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CLARITHROMYCIN film-coated tablets 250 mg, film-coated tablets 500 mg
Instruction
For medical use of the medicinal product
Composition:
Active ingredient: clarithromycin;
1 tablet contains clarithromycin, calculated as 100% substance - 250 mg or 500 mg;
excipients: microcrystalline cellulose; sodium starch glycolate (type A); sodium lauryl sulfate; hypromellose; calcium stearate; coating mixture "Opadry II Yellow" (contains: triacetin; hypromellose; lactose, monohydrate; titanium dioxide (E 171); polyethylene glycol, iron oxide yellow (E 172)).
Dosage form.
Film-coated tablets.
Main physicochemical properties: film-coated tablets, yellow in color, with a biconvex surface, with a score on one side of the tablet and embossing "KMP" on the other. A white core is visible on cross-section.
Pharmacotherapeutic group.
Antimicrobials for systemic use. Macrolides. ATS code j01f A09.
Pharmacological properties.
Pharmacodynamics.
Clarithromycin is a semisynthetic macrolide antibiotic. The antibacterial effect of clarithromycin is determined by its binding to the 5OS ribosomal subunit of sensitive bacteria and inhibition of protein biosynthesis. The drug exhibits high in vitro efficacy against a wide range of aerobic and anaerobic gram-positive and gram-negative microorganisms, including hospital strains. The minimum acceptable concentrations (MICs) of clarithromycin are usually 2 times lower than the MICs of erythromycin.
Clarithromycin is highly effective in vitro against Legionella pneumophila and Mycoplasma pneumoniae. It is bactericidal against H. pylori, and clarithromycin is more active at neutral pH than at acidic pH. In vitro and in vivo data demonstrate the high efficacy of clarithromycin against clinically relevant strains of mycobacteria. In vitro studies have shown that strains of Enterobacteriaceae and Pseudomonas, as well as gram-negative bacteria that do not produce lactose, are insensitive to clarithromycin.
Microbiology.
Clarithromycin is active in vitro and in clinical practice against most strains of the following microorganisms:
aerobic gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes.
Aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila.
Other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR).
Mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC), which include Mycobacterium avium, Mycobacterium intracellulare.
Beta-lactamases of microorganisms do not affect the effectiveness of clarithromycin.
Most methicillin- and oxacillin-resistant strains of staphylococci are insensitive to clarithromycin.
Clarithromycin is active in vitro against most strains of the following microorganisms, however, the clinical efficacy and safety of its use have not been established:
aerobic gram-positive microorganisms: Streptococcus agalactiae, Streptococci (groups C, F, G), Viridans group streptococci.
Aerobic gram-negative microorganisms: Bordetella pertussis, Pasteurella multocida.
Other microorganisms: Chlamydia trachomatis.
Anaerobic gram-positive microorganisms: Clostridium perfringens, Peptococcus niger, Propionibacterium acnes.
Anaerobic Gram-negative microorganisms: Bacteriodes melaninogenicus.
Spirochetes: Borrelia burgdorferi, Treponema pallidum
Campylobacter: Campylobacter jejuni.
Clarithromycin has bactericidal activity against several strains of bacteria: Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, H. pylori and Campylobacter spp.
The main metabolite of clarithromycin in humans is the microbiologically active 14-hydroxyclarithromycin (14-OH-clarithromycin). For most microorganisms, the microbiological activity of the metabolite is equal to or 1-2 times weaker than the parent substance, with the exception of H. influenzae, against which the effectiveness of the metabolite is 2 times higher. In vitro and in vivo, the parent substance and its main metabolite exhibit either an additive or synergistic effect against H. influenzae, depending on the strain of the microorganism.
Pharmacokinetics.
Clarithromycin is rapidly and well absorbed from the gastrointestinal tract after oral administration of the drug in tablet form. The microbiologically active metabolite 14-hydroxyclarithromycin is formed by first-pass metabolism. Clarithromycin can be used regardless of food intake, since food does not affect the bioavailability of clarithromycin tablets. Food slightly delays the onset of clarithromycin absorption and the formation of the 14-hydroxymetabolite.
The pharmacokinetics of clarithromycin are nonlinear; however, steady-state concentrations are reached within 2 days of dosing. When administered at a dose of 250 mg twice daily, 15-20% of the unchanged drug is excreted in the urine. At a dose of 500 mg twice daily, urinary excretion is more intense (approximately 36%).
14-hydroxyclarithromycin is the major metabolite, which is excreted in the urine in an amount of 10-15% of the administered dose. Most of the remainder of the dose is excreted in the feces, mainly in the bile. 5-10% of the parent compound is found in the feces.
When 500 mg of clarithromycin is administered 3 times daily, plasma concentrations of clarithromycin are increased compared to a dose of 500 mg twice daily.
Clarithromycin penetrates the gastric mucosa. The content of clarithromycin in the gastric mucosa and tissue is higher when clarithromycin is used together with omeprazole than when clarithromycin is used alone.
Clinical characteristics.
Indication.
Treatment of infections caused by microorganisms susceptible to clarithromycin:
Upper respiratory tract infections, i.e. nasopharynx (tonsillitis, pharyngitis) and paranasal sinus infections; Lower respiratory tract infections (e.g. bronchitis, acute croupous pneumonia, primary atypical pneumonia); Skin and soft tissue infections (such as impetigo, folliculitis, erysipeloid, furunculosis, infected wounds); Acute and chronic odontogenic infections; Disseminated or localized mycobacterial infections caused by Mycobacterium avium or Mycobacterium intracellulare. Localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum or Mycobacterium kansasii; Eradication of H. pylori in patients with duodenal ulcer when suppressing hydrochloric acid secretion (the activity of clarithromycin against H. pylori at neutral pH is higher than at acidic pH).
Contraindication.
Hypersensitivity to macrolide antibiotics and other components of the drug. simultaneous use of astemizole, cisapride, pimozide, terfenadine (as this may lead to prolongation of the QT interval and the development of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, torsades de pointes), ergot alkaloids, such as ergotamine, dihydroergotamine (as this may lead to ergotoxicity), HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin) due to the risk of myopathy, including rhabdomyolysis. simultaneous use of clarithromycin and oral midazolam. patients with a history of QT prolongation or ventricular cardiac arrhythmias, including torsades de pointes. hypokalemia (risk of QT prolongation). severe hepatic impairment and concomitant renal impairment. concomitant use of clarithromycin (and other strong CYP3A4 inhibitors) with colchicine. concomitant use of clarithromycin with ticagrelor or ranolazine.
Interaction with other drugs and other types of interactions.
Clarithromycin does not interact with oral contraceptives.
The use of the following drugs is strictly contraindicated due to the possible development of severe interaction effects.
Cisapride, pimozide, astemizole, terfenadine. Increased serum levels of cisapride, pimozide, and terfenadine may occur when coadministered with clarithromycin, which may cause QT prolongation and arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes.
Similar effects were observed with the combined use of astemizole and other macrolides.
Ergot alkaloids: Concomitant use of clarithromycin and ergotamine or dihydroergotamine has been reported to be associated with signs of acute ergotism, characterized by vasospasm and ischemia of the extremities and other tissues, including the central nervous system. Concomitant use of clarithromycin and ergot derivatives is contraindicated (see Contraindications).
HMG-CoA reductase inhibitors (statins).
The combined use of clarithromycin with lovastatin or simvastatin is contraindicated (see "Contraindications"), since these statins are extensively metabolized by CYP3A4 and simultaneous use with clarithromycin increases their plasma concentrations, which in turn increases the risk of myopathy, including rhabdomyolysis. There is evidence of the development of rhabdomyolysis in patients with the combined use of clarithromycin and these statins.
If clarithromycin therapy cannot be avoided, lovastatin or simvastatin should be discontinued during the course of treatment. Clarithromycin should be administered concomitantly with other statins with caution. If concomitant administration of clarithromycin with statins cannot be avoided, the lowest effective dose of the statin is recommended. A statin that is not metabolized by CYP3A4 (e.g., fluvastatin) may be used.
Patients should be monitored for signs and symptoms of myopathy when combined with statins.
Effect of other drugs on the pharmacokinetics of clarithromycin.
Medicinal products that are CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) may induce the metabolism of clarithromycin. This may lead to subtherapeutic levels of clarithromycin and reduced efficacy. In addition, monitoring of plasma levels of the CYP3A inducer may be necessary, as they may be increased due to inhibition of CYP3A by clarithromycin (see also the Summary of Product Characteristics of the relevant CYP3A4 inducer). Concomitant use of rifabutin and clarithromycin may result in increased serum levels of rifabutin and decreased serum levels of clarithromycin, with a concomitant increase in the risk of uveitis.
Efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine. Potent inducers of cytochrome P450 enzymes, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine, may accelerate the metabolism of clarithromycin, decreasing its plasma concentration but increasing the concentration of 14-OH-clarithromycin, the microbiologically active metabolite. Since the microbiological activity of clarithromycin and 14-OH-clarithromycin is different against different bacteria, the expected therapeutic effect may not be achieved due to the combined use of clarithromycin and inducers of cytochrome P450 enzymes.
Etravirine: The efficacy of clarithromycin may be reduced by etravirine, but concentrations of the active metabolite 14-OH-clarithromycin are increased. Since 14-OH-clarithromycin has reduced activity against Mycobacterium avium complex (MAC), the overall activity against this pathogen may be altered. Therefore, alternative agents to clarithromycin should be considered for the treatment of MAC.
Fluconazole: The steady-state concentrations of the active metabolite 14-OH-clarithromycin are not significantly altered by co-administration with fluconazole. No dose adjustment of clarithromycin is required.
Ritonavir. The use of ritonavir and clarithromycin leads to a significant inhibition of the metabolism of clarithromycin. C max of clarithromycin increases by 31%, C min - by 182% and AUC - by 77%. There is a complete suppression of the formation of 14-OH-clarithromycin. Due to the large therapeutic window, a reduction in the dose of clarithromycin in patients with normal renal function is not required. However, dose adjustment is necessary for patients with renal insufficiency: for patients with CL CR 30-60 ml/min, the dose of clarithromycin should be reduced by 50%. For patients with severe renal insufficiency (CL CR should be reduced by 75%). Doses of clarithromycin exceeding 1 g/day should not be used together with ritonavir.
The same dose adjustment should be made in patients with renal impairment when ritonavir is used as a pharmacokinetic enhancer with other HIV protease inhibitors, including atazanavir and saquinavir.
Effect of clarithromycin on the pharmacokinetics of other drugs.
Antiarrhythmics. There have been postmarketing reports of torsades de pointes associated with concomitant use of clarithromycin with quinidine or disopyramide. ECG monitoring is recommended for early detection of QT prolongation. Serum concentrations of these drugs should be monitored during clarithromycin therapy.
During post-marketing use of clarithromycin preparations, there have been reports of hypoglycemia with the simultaneous use of clarithromycin and disopyramide, therefore, monitoring of blood glucose levels is necessary when these agents are used simultaneously.
Oral hypoglycemic agents/insulin: Concomitant use of clarithromycin with certain hypoglycemic agents, such as nateglinide and repaglinide, may cause hypoglycemia. Careful monitoring of glucose levels is recommended in this case.
CYP3A-related interactions. Concomitant use of clarithromycin, a known inhibitor of the CYP3A enzyme, and a drug that is primarily metabolized by CYP3A may result in increased plasma concentrations of the latter, which in turn may increase or prolong its therapeutic effect and the risk of adverse reactions. Caution should be exercised when administering clarithromycin to patients receiving therapy with drugs that are CYP3A substrates, especially if the CYP3A substrate has a narrow therapeutic index (e.g., carbamazepine) and/or is extensively metabolized by this enzyme. Dosage adjustment and, if possible, close monitoring of serum concentrations of the drug metabolized by CYP3A in patients receiving concomitant clarithromycin may be necessary.
The following drugs or drug classes are known (or suspected) to be metabolized by the same CYP3A isoenzyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (e.g., warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam, and vinblastine, but this list is not exhaustive. A similar mechanism of interaction has been observed with phenytoin, theophylline, and valproate, which are metabolized by a different cytochrome P450 isoenzyme.
Omeprazole: There is evidence that the use of clarithromycin in combination with omeprazole in healthy adult volunteers leads to an increase in the equilibrium concentrations of omeprazole. When using omeprazole alone, the average pH of gastric juice measured over 24 hours is 5.2, when using omeprazole with clarithromycin - 5.7.
Sildenafil, tadalafil and vardenafil: There is a potential for increased plasma concentrations of phosphodiesterase inhibitors (sildenafil, tadalafil and vardenafil) when co-administered with clarithromycin, which may require a reduction in the dose of the phosphodiesterase inhibitor.
Tolterodine. Tolterodine is primarily metabolized by the 2D6 isoform of P450 (CYP2D6). However, in the CYP2D6 deficient patient population, metabolism occurs via CYP3A. In this population, inhibition of CYP3A results in significantly increased plasma concentrations of tolterodine. In such patients, a reduction in the dose of tolterodine may be necessary when coadministered with CYP3A inhibitors such as clarithromycin.
Triazolebenzodiazepines (e.g. alprazolam, midazolam, triazolam). The combined use of oral midazolam and clarithromycin should be avoided. When intravenous midazolam is used with clarithromycin, the patient's condition should be carefully monitored for timely dose adjustment.
The same precautions should be observed when using other benzodiazepines that are metabolized by CYP3A, including triazolam and alprazolam.
For benzodiazepines, the elimination of which does not depend on CYP3A (temazepam, nitrazepam, lorazepam), the development of a clinically significant interaction with clarithromycin is unlikely.
There is evidence of drug interactions and the development of central nervous system adverse events (such as drowsiness and confusion) with the combined use of clarithromycin and triazolam. The patient should be monitored, taking into account the possible increase in pharmacological effects from the CNS.
Other types of interactions.
Aminoglycosides: Clarithromycin should be used with caution in combination with other ototoxic agents, especially aminoglycosides.
Colchicine. Colchicine is a substrate for CYP3A and P-glycoprotein (Pgp). Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. When clarithromycin and colchicine are coadministered, inhibition of Pgp and CYP3A by clarithromycin may lead to increased exposure to colchicine. Patients should be monitored for clinical signs of colchicine toxicity. The dose of colchicine should be reduced when coadministered with clarithromycin in patients with normal renal and hepatic function. Concomitant use of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment (see Contraindications, Precautions for Use).
Digoxin. Digoxin is considered a substrate for P-glycoprotein (Pgp). Clarithromycin is known to inhibit Pgp. Concomitant use of Pgp inhibition may result in increased digoxin exposure. Increased serum digoxin concentrations have been reported in patients receiving clarithromycin and digoxin. Some patients have developed signs of digitalis toxicity, including potentially fatal arrhythmias. Serum digoxin concentrations should be closely monitored in patients receiving clarithromycin.
Zidovudine. Concomitant administration of clarithromycin immediate-release tablets and zidovudine in HIV-infected patients may result in decreased steady-state serum concentrations of zidovudine. Since clarithromycin may interfere with the absorption of oral zidovudine when administered concomitantly, a 4-hour interval should be maintained between the administration of clarithromycin and zidovudine. No such interaction has been reported with clarithromycin suspension and zidovudine or dideoxynazine in children.
Phenytoin and valproate. There have been published reports of interactions between CYP3A inhibitors, including clarithromycin, and drugs not metabolized by CYP3A (phenytoin and valproate). It is recommended that serum levels of these drugs be monitored when co-administered with clarithromycin. There have been reports of increased serum levels.
Bidirectional drug interactions.
Atazanavir. Coadministration of clarithromycin (500 mg twice daily) with atazanavir (400 mg once daily), which are substrates and inhibitors of CYP3A, resulted in a 2-fold increase in clarithromycin exposure and a 70% decrease in 14-OH-clarithromycin exposure with a 28% increase in atazanavir AUC. Since clarithromycin has a wide therapeutic range, no dose reduction is necessary for patients with normal renal function. The dose of clarithromycin should be reduced by 50% in patients with creatinine clearance 30-60 mL/min and by 75% in patients with creatinine clearance <10 mL/min. Atazanavir should not be used with protease inhibitors.
Calcium channel blockers. Due to the risk of hypotension, caution should be exercised when clarithromycin is used concomitantly with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem). The interaction may result in increased plasma concentrations of both clarithromycin and the calcium channel blocker. Hypotension, bradyarrhythmias, and lactic acidosis have been reported in patients receiving clarithromycin and verapamil.
Saquinavir. It is known that the use of clarithromycin (500 mg 2 times a day) with saquinavir (soft gelatin capsules, 1200 mg 3 times a day), which are substrates and inhibitors of CYP3A, leads to an increase in steady-state AUC by 177% and C max by 187% compared to the use of saquinavir alone. At the same time, the AUC and C max of clarithromycin increased by approximately 40% compared to the use of clarithromycin alone. No dose adjustment is necessary if both drugs are used simultaneously for a limited period of time and in the above doses and dosage forms. Drug interaction data with the use of soft gelatin capsules may not correspond to the effects observed with the use of saquinavir in the form of hard gelatin capsules. Drug interaction data with the use of saquinavir alone may not correspond to the effects observed with saquinavir / ritonavir therapy. When saquinavir is used with ritonavir, the possible effects of ritonavir on clarithromycin should be considered (see above).
Application features.
The drug contains lactose as an excipient, so the drug should not be used in patients with galactose intolerance, lactase deficiency or glucose/galactose malabsorption.
Prolonged or repeated use of antibiotics may cause overgrowth of nonsusceptible bacteria and fungi. If superinfection occurs, clarithromycin should be discontinued and appropriate therapy initiated.
The drug should be used with caution in patients with severe renal insufficiency.
Hepatic dysfunction, including elevated liver enzymes, and hepatocellular and/or cholestatic hepatitis with or without jaundice, have been reported with clarithromycin. These hepatic dysfunctions may be severe and are usually reversible. In some cases, fatal hepatic failure has been reported, and these have mostly been associated with serious underlying diseases and/or concomitant medication. Clarithromycin should be discontinued immediately if signs and symptoms of hepatitis such as anorexia, jaundice, dark urine, pruritus, or abdominal pain occur.
Clostridium difficile-associated diarrhea, ranging from mild to fatal, has been reported with nearly all antibacterial agents, including clarithromycin. The possibility of Clostridium difficile-associated diarrhea should be kept in mind in all patients presenting with diarrhea following antibiotic therapy. A careful history should also be taken, as Clostridium difficile-associated diarrhea has been reported up to 2 months after antibiotic therapy.
Exacerbation of myasthenia gravis symptoms has been reported in patients taking clarithromycin.
The drug is excreted through the liver and kidneys. Caution should be exercised when using the drug in patients with impaired liver function, with moderate or severe renal impairment.
Colchicine toxicity (including fatal outcomes) has been reported with concomitant use of clarithromycin and colchicine, particularly in the elderly, including patients with renal impairment. If concomitant use of colchicine and clarithromycin is necessary, patients should be observed for possible clinical signs of colchicine toxicity. The dose of colchicine should be reduced in all patients receiving concomitant colchicine and clarithromycin. Concomitant use of clarithromycin with colchicine is contraindicated in patients with renal or hepatic impairment (see Contraindications).
Caution should be exercised when clarithromycin is administered concomitantly with triazolebenzodiazepines, e.g. triazolam, intravenous midazolam (see Interactions with other medicinal products and other forms of interaction).
Clarithromycin should be used with caution in combination with other ototoxic agents, especially aminoglycosides. Vestibular and auditory function should be monitored during and after treatment.
Due to the risk of QT prolongation, clarithromycin should be used with caution in patients with ischemic heart disease, severe heart failure, hypomagnesemia, bradycardia (drugs associated with QT prolongation (see Interactions with other medicinal products and other forms of interaction). Clarithromycin should not be used in patients with congenital or history of QT prolongation, or with a history of ventricular cardiac arrhythmia (see Contraindications).
Mild to moderate skin and soft tissue infections. These infections are most commonly caused by Staphylococcus aureus and Streptococcus pyogenes, which may be resistant to macrolides. Susceptibility testing is therefore important. In cases where beta-lactam antibiotics cannot be used (e.g. allergy), other antibiotics such as clindamycin may be used as first-line agents. Macrolides currently have a role only in the treatment of some skin and soft tissue infections (e.g. infections caused by Corynebacterium minutissimum (erythrasma), acne vulgaris, erysipelas) and in situations where penicillin treatment is not appropriate.
In the event of severe acute hypersensitivity reactions such as anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, Henoch-Schonlein-Schönlein disease, clarithromycin therapy should be discontinued immediately and appropriate treatment should be initiated immediately.
Attention should be paid to the possibility of cross-resistance between clarithromycin and other macrolides, as well as lincomycin and clindamycin.
The use of any antimicrobial therapy, including clarithromycin, for the treatment of H. pylori infection may result in the emergence of microbial resistance. In a small number of patients, H. pylori may develop resistance to clarithromycin.
Oral hypoglycemic agents/insulin. Concomitant use of clarithromycin and oral hypoglycemic agents and/or insulin may cause severe hypoglycemia. When used concomitantly with hypoglycemic agents such as nateglinide, pioglitazone, repaglinide, and rosiglitazone, clarithromycin may inhibit the CYP3A enzyme, which may cause hypoglycemia. Close monitoring of glucose levels is recommended.
Oral anticoagulants. Concomitant use of clarithromycin with warfarin has been associated with a risk of serious bleeding, significant increases in INR (international normalized ratio) and prothrombin time. INR and prothrombin time should be monitored regularly while patients are receiving clarithromycin and oral anticoagulants.
HMG-CoA reductase inhibitors (statins). The combined use of clarithromycin with lovastatin or simvastatin is contraindicated (see "Contraindications"). Clarithromycin should be prescribed with caution in parallel with other statins. There are data on the development of rhabdomyolysis in patients with the combined use of clarithromycin and statins. With combined therapy with statins, monitoring of the condition of patients is necessary in order to detect signs and symptoms of myopathy. In situations where the simultaneous use of clarithromycin with statins cannot be avoided, it is recommended to prescribe the lowest effective dose of the statin. It is possible to use a statin that does not depend on CYP3A metabolism (for example, fluvastatin).
Clarithromycin should be used with caution when co-administered with inducers of the cytochrome CYP3A4 enzyme.
Use during pregnancy or breastfeeding.
The safety of clarithromycin during pregnancy and breastfeeding has not been established.
Clarithromycin should not be used during pregnancy (especially in the first trimester) without careful assessment of the benefit/risk ratio.
Clarithromycin passes into breast milk.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
There are no data. However, when driving or working with other mechanisms, the likelihood of adverse reactions from the nervous system, such as seizures, dizziness, vertigo, hallucinations, confusion, disorientation, etc., should be taken into account.
Method of administration and doses.
The recommended dose of clarithromycin for adults and children over 12 years of age is 250 mg every 12 hours, in more severe infections the dose can be increased to 500 mg every 12 hours. The usual duration of treatment depends on the severity of the infection and is from 6 to 14 days.
Clarithromycin can be taken without regard to meals, as food does not affect the bioavailability of clarithromycin.
Treatment of odontogenic infections. The recommended dose is 250 mg every 12 hours for 5 days.
Use in patients with mycobacterial infections. The initial dose for adults is 500 mg twice daily. If there is no improvement in clinical signs or bacteriological parameters within 3-4 weeks of treatment, the dose of clarithromycin may be increased to 1000 mg twice daily.
Treatment of disseminated infections caused by MAOIs in AIDS patients should be continued for as long as the clinical and microbiological efficacy of the drug is medically proven. Clarithromycin can be used in combination with other antimycobacterial agents.
Eradication of H. pylori in patients with duodenal ulcer (adults).
Triple therapy (7-10 days): Clarithromycin (500 mg) twice daily should be used with amoxicillin 1000 mg twice daily and omeprazole 20 mg daily for 7-10 days.
Triple therapy (10 days): Clarithromycin (500 mg) twice daily, lansoprazole 30 mg twice daily, and amoxicillin 1000 mg twice daily for 10 days.
Dual therapy (14 days): Clarithromycin (500 mg) 3 times daily with lansoprazole 60 mg orally once daily for 14 days. Further acid suppression may be required to reduce ulcer symptoms.
Clarithromycin has also been used in the following therapeutic regimens:
clarithromycin + tinidazole and omeprazole or lansoprazole; clarithromycin + metronidazole and omeprazole or lansoprazole; clarithromycin + tetracycline, bismuth subsalicylate and ranitidine; clarithromycin + amoxicillin and lansoprazole; clarithromycin + ranitidine bismuth citrate.
Use in the elderly: as for adults.
Use in patients with renal insufficiency: For patients with severe renal insufficiency (creatinine clearance halved, e.g. 250 mg once daily or 250 mg twice daily for more severe infections. In such patients, the duration of treatment should not exceed 14 days.
Children.
Clarithromycin in this dosage form is contraindicated in children under 12 years of age. Children under 12 years of age should use clarithromycin in the form of an oral suspension.
Overdose.
Symptoms: There are reports that clarithromycin overdose may cause gastrointestinal symptoms.
There is data on 1 case of development of changes in mental status, paranoid behavior, hypokalemia and hypoxemia in a patient with a history of bipolar psychosis who took 8 grams of clarithromycin.
Treatment: Adverse reactions associated with overdose should be treated with gastric lavage and symptomatic therapy. As with other macrolides, hemodialysis or peritoneal dialysis is unlikely to significantly affect serum clarithromycin levels.
Adverse reactions.
The most frequent and common adverse reactions in adults and children treated with clarithromycin are abdominal pain, diarrhea, nausea, vomiting, and taste disturbance. Adverse reactions associated with clarithromycin are listed by system organ class. Within each group, adverse reactions are presented in order of decreasing severity, if severity can be assessed.
Infections and infestations: cellulitis, oral candidiasis, gastroenteritis, infection, vaginal infection, pseudomembranous colitis, erysipelas.
From the blood and lymphatic system: leukopenia, neutropenia, thrombocythemia, eosinophilia, agranulocytosis, thrombocytopenia.
Immune system disorders: anaphylactoid reactions, hypersensitivity, anaphylactic reactions.
Metabolism and nutrition disorders: anorexia, decreased appetite, hypoglycemia.
On the part of the psyche: insomnia, anxiety, nervousness, psychosis, confusion, depersonalization, depression, disorientation, hallucinations, nightmares, mania.
From the side of the central nervous system: dysgeusia (impaired taste sensation), headache, taste distortion, loss of consciousness, dyskinesia, dizziness, drowsiness, tremor, convulsions, ageusia (loss of taste sensation), parosmia, anosmia, paresthesia.
From the side of the organs of hearing and labyrinth: dizziness, hearing impairment, tinnitus, hearing loss.
Cardiac disorders: cardiac arrest, atrial fibrillation, QT prolongation, extrasystoles, palpitations, torsades de pointes, ventricular tachycardia.
Vascular disorders: vasodilation, hemorrhage.
From the respiratory system, chest organs and mediastinum: asthma, nosebleeds, pulmonary embolism.
On the part of the digestive system: diarrhea, vomiting, dyspepsia, nausea, abdominal pain, esophagitis, gastroesophageal reflux disease, gastritis, proctalgia, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence, acute pancreatitis, tongue discoloration, tooth discoloration.
On the part of the hepatobiliary system: abnormal liver function tests, cholestasis, hepatitis, increased levels of ALT, AST, GGT, liver failure, cholestatic jaundice, hepatocellular jaundice.
Skin and subcutaneous tissue disorders: rash, hyperhidrosis, bullous dermatitis, pruritus, urticaria, maculopapular rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.
