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Puroxan

Puroxan

doxofylline

Manufacturer:

Eurodrug

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Doxofylline.
Description
Each tablet contains Doxofylline - 400 mg.
Action
Therapeutic Properties: Doxofylline is a bronchodilator classified as a xanthine derivative.
Doxofylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels; main action is bronchodilation and anti-spasmodic; also contains anti-inflammatory properties.
Pharmacology: Pharmacodynamics: Doxofylline did not antagonise adenosine A1, A2B and A3 receptors; there was only a modest inhibition at the highest tested concentration (104 M) against A2A receptors. This may explain the improved tolerability profile of doxofylline in comparison with other xanthine based medicines.
Doxofylline does not inhibit any of the PDE enzyme subtypes, except a modest inhibition at the highest tested concentration (104 M) against PDE2A1. Lacks effect on PDE3, thus no vasodilation and cardiac effects.
Doxofylline does not exert any significant inhibitory effect against any of the 11 HDAC enzymes.
Doxofylline significantly inhibited the migration of neutrophils and the release of IL-6 and TNF-α into the lung lumen, demonstrating the anti-inflammatory action of doxofylline.
Clinical Data: Proven efficacy in Asthma and COPD. In a multicenter, randomized clinical trial, 139 COPD patients received Doxofylline 400 mg b.i.d. or Theophylline 250 mg b.i.d. for 28 days. Doxofylline is as effective as Theophylline in reducing spirometic parameters (p<0.001 for all tests). Doxofylline significantly decreased the daily use of Salbutamol inhaler (p<0.001 for both drugs). Doxofylline had significantly fewer adverse events than patients treated with Theophylline (Melillo et al, 1989).
The pooled-analysis of 483 asthma patients demonstrated that both doxofylline 400 mg and theophylline 250 mg significantly increased FEV1, reduced the rate of asthma events and use of salbutamol to relieve asthma symptoms compared to placebo (p<0.01). No significant differences between doxofylline 400 mg and theophylline 250 mg.
Doxofylline 400 mg did not significantly (p>0.05) increase the risk of AEs compared to placebo, risk of AEs was significantly higher in theophylline 250 mg group (p<0.05) compared to placebo (Calzetta et al, 2018).
In a RCT performed in the USA, 263 patients with chronic reversible bronchial asthma received Doxofylline 400 mg t.i.d., Theophylline 250 mg t.i.d. or placebo for 12 weeks. Doxofylline was as effective as Theophylline. Doxofylline was better tolerated than Theophylline, significantly more patients had to interrupt treatment with Theophylline because of AEs (p=0.001). Doxofylline significantly reduced the number of daily asthma attacks (p<0.05) (Goldstein et al, 2002).
Meta-analysis data obtained from 998 COPD patients. When coupling relative effects for efficacy and safety, doxofylline appeared to be superior in safety and efficacy compared to all other Xanthines (Aminophylline, Bamiphylline and Theophylline) (Cazzola et al, 2018).
Pharmacokinetics: The half-life of Doxofylline is greater than six hours; allows effective constant plasma levels with a t.i.d. dose regimen. ADME principles defined in Single dose pharmacokinetic studies in man after oral and IV administration. Doxofylline followed bi-compartmental model, mean half-life after i.v. was 65 min.
After oral administration, peak plasma levels reached after one hour. Absolute bioavailability is about 62.6%. Less than 4% is excreted through urine unchanged; almost completely metabolized in the liver (<90% drug clearance).
Following repeated administration Doxofylline reaches the steady-state after app. 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/Uses
Puroxan is indicated for the treatment of bronchial asthma and Chronic Obstructive Pulmonary Disease (COPD) associated with bronchospasm.
Dosage/Direction for Use
Adults: 1 tablet (400 mg) 2 times daily.
The dosage may be increased to three times daily according to the prescribing physician.
Mode of Administration: Puroxan tablets should be swallowed whole with sufficient amounts of liquid (approximately ½ a glass).
Overdosage
Although no major arrhythmias have been documented with doxofylline, 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 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.
Contraindications
This product 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.
Special Precautions
The half-life of Doxofylline 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.
Use with caution in patients with hypertension, heart disease, hypoxemia, hyperthyroidism, chronic right ventricular failure, 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.
Doxofylline does not cause any risk of tolerance or addiction.
The safety and efficacy of Puroxan tablet is not established in children < 18 years old.
Use In Pregnancy & Lactation
Animal reproduction studies indicate that Doxofylline does not cause foetal 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.
Adverse Reactions
After administration occasionally nausea, vomiting, headache, irritability, insomnia, palpitations and tachycardia may occur.
Drug Interactions
Doxofylline should not be administered together with other xanthine derivatives, including beverages and foods containing excessive amounts of caffeine. Toxic synergism with ephedrine has been documented for xanthines.
Concomitant therapy with erythromycin, troleandomycin, lincomycin, clindamycin, and other antibiotics of the same group, allopurinol, propranolol, digoxin and anti-flu vaccine may decrease the hepatic clearance of xanthines causing an increase in blood levels. A lower dose of Doxofylline may be needed.
Phenytoin, other anticonvulsants and smoking may cause an increase in clearance with a 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 the previously mentioned situations.
Storage
Store below 30°C.
Shelf Life: 36 Months.
MIMS Class
Antiasthmatic & COPD Preparations
ATC Classification
R03DA11 - doxofylline ; Belongs to the class of xanthines. Used in the systemic treatment of obstructive airway diseases.
Presentation/Packing
Tab 400 mg (white, round, scored with smooth surface) x 2 x 10's.
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