Clacid, 250 mg/5 ml 49.5 g 1 ml

– Infectious and inflammatory diseases caused by microorganisms sensitive to clarithromycin: 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;

– acute otitis media.

Active ingredient

Composition

How to take, the dosage

Interaction

Interaction with cytochrome P450

Clarithromycin is metabolized in the liver by the cytochrome P4503A isoenzyme (CYP3A). This mechanism determines many interactions with other drugs. Clarithromycin can inhibit the biotransformation of other drugs by this system, which may increase their serum levels.

The following drugs or 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.

Similar mechanisms of interaction, which are mediated by other cytochrome P450 isoenzymes, are typical for phenytoin, theophylline and valproic acid. In clinical studies when combining theophylline or carbamazepine with clarithromycin a small but statistically significant (p

The following CYP3A-mediated interactions have been reported in clinical practice when using erythromycin and/or clarithromycin.

In combined use of clarithromycin with HMG-CoA reductase inhibitors such as lovastatin and simvastatin, rhabdomyolysis has rarely developed.

In concomitant use of clarithromycin with cisapride, increased levels of the latter have been observed. This may result in prolongation of the QT interval and development of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation and pirouette-type polymorphic ventricular tachycardia. Similar effects have been reported in patients receiving clarithromycin with pimozide.

The macrolides disrupted terfenadine metabolism, resulting in increased plasma levels and were sometimes associated with the development of arrhythmias, including prolonged QT interval, ventricular tachycardia, ventricular fibrillation and pirouette ventricular tachycardia.

In one study in 14 healthy volunteers, combined use of clarithromycin and terfenadine tablets resulted in a 2-3-fold increase in serum levels of the acidic metabolite terfenadine and prolongation of the QT interval that was not accompanied by any clinical effects.

In clinical practice, cases of pirouette-type ventricular tachycardia have been reported when clarithromycin is combined with quinidine or disopyramide. Serum levels of these drugs should be monitored during treatment with clarithromycin.

Ergotamine/dihydroergotamine. In clinical practice when clarithromycin is combined with ergotamine or dihydroergotamine there have been cases of acute toxicity of the latter, characterized by vasospasm and ischemia of the extremities and other tissues, including the CNS.

Interaction with other drugs. In patients who received clarithromycin tablets in combination with digoxin, increased serum concentrations of the latter were observed. It is reasonable to monitor serum levels of digoxin.

Colchicine. It is a substrate for CYP3A and P-glycoprotein. Clarithromycin and other macrolides are inhibitors of CYP3A and P-glycoprotein. When colchicine and clarithromycin are coadministered, inhibition of P-glycoprotein and/or CYP3A may increase the effect of colchicine. Patients should be closely monitored for symptoms of colchicine toxicity.

Interaction with antiretroviral agents. Concomitant oral administration of clarithromycin tablets with zidovudine in HIV-infected adult patients may result in decreased Css of zidovudine. A similar interaction was not observed in HIV-infected children taking clarithromycin infant suspension with zidovudine or dideoxynosine.

In a pharmacokinetic study, the combined use of ritonavir at a dose of 200 mg every 8 h and clarithromycin at a dose of 500 mg every 12 h resulted in significant inhibition of clarithromycin metabolism. The Cmax of clarithromycin when combined with ritonavir increased by 31%, the Cmin by 182%, and the AUC by 77%.

There was virtually complete inhibition of 14-hydroxyclarithromycin formation. Given the high therapeutic index of clarithromycin, dose reduction is not required in patients with normal renal function. However, in patients with impaired renal function it is reasonable to adjust the dose.

In patients with creatinine Cl 30-60 ml/min, the dose of clarithromycin is reduced by 50%, and in patients with creatinine Cl

Special Instructions

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

With caution, use with drugs that are metabolized by the liver.

In case of co-administration with warfarin or other indirect anticoagulants, PV should be monitored.

In children, it is preferable to use Clacid in the dosage form of oral suspension powder 125 mg/5 ml and 250 mg/5 ml.

Contraindications

With caution: moderate to severe renal failure; moderate to severe hepatic failure; myasthenia gravis (possible worsening of symptoms); concomitant administration of clarithromycin with benzodiazepines such as alprazolam, triazolam, midazolam for intravenous use; concomitant use with drugs that are metabolized by CYP3A isoenzymes, such as carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (e.g., warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine; concomitant use with drugs that induce the CYP3A4 isoenzyme, e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort; concomitant use with calcium channel blockers that are metabolized by the CYP3A4 isoenzyme (e.g. verapamil, amlodipine, diltiazem) Patients with coronary heart disease (CHD), severe heart failure, hypomagnesemia, significant bradycardia (less than 50 bpm), as well as patients concomitantly taking antiarrhythmic drugs of class IA (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol); pregnancy; diabetes (the drug contains sucrose).

Side effects

Gastrointestinal adverse events, including diarrhea, vomiting, abdominal pain, and nausea, were the most common. Other adverse reactions included headache, impaired taste, and a transient increase in liver enzyme activity.

Postmarketing experience

In treatment with clarithromycin, hepatic dysfunction, including increased hepatic enzyme activity, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, have been infrequently reported. Hepatic dysfunction can be severe and is usually reversible. Very rare cases of death from liver failure have been reported, which have usually been observed in the presence of serious comorbidities and/or concomitant use of other drugs.

In isolated cases of increased serum creatinine levels have been described, but their association with the drug has not been established.

In oral use of clarithromycin, allergic reactions have been described, which have ranged from urticaria and minor rashes to anaphylaxis and Stevens-Johnson syndrome/toxic epidermal necrolysis.

Transient CNS effects including dizziness, anxiety, insomnia, nightmares, tinnitus, confusion, disorientation, hallucinations, psychosis, and depersonalization have been reported; their causal relationship to the drug has not been established.

Hearing loss has been described with clarithromycin treatment; after discontinuation of treatment, hearing usually recovered. There have also been known cases of olfactory disturbances, usually combined with a perversion of taste.

In treatment with clarithromycin, glossitis, stomatitis, oral thrush, and discoloration of the tongue have been described. There have been known cases of discoloration of the teeth in patients treated with clarithromycin. These changes are usually reversible and can be corrected by a dentist.

Rare cases of hypoglycemia have been described, some of which have occurred in patients who received oral antidiabetic drugs or insulin.

In isolated cases of leukopenia and thrombocytopenia have been reported.

In treatment with clarithromycin, as well as other macrolides, prolongation of QT interval, ventricular tachycardia and pirouette-type ventricular tachycardia have been noted in rare cases.

Rare cases of pancreatitis and seizures have been described.

There have been reports of the development of interstitial nephritis during treatment with clarithromycin.

In clinical practice, there have been described cases of colchicine toxicity when combined with clarithromycin, especially in the elderly. Some of these have been seen in patients with renal failure; several deaths have been reported in such patients.

Children 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 differentiate adverse effects of the drug from symptoms of HIV infection or intercurrent disease.

The main adverse events in patients taking clarithromycin orally at a dose of 1 g were nausea, vomiting, perversion of taste, abdominal pain, diarrhea, rash, abdominal bloating, headache, hearing loss, constipation, and elevated AST and ALT levels. Dyspnea, insomnia, and dry mouth have also been reported less frequently.

In this group of immunocompromised patients, significant deviations of laboratory values from normal values in specific tests (sharp increase or decrease) were recorded.

Based on this, approximately 2-3% of patients who took clarithromycin orally at a dose of 1 g/day had significant abnormal lab values, such as elevated AST and ALT levels and decreased white blood cell and platelet counts. Fewer patients also had elevated blood urea nitrogen levels.

Overdose

Symptoms: Taking a large dose of clarithromycin may cause symptoms of gastrointestinal disorders. In one patient with a history of bipolar disorder after taking 8 g of clarithromycin mental changes, paranoid behavior, hypokalemia and hypoxemia have been described.

Treatment: in case of overdose the unabsorbed drug should be removed from the gastrointestinal tract and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis have no significant effect on serum levels of clarithromycin as well as other drugs of macrolide group.

Pregnancy use

Similarities