General MedicationsORALHigh Alert

Theophylline Anhydrous

THEOPHYLLINE

Standard Dose

DOSAGE AND ADMINISTRATION Theophylline (anhydrous) extended-release tablets 400 mg can be taken once a day in the morning or evening. It is recommended that theophylline (anhydrous) extended-release tablets be taken with meals. Patients should be advised that if they choose to take theophylline (anhydrous) extended-release tablets with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food. Theophylline (anhydrous) extended-release tablets are not to be chewed or crushed because it may lead to a rapid release of theophylline with the potential for toxicity. The scored tablet may be split. Infrequently, patients receiving theophylline (anhydrous) extended-release tablets 400 mg may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual theophylline. Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release theophylline product may be transferred to once-daily administration of 400 mg theophylline (anhydrous) extended-release tablets on a mg-for-mg basis. It must be recognized that the peak and trough serum theophylline levels produced by the once-daily dosing may vary from those produced by the previous product and/or regimen. General Considerations The steady-state peak serum theophylline concentration is a function of the dose, the dosing interval, and the rate of theophylline absorption and clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a peak serum theophylline concentration in the 10 to 20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance (e.g., 400 to 1600 mg/day in adults 45 kg and adults 1. Starting Dosage 12 to 14 mg/kg/day up to a maximum of 300 mg/day admin. QD 300 to 400 mg/day If caffeine-like adverse effects occur, then consideration should be given to a lower dose and titrating the dose more slowly (see ADVERSE REACTIONS ). admin. QD 2. After 3 days, if tolerated, increase dose to: 16 mg/kg/day up to a maximum of 400 mg/day admin. QD 400 to 600 mg/day admin. QD 3. After 3 more days, if tolerated, and if needed increase dose to: 20 mg/kg/day up to a maximum of 600 mg/day admin. QD As with all theophylline products, doses greater than 600 mg should be titrated according to blood level (see Table VI ). B. Patients with risk factors for impaired clearance, the elderly (>60 years), and those in whom it is not feasible to monitor serum theophylline concentrations: In children 12 to 15 years of age, the theophylline dose should not exceed 16 mg/kg/day up to a maximum of 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS ) or if it is not feasible to monitor serum theophylline concentrations. In adolescents ≥16 years and adults, including the elderly, the theophylline dose should not exceed 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS ) or if it is not feasible to monitor serum theophylline concentrations. Table VI. Dosage adjustment guided by serum theophylline concentration. Peak Serum Concentration Dosage Adjustment ¶Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g. sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS ). 30 mcg/mL Treat overdose as indicated (see recommendations for chronic overdosage ). If theophylline is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment.

Max Dose

See official label

Primary Use

INDICATIONS AND USAGE Theophylline is indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

Summary

Dosage and administration DOSAGE AND ADMINISTRATION Theophylline (anhydrous) extended-release tablets 400 mg can be taken once a day in the morning or evening.

Structured Monograph

Clinical summary

Indications and usage INDICATIONS AND USAGE Theophylline is indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis. Dosage and administration DOSAGE AND ADMINISTRATION Theophylline (anhydrous) extended-release tablets 400 mg can be taken once a day in the morning or evening. It is recommended that theophylline (anhydrous) extended-release tablets be taken with meals. Patients should be advised that if they choose to take theophylline (anhydrous) extended-release tablets with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food. Theophylline (anhydrous) extended-release tablets are not to be chewed or crushed because it may lead to a rapid release of theophylline with the potential for toxicity. The scored tablet may be split. Infrequently, patients receiving theophylline (anhydrous) extended-release tablets 400 mg may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual theophylline. Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release theophylline product may be transferred to once-daily administration of 400 mg theophylline (anhydrous) extended-release tablets on a mg-for-mg basis. It must be recognized that the peak and trough serum theophylline levels produced by the once-daily dosing may vary from those produced by the previous product and/or regimen. General Considerations The steady-state peak serum theophylline concentration is a function of the dose, the dosing interval, and the rate of theophylline absorption and clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a peak serum theophylline concentration in the 10 to 20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance (e.g., 400 to 1600 mg/day in adults 45 kg and adults 1. Starting Dosage 12 to 14 mg/kg/day up to a maximum of 300 mg/day admin. QD 300 to 400 mg/day If caffeine-like adverse effects occur, then consideration should be given to a lower dose and titrating the dose more slowly (see ADVERSE REACTIONS ). admin. QD 2. After 3 days, if tolerated, increase dose to: 16 mg/kg/day up to a maximum of 400 mg/day admin. QD 400 to 600 mg/day admin. QD 3. After 3 more days, if tolerated, and if needed increase dose to: 20 mg/kg/day up to a maximum of 600 mg/day admin. QD As with all theophylline products, doses greater than 600 mg should be titrated according to blood level (see Table VI ). B. Patients with risk factors for impaired clearance, the elderly (>60 years), and those in whom it is not feasible to monitor serum theophylline concentrations: In children 12 to 15 years of age, the theophylline dose should not exceed 16 mg/kg/day up to a maximum of 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS ) or if it is not feasible to monitor serum theophylline concentrations. In adolescents ≥16 years and adults, including the elderly, the theophylline dose should not exceed 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS ) or if it is not feasible to monitor serum theophylline concentrations. Table VI. Dosage adjustment guided by serum theophylline concentration. Peak Serum Concentration Dosage Adjustment ¶Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g. sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS ). 30 mcg/mL Treat overdose as indicated (see recommendations for chronic overdosage ). If theophylline is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment. Warnings and cautions WARNINGS Concurrent Illness Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition: Active peptic ulcer disease Seizure disorders Cardiac arrhythmias (not including bradyarrhythmias) Conditions That Reduce Theophylline Clearance There are several readily identifiable causes of reduced theophylline clearance . If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal theophylline toxicity can occur. Careful consideration must be given to the benefits and risks of theophylline use and the need for more intensive monitoring of serum theophylline concentrations in patients with

Monitoring

• WARNINGS Concurrent Illness Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition: Active peptic ulcer disease Seizure disorders Cardiac arrhythmias (not including bradyarrhythmias) Conditions That Reduce Theophylline Clearance There are several readily identifiable causes of reduced theophylline clearance .
• If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal theophylline toxicity can occur.
• Careful consideration must be given to the benefits and risks of theophylline use and the need for more intensive monitoring of serum theophylline concentrations in patients with the following risk factors: Age Neonates (term and premature) Children 60 years) Concurrent Diseases Acute pulmonary edema Congestive heart failure Cor-pulmonale Fever; ≥102° for 24 hours or more; or lesser temperature elevations for longer periods Hypothyroidism Liver disease; cirrhosis, acute hepatitis Reduced renal function in infants <3 months of age Sepsis with multi-organ failure Shock Cessation of Smoking Drug Interactions Adding a drug that inhibits theophylline metabolism (e.g., cimetidine, erythromycin, tacrine) or stopping a concurrently administered drug that enhances theophylline metabolism (e.g., carbamazepine, rifampin).
• (see PRECAUTIONS, Drug Interactions, Table II ) .

Interaction Notes

• Drug Interactions Theophylline interacts with a wide variety of drugs.
• The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to theophylline or another drug or occurrence of adverse effects without a change in serum theophylline concentration.
• More frequently, however, the interaction is pharmacokinetic, i.e., the rate of theophylline clearance is altered by another drug resulting in increased or decreased serum theophylline concentrations.
• Theophylline only rarely alters the pharmacokinetics of other drugs.