Brands, Medical Use, Clinical Data
Drug Category
- Vasodilator Agents
- Bronchodilator Agents
- Respiratory Smooth Muscle Relaxants
Dosage Forms
- Capsule (sustained-release)
- Elixir
- Liquid
- Tablet
- Tablet (extended-release)
Brands / Synonyms
Accurbron; Acet-Theocin; Aerobin; Aerolate; Aerolate III; Aerolate SR; Afonilm; Afonilum; Aminophylline; Aquaphyllin; Armophylline; Asbron; Asmalix; Asmax; Austyn; Bilordyl; Bronchoretard; Bronkodyl; Bronkodyl SR; Cetraphylline; Choledyl SA; Chronophyllin; Constant T; Diffumal; Dimethylxanthine; Diphyllin; Doraphyllin; Duraphyl; Duraphyllin; Dyspne-Inhal; Egifilin; Elan; Elixex; Elixicon; Elixomin; Elixophyllin; Elixophyllin SR; Elixophylline; Etheophyl; Euphyllin; Euphylline; Euphylong; Labid; Lanophyllin; Lasma; Liquophylline; Liquorice; Maphylline; Medaphyllin; Nuelin; Optiphyllin; Parkophyllin; Physpan; Pro-Vent; Pseudotheophylline; Pulmidur; Pulmo-Timelets; Quibron; Quibron T; Quibron T / SR; Quibron-T; Quibron-T/SR; Respbid; Respicur; Respid; Slo-Bid; Slo-Phyllin; Solosin; Somophyllin CRT; Somophyllin T; Somophyllin-CRT; Somophyllin-DF; Somophyllin-T; Spophyllin Retard; Sustaire; Synophylate; Synophylate-L.A. Cenules; T-Phyl; Talotren; Tefamin; Telb-DS; Telbans Dry Syrup; Teocen 200; Teofilina; Teofyllamin; Teolair; Teonova; Teosona; Tesona; Theacitin; Theal Tablets; Theo 24; Theo-11; Theo-24; Theo-DS; Theo-Dur; Theo-Nite; Theo-Sav; Theobid; Theobid Duracap; Theobid Jr.; Theochron; Theocin; Theoclair-SR; Theoclear; Theoclear 80; Theoclear L.A.-130; Theoclear LA; Theoclear-200; Theoclear-80; Theocontin; Theodel; Theodrip; Theodur Dry Syrup; Theofol; Theograd; Theolair; Theolair-SR; Theolix; Theolixir; Theon; Theona P; Theopek; Theophyl; Theophyl-225; Theophyl-SR; Theophyline; Theophyllin; Theophylline Anhydrous; Theophylline, Anhydrous; Theophylline-SR; Theoplus; Theospan; Theostat; Theostat 80; Theotard; Theovent; Uni-Dur; Unifyl; Unilong; Uniphyl; Uniphyllin; Xanthium; Xantivent
Indications
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.
Absorption
Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.
Toxicity
Symptoms of overdose include seizures, arrhythmias, and GI effects.
Biotrnasformation / Drug Metabolism
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.
Contraindications
This product is contraindicated in individuals who have shown hypersensitivity to its components. It is also
contraindicated in patients with active peptic ulcer disease, and in individuals with underlying seizure disorders
(unless receiving appropriate anti-convulsant medication).
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.
The drugs listed in TABLES 2A and 2B have the potential to produce clinically significant pharmacodynamic or
pharmacokinetic interactions with theophylline. The information in the "Effect" column of TABLES 2A and 2B assumes
that the interacting drug is being added to a steady-state theophylline regimen. If theophylline is being initiated
in a patient who is already taking a drug that inhibits theophylline clearance (e.g., cimetidine,
erythromycin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be
smaller. Conversely, if theophylline is being initiated in a patient who is already taking a drug that enhances
theophylline clearance (e.g., rifampin), the dose of theophylline required to achieve a therapeutic serum
theophylline concentration will be larger. Discontinuation of a concomitant drug that increases theophylline
clearance will result in accumulation of theophylline to potentially toxic levels, unless the theophylline dose is
appropriately reduced. Discontinuation of a concomitant drug that inhibits theophylline clearance will result in
decreased serum theophylline concentrations, unless the theophylline dose is appropriately increased.
The listing of drugs in TABLES 2A and 2B is current as of April 3, 1995. New interactions are continuously being
reported for theophylline, especially with new chemical entities. The clinician should not assume that a drug does
not interact with theophylline if it is not listed in TABLES 2A and 2B.Before addition of a newly available drug
in a patient receiving theophylline, the package insert of the new drug and/or the medical literature should be
consulted to determine if an interaction between the new drug and theophylline has been reported.
TABLE 2A - Clinically significant drug interactions with theophylline*
| Drug |
Type of Interaction |
Effect** |
| Adenosine |
Theophylline blocks adenosine receptors. |
Higher doses of adenosine may be required to achieve desired effect. |
| Alcohol |
A single large dose of alcohol (3 ml/kg of whiskey) decreases theophylline clearance for up to
24 hours. |
30% increase |
| Allopurinol |
Decreases theophylline clearance at allopurinol doses ³600
mg/day. |
25% increase |
| Aminoglutethimide |
Increases theophylline clearance by induction of microsomal enzyme activity. |
25% decrease |
| Carbamazepine |
Similar to aminoglutethimide. |
30% decrease |
| Cimetidine |
Decreases theophylline clearance by inhibiting cytochrome P450 1A2. |
70% increase |
| Ciprofloxacin |
Similar to cimetidine. |
40% increase |
| Clarithromycin |
Similar to erythromycin. |
25% increase |
| Diazepam |
Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while
theophylline blocks adenosine receptors. |
Larger diazepam doses may be required to produce desired level of sedation. |
| Discontinuation of theophylline without reduction of diazepam dose may result in
respiratory depression. |
| Disulfiram |
Decreases theophylline clearance by inhibiting hydroxylation and demethylation. |
50% increase |
| Enoxacin |
Similar to cimetidine. |
300% increase |
| Ephedrine |
Synergistic CNS effects |
Increased frequency of nausea, nervousness, and insomnia. |
| Erythromycin |
Erythromycin metabolite decreases theophylline clearance by inhibiting cytochrome P450
3A3. |
35% increase. |
| Erythromycin steady-state serum concentrations decreased by a similar amount. |
| Estrogen |
Estrogen containing oral contraceptives decrease theophylline clearance in a dose-dependent
fashion. The effect of progesterone on theophylline clearance is unknown. |
30% increase |
| Flurazepam |
Similar to diazepam. |
Similar to diazepam. |
| Fluvoxamine |
Similar to cimetidine myocardium to catecholamines, theophylline increases release of
endogenous catecholamines. |
Similar to cimetidine ventricular arrhythmias. |
| Interferon, human recombinant alpha-A |
Decreases theophylline clearance. |
100% increase |
| Isoproterenol (IV) |
Increases theophylline clearance. |
20% decrease |
| Ketamine |
Pharmacologic |
May lower theophylline seizure threshold. |
| Lithium |
Theophylline increases renal lithium clearance. |
Lithium dose required to achieve a therapeutic serum concentration increased an average of
60%. |
| Lorazepam |
Similar to diazepam. |
Similar to diazepam. |
TABLE 2B - Clinically significant drug interactions with theophylline*
| Drug |
Type of Interaction |
Effect** |
| Methotrexate (MTX) |
Decreases theophylline clearance. |
20% increase after low dose MTX, higher dose MTX may have a greater effect. |
| Mexiletine |
Similar to disulfiram. |
80% increase |
| Midazolam |
Similar to diazepam. |
Similar to diazepam. |
| Moricizine |
Increases theophylline clearance. |
25% decrease |
| Pancuronium |
Theophylline may antagonize non-depolarizing neuromuscular blocking effects; possibly due to
phosphodiesterase inhibition. |
Larger dose of pancuronium may be required to achieve neuromuscular blockade. |
| Pentoxifylline |
Decreases theophylline clearance. |
30% increase |
| Phenobarbital (PB) |
Similar to aminoglutethimide. |
25% decrease after two weeks of concurrent PB. |
| Phenytoin |
Phenytoin increases theophylline clearance by increasing microsomal enzyme activity.
Theophylline decreases phenytoin absorption. |
Serum theophylline and phenytoin concentrations decrease about 40%. |
| Propafenone |
Decreases theophylline clearance and pharmacologic interaction. |
40% increase. Beta-2 blocking effect may decrease efficacy of theophylline. |
| Propranolol |
Similar to cimetidine and pharmacologic interaction. |
100% increase. Beta-2 blocking effect may decrease efficacy of theophylline. |
| Rifampin |
Increases theophylline clearance by increasing cytochrome P450 1A2 and 3A3 activity. |
20-40% decrease |
| Sulfinpyrazone |
Increases theophylline clearance by increasing demethylation and hydroxylation. |
20% decrease |
| Decreases renal clearance of theophylline. |
| Tacrine |
Similar to cimetidine, also increases renal clearance of theophylline. |
90% increase |
| Thiabendazole |
Decreases theophylline clearance. |
190% increase |
| Ticlopidine |
Decreases theophylline clearance. |
60% increase |
| Troleandomycin |
Similar to erythromycin. |
33-100% increase depending on troleandomycin dose. |
| Verapamil |
Similar to disulfiram. |
20% increase |
|
* Refer to
for further information regarding table.
|
|
** Average effect on steady state theophylline concentration or other clinical effect for pharmacologic
interactions. Individual patients may experience larger changes in serum theophylline concentration than the
value listed.
|
The Effect of Other Drugs on Theophylline Serum Concentration Measurements: Most serum theophylline assays in
clinical use are immunoassays which are specific for theophylline. Other xanthines such as caffeine, dyphylline, and
pentoxifylline are not detected by these assays. Some drugs (e.g., cefazolin, cephalothin), however, may
interfere with certain HPLC techniques. Caffeine and xanthine metabolites in neonates or patients with renal
dysfunction may cause the reading from some dry reagent office methods to be higher than the actual serum
theophylline concentration.
|
