Clabax, 500 mg 14 pcs

A semi-synthetic antibiotic of macrolide group. It suppresses protein synthesis in a microbial cell by interaction with 50S ribosomal subunit of bacteria. It acts mainly bacteriostatic and also bactericidal.

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.

It is also active against Toxoplasma gondii, Mycobacterium spp. (except Mycobacterium tuberculosis).

Indications

Active ingredient

Composition

How to take, the dosage

Individual. When administered orally for adults and children over 12 years old a single dose is 0.25-1 g, the frequency of administration is 2 times/day.

In children under 12 years of age the daily dose is 7.5-15 mg/kg/day in 2 doses.

In children, clarithromycin should be used in the appropriate dosage form for this patient category.

The duration of treatment depends on the indication.

Patients with impaired renal function (CKG less than 30 ml/min or serum creatinine greater than 3.3 mg/dL) should reduce the dose by half or double the interval between doses.

The maximum daily dose is 2 g in adults and 1 g in children.

Interaction

Clarithromycin inhibits the activity of CYP3A4 isoenzyme, which leads to slower metabolic rate of astemizole when using them simultaneously. As a consequence, the QT interval is prolonged and the risk of ventricular pirouette arrhythmia increases.

Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated due to the fact that these statins are largely metabolized by CYP3A4 isoenzyme, and co-administration with clarithromycin increases their serum concentrations, which leads to increased risk of myopathy, including rhabdomyolysis. Rhabdomyolysis has been reported in patients taking clarithromycin in combination with these drugs. If clarithromycin should be used, lovastatin or simvastatin should be discontinued for the duration of therapy.

Clarithromycin should be used with caution when combined therapy with other statins. It is recommended to use statins that do not depend on CYP3A isoenzyme metabolism (e.g., fluvastatin). If coadministration is necessary, it is recommended to take the lowest dose of statin. The development of signs and symptoms of myopathy should be monitored. Concomitant use with atorvastatin moderately increases plasma concentrations of atorvastatin and increases the risk of myopathy.

Drugs that are CYP3A inducers (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort) can induce clarithromycin metabolism, which may lead to subtherapeutic concentration of clarithromycin and decrease its effectiveness. Plasma concentration of CYP3A inducer must be monitored, which may increase due to inhibition of CYP3A by clarithromycin.

The co-administration with rifabutin increases plasma concentrations of rifabutin, increases the risk of uveitis, and decreases plasma concentrations of clarithromycin.

The plasma concentrations of phenytoin, carbamazepine, valproic acid may increase when co-administered with clarithromycin.

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

Plasma concentrations of clarithromycin are decreased when etravirine is used and concentrations of the active metabolite 14-OH-clariotromycin are increased. Since 14-OH clarithromycin has low activity against MAC infections, the overall activity against their pathogens may change, so alternative treatments should be considered for the treatment of MAC.

A pharmacokinetic study showed that co-administration of ritonavir at a dose of 200 mg every 8 h and clarithromycin at a dose of 500 mg every 12 h resulted in marked inhibition of clarithromycin metabolism. When ritonavir was coadministered, the Cmax of clarithromycin increased by 31%, the Cmin increased by 182% and the AUC increased by 77%, while the concentration of its metabolite 14-OH-clarithromycin decreased significantly. Ritonavir should not be coadministered with clarithromycin in doses greater than 1 g/day.

Clarithromycin, atazanavir, and saquinavir are substrates and inhibitors of CYP3A, which determines their bidirectional interaction. When taking saquinavir together with ritonavir, the potential effect of ritonavir on clarithromycin should be considered.

The bioavailability of zidovudine is slightly reduced when used concomitantly with zidovudine.

Colchicine is a substrate of both CYP3A and P-glycoprotein. Clarithromycin and other macrolides are known to be CYP3A and P-glycoprotein inhibitors. If clarithromycin and colchicine are coadministered, inhibition of P-glycoprotein and/or CYP3A may increase the effect of colchicine. The development of clinical symptoms of colchicine poisoning should be controlled. Post-marketing reports on cases of colchicine poisoning when taking it concomitantly with clarithromycin have been registered, more often in elderly patients. Some of the described cases occurred in patients with renal insufficiency. Some cases have been reported to be fatal. Concomitant use of clarithromycin and colchicine is contraindicated.

The concomitant use of midazolam and clarithromycin (oral 500 mg twice daily) showed a 2.7-fold increase in the AUC of midazolam after intravenous administration of midazolam and a 7-fold increase after oral administration. Simultaneous oral administration of clarithromycin and midazolam is contraindicated. If an intravenous form of midazolam is used together with clarithromycin, the patient’s condition should be closely 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 excretion is not dependent on CYP3A (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely.

When clarithromycin and triazolam are used together, CNS effects such as drowsiness and confusion may occur. It is recommended to monitor for CNS disturbance symptoms with this combination.

Concomitant use with warfarin may increase the anticoagulant effect of warfarin and increase the risk of bleeding.

It is assumed that digoxin is a substrate for P-glycoprotein. Clarithromycin is known to inhibit P-glycoprotein. Concomitant use with digoxin may significantly increase plasma concentrations of digoxin and risk of glycoside intoxication.

Ventricular pirouette tachycardia may occur if clarithromycin and quinidine or disopyramide are used concomitantly. If clarithromycin is coadministered with these drugs, regular ECG monitoring for QT interval prolongation should be performed, and serum concentrations of these drugs should be monitored. Cases of hypoglycemia have been reported with clarithromycin and disopyramide in post-marketing use. Blood glucose concentrations should be monitored during concomitant use of clarithromycin and disopyramide. It is believed that plasma concentration of disopyramide may increase due to inhibition of its metabolism in the liver by clarithromycin.

The co-administration of fluconazole in dose of 200 mg daily and clarithromycin in dose of 500 mg 2 times per day caused increase in mean value of minimum equilibrium concentration of clarithromycin (Cmin) and AUC by 33% and 18% respectively. However, co-administration had no significant effect on the mean equilibrium concentration of the active metabolite 14-OH-clarithromycin. No dose adjustment of clarithromycin is required in case of concomitant administration of fluconazole.

Clarithromycin and itraconazole are substrates and inhibitors of CYP3A, which determines their bidirectional interaction. Clarithromycin can increase the plasma concentration of itraconazole, while itraconazole can increase the plasma concentration of clarithromycin.

Concomitant use with methylprednisolone decreases clearance of methylprednisolone; cases of acute mania and psychosis have been described with prednisone.

Concomitant use with omeprazole significantly increases concentrations of omeprazole and slightly increases plasma concentrations of clarithromycin; with lansoprazole – possible glossitis, stomatitis and/or dark coloration of the tongue.

In concomitant use with sertraline – theoretically we cannot rule out the development of serotonin syndrome; with theophylline – possible increase in plasma concentration of theophylline.

In concomitant use with terfenadine, slowing of terfenadine metabolism rate and increasing of its plasma concentration is possible, which may lead to prolongation of QT interval and increase risk of ventricular pirouette arrhythmia.

Inhibition of CYP3A4 isoenzyme activity by clarithromycin leads to slower metabolic rate of cisapride when using them concomitantly. Consequently, plasma concentrations of cisapride increase and the risk of life-threatening cardiac arrhythmias, including pirouette-type ventricular arrhythmias, increases.

The primary metabolism of tolterodine is via CYP2D6. However, in a portion of the population lacking CYP2D6, metabolism occurs with the participation of CYP3A. In this population, suppression of CYP3A leads to significantly higher serum concentrations of tolterodine. Therefore, patients with low CYP2D6-mediated metabolism may require a dose reduction of tolterodine in the presence of CYP3A inhibitors such as clarithromycin.

When clarithromycin and oral hypoglycemic agents (e.g., sulfonylurea derivatives) and/or insulin are coadministered, severe hypoglycemia may be observed. Concomitant use of clarithromycin with some hypoglycemic drugs (e.g. nateglinide, pioglitazone, repaglinide and rosiglitazone) may lead to inhibition of CYP3A isoenzymes by clarithromycin, which may lead to hypoglycemia. It is believed that when used concomitantly with tolbutamide, there is a possibility of developing hypoglycemia.

A case of fluoxetine-induced toxic effects has been described when used concomitantly with fluoxetine.

Concomitant use of clarithromycin with other ototoxic drugs, especially aminoglycosides, requires caution and monitoring of vestibular and auditory function both during and after therapy.

Concomitant use with cyclosporine increases plasma concentrations of cyclosporine, there is a risk of increased side effects.

In concomitant use with ergotamine, dihydroergotamine there have been described cases of increased side effects of ergotamine and dihydroergotamine. Postmarketing studies indicate that concomitant use of clarithromycin with ergotamine or dihydroergotamine may cause the following effects associated with acute poisoning by drugs of the ergotamine group: vascular spasm, ischemia of limbs and other tissues, including CNS. Concomitant use of clarithromycin and ergot alkaloids is contraindicated.

Each of these FDE inhibitors is metabolized at least in part by CYP3A. Clarithromycin, on the other hand, is able to inhibit CYP3A. Concomitant use of clarithromycin with sildenafil, tadalafil or vardenafil may lead to increased inhibitory effects on FDE. In these combinations, consideration should be given to reducing the dose of sildenafil, tadalafil and vardenafil.

When concomitant use of clarithromycin and calcium channel blockers that are metabolized by CYP3A4 isoenzymes (e.g., verapamil, amlodipine, diltiazem), caution should be exercised because of the risk of arterial hypotension. Plasma concentrations of clarithromycin, as well as calcium channel blockers may increase with concomitant use. Arterial hypotension, bradyarrhythmia and lactacidosis are possible with concomitant use of clarithromycin and verapamil.

Special Instructions

Caution should be used with clarithromycin in patients with moderate to severe renal impairment; moderate to severe hepatic impairment, with CHD, severe heart failure, hypomagnesemia, marked bradycardia (less than 50 bpm); concomitantly with benzodiazepines such as alprazolam, triazolam, midazolam, and intravenous drugs./min); simultaneously with benzodiazepines, such as alprazolam, triazolam, midazolam for IV administration; simultaneously with other ototoxic drugs, especially aminoglycosides; simultaneously with drugs that are metabolized by CYP3A isoenzymes (incl. carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants, quinidine, rifabutin, sildenafil, tacrolimus, vinblastine; simultaneously with CYP3A4 inducers (incl.Rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort); simultaneously with statins, metabolism of which does not depend on CYP3A isoenzyme (incl.including fluvastatin); simultaneously with slow calcium channel blockers, which are metabolized by CYP3A4 isoenzymes (including verapamil, amlodipine, diltiazem); simultaneously with antiarrhythmic agents of class I A (quinidine, procainamide) and class III (dofetilide, amiodarone, sotalol).

There is cross-resistance between antibiotics from the macrolide group.

Treatment with antibiotics changes the normal gut flora, so superinfection caused by resistant microorganisms may develop.

We should note that severe persistent diarrhea may be due to development of pseudomembranous colitis.

Protrombin time should be monitored periodically in patients receiving clarithromycin concomitantly with warfarin or other oral anticoagulants.

Contraindications

Side effects

The digestive system: frequent – diarrhea, vomiting, dyspepsia, nausea, abdominal pain; infrequent – esophagitis, gastroesophageal reflux disease, gastritis, proctalgia, stomatitis, glossitis, bloating, constipation, dry mouth, belching, flatulence, increased blood bilirubin concentration, increased activity of ALT, ACT, GGT, ALF, LDH, cholestasis, hepatitis, including.including cholestatic and hepatocellular; frequency is unknown – acute pancreatitis, discoloration of tongue and teeth, liver failure, cholestatic jaundice.

Allergic reactions: frequent – rash; infrequent – anaphylactoid reaction, hypersensitivity, bullous dermatitis, pruritus, urticaria, maculopapular rash; frequency unknown – anaphylactic reaction, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).

Nervous system disorders: frequent – headache, insomnia; infrequent – loss of consciousness, dyskinesia, dizziness, somnolence, tremor, anxiety, increased excitability; frequency unknown – seizures, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, nightmares, paresthesia, mania.

Skin disorders: often – intense sweating; frequency unknown – acne, hemorrhages.

Senses: frequent – dysgeusia; infrequent – vertigo, hearing impairment, tinnitus; frequency unknown – deafness, agueusia, parosmia, anosmia.

Cardiovascular system: often – vasodilation; infrequent – cardiac arrest, atrial fibrillation, prolongation of QT interval in ECG, extrasystole, atrial flutter; frequency unknown – ventricular tachycardia, including “pirouette” type.

Urinary system disorders: infrequent – increased concentration of creatinine, discoloration of urine; frequency unknown – renal failure, interstitial nephritis.

Metabolism and nutrition: infrequent – anorexia, decreased appetite, increased concentration of urea, albumin-globulin ratio.

Muscular system disorders: infrequent – muscle spasm, musculoskeletal stiffness, myalgia; frequency unknown – rhabdomyolysis, myopathy.

Respiratory system: infrequent – asthma, nasal bleeding, pulmonary embolism.

Hematopoietic system: infrequent – leukopenia, neutropenia, eosinophilia, thrombocythemia; frequency unknown – agranulocytosis, thrombocytopenia.

With coagulation system: infrequent – increase of MHO value, prolongation of prothrombin time.

Infectious and parasitic diseases: infrequent – cellulitis, candidiasis, gastroenteritis, secondary infections (including vaginal); frequency is unknown – pseudomembranous colitis, rye.

Local reactions: very common – phlebitis at the injection site, common – pain at the injection site, inflammation at the injection site.

The body in general: infrequent – malaise, hyperthermia, asthenia, chest pain, chills, fatigue.

Overdose

Similarities