FORMULATION

Each tablet contains:

Doxofylline……………………………200 mg

Doxofylline……………………………400 mg

MECHANISM OF ACTION

Doxofylline is chemically designated as 7-(1, 3-dioxolar-2-ylmethyl)-theophylline. It differs from theophylline by the presence of a dioxolone group in position 7. The mechanism of action is similar to that of theophylline. However, unlike theophylline, Doxofylline has greatly decreased affinity towards adenosine A1 and A2 receptors which explain its better safety profile. Moreover; it does not interfere with calcium influx into the cells nor antagonize calcium channel blockers. In experimental studies, Doxofylline has been shown to be a more potent bronchodilator with fewer side effects than theophylline. In mechanically ventilated patients with acute respiratory failure, it results in rapid and efficient bronchodilation, thus decreasing the airway resistance.

PHARMACOKINETICS

After oral administration, peak plasma levels were reached after one hour. Absolute bioavailability is about 62.6%; at pH 7.4 plasma proteins binding the compound is 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). Hydroxyethyltheophylline is the only detectable circulating metabolite of Doxofylline.

After repeated administrations Doxofylline reaches the steady-state in about 4 days; the elimination half-life during long-term treatment is 8-10 hours: this allows a twice daily dose regimen. No accumulation of the drug was noted after one week of treatment.

INDICATIONS

Doxofylline is indicated for the treatment of bronchial asthma, pulmonary disease with spastic bronchial component and Chronic Obstructive Pulmonary Disease (COPD).

CONTRAINDICATIONS

This product is contraindicated in individuals who have shown hypersensitivity to its components. It is also contraindicated in patients with acute myocardial infarction, gipotenzia arterial (hypotension), arrhythmia, duodenal ulcer, epilepsy, convulsion and in lactating and pregnant women.

ADVERSE EFFECTS

After xanthine administration, nausea, vomiting, epigastric pain, headache, cephalalgia, 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 first sign of intoxication. Adverse reactions may cause the withdrawal from treatment; a lower dose rechallenge may start only after the advice of physician.

WARNINGS & PRECAUTIONS

Use with caution in patients with hypertension, heart disease, hypoxemia, hyperthyroidism, chrome right ventricular failure, congestive heart failure, liver disease, renal disease, in those with history of peptic ulcer and in elderly. Frequently, patients with congestive heart failure have markedly prolonged drug serum 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 lung disease 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, a lower dose of Doxofylline may be needed. Phenytoins, other anti-convu lsants and smoking may cause an increase in clearance with a shorter mean half-life: in these cases higher doses of Doxofylline may be needed.

USE IN PREGNANCY AND LACTATION

Animal reproduction studies indicate that Doxofylline does not cause fetal harm when administered to pregnant animals nor can affect reproduction capacity. However, since there is limited experience in humans during pregnancy, xanthines should be given to a pregnant woman only if clearly needed. Doxofylline is contraindicated in nursing mothers.

DOSAGE AND ADMINISTRATION

Elderly Patients: 200 mg tablet two or three times daily.
Adults: 400 mg tablet two or three times daily. Or as prescribed by the physician.

DRUG INTERACTIONS

Doxofylline should not be administered together with other xanthine derivatives, including beverages and foods containing caffeine.

Toxic synergism with ephedrine has been documented for xanthines.

Concomitant therapy with erythromycin, troleandomycin, lincomycin, clindamycin, allopurinol, cimetidine, propranolol and anti-flu vaccine may decrease the hepatic clearance of xanthines causing an increase in blood levels.

OVERDOSAGE

Although no major arrhythmias have been documented with Doxofylline tablets the occurrence of major cardiac rhythm disturbances cannot be excluded in case of overdosage of xanthine compounds. If a potential oral overdose is established the patient may present with seizures; these symptoms could be the first sign of intoxication. Adverse reactions may cause the withdrawal from treatment. A lower dose-re-challenge may start only after the advice of the physician.

There is no specific antidote. It is suggested that the management principles should be instituted according to a symptomatic relief of cardio circulatory shock. Doxofylline tablets does not cause any risk of tolerance or addiction.

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.

STORE AT TEMPERATURES NOT EXCEEDING 30ºC. Protect from light.

AVAILABILITY

Doxofylline (Maxivent) 200mg Tablet X Alu PVC/PVDC blister pack of 10’s, box of 30 tablets

Doxofylline (Maxivent) 400mg Tablet X Alu PVC/PVDC blister pack of 10’s, box of 30 tablets