Brophyle SR Tablets

Acebrophylline Prolonged release Tablets

Each uncoated prolonged-release tablet contains:

Acebrophylline……………………………………. 200 mg

Excipients q.s.

Tablet 200 mg

4.1 Therapeutic indication

For the treatment of adult patients with chronic obstructive pulmonary disease (COPD) and bronchial asthma.

4.2 Posology and method of administration

Adults

Acebrophylline is administered at a recommended dose of 1 tablet once daily.

4.3 Contraindications

Hypersensitivity to xanthine derivatives like theophylline or to ambroxol.

4.4 Special warnings and precautions for use

Acebrophylline should be administered with caution in patients with hypertension, heart diseases, peptic ulcers and severe hypoxemia.

4.5 Drugs interactions

Theophylline should not be administered concurrently with other xanthine preparations and caution is required due to the interaction between theophylline and ephedrine or other sympathomimetic bronchodilators. The concomitant administration of reserpine may result in tachycardia.

4.6 Use in special populations

Pregnancy & Lactation

Although there are no clinical studies in pregnant or lactating women, Acebrophylline should be avoided in these women, unless the benefits outweigh the risks.

4.7 Effects on ability to drive and use machines

Brophyle SR Tablet does not usually affect the ability to drive.

4.8 Undesirable effects

Commonly reported adverse effects with Acebrophylline include abdominal discomfort, stomach/abdominal distension, vomiting, abdominal pain, diarrhea, constipation, heart burn, loss of appetite, esophageal bleeding, rashes, urticaria, itching, drowsiness, difficulty in breathing, leukocytosis and nasal inflammation. If chills and fever occur the drug should be immediately discontinued.

Rarely occurring adverse events include headache, occasional numbness including numbness in arm, insomnia, tachycardia, fatigue, hypertension, albuminuria, glycosuria, hypotension and occasionally hyperglycemia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

Website: http://www.zuventus.co.in/safety.aspx

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

In the event of overdose, the stomach may be emptied by gastric lavage within 2 hrs of overdose. Elimination may also be enhanced by repeated oral doses of activated charcoal. Treatment is symptomatic and supportive.

5.1 Mechanism of Action / Pharmacodynamic Properties

Acebrophylline is an airway mucus regulator with anti-inflammatory actions. It has a multimodal mechanism of action involving effects on the pulmonary surfactant, bronchial secretions, phospholipase A and Phosphodiesterases. Theophylline-7-acetate, as with other xanthine derivatives, has a bronchodilator effect due to inhibition of the intracellular phosphodiesterases, followed by an increase of cyclic adenosine monophosphate levels, which promote the relaxation of bronchial muscles. Acebrophylline produces bronchodilation by specifically inhibiting phosphodiesterase III and IV.

Acebrophylline inhibits phospholipase A, and phosphatidylcholine leading to lesser production of the powerful pro-inflammatory substances like leukotrienes and tumour necrosis factor. By inhibiting the synthesis and release of these inflammatory mediators, Acebrophylline reduces inflammation, a key factor in airway obstruction, especially in chronic forms.

Acebrophylline increases the synthesis and secretion of pulmonary surfactants by acting on two levels of surfactant synthesis: the first involving ambroxol’s established action on phosphocholine-cytidyl-transferase and the second probably because of theophylline-7 acetic acid’s action on choline-kinase.

Ambroxol modifies the mucous gel phase of secretions by decreasing the viscosity and increasing the serous gel phase. It increases the mucociliary clearance by stimulating cilia motility. Thus, it has mucoregulatory, mucosecretory as well as mucokinetic actions, thereby normalizing the quantity & quality of pulmonary secretions.

5.2 Pharmacokinetic properties

On administration of 200 mg SR oral Acebrophylline, the two components of the molecule – ambroxol and theophylline-7-acetate are released in the stomach and absorbed in the intestines, reaching optimal concentrations of ambroxol and very low levels of theophylline- 7- acetic acid.

Thus it appears that the latter is either poorly absorbed or metabolized very fast and is eliminated in a fairly short time. Its low blood levels mean it is not likely to cause the untoward effects seen after theophylline, whose therapeutic window corresponds to much higher plasma concentrations (10-20 mcg/mL). Acebrophylline reaches its peak in serum (mean Cmax 136.458 +/- 7.079 ng/mL) at 1.708 +/- 0.550 hrs.

The elimination half-life of Acebrophylline is about 6.632 +/- 0.439 hrs. The drug is metabolized in the liver and eliminated renally.

6.1 Animal Toxicology or Pharmacology

No known animal toxicology data

Acebrophylline (Ambroxol theophylline-7-acetate) is the salt obtained by reaction of equimolar amounts of ambroxol, a drug showing mucolytic and expectorant properties, and theophylline-7-acetic acid, a xanthine derivative with specific bronchodilator activity.

Acebrophylline is obtained by targeted salification of the ambroxol base [trans-4(2-amino-3, 5 dibromobenzylamino)cyclohexanol] and theophylline 7 acetic acid. The carboxyl group of theophylline-7-acetic acid is salified with ambroxol’s amine group in a stoichiometric ratio (38.7% acid and 61.3% base) that ensures, after absorption, high plasma levels of ambroxol with low levels of the xanthine derivative which are nevertheless high enough to ensure a carrier effect for ambroxol. This means that one hour after administration lung levels of ambroxol are 45% higher than in subjects treated with ambroxol alone.

Its molecular formula is C₂₂H₂₈Br₂N₆O₅ and its molecular weight is 616.3.

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on pack

8.3 Storage and handing instructions

Store below 30°C. Protect from light & moisture.

Keep out of reach of children.

• You have been prescribed Brophyle SR Tablet for prevention and treatment of asthma and chronic obstructive pulmonary disease (COPD).
• It should be taken at the same time each day, preferably in the evening after food.
• It does not work right away and should not be used to relieve sudden breathing problems. Always keep a fast-acting (rescue) inhaler with you.
• Your doctor may take regular blood test to monitor potassium level and the level of this medicine in your body.
• Notify your doctor if you have ever been diagnosed with kidney, liver or heart disease, or if you have a smoking history. Your dose may need to be adjusted.
• Do not discontinue use without consulting your doctor, even if you feel better.

16.09.2022