THEOPHYLLINE CLEARANCE IS DECREASED BY 50% OR MORE IN PATIENTS WITH CHF & IS DIRECTLY CORRELATED TO THE SEVERITY OF THE CARDIAC DISEASE. TOBACCO AND MARIJUANA SMOKING APPEAR TO INCREASE THE CLEARANCE OF
THEOPHYLLINE BY INDUCTION OF METABOLIC PATHWAYS BY APPROXIMATELY 50%
IN YOUNG ADULT TOBACCO SMOKERS AND BY APPROXIMATELY 80% IN ELDERLY TOBACCO SMOKERS COMPARED TO NONSMOKING SUBJECTS. ABSTINENCE FROM TOBACCO SMOKING FOR 1 WEEK CAUSES A REDUCTION OF APPROXIMATELY 40% IN THEOPHYLLINE CLEARANCE. FEVER, REGARDLESS OF ITS UNDERLYING CAUSE, CAN DECREASE THE CLEARANCE OF THEOPHYLLINE. OTHER FACTORS ASSOCIATED WITH DECREASED THEOPHYLLINE CLEARANCE INCLUDE THE THIRD TRIMESTER OF PREGNANCY, SEPSIS WITH MULTIPLE ORGAN FAILURE, AND HYPOTHYROIDISM & LIVER DISEASES.
DRUGS THAT DECREASE THEOPHYLLINE CLEARANCE - ALCOHOL, ALLOPURINOL, CARBAMAZEPINE, CIMETIDINE, CIPROFLOXACIN, DISULFIRAM, ENOXACIN, ERYTHROMYCIN, CLARITHROMYCIN, OESTROGENS, FLUVOXAMINE, INTERFERON, METHOTREXATE, MEXILETINE, NORFLOXACIN, OFLOXACIN, PENTOXIPHYLLINE,
PROPAFENONE, PROPRANOLOL, THIABENDAZOLE, TROLEANDOMYCIN, VERAPAMIL.
DRUGS THAT INCREASES THEOPHYLLINE CLEARANCE - AMINOGLUTETHIMIDE, ISOPROTERENOL, MORICIZINE, PHENOBARBITONE, PHENYTOIN, RIFAMPICIN, RITONAVIR, SULPHINPYRAZONE, TICLOPIDINE.
EPHEDRINE INCREASES FREQUENCY OF SIDE EFFECTS LIKE NAUSEA, NERVOUSNESS, INSOMNIA.
DIAZEPAM OR OTHER BENZODIAZRPAMS DOSE IS TO BE INCREASED TO ACHIEVE SEDATION & DOSE SHOULD BE REDUCED ONCE THEOPHYLLINE IS STOPPED OTHERWISE TOXICITY APPEARS. HALOTHANE , KETAMINE USE MAY INCREASE RISK OF VENTRICULAR ARRHYTHMIAS. RENAL CLEARANCE OF LITHIUM IS INCREASED. THEOPHYLLINE ANTAGONISES ADENOSINE & NEUROMUSCULAR BLOCKING EFFECTS OF PANCURONIUM. THEOPHYLLINE DECREASES PHENYTOIN ABSORPTION. SUCRALFATE REDUCES THEOPHYLLINE ABSORPTION. TOXIC EFFECTS OF THEOPHYLLINE, AMINOPHYLLINE & OTHER XANTHINES ARE ADDITIVE. XANTHINES CAN POTENTIATE HYPOKALEMIA IN ASSOCIATION WITH BETA-2 AGONIST, CORTICOSTEROIDS & DIURETICS ADMINISTRATION. THE INTERACTION BETWEEN THEOPHYLLINE & BETABLOCKERS IS COMPLEX BUT CONCOMITANT ADMINISTRATION IS AVOIDED ON PHARMACOLOGICAL GROUNDS SINCE BETABLOCKERS PRODUCE BRONCHOSPASM.