Doxofree

Doxofylline (Doxofree) is white to off-white round, biconvex tablet, plain on both sides.
Doxofylline is a theophylline derivative which is used as a bronchodilator in reversible airways obstruction. It is given by mouth in doses of up to 1200 mg daily.
Each tablet contains: Doxofylline 400 mg.

Pharmacologic Category: Bronchodilator (Xanthine).
Pharmacology: Pharmacodynamics: Doxofylline is a methylxanthine derivative that possesses potent bronchodilator activity by inhibiting phosphodiesterase enzymes followed by an increase in cyclic-3',5' adenosine monophosphate (cAMP) resulting in smooth muscle relaxation.
Pharmacokinetics: The half-life of Doxofylline is greater than 6 hours; so, this allows effective constant plasma levels with a thrice a day dose regimen. Single dose pharmacokinetics studies in humans after oral administration defined distribution and absorption of the drug.
After administration, peak plasma levels are reached after 1 hour. Absolute bioavailability is about 62.6%; at pH 7.4, plasma proteins binding the compound are about 48%. Less than 4% of an orally administered dose is excreted unchanged in the urine.
Doxofylline is almost completely metabolized in the liver (90% of the total drug clearance). Hydroxy ethyl theophylline is the only detectable circulating metabolite of Doxofylline.
After repeated administration, Doxofylline (Doxofree) reaches the steady state in about 4 days; the elimination half-life during long-term treatment is 8-10 hours: this may decrease the hepatic clearance of xanthines, causing an increase in blood levels. No evidence of a relationship between Doxofylline (Doxofree) serum concentration and toxic events has been reported.

For the treatment of bronchial asthma and pulmonary disease with spastic bronchial component.

Adults: 1 tablet 2 or 3 times daily.
Elderly: ½ tablet 2 or 3 times daily.
Or as prescribed by the physician.

Common clinical manifestations of xanthine overdosage include nausea, vomiting, gastrointestinal bleeding, metabolic acidosis, hypokalemia, hypotension, cardiac arrhythmias, and seizures, often ending in death. Treatment of xanthine overdosage is symptomatic and supportive. It includes withdrawal of the drug. If seizures have not occurred following acute overdosage, the stomach should be emptied immediately by inducing emesis or by gastric lavage, followed by administration of activated charcoal and cathartic. If the patient is having seizures, an adequate airway should first be established and maintained. Seizures may be treated with intravenous diazepam, Phenobarbital or in combination. There is no adequate evidence to support the use of dialysis in the treatment of Doxofylline (Doxofree) overdose.

Doxofylline (Doxofree) is contraindicated in individuals who have shown hypersensitivity to its components. It is also contraindicated in patients with acute myocardial infarction, hypotension, and in lactating women.

Use with caution in patients with hypertension, heart disease, hypoxaemia, hyperthyroidism, chronic right ventricular failure, congestive heart failure, liver disease, renal disease, in those with history of peptic ulcer, and in the elderly.
Frequently, patients with congestive heart failure have markedly prolonged drug plasma levels following discontinuation of the drug.
The half-life of xanthine derivatives is influenced by a number of known variables. It may be prolonged in patients with liver disease, in patients with congestive heart failure, in those affected with Chronic Obstructive Pulmonary Disease (COPD) or concomitant infections, and in those patients taking certain other drugs (erythromycin, troleandomycin, lincomycin and other antibiotics of the same group, allopurinol, cimetidine, propranolol and anti-flu vaccine). In these cases, lower dose of Doxofylline (Doxofree) may be needed.
Use with caution in patients with hypoxemia, hyperthyroidism, liver disease, renal disease, in those with history of peptic ulcer and in elderly. Frequently, patients with Congestive Heart Failure (CHF) have markedly prolonged drug serum levels following discontinuation of doxofylline. Laboratory monitoring of plasma concentration of Doxofylline (Doxofree) is recommended in all the previously mentioned situations.

Pregnancy: Animal reproduction studies indicated that Doxofylline (Doxofree) does not cause fetal harm when administered to pregnant animals nor can affect reproduction capacity. However, since there is limited experience in human during pregnancy, xanthines should be given to pregnant women if only clearly needed.
Lactation: Doxofylline (Doxofree) is contraindicated in nursing mothers.

After xanthine administration, nausea, vomiting, epigastric pain, cephalgia (headache), irritability, insomnia, tachycardia, extrasystole, tachypnea and occasionally, hyperglycemia and albuminuria, may occur.
If a potential oral overdose is established, the patient may present with severe arrhythmias and seizure; these symptoms could be the 1st sign of an intoxication. Adverse reactions may cause the withdrawal from treatment; lower dose rechallenge may start only after the advice of a physician.

Doxofylline (Doxofree) should not be administered together with other xanthine derivatives. Toxic synergism with ephedrine has been demonstrated for xanthine. Like other xanthines, concomitant therapy with erythromycin, troleandomycin, lincomycin, clindamycin, allopurinol, cimetidine, ranitidine, propranolol and anti-flu vaccine may decrease the hepatic clearance of xanthines, causing an increase in blood levels. No evidence of a relationship between Doxofylline (Doxofree) serum concentration and toxic events has been reported.

Store at temperatures not exceeding 30°C.

Antiasthmatic & COPD Preparations

R03DA11 - doxofylline ; Belongs to the class of xanthines. Used in the systemic treatment of obstructive airway diseases.

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