COMPOSITION:

Clariva -250: Each film coated tablet contains clarithromycin USP 250 mg.

PHARMACOLOGICAL ACTION:

Clarithromycin is a new macrolide antibiotic. It exerts its antibacterial activity by means of inhibition of protein synthesis, linking to the 50S ribosomal subunit of susceptible bacteria. Clarithromycin is highly potent against a wide variety of aerobic and anaerobic, gram-positive and gram-negative organisms.

CONTRAINDICATIONS:

-           Clariva is contra-indicated in patients with known hypersensitivity to macrolide antibiotic drugs.

-           It is also contraindicated in patients with severe liver insufficiency. Clariva and ergot  derivatives should not be co-administered.

WARNINGS AND PRECAUTIONS:

Clarithromycin is principally excreted by the liver and kidney. Caution should be exercised in administering this antibiotic to patients with impaired hepatic or renal function and to elderly patients (> 65 years). Prolonged or repeated use of Clariva may result in an overgrowth of non susceptible bacteria or fungi. If super-infection occurs, Clariva should be discontinued and appropriate therapy instituted. H. pylori organisms may develop resistance to clarithromycin in a small number of patients.

USAGE DURING PREGNANCY & LACTATION: 

Its safety during pregnancy & lactation has not been established.

DRUG INTERACTIONS:

Clariva has been shown not to interact with oral contraceptives. As with other macrolide antibiotics, the use of clarithromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system (eg. warfarin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporin and tacrolimus) may be associated with elevations in serum levels of these drugs. Rhabdomyolysis, coincident with the co-administration of clarithromycin and lovastatin or simvastatin has been reported. The administration of Clariva to patients who are receiving theophylline has been associated with increased serum theophylline levels and potential theophylline toxicity. The use of Clariva in patients receiving warfarin may result in potentiation of the effects of warfarin. Prothrombin time should be frequently monitored in these patients. The effects of digoxin may be potentiated with concomitant administration of Clariva. Monitoring of serum digoxin levels should be considered. Macrolides have been reported to alter the metabolism of terfenadine, cisapride and pimozide resulting in increased plasma levels of these drugs. This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsade de pointes. Similar effects have been observed with concomitant administration of astemizole and other macrolides. Clariva may potentiate the effects of carbamazepine due to a reduction in the rate of excretion. Simultaneous oral administration of Clariva tablets and zidovudine to HIV infected adults may result in decreased steady state zidovudine levels. This can be largely avoided by staggering the doses of Clariva and zidovudine by 1-2 hours. No such reaction has been reported in children. Ritonavir increases the area under curve (AUC), Cmax and Cmin of clarithromycin when administered concurrently. Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. However, for patients with renal  impairment,  the following dosage adjustment should be considered: For patients with CLCR 30 to 60 ml/ min the dose of clarithromycin should be reduced by 50%. For patients with CLCR < 30 ml/ min the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin greater than 1g/day should not be co-administered with ritonavir. Although total plasma concentrations of clarithromycin and omeprazole may be increased when they are administered concurrently, no adjustment to the dosage is necessary. At the dosages recommended, there is no clinically significant interaction between clarithromycin and lansoprazole. Increased plasma concentrations of clarithromycin may also occur when it is co-administered with Maalox or Ranitidine. No adjustment to the dosage is necessary.

INDICATIONS:

Clariva is used in the treatment of infections caused by the following pathogens which are sensitive to Clarithromycin:

Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Neisseria gonorrheae, Listeria monocytogenes, Legionella pneumophila, Mycoplasma pneumoniae, Helicobacter pylori, Campylobacter jejuni, Chlamydia trachomatis, Moraxilla (Branhamella) catarrhalis, Bordetella pertussis, Staphylococcus aureus, Propionibacterium acnes, Mycobacterium avium, M. leprae, M. kansasii, M. chelonae, M. fortuitum, M. intracellulare.

Clariva is indicated in the treatment of:

-           Infections of upper respiratory tract as: pharyngitis, tonsillitis, sinusitis and otitis   media.

-           Infections of the lower respiratory tract as: bronchitis, bacterial pneumonia and atypical pneumonia.

-           Skin infections: impetigo, erysipelas, folliculitis, furunculosis and septic wounds.

-           Helicobacter pylori infection when used in combination with omeprazole or and amoxicillin as dual or triple therapy.

DOSAGE AND ADMINISTRATION:

Clarithromycin recommended dosage in adults is one 250 mg tablet every 12 hours. In cases of severe infections, dosage can be increased up to 500 mg every 12 hours. Administration must be continued, according to severity of infection up to 6-14 days.

In patients with renal impairment with creatinine clearance less than 30 ml/min, the dosage should be reduced by one-half. Dosage should not be continued beyond 14 days in these patients.

For Helicobacter pylori infections, as dual therapy clarithromycin 500 mg three times a day with omeprazole 40 mg once daily for two weeks or as triple therapy clarithromycin 500 mg, omeprazole 20 mg and amoxicillin 1 g, all twice a day for one week are recommended.

OVERDOSAGE:

In case high dosages of clarithromycin have been ingested, G.I. disturbances can occur. A systemic reaction can also follow, to be readily treated by means of gastric lavage and supportive measures. Providing that clarithromycin cannot be removed by haemodialysis or peritoneal dialysis, a rapid action is needed aimed to eliminate the amount of drug not yet absorbed, applying at the same time a suitable symptomatic therapy.

SIDE EFFECTS:

Side effects reported include nausea, dyspepsia, diarrhoea, vomiting, abdominal pain and paraesthesia. Stomatitis, glossitis, oral monilia and tongue discoloration have been reported. Other side effects include headache, arthralgia, myalgia, and allergic reactions ranging from urticaria, mild skin eruptions and angioedema to anaphylaxis and rarely Stevens-Johnson syndrome / toxic epidermal necrolysis. Reports of alteration of the sense of smell, usually in conjunction with taste perversion have also been received. There have been reports of tooth discoloration in patients treated with clarithromycin. Tooth discoloration is usually reversible with professional dental cleaning. There have been reports of transient central nervous system side effects including dizziness, vertigo, anxiety, insomnia, bad dreams, tinnitus, confusion, disorientation, hallucination, psychosis and depersonalization. There have been reports of hearing loss with clarithromycin, which is usually reversible upon withdrawal of therapy. Pseudomembranous colitis has been reported rarely with clarithromycin and may range in severity from mild to life threatening. There have been rare reports of hypoglycaemia, some of which have occurred in patients on concomitant oral hypoglycaemic agents or insulin. Isolated cases of leukopenia and thrombocytopenia have been reported. As with other macrolides, hepatic dysfunction (which is usually reversible) including altered liver function tests, hepatitis and cholestasis with or without jaundice, has been reported. Dysfunction may be severe and very rarely fatal hepatic failure has been reported. Cases of increased serum creatinine, interstitial nephritis, renal failure, pancreatitis and convulsions have been reported rarely. As with other macrolides, QT prolongation, ventricular tachycardia and Torsade de Pointes have been rarely reported with clarithromycin.

STORAGE  INSTRUCTIONS: 

Store below 30oC

Protect from light and moisture.

Keep out of the reach of children.