Clarithromycin-OBL, 500 mg 14 pcs.

Boils, Tonsillitis, Sinusitis, Angina, Colds, Pharyngitis, Skin infections, GI infections caused by Helicobacter pylori, Otitis media, Bronchitis, Gastric and duodenal ulcers

Infectious and inflammatory diseases caused by clarytromycin-sensitive microorganisms:

– Lower respiratory tract infections (such as bronchitis, pneumonia);

– Upper respiratory tract infections (such as pharyngitis, sinusitis);

– Skin and soft tissue infections (such as folliculitis, subcutaneous tissue inflammation, rye);

– Disseminated or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare;

– Localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii;

– Preventing the spread of infection caused by Mycobacterium avium complex (MAC) to HIV-infected patients with a CD4 (Tcheloper lymphocyte) count of 100 or less in 1 mm3;

– Eradication of H. pylori and reduced recurrence rate of duodenal ulcer;

– Odontogenic infections.

Active ingredient

Composition

1 film-coated tablet contains:

The active ingredient:

Clarithromycin (in terms of 100% substance) 250 mg/500 mg;

Excipients:

Microcrystalline cellulose 130.385 mg/260.77 mg, sodium lauryl sulfate 17.25 mg/34.5 mg, croscarmellose sodium 7.77 mg/15.54 mg, colloidal silica (aerosil) 20 mg/40 mg, povidone (polyvinylpyrrolidone low-molecular) 0.195 mg/0.39 mg, magnesium stearate 4.4 mg/8.8 mg;

Shell excipients:

Hypromellose (hydroxypropyl methylcellulose) 11.76 mg/23.52 mg, macrogol 6000 (polyethylene glycol 6000) 3.04 mg/6.08 mg, titanium dioxide 2.9 mg/5.8 mg, hyprolose (hydroxypropyl cellulose) 1.18 mg/2.36 mg, quinoline yellow dye 0.55 mg/1.1 mg, vanillin 0.57 mg/1.14 mg.

How to take, the dosage

For oral administration. Regardless of food intake.

The usual recommended dose of clarithromycin in adults and children over 12 years is 250 mg twice daily.

In more severe infections, the dose is increased to 500 mg twice a day.

The usual duration of treatment is from 5 to 14 days.

The exceptions are community-acquired pneumonia and sinusitis, which require 6 to 14 days of treatment.

Doses for treatment of mycobacterial infections other than tuberculosis:

The recommended dose for mycobacterial infections is clarithromycin 500 mg twice daily.

The treatment of disseminated MAC infections in patients with AIDS should be continued as long as there is clinical and microbiological efficacy. Clarithromycin should be administered in combination with other antimicrobials active against these pathogens. The duration of treatment of other non-tuberculous mycobacterial infections is determined by the physician.

For prevention of infections caused by MAC:

The recommended dose of clarithromycin for adults is 500 mg twice daily.

For odontogenic infections, the dose of clarithromycin is 250 mg 2 times a day for 5 days.

For eradication of H. pylori:

In patients with peptic ulcer disease caused by H. pylori infection, clarithromycin may be given 500 mg twice daily in combination with other antimicrobials and proton pump inhibitors for 7-14 days, according to national and international guidelines for the treatment of H. pylori infection.

Patients with renal impairment

Patients with a creatinine clearance (CK) of less than 30 mL/min are prescribed half the usual dose of clarithromycin, i.e. 250 mg once daily or, for more severe infections, 250 mg twice daily. Treatment in such patients is continued for no more than 14 days.

Interaction

The following drugs are contraindicated with clarithromycin due to the potential for serious adverse effects

Cyzapride, pimozide, terfenadine and astemizole

The following drugs are contraindicated with clarithromycin. When clarithromycin is coadministered with cisapride, pimozide, terfenadine or astemizole, an increase in plasma concentrations of the latter has been reported which may prolong QT interval and result in cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and ventricular pirouette tachycardia (see Contraindications. See Contraindications).

After-marketing studies have shown that the following effects associated with acute poisoning with ergotamine or dihydroergotamine can occur when clarithromycin is coadministered: vasospasm, ischemia of the extremities and other tissues, including the central nervous system. Concomitant use of clarithromycin and ergot alkaloids is contraindicated (see section “Contraindications”).

HMG-CoA reductase inhibitors (statins)

The concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see “Contraindications. Concurrent use of clarithromycin is contraindicated (see section “Contraindications”) due to the fact that these statins are largely metabolized by CYP3A4 isoenzyme and co-administration with clarithromycin increases their serum concentrations, which leads to increased risk of myopathy, including rhabdomyolysis. Rhabdomyolysis has been reported in patients taking clarithromycin in combination with these drugs. If clarithromycin should be used, lovastatin or simvastatin should be discontinued for the duration of therapy.

Clarithromycin should be used with caution when combined therapy with other statins. It is recommended to use statins that do not depend on CYP3A isoenzyme metabolism (e.g., fluvastatin). If coadministration is necessary, it is recommended to take the lowest dose of statin. The development of signs and symptoms of myopathy should be monitored.

The effect of other drugs on clarithromycin

Drugs that are inducers of the CYP3A isoenzyme (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort) may induce the metabolism of clarithromycin. This can lead to subtherapeutic concentrations of clarithromycin, resulting in decreased efficacy. In addition, plasma concentration of CYP3A isoenzyme inducer should be monitored, which may increase due to inhibition of CYP3A isoenzyme by clarithromycin. When rifabutin and clarithromycin are used together, there was an increase in plasma concentration of rifabutin and a decrease in serum concentration of clarithromycin with increased risk of uveitis.

The following drugs have proven or suspected effects on plasma concentrations of clarithromycin; doses may need to be adjusted or alternative treatment may be necessary if used in combination with clarithromycin.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin

. Strong cytochrome P450 inducers such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine can accelerate the metabolism of clarithromycin and thus decrease the plasma concentration of clarithromycin and weaken the therapeutic effect, and simultaneously increase the concentration of 14OHclarithromycin, a metabolite that is also microbiologically active. Because the microbiological activity of clarithromycin and 14OH-clarithromycin is different for different bacteria, the therapeutic effect may be reduced when clarithromycin and enzyme inducers are used together.

Etravirine

The concentration of clarithromycin is reduced with etravirine, but the concentration of the active metabolite 14OHclarithromycin is increased. Because 14OHclarithromycin has low activity against Mycobacterium avium complex (MAC) infections, the overall activity against these pathogens may change, so alternative treatments should be considered for MAC treatment.

Fluconazole

The co-administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 500 mg twice daily in 21 healthy volunteers resulted in a 33% and 18% increase in the mean clarithromycin minimum equilibrium concentration (Cmin) and AUC, respectively. However, co-administration had no significant effect on the mean equilibrium concentration of the active metabolite 14OH clarithromycin. No dose adjustment of clarithromycin is required for concomitant administration of fluconazole.

Ritonavir

A pharmacokinetic study has shown that co-administration of ritonavir at a dose of 200 mg every eight hours and clarithromycin at a dose of 500 mg every 12 hours resulted in marked inhibition of clarithromycin metabolism. When ritonavir was coadministered, the Cmax of clarithromycin increased by 31%, the Cmin increased by 182%, and the AUC increased by 77%. Complete inhibition of 14OH formation of clarithromycin was observed. Due to the wide therapeutic range of clarithromycin, no dose reduction is required in patients with normal renal function. In patients with renal impairment, it is reasonable to consider the following dose adjustments: at CKR 30-60 ml/min, the dose of clarithromycin should be reduced by 50%; at CKR less than 30 ml/min, the dose of clarithromycin should be reduced by 75%. Ritonavir should not be coadministered with clarithromycin in doses greater than 1 g/day.

The effect of clarithromycin on other drugs

Antirhythmic drugs (quinidine and disopyramide)

Ventric pirouette tachycardia may occur when clarithromycin and quinidine or disopyramide are used together. If clarithromycin is taken concomitantly with these drugs, electrocardiograms should be monitored regularly to detect prolongation of QT interval, and serum concentrations of these drugs should be monitored.

In post-marketing use, hypoglycemia has been reported with clarithromycin and disopyramide. Blood glucose concentrations should be monitored when using clarithromycin and disopyramide concomitantly.

Peroral hypoglycemic agents/insulin

The co-administration of clarithromycin and oral hypoglycemic agents (e.g. sulfonylurea derivatives) and/or insulin may cause significant hypoglycemia. Concomitant use of clarithromycin with some hypoglycemic drugs (e.g. nateglinide, pioglitazone, repaglinide and rosiglitazone) may lead to inhibition of CYP3A isoenzyme by clarithromycin, which may result in hypoglycemia. Close monitoring of glucose concentration is recommended.

CYP3A isoenzyme-dependent interactions

Co-administration of clarithromycin, which is known to inhibit the CYP3A isoenzyme, and drugs primarily metabolized by CYP3A may be associated with a mutual increase in their concentrations, which may enhance or prolong both therapeutic and adverse effects. Clarithromycin should be used with caution in patients receiving drugs that are substrates of CYP3A isoenzyme, especially if these drugs have a narrow therapeutic range (e.g., carbamazepine), and/or are intensively metabolized by this enzyme. If necessary, the dose of the drug taken with clarithromycin should be adjusted. The serum concentrations of drugs primarily metabolized by CYP3A isoenzyme should also be monitored if possible.

. The following drugs/classes are metabolized by the same CYP3A isoenzyme as clarithromycin, such as alprazolam, carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, midazolam, omeprazole, indirect anticoagulants (e.g., warfarin), quinidine, rifabutin, sildenafil, tacrolimus, triazolam and vinblastine. CYP3A isoenzyme agonists also include the following drugs that are contraindicated for co-administration with clarithromycin: astemizole, cisapride, pimozide, terfenadine, lovastatin, simvastatin and ergot alkaloids (see section “Contraindications”). Drugs that interact similarly through other isoenzymes within the cytochrome P450 system include phenytoin, theophylline and valproic acid.

Indirect anticoagulants

Coadministration of warfarin and clarithromycin may cause bleeding, marked increase in INR and prothrombin time. If combined with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored.

Omeprazole

Clarithromycin (500 mg every 8 hours) was studied in healthy adult volunteers in combination with omeprazole (40 mg daily). When clarithromycin and omeprazole were used together, equilibrium plasma concentrations of omeprazole were increased (Cmax, AUC024 and T1/2 increased by 30%, 89% and 34%, respectively). Mean gastric pH over 24 hours was 5.2 when omeprazole was taken alone and 5.7 when omeprazole was taken together with clarithromycin.

Sildenafil, tadalafil and vardenafil

Each of these phosphodiesterase inhibitors is metabolized at least in part with the CYP3A isoenzyme. However, the CYP3A isoenzyme may be inhibited in the presence of clarithromycin. Co-use of clarithromycin with sildenafil, tadalafil or vardenafil may lead to increased inhibitory effects on phosphodiesterase. When using these drugs together with clarithromycin, consideration should be given to reducing the dose of sildenafil, tadalafil and vardenafil.

Theophylline, carbamazepine

The combined use of clarithromycin and theophylline or carbamazepine may increase systemic drug concentrations.

Tolterodine

The primary metabolism of tolterodine is through the 2D6 isoform of cytochrome P450 (CYP2D6). However, in a portion of the population lacking the CYP2D6 isoenzyme, metabolism occurs via the CYP3A isoenzyme. In this population, suppression of the CYP3A isoenzyme leads to significantly higher serum concentrations of tolterodine. In a population with low levels of metabolism through the CYP2D6 isoenzyme, a dose reduction of tolterodine in the presence of CYP3A isoenzyme inhibitors such as clarithromycin may be required.

Benzodiazepines (e.g., alprazolam, midazolam, triazolam)

The co-administration of midazolam and clarithromycin tablets (500 mg twice daily) showed a 2.7-fold increase in AUC of midazolam after intravenous administration of midazolam and 7-fold increase after oral administration. Simultaneous use of clarithromycin with oral midazolam is contraindicated. If intravenous midazolam is used with clarithromycin, the patient should be closely monitored for possible dose adjustment.

The same precautions should be applied to other benzodiazepines that are metabolized by the CYP3A isoenzyme, including triazolam and alprazolam. For benzodiazepines whose excretion is not dependent on CYP3A isoenzyme (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

When clarithromycin and triazolam are used together, central nervous system (CNS) effects such as drowsiness and confusion are possible. Therefore, it is recommended to monitor for CNS disturbance symptoms if used together.

Interactions with other drugs

Aminoglycosides

When clarithromycin is coadministered with other ototoxic drugs, especially aminoglycosides, care should be taken to monitor vestibular and auditory function both during and after therapy.

Colchicine

Colchicine is a substrate of both the CYP3A isoenzyme and the Rglycoprotein transporter protein (Pgp). Clarithromycin and other macrolides are known to be CYP3A and Pgp isoenzyme inhibitors. If clarithromycin and colchicine are taken together, inhibition of Pgp and/or CYP3A isoenzyme may increase the effect of colchicine. The development of clinical symptoms of colchicine poisoning should be monitored.

Postmarketing reports of cases of colchicine poisoning have been reported when colchicine is taken concomitantly with clarithromycin, more often in elderly patients. Some of the cases described have occurred in patients with renal impairment. Some cases have been reported to be fatal. Concomitant use of clarithromycin and colchicine is contraindicated (see section “Contraindications”).

Digoxin

Digoxin is believed to be a substrate of Pgp. Clarithromycin is known to inhibit Pgp. When clarithromycin and digoxin are coadministered, the inhibition of Pgp by clarithromycin may enhance the effects of digoxin. Co-administration of digoxin and clarithromycin may also lead to increased serum concentrations of digoxin. Clinical symptoms of digoxin poisoning, including potentially fatal arrhythmias, have been reported in some patients. Serum digoxin concentrations should be closely monitored when clarithromycin and digoxin are coadministered.

Zidovudine

The concomitant oral administration of clarithromycin tablets and zidovudine in HIV-infected adults may decrease the equilibrium concentration of zidovudine.

Because clarithromycin affects oral absorption of zidovudine, interactions can be largely avoided by taking clarithromycin and zidovudine 4 hours apart.

A similar interaction was not observed in HIV-infected children taking clarithromycin infant suspension with zidovudine or dideoxynosine. Because clarithromycin can interfere with the absorption of zidovudine when they are taken simultaneously orally in adult patients, this interaction is unlikely to occur with intravenous clarithromycin.

Phenytoin and valproic acid

There are data on interactions of CYP3A inhibitors (including clarithromycin) with drugs that are not metabolized by CYP3A (phenytoin and valproic acid). For these drugs, when combined with clarithromycin, determination of their serum concentrations is recommended, since there have been reports of elevated concentrations.

Bidirectional drug interactions

Atazanavir

Clarithromycin and atazanavir are both substrates and inhibitors of the CYP3A isoenzyme. There is evidence of a bidirectional interaction between these drugs. The combined use of clarithromycin (500 mg twice daily) and atazanavir (400 mg once daily) may result in a twofold increase in exposure to clarithromycin and a 70% decrease in exposure to 14OHclarithromycin, with a 28% increase in AUC of atazanavir. Because of the wide therapeutic range of clarithromycin, no dose reduction is required in patients with normal renal function.

In patients with moderate renal impairment (CK 30-60 ml/min), the dose of clarithromycin should be reduced by 50%. In patients with a CKR less than 30 ml/min, the dose of clarithromycin should be reduced by 75% using the appropriate clarithromycin dosage form. Clarithromycin in doses greater than 1000 mg per day should not be used with protease inhibitors.

Slow calcium channel blockers

Care should be taken with clarithromycin and slow calcium channel blockers that are metabolized by CYP3A4 (e.g. verapamil, amlodipine, diltiazem) simultaneously because of the risk of arterial hypotension. Plasma concentrations of clarithromycin, as well as of “slow” calcium channel blockers may increase with concomitant use. Arterial hypotension, bradyarrhythmia and lactoacidosis are possible with concomitant use of clarithromycin and verapamil.

Itraconazole

Clarithromycin and itraconazole are substrates and inhibitors of CYP3A isoenzyme, which determines the bidirectional interaction of the drugs. Clarithromycin may increase the plasma concentration of itraconazole, while itraconazole may increase the plasma concentration of clarithromycin. Patients taking itraconazole and clarithromycin concomitantly should be carefully examined for symptoms of increased or prolonged duration of pharmacological effects of these drugs.

Saquinavir

Clarithromycin and saquinavir are substrates and inhibitors of CYP3A isoenzyme, which determines the bidirectional interaction of the drugs. Concomitant use of clarithromycin (500 mg twice daily) and saquinavir (in soft gelatin capsules, 1200 mg three times daily) in 12 healthy volunteers caused a 177% and 187% increase in AUC and Cmax of saquinavir, respectively, compared with taking saquinavir alone. The AUC and Cmax values of clarithromycin were approximately 40% higher than those of clarithromycin monotherapy.

Dose adjustments are not required when the two drugs are used together for a limited time in the doses/compositions listed above. The results of drug interaction studies using saquinavir in soft gelatin capsules may not be consistent with the effects observed with saquinavir in hard gelatin capsules. The results of studies of drug interactions with saquinavir monotherapy may not correspond to the effects observed with saquinavir/ritonavir therapy. The potential effects of ritonavir on clarithromycin should be considered when taking saquinavir together with ritonavir.

Special Instructions

Prolonged use of antibiotics can lead to the formation of colonies with increased numbers of insensitive bacteria and fungi. In case of superinfection, appropriate therapy should be prescribed.

Given the increasing resistance of Streptococcus pneumoniae to macrolides, it is important to perform sensitivity testing when prescribing clarithromycin to patients with community-acquired pneumonia. In hospital pneumonia, clarithromycin should be used in combination with appropriate antibiotics. Skin and soft tissue infections of mild to moderate severity are most often caused by Staphylococcus aureus and Streptococcus pyogenes. Both pathogens can be resistant to macrolides. Therefore, it is important to test for sensitivity.

Macrolides can be used for infections caused by Corynebacterium minutissimum, Acne vulgaris and rye, and in situations where penicillin cannot be used.

Cross-resistance to clarithromycin and other antibiotics of the macrolide group as well as to lincomycin and clindamycin may develop.

Clarithromycin should be used with caution in patients with coronary heart disease (CHD), severe heart failure, hypomagnesemia, severe bradycardia (less than 50 bpm), and concomitant use with class IA antiarrhythmic drugs (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol). In these conditions and when concomitant use of clarithromycin with these drugs, regular electrocardiogram monitoring for QT interval prolongation should be performed.

Hepatic dysfunction (increased hepatic enzyme concentrations in blood, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with clarithromycin. Liver dysfunction can be severe, but is usually reversible. There are cases of hepatic failure with fatal outcome, mainly associated with the presence of serious comorbidities and/or concomitant use of other drugs. In case of signs and symptoms of hepatitis, such as anorexia, jaundice, darkened urine, itching, abdominal pain on palpation, clarithromycin therapy should be stopped immediately.

In the presence of chronic liver disease, regular monitoring of serum enzymes is necessary.

In case of co-administration with warfarin or other indirect anticoagulants, INR and prothrombin time should be monitored.

In treatment with virtually all antibacterials, including clarithromycin, there have been cases of pseudomembranous colitis, the severity of which may range from mild to life-threatening. Antibacterials can alter the normal intestinal microflora, which can lead to growth of C. difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who experience diarrhea after antibiotic use. After a course of antibiotic therapy, careful medical follow-up of the patient is necessary. Cases of pseudomembranous colitis have been described 2 months after antibiotic treatment.

In case of acute hypersensitivity reactions such as anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), clarithromycin should be stopped immediately and appropriate therapy started.

Influence on driving and operating ability

There are no data on the effect of clarithromycin on driving and operating ability.

Caution should be exercised when driving vehicles and operating machinery, given the potential for dizziness, vertigo, confusion, and disorientation that may occur with this drug.

Contraindications

Hypersensitivity to clarithromycin, other drug components and other macrolides;

– Concomitant administration of clarithromycin with the following drugs: astemizole, cisapride, pimozide and terfenadine (see “Interaction with other drugs.

Simultaneous use of clarithromycin with ergot alkaloids, e.g. ergotamine, dihydroergotamine (see Interaction with other medicinal products).

Simultaneous use of clarithromycin with oral midazolam (see “Interaction with other drugs”).

Concomitant use of clarithromycin with HMG-CoA reductase inhibitors (statins) that are significantly metabolized by CYP3A4 isoenzymes (lovastatin, simvastatin) due to an increased risk of myopathy, including rhabdomyolysis (see “Interaction with other drugs”). Interaction with other drugs);

– Concomitant use of colchicine;

– Concurrent use with ticagrelor or ranolazine;

– History of QT interval prolongation, ventricular arrhythmia, or pirouette-type ventricular tachycardia;

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– Hypokalemia (risk of QT interval prolongation);

– Severe hepatic impairment concurrent with renal impairment;

– A history of cholestatic jaundice/hepatitis with clarithromycin (for a history of clarithromycin);

– Cholestatic jaundice/hepatitis developed with clarithromycin (see Special Indications);

– Porphyria;

– Breastfeeding period;

– Under 12 years of age.

With caution

– Moderate to severe renal failure;

– Moderate to severe hepatic failure;

– Concomitant use of clarithromycin with other ototoxic drugs, particularly aminoglycosides (see “Interaction with other ototoxic drugs, especially aminoglycosides. Interaction with other medicinal products).

Concomitantly taking clarithromycin with other ototoxic drugs, especially aminoglycosides (see Interaction with other medicinal products). – Concomitant use with drugs that are metabolized by the CYP3A isoenzyme, e.g., carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (e.g., warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine (see

– Concomitant use with drugs that induce the CYP3A4 isoenzyme, e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort (see “Interaction with other medicinal products”).

– Concomitant administration of clarithromycin with statins that do not depend on CYP3A isoenzyme metabolism (e.g., fluvastatin) (see “Interaction with other medicinal products”).

– Concurrent use with benzodiazepines such as alprazolam, triazolam, midazolam for intravenous administration;

– Concurrent use of class IA antiarrhythmic drugs (quinidine, procainamide) and class III drugs (dofetilide, amiodarone, sotalol);

– Concomitant use with “slow” calcium channel blockers that are metabolized by the CYP3A4 isoenzyme (e.g., verapamil, amlodipine, diltiazem);

– Coronary heart disease, severe heart failure, hypomagnesemia, significant bradycardia (less than 50 bpm);

– Pregnancy.

Side effects

Classification of adverse reactions by frequency of development (number of reported cases/number of patients):

Very common (≥1/10),

Frequent (≥1/100, < 1/10),

Infrequent (≥1/1000, < 1/100),

Frequency unknown (side effects from postmarketing experience; frequency cannot be estimated from available data).

Allergic reactions

Often: rash.

Infrequent: hypersensitivity, itching, urticaria, maculopapular rash2.

Frequent unknown: anaphylactic reaction, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).

Nervous system disorders

Often: headache, insomnia.

Infrequently: dizziness, somnolence, tremor, restlessness, increased excitability2.

Prevalence unknown: seizures, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dream disorders (“nightmares” dreams), paresthesia, mania.

Skin disorders

Often: intense sweating.

Prevalence unknown: acne, hemorrhages.

Urinary system disorders

Prevalence unknown: renal failure, interstitial nephritis.

Metabolism and nutrition disorders

Infrequent: anorexia, decreased appetite.

Musculoskeletal disorders

Infrequent: muscle spasm2, myalgia1.

Infrequent unknown: rhabdomyolysis1*, myopathy.

Digestive system disorders

Often: diarrhea, vomiting, dyspepsia, nausea, abdominal pain.

Infrequent: gastroesophageal reflux disease1, gastritis, proctalgia1, stomatitis, glossitis, bloating3, constipation, dry mouth, belching, flatulence, cholestasis3, hepatitis including cholestatic or hepatocellular3.

Frequency unknown: acute pancreatitis, discoloration of tongue and teeth, liver failure, cholestatic jaundice.

Respiratory system disorders

Infrequent: nasal bleeding1.

Sensory system disorders

Often: dysgeusia, perversion of taste.

Infrequent: vertigo, hearing impairment, tinnitus.

Frequent unknown: deafness, agueusia (loss of taste), parosmia, anosmia.

Cardiovascular system disorders

Infrequent: prolongation of the QT interval in the electrocardiogram, atrial flutter.

Infrequent unknown: ventricular tachycardia, including pirouette type.

Laboratory indices

Often: abnormal liver function test.

Infrequent: leukopenia, neutropenia3, eosinophilia3, thrombocythemia2, increased activity of: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyltransferase (GGTP)3, alkaline phosphatase3, lactate dehydrogenase (LDH)3.

Frequency unknown: agranulocytosis, thrombocytopenia, increased international normalized ratio (INR), prolongation of prothrombin time, color changes in urine, increased blood bilirubin concentration.

General disorders

Infrequent: malaise3, hyperthermia2, asthenia, chest pain3, chills3, fatigue3.

Infectious and parasitic diseases

Infrequent: candidiasis, gastroenteritis1, secondary infections2 (including vaginal).

Infrequent unknown: pseudomembranous colitis, rye.

Patients with suppressed immunity

In patients with AIDS and other immunodeficiencies who receive clarithromycin at higher doses for long term treatment of mycobacterial infections, it is often difficult to distinguish adverse effects of the drug from symptoms of HIV infection or comorbidities.

The most common adverse events in patients taking a daily dose of clarithromycin equal to 1000 mg were: nausea, vomiting, perversion of taste, abdominal pain, diarrhea, rash, flatulence, headache, constipation, hearing loss, and increased AST and ALT activity in blood. There have also been cases of adverse events with low frequency of occurrence, such as dyspnea, insomnia, and dry mouth.

In patients with suppressed immunity, laboratory parameters were evaluated by analyzing their significant deviations from the norm (sharp increase or decrease). Based on this criterion, 2-3% of patients who received clarithromycin at a dose of 1000 mg daily registered a significant increase in AST and ALT activity in the blood, as well as a decrease in leukocyte and platelet counts. A small number of patients also registered an increase in residual urea nitrogen concentration.

* In some reports of rhabdomyolysis, clarithromycin has been taken together with other drugs known to be associated with rhabdomyolysis (statins, fibrates, colchicine or allopurinol).

1 These adverse reactions have only been reported with clarithromycin in its dosage form: sustained release film-coated tablets.

2 These adverse reactions have only been reported with clarithromycin in the dosage form: powder for oral suspension.

3 These adverse reactions have only been reported with clarithromycin in the dosage form of film-coated tablets.

Overdose

Symptoms: Taking a large dose of clarithromycin may cause gastrointestinal symptoms.

One patient with a history of bipolar disorder has described mental status changes, paranoid behavior, hypokalemia and hypoxemia after taking 8 g of clarithromycin.

Treatment: in case of overdose the unabsorbed drug should be removed from the gastrointestinal tract (gastric lavage, administration of activated charcoal, etc.) and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis have no significant effect on serum concentrations of clarithromycin, as is the case with other drugs of the macrolide group.

Pregnancy use

The safety of clarithromycin use during pregnancy and breastfeeding has not been established.

The use of clarithromycin in pregnancy (especially in the first trimester) is possible only if there is no alternative therapy and the potential benefit to the mother exceeds the potential risk to the fetus.

Clarithromycin is excreted with the breast milk. Breast-feeding should be discontinued if it is necessary during breast-feeding.

Similarities