Instructions for use FROMILID® UNO
The use of the following drugs is strictly contraindicated due to the possible development of severe consequences of drug interactions
Cisapride, pimozide, astemizole, terfenadine
An increase in the concentration of cisapride in the blood serum was observed when used together with clarithromycin, which can lead to a prolongation of the QT interval and the occurrence of arrhythmias, incl. ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the “pirouette” type. Similar effects were observed with the combined use of clarithromycin and pimozide.
It was noted that antibiotics of the macrolide group change the metabolism of terfenadine, as a result of which its concentration in the blood serum increases, which can also lead to a prolongation of the QT interval and the appearance of arrhythmias, incl. ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the “pirouette” type. In one study of 14 healthy volunteers, the simultaneous use of clarithromycin and terfenadine showed an increase in serum concentrations of the acid metabolite terfenadine by 2-3 times and a prolongation of the QT interval, which was not clinically significant. Similar effects were observed with the combined use of astemizole and other macrolide antibiotics.
Ergotamine/dihydroergotamine
Concomitant use of clarithromycin and ergotamine or dihydroergotamine has been associated with signs of acute ergotism, which is characterized by vasospasm and ischemia of the limbs and other tissues, including the central nervous system. The use of clarithromycin and these drugs is contraindicated.
Effect of other drugs on the pharmacokinetics of clarithromycin
Medicines that are CYP3A inducers (for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) may induce the metabolism of clarithromycin. This may result in subtherapeutic concentrations of clarithromycin and reduced effectiveness. In addition, it may be necessary to monitor plasma concentrations of the CYP3A inducer, which may be increased due to the inhibition of CYP3A by clarithromycin (see also the prescribing information for the corresponding CYP3A4 inducer). Concomitant use of rifabutin and clarithromycin resulted in increased rifabutin concentrations and decreased clarithromycin plasma concentrations, while increasing the risk of uveitis.
The following drugs have known or suspected effects on clarithromycin blood concentrations, so dose adjustments or alternative therapy may be necessary.
Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine
Potent inducers of cytochrome P450 isoenzymes, such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentine, can accelerate the metabolism of clarithromycin, reducing its concentration in the blood plasma, but increasing the concentration of 14-OH-clarithromycin, a microbiologically active metabolite. Because 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 isoenzymes of the cytochrome P450 system.
Fluconazole
Css of the active metabolite 14-OH-clarithromycin did not change significantly when combined with fluconazole. No clarithromycin dose change is required.
Ritonavir
The use of ritonavir and clarithromycin led to a significant inhibition of clarithromycin metabolism. Cmax of clarithromycin increased by 31%, Cmin by 182%, AUC increased by 77%. There was complete inhibition of the formation of 14-OH-clarithromycin. Due to the large therapeutic range, a dose reduction of clarithromycin is not required in patients with normal renal function. In patients with renal failure, dose adjustment is necessary:
- with a CC of 30-60 ml/min, the dose of clarithromycin should be reduced by 50%; with a CC of <30 ml/min, the dose of clarithromycin should be reduced by 75%. Doses of clarithromycin exceeding 1 mg/day should not be used with ritonavir.
The same dose adjustment should be made in patients with renal impairment when ritonavir is used as a pharmacokinetic enhancer with other HIV protease inhibitors, including atazanavir and saquinavir.
Effect of clarithromycin on the pharmacokinetics of other drugs that are CYP3A substrates
Concomitant use of clarithromycin, a known inhibitor of the CYP3A isoenzyme, and a drug primarily metabolized by CYP3A, leads to an increase in the concentration of this drug in the blood plasma, which, in turn, may enhance or prolong the therapeutic effect and the risk of adverse reactions.
Caution should be exercised when using clarithromycin in patients receiving therapy with drugs that are CYP3A substrates, especially if these drugs have a narrow therapeutic index (for example, carbamazepine) and/or are extensively metabolized by this isoenzyme.
Dosage adjustments and, if possible, close monitoring of serum concentrations of a drug metabolized by CYP3A in patients concomitantly receiving clarithromycin may be necessary.
The following drugs or groups of drugs are known (or suspected) to be metabolized by the same isoenzyme CYP3A:
- alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (eg, warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfen adin, triazolam and vinblastine . A similar mechanism of interaction was noted with the use of phenytoin, theophylline and valproate, which are metabolized by another isoenzyme of the cytochrome P450 system.
Antiarrhythmic drugs
There are post-marketing reports of the development of ventricular tachycardia of the torsade de pointes type that occurred with the simultaneous use of clarithromycin with quinidine or disopyramide. It is recommended to carry out ECG monitoring for timely detection of QT interval prolongation. Plasma concentrations of these drugs should be monitored during clarithromycin therapy.
Omeprazole
The use of clarithromycin in combination with omeprazole in healthy adult volunteers resulted in an increase in the Css of omeprazole. When omeprazole was used alone, the average pH value of gastric juice when measured over 24 hours was 5.2, when omeprazole was used together with clarithromycin - 5.7.
Sildenafil, tadalfil and vardenafil
There is a possibility of increased plasma concentrations of PDE inhibitors (sildenafil, tadalafil and vardenafil) when used together with clarithromycin, which may require a reduction in the dose of PDE inhibitors.
Theophylline, carbamazepine
The results of clinical studies have shown that there is a slight but statistically significant increase in the concentration of theophylline or carbamazepine in the blood plasma when used simultaneously with clarithromycin. A dose reduction may be required.
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. When administering midazolam intravenously with clarithromycin, the patient should be carefully monitored for timely dose adjustment.
The same precautions should be taken when using other benzodiazepines that are metabolized by CYP3A, including triazolam and alprazolam. For benzodiazepines whose elimination does not depend on CYP3A (temazepam, nitrazepam, lorazepam), the development of a clinically significant interaction with clarithromycin is unlikely. There are post-marketing reports of drug interactions and CNS side effects (such as drowsiness and confusion) when clarithromycin and triazolam are used together. The patient's condition should be monitored, taking into account the possibility of enhancing the pharmacological effect on the central nervous system.
Other types of interaction
Colchicine is a substrate of CYP3A and P-glycoprotein (Pgp). It is known that clarithromycin and other macrolide antibiotics are capable of inhibiting CYP3A and Pgp. 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 signs of colchicine toxicity.
With the simultaneous use of clarithromycin and statins, fibrates, colchicine, allopurinol, cases of rhabdomyolysis have been reported.
According to post-marketing studies, the simultaneous use of colchicine and clarithromycin can cause colchicine toxicity (sometimes fatal), especially in elderly patients, incl. against the background of renal failure.
During post-marketing surveillance, increased digoxin plasma concentrations have been reported in patients receiving clarithromycin concomitantly with digoxin. Some patients developed signs of digoxin toxicity, incl. potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored in patients receiving it with clarithromycin.
Concomitant use of clarithromycin tablets and zidovudine in HIV-infected patients may cause a decrease in plasma Css of zidovudine. This can be largely avoided by maintaining an interval between doses of clarithromycin and zidovudine. This interaction has not been reported with the use of clarithromycin suspension and zidovudine or dideoxynosine in children. This interaction is unlikely with intravenous infusions of clarithromycin.
There have been spontaneous or published reports of interactions between CYP3A inhibitors, including clarithromycin, and drugs not believed to be metabolized by CYP3A (eg, phenytoin and valproate). It is recommended to determine plasma concentrations of these drugs when coadministering them with clarithromycin. Increased plasma concentrations have been reported.
Bidirectional drug interactions between clarithromycin and atazanavir, itraconazole, and saquinavir are also possible.
The development of arterial hypotension, bradycardia and lactic acidosis has been reported with the combined use of clarithromycin and verapamil.
Clarithromycin does not interact with oral contraceptives.
Fromilid uno (tablet p/o 500 mg No. 5 prolong)
A country
Slovenia
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Clarithromycin
Compound
1 tablet contains: clarithromycin 500 mg.
Excipients: sodium alginate - 80 mg, sodium calcium alginate - 90 mg, lactose monohydrate - 225 mg, povidone - 30 mg, polysorbate 80 - 30 mg, colloidal anhydrous silicon dioxide - 5 mg, magnesium stearate - 10 mg, talc - 30 mg. Shell composition: hypromellose - 14.45 mg, talc - 1.33 mg, quinoline yellow dye (E104) - 0.5 mg, titanium dioxide - 2.64 mg, propylene glycol - 1.08 mg. Extended-release tablets, yellow, oval, biconvex, film-coated, marked “U” on one side.
pharmachologic effect
Semi-synthetic antibiotic of the macrolide group. Suppresses protein synthesis in microbial cells by interacting with the 50S ribosomal subunit of bacteria. It acts mainly bacteriostatically and also bactericidally. Active against gram-positive bacteria: - Streptococcus spp., Staphylococcus spp., Listeria monocytogenes, Corynebacterium spp.; — gram-negative bacteria: Helicobacter pylori, Haemophilus influenzae, Haemophilus ducreyi, Moraxella catarrhalis, Bordetella pertussis, Neisseria gonorrhoeae, Neisseria meningitidis, Borrelia burgdorferi; — anaerobic bacteria: Eubacterium spp., Peptococcus spp., Propionibacterium spp., Clostridium perfringens, Bacteroides melaninogenicus; — intracellular microorganisms: Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae, Ureaplasma urealyticum, Mycoplasma pneumoniae. Also active against Toxoplasma gondii, Mycobacterium spp. (except Mycobacterium tuberculosis).
Indications for use
Treatment of infectious and inflammatory diseases caused by pathogens sensitive to clarithromycin: - infections of the upper respiratory tract and ENT organs (tonsillopharyngitis, otitis media, acute sinusitis); - infections of the lower respiratory tract (acute bronchitis, exacerbation of chronic bronchitis, community-acquired bacterial and atypical pneumonia); - odontogenic infections; - infections of the skin and soft tissues; — mycobacterial infections (M.avium complex, M.kansasii, M.marinum, M.leprae) and their prevention in AIDS patients; — eradication of Helicobacter pylori in patients with duodenal or gastric ulcer (only as part of combination therapy).
Mode of application
Individual. When taken orally for adults and children over 12 years of age, the single dose is 0.25-1 g, the frequency of administration is 2 times a day. For children under 12 years of age, the daily dose is 7.5-15 mg/kg/day in 2 divided doses. In children, clarithromycin should be used in the appropriate dosage form intended for this category of patients. The duration of treatment depends on the indications. In patients with impaired renal function (creatinine clearance less than 30 ml/min or serum creatinine level more than 3.3 mg/dl), the dose should be halved or the interval between doses should be doubled. Maximum daily doses: for adults - 2 g, for children - 1 g.
Interaction
Clarithromycin inhibits the activity of the CYP3A4 isoenzyme, which leads to a slower rate of metabolism of astemizole when used simultaneously. As a result, there is an increase in the QT interval and an increased risk of developing ventricular arrhythmias. Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated due to the fact that these statins are largely metabolized by the CYP3A4 isoenzyme, and co-administration 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 CYP3A isoenzymes (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. When used simultaneously with atorvastatin, the concentration of atorvastatin in the blood plasma increases moderately and the risk of developing myopathy increases. Drugs that are CYP3A inducers (for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) can induce the metabolism of clarithromycin, which can lead to subtherapeutic concentrations of clarithromycin and a decrease in its effectiveness. It is necessary to monitor the plasma concentration of the CYP3A inducer, which may increase due to the inhibition of CYP3A by clarithromycin. When used together with rifabutin, the concentration of rifabutin in the blood plasma increases, the risk of developing uveitis increases, and the concentration of clarithromycin in the blood plasma decreases. When used together with clarithromycin, plasma concentrations of phenytoin, carbamazepine, and valproic acid may increase. Strong inducers of isoenzymes 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 plasma and weaken its therapeutic effect, and at the same time increase the concentration of 14-OH-clarithromycin - metabolite, which 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. The plasma concentration of clarithromycin decreases with the use of etravirine, while the concentration of the active metabolite 14-OH-clarithromycin increases. Because 14-OH-clarithromycin has low activity against MAC infections, overall activity against MAC infections may be affected, and alternative treatments should be considered for the treatment of MAC. A pharmacokinetic study showed that co-administration of ritonavir 200 mg every 8 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%, while the concentration of its metabolite 14-OH-clarithromycin was significantly reduced. Ritonavir should not be co-administered with clarithromycin in doses exceeding 1 g/day. Clarithromycin, atazanavir, and saquinavir are substrates and inhibitors of CYP3A, which determines their bidirectional interaction. When taking saquinavir with ritonavir, consider the potential effect of ritonavir on clarithromycin. When used simultaneously with zidovudine, the bioavailability of zidovudine is slightly reduced. Colchicine is a substrate of both CYP3A and P-glycoprotein. Clarithromycin and other macrolides are known to be inhibitors of CYP3A and P-glycoprotein. When clarithromycin and colchicine are taken together, inhibition of P-glycoprotein 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 with renal failure. Some cases were reported to be fatal. The simultaneous use of clarithromycin and colchicine is contraindicated. When midazolam and clarithromycin were used together (500 mg orally 2 times a day), an increase in midazolam AUC was noted: 2.7 times after intravenous administration of midazolam and 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. 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 CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely. When clarithromycin and triazolam are used together, effects on the central nervous system, such as drowsiness and confusion, are possible. With this combination, it is recommended to monitor symptoms of central nervous system disorders. When used simultaneously with warfarin, the anticoagulant effect of warfarin may be enhanced and the risk of bleeding may increase. Digoxin is thought to be a substrate for P-glycoprotein. Clarithromycin is known to inhibit P-glycoprotein. When used simultaneously with digoxin, there may be a significant increase in the concentration of digoxin in the blood plasma and the risk of developing glycoside intoxication. 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 interval 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. It is believed that it is possible to increase the concentration of disopyramide in the blood plasma due to inhibition of its metabolism in the liver under the influence of clarithromycin. Co-administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 500 mg 2 times a day caused an increase in the mean minimum equilibrium concentration of clarithromycin (Cmin) 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. Clarithromycin and itraconazole are substrates and inhibitors of CYP3A, which determines their bidirectional interaction. Clarithromycin may increase plasma concentrations of itraconazole, while itraconazole may increase plasma concentrations of clarithromycin. When used simultaneously with methylprednisolone, the clearance of methylprednisolone decreases; with prednisone - cases of acute mania and psychosis have been described. When used simultaneously with omeprazole, the concentration of omeprazole increases significantly and the concentration of clarithromycin in the blood plasma increases slightly; with lansoprazole - glossitis, stomatitis and/or the appearance of a dark color of the tongue are possible. When used simultaneously with sertraline, the development of serotonin syndrome cannot be theoretically excluded; with theophylline - it is possible to increase the concentration of theophylline in the blood plasma. When used simultaneously with terfenadine, it is possible to slow down the rate of metabolism of terfenadine and increase its concentration in the blood plasma, which can lead to an increase in the QT interval and an increased risk of developing ventricular arrhythmias. Inhibition of the activity of the CYP3A4 isoenzyme under the influence of clarithromycin leads to a slower rate of metabolism of cisapride when used simultaneously. As a result, the concentration of cisapride in the blood plasma increases and the risk of developing life-threatening cardiac arrhythmias, including ventricular arrhythmias, increases. The primary metabolism of tolterodine is carried out with the participation of CYP2D6. However, in the part of the population lacking CYP2D6, metabolism occurs with the participation of CYP3A. In this population, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. Therefore, in patients with low levels of CYP2D6-mediated metabolism, a reduction in the dose of tolterodine may be required in the presence of CYP3A inhibitors such as clarithromycin. 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 result in inhibition of CYP3A isoenzymes by clarithromycin, which may lead to hypoglycemia. It is believed that when used concomitantly with tolbutamide, there is a risk of developing hypoglycemia. When used simultaneously with fluoxetine, a case of the development of toxic effects due to the action of fluoxetine has been described. When taking clarithromycin concomitantly with other ototoxic drugs, especially aminoglycosides, caution should be exercised and the functions of the vestibular and auditory systems should be monitored both during and after therapy. When used simultaneously with cyclospor...
Side effect
From the digestive system: - often - diarrhea, vomiting, dyspepsia, nausea, abdominal pain; - uncommon - esophagitis, gastroesophageal reflux disease, gastritis, proctalgia, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence, increased concentration of bilirubin in the blood, increased activity of ALT, AST, GGT, ALP, LDH, cholestasis, hepatitis, incl. cholestatic and hepatocellular; - frequency unknown - acute pancreatitis, discoloration of the tongue and teeth, liver failure, cholestatic jaundice. Allergic reactions: - often - rash; - uncommon - anaphylactoid reaction, hypersensitivity, bullous dermatitis, itching, urticaria, maculopapular rash; - frequency unknown - anaphylactic reaction, angioedema, 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 consciousness, dyskinesia, dizziness, drowsiness, tremor, anxiety, increased excitability; - frequency unknown - convulsions, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, nightmares, paresthesia, mania. From the skin: - often - intense sweating; — frequency unknown — acne, hemorrhages. From the senses: - often - dysgeusia, taste perversion; - uncommon - vertigo, hearing loss, ringing in the ears; - frequency unknown - deafness, ageusia, parosmia, anosmia. From the cardiovascular system: - often - vasodilation; - uncommon - cardiac arrest, atrial fibrillation, prolongation of the QT interval on the ECG, extrasystole, atrial flutter; - frequency unknown - ventricular tachycardia, incl. "pirouette" type. From the urinary system: - uncommon - increased creatinine concentration, change in urine color; - frequency unknown - renal failure, interstitial nephritis. From the side of metabolism and nutrition: infrequently - anorexia, decreased appetite, increased urea concentration, change in the albumin-globulin ratio. From the musculoskeletal system: - uncommon - muscle spasm, musculoskeletal stiffness, myalgia; - frequency unknown - rhabdomyolysis, myopathy. From the respiratory system: infrequently - asthma, nosebleeds, pulmonary embolism. From the hematopoietic system: - uncommon - leukopenia, neutropenia, eosinophilia, thrombocythemia; - frequency unknown - agranulocytosis, thrombocytopenia. From the blood coagulation system: infrequently - increase in MHO value, prolongation of prothrombin time. Infectious and parasitic diseases: - uncommon - cellulitis, candidiasis, gastroenteritis, secondary infections (including vaginal); - frequency unknown - pseudomembranous colitis, erysipelas. Local reactions: very often - phlebitis at the injection site, often - pain at the injection site, inflammation at the injection site. From the body as a whole: infrequently - malaise, hyperthermia, asthenia, chest pain, chills, fatigue.
Contraindications
A history of QT interval prolongation, ventricular arrhythmia, or torsade de pointes;
- hypokalemia (risk of QT interval prolongation); - severe liver failure occurring simultaneously with renal failure; - a history of cholestatic jaundice/hepatitis that developed during the use of clarithromycin; - porphyria; — I trimester of pregnancy; - lactation period (breastfeeding); - simultaneous use of clarithromycin with astemizole, cisapride, pimozide, terfenadine; - with ergot alkaloids, for example, ergotamine, dihydroergotamine; - with midazolam for oral administration; - with HMG-CoA reductase inhibitors (statins), which are largely metabolized by the CYP3A4 isoenzyme (lovastatin, simvastatin), with colchicine; - with ticagrelor or ranolazine; - hypersensitivity to clarithromycin and other macrolides. Use during pregnancy and breastfeeding Use in the first trimester of pregnancy is contraindicated. Use in the second and third trimesters of pregnancy is possible only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. If necessary, use during lactation should stop breastfeeding.
Use in children Currently, there is insufficient data on the effectiveness and safety of clarithromycin in children under 6 months of age.
special instructions
Clarithromycin should be used with caution in patients with moderate to severe renal impairment; moderate to severe liver failure, with ischemic heart disease, severe heart failure, hypomagnesemia, severe bradycardia (less than 50 beats/min); simultaneously with benzodiazepines, such as alprazolam, triazolam, midazolam for intravenous administration; simultaneously with other ototoxic drugs, especially aminoglycosides; simultaneously with drugs that are metabolized by CYP3A isoenzymes (including carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants, quinidine, rifabutin, sildenafil, tacrolimus, vinblastine; simultaneously with CYP3A4 inducers (including rifampicin , phenytoin, carbamazepine, phenobarbital, St. John's wort); simultaneously with statins, the metabolism of which does not depend on the CYP3A isoenzyme (including fluvastatin); simultaneously with blockers of slow calcium channels, which are metabolized by the CYP3A4 isoenzyme (including verapamil, amlodipine, diltiazem); simultaneously with antiarrhythmic drugs of class IA (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol). Cross-resistance is observed between antibiotics from the macrolide group. Treatment with antibiotics changes the normal intestinal flora, so the development of superinfection caused by resistant microorganisms.It should be borne in mind that severe persistent diarrhea may be due to the development of pseudomembranous colitis. Prothrombin time should be periodically monitored in patients receiving clarithromycin concomitantly with warfarin or other oral anticoagulants.
Storage conditions
Room temperature
Dispensing conditions in pharmacies
On prescription
