Each capsule contains 200 mg of theophylline. Theophylline (3, 7-dihydro-1,3-dimethyl-1-H-purine-2,6-dione) is a xanthine bronchodilator.
Pharmacology: Theophylline directly relaxes the smooth muscle of the bronchial airway and pulmonary blood vessels, thus acting mainly as a bronchodilator and smooth muscle relaxant. It has also been demonstrated that aminophylline has a potent effect on diaphragmatic contractility in normal persons and may then be capable of reducing fatigability and thereby improve contractility in patients with chronic obstructive airway disease. Theophylline is also a central respiratory stimulant.
For many years, the proposed main mechanism of action of the xanthines was inhibition of phosphodiesterase, which results in an increase in cyclic adenosine monophosphate (cAMP). However, this effect is negligible at therapeutic concentrations. Other effects that appear to occur at therapeutic concentrations and may collectively play a role in the mechanism of xanthines including inhibition of extracellular adenosine (which causes bronchoconstriction), stimulation of endogenous catecholamines, antagonism of prostaglandins, PGE2 and PGF2, direct effect on mobilization of intracellular calcium resulting in smooth muscle relaxation and β-adrenergic agonist activity on the airways.
Pharmacokinetics: Absorption: Theophylline is completely absorbed after oral administration. After administration of 400 mg Duralyn-CR, mean peak plasma concentrations of about 4.65 mcg/mL were reached at a mean of 3.83 hrs. The area under the plasma curve (AUC) is 56.64 mcg·hr/mL.
Distribution: Average volume of distribution is 0.45 L/kg (range 0.3-0.7 L/kg). Theophylline does not distribute into fatty tissue, but readily crosses the placenta and is excreted into breast milk. Approximately 40% are bound to plasma proteins.
Metabolism and Excretion: Xanthines are biotransformed in the liver (85-90%) to 1,3-dimethyluric acid, 3 methylxanthine and 1-methyluric acid. Excretion is by the kidneys; <15% of the drug is excreted unchanged. The half-life of theophylline is influenced by a number of known variables. It may be prolonged in chronic alcoholics, particularly those with liver disease (cirrhosis or alcoholic liver disease), in patients with congestive heart failure, and in patients taking certain other drugs. In cigarette smokers (1-2 packs/day), the mean half-life is much shorter than in non-smokers. The increase in clearance associated with smoking is presumably due to stimulation of the hepatic metabolic pathway by components of cigarette smoke.
Symptomatic relief or prevention of bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema.
Adults: 1 cap daily, preferably between 6-8 PM (because of circadian rhythm).
Symptoms: Anorexia, nausea, vomiting, nervousness, insomnia, agitation, irritability, headache, tachycardia, extrasystoles, tachypnea and tonic/clonic convulsions.
Treatment: If Seizure has not Occurred: Induce vomiting, even if emesis has occurred spontaneously. However, do not induce in patients with impaired consciousness.
If Seizures Occur: Establish an airway and administer oxygen. Administer IV diazepam 0.1-0.3 mg/kg up to 10 mg. Monitor vital signs, maintain blood pressure and provide adequate hydration.
Post-Seizure Coma: Maintain airway and oxygenation. Perform intubation and lavage instead of inducing emesis. Introduce the cathartic and activated charcoal via a large bore gastric lavage tube. Provide full supportive care and adequate hydration while the drug is metabolized. If repeated, oral activated charcoal is inactive, a charcoal hemoperfusion may be indicated.
Hypersensitivity to any xanthine; peptic ulcer; underlying seizure disorders (unless receiving appropriate anticonvulsant medication).
Status asthmaticus is a medical emergency and is not rapidly responsive to usual doses of conventional bronchodilators. Oral theophylline products alone are not appropriate for status asthmaticus.
Toxicity: Excessive doses may cause severe toxicity. Incidence of toxicity increased significantly at serum levels >20 mcg/mL. Serum levels >20 mcg/mL are rarely found after appropriate administration of recommended doses. However, in patients in whom theophylline plasma clearance is reduced for any reason (eg, hepatic function impairment; patients >55 years, particularly males and those with chronic lung disease; cardiac failure and sustained high fever), even conventional doses may result in increased serum levels and potential toxicity. Serious side effects eg, ventricular arrhythmias, convulsions or even death may appear as the 1st sign of toxicity without any previous warning. Less serious signs of toxicity (eg, nausea) may occur frequently when initiating therapy, but are usually transient; when such signs are persistent during maintenance therapy, they are often associated with serum concentrations >20 mcg/mL.
Cardiac Effects: Theophylline may cause dysrhythmias or worsen preexisting arrhythmias. Any significant change in cardiac rate or rhythm warrants monitoring and further investigation.
Theophylline should not be administered concomitantly with other xanthines. Use with caution in patients with hyperemia, hypertension, cardiac disease, congestive heart failure, alcoholism, elderly patients and patients with history of peptic ulcer. Theophylline may occasionally acts as a local irritant to the gastrointestinal tract when administered orally, although gastrointestinal symptoms are more commonly centrally mediated and associated with serum drug concentrations >20 mcg/mL.
Use in pregnancy: It is not known whether theophylline can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. There are no adequate and well-controlled studies in pregnant women. Theophylline should only be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: Theophylline is distributed into breast milk and may cause irritability or other signs of toxicity in nursing infants. Because of the potential for serious adverse reactions in nursing infants from theophylline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Use in children: Safety and effectiveness in children <12 years have not been established with Duralyn-CR.
Use in pregnancy: It is not known whether theophylline can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. There are no adequate and well-controlled studies in pregnant women. Theophylline should only be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in lactation: Theophylline is distributed into breast milk and may cause irritability or other signs of toxicity in nursing infants. Because of the potential for serious adverse reactions in nursing infants from theophylline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Adverse reactions/toxicity are uncommon at serum theophylline levels <20 mcg/mL. The most consistent adverse reactions are due to overdosage.
Gastrointestinal: Nausea, vomiting, epigastric pain, diarrhoea.
Central Nervous System: Headache, irritability, insomnia, muscle twitching, clonic and tonic generalized convulsions.
Cardiovascular System: Palpitation, tachycardia, extrasystoles, flushing, hypotension, ventricular arrhythmias.
Respiratory: Tachypnea.
Renal: Potentiation of diuresis.
Others: Alopecia, rash.
Agents that decrease theophylline levels include barbiturates, charcoal, ketoconazole, rifampin, smoking and sulfinpyrazone. Agents that increase theophylline levels include allopurinol, β-blockers (nonselective), calcium-channel blockers, cimetidine, oral contraceptives, corticosteroids, disulfiram, ephedrine, interferon, macrolides and quinolones.
Protect from heat and humidity.
R03DA04 - theophylline ; Belongs to the class of xanthines. Used in the systemic treatment of obstructive airway diseases.
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