theophylline Pharmacologic classification: xanthine derivative
Accurbron, Aquaphyllin, Asmalix, Bronkodyl, Elixophyllin, Lanophyllin, Quibron-T, Respbid, Slo-bid Gyrocaps, Slo-Phyllin, Sustaire, Theobid Duracaps, Theochron, Theoclear-80, Theoclear L.A., Theolair, Theo-Sav, Theo-24, Theospan-SR, Theostat 80, Theovent, Theo-X, T-Phyl, Uniphyl
Therapeutic classification: bronchodilator
Pregnancy risk category C
Available by prescription only
Capsules: 100 mg, 200 mg
Capsules (extended-release): 50 mg, 60 mg, 65 mg, 75 mg, 100 mg, 125 mg, 130 mg, 200 mg, 250 mg, 260 mg, 300 mg, 400 mg
D5W injection: 200 mg in 50 ml or 100 ml; 400 mg in 100 ml, 250 ml, 500 ml, or 1,000 ml; 800 mg in 500 ml or 1,000 ml
Elixir: 50 mg/5 ml, 80 mg/15 ml
Syrup: 50 mg/5 ml, 80 mg/15 ml, 150 mg/15 ml
Tablets: 100 mg, 125 mg, 200 mg, 250 mg, 300 mg
Tablets (extended-release): 100 mg, 200 mg, 250 mg, 300 mg, 400 mg, 500 mg, 600 mg
Indications and dosages
Symptomatic relief of bronchospasm in patients not currently receiving theophylline who require rapid relief of acute symptoms.
Loading dose: 6 mg/kg anhydrous theophylline, then:
Adults (nonsmokers): 3 mg/kg P.O. q 6 hours for two doses; then 3 mg/kg q 8 hours.
Older adults with cor pulmonale: 2 mg/kg P.O. q 6 hours for two doses; then 2 mg/kg q 8 hours.
Adults with heart failure: 2 mg/kg P.O. q 8 hours for two doses; then 1 to 2 mg/kg q 12 hours.
Children and adolescents ages 9 to 16 and young adult smokers: 3 mg/kg P.O. q 4 hours for three doses; then 3 mg/kg q 6 hours.
Neonates and children ages 6 months to 9 years: 4 mg/kg P.O. q 4 hours for three doses; then 4 mg/kg q 6 hours.
Neonates and infants younger than age 6 months ◇: Dosage is highly individualized. Serum theophylline levels should be maintained at less than 10 mcg/ml in neonates and less
than 20 mcg/ml in older infants. After loading dose of 1 mg/kg P.O. or I.V. for each 2 mcg/ml increase in theophylline level,
infants ages 8 weeks to 6 months receive 1 to 3 mg/kg q 6 hours. Infants ages 4 to 8 weeks receive 1 to 2 mg/kg q 8 hours.
Neonates up to age 4 weeks receive 1 to 2 mg/kg q 12 hours. And premature neonates (less than 40 weeks’ gestational age) receive
1 mg/kg q 12 hours.
Parenteral theophylline for patients not currently receiving theophylline. Loading dose: 4.7 mg/kg (equivalent to 6 mg/kg anhydrous aminophylline) I.V. slowly; then maintenance infusion.
Adults (nonsmokers): 0.55 mg/kg/hour (equivalent to 0.7 mg/kg/hour anhydrous aminophylline) for 12 hours, then 0.39 mg/kg/hour (equivalent to 0.5
mg/kg/hour anhydrous aminophylline).
Older adults with cor pulmonale: 0.47 mg/kg/hour (equivalent to 0.6 mg/kg/hour anhydrous aminophylline) for 12 hours; then 0.24 mg/kg/hour (equivalent to
0.3 mg/kg/hour anhydrous aminophylline).
Adults with heart failure or liver disease: 0.39 mg/ kg/hour (equivalent to 0.5 mg/kg/hour anhydrous aminophylline) for 12 hours; then 0.08 to 0.16 mg/ kg/hour (equivalent
to 0.1 to 0.2 mg/kg/hour anhydrous aminophylline).
Children ages 9 to 16: 0.79 mg/kg/hour (equivalent to 1 mg/kg/hour anhydrous aminophylline) for 12 hours; then 0.63 mg/kg/hour (equivalent to 0.8
mg/kg/hour anhydrous aminophylline).
Infants and children ages 6 months to 9 years: 0.95 mg/kg/hour (equivalent to 1.2 mg/kg/hour anhydrous aminophylline) for 12 hours; then 0.79 mg/ kg/hour (equivalent to
1 mg/kg/hour anhydrous aminophylline).
Switch to oral theophylline as soon as patient shows adequate improvement.
Symptomatic relief of bronchospasm in patients currently receiving theophylline. Adults and children: Each 0.5 mg/kg I.V. or P.O. (loading dose) increases plasma levels by 1 mcg/ml. Ideally, dose is based on current theophylline
level and lean body weight. In emergency situations, may use a 2.5 mg/kg P.O. dose of rapidly absorbed form if no obvious
signs of theophylline toxicity are present.
Prophylaxis of bronchial asthma, bronchospasm of chronic bronchitis, and emphysema. Adults and children: Using rapidly absorbed dose forms, initial dose is 16 mg/kg or 400 mg P.O. daily (whichever is less) divided q 6 to 8 hours;
dose may be increased in approximate increments of 25% at 2- to 3-day intervals. Using extended-release dose forms, initial
dosage is 12 mg/kg or 400 mg P.O. daily (whichever is less) divided q 8 to 12 hours; dose may be increased, if tolerated,
by 2 to 3 mg/kg daily at 3-day intervals. Regardless of dose form used, dose may be increased, if tolerated, up to the following
maximum daily doses, without measurements of serum theophylline level.
Adults and adolescents age 16 and older: 13 mg/kg P.O. or 900 mg P.O. daily in divided doses.
Adolescents ages 12 to 16: 18 mg/kg P.O. daily in divided doses.
Children ages 9 to 12: 20 mg/kg P.O. daily in divided doses.
Children younger than age 9: 24 mg/kg P.O. daily in divided doses.
Note: Dose individualization is required. Use peak plasma and trough levels to estimate dose. Therapeutic range is 10 to 20
mcg/ml. All doses are based on theophylline anhydrous and lean body weight.
Cystic fibrosis ◇. Infants: 10 to 20 mg/kg I.V. daily.
Promotion of diuresis ◇, treatment of Cheyne-Stokes respirations ◇, paroxysmal nocturnal dyspnea ◇. Adults: 200 to 400 mg I.V. bolus (single dose).
Bronchodilator action: Drug may act by inhibiting phosphodiesterase, elevating cellular cyclic AMP levels, or antagonizing adenosine receptors in
the bronchi, resulting in relaxation of the smooth muscle.
Drug also increases sensitivity of the medullary respiratory center to carbon dioxide, to reduce apneic episodes. It prevents
muscle fatigue, especially that of the diaphragm. It also causes diuresis and cardiac and CNS stimulation.
Absorption: Well absorbed. Rate and onset of action depend on the dose form. Food may further alter absorption, especially of some extended-release
Distribution: Distributed throughout the extracellular fluids; equilibrium between fluid and tissues occurs within an hour of an I.V. loading
dose. Therapeutic plasma levels are 10 to 20 mcg/ml, but many patients respond to lower levels.
Metabolism: Metabolized in the liver to inactive compounds. Half-life is 7 to 9 hours in adults, 4 to 5 hours in smokers, 20 to 30 hours
in premature infants, and 3 to 5 hours in children.
Excretion: About 10% of dose is excreted in urine unchanged. The other metabolites include 1,3-dimethyluric acid, 1-methyluric acid,
Contraindications and precautions
Contraindicated in patients hypersensitive to xanthine compounds, such as caffeine and theobromine, and in those with active
peptic ulcer and seizure disorders.
Use cautiously in elderly patients, neonates, infants, young children, and in patients with COPD, cardiac failure, cor pulmonale,
renal or hepatic disease, peptic ulcer, hyperthyroidism, diabetes mellitus, glaucoma, severe hypoxemia, hypertension, compromised
cardiac or circulatory function, angina, acute MI, or sulfite sensitivity.
Drug-drug. Activated charcoal, barbiturates, ketoconazole, phenytoin, rifampin: Decreases theophylline levels. Monitor patient closely. Dosage adjustment may be needed if use together can’t be avoided.
Allopurinol (high dose), calcium channel blockers, cimetidine, corticosteroids, erythromycin, hormonal contraceptives, interferon,
mexiletine, propranolol, quinolones, troleandomycin: May increase theophylline levels. Monitor patient closely. Dosage adjustment may be needed if use together can’t be avoided.
Beta blockers: Causes antagonistic pharmacologic effect. Avoid use together.
Carbamazepine, isoniazid, loop diuretics: May alter theophylline levels. Monitor patient closely. Dosage adjustment may be needed if use together can’t be avoided.
Lithium: Increases lithium excretion. Lithium dosage may require adjustment. Monitor patient carefully.
Drug-herb. Cacao tree: May inhibit theophylline metabolism. Discourage ingesting large amounts of cocoa when taking theophylline.
Caffeine, guarana: Causes additive CNS and CV effects. Discourage use together.
Ephedra: Increases risk of adverse reactions. Discourage use together.
St. John’s wort: Decreases theophylline levels and efficacy. Discourage use together if possible. If not, monitor theophylline levels and adjust dosage as needed.
Drug-food. Any food: Accelerates absorption. Advise patient to take drug on an empty stomach.
Drug-lifestyle. Smoking (cigarettes, marijuana): Increases elimination of theophylline. Monitor theophylline response and serum levels; dosage adjustment may be needed. Discourage smoking.
CNS: restlessness, dizziness, insomnia, headache, irritability, seizures, muscle twitching.
CV: palpitations, sinus tachycardia, extrasystoles, flushing, marked hypotension, arrhythmias.
GI: nausea, vomiting, diarrhea, epigastric pain.
Respiratory: tachypnea, respiratory arrest.
Effects on lab test results
May increase plasma free fatty acid levels.
Overdose and treatment
Signs and symptoms of overdose include nausea, vomiting, insomnia, irritability, tachycardia, extrasystoles, tachypnea, or
tonic-clonic seizures. The onset of toxicity may be sudden and severe, with arrhythmias and seizures as the first signs.
Induce emesis except in patients experiencing seizures, then use activated charcoal and cathartics. Treat arrhythmias with
lidocaine and seizures with I.V. diazepam; support respiratory and CV systems.
Theophylline has a low therapeutic index.
Dosage is determined by monitoring response, tolerance, pulmonary function, and serum theophylline levels. Target range is
10 to 20 mcg/ml.
Use cautiously in young children, infants, neonates, and elderly patients.
Depending on assay used, theophylline levels may be falsely elevated in the presence of furosemide, phenylbutazone, probenecid,
theobromine, caffeine, tea, chocolate, cola beverages, and acetaminophen. Falsely elevates serum uric acid as measured by
the Bittner or calorimetric method.
Monitor vital signs and watch for signs and symptoms of toxicity.
Obtain serum theophylline measurements in patients receiving long-term therapy. Ideal levels are between 10 and 20 mcg/ml,
although some patients may respond adequately with lower serum levels. Check every 6 months. If levels are less than 10 mcg/ml,
increase dose by about 25% each day. If levels are 20 to 25 mcg/ml, decrease dose by about 10% each day. If levels are 25
to 30 mcg/ml, skip next dose and decrease by 25% each day. If levels are more than 30 mcg/ml, skip next two doses and decrease
by 50% each day. Repeat serum level determination.
Drug appears in breast milk and may cause irritability, insomnia, or fretfulness in the breast-fed infant. A decision must
be made to stop either breast-feeding or drug.
Use cautiously in neonates. Children usually require higher doses (on a mg/kg basis) than adults. Maximum recommended daily
doses are 24 mg/kg in children younger than age 9; 20 mg/kg in children age 9 to 12; 18 mg/kg in adolescents ages 12 to 16;
13 mg/kg or 900 mg (whichever is less) in adolescents and adults age 16 and older.
Tell patient to take drug with food if GI upset occurs with liquid preparations or non-sustained-release forms.
Instruct patient to continue to use the same brand of theophylline.
ALERT If patient smokes, tell him to call if he quits because theophylline dose may need to be reduced to avoid toxicity.
Advise patient to take drug at regular intervals as instructed, around-the-clock.
If patient misses a dose, tell him to take it as soon as possible but not to double the dose.
Inform patient of adverse effects and possible signs of toxicity.
Reactions may be common, uncommon, life-threatening, or
COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use