Data from FDA - Curated by EPG Health - Last updated 01 April 2018

Indication(s)

INDICATIONS AND USAGE Theophylline is indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

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Advisory information

contraindications
CONTRAINDICATIONS THEOPHYLINE ORAL SOLUTION, USP is contraindicated in patients with a history of hypersensitivity to theophylline or other components in the product.
Special warnings and precautions
PRECAUTIONS General: 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, prior to increases in theophylline dose, and during follow up (see WARNINGS). The dose of theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of a week or longer with the final dose guided by monitoring serum theophylline concentrations and the patient's clinical response (see DOSAGE AND ADMINISTRATION, Table V). Monitoring Serum Theophylline Concentrations: Serum theophylline concentration measurements are readily available and should be used to determine whether the dosage is appropriate. Specifically, the serum theophylline concentration should be measured as follows: 1. When initiating therapy to guide final dosage adjustment after titration. 2. Before making a dose increase to determine whether the serum concentration is sub-therapeutic in a patient who continues to be symptomatic. 3. Whenever signs or symptoms of theophylline toxicity are present. 4. Whenever there is a new illness, worsening of a chronic illness or a change in the patient's treatment regimen that may alter theophylline clearance (e.g., fever >102°F sustained for 24 hours, hepatitis, or drugs listed in Table II are added or discontinued). To guide a dose increase, the blood sample should be obtained at the time of the expected peak serum theophylline concentration; 1-2 hours after a dose at steady-state. For most patients, steady-state will be reached after 3 days of dosing when no doses have been missed, no extra doses have been added, and none of the doses have been taken at unequal intervals. A trough concentration (i.e., at the end of the dosing interval) provides no additional useful information and may lead to an inappropriate dose increase since the peak serum theophylline concentration can be two or more times greater than the trough concentration with an immediate-release formulation. If the serum sample is drawn more than two hours after the dose, the results must be interpreted with caution since the concentration may not be reflective of the peak concentration. In contrast, when signs or symptoms of theophylline toxicity are present, the serum sample should be obtained as soon as possible, analyzed immediately, and the result reported to the clinician without delay. In patients in whom decreased serum protein binding is suspected (e.g., cirrhosis, women during the third trimester of pregnancy), the concentration of unbound theophylline should be measured and the dosage adjusted to achieve an unbound concentration of 6-12 mcg/mL. Saliva concentrations of theophylline cannot be used reliably to adjust dosage without special techniques. Effects on Laboratory Tests: As a result of its pharmacological effects, theophylline at serum concentrations within the 10-20 mcg/mL range modestly increases plasma glucose (from a mean of 88 mg% to 98 mg%), uric acid (from a mean of 4 mg/dl to 6 mg/dl), free fatty acids (from a mean of 451 μeq/l to 800 μeq/l), total cholesterol (from a mean of 140 vs 160 mg/dl), HDL (from a mean of 36 to 50 mg/dl), HDL/LDL ratio (from a mean of 0.5 to 0.7), and urinary free cortisol excretion (from a mean of 44 to 63 mcg/24 hr). 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). The clinical importance of these changes should be weighed against the potential therapeutic benefit of theophylline in individual patients. Information for Patients: The patient (or parent/care giver) should be instructed to seek medical advice whenever nausea, vomiting, persistent headache, insomnia or rapid heart beat occurs during treatment with theophylline, even if another cause is suspected. The patient should be instructed to contact their clinician if they develop a new illness, especially if accompanied by a persistent fever, if they experience worsening of a chronic illness, if they start or stop smoking cigarettes or marijuana, or if another clinician adds a new medication or discontinues a previously prescribed medication. Patients should be instructed to inform all clinicians involved in their care that they are taking theophylline, especially when a medication is being added or deleted from their treatment. Patients should be instructed to not alter the dose, timing of the dose, or frequency of administration without first consulting their clinician. If a dose is missed, the patient should be instructed to take the next dose at the usually scheduled time and to not attempt to make up for the missed dose. 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 Table II have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with theophylline. The information in the “Effect” column of Table II 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 drugs listed in Table III have either been documented not to interact with theophylline or do not produce a clinically significant interaction (i.e., <15% change in theophylline clearance). The listing of drugs in Table II and III are current as of February 9, 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 Table II. 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 II. Clinically significant drug interactions with theophylline*. Drug Type of Interaction Effect** *Refer to PRECAUTIONS, Drug Interactions 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. 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 >600 mg/day. 25% increase Amino glutethimide 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 decrease 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 Similar to cimetidine Halothane Halothane sensitizes the myocardium to catecholamines, theophylline increases release of endogenous catecholamines. Increased risk of 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. 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. Decreases renal clearance of theophylline. 20% decrease 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 Table III. Drugs that have been documented not to interact with theophylline or drugs that produce no clinically significant interaction with theophylline.* *Refer to PRECAUTIONS, Drug Interactions for information regarding table. albuterol, systemic and inhaled felodipinefinasteride nizatidinenorfloxacin amoxicillin hydrocortisone ofloxacin ampicillin, with or without sulbactam isoflurane isoniazid omeprazole prednisone, prednisolone atenolol isradipine ranitidine azithromycin influenza vaccine rifabutin caffeine, dietary ingestion ketoconazo lelomefloxacin roxithromycin sorbitol cefaclor mebendazole (purgative doses do not co-trimoxazole (trimethoprim and sulfamethoxazole) medroxyprogesteronemethylprednisolone inhibit theophylline absorption) diltiazem metronidazole sucralfate dirithromycin metoprolol terbutaline, systemic enflurane nadolol terfenadine famotidine nifedipine tetracycline tocainide 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. 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 5-75mg/kg). Results are pending. Theophylline has been studied in Ames salmonella, in vivo and in vitro cytogenetics, micronucleus and Chinese hamster ovary test systems and has not been shown to be genotoxic. In a 14 week continuous breeding study, theophylline, administered to mating pairs of B6C3F1 mice at oral doses of 120, 270 and 500 mg/kg (approximately 1.0-3.0 times the human dose on a mg/m2 basis) impaired fertility, as evidenced by decreases in the number of live pups per litter, decreases in the mean number of litters per fertile pair, and increases in the gestation period at the high dose as well as decreases in the proportion of pups born alive at the mid and high dose. In 13 week toxicity studies, theophylline was administered to F344 rats and B6C3F1 mice at oral doses of 40-300 mg/kg (approximately 2.0 times the human dose on a mg/m2 basis). At the high dose, systemic toxicity was observed in both species including decreases in testicular weight. Pregnancy: CATEGORY C: There are no adequate and well controlled studies in pregnant women. Additionally, there are no teratogenicity studies in non-rodents (e.g., rabbits). Theophylline was not shown to be teratogenic in CD-1 mice at oral doses up to 400 mg/kg, approximately 2.0 times the human dose on a mg/m2 basis or in CD-1 rats at oral doses up to 260 mg/kg, approximately 3.0 times the recommended human dose on a mg/m2 basis. At a dose of 220 mg/kg, embryotoxicity was observed in rats in the absence of maternal toxicity. Nursing Mothers: Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. The concentration of theophylline in breast milk is about equivalent to the maternal serum concentration. An infant ingesting a liter of breast milk containing 10-20 mcg/mL of theophylline per day is likely to receive 10-20 mg of theophylline per day. Serious adverse effects in the infant are unlikely unless the mother has toxic serum theophylline concentrations. Pediatric Use: Theophylline is safe and effective for the approved indications in pediatric patients (See INDICATIONS AND USAGE). The maintenance dose of theophylline must be selected with caution in pediatric patients since the rate of theophylline clearance is highly variable across the age range of neonates to adolescents (see CLINICAL PHARMACOLOGY, Table I, WARNINGS, and DOSAGE AND ADMINISTRATION, Table V). Due to the immaturity of theophylline metabolic pathways in infants under the age of one year, particular attention to dosage selection and frequent monitoring of serum theophylline concentrations are required when theophylline is prescribed to pediatric patients in this age group. Geriatric Use: Elderly patients are at significantly greater risk of experiencing serious toxicity from theophylline than younger patients due to pharmacokinetic and pharmacodynamic changes associated with aging. Theophylline clearance is reduced in patients greater than 60 years of age, resulting in increased serum theophylline concentrations in response to a given theophylline dose. Protein binding may be decreased in the elderly resulting in a larger proportion of the total serum theophylline concentration in the pharmacologically active unbound form. Elderly patients also appear to be more sensitive to the toxic effects of theophylline after chronic overdosage than younger patients. For these reasons, the maximum daily dose of theophylline in patients greater than 60 years of age ordinarily should not exceed 400 mg/day unless the patient continues to be symptomatic and the peak steady state serum theophylline concentration is <10 mcg/mL (see DOSAGE AND ADMINISTRATION). Theophylline doses greater than 400 mg/d should be prescribed with caution in elderly patients.
Adverse reactions
ADVERSE REACTIONS Adverse reactions associated with theophylline are generally mild when peak serum theophylline concentrations are <20 mcg/ mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia. When peak serum theophylline concentrations exceed 20 mcg/mL, however, theophylline produces a wide range of adverse reactions including persistent vomiting, cardiac arrhythmias, and intractable seizures which can be lethal (see OVERDOSAGE). The transient caffeine-like adverse reactions occur in about 50% of patients when theophylline therapy is initiated at doses higher than recommended initial doses (e.g., >300 mg/day in adults and >12 mg/kg/day in children beyond >1 year of age). During the initiation of theophylline therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists. Initiation of theophylline therapy at a low dose with subsequent slow titration to a predetermined age-related maximum dose will significantly reduce the frequency of these transient adverse effects (see DOSAGE AND ADMINISTRATION, Table V). In a small percentage of patients (<3% of children and <10% of adults) the caffeine-like adverse effects persist during maintenance therapy, even at peak serum theophylline concentrations within the therapeutic range (i.e., 10-20 mcg/mL). Dosage reduction may alleviate the caffeine-like adverse effects in these patients, however, persistent adverse effects should result in a reevaluation of the need for continued theophylline therapy and the potential therapeutic benefit of alternative treatment. Other adverse reactions that have been reported at serum theophylline concentrations <20 mcg/mL include diarrhea, irritability, restlessness, fine skeletal muscle tremors, and transient diuresis. In patients with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been reported at serum theophylline concentrations 15 mcg/mL. There have been a few isolated reports of seizures at serum theophylline concentrations <20 mcg/mL in patients with an underlying neurological disease or in elderly patients. 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. The clinical characteristics of the seizures reported in patients with serum theophylline concentrations <20 mcg/mL have generally been milder than seizures associated with excessive serum theophylline concentrations resulting from an overdose (i.e., they have generally been transient, often stopped without anticonvulsant therapy, and did not result in neurological residua). Table IV. Manifestations of theophylline toxicity.* Percentage of patients reported with sign or symptom Acute Overdose (Large Single Ingestion) Chronic Overdosage (Multiple Excessive Doses) Sign/Symptom Study 1 (n=157) Study 2 (n=14) Study 1 (n=92) Study 2 (n=102) *These data are derived from two studies in patients with serum theophylline concentrations >30 mcg/mL. In the first study (Study #1 - Shanon, Ann Intern Med 1993;119:1161-67), data were prospectively collected from 249 consecutive cases of theophylline toxicity referred to a regional poison center for consultation. In the second study (Study #2 - Sessler, Am J Med 1990;88:567-76), data were retrospectively collected from 116 cases with serum theophylline concentrations >30 mcg/mL among 6000 blood samples obtained for measurement of serum theophylline concentrations in three emergency departments. Differences in the incidence of manifestations of theophylline toxicity between the two studies may reflect sample selection as a result of study design (e.g., in Study #1, 48% of the patients had acute intoxications versus only 10% in Study #2) and different methods of reporting results. **NR = Not reported in a comparable manner. Asymptomatic NR** 0 NR** 6 Gastrointestinal Vomiting 73 93 30 61 Abdominal Pain NR** 21 NR** 12 Diarrhea NR** 0 NR** 14 Hematemesis NR** 0 NR** 2 Metabolic/Other Hypokalemia 85 79 44 43 Hyperglycemia 98 NR** 18 NR** Acid/base disturbance 34 21 9 5 Rhabdomyolysis NR** 7 NR** 0 Cardiovascular Sinus tachycardia 100 86 100 62 Other supraventricular tachycardias 2 21 12 14 Ventricular premature beats 3 21 10 19 Atrial fibrillation or flutter 1 NR** 12 NR** Multifocal atrial tachycardia 0 NR** 2 NR** Ventricular arrhythmias with hemodynamic instability 7 14 40 0 Hypotension/shock NR** 21 NR** 8 Neurologic Nervousness NR** 64 NR** 21 Tremors 38 29 16 14 Disorientation NR** 7 NR** 11 Seizures 5 14 14 5 Death 3 21 10 4

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION General Considerations: The steady-state peak serum theophylline concentration is a function of the dose, the dosing interval, and the rate of theophylline absorption and clearance in the individual patient. Because of marked individual differences in the rate of theophylline clearance, the dose required to achieve a peak serum theophylline concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter theophylline clearance (e.g., 400- 1600 mg/day in adults <60 years old and 10-36 mg/kg/day in children 1-9 years old). For a given population there is no single theophylline dose that will provide both safe and effective serum concentrations for all patients. Administration of the median theophylline dose required to achieve a therapeutic serum theophylline concentration in a given population may result in either sub-therapeutic or potentially toxic serum theophylline concentrations in individual patients. For example, at a dose of 900 mg/d in adults <60 years or 22 mg/kg/d in children 1-9 years, the steady state peak serum theophylline concentration will be <10 mcg/mL in about 30% of patients, 10-20 mcg/mL in about 50% and 20-30 mcg/mL in about 20% of patients. The dose of theophylline must be individualized on the basis of peak serum theophylline concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk to adverse effects. Transient caffeine-like adverse effects and excessive serum concentrations in slow metabolizers can be avoided in most patients by starting with a sufficiently low dose and slowly increasing the dose, if judged to be clinically indicated, in small increments (See Table V). Dose increases should only be made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum theophylline concentrations to reach the new steady state. Dosage adjustment should be guided by serum theophylline concentration measurement (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION, Table VI). Health care providers should instruct patients and care givers to discontinue any dosage that causes adverse effects, to withhold the medication until these symptoms are gone and to then resume therapy at a lower, previously tolerated dosage (see WARNINGS). If the patient's symptoms are well controlled, there are no apparent adverse effects, and no intervening factors that might alter dosage requirements (see WARNINGS and PRECAUTIONS), serum theophylline concentrations should be monitored at 6 month intervals for rapidly growing children and at yearly intervals for all others. In acutely ill patients, serum theophylline concentrations should be monitored at frequent intervals, e.g., every 24 hours. Theophylline distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight. Table V contains theophylline dosing titration schema recommended for patients in various age groups and clinical circumstances. Table VI contains recommendations for theophylline dosage adjustment based upon serum theophylline concentrations. Application of these general dosing recommendations to individual patients must take into account the unique clinical characteristics of each patient. In general, these recommendations should serve as the upper limit for dosage adjustments in order to decrease the risk of potentially serious adverse events associated with unexpected large increases in serum theophylline concentration. Table V. Dosing initiation and titration (as anhydrous theophylline).* A. Infants <1 year old. Initial Dosage. Premature Neonates: < 24 days postnatal age; 1.0 mg/kg every 12 hr ≥ 24 days postnatal age; 1.5 mg/kg every 12 hr Full term infants and infants up to 52 weeks of age: Total daily dose (mg) = [(0.2 x age in weeks)+5.0] x (Kg body Wt). up to age 26 weeks; divide dose into 3 equal amounts administered at 8 hour intervals. ≥26 weeks of age; divide dose into 4 equal amounts administered at 6 hour intervals. Final Dosage. Adjusted to maintain a peak steady state serum theophylline concentration of 5-10 mcg/ml in neonates and 10-15 mcg/mL in older infants (see Table VI). Since the time required to reach steady-state is a function of theophylline half-life, up to 5 days may be required to achieve steady state in a premature neonate while only 2-3 days may be required in a 6 month old infant without other risk factors for impaired clearance in the absence of a loading dose. If a serum theophylline concentration is obtained before steady state is achieved, the maintenance dose should not be increased, even if the serum theophylline concentration is <10 mcg/mL. B. Children (1-15 years) and adults (16-60 years) without risk factors for impaired clearance. Titration Step Children < 45 kg Children > 45 kg and adults 1. Starting Dosage 12-14 mg/kg/day up to a maximum of 300 mg/day divided Q4-6 hrs* 300 mg/day divided Q6-8 hrs* 2. After 3 days, if tolerated, increase dose to: 16 mg/kg/day up to a maximum of 400 mg/day divided Q4-6 hrs* 400 mg/day divided Q6-8 hrs* 3. After 3 more days, if tolerated, increase dose to: 20 mg/kg/day up to a maximum of 600 mg/day divided Q4-6 hrs* 600 mg/day divided Q6-8 hrs* C. Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum Theophylline Concentrations: In children 1-15 years of age, the final theophylline dose should not exceed 16 mg/kg/day up to a maximum of 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations. In adolescents ≥16 years and adults, including the elderly, the final theophylline dose should not exceed 400 mg/day in the presence of risk factors for reduced theophylline clearance (see WARNINGS) or if it is not feasible to monitor serum theophylline concentrations. D. Loading Dose for Acute Bronchodilatation: An inhaled beta-2 selective agonist, alone or in combination with a systemically administered corticosteroid, is the most effective treatment for acute exacerbations of reversible airways obstruction. Theophylline is a relatively weak bronchodilator, is less effective than an inhaled beta-2 selective agonist and provides no added benefit in the treatment of acute bronchospasm. If an inhaled or parenteral beta agonist is not available, a loading dose of an oral immediate release theophylline can be used as a temporary measure. A single 5 mg/kg dose of theophylline, in a patient who has not received any theophylline in the previous 24 hours, will produce an average peak serum theophylline concentration of 10 mcg/mL (range 5-15 mcg/mL). If dosing with theophylline is to be continued beyond the loading dose, the guidelines in Sections A.1.b., B.3, or C., above, should be utilized and serum theophylline concentration monitored at 24 hour intervals to adjust final dosage. * Patients with more rapid metabolism, clinically identified by higher than average dose requirements, should receive a smaller dose more frequently to prevent breakthrough symptoms resulting from low trough concentrations before the next dose. A reliably absorbed slow-release formulation will decrease fluctuations and permit longer dosing intervals. Table VI. Dosage adjustment guided by serum theophylline concentration. Peak Serum Concentration Dosage Adjustment ¶ Dose reduction and/or serum theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce theophylline clearance occur (e.g., sustained fever), or a drug that interacts with theophylline is added or discontinued (see WARNINGS). <9.9 mcg/mL If symptoms are not controlled and current dosage is tolerated, increase dose about 25%. Recheck serum concentration after three days for further dosage adjustment. 10 to 14.9 mcg/mL If symptoms are controlled and current dosage is tolerated, maintain dose and recheck serum concentration at 6-12 month intervals.¶ If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen. 15-19.9 mcg/mL Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated.¶ 20-24.9 mcg/mL Decrease dose by 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. 25-30 mcg/mL Skip next dose and decrease subsequent doses at least 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. If symptomatic, consider whether overdose treatment is indicated (see recommendations for chronic overdosage). >30 mcg/mL Treat overdose as indicated (see recommendations for chronic overdosage). If theophylline is subsequently resumed, decrease dose by at least 50% and recheck serum concentration after 3 days to guide further dosage adjustment.

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Category Value
Authorisation number ANDA091156
Agency product number 0I55128JYK
Orphan designation No
Product NDC 54838-556
Date Last Revised 22-02-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 313306
Marketing authorisation holder Lannett Company, Inc.