Doxosal

Uses

Doxophylline is used to treat asthma, COPD and bronchospasm.

Doxosal is also used to associated treatment for these conditions: Bronchial Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pulmonary Diseases

How Doxosal works

The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation.

The interaction of doxofylline with beta-2 adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking [A31646]. Serine 169 and serine 173 residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed [A31646]. Via mediating the actions of beta-2 adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation.

There is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study [A31646]. It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro .Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells.

Dosage

Doxosal dosage

Adult:400 mg daily in the evening. However, in certain cases, 400 mg twice daily is recommended on the basis of the clinical response. Doses as high as 1200 mg/day (400 mg 3 times daily) may also be prescribed. In elderly patients with concomitant cardiovascular, hepatic and renal diseases recommended dosage should be 200 mg twice daily.

Children (above 6 years of age):The recommended dosage of Doxophylline is 6 mg/kg twice daily. The dose may be increased up to 18 mg/kg daily on the basis of clinical response.

Dosage Type: 6 mg/kg b.i.d

• Weight of the Child: 10 kg > Dosage: 3 ml
• Weight of the Child: 15 kg > Dosage: 4.5 ml
• Weight of the Child: 20 kg > Dosage: 6 ml
• Weight of the Child: 25 kg > Dosage: 7.5 ml
• Weight of the Child: 30 kg > Dosage: 9 ml
• Weight of the Child: 35 kg > Dosage: 10.5 ml
• Weight of the Child: 40 kg > Dosage: 12 ml

Side Effects

Patients treated with Xanthine derivatives may suffer nausea, vomiting, epigastric pain, headache, irritability, insomnia, tachycardia, extrasystoles, tachypnea, and in rare cases, hyperglycemia or albuminuria.

Toxicity

Oral LD50 in rat and mouse are 965 mg/kg and 841 mg/kg, respectively. Intraperitoneal LD50 in rat and mouse are 426 mg/kg and 396 mg/kg, respectively .

Precaution

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 Doxosal.

Interaction

Doxophylline should not be administered together with other xanthine derivatives. Toxic synergism with ephedrine has been documented for xanthines. Like other xanthines, concomitant therapy with erythromycin, troleandomycin, lincomycin, allopurinol, cimetidine, ranitidine, propranolol and anti-flu vaccine may decrease the hepatic clearance of xanthines causing an increase in blood levels.

Volume of Distribution

Doxosal demonstrates a short distribution phase following intravenous administration of 100 mg given in adults with chronic bronchitis . As methylxanthines are distributed to all body compartments, doxofylline may be detected in breast milk and placenta .

Elimination Route

After repeated administrations doxofylline reaches the steady-state in about 4 days. Following oral administration of 400 mg doxofylline twice daily for 5 days in adults with chronic bronchitis, the peak plasma concentrations (Cmax) at steady state ranged from 5.78 to 20.76 mcg/mL. The time to reach maximum concentration (Tmax) was 1.19 ± 0.19 hours . The absolute bioavailability of doxofylline in healthy subjects was 63 ± 25% .

Half Life

Following administration of a single intravenous dose of 100 mg over 10 minutes in adults with chronic bronchitis, the elimination half life of doxofylline was 1.83 ± 0.37 hours. Following oral administration of 400 mg twice daily for 5 days in adults with chronic bronchitis, the mean elimination half life was 7.01 ± 0.80 hours .

Clearance

Following oral administration of 400 mg doxofylline twice daily for 5 days, the total clearance was 555.2 ± 180.6 mL/min .

Elimination Route

Less than 4% of an orally administered dose is excreted unchanged in the urine due to extensive hepatic metabolism .

Pregnancy & Breastfeeding use

Use in pregnancy: Animal reproduction studies indicate that Doxophylline 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, Doxophylline should be given to pregnant women only if clearly needed.

Use in nursing mothers: Doxophylline is contraindicated in nursing mothers.

Contraindication

This is contraindicated for individuals who have shown hypersensitivity to Doxosal and its components. It is also contraindicated in patients with acute myocardial infarction, hypotension, and in lactating women.

Acute Overdose

In case of overdose severe cardiac arrhythmias and tonic-clonic seizure may occur. These effects may represent the first signs of intoxication. The appearance of side effects may require discontinuation of the treatment which, if necessary, at the physician’s discretion, may be resumed at lower doses after all signs and symptoms of toxicity have subsided.

As there is no specific antidote, in case of overdose a symptomatic treatment of cardiovascular collapse should be instituted.

Storage Condition

Store at room temperature (not exceeding 25°C). Store in cool and dry place, protected from light.

Innovators Monograph

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