pH is 8.8 (8.6 to 9.0). 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. In patients with end-stage renal disease, 3-methylxanthine may accumulate to concentrations that approximate the unmetabolized theophylline concentration. Newborn and especially preterm infants are most likely to be affected because of their slow elimination and low serum protein binding of theophylline. About 6% of a theophylline dose is N-methylated to caffeine. The apparent volume of distribution of theophylline is approximately 0.45 L/kg (range 0.3 - 0.7 L/kg) based on ideal body weight.
The dose of theophylline must be individualized on the basis of serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects.When theophylline is used as an acute bronchodilator, the goal of obtaining a therapeutic serum concentration is best accomplished with an intravenous loading dose. 1998 Aug;473:1-326. Table VI. Theophylline at serum concentrations within the 10 - 20 mcg/mL range may also transiently decrease serum concentrations of triiodothyronine (144 before, 131 after one week and 142 ng/dl after 4 weeks of theophylline). Discard unused portion. Caffeine concentrations are usually undetectable in adults regardless of renal function. Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in patients with reduced hepatic function (see
Aminophylline occurs as a white or slightly yellowish granule or powder, with a slight ammoniacal odor. you are taking cisapride, astemizole, terfenadine, mibefradil, dofetilide, or a theophylline (e.g., aminophylline). Manifestations of Theophylline Toxicity* Percentage of Patients Reported With Sign or Symptom* These data are derived from two studies in patients with serum theophylline concentrations
Careful consideration of the various interacting drugs and physiologic conditions that can alter theophylline clearance and require dosage adjustment should occur prior to initiation of theophylline therapy and prior to increases in theophylline dose (see If only total serum theophylline concentration is measured, this may lead to an unnecessary and potentially dangerous dose increase. Theophylline clearance is reduced in patients greater than 60 years of age, resulting in increased serum theophylline concentrations in response to a given theophylline infusion rate.
Avoiding breastfeeding for 2 hours after intravenous or 4 hours after an immediate-release oral aminophylline product can The clinical importance of these changes should be weighed against the potential therapeutic benefit of theophylline in individual patients.Theophylline interacts with a wide variety of drugs. New interactions are continuously being reported for theophylline, especially with new chemical entities. Bethesda (MD): National Library of Medicine (US); 2006–.Natl Toxicol Program Tech Rep Ser. In general, patients who experience an acute overdose are less likely to experience seizures than patients who have experienced a chronic overdosage, unless the peak serum theophylline concentration is >100 mcg/mL. [See USP Controlled Room Temperature. Please enable it to take advantage of the complete set of features! Passive smoke exposure has also been shown to increase theophylline clearance by up to 50%. 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). After a chronic overdosage, generalized seizures, life-threatening cardiac arrhythmias, and death may occur at serum theophylline concentrations >30 mcg/mL. Other xanthines such as caffeine, dyphylline, and pentoxifylline are not detected by these assays.
The activity of these pathways slowly increases to maximal levels by one year of age.Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity. In these patients, 5 days may be required before steady-state is reached.Theophylline distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight.Table V contains initial theophylline infusion rates following an appropriate loading dose recommended for patients in various age groups and clinical circumstances. Bethesda (MD): National Library of Medicine (US); 2006–.2018 Oct 31. The occurrence of seizures in elderly patients with serum theophylline concentrations <20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum theophylline concentration in the pharmacologically active unbound form. For these reasons, the maximum infusion rate of theophylline in patients greater than 60 years of age ordinarily should not exceed 17 mg/hr (21 mg/hr as aminophylline) unless the patient continues to be symptomatic and the peak steady state serum theophylline concentration is <10 mcg/mL (see Pediatrics: The clearance of theophylline is very low in neonates (see
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