Doxofylline is a new generation xanthine derivative that has a dioxolane group at the N-7 position of its chemical structure. Doxofylline inhibits phosphodiesterase activities. Moreover, Doxofylline appears to have less affinity towards adenosine A1 and A2 receptors which is account for the better safety profile of the drug. Doxofylline also inhibits platelet-activating factor and the generation of leukotrienes.
Doxofylline
Pharmacology of Doxofylline
Doxofylline is a new generation xanthine derivative that has a dioxolane group at the N-7 position of its chemical structure. Doxofylline inhibits phosphodiesterase activities. Moreover, Doxofylline appears to have less affinity towards adenosine A1 and A2 receptors which is account for the better safety profile of the drug. Doxofylline also inhibits platelet-activating factor and the generation of leukotrienes. Doxofylline also has antitussive and bronchodilator effects and acts as a phosphodiesterase inhibitor.
Indication of Doxofylline
Doxofylline is mostly administered for maintenance treatment in subjects experiencing
COPD (Chronic Obstructive Pulmonary Disease) and bronchial asthma.
Doxofylline is not designed for use as an emergency treatment during an asthma attack.
Doxofylline offers
In COPD, effectively reduces exacerbations
In asthma, provides better symptom control
No effect on sleep pattern and awakenings
Safe for cardiac patients
Lesser effect on gastric secretion
Better patient compliance
Dosage and administration of Doxofylline
Adult dose: 400 mg (1 tablet) 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 Doxofylline 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
Dosage Type: Total Daily Dose
Weight of the Child: 10 kg > Dosage: 6 ml Weight of the Child: 15 kg > Dosage: 9 ml Weight of the Child: 20 kg > Dosage: 12 ml Weight of the Child: 25 kg > Dosage: 15 ml Weight of the Child: 30 kg > Dosage: 18 ml Weight of the Child: 35 kg > Dosage: 21 ml Weight of the Child: 40 kg > Dosage: 24 ml
Doxofylline may be taken with or without food.
Adverse effects of Doxofylline
After xanthine administration, nausea, vomiting, epigastric pain, cephalalgia, irritability, insomnia, tachycardia, 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 of treatment; a lower dose rechallenge may start only after the advice of a physician.
Contraindications of Doxofylline
Individuals who have shown hypersensitivity to Doxofylline. Patients with acute myocardial infarction and hypotension.
In Lactation use of Doxofylline
Doxofylline is contraindicated in nursing mothers.
In Pregnancy use of Doxofylline
Animal reproduction studies indicate that doxofylline does not cause fetal harm when administered to pregnant animals or 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.
Special Precaution of Doxofylline
The t ½ 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 (CHF), 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. Phenytoin, other anticonvulsants, and smoking may cause an increase in clearance with a shorter mean t ½.
In these cases, higher doses of doxofylline may be needed. Use with caution in patients with hypoxemia, hyperthyroidism, liver disease, renal disease, in those with a history of peptic ulcer, and in the elderly. Frequently, patients with CHF have markedly prolonged drug serum levels following discontinuation of doxofylline.
Drug Interactions of Doxofylline
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 the anti-flu vaccine may decrease the hepatic clearance of xanthines causing an increase in blood levels.
Overdosages of Doxofylline
Although no major arrhythmia has been documented with Doxofylline tablets, the occurrence of major cardiac rhythm disturbances cannot be excluded in the 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 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 principle should be instituted according to symptomatic relief of cardiocirculatory shock. Doxofylline tablets do not cause any risk of tolerance or addiction.
