Theophylline information from DrugsUpdate
L - Caution when used during lactation
FI - Food *
LI - Lab *
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side-effects, these drugs are now rarely administered for clinical use. As a member of the xanthine family, it bears structural and pharmacological similarity to caffeine. It is naturally found in tea, although in trace amounts (~1 mg/L), significantly less than therapeutic doses. It is found also in cocoa beans. Amounts as high as 3.7 mg/g have been reported in Criollo cocoa beans.
Theophylline competitively blocks phosphodiesterase which increases cAMP tissue concentrations causing bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric acid secretion.
Rapid and completely absorbed following oral and rectal (enemas) administration, slow after rectal (suppositories) and IM administration. Food delays rate but not extent of absorption. Peak serum concentrations: 1-2 hours (liquid, capsules or uncoated tablets); 4 hours (modified-release preparations).
Rapidly distributed throughout extracellular fluids and body tissues. Crosses the placenta and enters breast milk. Protein binding: 40%.
Hepatic metabolism via cytochrome P450 isoenzyme CYP1A2, CYP2E1 and CYP3A3. Serum half-life: 6-12 hours (healthy, non-smoking asthmatic adult); 1-5 hours (children); 4-5 hours (cigarette smokers); 10-45 hours (neonates and premature infants).
Via urine as metabolites and unchanged drug; small amount via faeces as unchanged drug
Nausea, vomiting, abdominal pain, diarrhoea, headache, insomnia, dizziness, anxiety, restlessness, tremor, palpitations.
Potentially Fatal: Convulsions, cardiac arrhythmias, hypotension and sudden death after too rapid IV injection.
Frequently monitor theophylline levels in elderly patients and smokers, as well as in patients with hepatic or renal impairment. Determine appropriate theophylline concentrations before making a dose increase as follows: determine whether the plasma concentration is subtherapeutic in a patient who continues to be symptomatic; whenever signs or symptoms of theophylline toxicity are present; and whenever there is a new illness, worsening of an existing concurrent illness, or a change in the treatment regimen.
Nausea, vomiting, diarrhoea, agitation, tremor, hypertonicity, hyperventilation, diuresis and repeated vomiting (sometimes haematemesis), cardiac arrhythmias including tachycardia, hypotension, electrolyte disturbances including hypokalaemia, hyperglycaemia, hypophosphataemia, hypercalcaemia, metabolic acidosis, respiratory alkalosis and convulsions. Other reported effects include dementia, toxic psychosis, symptoms of acute pancreatitis, rhabdomyolysis with renal failure and acute compartment syndrome. Empty stomach by lavage if within 2 hr of overdose, with repeated oral doses of activated charcoal and osmotic laxative, especially if modified-release tablets taken. Symptomatic and supportive treatment with monitoring of serum theophylline concentrations. Non-selective βblockers to be used in non-asthmatic patient for tachycardia, IV diazepam or a barbiturate to control convulsions, disopyramide may be used in patients with both ventricular arrhythmias and convulsions. In severe cases, general anaesthesia and neuromuscular blockade with ventilation may be needed. Charcoal haemoperfusion or haemodialysis may be helpful especially in CHF or liver disease.
Admin IV injection very slowly to avoid direct stimulation of the CNS and CVS. Cardiac failure, hypertension, epilepsy, hyperthyroidism, history of peptic ulcer disease, renal or hepatic dysfunction, glaucoma, DM, severe hypoxaemia, chronic alcoholism, acute febrile illness. On influenza immunization or active influenza infection, COPD and cor pulmonale. Smokers may need higher dose. Pregnancy, lactation, children and elderly.
Other xanthines. Theophylline clearance reduced by high dose allopurinol, some antiarrhythmics, cimetidine, disulfiram, propranolol, methotrexate, aciclovir, mexiletine, pentoxifylline, tacrine, ticlopidine, fluvoxamine, interferon-α, macrolide antibiotics, quinolones, oral contraceptives, thiabendazole and viloxazine. Theophylline clearance increased by phenytoin, anticonvulsants, ritonavir, rifampicin, sulfinpyrazone, aminoglutethimide, barbiturates, ipriflavone, cigarette smoking. Concurrent use decreased lithium, alprazolam levels. Increased risk of arrhythmias with ephedrine, sympathomimetic, general anaesthetics. Increased heart rate with tadalafil.
St John's wort may increase theophylline levels. Avoiding giving enteral feed for 1 hour before or after theophylline to prevent reduction in theophylline levels.
Adult: As conventional tablet: 5 mg/kg every 6-8 hours.
Child: As conventional tablet: 5 mg/kg every 4-6 hours.
Hepatic impairment: Dose adjustment needed.
Adult: As conventional dosage form: 300-1000 mg in divided doses, every 6-8 hours daily. As modified-release preparations: 175-500 mg every 12 hours. Rate of absorption of modified released preparations varies for different brands.
Child: <2 years: Not recommended; 2-6 years: ¼ the adult dose; 20-35 kg (about 6-12 years old): ½ the adult dose. Rate of absorption of modified released preparations varies for different brands.
Hepatic impairment: Dose adjustment needed.
Apnoea in infants
Child: Initial dose in neonates: ≤24 days: 1 mg/kg every 12 hours; >24 days: 1.5 mg/kg every 12 hours. Full-term infants: initial daily dosage calculated based on formula, given in 3-4 divided doses: daily dose (mg/kg) = (0.2 X age in weeks) + 5.0. If loading dose is needed, 5 mg/kg (or in those already on theophylline, 1 mg/kg for each 2 mcg/ml increase in serum-theophylline concentration).
Adult: Patients who are not taking theophylline or other xanthine medication: 4-5 mg/kg as loading dose by IV infusion over 20-30 minutes followed by maintenance: 0.4 mg/kg/hours.
Child: Patients who are not taking theophylline or other xanthine medication: 4-5 mg/kg as loading dose by IV infusion over 20-30 minutes, followed by maintenance dose: 1-9 years: 0.8 mg/kg/hours; >9 years: 0.6-0.7 mg/kg/hours.
Hepatic impairment: Dose adjustment needed.
Reduce dose in patients with cor pulmonale, heart failure, liver disease and in the elderly. Increase maintenance dose for smokers.
May be taken with or without food. (May be taken with meals to reduce GI discomfort. Some individual prep must be taken with meals or on an empty stomach. Refer to monographs for individual formulations.)
List of Contraindications
Caution when used during pregnancy
Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Caution when used during lactation
Safe and effective for the approved indications in children.
Elderly patients are at increased risk of experiencing serious theophylline adverse reactions and toxicity compared with younger patients because of pharmacodynamic and pharmacokinetic changes associated with aging.
Hypersensitivity to xanthine derivatives, porphyria.
May cause false positive elevations of serum uric acid (by Bittner or colorimetric method) and increase in urinary catecholamines. Serum theophylline concentrations may be falsely elevated by furosemide, sulfathiazole, phenylbutazone, probenecid, theobromine, caffeine-containing beverages, chocolate and paracetamol if measured by spectrophotometric methods. Theophylline can inhibit the effects of adenosine infusions used in conjunction with radionuclide myocardial imaging, if not withheld 12-24 hours before procedure; reduces the diagnostic accuracy of myocardial imaging using dipyridamole.
Available brands of Theophylline
- Agrophyllin (Argon)
- Alergin (Cipla)
- Asmapax Depot (AHPL)
- Asmatide-BR (Systopic)
- Biryth (Emcure)
- Broncordil (USV)
- Broncordil Xl (USV (Corvette))
- Cadiphylate (Cadila)
- Delin (Ind- Swift)
- Delin Tab (Ind- Swift)
- Dericip (Cipla)
- Deriphyllin (Zy. Cad (G.Rem))
- Deriphyllin OD (Zydus (G. Rem))
- Deriphyllin Retard 150 (Zy. Cad (G.Rem))
- Deriphyllin Retard 300 (Zy. Cad (G.Rem))
- Deriphyllin SYR (Zydus (G. Rem))
- Deriphyllin TAB (Zy. Cad (G.Rem))
- Deriphylline Retard 450 (Zy. Cad (G.Rem))
- Deripil (PIL)
- Deripil Retard (PIL)
- Duralyn-CR (Raptakos)
- Etophylate (Walter Bushnell)
- Glophyllin (Global MS (Intraways))
- Intaphylline (Intas)
- Lontif (Strassenburg)
- Lungfyl-SR (Yash Vision)
- Marax (Unimed)
- Multimix (Indo French Labs)
- OD Phyllin (Sun)
- Phylobid (Wockhardt (Tridoss))
- Phyloday (Wockhardt)
- Relasmin (Tablets)
- Respiphylline Inj (Haffkine)
- Slowthylline (Duckbill)
- T R Phyllin (Sun (Solares))
- T R Phyllin Inj (Sun (Solares))
- Tedral (Pfizer)
- Tedral-SA (Pfizer)
- Theo PA (GSK)
- Theo-SR (Alembic)
- Theobid (Cipla (Protec))
- Theobus (Globus Remedies)
- Theocort (Zydus Cadila)
- Theoday (Cipla (Protec))
- Theoder (Sun)
- Theofil (Intra (Invision))
- Theoped (Cipla (Protec))
- Theophylline (Intra Labs)
- Theoresp (Life Medicare)
- Theostan-CR (Ranbaxy (Stancare))
- Thp-1 (Kee Pharma)
- TR Phyllin (Sun)
- TSR (Bestochem)
- Unicontin-E (Modi Mundi)
- Vent-T (Kopran (Kresp))
- Zomont Theo (Panacea)
- Zytho (Arrowin)
Theophylline brands in India
Deriphyllin Retard 150
Deriphyllin Retard 300
Deriphylline Retard 450
T R Phyllin
T R Phyllin Inj