Clarithromycin-Teva, 500 mg 14 pcs.

Indications

Infectious inflammatory diseases caused by clarithromycin-sensitive microorganisms in adults and children over 12 years:

Active ingredient

Composition

1 tablet contains:

acting substance:

clarithromycin – 500.0 mg;

excipients: povidone – 20.0 mg, microcrystalline cellulose – 24.0 mg, croscarmellose sodium – 40.0 mg, colloidal silicon dioxide – 6.0 mg, magnesium stearate – 10.0 mg;

film coating Opadray II 31F58914 white – 20.0 mg: Hypromellose (E464) – 6.990 mg, lactose monohydrate – 5.436 mg, titanium dioxide (E171) – 5.048 mg, macrogol 4000 – 1.940 mg, sodium citrate dihydrate (E331) – 0.586 mg, purified water* q.s.

* The purified water used in the granulation and coating process is evaporated during the manufacturing process.

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 of age is 250 mg 2 times daily (in this case the use of Clarithromycin-Teva film-coated tablets 250 mg is possible).

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

The usual duration of treatment is 5 to 14 days.

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

Dosages for treatment of mycobacterial infections except tuberculosis

In mycobacterial infections, a clarithromycin dose of 500 mg 2 times daily is recommended.

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 the prevention of infections caused by MAC.

The recommended dose of clarithromycin for adults is 500 mg 2 times daily.

For odontogenic infections the dose of clarithromycin is 250 mg 2 times daily for 5 days (for film-coated Clarithromycin-Teva, 250 mg).

For eradication of H. pylori

In patients with peptic ulcer disease caused by H.pylori, clarithromycin may be administered at 500 mg 2 times 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.

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.or, in more severe infections, 250 mg twice daily. Treatment of such patients is continued for no more than 14 days.

Use in children younger than 12 years

The use of clarithromycin in tablet form in children younger than 12 years has not been studied.

Interaction

The following drugs are contraindicated with clarithromycin due to the possibility of serious side effects:

Cisapride, pimozide, terfenadine and astemizole

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

Argot alkaloids

. Post-marketing studies indicate that the following effects associated with acute poisoning with ergotamine or dihydroergotamine are possible when clarithromycin is coadministered with ergotamine or dihydroergotamine Vascular spasm, ischemia of the extremities and other tissues, including the central nervous system. Concomitant administration of clarithromycin with ergot alkaloids is contraindicated (see section “Contraindications”).

Midazolam for oral use

. Co-administration of midazolam and clarithromycin in tablet form (500 mg twice daily) showed a 7-fold increase in AUC of midazolam after oral administration. Simultaneous oral administration of clarithromycin and midazolam is contraindicated (see section “Contraindications”).

HMG-CoA reductase inhibitors (statins)

The concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see “Contraindications. Concomitant use of lovastatin or simvastatin is contraindicated (see section “Contraindications”) due to the fact that these statins are largely metabolized by CYP3A4 isoenzyme and their serum concentrations are increased with clarithromycin, 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.

Influence 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 therapeutic effect, while increasing the concentration of 14-OH clarithromycin, a metabolite that is also microbiologically active. Because the microbiological activity of clarithromycin and 14-OH clarithromycin is different for different bacteria, the therapeutic effect may be reduced when clarithromycin and enzyme inducers are used together.

Etravirin

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

Fluconazole

. Co-treatment with 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 minimum equilibrium concentration of clarithromycin (Cmin) and AUC, respectively. However, co-administration did not significantly affect the mean equilibrium concentration of the active metabolite 14-OH-clarithromycin. No dose adjustment of clarithromycin in case of concomitant administration of fluconazole is required.

Ritonavir

. A pharmacokinetic study showed 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 14-OH clarithromycin formation was noted. 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.

Similar dose adjustments should be considered in patients with reduced renal function if ritonavir is used as a pharmacokinetic “enhancer” when other HIV protease inhibitors, including atazanavir and saquinavir are used (see subsection “Bidirectional Drug Interactions”).

Effects of clarithromycin on other drugs

Antiarrhythmic agents (quinidine and disopyramide).

Ventricular pirouette tachycardia may occur if clarithromycin and quinidine or disopyramide are used together. If clarithromycin is coadministered with these drugs, regular ECG monitoring for QT interval prolongation should be performed, and serum concentrations of these drugs should be monitored.

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

Peroral hypoglycemic agents/insulin

. Severe hypoglycemia may occur when clarithromycin and oral hypoglycemic agents (e.g., sulfonylurea derivatives) and/or insulin are used together. 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 concentrations is recommended.

Interactions due to isoenzyme .CYP3A

Co-administration of clarithromycin, which is known to inhibit the CYP3A isoenzyme, and drugs primarily metabolized by the CYP3A isoenzyme may be associated with a mutual increase in their concentrations, which may increase 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, e.g., alprazolam, carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, Midazolam, omeprazole, indirect anticoagulants (e.g., warfarin), atypical antipsychotics (e.g., quetiapine), quinidine, rifabutin, sildenafil, tacrolimus, triazolam, vinblastine, and others. 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.

Direct anticoagulants

The co-administration of warfarin and clarithromycin may cause bleeding, marked increase in MHO and prothrombin time. If combined with warfarin or other indirect anticoagulants, MHO and prothrombin time should be monitored.

Omeprazole

Clarithromycin (500 mg every 8 hours) has been 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 , AUC0-24 and T1/2 were increased by 30%, 89% and 34% respectively). The 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. Consider reducing the dose of sildenafil, tadalafil, and vardenafil when using these drugs in conjunction with clarithromycin.

Theophylline, carbamazepine

The combined use of clarithromycin and theophylline or carbamazepine may increase the concentration of these drugs in the systemic blood stream.

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 via 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)

. When midazolam and clarithromycin tablets (500 mg twice daily) were used together, there was an increase in the AUC of midazolam: 2.7-fold after intravenous administration of midazolam and 7-fold after oral administration. Simultaneous use of clarithromycin with oral midazolam is contraindicated. If intravenous form of midazolam is used together with clarithromycin, the patient’s condition should be closely monitored for possible dose adjustment. Administration of the drug through the oral mucosa, which allows bypassing presystemic elimination, is likely to result in interactions similar to those seen with intravenous midazolam rather than with oral administration.

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

Colchicine.

Colchicine is a substrate of both the CYP3A isoenzyme and the carrier protein P-glycoprotein (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 controlled. There have been post-marketing reports of cases of colchicine poisoning when concomitantly administered with clarithromycin, more often in elderly patients. Some of the described cases occurred with patients suffering from renal insufficiency. Some cases have been reported to be fatal.

The concomitant use of clarithromycin and colchicine is contraindicated (see section on 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 simultaneous 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 at 4-hour intervals.

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

Directional drug interactions

Atazanavir

Special Instructions

Long-term antibiotic use may lead to colonies with increased numbers of insensitive bacteria and fungi. Appropriate therapy should be prescribed for superinfections.

Prescribing clarithromycin to pregnant women should be done with careful risk-benefit assessment, especially during the first three months of pregnancy.

Hepatic dysfunction (increased hepatic enzyme activity in the 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 should be performed.

In the treatment with almost 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 gut microflora, which can lead to the growth of Clostridium difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who experience the appearance of diarrhea after using antibiotics. After a course of antibiotic therapy, close medical follow-up of the patient is necessary. Cases of pseudomembranous colitis have been described 2 months after antibiotic treatment.

Treatment with macrolides, including clarithromycin, has been observed to prolong cardiac repolarization and the QT interval, causing the risk of cardiac arrhythmias and pirouette-type ventricular tachycardia.

Clarithromycin should not be used in the following patient categories:

Clarithromycin should be used with caution in the following categories of patients:

Synopsis

Contraindications

Side effects

Classification of adverse reactions by frequency of development (number of cases/number of patients reported): very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), frequency unknown (adverse effects from postmarketing experience; frequency cannot be estimated based on available data).

Allergic reactions: frequently – rash; infrequent – anaphylactoid reaction1, hypersensitivity, bullous dermatitis1, pruritus, urticaria, maculopapular rash3; incidence unknown -anaphylactic reaction, angioedema, serious skin adverse reactions (e.g., acute generalized exanthematous pustulosis), Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).

From the central nervous system: frequent – headache, insomnia; infrequent – loss of consciousness1, dyskinesia1, dizziness, somnolence, tremor, anxiety, hyperexcitability3; frequency unknown – seizures, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dream disorders (“nightmare” dreams), paresthesia, mania.

Skin: often – intense sweating; frequency unknown – acne.

Since the urinary system: frequency unknown – renal failure, interstitial nephritis.

From the metabolic side: infrequently – anorexia, decreased appetite.

Motor system disorders: infrequent- muscle spasm3, musculoskeletal stiffness1, myalgia2; frequency unknown – rhabdomyolysis2*, myopathy.

From the digestive system: frequent – diarrhea, vomiting, dyspepsia, nausea, abdominal pain; infrequent – esophagitis1, gastroesophageal reflux disease2, gastritis, proctalgia2, stomatitis, glossitis, abdominal bloating4, constipation, dry mouth, belching, flatulence, cholestasis4, hepatitis incl.including cholestatic or hepatocellular4; frequency unknown – acute pancreatitis, discoloration of tongue and teeth, liver failure, cholestatic jaundice.

Respiratory system: infrequent – asthma1, nasal bleeding2, pulmonary embolism1.

Sense organs: frequent – dysgeusia; infrequent – vertigo, hearing impairment, tinnitus; frequency unknown – deafness, agueusia (loss of taste sensation), parosmia, anosmia.

Cardiovascular system side: frequent – vasodilation1; infrequent – cardiac arrest1atrial fibrillation1, prolongation of QT interval on electrocardiogram (ECG), extrasystole -susup>1, palpitations; frequency unknown – ventricular tachycardia, including pirouette type, ventricular fibrillation, bleeding.

Laboratory findings: frequent – abnormality in hepatic sample; infrequent – increase in creatinine1 concentration, increase in urea1 concentration., change in albumin-globulin ratio1, leukopenia, neutropenia4, eosinophilia4, thrombocythemia3, increased activity: alanine aminotransferase (ALT), aspartate aminotransferase (ACT), gammaglutamyltransferase (GGTP)4/sup>, alkaline phosphatase4, lactate dehydrogenase (LDH)4; frequency unknown – agranulocytosis, thrombocytopenia, increased international normalized ratio (MHO) value, prolongation of prothrombin time, change in urine color, increased blood bilirubin concentration.

General disorders: very often – phlebitis at the injection site1; often –

Overdose

Symptoms:The high 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 performed. 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

Pregnancy

The safety of clarithromycin in pregnancy has not been studied. Use 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.

Breastfeeding

The safety of clarithromycin during breastfeeding has not been studied. The drug penetrates into the breast milk. If it is necessary to use Clarithromycin-Teva during lactation, breastfeeding should be stopped.

Similarities