CLABACT 500

Print
Barcode:
Description

CLABACT 500

Keep out of reach of children.

Read the instruction thoroughly before use.

Prescription only.

QUANLITATIVE AND QUANQUATATIVE COMPOSITION

Active ingredient: Clarithromycin …………… 500 mg

Excipients: Avicel M101, croscarmellose sodium, HPMC 2910, polysorbate 80 (sepitrap 80), stearic acid, magnesium stearate, aerosil, PVP K30, HPMC 606, HPMC 615, PEG 6000, titanium dioxide, quinoline, talc.

PHARMACAUTICAL FORM: Film coated tablet.

Product description: A yellow, oval, film-coated tablet, plain on both sides, intact edges.

THERAPEUTIC INDICATIONS

Clarithromycin is indicated for treatment of infections due to one or more susceptible organisms. Such infections include:

  • Lower respiratory tract infections, e.g., acute and chronic bronchitis, pneumonia (see sections Special warnings and precautions for use; Pharmacodynamic properties).
  • Upper respiratory tract infections, e.g., sinusitis and pharyngitis.
  • Skin and soft tissue infections, e.g., folliculitis, cellulitis, and erysipelas (see sections Special warnings and precautions for use; Pharmacodynamic properties).
  • Disseminated or localised mycobacterial infections due to Mycobacterium avium or Mycobacterium intracellulare. Localised infections due to Mycobacterium chelonae, Mycobacterium fortuitum or Mycobacterium kansasii
  • Clarithromycin is indicated for the prevention of disseminated Mycobacterium avium complex (MAC) infection in HIV infected patients with CD4 lymphocyte counts less than or equal to 100/mm3.
  • Clarithromycin in the presence of acid suppression is indicated for the eradication of H. pylori, resulting in decreased recurrence of duodenal ulcer (see section Posology and method of administration)

POSOLOGY AND METHOD OF ADMINISTRATION

Adults: In more severe infections, the dosage can be increased to 500 mg twice daily. The usual duration of therapy is 5 to 14 days. Case of community-acquired pneumonia and sinusitis require a 6-14 day therapy.

  • Dosage in patients with mycobacterial infections: The recommended dosage of clarithromycin in adults is 500 mg twice daily.
  • Treatment of disseminated MAC infections in AIDS patients should be continued, as long as clinical microbiological benefit is demonstrated. Clarithromycin should be used in conjunction with other antimycobacterial agents.
  • Treatment of other non-tuberculous mycobacterial infections should continue at the discretion of the physician.
  • Dosage for MAC prophylaxis: The recommended dosage of clarithromycin in adults is 500 mg twice daily.

Eradication of H. pylori:

In patients with peptic ulcer caused by H. pylori infection, clarithromycin can be administered at a dose of 500 mg twice daily in combination with other appropriate antibiotics and a proton pump inhibitor for 7-14 days.

Official reference for H. pylori eradication should be consulted.

Here are some examples of H. pylori eradication regimens:

Triple therapy:

Clarithromycin 500 mg twice daily should be given with amoxicillin 1000 mg twice daily and a proton pump inhibitor with a standard dose twice daily, for 14 days.

Quadruple therapy:

A proton pump inhibitor twice daily should be used with amoxicillin 1000 mg twice daily, clarithromycin 500 mg twice daily and tinidazole 500 mg or metronidazole 500 mg twice daily, for 14 days.

10 day sequential therapy:

A proton pump inhibitor twice daily should be given with amoxicillin 1000 mg twice daily for 5 consecutive days.

A proton pump inhibitor twice daily should be given with clarithromycin 500 mg twice daily and tinidazole 500 mg twice daily for 5 consecutive days.

Renal impairment

In patients with renal impairment with creatinine clearance less than 30 ml/min, the dosage of clarithromycin should be reduced by one-half, i.e. 250 mg once daily or 250 mg twice daily in more severe infections. Treatment should not be continued beyond 14 days in these patients.

Children

The use of clarithromycin rapid release tablets has not been studied in children under 12 years. Therefore, children should use clarithromycin paediatric suspension.

Clarithromycin may be given without regard to meals as food does not affect the extent of bioavailability.

CONTRAINDICATIONS

Clarithromycin is contraindicated in patients with known hypersensitivity to macrolide antibiotic drugs or any of its excipients (see section excipients).

Concomitant administration of clarithromycin and any of the following drugs is contraindicated: astemizole, cisapride, pimozide or terfenadine as this may result in QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes (see section Interactions).

Concomitant administration of clarithromycin and ergot alkaloids (e.g. ergotamine or dihydroergotamine) is contraindicated, as this may result in ergot toxicity (see section Interactions).

Concomitant administration of clarithromycin and oral midazolam is contraindicated (see section Interactions).

Clarithromycin should not be given to patients with a history of QT prolongation (congenital or documented acquired QT prolongation) or ventricular cardiac arrhythmia, including torsades de pointes (see sections Special warnings and precautions for use and Interactions).

Clarithromycin should not be given to patients with hypokalaemia (a risk of prolongation of QT-time).

Clarithromycin should not be used in patients who suffer from severe hepatic failure in combination with renal impairment.

Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins), that are extensively metabolised by CYP3A4, (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis (see section Special warnings and precautions for use).

As with other strong CYP3A4 inhibitors, clarithromycin should not be used in patients taking colchicine (see sections Special warnings and precautions for use and Interactions).

Concomitant administration of clarithromycin with ticagrelor or ranolazine is contraindicated.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Use of any antimicrobial therapy, such as clarithromycin, to treat H. pylori infection may select for drug-resistant organisms.

The physician should not prescribe clarithromycin to pregnant women without carefully weighing the benefits against risk, particularly during the first three months of pregnancy.

Long-term use of clarithromycin may, as with other antibiotics, result in colonisation with increased numbers of non-susceptible bacteria and fungi. If superinfections occur, appropriate therapy should be instituted.

Clarithromycin is principally metabolised by the liver. Therefore, caution should be exercised in administering this antibiotic to patients with impaired hepatic function. Caution should also be exercised when administering clarithromycin to patients with moderate to severe renal impairment.

Caution is advised in patients with severe renal insufficiency.

Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin. This hepatic dysfunction may be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has
been reported and generally has been associated with serious underlying diseases and/or
concomitant medications. Patients should be advised to stop treatment if signs and symptoms of hepatitis develop, such as anorexia, jaundice, dark urine, pruritus, or tender abdomen.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening. Clostridium difficile- associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents including clarithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. difficile. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Colchicine

There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such patients (see section Interactions). Concomitant administration of clarithromycin and colchicine is contraindicated (see section Contraindications).

Caution is advised regarding concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam, and intravenous or oromucosal midazolam (see section Interactions).

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 macrolides including clarithromycin (see section Undesirable effects). Therefore, as the following situations may lead to an increased risk for ventricular arrhythmias (including torsades de pointes), clarithromycin should be used with caution in the following patients:

  • • Patients with a coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia.
  • • Patients with electrolyte disturbances such as hypomagnesaemia. Clarithromycin must not be given to patients with hypokalaemia (see Contraindications).
  • • Patients concomitantly taking other medicinal products associated with a QT prolongation (see section Interactions).
  • • Concomitant administration of clarithromycin with astemizole, cisapride, pimozide and terfendine is contraindicated (see section Contraindications).
  • • Clarithromycin must not be used in patients with congenital or documented acquired QT prolongation or history of ventricular arrhythmia (see section Contraindications).

Pneumonia

In view of the emerging resistance of Streptococcus pneumoniae to macrolides, it is important that sensitivity testing be performed when prescribing clarithromycin for community-acquired pneumonia. In hospital-acquired pneumonia, clarithromycin should be used in combination with additional appropriate antibiotics.

Skin and soft tissue infections of mild to moderate severity

These infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes, both of which may be resistant to macrolides. Therefore, it is important that sensitivity testing be performed. In cases where beta-lactam antibiotics cannot be used (e.g. allergy), other antibiotics, such as clindamycin, may be the drug of first choice. Currently, macrolides are only considered to play a role in some skin and soft tissue infections, such as those caused by Corynebacterium minutissimum (erythrasma), acne vulgaris, and erysipelas and in situations where penicillin treatment cannot be used.

In the event of severe acute hypersensitivity reactions, such as anaphylaxis, severe cutaneous adverse reactions (SCAR) (e.g. acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome, toxic epidermal necrolysis and drug rash with eosinophilia and systemic symptoms (DRESS)) clarithromycin therapy should be discontinued immediately and appropriate treatment should be urgently initiated.

Clarithromycin should be used with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme (see section Interactions).

Attention should also be paid to the possibility of cross resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.

HMG-CoA reductase inhibitors (statins)

Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see section Contraindications). Caution should be exercised when prescribing clarithromycin with other statins. Rhabdomyolysis has been reported in patients taking clarithromycin and statins. Patients should be monitored for signs and symptoms of myopathy. In situations where the concomitant use of clarithromycin with statins cannot be avoided, it is recommended to prescribe the lowest registered dose of the statin. Use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin) can be considered.

Oral hypoglycaemic agents/Insulin

The concomitant use of clarithromycin and oral hypoglycaemic agents (such as sulphonylurias) and/or insulin can result in significant hypoglycaemia. Careful monitoring of glucose is recommended.

Oral anticoagulants

There is a risk of serious haemorrhage and significant elevations in International Normalized Ratio (INR) and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.

INTERACTIONS

The use of the following drugs is strictly contraindicated due to the potential for severe drug interaction effects:

Cisapride, pimozide, astemizole and terfenadine

Elevated cisapride levels have been reported in patients receiving clarithromycin and cisapride concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsades de pointes. Similar effects have been observed in patients taking clarithromycin and pimozide concomitantly (see section Contraindications).

Macrolides have been reported to alter the metabolism of terfenadine resulting in increased levels of terfenadine which has occasionally been associated with cardiac arrhythmias, such as QT prolongation, ventricular tachycardia, ventricular fibrillation and torsades de pointes (see section Contraindications). In one study in 14 healthy volunteers, the concomitant administration of clarithromycin and terfenadine resulted in 2- to 3-fold increase in the serum level of the acid metabolite of terfenadine and in prolongation of the QT interval which did not lead to any clinically detectable effect. Similar effects have been observed with concomitant administration of astemizole and other macrolides.

Ergot alkaloids

Post-marketing reports indicate that co-administration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm, ischaemia of the extremities and other tissues including the central nervous system. Concomitant administration of clarithromycin and ergot alkaloids is contraindicated (see section Contraindications).

Oral midazolam

When midazolam was coadministered with clarithromycin tablets (500 mg twice daily), midazolam AUC was increased 7-fold after oral administration of midazolam. Concomitant administration of oral midazolam and clarithromycin is contraindicated (see section Contraindications)

HMG-CoA reductase inhibitors (statins)

Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated as these statins are extensively metabolized by CYP3A4 and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Reports of rhabdomyolysis have been received for patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.

Caution should be exercised when prescribing clarithromycin with statins. In situations where the concomitant use of clarithromycin with statins cannot be avoided, it is recommended to prescribe the lowest registered dose of the statin. Use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin) can be considered. Patients should be monitored for signs and symptoms of myopathy.

Effects of other medicinal products on clarithromycin

Drugs that are inducers of CYP3A (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St John's wort) may induce the metabolism of clarithromycin. This may result in sub-therapeutic levels of clarithromycin leading to reduced efficacy. Furthermore, it might be necessary to monitor the plasma levels of the CYP3A inducer, which could be increased owing to the inhibition of CYP3A by clarithromycin (see also the relevant product information for the CYP3A4 inhibitor administered).

Concomitant administration of rifabutin and clarithromycin resulted in an increase in rifabutin, and decrease in clarithromycin serum levels together with an increased risk of uveitis.

The following drugs are known or suspected to affect circulating concentrations of clarithromycin; clarithromycin dosage adjustment or consideration of alternative treatments may be required.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine

Strong inducers of the cytochrome P450

Reviews

There are yet no reviews for this product.