Oxtriphylline is a bronchodilator . It contains 64% theophylline and has the properties attributed to theophylline.
INDICATIONS AND USAGE
The symptomatic treatment of reversible bronchoconstriction associated with bronchial asthma, chronic obstructive pulmonary emphysema, chronic bronchitis and related bronchospastic disorders.
CONTRA-INDICATIONS
Hypersensitivity to xanthines; active peptic ulcer; in coronary artery disease when myocardial stimulation might prove harmful.
PRECAUTIONS
Parents should be cautioned against overdosage to children - children are very sensitive to xanthines; the margin of safety above therapeutic doses is small. Ensure that children receiving oral oxtriphylline are not also receiving xanthines by the rectal route.
There is a marked variation in blood concentrations achieved in different patients given the same dose of oxtriphylline. This may lead to serious adverse effects in some patients. This variability in blood concentrations is probably due to differences in drug distribution and metabolism. Therefore, it is advisable to individualize the dose regimens. Ideally, all individuals should have serum theophylline concentrations measured and a theophylline half-life calculated. This would enable doses and dosing regimens to be tailored to each patient to maintain a therapeutic concentration, to ensure optimal clinical response and to avoid toxicity. Concurrent administration of other drugs and xanthine containing beverages can affect assay results (Schack and Waxler method).
In patients with severe pulmonary or cardiovascular disease and in patients with hepatic dysfunction, oxtriphylline metabolism may be impaired and thus toxic concentrations may be reached with standard dose regimens.
Exercise caution when oxtriphylline is used concurrently with sympathomimetic amines or other xanthines. In general, oxtriphylline should not be given more frequently than every 6 hours or within 12 hours of the ingestion of other xanthines.
Oxtriphylline may cause an elevation of serum uric acid, urinary catecholamines and plasma free fatty acids.
DRUG INTERACTIONS
Synergism with ephedrine has been documented and may occur with other sympathomimetic amines. Theophylline may cause increased excretion of lithium carbonate. Theophylline antagonizes the effect of propranolol. Theophylline potentiates the effects of diuretics and the cardiac effect of digitalis glycosides. The concomitant use of morphine, stilbamidine, curare may antagonize the effect of theophylline since these drugs stimulate histamine release and thereby induce bronchoconstriction.
Cigarette smoking and phenobarbital shorten, while alcohol consumption increases the half-life of theophylline.
Xanthines have been shown to be nephrotoxic with prolonged use at high dosage. Coincident toxicity should therefore be borne in mind when other potentially nephrotoxic drugs are administered concurrently.
Acidifying agents, by increasing urinary excretion of weak bases like the xanthines, inhibit theophylline action.
Alkalinizing agents, by decreasing urinary excretion of weak bases like the xanthines, potentiate theophylline action.
Combined use of several xanthines may cause excessive CNS stimulation.
Toxic reactions as a result of significant elevations of serum theophylline levels have been observed in patients after initiation of treatment with erythromycin preparations. Particular attention should therefore be directed toward monitoring the serum theophylline levels in such patients.
The methylxanthines increase blood levels of prothrombin and fibrinogen, shorten the prothrombin time and thus antagonize the effects of coumarin anticoagulants.
Xanthines antagonize the uricosuric action of probenecid and of sulfinpyrazone and uricosuric activity of pyrazolon derivatives.
Combined use of xanthines with sympathomimetics may cause excessive CNS stimulation.
Oxtriphylline potentiates the diuretic action of thiazide diuretics and the cardiac effect of digitalis glycosides. Oxtriphylline increases the ratio of clearances of lithium/ creatinine, and may thus decrease serum lithium to ineffective concentrations
ADVERSE REACTIONS
Toxicity of theophylline and its derivatives may present as follows:
CNS: In addition to those cited above, the patient may exhibit hyperreflexia, fasciculations and clonic and tonic convulsions. These are especially prone to occur in cases of overdosage in infants and small children.
Cardiovascular: In addition to those outlined above, marked hypotension and circulatory failure may be manifest.
Respiratory: Tachypnea and respiratory arrest may occur.
Renal: Albuminuria and microhematuria may occur. Increased excretion of renal tubular cells has been observed.
General systemic effects: syncope, collapse, fever and dehydration.
Treatment: 1. Discontinue drug immediately. 2. There is no known specific antidote. 3. Gastric lavage. 4. Emetic medication may be of value. 5. Avoid administration of sympathomimetic drugs. 6. I.V. fluids, oxygen and other supportive measures to prevent hypotension and overcome dehydration. 7. CNS stimulation and seizures may respond to i.v. diazepam, phenytoin sodium or phenobarbital sodium. 8. Monitor blood concentrations until below 20 �g/mL.