Clarithromycin SR-Vertex, 500 mg 14 pcs

Pharyngitis, Chlamydia, Lung inflammation (pneumonia), Sinusitis, Bronchitis, Skin infections, Otitis media, Gastrointestinal infections

Infectious and inflammatory diseases caused by clarithromycin-sensitive microorganisms:

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

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

– infections of the skin and soft tissues (such as folliculitis, inflammation of the subcutaneous tissue, rye).

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to clarithromycin:

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

– infections of the upper respiratory tract and ENT organs (such as pharyngitis, sinusitis);

– infections of the skin and soft tissues (such as folliculitis, inflammation of the subcutaneous tissue, erysipelas).

Special instructions

Most strains of staphylococci resistant to methicillin and oxacillin are resistant to clarithromycin.

Long-term use of antibiotics can lead to the formation of colonies with an increased number of insensitive bacteria and fungi. In case of superinfection, appropriate therapy must be prescribed.

Liver dysfunction (increased activity of liver enzymes in the blood plasma, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with the use of clarithromycin.

Liver dysfunction can be severe but is usually reversible. There have been cases of fatal liver failure, mainly associated with the presence of serious concomitant diseases and/or concomitant use of other drugs. If signs and symptoms of hepatitis appear, such as anorexia, jaundice, dark urine, itching, abdominal tenderness on palpation, clarithromycin therapy should be stopped immediately. In the presence of chronic liver diseases, it is necessary to regularly monitor the activity of blood plasma enzymes.

Antibacterial drugs can change the normal intestinal microflora, which can lead to the growth of C. difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who experience diarrhea after using antibacterial agents.

After a course of antibiotic therapy, careful medical monitoring of the patient is necessary. Cases of the development of pseudomembranous colitis 2 months after taking antibiotics have been described.

Clarithromycin should be used with caution in patients with coronary artery disease, severe heart failure, hypomagnesemia, severe bradycardia (less than 50 beats/min), as well as when used simultaneously with class IA (quinidine, procainamide) and class III antiarrhythmic drugs (dofetilide, amiodarone, sotalol). In these conditions and when clarithromycin is taken concomitantly with these drugs, the electrocardiogram should be regularly monitored for an increase in the QT interval.

It is possible to develop cross-resistance to clarithromycin and other macrolide antibiotics, as well as lincomycin and clindamycin.

Given the increasing resistance of Streptococcus pneumoniae to macrolides, it is important to perform susceptibility testing when using clarithromycin in patients with community-acquired pneumonia. For hospital-acquired pneumonia, clarithromycin should be used in combination with appropriate antibiotics.

Mild to moderate skin and soft tissue infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes. Moreover, both pathogens can be resistant to macrolides. Therefore, it is important to provide a sensitivity test.

Macrolides can be used for infections caused by Corynebacterium minutissimum (erythrasma), acne vulgaris and erysipelas, as well as in situations where penicillin cannot be used.

In the event of acute hypersensitivity reactions, such as anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), Henoch-Schönlein purpura, you should immediately stop taking clarithromycin and begin appropriate therapy.

Worsening of myasthenia gravis symptoms has been reported in patients taking clarithromycin.

In case of combined use with warfarin or other indirect anticoagulants, it is necessary to monitor the INR and prothrombin time (see section “Interaction with other drugs”).

Active ingredient

Clarithromycin

Composition

extended-release film-coated tablets

1 tablet, long-acting, film-coated, contains:

active substance:

clarithromycin 500,000 mg;

excipients:

hypromellose 2208 (100 mPa s) 200,000 mg,

hypromellose 2910 (50 mPa s) 150,000 mg,

microcrystalline cellulose 137,500 mg,

colloidal silicon dioxide 2,500 mg,

magnesium stearate 10,000 mg;

film shell:

[hypromellose 2910 (6 mPa s) 15,000 mg, hyprolose (hydroxypropyl cellulose) 5,820 mg, talc 5,778 mg, titanium dioxide 3,261 mg, iron oxide yellow (iron oxide) 0,141 mg] or [dry film coating mixture containing hypromellose 2910 (6 mPa s) (50%), hyprolose (hydroxypropylcellulose) (19.4%), talc (19.26%), titanium dioxide (10.87%), iron oxide yellow (iron oxide) (0.47%)] 30,000 mg.

Contraindications

Hypersensitivity to clarithromycin, other components of the drug and other macrolides;

– simultaneous use of clarithromycin with astemizole, cisapride, pimozide, terfenadine (see section “Interaction with other drugs”);

– severe renal failure – creatinine clearance (CC) less than 30 ml/min;

– simultaneous use of clarithromycin with ergot alkaloids, for example,

ergotamine, dihydroergotamine (see section “Interaction with other drugs”);

– simultaneous use of clarithromycin with midazolam for oral use (see section “Interaction with other drugs”);

– patients with a history of QT interval prolongation, ventricular arrhythmia or torsade de pointes;

– patients with hypokalemia (risk of QT interval prolongation);

– patients with severe liver failure occurring simultaneously with renal failure;

– simultaneous use of clarithromycin with HMG-CoA reductase inhibitors

(statins), which are significantly metabolized by the CYP3A4 isoenzyme (lovastatin, simvastatin), due to an increased risk of myopathy, including rhabdomyolysis (see section “Interaction with other drugs”);

– simultaneous use of clarithromycin with colchicine in patients with impaired liver or kidney function;

– patients with a history of cholestatic jaundice/hepatitis that developed while using clarithromycin (see section “Special Instructions”);

– breastfeeding period;

– children under 12 years of age (efficacy and safety have not been established);

– porphyria;

– lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Moderate renal failure;

– moderate to severe liver failure;

– myasthenia gravis (possibly increased symptoms);

– simultaneous use of clarithromycin with benzodiazepines, such as alprazolam, triazolam, midazolam for intravenous use (see section “Interaction with other drugs”);

– simultaneous use with drugs that are metabolized by the CYP3A isoenzyme, for example, carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (for example, warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine (see section “Interaction with other drugs”);

– simultaneous use with drugs that induce the CYP3A4 isoenzyme, for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort (see section “Interaction with other drugs”);

– simultaneous use with blockers of “slow” calcium channels that are metabolized by the CYP3A4 isoenzyme (for example, verapamil, amlodipine, diltiazem);

– patients with coronary heart disease (CHD), severe heart failure, hypomagnesemia, severe bradycardia (less than 50 beats/min), as well as patients simultaneously taking class IA (quinidine, procainamide) and class III antiarrhythmic drugs (dofetilide, amiodarone, sotalol);

– pregnancy.

Side Effects

Adverse reactions are presented depending on the effect on organs and organ systems.

Classification of adverse reactions by frequency (number of reported cases/number of patients): very common (> 1/10), common (> 1/100, 1/1000, < 1/100), unknown (side effects from post-marketing experience; frequency cannot be estimated based on available data).

Allergic reactions

Often – rash.

Uncommon: anaphylactoid reaction1, hypersensitivity, bullous dermatitis1, itching, urticaria, maculopapular rash.

Unknown – anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

From the nervous system

Often – headache, insomnia.

Uncommon – loss of consciousness1, dyskinesia1, dizziness, drowsiness, tremor, anxiety, increased excitability, screaming.

Unknown – convulsions, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dream disturbances (nightmare dreams), paresthesia, mania.

From the skin

Often – intense sweating.

Uncommon: acne, Henoch-Schönlein purpura, hemorrhages.

From the urinary system

Unknown – renal failure, interstitial nephritis.

Metabolism and nutrition: Uncommon – anorexia, loss of appetite.

Unknown – hypoglycemia.

From the musculoskeletal system

Uncommon: muscle spasm, musculoskeletal stiffness1, myalgia.

Unknown – rhabdomyolysis*, myopathy, increased symptoms of myasthenia gravis.

From the digestive system

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

Uncommon – esophagitis1, gastroesophageal reflux disease, gastritis, proctalgia, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence, cholestasis, hepatitis, including cholestatic and hepatocellular.

Unknown – acute pancreatitis, discoloration of the tongue and teeth, liver failure, cholestatic jaundice.

From the respiratory system

Uncommon: asthma1, epistaxis, pulmonary embolism1.

From the senses

Often – dysgeusia, taste perversion.

Uncommon: vertigo, hearing loss, ringing in the ears.

Unknown – deafness, ageusia (loss of taste), parosmia, anosmia.

From the cardiovascular system: Often – vasodilation.

Uncommon: atrial flutter, prolongation of the QT interval on the electrocardiogram, atrial fibrillation1, extrasystole1, cardiac arrest1.

Unknown: ventricular tachycardia, including torsade de pointes.

Laboratory indicators

Often – a deviation in the liver test.

Uncommon – increased creatinine concentration1, increased urea concentration1, change in albumin-globulin ratio1, leukopenia, neutropenia, eosinophilia, thrombocythemia, increased activity: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH).

Unknown – agranulocytosis, thrombocytopenia, increased international normalized ratio (INR), prolonged prothrombin time, change in urine color, increased bilirubin concentration in the blood.

General disorders

Uncommon: malaise, hyperthermia, asthenia, chest pain, chills, fatigue.

Infectious and parasitic diseases

Uncommon – cellulitis1, candidiasis, gastroenteritis, secondary infections (including vaginal).

Unknown – pseudomembranous colitis, erysipelas, erythrasma.

Immunosuppressed patients

In patients with AIDS and other immunodeficiencies receiving clarithromycin in higher doses over a long period of time for the treatment of mycobacterial infections, it is often difficult to distinguish adverse effects of the drug from symptoms of HIV infection or concomitant disease.

The most common adverse events in patients taking a daily dose of clarithromycin of 1000 mg were: nausea, vomiting, taste disturbance, abdominal pain, diarrhea, rash, flatulence, headache, constipation, hearing loss, increased AST and ALT activity in the blood. Low incidence adverse events such as shortness of breath, insomnia and dry mouth were also reported.

In patients with suppressed immunity, laboratory parameters were assessed, analyzing their significant deviations from the norm (sharp increase or decrease). Based on this criterion, a significant increase in AST and ALT activity in the blood, as well as a decrease in the number of leukocytes and platelets, was observed in 2-3% of patients receiving clarithromycin at a dose of 1000 mg daily. Increases in residual urea nitrogen concentrations have also been reported in a small number of patients.

*In some reports of rhabdomyolysis, clarithromycin was co-administered with other drugs known to be associated with rhabdomyolysis (statins, fibrates, colchicine or allopurinol).

1 Reports of these adverse reactions have been received during clinical trials, as well as post-marketing use of clarithromycin in the form of a lyophilisate for solution for infusion.

Interaction

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

Cisapride, pimozide

When used together, it is possible: an increase in the concentration of cisapride/pimozide, an increase in the QT interval, the appearance of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, ventricular tachycardia of the “pirouette” type.

Terfenadine and astemizole

When used together, it is possible: an increase in the concentration of terfenadine/astemizole in the blood, the occurrence of cardiac arrhythmias, an increase in the QT interval, ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the pirouette type.

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. The simultaneous use of clarithromycin and ergot alkaloids is contraindicated (see section “Contraindications”).

Effect of other drugs on clarithromycin

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

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 concentrations of rifabutin and a decrease in plasma concentrations of clarithromycin were observed with an increased risk of developing uveitis.

Efavirenz, nevirapine, rifampicin, rifabutin, rifapentine

Strong inducers of the cytochrome P450 system, such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine, can accelerate the metabolism of clarithromycin and, thus, reduce the concentration of clarithromycin in the blood plasma 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

The concentration of clarithromycin decreases with the use of etravirine, but the concentration of the active metabolite 14-OH-clarithromycin increases. Because 14-OH-clarithromycin has low activity against MAC infections, overall activity against these pathogens may be altered, and alternative treatments should be considered for the treatment of MAC.

Oral hypoglycemic agents/insulin

When clarithromycin is used concomitantly with oral hypoglycemic agents and/or insulin, severe hypoglycemia may occur. During concomitant use of clarithromycin and certain drugs that lower glucose concentrations, such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of the CYP3 isoenzyme by clarithromycin may occur, which may result in hypoglycemia. Careful monitoring of glucose concentrations is recommended.

Fluconazole

Coadministration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily in 21 healthy volunteers resulted in an increase in clarithromycin mean steady-state concentration (Cssmin) and AUC of 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 index 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 clarithromycin should be reduced by 50% (no more than one tablet of Clarithromycin SR per day). Patients with severe renal failure (creatinine clearance <30 ml/min) should not take Clarithromycin SR due to the impossibility of adequate dose adjustment (reduction) (see section "Contraindications"). In such groups of patients, clarithromycin regular release tablets can be used. Ritonavir should not be co-administered with clarithromycin in doses exceeding 1 g/day.

Effect of clarithromycin on other drugs

Antiarrhythmic drugs (quinidine and disopyramide)

Torsade de pointes-type ventricular tachycardia may occur with the combined use of clarithromycin and quinidine or disopyramide. When clarithromycin is coadministered with these drugs, the electrocardiogram should be regularly monitored for prolongation of the QT interval, and plasma concentrations of these drugs should also be monitored.

Interactions due to CYP3A isoenzyme

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 CYP3A substrates, especially if the CYP3A substrate has a narrow therapeutic range (eg, carbamazepine) and/or is extensively metabolized by this enzyme.

If necessary, the dose of the drug taken together with Clarithromycin SR should be adjusted, and the joint use of certain drugs is contraindicated (see section “Contraindications”). Also, whenever possible, plasma 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: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, indirect anticoagulants (e.g. warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam and vinblastine. Drugs that interact in this manner through other isoenzymes within the cytochrome P450 system include phenytoin, theophylline, and valproic acid.

HMG-CoA reductase inhibitors (statins)

Like other macrolides, clarithromycin increases concentrations of HMG-CoA reductase inhibitors (for example, lovastatin and simvastatin). Co-administration 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 plasma 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 statins. If coadministration is necessary, it is recommended to take the lowest dose of statin. It is necessary to use statins that do not depend on the metabolism of the CYP3A isoenzyme (for example, fluvastatin).

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.

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.

Sildenafil, tadalafil, 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, consider reducing the dose of sildenafil, tadalafil, and vardenafil.

Theophylline, carbamazepine

When clarithromycin and theophylline or carbamezepine 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 isoenzyme). 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 plasma concentrations of tolterodine. 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 and clarithromycin (500 mg twice daily) were used together, an increase in midazolam AUC was observed: 2.7 times after intravenous administration of midazolam and 7 times after oral administration. Concomitant oral administration of midazolam and clarithromycin should be avoided. If clarithromycin is used concomitantly with intravenous midazolam, the patient’s condition should be carefully monitored for possible dose adjustment. The same precautions should be applied to other benzodiazepines that are metabolized by the CYP3A isoenzyme, including triazolam, 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.

Interaction with other drugs

Colchicine

Colchicine is a substrate of both the CYP3A isoenzyme and the transport protein responsible for drug excretion, P-glycoprotein (Pgp). Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. When clarithromycin and colchicine are taken together, inhibition of Pgp and/or CYP3A may result in an increased effect of colchicine. 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 with renal failure. Some cases were reported to be fatal.

The development of clinical symptoms of colchicine poisoning should be monitored. In patients with normal renal and hepatic function, the dose of colchicine should be reduced when used concomitantly with clarithromycin.

The simultaneous use of clarithromycin and colchicine is contraindicated in patients with impaired liver or kidney function (see section “Contraindications”).

Digoxin

Digoxin is thought to be a substrate for Pgp. 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 plasma digoxin concentrations in patients, leading to the development of clinical symptoms of digoxin toxicity, including potentially fatal arrhythmias. When taking clarithromycin and digoxin together, the concentration of digoxin in the blood plasma should be carefully monitored.

Zidovudine

Concomitant oral administration of clarithromycin regular-release tablets and zidovudine in 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 zidovudine at 4-hour intervals.

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 administered intravenously. Interaction studies between clarithromycin extended-release tablets and zidovudine have not been conducted.

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 plasma concentrations, as there are reports of their increase.

Bidirectional drug interactions

Atazanavir

Clarithromycin and atazanavir are substrates and inhibitors of the CYP3A isoenzyme. There is evidence of a bidirectional interaction between these drugs. Co-administration of clarithromycin (500 mg twice daily) and atazanavir (400 mg daily daily) may result in a 28% increase in atazanavir AUC, a 2-fold increase in clarithromycin AUC, and a 70% decrease in 14-OH-clarithromycin AUC. Due to the wide therapeutic index of clarithromycin, no dose reduction is 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%. 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 the drugs. Coadministration 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 alone. The AUC and Cmax 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. The results of 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, the potential effect of ritonavir on clarithromycin should be considered.

Overdose

Symptoms

Taking a large dose of clarithromycin may cause symptoms of gastrointestinal problems. In one patient with a history of bipolar disorder, changes in mental status, paranoid behavior, hypokalemia, and hypoxemia were described after taking 8 g of clarithromycin.

Treatment

In case of overdose, the unabsorbed drug should be removed from the gastrointestinal tract (gastric lavage, taking activated charcoal, etc.) and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis do not have a significant effect on the concentration of clarithromycin in the blood plasma, which is also typical for other drugs of the macrolide group.

Storage conditions

In a dry place, protected from light, out of reach of children, at a temperature not exceeding 25°C.

Shelf life

2 years.

Manufacturer

Vertex, Russia