This inhaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether the components of Salbutamol inhaler are excreted in human milk. Caution should be exercised when this inhaler is administered to a nursing woman.

Use in children: The safety and effectiveness of Salbutamol inhaler in children 4 years of age and older have been established.

Pressurized canister. Do not puncture, break or burn even when apparently empty. Keep away from sunlight and heat. Store below 30°C. Do not freeze. Keep away from eyes. Keep away from children. To be dispensed only on or by the prescription of a registered physician.

This inhalation aerosol is indicated for use in patients with chronic obstructive pulmonary disease (COPD) on a regular aerosol bronchodilator who continues to have evidence of bronchospasm and who requires a second bronchodilator.

Combined bronchodilators

This inhalation aerosol is a combination of Salbutamol (as Sulphate) and Ipratropium Bromide. It is a hydrofluoroalkane (HFA) based environment friendly inhaler. Because it does not contain chlorofluorocarbon (CFC) as propellant which is one of the main reasons of ozone layer depletion.

Salbutamol is a short acting beta2-adrenergic bronchodilator and Ipratropium Bromide is an anticholinergic bronchodilator. When used in combination, Ipratropium Bromide prevents the increase in intracellular concentration of cyclic guanosine monophosphate, which are caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle. This inhalation aerosol is expected to maximize the response of the treatment in patients with chronic obstructive pulmonary disease (COPD) by reducing bronchospasm through two distinctly different mechanisms, anticholinergic (parasympatholytic) and sympathomimetic. Simultaneous administration of an anticholinergic (Ipratropium Bromide) and a beta 2-sympathomimetic (Salbutamol) is designed to benefit the patient by producing a greater bronchodilatory effect than when either drug is utilized alone at its recommended dosage.

Adult dose (Including the elderly): 2 puffs of Salpium 4 times a day (Patients may take additional puffs as required but a total number of puffs should not exceed 12 in 24 hours). Or as directed by the physician.

Using an Inhaler seems simple, but most patients do not know how to use it in the right way. If the Inhaler is used in the wrong way, less medicine can reach the lungs. Correct and regular use of the Inhaler will prevent or lessen the severity of asthma attacks.

Following simple steps can help to use Inhaler effectively (According to "National Asthma Guidelines for Medical Practitioners" published by Asthma Association):

1. Take off the cap.
2. Shake the inhaler (at least six times) vigorously before each use.
3. If the inhaler is new or if it has not been used for a week or more, shake it well and release one puff into the air to make sure that it works.
4. Breathe out as full as comfortably possible & hold the inhaler upright.
5. Place the actuator into mouth between the teeth and close lips around the mouthpiece.
6. While breathing deeply and slowly through the mouth, press down firmly add fully on the canister to release medicine.
7. Remove the inhaler from mouth. Continue holding breath for at least for 10 seconds or as long as it is comfortable.
8. If doctor has prescribed more than one inhalation per treatment, wait 1 minute between puffs (inhalations). Shake the inhaler well and repeat steps 4 to 7.
9. After use, replace the cap on the mouthpiece. After each treatment, rinse mouth with water.
10. Check your technique in front of a mirror from time to time, if you see a white mist during the inhalation, you may not have closed your lips properly around mouthpiece, or you may not be breathing in as you press the can. This indicates failure of technique. If this happens, repeat the procedure from step 4 carefully.

Instructions for Cleaning Inhaler: Clean your Inhaler at least once a week. Remove canister and rinse the plastic actuator and cap in warm water but do not put the metal canister into water. Dry the actuator and cap thoroughly and gently replace the metal canister into the actuator with a twisting motion. Put the cap on the mouthpiece.

Due to presence of Salbutamol, mild tremor and headache have been reported. These usually disappear with continuous treatment. There have been very rare reports of treatments muscle cramp, hypersensitivity reactions including angioedema, urticaria, bronchospasm and hypotension.

For the presence of Ipratropium Bromide headache, influenza, chest pain, nausea, dyspnea, coughing, pharyngitis, sinusitis are rarely reported.

This inhalation aerosol is contraindicated in patients with a history of hypersensitivity to Soya-Lecithin or related food products such as soybean and peanut. This inhalation aerosol is also contraindicated in patients hypersensitive to any other components of the drug product or to atropine or its derivatives.

This inhalation aerosol has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines and steroids, commonly used in the treatment of COPD. No formal drug interaction studies have been performed with this inhalation aerosol and these or other medications commonly used in the treatment of COPD. Ipratropium Bromide should be co-administered cautiously with other anticholinergic agents and sympathomimetic agents, which may increase the risk of adverse cardiovascular effects. Beta-2-agonist containing drugs, like this inhalation aerosol, should be administrated with extreme caution in patients with non-potassium sparing diuretics, monoamine oxidase inhibitors or tricyclic antidepressants.

Ipratropium Bromide: Pregnancy category B. Studies have demonstrated no teratogenic effects as a result of ipratropium.

Salbutamol: Pregnancy category C. Salbutamol has been shown to be teratogenic in animals.

There are, however no adequate and well-controlled studies of Salpium Inhalation Aerosol (Salbutamol and Ipratropium Bromide combination) in pregnant woman. This inhalation aerosol should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether the components of the Salpium InhalationAerosol are excreted in human milk. As many drugs are excreted in human milk, Salpium should be cautiously administered to a nursing mother.

This inhalation aerosol contains Ipratropium Bromide and, therefore, should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy or bladder-neck obstruction. Preparations containing sympathomimetic amines such as Salbutamol Sulphate should be used with caution in patients with convulsive disorders, hyperthyroidism, diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines.

The effects of overdosage are expected to be related primarily to Salbutamol Sulphate. Manifestations of overdosage with Salbutamol may include anginal pain, hypertension, hypokalemia and tachycardia.

Do not puncture, break or incinerate the pressurized canister even when apparently empty. Avoid storage in direct sunlight or heat. Store in a cool and dry place. Keep away from children. Keep away from eyes.

Montelukast Sodium is indicated for:

• Prophylaxis and chronic treatment of asthma
• Acute prevention of Exercise-Induced Bronchoconstriction (EIB)
• Relief of symptoms of Allergic Rhinitis (AR): Seasonal & Perennial Allergic Rhinitis

Leukotriene receptor antagonists

Montelukast is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor (CysLT₁). The cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma & allergic rhinitis, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

Adults & adolescents (15 years & older)-

• Asthma & Allergic Rhinitis: 10 mg/day 
• Exercise-Induced Bronchoconstriction: 10 mg/day

Pediatric patients (6 to 14 years)-

• Asthma & Allergic Rhinitis: 5 mg/day 
• Exercise-Induced Bronchoconstriction: 5 mg/day

Pediatric patients (6 months to 5 years)-

• Asthma & Allergic Rhinitis: 4 mg/day 
• Exercise-Induced Bronchoconstriction: Not recommended

Patients with both asthma and allergic rhinitis should take only one dose daily in the evening. For prevention of Acute prevention of Exercise-Induced Bronchoconstriction, a single dose should be taken at least 2 hours before exercise.

Route of administration: Oral. Montelukast may be taken with or without food or as directed by the physician.

Common: Diarrhoea, fever, gastrointestinal discomfort, headache, nausea, vomiting, skin reactions, upper respiratory tract infection.

Uncommon: Akathisia, anxiety, arthralgia, asthenia, abnormal behavior, depression, dizziness, drowsiness, dry mouth, haemorrhage, irritability, malaise, muscle complaints, oedema, seizure, abnormal sensation, sleep disorders.

Rare: Angioedema, concentration impaired, disorientation, eosinophilic granulomatosis with polyangiitis, erythema nodosum, hallucination, hepatic disorders, memory loss, palpitations, pulmonary eosinophilia, suicidal tendencies, tremor.

Montelukast is contraindicated in patients who are hypersensitive to any component of this product.

Montelukast is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmatic. Neuropsychiatric events including agitation, hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide) and tremor.

With medicine: No dose adjustment is needed when montelukast is co-administered with theophylline, prednisone, prednisolone, terfenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative-hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, oral contraceptives, and Cytochrome P450 (CYP) enzyme inducers.

With food and others: Bioavailability and other conditions were not significantly observed with food & other conditions.

There are no adequate and well-controlled studies in pregnant women. Montelukast should be used during pregnancy only if clearly needed. Montelukast is excreted in breast milk. So caution should be exercised when Montelukast is given to a nursing mother.

There were no adverse experiences in the majority of overdosage reports. The most frequently occurring adverse experiences were consistent with the safety profile of Montelukast and included abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity. In the event of overdose, it is reasonable to employ the usual supportive measures; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.

Store in cool & dry place below 30°C, protect from light & moisture. Keep out of reach of children.

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Levosalbutamol is indicated for the treatment or prevention of bronchospasm in adults, adolescents and children 6 years of age and older with reversible obstructive airway disease.

Short-acting selective & β2-adrenoceptor stimulants

Levosalbutamol is a single isomer beta 2-agonist that differs from racemic salbutamol by elimination of (S)-salbutamol. Levosalbutamol is an effective bronchodilator whose primary mechanism of action is unimpeded by (S)-salbutamol. Thus, when compared with racemic salbutamol, clinically comparable bronchodilation can be achieved with doses that substantially lessen beta-mediated side effects.

Tablet-

• Adults and adolescents above 12 years: 1-2 mg three times daily.
• Children (6 -11 years): 1 mg three times daily.

Syrup-

• Adults : 5-10 ml three times daily.
• Childrn (6-11 years): 5 ml three times daily.

Hypocalcaemia, palpitation, fine tremors of the skeletal muscle and muscle cramps may occur. The other likely side effects are nausea, vomiting, burning substernal or epigastric pain and diarrhoea.

Levosalbutamol is contraindicated in patients with a history of hypersensitivity to levosalbutamol or any of its components.

Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations.

Other short acting sympathomimetic bronchodilators or epinephrine should be used with caution with Levosalbutamol. If additional adrenergic drugs are to be administered by any route, they will be used with caution to avoid deleterious cardiovascular effects.

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether Levosalbutamol is excreted in human milk. Caution should be exercised when oral Levosalbutamol is administered to a nursing woman.

The expected symptoms with over dosage are those of excessive beta-adrenergic stimulation and the symptoms listed under side effects. In the event of serious poisoning, the stomach should be emptied and, if necessary, a beta-blocker administered with caution in patients with a history of bronchospasm.

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

Levosalbutamol is indicated for the treatment or prevention of bronchospasm in adults, adolescents and children 6 years of age and older with reversible obstructive airway disease.

Short-acting selective & β2-adrenoceptor stimulants

Levosalbutamol is a single isomer beta 2-agonist that differs from racemic salbutamol by elimination of (S)-salbutamol. Levosalbutamol is an effective bronchodilator whose primary mechanism of action is unimpeded by (S)-salbutamol. Thus, when compared with racemic salbutamol, clinically comparable bronchodilation can be achieved with doses that substantially lessen beta-mediated side effects.

Tablet-

• Adults and adolescents above 12 years: 1-2 mg three times daily.
• Children (6 -11 years): 1 mg three times daily.

Syrup-

• Adults : 5-10 ml three times daily.
• Childrn (6-11 years): 5 ml three times daily.

Hypocalcaemia, palpitation, fine tremors of the skeletal muscle and muscle cramps may occur. The other likely side effects are nausea, vomiting, burning substernal or epigastric pain and diarrhoea.

Levosalbutamol is contraindicated in patients with a history of hypersensitivity to levosalbutamol or any of its components.

Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations.

Other short acting sympathomimetic bronchodilators or epinephrine should be used with caution with Levosalbutamol. If additional adrenergic drugs are to be administered by any route, they will be used with caution to avoid deleterious cardiovascular effects.

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether Levosalbutamol is excreted in human milk. Caution should be exercised when oral Levosalbutamol is administered to a nursing woman.

The expected symptoms with over dosage are those of excessive beta-adrenergic stimulation and the symptoms listed under side effects. In the event of serious poisoning, the stomach should be emptied and, if necessary, a beta-blocker administered with caution in patients with a history of bronchospasm.

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

Doxophylline is used to treat in following indications:

• Bronchial asthma
• Bronchospasm
• Chronic obstructive pulmonary disease (COPD)
• Pulmonary disease with spastic bronchial component.

Bronchodilator, Methyl xanthine derivatives

Doxophylline is a novel bronchodilator. It structurally differs from Theophylline due to the presence of a dioxolane group in position 7. Doxophylline selectively inhibits phosphodiesterase 4 thereby relaxes bronchial smooth muscle. However, differently from Theophylline, Doxophylline appears to have decreased affinities toward adenosine A1 and A2 receptors, which may account for the better safety profile of the drug. Doxophylline is reported to inhibit platelet activating factor (PAF) and generation of leukotriene production.

Elderly: 200 mg tablet two or three times daily.

Adults: 400 mg tablet two or three times daily or as prescribed by the physician.

Children:

• >12 years of age: 10 ml syrup or 200 mg tablet two or three times daily.
• 6-12 years of age: 6-9 mg/kg body weight two times daily, i.e. if body weight is 10 kg, 3 ml (60 mg) two times daily or as prescribed by the physician.

If required daily dose of Doxophylline is 400 mg then Doxophylline SR tablet to be taken once daily or as prescribed by the physician

Doxophylline rarely causes serious side effects, however possible side effects are similar for taking excess amount of caffeine. These include: nausea, vomiting, headache, upset stomach and heartburn.

Doxophylline is contraindicated in acute myocardial infarction. It is also contraindicated in patients with hypotension, in lactating women & patients who have shown hypersensitivity to its components.

The half-life of xanthine derivatives is influenced by a number of known variables. It may be prolonged in patients with liver disease, in patients with congestive heart failure and in those patients taking certain other drugs like erythromycin, troleandomycin, lincomycin, allopurinol, cimetidine, propanolol and anti-flu vaccine. In these cases, a lower dose of Doxophylline may be needed. Phenytoin, other anticonvulsants and smoking may cause an increase in clearance with a shorter mean half-life. In these cases higher doses of Doxophylline may be needed.

Doxophylline should not be administered together with other xanthine derivatives. Toxic synergism with ephedrine has been documented for xanthines. Like other xanthines, concomitant therapy with troleandomycin, lincomycin, clindamycin, allopurinol, cimetidine, ranitidine, propranolol and anti-flu vaccine may decrease the hepatic clearance of xanthines causing an increase in blood levels. No evidence of a relationship between Doxophylline serum concentrations and toxic events have been reported.

Animal reproduction studies indicate that, Doxophylline does not cause fetal harm when administered to pregnant animals or can not affect reproduction capacity. However, since there is limited experience in human during pregnancy, xanthines should be given to pregnant women only if clearly needed. Doxophylline is contraindicated in nursing mothers.

In case of overdose severe cardiac arrhythmias and tonic-clonic seizure may occur. These effects may represent the first signs of intoxication. The appearance of side effects may require discontinuation of the treatment which, if necessary, at the physician’s discretion, may be resumed at lower doses after all signs and symptoms of toxicity have subsided.

As there is no specific antidote, in case of overdose a symptomatic treatment of cardiovascular collapse should be instituted.

Keep in a dry place away from light and heat. Keep out of the reach of children. Doxophylline should be used only on prescription of specialist physician.

Doxophylline is used to treat in following indications:

• Bronchial asthma
• Bronchospasm
• Chronic obstructive pulmonary disease (COPD)
• Pulmonary disease with spastic bronchial component.

Bronchodilator, Methyl xanthine derivatives

Doxophylline is a novel bronchodilator. It structurally differs from Theophylline due to the presence of a dioxolane group in position 7. Doxophylline selectively inhibits phosphodiesterase 4 thereby relaxes bronchial smooth muscle. However, differently from Theophylline, Doxophylline appears to have decreased affinities toward adenosine A1 and A2 receptors, which may account for the better safety profile of the drug. Doxophylline is reported to inhibit platelet activating factor (PAF) and generation of leukotriene production.

Elderly: 200 mg tablet two or three times daily.

Adults: 400 mg tablet two or three times daily or as prescribed by the physician.

Children:

• >12 years of age: 10 ml syrup or 200 mg tablet two or three times daily.
• 6-12 years of age: 6-9 mg/kg body weight two times daily, i.e. if body weight is 10 kg, 3 ml (60 mg) two times daily or as prescribed by the physician.

If required daily dose of Doxophylline is 400 mg then Doxophylline SR tablet to be taken once daily or as prescribed by the physician

Doxophylline rarely causes serious side effects, however possible side effects are similar for taking excess amount of caffeine. These include: nausea, vomiting, headache, upset stomach and heartburn.

Doxophylline is contraindicated in acute myocardial infarction. It is also contraindicated in patients with hypotension, in lactating women & patients who have shown hypersensitivity to its components.

The half-life of xanthine derivatives is influenced by a number of known variables. It may be prolonged in patients with liver disease, in patients with congestive heart failure and in those patients taking certain other drugs like erythromycin, troleandomycin, lincomycin, allopurinol, cimetidine, propanolol and anti-flu vaccine. In these cases, a lower dose of Doxophylline may be needed. Phenytoin, other anticonvulsants and smoking may cause an increase in clearance with a shorter mean half-life. In these cases higher doses of Doxophylline may be needed.

Doxophylline should not be administered together with other xanthine derivatives. Toxic synergism with ephedrine has been documented for xanthines. Like other xanthines, concomitant therapy with troleandomycin, lincomycin, clindamycin, allopurinol, cimetidine, ranitidine, propranolol and anti-flu vaccine may decrease the hepatic clearance of xanthines causing an increase in blood levels. No evidence of a relationship between Doxophylline serum concentrations and toxic events have been reported.

Animal reproduction studies indicate that, Doxophylline does not cause fetal harm when administered to pregnant animals or can not affect reproduction capacity. However, since there is limited experience in human during pregnancy, xanthines should be given to pregnant women only if clearly needed. Doxophylline is contraindicated in nursing mothers.

In case of overdose severe cardiac arrhythmias and tonic-clonic seizure may occur. These effects may represent the first signs of intoxication. The appearance of side effects may require discontinuation of the treatment which, if necessary, at the physician’s discretion, may be resumed at lower doses after all signs and symptoms of toxicity have subsided.

As there is no specific antidote, in case of overdose a symptomatic treatment of cardiovascular collapse should be instituted.

Keep in a dry place away from light and heat. Keep out of the reach of children. Doxophylline should be used only on prescription of specialist physician.

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Short-acting selective & β2-adrenoceptor stimulants

Salbutamol is a selective β2-adrenoceptor agonist. At therapeutic doses, it acts on the β2-adrenoceptors of bronchial smooth muscle, with little or no action on the β1-adrenoceptors of cardiac muscle. Salbutamol provides short-acting (4-6 hours) bronchodilatation with a fast onset (within 5 minutes) in reversible airway obstruction. It also has an anti-inflammatory effect on mast cells causing inhibition of release of bronchoconstrictor mediators including histamine, neutrophil chemotactive factor (NCF) and prostaglandin D2.

Administer Salbutamol Inhaler by oral inhalation only. Shake Salbutamol Inhaler well before each spray.

For relief of acute episodes of bronchospasm:

• Adults: 1 or 2 puffs as necessary. The maximum dose is up to 8 puffs in 24 hours.
• Children: Half the adult dose.

To prevent allergen-or exercise-induced bronchospasm:

• Adults: 2 puffs 15 minutes prior to exercise or exposure to the allergen. The maximum dose is 2 puffs, up to 4 times a day.
• Children: Half the adult dose.

Chronic therapy:

• Adults: Up to 200 mcg (2 puffs) four times daily.
• Children: Up to 200 mcg (2 puffs) four times daily.

Using an Inhaler seems simple, but most patients do not know how to use it in the right way. If the Inhaler is used in the wrong way, less medicine can reach the lungs. Correct and regular use of the Inhaler will prevent or lessen the severity of asthma attacks.

Following simple steps can help to use Inhaler effectively (According to "National Asthma Guidelines for Medical Practitioners" published by Asthma Association):

1. Take off the cap.
2. Shake the inhaler (at least six times) vigorously before each use.
3. If the inhaler is new or if it has not been used for a week or more, shake it well and release one puff into the air to make sure that it works.
4. Breathe out as full as comfortably possible & hold the inhaler upright.
5. Place the actuator into mouth between the teeth and close lips around the mouthpiece.
6. While breathing deeply and slowly through the mouth, press down firmly add fully on the canister to release medicine.
7. Remove the inhaler from mouth. Continue holding breath for at least for 10 seconds or as long as it is comfortable.
8. If doctor has prescribed more than one inhalation per treatment, wait 1 minute between puffs (inhalations). Shake the inhaler well and repeat steps 4 to 7.
9. After use, replace the cap on the mouthpiece. After each treatment, rinse mouth with water.
10. Check your technique in front of a mirror from time to time, if you see a white mist during the inhalation, you may not have closed your lips properly around mouthpiece, or you may not be breathing in as you press the can. This indicates failure of technique. If this happens, repeat the procedure from step 4 carefully.

Instructions for Cleaning Inhaler: Clean your Inhaler at least once a week. Remove canister and rinse the plastic actuator and cap in warm water but do not put the metal canister into water. Dry the actuator and cap thoroughly and gently replace the metal canister into the actuator with a twisting motion. Put the cap on the mouthpiece.

Salbutamol is generally well tolerated. Few side effects have been observed during inhalation. There are tremors, anxiety, muscle cramps, headache, palpitation, a compensatory small increase in heart rate, cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles), tachycardia may occur in some patients. Mouth and throat irritation may occur with inhaled salbutamol

Salbutamol inhaler is contraindicated in patients with a history of hypersensitivity to salbutamol or any other components of Salbutamol inhaler.

Paradoxical Bronchospasm: Inhaled salbutamol sulfate can produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs, the Salbutamol inhaler should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm when associated with inhaled formulations; frequently occurs with the first use of a new canister.

Cardiovascular Effects: Salbutamol inhaler, like all other β2-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients such as changes in pulse rate or blood pressure. If such effects occur, Salbutamol inhaler may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiograms (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression. The clinical relevance of these findings is unknown. Therefore, Salbutamol inhaler, like all other sympathomimetic amines, should be used with caution in patients with underlying cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Immediate Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur after administration of salbutamol sulfate inhalation aerosol, as demonstrated by cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Discontinue Salbutamol inhaler if immediate hypersensitivity reactions occur.

Coexisting Conditions: Salbutamol inhaler, like other sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines. Large doses of intravenous salbutamol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

Salbutamol and non-selective beta-blocking drugs such as propranolol should generally not be prescribed together. Potentially serious hypokalaemia may result from β2-agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids, diuretics, and by hypoxia. It is recommended that serum potassium levels are monitored in such situations.

Pregnancy Category C. There are no adequate and well-controlled studies of Salbutamol inhaler or salbutamol sulfate in pregnant women. This inhaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether the components of Salbutamol inhaler are excreted in human milk. Caution should be exercised when this inhaler is administered to a nursing woman.

Use in children: The safety and effectiveness of Salbutamol inhaler in children 4 years of age and older have been established.

Pressurized canister. Do not puncture, break or burn even when apparently empty. Keep away from sunlight and heat. Store below 30°C. Do not freeze. Keep away from eyes. Keep away from children. To be dispensed only on or by the prescription of a registered physician.

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Salbutamol is indicated as a bronchodilator for use in-

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

Short-acting selective & β2-adrenoceptor stimulants

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

Salbutamol tablet or syrup-
Children:

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

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

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

Method-1 (Intermittent Administration):

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

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

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

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

Salbutamol injection:
Adults:

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

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

Salbutamol Inhalation Capsule:

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

Excercise-induced Asthma:

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

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

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

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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

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

Cytotoxic Chemotherapy

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.

The starting dose is 20 mg of Venetoclax once daily for 7 days. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg. The 5-week dose-titration schedule is designed to gradually reduce tumour burden (debulk) and decrease the risk of tumor lysis syndrome.

Post-titration dose for Venetoclax in combination with Rituximab: The recommended dose of Venetoclax in combination with Rituximab is 400 mg once daily. Rituximab should be administered after the patient has completed the dose-titration schedule and has received the recommended daily dose of 400 mg Venetoclax for 7 days. Venetoclax should be taken for 24 months from Cycle 1 Day 1 of Rituximab.

Post-titration dose for Venetoclax monotherapy: The recommended dose of Venetoclax is 400 mg once daily. Treatment should be continued until disease progression or no longer tolerated by the patient.

The most commonly occurring side effects (>20%) of any grade in patients receiving Venetoclax in the combination study with Rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common side effects were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection. The most frequently reported serious side effects (>2%) in patients receiving Venetoclax in combination with Rituximab were pneumonia, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious side effects (>2%) were pneumonia and febrile neutropenia.

Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. Concomitant use of preparations containing St. John's wort

Tumour lysis syndrome: Tumour lysis syndrome, including fatal events, has occurred in patients with previously treated CLL with high tumour burden when treated with Venetoclax. Venetoclax can cause rapid reduction in tumour, and thus poses a risk for TLS in the initial 5-weeks dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venetoclax and at each dose increase. The risk of TLS is a continuum based on multiple factors, including comorbidities. Patients with high tumour burden (e.g., any lymph node with a diameter >5 cm or high ALC >25 x 109/1) are at greater risk of TLS when initiating enetoclax. Reduced renal function (CrCI <80 ml/min) further increases the risk. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricaemics. Blood chemistries should be monitored and abnormalities managed promptly. Dosing should be interrupted if needed. More intensive measures (intravenous hydration, frequent monitoring, hospitalization) should be employed as overall risk increases. The instructions for "Prevention of tumour lysis syndrome" should be followed. Concomitant use of this medicinal product with strong or moderate CYP3A inhibitors increases Venetoclax exposure and may increase the risk for TLS at initiation and during the dose-titration phase. Also, inhibitors of P-gp or BCRP may increase Venetoclax exposure.

Neutropenia: Grade 3 or 4 neutropenia has been reported in patients treated with Venetoclax in the combination study with Rituximab (G028667/MURANO) and in the monotherapy studies. Complete blood counts should be monitored throughout the treatment period. Dose interruptions or reductions are recommended for patients with severe neutropenia. Serious infections including events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.

Immunization: The safety and efficacy of immunization with live attenuated vaccines during or following Venetoclax therapy have not been studied. Live vaccines should not be administered during treatment and thereafter until B-cell recovery.

CYP3A inducers: Co-administration of CYP3A4 inducers may lead to decreased Venetoclax exposure and consequently a risk for lack of efficacy. Concomitant use of Venetoclax with strong or moderate CYP3A4 inducers should be avoided.

Women of childbearing potential: Women of childbearing potential must use a highly effective method of contraception while taking Venetoclax.

CYP3A inhibitors: Co-administration of 400 mg once daily ketoconazole, a strong CYP3A, P-gp and BCRP inhibitor, for 7 days in 11 previously treated patients with NHL increased Venetoclax Cmax by 2.3-fold and AUC by 6.4-fold. Co-administration of 50 mg once daily ritonavir, a strong CYP3A and P-gp inhibitor, for 14 days in 6 healthy subjects increased Venetoclax Cmax by 2.4-fold and AUC by 7.9-fold. Co-administration of Venetoclax with other strong CYP3A4 inhibitors is predicted to increase Venetoclax AUC by on average 5.8- to 7.8-fold. Concomitant use of Venetoclax with strong CYP3A inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) at initiation and during the dose-titration phase is contraindicated due to increased risk for TLS.

At initiation and during the dose-titration phase, concomitant use of Venetoclax with moderate CYP3A inhibitors (e.g., ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) should be avoided. Alternative treatments should be considered. If a moderate CYP3A inhibitor must be used, the initiation dose of Venetoclax and the doses for the titration phase should be reduced by at least 50%. Patients should be monitored more closely for signs and symptoms of TLS.

For patients who have completed the dose-titration phase and are on a steady daily dose of Venetoclax, the Venetoclax dose should be reduced by 50% when used concomitantly with moderate CYP3A inhibitors and by 75% when used concomitantly with strong CYP3A inhibitors. Patients should be monitored more closely for signs of toxicities and the dose may need to be further adjusted. The Venetoclax dose that was used prior to initiating the CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of the inhibitor. Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with Venetoclax as they contain inhibitors of CYP3A.

P-gp and BCRP inhibitors: Venetoclax is a substrate for P-gp and BCRP , Co-administration of a 600 mg single dose of rifampin, a P-gp inhibitor, in 11 healthy subjects increased Venetoclax Cmax by 106% and AUC by 78%. Concomitant use of Venetoclax with P-gp and BCRP inhibitors at initiation and during the dose-titration phase should be avoided; if a P-gp and BCRP inhibitor must be used, patients should be monitored closely for signs of toxicities.

CYP3A inducers: Co-administration of 600 mg once daily rifampin, a strong CYP3A inducer, for 13 days in 10 healthy subjects decreased Venetoclax Cmax by 42% and AUC°° by 71%. Concomitant use of Venetoclax with strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided. Alternative treatments with less CYP3A induction should be considered. Preparations containing St. John's wort are contraindicated during treatment with Venetoclax, as efficacy may be reduced.

Women of childbearing potential/Contraception in females: Women should avoid becoming pregnant while taking Venetoclax and for at least 30 days after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking Venetoclax and for 30 days after stopping treatment. It is currently unknown whether Venetoclax may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method.

Pregnancy: Based on embryo-foetal toxicity studies in animals, Venetoclax may harm the fetus when administered to pregnant women. There is no adequate and well-controlled data from the use of Venetoclax in pregnant women. Studies in animals have shown reproductive toxicity. Venetoclax is not recommended during pregnancy and in women of childbearing potential not using highly effective contraception.

Breast-feeding: It is unknown whether Venetoclax or its metabolites are excreted in human milk. A risk to the breast-feeding child cannot be excluded. Breast-feeding should be discontinued during treatment with Venetoclax.

Fertility: No human data on the effect of Venetoclax on fertility are available. Based on testicular toxicity in dogs at clinically relevant exposures, male fertility may be compromised by treatment with Venetoclax. Before starting treatment, counselling on sperm storage may be considered in some male patients.

Elderly: No specific dose adjustment is required for elderly patients (aged >65 years).

Renal impairment: No dose adjustment is needed for patients with mild or moderate renal impairment (CrCI >30 ml/min and <90 mi/min). Patients with reduced renal function (CrCI <80 ml/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCI <30 ml/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. Venetoclax should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

Hepatic impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Patients with moderate hepatic impairment should be monitored more closely for signs of toxicity at initiation and during the dose-titration phase. A dose reduction of at least 50% throughout treatment is recommended for patients with severe hepatic impairment. These patients should be monitored more closely for signs of toxicity.

Pediatric population: The safety and efficacy of Venetoclax in children aged less than 18 years have not been established. No data is available.

There is no specific antidote for Venetoclax. Patients who experience overdose should be closely monitored and appropriate supportive treatment provided. During dose-titration phase, treatment should be interrupted and patients should be monitored carefully for signs and symptoms of TLS (fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle or joint pain, abdominal pain and distension) along with other toxicities.

Store below 30°C. Keep Venetoclax out of the sight and reach of children. Protect from moisture and light.

Cytotoxic Chemotherapy

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.

The starting dose is 20 mg of Venetoclax once daily for 7 days. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg. The 5-week dose-titration schedule is designed to gradually reduce tumour burden (debulk) and decrease the risk of tumor lysis syndrome.

Post-titration dose for Venetoclax in combination with Rituximab: The recommended dose of Venetoclax in combination with Rituximab is 400 mg once daily. Rituximab should be administered after the patient has completed the dose-titration schedule and has received the recommended daily dose of 400 mg Venetoclax for 7 days. Venetoclax should be taken for 24 months from Cycle 1 Day 1 of Rituximab.

Post-titration dose for Venetoclax monotherapy: The recommended dose of Venetoclax is 400 mg once daily. Treatment should be continued until disease progression or no longer tolerated by the patient.

The most commonly occurring side effects (>20%) of any grade in patients receiving Venetoclax in the combination study with Rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common side effects were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection. The most frequently reported serious side effects (>2%) in patients receiving Venetoclax in combination with Rituximab were pneumonia, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious side effects (>2%) were pneumonia and febrile neutropenia.

Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. Concomitant use of preparations containing St. John's wort

Tumour lysis syndrome: Tumour lysis syndrome, including fatal events, has occurred in patients with previously treated CLL with high tumour burden when treated with Venetoclax. Venetoclax can cause rapid reduction in tumour, and thus poses a risk for TLS in the initial 5-weeks dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venetoclax and at each dose increase. The risk of TLS is a continuum based on multiple factors, including comorbidities. Patients with high tumour burden (e.g., any lymph node with a diameter >5 cm or high ALC >25 x 109/1) are at greater risk of TLS when initiating enetoclax. Reduced renal function (CrCI <80 ml/min) further increases the risk. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricaemics. Blood chemistries should be monitored and abnormalities managed promptly. Dosing should be interrupted if needed. More intensive measures (intravenous hydration, frequent monitoring, hospitalization) should be employed as overall risk increases. The instructions for "Prevention of tumour lysis syndrome" should be followed. Concomitant use of this medicinal product with strong or moderate CYP3A inhibitors increases Venetoclax exposure and may increase the risk for TLS at initiation and during the dose-titration phase. Also, inhibitors of P-gp or BCRP may increase Venetoclax exposure.

Neutropenia: Grade 3 or 4 neutropenia has been reported in patients treated with Venetoclax in the combination study with Rituximab (G028667/MURANO) and in the monotherapy studies. Complete blood counts should be monitored throughout the treatment period. Dose interruptions or reductions are recommended for patients with severe neutropenia. Serious infections including events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.

Immunization: The safety and efficacy of immunization with live attenuated vaccines during or following Venetoclax therapy have not been studied. Live vaccines should not be administered during treatment and thereafter until B-cell recovery.

CYP3A inducers: Co-administration of CYP3A4 inducers may lead to decreased Venetoclax exposure and consequently a risk for lack of efficacy. Concomitant use of Venetoclax with strong or moderate CYP3A4 inducers should be avoided.

Women of childbearing potential: Women of childbearing potential must use a highly effective method of contraception while taking Venetoclax.

CYP3A inhibitors: Co-administration of 400 mg once daily ketoconazole, a strong CYP3A, P-gp and BCRP inhibitor, for 7 days in 11 previously treated patients with NHL increased Venetoclax Cmax by 2.3-fold and AUC by 6.4-fold. Co-administration of 50 mg once daily ritonavir, a strong CYP3A and P-gp inhibitor, for 14 days in 6 healthy subjects increased Venetoclax Cmax by 2.4-fold and AUC by 7.9-fold. Co-administration of Venetoclax with other strong CYP3A4 inhibitors is predicted to increase Venetoclax AUC by on average 5.8- to 7.8-fold. Concomitant use of Venetoclax with strong CYP3A inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) at initiation and during the dose-titration phase is contraindicated due to increased risk for TLS.

At initiation and during the dose-titration phase, concomitant use of Venetoclax with moderate CYP3A inhibitors (e.g., ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) should be avoided. Alternative treatments should be considered. If a moderate CYP3A inhibitor must be used, the initiation dose of Venetoclax and the doses for the titration phase should be reduced by at least 50%. Patients should be monitored more closely for signs and symptoms of TLS.

For patients who have completed the dose-titration phase and are on a steady daily dose of Venetoclax, the Venetoclax dose should be reduced by 50% when used concomitantly with moderate CYP3A inhibitors and by 75% when used concomitantly with strong CYP3A inhibitors. Patients should be monitored more closely for signs of toxicities and the dose may need to be further adjusted. The Venetoclax dose that was used prior to initiating the CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of the inhibitor. Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with Venetoclax as they contain inhibitors of CYP3A.

P-gp and BCRP inhibitors: Venetoclax is a substrate for P-gp and BCRP , Co-administration of a 600 mg single dose of rifampin, a P-gp inhibitor, in 11 healthy subjects increased Venetoclax Cmax by 106% and AUC by 78%. Concomitant use of Venetoclax with P-gp and BCRP inhibitors at initiation and during the dose-titration phase should be avoided; if a P-gp and BCRP inhibitor must be used, patients should be monitored closely for signs of toxicities.

CYP3A inducers: Co-administration of 600 mg once daily rifampin, a strong CYP3A inducer, for 13 days in 10 healthy subjects decreased Venetoclax Cmax by 42% and AUC°° by 71%. Concomitant use of Venetoclax with strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided. Alternative treatments with less CYP3A induction should be considered. Preparations containing St. John's wort are contraindicated during treatment with Venetoclax, as efficacy may be reduced.

Women of childbearing potential/Contraception in females: Women should avoid becoming pregnant while taking Venetoclax and for at least 30 days after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking Venetoclax and for 30 days after stopping treatment. It is currently unknown whether Venetoclax may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method.

Pregnancy: Based on embryo-foetal toxicity studies in animals, Venetoclax may harm the fetus when administered to pregnant women. There is no adequate and well-controlled data from the use of Venetoclax in pregnant women. Studies in animals have shown reproductive toxicity. Venetoclax is not recommended during pregnancy and in women of childbearing potential not using highly effective contraception.

Breast-feeding: It is unknown whether Venetoclax or its metabolites are excreted in human milk. A risk to the breast-feeding child cannot be excluded. Breast-feeding should be discontinued during treatment with Venetoclax.

Fertility: No human data on the effect of Venetoclax on fertility are available. Based on testicular toxicity in dogs at clinically relevant exposures, male fertility may be compromised by treatment with Venetoclax. Before starting treatment, counselling on sperm storage may be considered in some male patients.

Elderly: No specific dose adjustment is required for elderly patients (aged >65 years).

Renal impairment: No dose adjustment is needed for patients with mild or moderate renal impairment (CrCI >30 ml/min and <90 mi/min). Patients with reduced renal function (CrCI <80 ml/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCI <30 ml/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. Venetoclax should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

Hepatic impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Patients with moderate hepatic impairment should be monitored more closely for signs of toxicity at initiation and during the dose-titration phase. A dose reduction of at least 50% throughout treatment is recommended for patients with severe hepatic impairment. These patients should be monitored more closely for signs of toxicity.

Pediatric population: The safety and efficacy of Venetoclax in children aged less than 18 years have not been established. No data is available.

There is no specific antidote for Venetoclax. Patients who experience overdose should be closely monitored and appropriate supportive treatment provided. During dose-titration phase, treatment should be interrupted and patients should be monitored carefully for signs and symptoms of TLS (fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle or joint pain, abdominal pain and distension) along with other toxicities.

Store below 30°C. Keep Venetoclax out of the sight and reach of children. Protect from moisture and light.