Fildox

Each extended-release tablet contains: Doxofylline 400 mg.
Doxofylline, a New Generation Xanthine belonging to a new class of drug referred as (Novofylline), which is chemically 1, 3-Dimethyl-3-7-dihydropurine-2, 6-dione. Its molecular formula is C₁₁H₁₁N₁O₁ and its molecular weight is 266.253 g/mol.

Pharmacology: Pharmacodynamics: Mechanism of Action: Doxofylline is a novel bronchodilator xanthine that differs from theophylline by a dioxalane group in position 7. Like theophylline, Doxofylline's mechanism of action is related to inhibition of phosphodiesterase activities. However, in contrast decreased affinity toward adenosine A1 and A2 receptors which may account for the better safety profile of the drug. Doxofylline is reported to inhibit platelet activating factor (PAF) induced bronchoconstriction and subsequent generation of thromboxane A2 (TXA2). It is also reported to inhibit PAF induced pleural exudation and generation of leukotriene C4 (LTC4) substances. This methylxanthine-induced inhibition of inflammatory response has useful action in the therapy of asthma.
Pharmacokinetics: Absorption: (A) Bioavailability: Oral, Tablets: 62.6%.
(B) Therapeutic Drug Concentration: a. Chronic Bronchitis, 8 to 20 mcg/mL.
(C) Time to Peak Concentration: Oral, tablets: 1.19 hours: a. The steady state is reached within 6 hrs at 9.43 mcg/mL.
(D) Area under the curve.
(E) 69.5 h x mcg/mL, oral administration.
Distribution: (1) Protein Binding: 48%.
(2) Distribution Half-Life: 0.19 hrs.
(3) Volume of Distribution: 1 L/kg.
Metabolism: (A) Kidney: Less than 4% of an administered dose of doxofylline is excreted unchanged in the urine.
(B) Total Body Clearance: 444 to 406 mcg/mL.
(C) Elimination Half-Life: Parent compound: 7 to 10 hrs. (Oral).

It is indicated for the treatment of bronchial asthma and pulmonary disease with spastic bronchial component.

Adults: Take tablet twice daily.
The dosage may be increased to t.i.d. according to the prescribing physician.
The dosage (800 mg/day) may be decreased according to medical prescription in the very elderly patients with concomitant cardiovascular, hepatic, renal and gastric disease to ½ tablets b.i.d.
Child: The recommended dosage of Doxofylline is 12 mg/kg daily, divided into 2 doses. In case of unsatisfactory response it can be increased up to 18 mg/kg daily under medical supervision.

Although no major arrhythmias have been documented with Doxofylline, the occurrence of major cardiac rhythm disturbances cannot be excluded in case of over dosage of xanthine compounds. If a potential oral overdose is established the patient may present 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.

Use with caution in patients with hypertension, heart disease, hypoxemia, hyperthyroidism, chronic 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 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 a patients with liver disease, in patients with congestive heart failure, in those affected with chronic obstructive pulmonary 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. Phenytoin, other anticonvulsants and smoking may cause an increase in clearance with shorter mean half-life: in these cases higher doses of doxofylline may be needed. Laboratory monitoring of plasma concentration of doxofylline is recommended in all above situations.
Use in Elderly: Use with caution in the elderly.

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

After administration, occasionally nausea, vomiting, cephalalgia (headache), irritability, insomnia, palpitations and tachycardia may occur. If a potential 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 a physician.

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

Incompatibilities: No incompatibilities reported till date.

Store at temperatures not exceeding 30°C. Store in a dry place and protect from light.

Antiasthmatic & COPD Preparations

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

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