INN monograph
Theophylline/ Etofylline
Methylxanthine [EPC] · POM
Verified · Updated 01 Aug 2026 · Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Component monographs (multi-source pipeline); Professional class pharmacology (Therapeutic agent (verify pharmacological class))
Kenya market
Wholesale / list prices where loaded
Risk first
Contraindications
- CONTRAINDICATIONS Theophylline (Anhydrous) Extended-Release Tablets are contraindicated in patients with a history of hypersensitivity to theophylline or other components in the product.
Precautions
- WARNINGS Concurrent Illness Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition: Active peptic ulcer disease Seizure disorders Cardiac arrhythmias (not including bradyarrhythmias) Conditions That Reduce Theophylline Clearance There are several readily identifiable causes of reduced theophylline clearance.
- If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal theophylline toxicity can occur .
- Careful consideration must be given to the benefits and risks of theophylline use and the need for more intensive monitoring of serum theophylline concentrations in patients with the following risk factors: Age Neonates (term and premature) Children <1 year Elderly (>60 years) Concurrent Diseases Acute pulmonary edema Congestive heart failure Cor-pulmonale Fever
- ��102° for 24 hours or more
- or lesser temperature elevations for longer periods Hypothyroidism Liver disease
- cirrhosis, acute hepatitis Reduced renal function in infants <3 months of age Sepsis with multi-organ failure Shock Cessation of Smoking Drug Interactions Adding a drug that inhibits theophylline metabolism (e.g., cimetidine, erythromycin, tacrine) or stopping a concurrently administered drug that enhances theophylline metabolism (e.g., carbamazepine, rifampin).
- (see PRECAUTIONS, Drug Interactions, Table II ).
- When Signs or Symptoms of Theophylline Toxicity Are Present Whenever a patient receiving theophylline develops nausea or vomiting, particularly repetitive vomiting, or other signs or symptoms consistent with theophylline toxicity (even if another cause may be suspected), additional doses of theophylline should be withheld and a serum theophylline concentration measured immediately .
- Patients should be instructed not to continue any dosage that causes adverse effects and to withhold subsequent doses until the symptoms have resolved, at which time the healthcare professional may instruct the patient to resume the drug at a lower dosage (see DOSAGE AND ADMINISTRATION, Dosing Guidelines, Table VI ).
- Dosage Increases Increases in the dose of theophylline should not be made in response to an acute exacerbation of symptoms of chronic lung disease since theophylline provides little added benefit to inhaled beta2-selective agonists and systemically administered corticosteroids in this circumstance and increases the risk of adverse effects.
- A peak steady‑state serum theophylline concentration should be measured before increasing the dose in response to persistent chronic symptoms to ascertain whether an increase in dose is safe.
- Before increasing the theophylline dose on the basis of a low serum concentration, the healthcare professional should consider whether the blood sample was obtained at an appropriate time in relationship to the dose and whether the patient has adhered to the prescribed regimen (see PRECAUTIONS, Laboratory Tests ).
Point of care
Dosing
Adult
DOSAGE AND ADMINISTRATION Theophylline (Anhydrous) Extended-Release Tablets 400 or 600 mg can be taken once a day in the morning or evening. It is recommended that Theophylline (Anhydrous) Extended-Release Tablets be taken with meals. Patients should be advised that if they choose to take Theophylline (Anhydrous) Extended-Release Tablets with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food. Theophylline (Anhydrous) Extended-Release Tablets are not to be chewed or crushed because it may lead to a rapid release of theophylline with the potential for toxicity. The scored tablet may be split. Infrequently, patients receiving Theophylline (Anhydrous) Extended-Release Tablets 400 or 600 mg may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual theophylline. Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release theophylline product may be transferred to once-daily administration of 400 or 600 mg Theophylline (Anhydrous) Extended-Release Tablets on a mg-for-mg basis. It must be recognized that the peak and trough serum theophylline levels produced by the once-daily dosing may vary from those produced by the previous product and/or regimen. 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 of 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 ). Healthcare providers should instruct patients and caregivers 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). Patients with more rapid metabolism clinically identified by higher than average dose requirements, should receive a smaller dose more frequently (every 12 hours) to prevent breakthrough symptoms resulting from low trough concentrations before the next dose. A. Children (12-15 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 admin. QD 300 mg/day If caffeine-like adverse effects occur, then consideration should be given to a lower dose and titrating the dose more slowly (see ADVERSE REACTIONS ). admin. QD 2. After 3 days, if tolerated , increase dose to: 16 mg/kg/day up to a maximum of 400 mg/day admin. QD 400-600 mg/day admin. QD 3. After 3 more days, if tolerated , and if needed increase dose to: 20 mg/kg/day up to a maximum of 600 mg/day admin. QD As with all theophylline products, doses greater than 600 mg should be titrated according to blood level (See Table VI ). B. 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 12-15 years of age, the 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 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. Table VI. Dosage adjustment guided by serum theophylline concentration. Peak Serum Concentration Dosage Adjustment <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. 10-14.9 mcg/mL If symptoms are controlled and current dosage is tolerated, maintain dose and recheck serum concentration at 6-12 month intervals. 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 ). 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.
Paediatric
Pediatric Use Theophylline is safe and effective for the approved indications in pediatric patients. The maintenance dose of theophylline must be selected with caution in pediatric patients since the rate of theophylline clearance is highly variable across the pediatric age range (see CLINICAL PHARMACOLOGY, Table I , WARNINGS , and DOSAGE AND ADMINISTRATION, Table V ).
Renal
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Safety
Drug interactions
- Drugs that increase its plasma levels:- thiabendazole, norfloxacin, ciprofloxacin, erythromycin. isoniazid, fluconazole, verapamil, diltiazem, cimetidine, oral contraceptives, disulfiram.
- Drugs that reduce its plasma level: carbamazepine, phenobarbitone, primidone, phenytoin, rifampicin
- Fixed-dose/multi-ingredient product.
- Clinical details partially inherited from component monographs: Theophylline.
- Confirm combination SmPC for exact dosing.
Safety
Adverse effects
- 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 abdominal pain, agitation, anaphylactic reaction, anaphylactiod reaction, anxiety, cardiac arrhythmias, diarrhea, dizziness, fine skeletal muscle tremors, gastric irritation, gastroesophageal reflux, hyperuricemia, irritability, palpitations, pruritus, rash, sinus tachycardia, restlessness, transient diuresis, urinary retention and urticaria.
- 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).
- To report SUSPECTED ADVERSE REACTIONS, contact Westminster Pharmaceuticals, LLC at 1-844-221-7294 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Table IV.
- Manifestations of theophylline toxicity.
Use
Indications
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.
Pharmacology
Mode of action
Mechanism of Action Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.
Full mechanism text
Mechanism of Action Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). While the mechanisms of action of theophylline are not known with certainty, studies in animals suggest that bronchodilation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors. Some of the adverse effects associated with theophylline appear to be mediated by inhibition of PDE III (e.g., hypotension, tachycardia, headache, and emesis) and adenosine receptor antagonism (e.g., alterations in cerebral blood flow). Theophylline increases the force of contraction of diaphragmatic muscles. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel.
ADME
Pharmacokinetics & PD
| Onset | Product-specific |
|---|---|
| Duration | Product-specific |
| Route | See product SmPC |
| Absorption | Theophylline (Anhydrous) Extended-Release Tablets administered in the fed state is completely absorbed after oral administration. In a single-dose crossover study, two 400 mg Theophylline (Anhydrous) Extended-Release Tablets were administered to 19 normal volunteers in the mornin... |
| Metabolism | has also been reported in some studies, especially in acutely ill patients. It is, therefore, recommended that serum theophylline concentrations be measured frequently in acutely ill patients (e.g., at 24-hr intervals) and periodically in patients receiving long-term therapy, e.g... |
| Elimination | and consequent dosage requirements have been observed among other peoples. Population Characteristics Total body clearance Clearance represents the volume of blood completely cleared of theophylline by the liver in one minute. Values listed were generally determined at serum theo... |
| Half-life | of theophylline related to age and altered physiological states. For various North American patient populations from literature reports. Different rates of |
Full PK/PD text
CLINICAL PHARMACOLOGY Mechanism of Action Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). While the mechanisms of action of theophylline are not known with certainty, studies in animals suggest that bronchodilation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors. Some of the adverse effects associated with theophylline appear to be mediated by inhibition of PDE III (e.g., hypotension, tachycardia, headache, and emesis) and adenosine receptor antagonism (e.g., alterations in cerebral blood flow). Theophylline increases the force of contraction of diaphragmatic muscles. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel. Serum Concentration-Effect Relationship Bronchodilation occurs over the serum theophylline concentration range of 5-20 mcg/mL. Clinically important improvement in symptom control has been found in most studies to require peak serum theophylline concentrations >10 mcg/mL, but patients with mild disease may benefit from lower concentrations. At serum theophylline concentrations >20 mcg/mL, both the frequency and severity of adverse reactions increase. In general, maintaining peak serum theophylline concentrations between 10 and 15 mcg/mL will achieve most of the drug's potential therapeutic benefit while minimizing the risk of serious adverse events. Pharmacokinetics Overview Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. The pharmacokinetics of theophylline vary widely among similar patients and cannot be predicted by age, sex, body weight or other demographic characteristics. In addition, certain concurrent illnesses and alterations in normal physiology (See Table I ) and co-administration of other drugs (See Table II ) can significantly alter the pharmacokinetic characteristics of theophylline. Within-subject variability in metabolism has also been reported in some studies, especially in acutely ill patients. It is, therefore, recommended that serum theophylline concentrations be measured frequently in acutely ill patients (e.g., at 24-hr intervals) and periodically in patients receiving long-term therapy, e.g., at 6-12 month intervals. More frequent measurements should be made in the presence of any condition that may significantly alter theophylline clearance (see PRECAUTIONS, Laboratory Tests ). Table I. Mean and range of total body clearance and half-life of theophylline related to age and altered physiological states. For various North American patient populations from literature reports. Different rates of elimination and consequent dosage requirements have been observed among other peoples. Population Characteristics Total body clearance Clearance represents the volume of blood completely cleared of theophylline by the liver in one minute. Values listed were generally determined at serum theophylline concentrations <20 mcg/mL; clearance may decrease and half-life may increase at higher serum concentrations due to non-linear pharmacokinetics. mean (range) Reported range or estimated range (mean±2 SD) where actual range not reported. (mL/kg/min) Half-life mean (range) (hr) Age Premature neonates postnatal age 3-15 days 0.29 (0.09-0.49) 30 (17-43) postnatal age 25-57 days 0.64 (0.04-1.2) 20 (9.4-30.6) Term infants postnatal age 1-2 days NR NR=not reported or not reported in a comparable format. 25.7 (25-26.5) postnatal age 3-30 weeks NR 11 (6-29) Children 1-4 years 1.7 (0.5-2.9) 3.4 (1.2-5.6) 4-12 years 1.6 (0.8-2.4) NR 13-15 years 0.9 (0.48-1.3) NR 6-17 years 1.4 (0.2-2.6) 3.7 (1.5-5.9) Adults (16-60 years) otherwise healthy non-smoking asthmatics 0.65 (0.27-1.03) 8.7 (6.1-12.8) Elderly (>60 years) non-smokers with normal cardiac, liver, and renal function 0.41 (0.21-0.61) 9.8 (1.6-18) Concurrent illness or altered physiological state Acute pulmonary edema 0.33 Median (0.07-2.45) 19 (3.1-82) COPD->60 years, stable non-smoker >1 year 0.54 (0.44-0.64) 11 (9.4-12.6) COPD with cor pulmonale 0.48 (0.08-0.88) NR Cystic fibrosis (14-28 years) 1.25 (0.31-2.2) 6.0 (1.8-10.2) Fever associated with acute viral respiratory illness (children 9-15 years) NR 7.0 (1.0-13) Liver disease cirrhosis 0.31 (0.1-0.7) 32 (10-56) acute hepatitis 0.35 (0.25-0.45) 19.2 (16.6-21.8) cholestasis 0.65 (0.25-1.45) 14.4 (5.7-31.8) Pregnancy 1st trimester NR 8.5 (3.1-13.9) 2nd trimester NR 8.8 (3.8-13.8) 3rd trimester NR 13.0 (8.4-17.6) Sepsis with multi-organ failure 0.47 (0.19-1.9) 18.8 (6.3-24.1) Thyroid disease hypothyroid 0.38 (0.13-0.57) 11.6 (8.2-25) hyperthyroid 0.8 (0.68-0.97) 4.5 (3.7-5.6) Note: In addition to the factors listed above, theophylline clearance is increased and half-life decreased by low carbohydrate/high protein diets, parenteral nutrition, and daily consumption of charcoal-broiled beef. A high carbohydrate/low protein diet can decrease the clearance and prolong the half-life of theophylline. Absorption Theophylline (Anhydrous) Extended-Release Tablets administered in the fed state is completely absorbed after oral administration. In a single-dose crossover study, two 400 mg Theophylline (Anhydrous) Extended-Release Tablets were administered to 19 normal volunteers in the morning or evening immediately following the same standardized meal (769 calories consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat). There was no evidence of dose dumping nor were there any significant differences in pharmacokinetic parameters attributable to time of drug administration. On the morning arm, the pharmacokinetic parameters were AUC=241.9±83.0 mcg hr/mL, C max =9.3±2.0 mcg/mL, T max =12.8±4.2 hours. On the evening arm, the pharmacokinetic parameters were AUC=219.7± 83.0 mcg hr/mL, C max =9.2±2.0 mcg/mL, T max =12.5±4.2 hours. A study in which Theophylline (Anhydrous) Extended-Release 400 mg Tablets were administered to 17 fed adult asthmatics produced similar theophylline level-time curves when administered in the morning or evening. Serum levels were generally higher in the evening regimen but there were no statistically significant differences between the two regimens. MORNING EVENING AUC (0-24 hrs) (mcg hr/mL) 236.0±76.7 256.0±80.4 C max (mcg/mL) 14.5±4.1 16.3±4.5 C min (mcg/mL) 5.5±2.9 5.0±2.5 T max (hours) 8.1±3.7 10.1±4.1 A single-dose study in 15 normal fasting male volunteers whose theophylline inherent mean elimination half-life was verified by a liquid theophylline product to be 6.9±2.5 (SD) hours were administered two or three 400 mg Theophylline (Anhydrous) Extended-Release Tablets. The relative bioavailability of Theophylline (Anhydrous) Extended-Release Tablets given in the fasting state in comparison to an immediate-release product was 59%. Peak serum theophylline levels occurred at 6.9±5.2 (SD) hours, with a normalized (to 800 mg) peak level being 6.2±2.1 (SD). The apparent elimination half-life for the 400 mg Theophylline (Anhydrous) Extended-Release Tablets was 17.2±5.8 (SD) hours. Steady-state pharmacokinetics were determined in a study in 12 fasted patients with chronic reversible obstructive pulmonary disease. All were dosed with two 400 mg Theophylline (Anhydrous) Extended-Release Tablets given once daily in the morning and a reference controlled-release BID product administered as two 200 mg tablets given 12 hours apart. The pharmacokinetic parameters obtained for Theophylline (Anhydrous) Extended-Release Tablets given at doses of 800 mg once daily in the morning were virtually identical to the corresponding parameters for the reference drug when given as 400 mg BID. In particular, the AUC, C max and C min values obtained in this study were as follows: Theophylline (Anhydrous) Extended-Release Tablets 800 mg Q24h±S.D. Reference Drug 400 mg Q12h±S.D. AUC, (0-24 hours), mcg hr/mL 288.9±21.5 283.5±38.4 C max , mcg/mL 15.7±2.8 15.2±2.1 C min , mcg/mL 7.9±1.6 7.8±1.7 C max -C min diff. 7.7±1.5 7.4±1.5 Single-dose studies in which subjects were fasted for twelve (12) hours prior to and an additional four (4) hours following dosing, demonstrated reduced bioavailability as compared to dosing with food. One single-dose study in 20 normal volunteers dosed with two (2) 400 mg tablets in the morning, compared dosing under these fasting conditions with dosing immediately prior to a standardized breakfast (769 calories, consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat). Under fed conditions, the pharmacokinetic parameters were: AUC=231.7±92.4 mcg hr/mL, C max =8.4±2.6 mcg/mL, T max =17.3±6.7 hours. Under fasting conditions, these parameters were AUC=141.2±6.53 mcg hr/mL, C max =5.5±1.5 mcg/mL, T max =6.5±2.1 hours. Another single-dose study in 21 normal male volunteers, dosed in the evening, compared fasting to a standardized high calorie, high fat meal (870-1,020 calories, consisting of 33 grams protein, 55-75 grams fat, 58 grams carbohydrates). In the fasting arm subjects received one Theophylline (Anhydrous) Extended-Release 400 mg Tablet at 8 p.m. after an eight hour fast followed by a further four hour fast. In the fed arm, subjects were again dosed with one 400 mg Theophylline (Anhydrous) Extended-Release Tablet, but at 8 p.m. immediately after the high fat content standardized meal cited above. The pharmacokinetic parameters (normalized to 800 mg) fed were AUC=221.8±40.9 mcg hr/mL, C max =10.9±1.7 mcg/mL, T max =11.8±2.2 hours. In the fasting arm, the pharmacokinetic parameters (normalized to 800 mg) were AUC=146.4±40.9 mcg hr/mL, C max = 6.7±1.7 mcg/mL, T max =7.3±2.2 hours. Thus, administration of single Theophylline (Anhydrous) Extended-Release doses to healthy normal volunteers, under prolonged fasted conditions (at least 10 hour overnight fast before dosing followed by an additional four (4) hour fast after dosing) results in decreased bioavailability. However, there was no failure of this delivery system leading to a sudden and unexpected release of a large quantity of theophylline with Theophylline (Anhydrous) Extended-Release Tablets even when they are administered with a high fat, high calorie meal. Similar studies were conducted with the 600 mg Theophylline (Anhydrous) Extended-Release Tablet. A single-dose study in 24 subjects with an established theophylline clearance of ≤ 4 L/hr, compared the pharmacokinetic evaluation of one 600 mg Theophylline (Anhydrous) Extended-Release Tablet and one and one-half 400 mg Theophylline (Anhydrous) Extended-Release Tablets under fed (using a standard high fat diet) and fasted conditions. The results of this 4-way randomized crossover study demonstrate the bioequivalence of the 400 mg and 600 mg Theophylline (Anhydrous) Extended-Release Tablets. Under fed conditions, the pharmacokinetic results for the one and one-half 400 mg tablets were AUC=214.64±55.88 mcg hr/mL, C max =10.58±2.21 mcg/mL and T max =9.00±2.64 hours, and for the 600 mg tablet were AUC=207.85±48.9 mcg hr/mL, C max =10.39±1.91 mcg/mL and T max =9.58±1.86 hours. Under fasted conditions the pharmacokinetic results for the one and one-half 400 mg tablets were AUC=191.85±51.1 mcg hr/mL, C max =7.37±1.83 mcg/mL and T max =8.08±4.39 hours; and for the 600 mg tablet were AUC=199.39±70.27 mcg hr/mL, C max =7.66±2.09 mcg/mL and T max =9.67±4.89 hours. In this study the mean fed/fasted ratios for the one and one-half 400 mg tablets and the 600 mg tablet were about 112% and 1
Kenya
Brands & prices
| Brand | Company | Pack | KES |
|---|---|---|---|
| Deriphyllin | Zydus Cadila Healthcare | Standard Commercial Pack | — |
Special populations
Pregnancy & lactation
Pregnancy
Use only if potential benefit justifies potential risk; prefer agents with better reproductive data when alternatives exist.
Lactation
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.
Diet
Food & alcohol
- Drug & food interactions (label) 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 healthcare professional 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 Refer to PRECAUTIONS, Drug Interactions for further information regarding table. . Drug Type of Interaction Effect 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
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Sources & disclaimer
Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Component monographs (multi-source pipeline); Professional class pharmacology (Therapeutic agent (verify pharmacological class))
Last reviewed: 01 Aug 2026
Decision support only — not a substitute for clinical judgment, product SmPC, or Kenya STG/EML.