APR DIANAREST (GREEN)

INFORMATION FOR THE USER

Azithromycin 250mg Tablets

Read all of this information carefully before you start taking this medicine because it contains important information for you.
• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

1. COMPOSITION:
Eachtablet contains:
Azithromycin- 250mg

For oral use only.

2. DESCRIPTION:
Azithromycin is an anti-bacterial. It belongs to the class of anti bacterials known as macrolides and is highly useful in curing bacterial infections.

3. PHARMACOLOGICAL ACTION:
Azithromycin is a macrolide antibiotic belonging to the azalide group. It binds to the 23S rRNA of the bacterial 50S ribosomal subunit. It blocks protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit.Azithromycin concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. The ratio of intracellular to extracellular concentration was >30 after 1-hour incubation. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.
4. CLINICAL PHARMACOKINETICS:
Following oral administration, the bioavailability of azithromycin is approximately 37 %. Peak plasma levels are reached after 2-3 hours after taking the medicinal product. Orally administered azithromycin is widely distributed over the whole body.Pharmacokinetic studies have shown considerably higher concentrations in the tissues (up to 50 times the maximum concentration observed in the plasma) than in the plasma. This indicates that the substance is extensively bound in the tissues.Binding to serum proteins varies according to plasma concentration and ranges from 12% at 0.5 microgram/ml up to 52% at 0.05 microgram azithromycin/ml serum. The mean volume of distribution at steady state has been calculated to be 31.1 l/kg.The terminal plasma elimination half-life follows the tissue depletion half-life of 2 to 4 days. Highconcentrations of unchanged azithromycin have been found in human bile. Also in bile, ten metabolites have been identified.Comparison of the results of liquid chromatography and microbiological analyses has shown that the metabolites of azithromycin are not microbiologically active. High concentrations of azithromycin have been found in phagocytes. It has also been established that during active phagocytosis higher concentrations of azithromycin are released from inactive phagocytes. This results in high concentrations of azithromycin being delivered to the site of infection.
5. INDICATIONS:
Azithromycin 250mg tablets are indicated for the treatment of the following bacterial infections induced by micro-organisms susceptible to azithromycin:
– Bronchitis- community-acquired pneumonia
– Sinusitis
– Pharyngitis/tonsillitis
– Otitis media
– Infections of the skin and soft tissues
– Uncomplicated genital infections due to Chlamydia trachomatis and Neisseria gonorrhoeae

6. CONTRAINDICATIONS:
The use of azithromycin is contraindicated in patients with hypersensitivity to azithromycin,erythromycin, any macrolide or ketolide antibiotic, or to any of the excipients

7. WARNINGS AND PRECAUTIONS:
Hypersensitivity:As with erythromycin and other macrolides, rare allergic reactions, including dermatologic reactions have been reported. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy should be instituted.
Hepatotoxicity: The use of azithromycin should be undertaken with caution in patients with significant hepatic disease. Cases of hepatitis potentially leading to liver failure have been reported.Azithromycin administration should be stopped if liver dysfunction has emerged.
Ergot derivatives:Because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be co-administered.
Prolongation of the QT interval:Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with other macrolides. Caution is required when treating patients:
– With congenital or documented QT prolongation
– Currently receiving treatment with other active substances known to prolong QT interval such as antiarrhythmics,cisaprideetc.
– With clinically relevant bradycardia, cardiac arrhythmia or severe cardiac insufficiency
Superinfections:As with any antibiotic preparation, observation for signs of superinfection with nonsusceptible organisms including fungi is recommended.
Clostridium difficile associated diarrhoea: Reported with use of nearly all antibacterial agents, including azithromycin, and may range in severity. CDAD must be considered in all patients who present with diarrhoea following antibiotic use.
Renal impairment:In patients with severe renal impairment (GFR <10 ml/min), increase in systemic exposure to azithromycin was observed.
Myasthenia gravis: Exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome have been reported in patients receiving azithromycin therapy.
8. ADVERSE EFFECTS:
Common adverse effects include:
– Cardiovascular: Chest pain
– Gastrointestinal: Dyspepsia, constipation, anorexia, enteritis, flatulence, gastritis, jaundice, loose stools
– Haematologic and Lymphatic: Anaemia &leucopenia
– Nervous System: Headache, hyperkinesia, dizziness, agitation, nervousness and insomnia
– General: Fever, face oedema, fatigue, fungal infection, malaise and pain
– Allergic: Rash and allergic reaction
– Respiratory: Cough increased, pharyngitis, pleural effusion and rhinitis
– Skin and Appendages: Eczema, fungal dermatitis, pruritus, sweating, urticaria and vesiculobullous rash
– Special Senses: Conjunctivitis

9. DRUG INTERACTIONS:
Antacids:Peak serum concentrations were reduced. Azithromycin and antacids should not be taken simultaneously.
Digoxinand colchicine: Increases serum levels of the P-glycoprotein substrate. Clinical monitoring& serum digoxin levels, during treatment with azithromycin & after discontinuation are necessary.
Ergot derivative:Due to the possibility of ergotism concurrent use of azithromycin with ergot derivatives is not recommended.
Ciclosporin:Caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.
Nelfinavir: Resulted in increased azithromycin concentrations.

10. DOSAGE:
Adults: 1-2 tabletsdaily.

11. ADMINISTRATION:
For oral administration only.
Azithromycin tablets are supplied for oral administration and should be swallowed whole with a sufficient quantity of liquid. Do not crush or chew the tablets.

12. STORAGE:
Do not store above 25°C. Store in the original package. Keep away from children. Do not expose to direct sunlight.

13. MANUFACTURED BY:

14. MARKETED BY:

Last revised on May 2019.