Trade Names:Elixophyllin- Elixir, oral 80 mg per 15 mL (26.7 mg per 5 mL)
Trade Names:Theo-24- Capsules, timed-release (24 h) 100 mg- Capsules, timed-release (24 h) 200 mg- Capsules, timed-release (24 h) 300 mg- Capsules, timed-release (24 h) 400 mg
Trade Names:Theophylline- Solution, oral 80 mg per 15 mL
Trade Names:Theophylline- Tablets, ER 100 mg- Tablets, ER 200 mg- Tablets, ER 300 mg- Tablets, ER 450 mg
Trade Names:Uniphyl- Tablets, controlled-release (24 h) 400 mg- Tablets, controlled-release (24 h) 600 mg
Apo-Theo LA (Canada)Relaxes bronchial smooth muscle and stimulates central respiratory drive.
Theophylline is rapidly and completely absorbed after oral administration. Theophylline C max is 10 mcg/mL (range, 5 to 15 mcg/mL) and T max is 1 to 2 h. Food and antacids do no cause any clinically significant changes. The therapeutic range is 10 to 20 mcg/mL.
Theophylline is approximately 40% protein bound (primarily to albumin). Unbound theophylline distributes throughout body water, but distributes poorly into body fat. Vd is approximately 0.45 L/kg (range, 0.3 to 0.7 L/kg) based on ideal body weight. Theophylline freely passes across the placenta, into breast milk, and into CSF.
Theophylline does not undergo any measurable first-pass elimination. In adults and children older than 1 yr of age, about 90% of the dose is metabolized in the liver. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.
Excretion is via the kidneys. In neonates, approximately 50% of a theophylline dose is excreted unchanged in the urine. Beyond 0 to 3 mo, 10% of a theophylline dose is excreted unchanged in the urine.
No dosage adjustment is required for adults or children older than 3 mo of age with renal function impairment. In neonates with reduced renal function, dose reduction and frequent monitoring of serum concentrations is required.
Hepatic Function ImpairmentCl is decreased at least 50% in patients with hepatic impairment. Select dose with care and frequently monitor theophylline levels
ElderlyCl is decreased by an average of 30% in healthy adults older than 60 yr of age compared with younger adults.
ChildrenCl is very low in neonates and reaches max values by 1 yr of age, remains relatively constant until about 9 yr of age, and then slowly decreases by approximately 50% to adult values at about 16 yr of age.
GenderPharmacokinetic differences between men and women are small and not expected to be clinically important.
RacePharmacokinetics have not been studied.
Concurrent illnessTheophylline Cl is decreased in patients with acute pulmonary edema, CHF, cor pulmonale, fever, hypothyroidism, liver disease (eg, acute hepatitis, cirrhosis), sepsis with multiorgan failure, and shock, and in infants younger than 3 mo of age with reduced renal function.
SmokingTheophylline Cl is increased by smoking (ie, marijuana or tobacco) by approximately 50% in young adult smokers and 80% in elderly tobacco smokers. Cessation of smoking for 1 wk improves theophylline Cl by 40%.
Prevention or treatment of reversible bronchospasm associated with asthma or COPD.
Hypersensitivity to theophyllines or any component of the product.
The steady-state theophylline C max is a function of the dose, the dosing interval, and the rate of theophylline absorption and Cl in individual patients. The dose required to achieve a theophylline C max in the 10 to 20 mcg/mL range varies 4-fold among similar patients in the absence of factors known to alter theophylline Cl. For a given population, there is no single dose that will provide both safe and effective concentrations for all patients. The dose of theophylline must be individualized on the basis of plasma theophylline concentration measurement in order to achieve a dose that provides max potential benefit with minimal risk of adverse reactions. The dose should be calculated based on ideal body weight.
Dosing Initiation and TitrationAdults 16 to 60 yr of age weighing more than 45 kgPO
Theophylline ER tabletStart with theophylline 300 mg/day divided every 12 h. After 3 days, if tolerated, increase dosage to theophylline 400 mg/day divided every 12 h. After 3 more days, if tolerated, increase dosage to theophylline 600 mg/day divided every 12 h.
Theophylline oral solutionStart with theophylline 300 mg/day divided every 6 to 8 h. After 3 days, if tolerated, increase dosage to theophylline 400 mg/day divided every 6 to 8 h. After 3 more days, if tolerated, increase dosage to theophylline 600 mg/day divided every 6 to 8 h.
Theo-24 ER capsules, Uniphyl controlled-release tabletsStart with theophylline 300 to 400 mg/day every 24 h. After 3 days, if tolerated, increase dosage to theophylline 400 to 600 mg/day every 24 h. After 3 more days, if tolerated, doses more than theophylline 600 mg should be titrated according to blood levels.
ChildrenPO
Children 1 to 15 yr of age weighing less than 45 kg Theophylline oral solutionStart with theophylline 12 to 14 mg/kg/day up to a max of 300 mg/day divided every 4 to 6 h. After 3 days, if tolerated, increase dosage to 16 mg/kg/day up to a max of 400 mg/day divided every 4 to 6 h. After 3 more days, if tolerated, increase dosage to 20 mg/kg/day up to a max of 600 mg/day divided every 4 to 6 h.
Children 1 to 15 yr of age weighing more than 45 kg Theophylline oral solutionStart with theophylline 300 mg/day divided every 6 to 8 h. After 3 days, if tolerated, increase dosage to theophylline 400 mg/day divided every 6 to 8 h. After 3 more days, if tolerated, increase dosage to theophylline 600 mg/day divided every 6 to 8 h.
Children 6 to 15 yr of age weighing less than 45 kg Theophylline ER tabletsStart with theophylline 12 to 14 mg/kg/day up to a max of 300 mg/day divided every 12 h. After 3 days, if tolerated, increase dosage to 16 mg/kg/day up to a max of 400 mg/day divided every 12 h. After 3 more days, if tolerated, increase dosage to 20 mg/kg/day up to a max of 600 mg/day divided every 12 h.
Children 6 to 15 yr of age weighing more than 45 kg Theophylline ER tabletsStart with theophylline 300 mg/day divided every 12 h. After 3 days, if tolerated, increase dosage to theophylline 400 mg/day divided every 12 h. After 3 more days, if tolerated, increase dosage to theophylline 600 mg/day divided every 12 h.
Children 12 to 15 yr of age weighing less than 45 kg Theo-24 ER capsules, Uniphyl controlled-release tabletsStart with theophylline 12 to 14 mg/kg/day up to a max of 300 mg/day dosed every 24 h. After 3 days, if tolerated, increase dosage to 16 mg/kg/day up to a max of 400 mg/day dosed every 24 h. After 3 more days, if tolerated, increase dosage to 20 mg/kg/day up to a max of 600 mg/day dosed every 24 h.
Children 12 to 15 yr of age weighing more than 45 kg Theo-24 ER capsules, Uniphyl controlled-release tabletsStart with theophylline 300 to 400 mg/day every 24 h. After 3 days, if tolerated, increase dosage to theophylline 400 to 600 mg/day every 24 h. After 3 more days, if tolerated, doses more than theophylline 600 mg should be titrated according to blood levels.
Patients With Risk Factors for Impaired Cl, Elderly Patients Older Than 60 Yr of Age, and Those in Whom it is Not Feasible to Monitor Plasma Theophylline LevelsAdults, including Elderly patients and Children 16 yr of age and olderPO The final theophylline dose should not exceed 400 mg/day.
ChildrenPO
Theophylline ER tablets Children 6 to 15 yr of ageThe final theophylline dose should not exceed 16 mg/kg/day, up to a max of 400 mg/day.
Theophylline oral solution Children 1 to 15 yr of ageThe final theophylline dose should not exceed 16 mg/kg/day, up to a max of 400 mg/day.
Theo-24 ER capsule, Uniphyl controlled-release tablets Children 12 to 15 yr of ageThe final theophylline dose should not exceed 16 mg/kg/day, up to a max of 400 mg/day. Note: Patients with more rapid metabolism, clinically identified by higher than average dose requirements, should receive a smaller dose more frequently to prevent breakthrough symptoms resulting from low trough levels before the next dose. A reliable absorbed slow-release formulation will decrease fluctuations and permit longer dosing intervals.
Infants younger than 1 yr oldPO
Theophylline oral solution Premature neonates younger than 24 days postnatal age1 mg/kg every 12 h.
Premature neonates older than 24 days postnatal age1.5 mg/kg every 12 h.
Full-term infants and infants up to 52 wk of ageTotal dose in mg is [(0.2 × age in wk) + 5] × weight in kg. In infants 26 wk of age and younger, divide the dose into 3 equal amounts administered at 8-h intervals. In infants older than 26 wk of age, divide the dose into 4 equal amounts administered at 6-h intervals.
Dosage Adjustments Guided by Plasma Theophylline ConcentrationPO
If C max is less than 9.9 mcg/mLIf symptoms are not controlled and current dosage is tolerated, increase dose by about 25%. Recheck plasma concentration after 3 days for further dosage adjustments.
If C max is 10 to 14.9 mcg/mLIf symptoms are controlled and current dosage is tolerated, maintain dose and recheck plasma concentration at 6- to 12-mo intervals. (Dose reduction and/or plasma theophylline concentration measurement is indicated whenever the following are present: physiologic abnormalities that can reduce theophylline Cl [eg, sustained fever], or a drug that interacts with theophylline is added or discontinued.) If symptoms are not controlled and current dosage is tolerated, consider adding additional medication(s) to the treatment regimen.
If C max is 15 to 19.9 mcg/mLConsider a 10% decrease in dose to provide a greater margin of safety even if current dosage is tolerated. (Dose reduction and/or plasma theophylline concentration measurement is indicated whenever the following are present: physiologic abnormalities that can reduce theophylline Cl [eg, sustained fever], or a drug that interacts with theophylline is added or discontinued.)
If C max is 20 to 24.9 mcg/mLDecrease dose by 25% even if no adverse reactions are present. Recheck plasma concentration after 3 days to guide further dosage adjustment.
If C max is 25 to 30 mcg/mLSkip next dose and decrease subsequent doses at least 25% even if no adverse reactions are present. Recheck plasma concentration after 3 days to guide further dosage adjustment. If symptomatic, consider whether overdose treatment is indicated.
If C max is more than 30 mcg/mLTreat overdose as indicated. If theophylline is resumed subsequently, decrease dose by at least 50% and recheck plasma concentration after 3 days to guide further dosage adjustment.
Store at 59° to 86°F. Protect from light.
Theo-24 ER capsulesStore below 77°F.
Theophylline ER tablets and oral solutionStore at 68° to 77°F.
Theophylline levels may be increased.
Aminoglutethimide, barbiturates (eg, pentobarbital, phenobarbital, primidone, secobarbital), hydantoins (eg, phenytoin), isoproterenol IV, ketoconazole, moricizine, rifampin, smoking (ie, marijuana and tobacco), St. John's wort, sulfinpyrazone, sympathomimetics (eg, albuterol, isoproterenol, terbutaline)Theophylline levels may be decreased.
Benzodiazepines, propofolTheophylline may antagonize sedative effects.
Beta-agonistsCV adverse reactions may be additive. However, may be used together for additive beneficial effects.
Carbamazepine, isoniazid, loop diureticsMay increase or decrease theophylline levels.
Ephedrine, tetracyclineIncreased risk of theophylline toxicity.
ErythromycinElevated theophylline levels, increasing the risk of toxicity, while erythromycin levels may be reduced.
HalothaneCoadministration has caused catecholamine-induced arrhythmias.
KetamineCoadministration may result in seizures.
LithiumTheophylline may reduce lithium levels.
Nondepolarizing muscle relaxantsTheophylline may antagonize neuromuscular blockade.
Do not mix following solutions with theophylline in IV fluids: ascorbic acid, chlorpromazine, corticotropin, dimenhydrinate, epinephrine hydrochloride, erythromycin gluceptate, hydralazine, hydroxyzine hydrochloride, insulin, levorphanol tartrate, meperidine, methadone, methicillin sodium, morphine sulfate, norepinephrine bitartrate, oxytetracycline, papaverine, penicillin G potassium, phenobarbital sodium, phenytoin sodium, procaine, prochlorperazine maleate, promazine, promethazine, tetracycline, vancomycin, vitamin B complex with C.
None well documented.
Atrial flutter and tachycardia, cardiac arrhythmias.
Headache, insomnia, irritability, restlessness, seizures.
Diarrhea, nausea, vomiting.
Transient diuresis.
Fine skeletal muscle tremors.
Death.
Category C .
Excreted in breast milk.
Safe and effective for the approved indications in children.
Elderly patients are at increased risk of experiencing serious theophylline adverse reactions and toxicity compared with younger patients because of pharmacodynamic and pharmacokinetic changes associated with aging.
Use with caution in patients with active peptic ulcer disease, cardiac arrhythmias, or seizure disorders.
Acute MI; death caused by cardiorespiratory arrest and/or hypoxic encephalopathy; increased serum calcium, creatine kinase, myoglobin, and leukocyte count; decreased serum phosphate and magnesium; urinary retention in men with obstructive uropathy. Many manifestations of acute and chronic overdosage are similar.
Acute overdosageAbdominal pain, acid/base disturbance, atrial fibrillation or flutter, death, disorientation, hyperglycemia, hypokalemia, hypotension/shock, nervousness, rhabdomyolysis, seizures, sinus tachycardia, supraventricular tachycardia, tremors, ventricular arrhythmias, ventricular premature beats, vomiting.
Chronic overdosageAbdominal pain, acid/base disturbance, atrial fibrillation or flutter, atrial tachycardia, death, diarrhea, disorientation, hematemesis, hyperglycemia, hypokalemia, hypotension/shock, nervousness, seizures, sinus tachycardia, supraventricular tachycardia, tremors, ventricular arrhythmias, ventricular premature beats, vomiting.
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