Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in patients with CHF (see Trembath PW, Boobis SW, Richens A. Theophylline and its derivatives, such as aminophylline, have an established role as bronchodilators, although their mode of action in man is not clear. When a loading dose becomes necessary in the patient who has already received theophylline, estimation of the serum concentration based upon the history is unreliable, and an immediate serum level determination is indicated. Evidence to suggest that aminophylline should not be used in mild to moderate COPD exacerbations Theophylline is one of those medications that has intrigued and possibly confused clinicians and pharmacologists alike since the mid 19th century. 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.Carcinogenesis, Mutagenesis, and Impairment of Fertility:Long term carcinogenicity studies have been carried out in mice (oral doses 30 - 150 mg/kg) and rats (oral doses 5 - 75 mg/kg). Pre-existing or concurrent disease may also significantly increase the susceptibility of a patient to a particular toxic manifestation, e.g., patients with neurologic disorders have an increased risk of seizures and patients with cardiac disease have an increased risk of cardiac arrhythmias for a given serum theophylline concentration compared to patients without the underlying disease.The frequency of various reported manifestations of oral theophylline overdose according to the mode of overdose are listed in Table IV.Other manifestations of theophylline toxicity include increases in serum calcium, creatine kinase, myoglobin and leukocyte count, decreases in serum phosphate and magnesium, acute myocardial infarction, and urinary retention in men with obstructive uropathy.Seizures associated with serum theophylline concentrations >30 mcg/mL are often resistant to anticonvulsant therapy and may result in irreversible brain injury if not rapidly controlled. If only total serum theophylline concentration is measured, this may lead to an unnecessary and potentially dangerous dose increase. Significant reduction in theophylline clearance, however, has been reported in women on the 20th day of the menstrual cycle and during the third trimester of pregnancy.Race: Pharmacokinetic differences in theophylline clearance due to race have not been studied.Renal Insufficiency: Only a small fraction, e.g., about 10%, of the administered theophylline dose is excreted unchanged in the urine of children greater than three months of age and adults. Avoiding breastfeeding for 2 hours after intravenous or 4 hours after an immediate-release oral aminophylline product can decrease the dose received by the breastfed infant.
Theophylline is structurally classified as a methylxanthine.
Table VI. Important : Betapace may cause Therefore, a second serum concentration should be obtained one expected half-life after starting the constant infusion (e.g., approximately 4 hours for children age 1 to 9 and 8 hours for nonsmoking adults; see Table I for the expected half-life in additional patient populations) to determine if the concentration is accumulating or declining from the post loading dose level. Theophylline only rarely alters the pharmacokinetics of other drugs.The drugs listed in Table II have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with theophylline. After a chronic overdosage, generalized seizures, life-threatening cardiac arrhythmias, and death may occur at serum theophylline concentrations >30 mcg/mL. The loading dose can then be determined as follows:where D is the loading dose, C is the serum theophylline concentration, and V is the volume of distribution. Name must be less than 100 characters
]PROTECT FROM LIGHT. Due to the wide intersubject variability of the rate of theophylline metabolism, nonlinearity of elimination may begin in some patients at serum theophylline concentrations <10 mcg/mL. Related agents caffeine and theobromine were used in the 1930s as bronchodilators, and theophylline developed an established … * To achieve a target concentration of 10 mcg/mL Aminophylline=theophylline/0.8. Infant serum theophylline concentrations can help to determine if signs of agitation are due to theophylline. Since little theophylline is excreted unchanged in the urine and since active metabolites of theophylline (i.e., caffeine, 3-methylxanthine) do not accumulate to clinically significant levels even in the face of end-stage renal disease, no dosage adjustment for renal insufficiency is necessary in adults and children >3 months of age.
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