Clarithromycin-Teva

The use of the following drugs with clarithromycin is contraindicated due to the potential for serious side effects:

Cisapride, pimozide, terfenadine and astemizole

When clarithromycin was co-administered with cisapride, pimozide, terfenadine or astemizole, increased plasma concentrations of the latter were reported, which may

And lead to prolongation of the QT interval and the appearance of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation and torsade de pointes (see section “Contraindications”).

Ergot alkaloids

Post-marketing studies show that when clarithromycin is used together with ergotamine or dihydroergotamine, the following effects associated with acute poisoning with ergotamine drugs are possible: vascular spasm, ischemia of the limbs and other tissues, including the central nervous system. Concomitant use of clarithromycin with ergot alkaloids is contraindicated (see section "Contraindications").

Midazolam for oral use

When midazolam and clarithromycin were used together in tablet form (500 mg 2 times daily), a 7-fold increase in midazolam AUC was observed after oral administration. Concomitant use of clarithromycin with oral midazolam is contraindicated (see section "Contraindications").

HMG-CoA reductase inhibitors (statins)

Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see section "Contraindications") due to the fact that these statins are largely metabolized by the CYP3A4 isoenzyme, and combined use with clarithromycin increases their serum concentrations, which leads to an increased risk of developing myopathy, including Rhabdomyolysis Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these drugs. If clarithromycin is necessary, lovastatin or simvastatin should be discontinued during therapy.

Clarithromycin should be used with caution in combination therapy with other statins. It is recommended to use statins that do not depend on the metabolism of the CYP3A isoenzyme (for example, 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.

Effect of other drugs on clarithromycin

Drugs that are inducers of the CYP3A isoenzyme (for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) can induce the metabolism of clarithromycin. This may result in subtherapeutic concentrations of clarithromycin, resulting in reduced effectiveness. In addition, it is necessary to monitor the concentration of the CYP3A inducer in the blood plasma, which may increase due to the inhibition of the CYP3A isoenzyme by clarithromycin. When rifabutin and clarithromycin were used together, an increase in plasma 12 concentrations of rifabutin and a decrease in serum concentrations of clarithromycin were observed with an increased risk of developing uveitis.

The following drugs have a proven or suspected effect on clarithromycin plasma concentrations; if used concomitantly with clarithromycin, dosage adjustments or switching to alternative treatment may be required.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine

Strong inducers of the cytochrome P450 system, such as efavirenz, nevirapine, rifampin, rifabutin and rifapentine, can accelerate the metabolism of clarithromycin and, thus, reduce the plasma concentration of clarithromycin and weaken the therapeutic effect, and at the same time increase the concentration of 14-OH-clarithromycin - a metabolite that is also microbiologically active. Since the microbiological activity of clarithromycin and 14-OH-clarithromycin differs against different bacteria, the therapeutic effect may be reduced when clarithromycin is used together with enzyme inducers.

Etravirine

Clarithromycin concentrations are reduced when etravirine is used. but the concentration of the active metabolite 14-OH-clarithromycin increases. Because 14-OH-clarithromycin has low activity against Mycobacterium avium complex (MAC) infections, overall activity against these pathogens may be affected, and alternative treatments should be considered for the treatment of MAC.

Fluconazole

Coadministration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily in 21 healthy volunteers resulted in an increase in mean clarithromycin trough concentration (CS) and AUC by 33% and 18%, respectively. However, co-administration did not significantly affect the average steady-state concentration of the active metabolite 14-OH-clarithromycin. No dose adjustment of clarithromycin is required when taking fluconazole concomitantly.

Ritonavir

A pharmacokinetic study showed that coadministration of ritonavir 200 mg every eight hours and clarithromycin 500 mg every 12 hours resulted in a marked suppression of the metabolism of clarithromycin. When co-administered with ritonavir, clarithromycin Cmax increased by 31%, Cmin increased by 182% and AUC increased by 77%. Complete suppression of the formation of 14-OH-clarithromycin was noted. Due to the wide therapeutic range of clarithromycin, dose reduction is not required in patients with normal renal function. In patients with renal failure, it is advisable to consider the following dose adjustment options: with CC 30-60 ml/min, the dose of 13 clarithromycin should be reduced by 50%; with CC less than 30 ml/min, the dose of clarithromycin should be reduced by 75%. Ritonavir should not be co-administered with clarithromycin in doses exceeding 1 g/day.

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

Effect of clarithromycin on other drugs

Antiarrhythmic drugs (quinidine and disopyramide).

Ventricular tachycardia of the “pirouette” type may occur with the combined use of clarithromycin and quinidine or disopyramide. When clarithromycin is coadministered with these drugs, ECG monitoring should be performed regularly to monitor for QT prolongation, and serum concentrations of these drugs should also be monitored.

During post-marketing use, cases of hypoglycemia have been reported during co-administration of clarithromycin and disopyramide. It is necessary to monitor the concentration of glucose in the blood while using clarithromycin and disopyramide.

Oral hypoglycemic agents/insulin

When clarithromycin is used together with oral hypoglycemic agents (for example, sulfonylureas) and/or insulin, severe hypoglycemia may occur. Concomitant use of clarithromycin with certain hypoglycemic drugs (for example, nateglinide, pioglitazone, repaglinide and rosiglitazone) may lead to inhibition of the CYP3A isoenzyme by clarithromycin, which may result in hypoglycemia. Careful monitoring of glucose concentrations is recommended.

Interactions due to CYP 3 A

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 side effects. Clarithromycin should be used with caution in patients receiving drugs that are substrates of the CYP3A isoenzyme, especially if these drugs have a narrow therapeutic index (for example, carbamazepine) and/or are extensively metabolized by this enzyme. If necessary, the dose of the drug taken together with clarithromycin should be adjusted. Also, whenever possible, serum concentrations of drugs primarily metabolized by the CYP3A isoenzyme should be monitored. 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. Also, agonists of the CYP3A isoenzyme include the following drugs that are contraindicated for combined use with clarithromycin: astemizole, cisapride, pimozide, terfenadine, lovastatin, simvastatin and ergot alkaloids (see section “Contraindications”). Drugs that interact in this manner through other isoenzymes within the cytochrome P450 system include phenytoin, theophylline, and valproic acid.

Indirect anticoagulants

When taking warfarin and clarithromycin together, bleeding and a marked increase in INR and prothrombin time are possible. In case of combined use with warfarin or other indirect anticoagulants, it is necessary to monitor the INR and prothrombin time.

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 co-administered, steady-state plasma concentrations of omeprazole were increased (Cmax, AUC0-24 and T1/2 increased by 30%, 89% and 34%, respectively). The mean 24-hour gastric pH was 5.2 when omeprazole was taken alone and 5.7 when omeprazole was taken with clarithromycin.

Sildenafil, tadalafil and vardenafil

Each of these phosphodiesterase inhibitors is metabolized, at least in part, by the CYP3A isoenzyme. At the same time, the CYP3A isoenzyme can be inhibited in the presence of clarithromycin. Concomitant use of clarithromycin with sildenafil, tadalafil or vardenafil may result in increased phosphodiesterase inhibitory effects. When using these drugs together with clarithromycin, consider reducing the dose of sildenafil, tadalafil and vardenafil.

Theophylline, carbamazepine

When clarithromycin and theophylline or carbamazepine are used together, the concentration of these drugs in the systemic circulation may increase.

Tolterodine

The primary metabolism of tolterodine occurs through the 2D6 isoform of cytochrome P450 (CYP2D6). However, in part of the population lacking the CYP2D6 isoenzyme, metabolism occurs through the CYP3A isoenzyme. In this population, inhibition of CYP3A results in significantly higher serum tolterodine concentrations. In populations that are poor metabolizers of CYP2D6, a dose reduction of tolterodine may be required in the presence of CYP3A inhibitors such as clarithromycin.

Benzodiazepines (eg, alprazolam, midazolam, triazolam)

When midazolam was co-administered with clarithromycin tablets (500 mg twice daily), midazolam AUC increased by 2.7 times after intravenous midazolam and by 7 times after oral administration. Concomitant use of clarithromycin with oral midazolam is contraindicated. If intravenous midazolam is used concomitantly with clarithromycin, the patient's condition should be carefully monitored for possible dose adjustment. Administration of a drug through the oral mucosa, which bypasses first-pass elimination, is likely to result in an interaction similar to that observed with intravenous midazolam rather than with oral administration.

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

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

Interactions with other drugs

Colchicine

Colchicine is a substrate of both CYP3A and the P-glycoprotein (Pgp) transporter protein. It is known that clarithromycin and other macrolides are inhibitors of the CYP3A and Pgp isoenzymes. When clarithromycin and colchicine are taken together, inhibition of Pgp and/or CYP3A may result in increased effects of colchicine. The development of clinical symptoms of colchicine poisoning should be monitored. There have been post-marketing reports of cases of colchicine poisoning when taken concomitantly with clarithromycin, most often in elderly patients. Some of the reported cases occurred in patients suffering from kidney failure. Some cases were reported to be fatal. The simultaneous use of clarithromycin and colchicine is contraindicated (see section "Contraindications").

Digoxin

Digoxin is suspected to be a Pgp substrate. Clarithromycin is known to inhibit Pgp. When clarithromycin and digoxin are co-administered, inhibition of Pgp by clarithromycin may result in increased effects of digoxin. Coadministration of digoxin and clarithromycin may also result in increased serum concentrations of digoxin. Some patients have experienced clinical symptoms of digoxin toxicity, including potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored when clarithromycin and digoxin are coadministered.

Zidovudine

Concomitant use of clarithromycin tablets and oral zidovudine by adult HIV-infected patients may result in decreased steady-state zidovudine concentrations.

Because clarithromycin interferes with the oral absorption of zidovudine, the interaction can be largely avoided by taking clarithromycin and zidovudine 4 hours apart.

This interaction was not observed in HIV-infected children taking clarithromycin pediatric suspension with zidovudine or dideoxyinosine. Since clarithromycin may interfere with the absorption of zidovudine when administered concomitantly orally in adult patients, such an interaction is unlikely to occur when clarithromycin is used intravenously.

Phenytoin and valproic acid

There is evidence of interactions between CYP3A inhibitors (including clarithromycin) and drugs that are not metabolized by CYP3A (phenytoin and valproic acid). For these drugs, when used together with clarithromycin, it is recommended to determine their serum concentrations, as there are reports of their increase.

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. Coadministration of clarithromycin (500 mg twice daily) and atazanavir (400 mg once daily) may result in a twofold increase in clarithromycin exposure and a 70% decrease in 14-OH-clarithromycin exposure, with a 28% increase in atazanavir AUC. Due to the wide therapeutic range of clarithromycin, dose reduction is not required in patients with normal renal function. In patients with moderate renal failure (creatinine clearance 30 - 60 ml/min), the dose of clarithromycin should be reduced by 50%. In patients with CC less than 30 ml/min, the dose of clarithromycin should be reduced by 75% using the appropriate dosage form of clarithromycin. Clarithromycin in doses exceeding 1000 mg per day should not be used in conjunction with protease inhibitors.

Blockers of "slow" calcium channels

When using clarithromycin simultaneously with blockers of “slow” calcium channels that are metabolized by the CYP3A4 isoenzyme (for example, verapamil, amlodipine, diltiazem), caution should be exercised as there is a risk of arterial hypotension. Plasma concentrations of clarithromycin, as well as slow calcium channel blockers, may increase with simultaneous use. Arterial hypotension, bradyarrhythmia and lactic acidosis are possible when taking clarithromycin and verapamil simultaneously.

Itraconazole

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

Saquinavir

Clarithromycin and saquinavir are substrates and inhibitors of the CYP3A isoenzyme. which determines the bidirectional interaction of drugs. Concomitant use of clarithromycin (500 mg twice daily) and saquinavir (soft gelatin capsules, 1200 mg three times daily) in 12 healthy volunteers increased the AUC and Cmax of saquinavir by 177% and 187%, respectively, compared with saquinavir administration at separately. The AUC and Cmax values of clarithromycin were approximately 40% higher than with clarithromycin monotherapy. When these two drugs are used together for a limited time at the doses/formulations indicated above, no dose adjustment is required. Results from drug interaction studies using saquinavir soft gelatin capsules may not be consistent with the effects observed with saquinavir hard gelatin capsules. The results of drug interaction studies with saquinavir monotherapy may not be consistent with the effects observed with saquinavir/ritonavir therapy. When taking saquinavir with ritonavir, consider the potential effect of ritonavir on clarithromycin.

Clarithromycin-teva 500 mg 14 pcs. film-coated tablets

pharmachologic effect

Clarithromycin is a semisynthetic broad-spectrum macrolide antibiotic.
The antibacterial effect of clarithromycin is carried out by suppressing protein synthesis due to binding to the 50s subunit of bacterial ribosomes. Clarithromycin has pronounced activity against a wide range of aerobic and anaerobic gram-positive and gram-negative organisms. The minimum inhibitory concentration (MIC) of clarithromycin is half that of erythromycin for most microorganisms. The 14-hydroxy metabolite of clarithromycin also has antimicrobial activity. The minimum inhibitory concentrations of this metabolite are equal to or greater than the MIC of clarithromycin; against H. influenzae, the 14-hydroxy metabolite is twice as active as clarithromycin.

Clarithromycin is active in vitro against the following organisms - gram-positive aerobic bacteria: Staphylococcus aureus (methicillin sensitive), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus viridans and Listeria monocytogenes; gram-negative aerobic bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoea, Legionella pneumophila, Bordetella pertussis, Helicobacter pylori, Campylobacter jejuni; predominantly intracellular microorganisms: Mycoplasma pneumonia, Ureaplasma urealyticum, Chlamydia trachomatis, Chlamydia pneumonia, Mycobacterium avium, Mycobacterium leprae, M. kansaii, M. chelonae, M. marinum, M. fortitum; anaerobic microorganisms: Bacteroides fragilis, Clostridium perfringens, Propionibacterium acnes, Peptococcus species; Peptostreptococcus species. In addition, the drug is active against Toxoplasma species.

Clarithromycin has bactericidal activity against certain bacterial strains: Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Helicobacter pylori and Campylobacter spp.

Composition and release form Clarithromycin-teva 500 mg 14 pcs. film-coated tablets

Tablets - 1 tablet:

Active substance: clarithromycin 500 mg.
Excipients: povidone, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate.
Shell composition: opadry II 31F58914 white (hypromelose, lactose monohydrate, titanium dioxide (E171), macrogol 4000, sodium citrate).

14 pcs. - blisters (1) - cardboard packs.

Description of the dosage form

White film-coated tablets, oblong, biconvex, scored on one side.

Directions for use and doses

Inside. Adults: the usual dose is 250 mg 2 times / day for 7 days, if necessary, the dose can be increased to 500 mg 2 times / day for a period of up to 14 days for severe infections.

Children over 12 years of age: dosage regimen as for adults.

For the treatment of duodenal ulcers caused by H. pylori (adults):

Triple therapy regimen (1-14 days): clarithromycin 500 mg 2 times a day; lansoprazole 30 mg 2 times/day; amoxicillin 1000 mg 2 times/day.

Triple therapy regimen (7 days): clarithromycin 500 mg 2 times a day; lansoprazole 30 mg 2 times/day; Metronidazole 400 mg 2 times/day.

Triple therapy regimen (7 days): clarigromycin 500 mg 2 times a day; omeprazole 40 mg/day; amoxicillin 1000 mg 2 times/day or metronidazole 400 mg 2 times/day.

Triple therapy regimen (10 days): clarithromycin 500 mg 2 times/day is prescribed with amoxicillin 100 mg 2 times/day and omeprazole 20 mg/day.

Dual therapy regimen (14 days): clarithromycin 500 mg 3 times a day, omeprazole orally 40 mg 1 time a day.

If renal function is impaired, dosage adjustment is usually not required, with the exception of patients with severe renal impairment (KC

When taking ritonavir concomitantly for patients with impaired renal function, a dose adjustment is recommended according to the following scheme: for patients with CC 30-60 ml/min, the dose of clarithromycin should be reduced by 50%. For patients with CC less than 30 ml/min, the dose of clarithromycin should be reduced by 75%. When using clarithromycin and ritonavir together, dosages of clarithromycin should not exceed 1 g/day.

Pharmacokinetics

Clarithromycin is quickly and well absorbed from the gastrointestinal tract after oral administration. The microbiologically active metabolite 14-hydroxyclarithromycin is formed after the first passage through the liver. Food intake does not affect the bioavailability of clarithromycin; however, it slightly slows down the onset of absorption of clarithromycin and the formation of the 14-hydroxy metabolite. The pharmacokinetics of clarithromycin is nonlinear; in this case, the equilibrium concentration is achieved 2 days after starting the drug.

Clarithromycin is excreted in the urine and also in feces, mainly through bile. When taking 250 mg of clarithromycin 2 times a day, 15-20% of the administered dose is excreted unchanged in the urine. When taking 500 mg 2 times a day, urinary excretion is about 36%. 14-hydroxyclarithromycin is the main metabolite found in urine, accounting for about 10-15%.

When taking 500 mg of clarithromycin 3 times a day, the plasma concentration of clarithromycin is higher than when taking this dose 2 times a day.

The content of clarithromycin in tissues, including glandular and pulmonary tissue, is several times higher than in circulating blood. At therapeutic concentrations, clarithromycin is 80% bound to plasma proteins.

Clarithromycin penetrates gastric mucus. The level of clarithromycin in gastric mucus and tissue increases during combination therapy with omeprazole. Clarithromycin passes into breast milk

Indications for use Clarithromycin-teva 500 mg 14 pcs. film-coated tablets

Infections caused by microorganisms sensitive to clarithromycin:

lower respiratory tract infections (including acute and chronic bronchitis, pneumonia);
upper respiratory tract infections (including sinusitis and pharyngitis);
skin and soft tissue infections;
duodenal ulcer for eradication of Helicobacter pylori (as part of complex therapy with proton pump inhibitors).

Contraindications

Simultaneous administration with ergot derivatives;
simultaneous administration of the following drugs: cisapride, pimozide, terfenadine;
children under 12 years of age;
pregnancy and lactation period.
hypersensitivity to macrolide antibiotics.

With caution: patients with impaired liver and kidney function.

Application of Clarithromycin-teva 500 mg 14 pcs. film-coated tablets during pregnancy and breastfeeding

The safety of clarithromycia during pregnancy and lactation has not been studied.

The drug passes into breast milk. If necessary, use during lactation should stop breastfeeding.

Use in children

Contraindication: children under 12 years of age.

special instructions

Taking clarithromycin tablets in children under 12 years of age is not recommended.

When clarithromycin and warfarin are co-administered, prothrombin time should be regularly monitored.

When clarithromycin and digoxin are co-administered, the level of digoxin concentration in the blood serum should be monitored.

Overdose

Symptoms: gastrointestinal symptoms; one of the patients, when taking 8 g of clarithromycin, had a case of mental state disturbance, paranoid behavior, hypoglycemia, hypoxemia.

Treatment: gastric lavage, maintenance therapy. Hemodialysis or peritoneal dialysis is ineffective, as for other macrolides.

Side effects Clarithromycin-teva 500 mg 14 pcs. film-coated tablets

Clarithromycin is generally well tolerated by patients

From the gastrointestinal tract: nausea, vomiting, dyspepsia, diarrhea, abdominal pain, stomatitis, glossitis, pancreatitis, oral candidiasis, discoloration of the tongue and teeth; rarely - pseudomembranous enterocolitis. Tooth discoloration is reversible and can usually be restored with special treatment at a dental clinic. As with other antibiotics from the macrolide group, liver function disorders are possible, incl. increased activity of liver enzymes, hepatocellular and/or cholestatic hepatitis with or without jaundice. These liver problems can be severe, but are usually reversible. Very rare cases of liver failure and death have been observed, mainly due to severe concomitant diseases and/or concomitant drug therapy.

From the blood system: in exceptional cases - leukopenia and thrombocytopenia; increase in serum creatinine level.

From the central and peripheral nervous system: paresthesia, headache, disturbances of smell, changes in taste; dizziness, agitation, insomnia, nightmares, fear, ringing in the ears, confusion, disorientation, hallucinations, psychosis, depersonalization; reversible hearing loss; convulsions.

From the cardiovascular system: as with other macrolides, prolongation of the QT interval, ventricular tachycardia, polymorphic ventricular tachyarrhythmia (torsades de pointes).

From the musculoskeletal system: arthralgia, myalgia.

From the urinary system: isolated cases of increased plasma creatinine, interstitial nephritis, renal failure.

Allergic reactions: urticaria, angioedema, anaphylactic shock, in rare cases - Stevens-Johnson syndrome, toxic elidermal necrolysis.

Other: rarely - hypoglycemia in patients taking oral hypoglycemic drugs or insulin.

Drug interactions

When clarithromycin is co-administered with cisapride, pimozide and terfenadine, increased plasma concentrations of these drugs are observed, which can cause prolongation of the QT interval and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, arrhythmia and torsade de pointes; similar effects are observed when taking astemizole and other macrolides simultaneously.

Clarithromycin does not interact with oral contraceptives.

As with other macrolide antibiotics, concomitant use of clarithromycin and other drugs metabolized by cytochrome P450 (warfarin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporine and tacrolimus) may be accompanied by an increase in serum concentrations of these drugs. blood.

With simultaneous use of clarithromycin and HMG-KoA reductase inhibitors (lovastatin, simvastatin), rhabdomyolysis may develop.

With the simultaneous administration of clarithromycin and theophylline, the concentration of theophylline in the blood serum and its toxicity increase.

The simultaneous administration of clarithromycin and warfarin or digoxin may be accompanied by an increase in the severity of their effects.

With the simultaneous administration of clarithromycin and carbamazepine, the effect of carbamazepine may be enhanced due to a decrease in the rate of excretion of carbamazepine.

When clarithromycin and zidovudine (orally) are taken simultaneously in HIV-infected adult patients, the steady-state concentration of zidovudine may decrease; this can be largely avoided by increasing the interval between doses of clarithromycin and zidovudine to 1-2 hours. For children, such an interaction was not observed.

When taking ritonavir and clarithromycin simultaneously, the values of the pharmacokinetic parameters for the latter increase: AUC, Cmax, Cmin. For patients with normal renal function, no dose adjustment is usually required due to the wide therapeutic dosage range of clarithromycin.

With the simultaneous use of clarithromycin and omeprazole, clarithromycin and lansoprazole, as well as clarithromycin and ranitidine, an increase in the concentration of drugs in the blood plasma is possible, but usually no dose adjustment is required.

With the simultaneous use of clarithromycin and hypoglycemic agents, including insulin, in rare cases, hypoglycemia may develop.

Clarithromycin-Teva tablet p/o 500 mg N14 (Teva)

The use of the following drugs with clarithromycin is contraindicated due to the potential for serious side effects:

Cisapride, pimozide, terfenadine and astemizole

When clarithromycin was co-administered with cisapride, pimozide, terfenadine or astemizole, increased plasma concentrations of the latter were reported, which may

Ergot alkaloids

Midazolam for oral use

HMG-CoA reductase inhibitors (statins)

Effect of other drugs on clarithromycin

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine

Etravirine

Fluconazole

Ritonavir

Effect of clarithromycin on other drugs

Antiarrhythmic drugs (quinidine and disopyramide).

Oral hypoglycemic agents/insulin

Interactions due to CYP3A isoenzyme

Indirect anticoagulants

Omeprazole

Sildenafil, tadalafil and vardenafil

Theophylline, carbamazepine

When clarithromycin and theophylline or carbamazepine are used together, the concentration of these drugs in the systemic circulation may increase.

Tolterodine

Benzodiazepines (eg, alprazolam, midazolam, triazolam)

Interactions with other drugs

Colchicine

Digoxin

Zidovudine

Concomitant use of clarithromycin tablets and oral zidovudine by adult HIV-infected patients may result in decreased steady-state zidovudine concentrations.

Because clarithromycin interferes with the oral absorption of zidovudine, the interaction can be largely avoided by taking clarithromycin and zidovudine 4 hours apart.

Phenytoin and valproic acid

Bidirectional drug interactions

Atazanavir

Blockers of "slow" calcium channels

Itraconazole

Saquinavir