indication

For the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, such as emphysema and chronic bronchitis.

pharmacology

Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).

mechanism of action

Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction.

toxicity

Symptoms of overdose include seizures, arrhythmias, and GI effects.

biotransformation

Hepatic. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.

absorption

Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.

half life

8 hours

route of elimination

Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.

drug interactions

Aciclovir: Acyclovir may increase the effect and toxicity of theophylline.

Adenosine: Theophylline may decrease the effect of adenosine.

Amobarbital: The barbiturate, amobarbital, decreases the effect of theophylline.

Aprobarbital: The barbiturate, aprobarbital, decreases the effect of theophylline.

Atracurium: Theophylline decreases the effect of the muscle relaxant

Bromazepam: Theophylline may decrease the therapeutic effect of bromazepam. Monitor for changes in the therapeutic effects of bromazepam if theophylline is initiated, discontinued or dose changed.

Butabarbital: The barbiturate, butabarbital, decreases the effect of theophylline.

Butalbital: The barbiturate, butalbital, decreases the effect of theophylline.

Butethal: The barbiturate, butethal, decreases the effect of theophylline.

Carbamazepine: Carbamazepine may decrease the serum concentration of theophylline. Theophylline may decrease the serum concentration of carbamazepine. Monitor for changes in the therapeutic effect of both agents if concomitant therapy is initiated, discontinued or dose changed.

Carteolol: Antagonism of action and increased effect of theophylline

Cimetidine: Cimetidine may increase the effect of theophylline.

Ciprofloxacin: Ciprofloxacin may increase the effect of theophylline.

Clarithromycin: Clarithromycin may increase the therapeutic and adverse effects of theophylline.

Dihydroquinidine barbiturate: The barbiturate, dihydroquinidine barbiturate, decreases the effect of theophylline.

Disulfiram: Disulfiram may increase the effect and toxicity of theophylline.

Doxacurium chloride: Theophylline decreases the effect of the muscle relaxant

Enoxacin: Enoxacin may increase the effect of theophylline.

Erythromycin: The macrolide, erythromycin, may increase the effect and toxicity of theophylline.

Ethinyl Estradiol: The contraceptive increases the effect and toxicity of theophylline

Ethotoin: Decreased effect of both products

Fluvoxamine: Fluvoxamine may increase the therapeutic and adverse effects of theophylline.

Fosphenytoin: Decreased effect of both products

Grepafloxacin: Grepafloxacin may increase the effect of theophylline.

Halothane: Increased risk of cardiac arrhythmia

Heptabarbital: The barbiturate, heptabarbital, decreases the effect of theophylline.

Hexobarbital: The barbiturate, hexobarbital, decreases the effect of theophylline.

Interferon Alfa-2a, Recombinant: Interferon increases the effect and toxicity of theophylline

Interferon Alfa-2b, Recombinant: Interferon increases the effect and toxicity of theophylline

Interferon alfa-n1: Interferon increases the effect and toxicity of theophylline

Isoniazid: Isoniazid may increase the therapeutic and adverse effects of theophylline.

Josamycin: The macrolide, josamycin, may increase the effect and toxicity of theophylline.

Lithium: Theophylline decreases serum levels of lithium

Mephenytoin: Decreased effect of both products

Mestranol: The contraceptive increases the effect and toxicity of theophylline

Methohexital: The barbiturate, methohexital, decreases the effect of theophylline.

Methylphenobarbital: The barbiturate, methylphenobarbital, decreases the effect of theophylline.

Metocurine: Theophylline decreases the effect of the muscle relaxant

Mexiletine: Mexiletine increases the effect and toxicity of theophylline

Mivacurium: Theophylline decreases the effect of the muscle relaxant

Nadolol: Antagonism of action and increased effect of theophylline

Norfloxacin: Norfloxacin may increase the effect of theophylline.

Pancuronium: Theophylline decreases the effect of the muscle relaxant

Pefloxacin: Pefloxacin may increase the effect of theophylline.

Peginterferon alfa-2a: Interferon increases the effect and toxicity of theophylline

Peginterferon alfa-2b: Interferon increases the effect and toxicity of theophylline

Penbutolol: Antagonism of action and increased effect of theophylline

Pentobarbital: The barbiturate, pentobarbital, decreases the effect of theophylline.

Pentoxifylline: Pentoxifylline increases the effect and toxicity of theophylline

Phenobarbital: The barbiturate, phenobarbital, decreases the effect of theophylline.

Phenytoin: Decreased effect of both products

Pindolol: Antagonism of action and increased effect of theophylline

Primidone: The barbiturate, primidone, decreases the effect of theophylline.

Propafenone: Propafenone increases the effect of theophylline

Propranolol: Antagonism of action and increased effect of theophylline

Quinidine barbiturate: The barbiturate, quinidine barbiturate, decreases the effect of theophylline.

Rifampin: Rifampin decreases the effect of theophylline

Ritonavir: Ritonavir decreases the effect of theophylline

Rofecoxib: Rofecoxib increases the effect and toxicity of theophylline

Secobarbital: The barbiturate, secobarbital, decreases the effect of theophylline.

Sotalol: Antagonism of action and increased effect of theophylline

St. John's Wort: St. John's Wort decreases the effect of theophylline

Tacrine: Tacrine may reduce the elimination rate of Theophylline. Monitor for changes in the therapeutic and toxic effects of theophylline if Tacrine is initiated, discontinued or if the dose is changed.

Talbutal: The barbiturate, talbutal, decreases the effect of theophylline.

Telithromycin: Telithromycin may reduce clearance of Theophylline. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Theophylline if Telithromycin is initiated, discontinued or dose changed.

Temazepam: Theophylline may decrease the efficacy of Temazepam. Monitor for changes in the therapeutic effect of Temazepam if Theophylline is initiated, discontinued or dose changed.

Terbinafine: Terbinafine increases the effect and toxicity of theophylline

Thiabendazole: The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Theophylline by decreasing Theophylline metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Theophylline if Thiabendazole is initiated, discontinued or dose changed.

Ticlopidine: Ticlopidine increases the effect and toxicity of theophylline

Timolol: Antagonism of action and increased effect of theophylline

Tipranavir: Tipranavir, co-administered with Ritonavir, may decrease the concentration of Theophylline.

Troleandomycin: The macrolide, troleandomycin, may increase the effect and toxicity of theophylline.

Tubocurarine: Theophylline decreases the effect of the muscle relaxant

Vecuronium: Theophylline decreases the effect of the muscle relaxant

Verapamil: Verapamil increases the effect of theophylline

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of theophylline by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of theophylline if voriconazole is initiated, discontinued or dose changed.

Zafirlukast: Zafirlukast serum concentrations may be decreased by Theophylline.

Zileuton: Zileuton may increase the therapeutic and adverse effects of theophylline by increasing its serum concentration. Monitor for changes in the therapeutic and adverse effects of theophylline if zileuton is initiated, discontinued or dose changed. Dose alterations should be considered.