The drug clarithromycin is indicated for use. "Clarithromycin": side effects, instructions for use, contraindications

Clarithromycin

(СLARITHROMYCIN)

Compound:

active substance: clarithromycin;

1 tablet contains clarithromycin 250 mg or 500 mg;

microcrystalline cellulose, sodium starch (type A), sodium lauryl sulfate, hypromellose, calcium stearate, Opadry II Yellow coating mixture (contains: lactose, monohydrate).

Dosage form. Film-coated tablets.

Pharmacotherapeutic group. Macrolides, lincosamides and streptogramins. Macrolides. ATC code J01F A09.

Clinical characteristics.

Lower respiratory tract infections (bronchitis, pneumonia, etc.);

Infections of the skin and soft tissues (folliculitis, erysipeloid, etc.)

Widespread or localized mycobacterial infections;

Odontogenic infections;

Eradication of Helicobacter pylori (H. pylori) in patients with duodenal ulcer when the secretion of hydrochloric acid is suppressed, which is caused by omeprazole or lansoprazole (the activity of clarithromycin against H. pylori at a neutral pH is higher than at an acidic pH).

Contraindications.

Hypersensitivity to clarithromycin, macrolides, as well as to other components of the drug;

Concomitant use with any of the following drugs: astemizole, cisapride, pimozide, terfenadine, ergotamine or dihydroergotamine;

Age up to 12 years;

Breastfeeding period.

Application.

Clarithromycin is taken orally without chewing, with a small amount of liquid, regardless of meals.

The dosage regimen and duration of treatment, which is usually 5-14 days, depend on the type and severity of the infection, as well as the sensitivity of the pathogen.

Treatment of mycobacterial infection. The recommended dose is 500 mg 2 times a day.

Treatment of MAC infections in AIDS patients continues as long as the clinical and microbiological effectiveness of the drug lasts. Clarithromycin should be used in combination with other antimycobacterial agents. The duration of treatment for other non-tuberculosis mycobacterial infections is determined by the doctor individually.

To eradicate H. pylori in patients with duodenal ulcer, Clarithromycin is prescribed as part of complex therapy according to approved international regimens:

1. "Triple" therapy:

For 1-2 weeks, 2 times a day: Clarithromycin 500 mg + amoxicillin 1000 mg + lansoprazole 30 mg;

for 1 week, 2 times a day: Clarithromycin 500 mg + metronidazole 400 mg + lansoprazole 30 mg;

for 1 week: Clarithromycin 500 mg 2 times a day + omeprazole 40 mg 1 time a day + amoxicillin 1000 mg 2 times a day (or metronidazole 400 mg 2 times a day);

for 10 days: Clarithromycin 500 mg 2 times a day + omeprazole 20 mg 1 time a day + amoxicillin 1000 mg 2 times a day.

2. "Double" therapy- for 2 weeks: Clarithromycin 500 mg 3 times a day + omeprazole 40 mg 1 time a day.

Patients with renal failure.

For patients with creatinine clearance less than 30 ml/min, the dose of clarithromycin should be reduced by 2 times - 250 mg 1 time per day or for more severe infections - 250 mg 2 times per day. Treatment of such patients lasts no more than 14 days.

Patients with impaired liver function.

Caution must be exercised when prescribing clarithromycin to patients with impaired liver function. However, while maintaining normal renal function, patients with moderate or severe liver dysfunction do not require clarithromycin dose adjustment.

In elderly patients with normal renal function, dosing is not required.

Adverse reactions.

General hypersensitivity reactions and reactions of the skin and its derivatives: urticaria, skin rash, rarely - angioneurotic edema, anaphylactic reactions, Stevens-Johnson syndrome, Lyell's syndrome.

From the digestive tract and metabolism: nausea, vomiting, abdominal pain, bloating, diarrhea, very rarely - acute pancreatitis, glossitis, stomatitis, dry mouth, fungal infection of the oral mucosa, discoloration of the tongue and teeth, pseudomembranous colitis.

From the central and peripheral nervous system: headache, dizziness, anxiety, very rarely - insomnia, depression, nightmares, ringing in the ears, temporary hearing loss, taste disturbance (dysgeusia, ageusia), smell disturbance (anosmia, parosmia), paresthesia, convulsions, confusion, disorientation, hallucinations, psychosis and depersonalization.

From the cardiovascular system: ventricular tachycardia and ventricular fibrillation, prolongation of the QT interval, ventricular tachycardia of the “pirouette” type.

From the liver and kidneys: increased activity of liver enzymes, increased creatinine levels in the blood serum, very rarely - liver failure, hepatitis (including cholestatic), jaundice (cholestatic, hepatocellular), interstitial nephritis, rarely - increased urea levels in blood.

From the hematopoietic system: rarely - leukopenia, platelet formation.

Others: hypoglycemia, development of superinfection, very rarely - myalgia, arthralgia, uveitis (mainly in patients receiving concomitant therapy with rifabutin), dyspnea. There are data on cases of colchicine toxicity (particularly fatal) with the combined use of clarithromycin and colchicine, especially in elderly patients, incl. against the background of renal failure.

Overdose. Symptoms: nausea, vomiting, diarrhea.

Treatment: immediate gastric lavage and symptomatic treatment. Hemodialysis and peritoneal dialysis do not lead to a significant change in clarithromycin serum levels.

There is evidence of 1 case of development of changes in mental state, paranoid behavior, hypokalemia and hypoxemia in a patient with a history of bipolar psychosis who took 8 g of clarithromycin.

Use during pregnancy and lactation. The safety of clarithromycin during pregnancy and lactation has not been established. The drug should not be used during pregnancy (especially in the first trimester) in the absence of vital indications for use and without a thorough preliminary assessment of the benefit/risk ratio. Clarithromycin is excreted in breast milk. If it is necessary to use the drug while breastfeeding, breastfeeding must be stopped for the period of treatment.

Children. Clarithromycin is contraindicated for use in children under 12 years of age.

Features of application.

Attention should be paid to the possibility of cross-resistance between clarithromycin and other macrolides, as well as lincomycin and clindamycin.

A long or repeated course of antibiotic therapy can lead to the rapid growth of resistant microflora and the development of superinfection.

Clarithromycin should be prescribed with caution to patients with impaired liver and/or kidney function, as well as to elderly patients (see section "Application").

When taking clarithromycin during the treatment period or 1-2 months after the end of the course of treatment, gastrointestinal disorders are possible, including pseudomembranous colitis caused by Clostridium difficile. If colitis occurs, clarithromycin should be discontinued and appropriate treatment administered.

In patients with AIDS and other patients with compromised immune systems who have used high doses of clarithromycin for longer than recommended for the treatment of mycobacterial infections, it is not always possible to distinguish drug-related adverse reactions from symptoms of the underlying or concomitant diseases.

Increased symptoms of myasthenia gravis have been reported in patients receiving clarithromycin.

Influence on the ability to drive vehicles or other mechanisms. There are no messages at the moment. However, when driving vehicles or other mechanisms, it is recommended to take special care, taking into account the possibility of developing adverse reactions from the nervous system.

IN interaction with other drugs and other types of interactions.

Clarithromycin is an inhibitor of the CYP3A enzyme, so clarithromycin should be prescribed with caution with drugs that are metabolized by the CYP3A enzyme of the cytochrome P 450 system, this may lead to an increase in the concentration of the latter in the blood plasma, which, in turn, may enhance or prolong its therapeutic effect and the risk of adverse reactions. These drugs include: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergot alkaloids, astatine, methyl prednisolone, midazolam, omeprazole, oral anticoagulants (eg warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus , terfenadine, triazolam and vinblastine. A similar mechanism of interaction was noted with the use of phenytoin, theophylline and valproate, which are metabolized by one of the isoenzymes of the cytochrome P 450 system.

Strong inducers of cytochrome P 450 enzymes, such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine, can increase the metabolism of clarithromycin, reducing its plasma concentration, but increasing the concentration of 14-OH-clarithromycin, a microbiologically active metabolite. Since the microbiological activity of clarithromycin and 14-OH-clarithromycin is different against different bacteria, the expected therapeutic effect may not be achieved due to the combined use of clarithromycin and inducers of cytochrome P 450 enzymes.

Fluconazole. Steady-state concentrations of the active metabolite 14-OH-clarithromycin did not change significantly when administered concomitantly with fluconazole. There is no need to change the dose of clarithromycin.

Ritonavir. The use of Ryton Vera and clarithromycin leads to a significant suppression of the metabolism of clarithromycin. The maximum concentration of clarithromycin increases by 31%, the minimum by 182% and the AUC increases by 77%. There is complete suppression of the formation of 14-OH-clarithromycin. Due to the large therapeutic range, it is not necessary to reduce the dose of clarithromycin in patients with normal renal function. In patients with impaired renal function, dose adjustment is necessary: ​​with creatinine clearance 30-60 ml/min, the dose of clarithromycin should be reduced by 50% of the maximum dose; with creatinine clearance ≤ 30 ml/min - by 75%. Doses of clarithromycin exceeding 1 g/day should not be used with ritonavir.

Anti-arrhythmic drugs. With simultaneous use of clarithromycin with quinidine or disopyramide, cases of ventricular arrhythmia of the “pirouette” type are possible. Therefore, it is necessary to conduct ECG monitoring and control the level of these drugs in the blood during treatment with clarithromycin.

Concomitant use of clarithromycin with terfenadine, cisapride, pimozide or astemizole may lead to prolongation of the QT interval and the occurrence of arrhythmias, in particular ventricular tachycardia, ventricular fibrillation and torsade de pointes (TdP). The simultaneous administration of these drugs should be avoided.

Concomitant use of clarithromycin and ergotamine or dihydroergotamine is associated with signs of acute ergotism, characterized by vasospasm and ischemia of the limbs and other tissues, including the central nervous system.

Rhabdomyolysis has been very rarely observed with the simultaneous use of clarithromycin and HMG-CoA reductase inhibitors, such as astatin or simvastatin.

Omeprazole. The use of clarithromycin in combination with omeprazole leads to an increase in the equilibrium concentration of omeprazole. When using omeprazole alone, the average pH value of gastric juice when measured over 24 hours is 5.2; with simultaneous use of omeprazole with clarithromycin - 5.7.

When used simultaneously with clarithromycin, the effect of oral anticoagulants is enhanced, so it is necessary to control the amount of prothrombi at a new time.

Phosphodiesterase inhibitors (PDE). There is a possibility of increased plasma concentrations of PDE inhibitors (sildenafil, tadalafil and vardenafil) when used with clarithromycin, which may require a reduction in the dose of PDE inhibitors.

Zidovudine. The simultaneous use of clarithromycin and zidovudine in HIV-infected patients may cause a decrease in the level of zidovudine in the blood.

Digoxin. When taking clarithromycin simultaneously with digoxin, the concentration of digoxin in the blood serum may increase, which requires monitoring the level of the latter in such cases.

With simultaneous use of clarithromycin with rifabutin or rifampicin, the concentration of clarithromycin in the blood serum is reduced (by more than 50%).

Tolterodine. A dose reduction of tolterodine may be necessary when used with clarithromycin.

Triazolbenzodiazepines (eg, alprazolam, midazolam, triazolam). The combined use of oral midazolam and clarithromycin should be avoided. For benzodiazepines whose elimination does not depend on CYP3A (temazepam, nitrazepam, lorazepam), the development of a clinically significant interaction with clarithromycin is unlikely. There is evidence of drug interactions and the development of side effects from the central nervous system (such as drowsiness and confusion) with the simultaneous use of clarithromycin and triazolam. The patient should be monitored, taking into account the possibility of increased pharmacological effects from the central nervous system.

Colchicine. When clarithromycin and colchicine are used concomitantly, inhibition of Pgp and/or CYP3A by clarithromycin may result in increased colchicine exposure. Patients should be monitored for clinical symptoms of colchicine toxicity.

Pharmacological properties.

Pharmacodynamics. Clarithromycin is a semisynthetic macrolide antibiotic. Has a bacteriostatic effect against sensitive microorganisms. In high concentrations it may have a bactericidal effect against individual microorganisms. The mechanism of antibacterial action is inhibition of protein synthesis by binding to the 50S ribosomal subunit of bacteria.

Clarithromycin is active in vitro and in clinical practice against the following microorganisms: gram positive bacteria: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes;

gram-negative bacteria: Haemophilus influenzae (parainfluenzae), Neisseria gonorrhoeae, Legionella pneumophila, Moraxella catarrhalis;

mycobacteria: Mycobacterium leprae, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium kansasii, Mycobacterium avium complex (MAC), which includes Mycobacterium avium and Mycobacterium intracellulare;

other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR).

Most methicillin- and oxacillin-resistant strains of staphylococci are insensitive to the action of clarithromycin.

Clarithromycin is active in vitro against most strains of such microorganisms, but the clinical effectiveness and safety of its use have not been established: Streptococcus agalactiae, Streptococci (groups C, F, G), Viridans group streptococci, Bordetella pertussis, Pasteurella multocida, Clostridium perfringens, Peptococcus niger , Propionibacterium acnes, Bacteriodes melaninogenicus, Borrelia burgdorferi, Treponema pallidum, Campylobacter jejuni.

Clarithromycin exhibits bactericidal activity against several strains of bacteria: Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, H. pylori and Campylobacter spp.

Pharmacokinetics. After oral administration, clarithromycin is rapidly absorbed, reaching maximum concentrations after 2-3 hours. Maintains stability in the acidic environment of the stomach. Administration with food reduces the rate, but not the extent, of absorption, which allows Clarithromycin to be used regardless of food intake. Bioavailability - about 50%.

Widely distributed in tissues and fluids of the whole body. Particularly high concentrations are achieved in the nasal mucosa, tonsils and lungs. Due to its high lipophilicity and affinity for cytoplasmic membranes, Clarithromycin forms higher concentrations in cells and tissues than in blood plasma. Accumulated is also heard in high concentrations in leukocytes and macrophages. Does not penetrate the blood-brain barrier. 80% of the drug is bound to proteins. Metabolized by the liver to form the active metabolite 14-hydroxyclarithromycin, which has antimicrobial activity, like the unchanged substance. 36% of the dose is excreted in urine and 52% in feces.

The half-life of clarithromycin with normal renal function: at a dose of 250 mg 2 times a day - 3-4 hours; at a dose of 500 mg 2 times a day - 4.5-4.8 hours. The half-life of 14-hydroxyclarithromycin with normal renal function: at a dose of 250 mg 2 times a day - 5-6 hours, at a dose of 500 mg 2 times a day - 6.9-8.7 hours.

If renal function is impaired, the half-life period increases according to the severity of renal failure.

Pharmaceutical characteristics.

Dosage form: film-coated tablets, yellow, with a biconvex surface, with a score on one side of the tablet and embossed “KMP” on the other side. The cross section shows a white core.

Best before date. 2 years.

Storage conditions. B: at a temperature not exceeding 25 º C.

Keep out of the reach of children.

Package. 10 film-coated tablets in a blister, 1 blister in a pack.

Vacation conditions. On prescription.

Manufacturer. OJSC "Kyiv Medpreparat"

Location. Ukraine, 01032, Kyiv, st. Saksaganskogo, 139.

A drug: CLARITHROMYCIN

Active substance: clarithromycin
ATX code: J01FA09
KFG: Macrolide antibiotic
ICD-10 codes (indications): A31.0, A46, H66, J00, J01, J02, J03, J04, J15, J20, J31, J32, J35.0, J37, J42, K25, K26, L01, L02, L03, L08.0
Reg. number: P N002496/01
Registration date: 07/21/09
Owner reg. credential: VERTEX (Russia)

DOSAGE FORM, COMPOSITION AND PACKAGING

Capsules hard gelatinous, white; the contents of the capsules are a powder or compacted mass of white or white with a yellowish tint, which disintegrates when pressed.

Excipients: lactose monohydrate - 27.4 mg, corn starch - 10.5 mg, povidone (low molecular weight medical polyvinylpyrrolidone) - 14.5 mg, croscarmellose sodium -6.4 mg, polysorbate 80 1.6 mg, calcium stearate - 3.2 mg, talc - 6.4 mg.

Composition of hard gelatin capsules: gelatin, titanium dioxide.

7 pcs. - contour cell packaging (2) - cardboard packs.
7 pcs. - contour cell packaging (4) - cardboard packs.
10 pieces. - contour cellular packaging (1) - cardboard packs.
10 pieces. - contour cell packaging (2) - cardboard packs.
10 pieces. - contour cell packaging (3) - cardboard packs.
14 pcs. - contour cellular packaging (1) - cardboard packs.
14 pcs. - contour cell packaging (2) - cardboard packs.

PHARMACHOLOGIC EFFECT

Macrolide bacteriostatic antibiotic of the second generation from the group of broad-spectrum macrolides. It disrupts the protein synthesis of microorganisms (by binding the 50S subunit of the ribosomal membrane of the microbial cell).

Active regarding: Streptococcus agalactiae (Staphylococcus pyogenes, Staphylococcus viridans, Staphylococcus pneumoniae), Haemophilus influenzae (parainfluenzae), Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, Listeria monocytogenes, Legionella pneumophila, Mycoplasma pneumoniae, Helicobacter (Campylobacter) pylori, Campylobacter jejuni, Chlamydia pneumoniae (trachomatis ), Moraxella (Branhamella) catarrhalis, Bordetella pertussis, Propionibacterium acnes, Mycobacterium avium, Mycobacterium leprae, Staphylococcus aureus, Ureaplasma urealyticum, Toxoplasma gondii, Corynebacterium spp., Borrelia burgdorferi, Pasteurella multocida, some anaerobes(Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus) and mycobacteria, except M. tuberculosis.

PHARMACOKINETICS

Absorption is fast. Food slows absorption without significantly affecting bioavailability. The bioavailability of clarithromycin in suspension form is equivalent to or slightly higher than when taken in tablet form. Communication with plasma proteins is more than 90%. After a single dose, 2 Cmax peaks are recorded. The second peak is due to the ability of the drug to concentrate in the gallbladder, followed by gradual or rapid release. The time to reach Cmax when taking 250 mg orally is 1-3 hours.

After oral administration, 20% of the dose taken is quickly hydroxylated in the liver by cytochrome P450 enzymes to form the main metabolite -14-hydroxyclarithromycin, which has pronounced antimicrobial activity against Haemophilus influenzae.

When taken regularly at 250 mg/day, the equilibrium concentrations of the unchanged drug and its main metabolite are 1 and 0.6 μg/ml, respectively; T 1/2 - 3-4 hours and 5-6 hours, respectively. When the dose is increased to 500 mg/day, the equilibrium concentration of the unchanged drug and its metabolite in plasma is 2.7-2.9 and 0.83-0.88 mcg/ml, respectively; T 1/2 - 4.8-5 hours and 6.9-8.7 hours, respectively. At therapeutic concentrations it accumulates in the lungs, skin and soft tissues (concentrations there are 10 times higher than the level in blood serum).

It is excreted by the kidneys and in feces (20-30% in unchanged form, the rest in the form of metabolites). With a single dose of 250 mg and 1.2 g, 37.9 and 46% are excreted by the kidneys, and 40.2 and 29.1% are excreted in the feces, respectively.

INDICATIONS

Lower respiratory tract infections (bronchitis, pneumonia);

Upper respiratory tract infections (pharyngitis, sinusitis, otitis);

Skin and soft tissue infections (folliculitis, erysipelas);

Widespread or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare;

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

Elimination of H. pylori and reduction in the frequency of relapses of duodenal ulcers.

DOSING REGIME

For adults The average dose for oral administration is 250 mg 2 times a day. If necessary, you can prescribe 500 mg 2 times a day. The duration of the course of treatment is 6-14 days.

For children the drug is prescribed at a dose of 7.5 mg/kg body weight/day. The maximum daily dose is 500 mg. The duration of treatment is 7-10 days.

For treatment infections caused by Mycobacterium avium, clarithromycin is prescribed orally - 1 g 2 times a day. The duration of treatment can be 6 months or more.

U patients with renal failure, with creatinine clearance less than 30 ml/min, the dose of the drug should be reduced by 2 times. The maximum course duration for patients in this group should be no more than 14 days.

SIDE EFFECT

Most frequently reported complaints from the digestive system: nausea, dyspepsia, abdominal pain, vomiting and diarrhea. Moderate to life-threatening pseudomembranous colitis has been reported. Other adverse reactions include headaches, taste disturbances, and transient increases in liver enzymes.

There are reports of rare cases of parasthesia.

There are reports of rare cases of hepatitis with increased levels of liver enzymes in the blood and the development of cholestasis and jaundice. These liver injuries were, in some cases, severe and usually reversible. In exceptional cases, liver failure with fatal outcome has been observed.

There are reports of rare cases of increased serum creatinine concentrations, the development of interstitial nephritis, and the development of renal failure.

When taking clarithromycin orally, allergic reactions were observed, the intensity of which varied from urticaria and skin rash to anaphylaxis and Stevens-Johnson syndrome.

There are reports of hearing loss during treatment with clarithromycin, which in most cases recovered after discontinuation of the drug. Changes in taste perception have also been reported, usually occurring in conjunction with taste disturbances.

There are reports of the development of glossitis, stomatitis, candidiasis of the oral mucosa and changes in the color of the tongue during treatment with clarithromycin. Changes in tooth color have also been reported in patients treated with clarithromycin. The change in tooth color was reversible in most cases.

In rare cases, hypoglycemia has been observed; in a number of these cases, hypoglycemia developed in patients who took oral hypoglycemic agents or insulin during clarithromycin treatment.

Isolated cases of thrombocytopenia and leukopenia have been reported.

When taking clarithromycin, transient side effects on the central nervous system were observed: dizziness, anxiety, fear, fear, insomnia, nightmares, tinnitus, confusion, disorientation, hallucinations, psychosis and depersonalization.

When treating with clarithromycin, as with the use of other macrolides, prolongation of the QT interval and ventricular arrhythmia, incl. ventricular paroxysmal tachycardia and ventricular flutter or fibrillation.

CONTRAINDICATIONS

Concomitant use of ergot derivatives;

When treating with clarithromycin, do not take cisapride, pimozide, astemizole and terfenadine; In patients taking these drugs simultaneously with clarithromycin, there is an increase in their concentration in the blood. In this case, it is possible to prolong the QT interval and develop cardiac arrhythmias, including ventricular paroxysmal tachycardia, ventricular fibrillation and ventricular flutter or fibrillation;

Severe liver and/or kidney dysfunction;

Hypersensitivity to macrolide antibiotics.

PREGNANCY AND LACTATION

The safety of clarithromycin during pregnancy and breastfeeding has not been established. Therefore, during pregnancy, clarithromycin is prescribed only in the absence of alternative therapy, if the expected benefit outweighs the possible risk to the fetus.

Clarithromycin passes into breast milk, so if it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

SPECIAL INSTRUCTIONS

In the presence of chronic liver diseases, it is necessary to regularly monitor serum enzymes.

Prescribe with caution against drugs metabolized by the liver (it is recommended to measure their concentration in the blood).

In case of co-administration with warfarin or other indirect anticoagulants, it is necessary to monitor the prothrombin time.

Attention should be paid to the possibility of cross-resistance between clarithromycin and other macrolide antibiotics, as well as lincomycin and clindamycin.

With prolonged or repeated use of the drug, the development of superinfection (growth of insensitive bacteria and fungi) is possible.

OVERDOSE

Symptoms: nausea, vomiting, diarrhea, headache, confusion.

Treatment: in case of overdose, immediate gastric lavage and symptomatic treatment are necessary. Hemodialysis and peritoneal dialysis do not lead to a significant change in clarithromycin serum levels.

DRUG INTERACTIONS

When taken simultaneously, it increases the concentration in the blood of drugs metabolized in the liver with the help of cytochrome P450 enzymes, indirect anticoagulants, carbamazepine, theophylline, astemizole, cisapride, terfenadine (2-3 times), triazolam, midazolam, cyclosporine, disopyramide, phenytoin, rifabutin, lovastatin, digoxin, ergot alkaloids

Rare cases of acute necrosis of skeletal muscles have been reported, coinciding with the simultaneous administration of clarithromycin and the HMC-CoA reductase inhibitors lovastatin and simvastatin.

There are reports of increased concentrations of digoxin in the plasma of patients receiving simultaneously digoxin and clarithromycin tablets. In such patients, it is necessary to constantly monitor the level of digoxin in the serum to avoid digitalis intoxication.

Clarithromycin may decrease the clearance of triazolam and thus increase its pharmacological effects resulting in drowsiness and confusion.

Concomitant use of clarithromycin and ergotamine (ergot derivatives) can lead to acute ergotamine toxicity, manifested by severe peripheral vasospasm and perverse sensitivity.

Concomitant administration of oral zidovudine and clarithromycin tablets to HIV-infected adults may result in decreased steady-state zidovudine concentrations. Given that clarithromycin is likely to alter the absorption of concomitantly administered orally administered zidovudine, this interaction is largely avoided by taking clarithromycin and zidovudine at different times of the day (at least 4 hours apart).

With the simultaneous administration of clarithromycin and ritonavir, the serum concentrations of clarithromycin increase. No dose adjustment of clarithromycin is required in these cases for patients with normal renal function. However, in patients with a creatinine clearance of 30 to 60 ml/min, the dose of clarithromycin should be reduced by 50%. When creatinine clearance is less than 30 ml/min, the dose of clarithromycin should be reduced by 75%. During concomitant treatment with ritonavir, clarithromycin should not be prescribed in doses exceeding 1 g/day.

CONDITIONS OF VACATION FROM PHARMACIES

The drug is available with a prescription.

CONDITIONS AND DURATION OF STORAGE

List B. In a dry place, protected from light, out of reach of children, at a temperature not exceeding 25°C. Shelf life - 2 years.