Klabaks - instructions for use, doses, side effects, contraindications

Excipients: cellulose microcrystalline 101.50 mg, povidone (PVP K-30) 17.50 mg, purified water * qs, magnesium stearate 6.50 mg, stearic acid 11.00 mg, talc purified 7.0 mg, silicon dioxide colloid 6 , 00 mg, croscarmellose sodium (AC-Di-Sol) 30.50 mg;

film coating: hypromellose 15.00 mg, giprolose 1.50 mg, propylene glycol 3.00 mg, sorbitan monoate 1.25 mg, titanium dioxide 1.77 mg, quinoline yellow lacquer (Cl N 47005) 0.071 mg, vanillin 1.77 mg, purified water * qs, talc purified 1,250 mg.

Tablet 500 mg:

active substance: clarithromycin 500 mg;

Excipients: microcrystalline cellulose 203.00 mg, povidone (PVP K-30) 35.00 mg, purified water * qs, magnesium stearate 13.00 mg, stearic acid 22.00 mg, talc purified 14.00 mg, silicon dioxide colloid 12 , 00 mg, croscarmellose sodium (AC-Di-Sol) 61.00 mg;

film coating: hypromellose 28.85 mg, giprolose 2.89 mg, propylene glycol q.s. sorbitan monooleate 2.4 mg, titanium dioxide 3.4 mg, lacquer quinoline yellow (Cl N 47005) 0.13 mg, vanillin 3.4 mg, purified water * q.s., talc purified 2.4 mg.

Inks for writing: black ink (Opacode S-1-27794) q.s., isopropyl alcohol *.

* evaporate in the production process.

Description:

Tablets 250 mg: light yellow in color, oval in shape, biconvex, covered with a film sheath, printed with black ink "SHT 250" on one side.

Tablets 500 mg: light yellow in color, oval in shape, biconvex, covered with a film shell, printed in black ink "СХТ 500" on one side.

Pharmacotherapeutic group:Antibiotic-macrolide

ATX: & nbsp

J.01.F.A.09 Clarithromycin

Pharmacodynamics:

Semisynthetic macrolide antibiotic of broad spectrum of action. It breaks the synthesis of the protein of microorganisms (binds to the 50S subunit of the ribosome membrane of the microbial cell). It acts on extracorporeal and intracellular pathogens.

The activity of clarithromycin in relation to most strains of the following microorganisms is proved as in vitro, and in clinical practice:

- aerobic Gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes;

- aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila;

- other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae;

- mycobacteria: Mycobacterium avium complex (MAC) - a complex, including: Mycobacterium avium and Mycobacterium intracellulare;

- Helicobacter pylori.

Beta-lactamases do not affect the activity of clarithromycin.

Activity of clarithromycin in vitro:

- aerobic Gram-positive microorganisms: Listeria monocytogenes, Streptococcus agalactiae, Streptococci groups C, F, G, Streptococci groups viridans;

- aerobic gram-negative microorganisms: Neisseria gonorrhoeae, Bordetella pertussis, Pasteurella multocida;

- anaerobic Gram-positive microorganisms: Clostridium perfringens, Peptococcus niger, Propionibacterium acnes;

- anaerobic gram-negative microorganisms: Bacteroides melaninogenicus;

- Spirochetes: Borrelia burgdorferi, Treponema pallidum;

- mycobacteria: Mycobacterium leprae, Mycobacterium chelonae;

- Campylobacteria: Campylobacter jejuni.

Microbiologically active metabolite of clarithromycin - 14 (R) -hydroxyclamirithromycin, is twice as active as the parent compound with respect to Haemophilus influenzae. Clarithromycin and its metabolite in combination can have both additive and synergistic effects on Haemophilus influenzae in vitro and in vivo, depending on the strain of the bacteria.

Most strains of staphylococci, resistant to methicillin and oxacillin, are resistant to clarithromycin. It is possible to develop cross-resistance to clarithromycin and other antibiotics of the macrolide group, as well as to lincomycin and clindamycin.

Pharmacokinetics:

Absorption is fast. Food slows down absorption, without significantly affecting bioavailability. The bioavailability of clarithromycin in the form of a suspension is equivalent to or slightly higher than when taken in the form of tablets. The connection with plasma proteins is 65-75%.

After a single dose, 2 peaks of maximum concentration are recorded. The second peak is due to the ability of the drug to concentrate in the gallbladder, followed by a gradual or rapid release. Time to reach the maximum concentration with oral intake of 250 mg - 1-3 hours.

After oral administration, 20% of the dose is rapidly hydroxylated in the liver by cytochrome CYP3A4, CYP3A5, and CYP3A7 isoenzymes to form the main metabolite - 14- (R) -hydroxyclarithromycin, which has a pronounced antimicrobial activity against Haemophilus influenzae.

With a regular intake of 250 mg / day, the equilibrium concentrations of the unchanged drug and its main metabolite are 1 and 0.6 μg / ml, respectively; the half-life is 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 μg / ml, respectively; the half-life is 4.8-5 hours and 6.9-8.7 hours, respectively.

In therapeutic concentrations, it accumulates in the lungs, skin and soft tissues (concentrations 10 times higher than serum).

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

It is an inhibitor of the isoenzymes CYP3A4, CYP3A5 and CYP3A7. In chronic renal failure, the maximum concentration, time of its attainment and the area under the concentration-time curve of clarithromycin and its metabolite increase.

Indications:

Clarithromycin is indicated for the treatment of infectious diseases caused by susceptible microorganisms. These diseases include:

- infection of the lower respiratory tract (bronchitis, pneumonia);

- infections of the upper respiratory tract (pharyngitis, sinusitis), acute, otitis media;

- infections of the skin and soft tissues (folliculitis, erysipelas);

- common or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare. Localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii;

- clarithromycin indicated for eradication H. pylori and a decrease in the frequency of recurrences of duodenal ulcers.

Contraindications:

- Hypersensitivity to antibiotics from the macrolide group;

- increased sensitivity to clarithromycin and other components of the drug;

- porphyria;

- children under 12 years of age with a body weight of less than 33 kg;

- simultaneous use of midazolam for oral administration;

- simultaneous application with ergot alkaloids (ergotamine, dihydroergotamine);

- simultaneous use with cisapride, pimozide, astemizole and terfenadine (see also Interactions with other medicinal products);

- the period of breastfeeding;

- simultaneous application with lovastatin or simvastatin;

- simultaneous application with colchicine;

- simultaneous application with ticagrelor or ranolazine;

- prolongation of QT interval on electrocardiogram (including in anamnesis), ventricular arrhythmia or "pirouette" ventricular tachycardia;

- Cholestatic jaundice / hepatitis, caused by the use of clarithromycin (in the anamnesis);

- severe hepatic insufficiency, which occurs simultaneously with renal insufficiency;

- hypokalemia.

Carefully:

- Renal and / or liver failure of moderate to severe severity;

- simultaneous use with drugs, inducing and metabolizing isoenzyme CYP3A4 (for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort, cilostazol, ciclosporin, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (for example, warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine), antiarrhythmic drugs of class IA and III, blockers of "slow" calcium channels, which are metabolized by the isoenzyme CYP3A4;

- simultaneous use with benzodiazepines, such as alprazolam, triazolam, midazolam for intravenous use;

- simultaneous application with other ototoxic drugs, especially aminoglycosides;

- simultaneous use with statins that are not dependent on the metabolism of the isoenzyme CYP3A4 (for example, fluvastatin);

- ischemic heart disease, severe heart failure, hypomagnesemia, severe bradycardia.

Pregnancy and lactation:

The safety of clarithromycin during pregnancy and lactation has not been established. Therefore, during pregnancy clarithromycin appoint only if there is no alternative therapy if the intended benefit to the mother exceeds the possible risk to the fetus.

Clarithromycin penetrates into breast milk, so if you need to take lactation during breastfeeding, you should stop breastfeeding.

Dosing and Administration:

Inside.

For adults and children over 12 years of age or with a body weight of more than 33 kg the average dose for oral administration is 250 mg 2 times / day. If necessary, you can prescribe 500 mg 2 times / day. The duration of the course of treatment is 6-14 days.

For the treatment of infections caused by the complex Mycobacterium avium, clarithromycin prescribe inside - 500 mg 2 times / day. Duration of treatment can be 6 months. and more. The maximum daily dose is 1000 mg.

In order to eradicate Helycobacter pylori in combination with other drugs: clarithromycin - 500 mg, lansoprazole - 30 mg and amoxicillin - 1000 mg, all drugs 2 times a day, for 10-14 days; clarithromycin - 500 mg, omeprazole - 20 mg and amoxicillin - 1000 mg, all drugs 2 times a day, for 10 days; clarithromycin - 500 mg 3 times a day, omeprazole 40 mg / day, for 14 days, with the appointment of omeprazole for the next 14 days at a dose of 20 mg / day.

In patients with renal insufficiency with a creatinine clearance of 10-30 ml / min, the dose of the drug should be reduced 2 times, or increase the interval by 2 times. The maximum duration of a course in patients of this group should be no more than 14 days.

Side effects:

Classification of adverse reactions according to the frequency of development (number of reported cases / number of patients): very often (≥1/10), often (≥1/100. <1/10), infrequently (≥1/1000, <1/100), is not known (side effects from the post-marketing application experience, the frequency can not be estimated from the available data).

From the nervous system: often - headache, insomnia; infrequently - loss of consciousness¹, dyskinesia¹, dizziness, drowsiness, tremor, anxiety, increased excitability³; unknown - convulsions, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dreaming ("nightmarish" or unusual dreams), paresthesia, mania.

From the side of the cardiovascular system: often - vasodilation¹; infrequently - cardiac arrest¹, atrial fibrillation, prolongation of QT interval on electrocardiogram, extrasystole¹, atrial flutter; unknown - ventricular tachycardia (including the "pirouette" type).

From the respiratory system: infrequently - asthma¹, nose bleed², pulmonary embolism¹.

From the urinary system: unknown - renal failure, interstitial nephritis.

From the digestive system: often - diarrhea, vomiting, dyspepsia, nausea, pain in the abdomen; infrequently - esophagitis¹, gastroesophageal reflux disease², gastritis, proctalgia², stomatitis, glossitis, bloating⁴, constipation, dry mouth, eructations, flatulence, cholestasis⁴, hepatitis (cholestatic or hepatocellular⁴); unknown - acute pancreatitis, discoloration of the tongue and teeth, liver failure, jaundice.

From the sense organs: often - dysgeusia, perversion of taste, infrequently - vertigo, hearing impairment, ringing in the ears: unknown - deafness, agevia (loss of taste sensations), parosmia, anosmia.

From the skin: often - intense sweating (hyperhidrosis), unknown - acne, hemorrhages.

From the musculoskeletal system: infrequently - muscle spasm³, musculoskeletal stiffness¹, myalgia²; unknown - rhabdomyolysis^2*. myopathy.

From the side of metabolism and nutrition: infrequently - anorexia, deterioration of appetite.

Allergic reactions: often - a rash, infrequently - anaphylactoid reaction¹, hypersensitivity, dermatitis bullous¹, itching. hives, maculopapular rash³, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS-syndrome); frequency unknown - anaphylactic reaction, angioedema.

Laboratory indicators: often - a deviation in the hepatic test; infrequent increase in creatinine concentration¹, increased urea concentration¹, a change in the albumin-globulin ratio, leukopenia, neutropenia⁴, eosinophilia⁴, thrombocythemia³, increased activity in the blood: alanine aminotransferase (ALT), aspartate aminotransferase (ACT), gamma-glutamyltransferase (GGT)⁴, alkaline phosphatase (AFP)⁴, lactate dehydrogenase (LDH)⁴; unknown - agranulocytosis, thrombocytopenia, increase in the value of the international normalized ratio (MPO), prolongation of prothrombin time, change in urine color, hyperbilirubinemia.

General disorders: very often phlebitis at the injection site¹; often - pain at the injection site¹, inflammation at the injection site¹; infrequent - malaise, hyperthermia, asthenia, pain in the chest⁴, fatigue⁴, chills⁴.

Infectious and parasitic diseases: infrequently - cellulite¹, candidiasis, gastroenteritis², secondary infections³ (including vaginal); unknown pseudomembranous colitis, erysipelas.

* In some reports of rhabdomyolysis clarithromycin was taken together with other drugs, the reception of which is known to be associated with the development of rhabdomyolysis (statins, fibrates, colchicine or allopurinol).

¹ Reports of these adverse reactions were obtained only with the use of Clacid®, a lyophilizate for the preparation of a solution for infusion.

²Reports of these adverse reactions were obtained only with the use of Clacid®, sustained-release tablets coated with a film coat.

³ These unwanted reactions were reported only with Clacid®, a powder for oral suspension.

⁴Reports of these adverse reactions were obtained only with the use of Clacid®, film-coated tablets.

Overdose:

Probably the development of symptoms from the gastrointestinal tract (nausea, vomiting, diarrhea); headache, confusion.

In case of an overdose, immediate gastric lavage and symptomatic treatment are necessary. Hemodialysis and peritoneal dialysis do not lead to a significant change in the level of clarithromycin in the blood serum.

Interaction:

When used simultaneously with astemisol, cisapride, pimozide, terfenadine reported increased concentrations of the latter in the blood,which can lead to the occurrence of cardiac arrhythmias (prolongation of the QT interval on the electrocardiogram, ventricular tachycardia, ventricular fibrillation, "pirouette" tachycardia). Simultaneous use of clarithromycin with astemizole, cisapride, pimozide, terfenadine is contraindicated.

Simultaneous use of clarithromycin and ergotamine or dihydroergotamine (ergot alkaloids) can lead to acute ergotamine intoxication accompanied by severe peripheral vasospasm (impaired sensitivity, paresthesia, pain and marked decrease in pulsations in the extremities, disorders of the central nervous system - dizziness, convulsions, coma).

Simultaneous reception of clarithromycin with alkaloids of ergot is contraindicated.

Care should be taken when using clarithromycin simultaneously with ototoxic drugs, primarily with aminoglycosides, due to the increase in ototoxicity. During and after the end of treatment, the function of the hearing organ and vestibular apparatus should be monitored.

Simultaneous application zidovudine in HIV-infected adult patients may lead to a decrease in equilibrium concentrations of zidovudine. As clarithromycin affects the absorption of concomitantly taken zidovudine inside, it is recommended to take these remedies at least with a 4-hour interval.

Clarithromycin inhibits the P-glycoprotein carrier, the substrate of which is digoxin. With the simultaneous use of clarithromycin and digoxin, the concentration of digoxin in the blood plasma should be carefully monitored (possibly increasing its concentration and the development of potentially fatal cardiac arrhythmias).

Interactions caused by CYP3A isoenzymes

Preparations that are inducers of the isoenzyme CYP3A4 (for example, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort pitted) can induce the metabolism of clarithromycin. This can lead to a sub-therapeutic concentration of clarithromycin, which leads to a decrease in its effectiveness. In addition, it is necessary to monitor the concentration of the inductor of the CYP3A isoenzyme in the blood plasma, which can be increased due to inhibition of the CYP3A isoenzyme by clarithromycin.

The following drugs have a proven or suspected effect on the concentration of clarithromycin in the blood plasma; In case of their joint application, it may be necessary to correct the transition to alternative treatment.

Efavirenz, nevirapine, rifampicin, rifabutin, rifapentin increase the metabolism of clarithromycin, reducing its concentration in the blood plasma and increasing the concentration of its biologically active metabolite 14-gndroksiklaritromitsina. Patients receiving inducers of CYP3A isoenzymes should consider alternative antibiotic therapies. Simultaneous use of clarithromycin and rifabutin leads to an increase in the concentration of rifabutin and a decrease in the concentration of clarithromycin in the blood plasma with a risk of uveitis.

The concentration of clarithromycin decreases with use etravirine, but the concentration of the active metabolite of 14-hydroxyclarithromycin is increased. Since 14-hydroxyclarithromycin has a low activity against infections Mycobacterium avium complex (MAC), the overall activity against their pathogens may change, therefore alternative treatment should be considered for MAC treatment.

Simultaneous application fluconazole leads to an increase in the equilibrium concentration and area under the concentration-time curve of clarithromycin by 33% and 18%, respectively. The equilibrium concentration of 14-hydroxyclarithromycin does not change. Correction of the dose of clarithromycin is not required.

Pharmacokinetic study showed that the joint application of ritonavir in a dose of 200 mg every eight hours and clarithromycin at a dose of 500 mg every 12 hours led to a marked suppression of the metabolism of clarithromycin. With the combined use of ritonavir, the maximum concentration of clarithromycin increased by 31%, the minimum concentration by 182% and the area under the concentration-time curve increased by 77%. A complete inhibition of the formation of 14-hydroxyclarithromycin was noted. At the host ritonavir patients with normal renal function clarithromycin can be applied without dose adjustment. In patients with chronic renal failure, dose adjustment is necessary: with creatinine clearance of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, and with creatinine clearance less than 30 ml / min, the dose of clarithromycin should be reduced by 75%. Ritonavir should not be taken with clarithromycin in a dose exceeding 1 g / day.

With the simultaneous use of clarithromycin and insulin, as well as some oral hypoglycemic drugs, reducing the concentration of glucose, such as nateglinide, pioglitazone, repaglinide and rosiglitazone, due to inhibition of the isoenzyme CYP3A with clarithromycin, hypoglycemia may develop. Careful monitoring of glucose concentration is recommended.

Simultaneous use of clarithromycin, which inhibits CYP3A, with a drug metabolized by CYP3A, can lead to an increase in the concentration of this drug, to an increase or prolongation of both its therapeutic effect and side effect. Clarithromycin with substrates CYP3A should be used with caution, especially in the case of a narrow security profile (for example, carbamazepine) and / or if the substrate is actively metabolized by CYP3A isoenzymes. If necessary, the dose of drugs is corrected. It is recommended to monitor the concentrations of drugs metabolized by CYP3A with the simultaneous use of clarithromycin.

Metabolism of the following drugs / classes is carried out by the same isoenzyme CYP3A as the metabolism of clarithromycin, for example, alprazolam, carbamazepine, cilostazol. ciclosporin, disopyramide, methylprednisolone, midazolam, omeprazole, indirect anticoagulants (for example, warfarin), quinidine, rifabutin, sildenafil, tacrolimus, triazolam and vinblastine. Also, the agonists of the CYP3A isoenzyme are the following drugs that are contraindicated for joint use with clarithromycin: astemizole, cisapride, pimozide, terfenadine, lovastatin, simvastatin, ergot alkaloids. To drugs interacting in a similar way through other isoenzymes within the cytochrome P450 system, phenytoin, theophylline and valproic acid.

With simultaneous application indirect anticoagulants (including warfarin), their action is likely to increase, therefore careful monitoring of prothrombin time and the international normalized ratio (INR) is recommended.

With simultaneous application with clarithromycin, an increase in equilibrium concentrations omeprazole (maximum concentration, area under the concentration-time curve and half-life increase by 30%, 89% and 34%, respectively). The average pH in the lumen of the stomach changes from 5.2 with the intake of omeprazole only to 5.7 with the simultaneous use of clarithromycin.

Metabolism withildenafil, tadalafil, vardenafil (inhibitors of phosphodiesterase-5-PDE5) passes with the participation of CYP3A isoenzymes. With the combined use of clarithromycin with sildenafil, tadalafil or vardenafil, an increase in the inhibitory effect on PDE5 is possible. When using these drugs together with clarithromycin should consider the possibility of reducing the dose of sildenafil, tadalafil and vardenafil.

Simultaneous use of clarithromycin and theophylline leads to an increase in the concentration of theophylline in the blood plasma. In patients receiving high doses of theophylline, control of the plasma concentration of theophylline is necessary.

Simultaneous use of clarithromycin and carbamazepine can lead to an increase in the concentration of carbamazepine in the blood plasma.

With the simultaneous use of clarithromycin with tolterodine in patients with a low activity of the CYP2D6 isoenzyme, a dose reduction of tolterodine may be required, since in this group of patients the metabolism of tolterodine is via CYP3A.

With the simultaneous use of clarithromycin (1 g / day) with midazolam, taken orally, it is possible to increase the area under the concentration-time curve of midazolam by a factor of 7. With the simultaneous use of midazolam for intravenous administration, this indicator increased 2.7 times. Simultaneous reception of clarithromycin with midazolam for oral administration is contraindicated.

Care must be taken to consider the possibility of dose adjustment with concurrent use of clarithromycin with midazolam administered intravenously, as well as with other benzodiazepines metabolized by CYP3A isozymes (triazolam and alprazolam).

Clarithromycin decreases clearance triazolam and thus can increase its effect with the development of drowsiness and confusion. Clinically significant interaction of clarithromycin with benzodiazepines, the metabolism of which does not depend on CYP3A isozymes (temazepam, nitrazepam, lorazepam) is unlikely.

With caution appoint with cilostazol, cyclosporine, methylprednisolone, tacrolimus, vinblastine, phenytoin and valproic acid (metabolized through other isoenzymes of cytochrome P450). It is necessary to correct the dose of the drug and monitor the concentration in the blood.

With a joint reception with antiarrhythmic drugs IA class (quinidine, procainamide, disopyramide) and III class (dofetilide, amiodarone, sotalol) there may be a "pirouette" ventricular tachycardia. It requires ECG monitoring (increasing the QT interval), serum concentrations of these drugs. There have been reports of cases of hypoglycemia in the joint use of clarithromycin and disopyramide. It is necessary to monitor the concentration of glucose in the plasma of kropi with simultaneous application of these drugs.

Simultaneous application with inhibitors of HMG-Co A-reductase (simvastatin, lovastatin) leads to an increased risk of myopathy and rhabdomyolysis. Simultaneous use of clarithromycin with simvastatin and lovastatin is contraindicated.

Clarithromycin should be used with caution in combination therapy with other statins.If it is necessary to share with statins, it is necessary to use statins that do not depend on the metabolism of CYP3A (for example, fluvastatin). It is recommended to take the lowest dose of statin. It should monitor the development of signs and symptoms of myopathy.

With the simultaneous use of clarithromycin and blockers of "slow" calcium channels, which is metabolized by the isoenzyme CYP3A4 (for example, verapamil, amlodipine, diltiazem), you should be careful, since there is a risk of arterial hypotension. Plasma concentrations of clarithromycin as well as blockers of "slow" calcium channels can increase with simultaneous application. Arterial hypotension, bradyarrhythmia and lactic acidosis are possible with concurrent administration of clarithromycin and verapamil.

Colchicine is a substrate for both CYP3A and P-glycoprotein, inhibited by clarithromycin. A single application of 0.6 mg colchicine against the background of the use of clarithromycin 250 mg twice daily for a week leads to an increase in the maximum concentration of colchicine by 197% and the area under the concentration-time curve by 239% compared to the isolated application of colchicine. Simultaneous use of clarithromycin and colchicine is contraindicated.

With the simultaneous use of clarithromycin (1g / day) and atazanavir (400 mg / day), it is possible to increase the area under the concentration-time curve of atazanavir by 28%. clarithromycin in 2 times, a decrease in the area under the concentration-time curve of 14-hydroxyclarithromycin by 70%. Due to the wide therapeutic range of clarithromycin, reducing its dose in patients with normal renal function is not required. In patients with creatinine clearance of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, and in patients with creatinine clearance less than 30 ml / min the dose should be reduced by 75%.

Doses of clarithromycin above 1000 mg can not be used concomitantly with protease inhibitors.

With the simultaneous use of clarithromycin and itraconazole possibly a mutual increase in the concentration of drugs in the plasma. For patients who simultaneously take itraconazole and clarithromycin. careful monitoring is necessary because of the possible increase or prolongation of the pharmacological effects of these drugs.

With the simultaneous use of clarithromycin (1 r / day) and saquinavir (in soft gelatin capsules,1200 mg 3 times a day) it is possible to increase the area under the concentration-time curve and the equilibrium concentration of saquinavir by 177% and 187%, respectively, and clarithromycin by 40%. With the simultaneous use of these two drugs for a limited time in doses and dosage forms indicated above, dose adjustment is not required. The results of a study of drug interactions using saquinavir in soft gelatin capsules may not correspond to the effects observed with the use of saquinavir in hard gelatinous chapels. The results of the study of drug interactions with saquinavir monotherapy may not correspond to the effects observed with saquinarine / ritonavir therapy. When taking saquinavir together with ritonavir, the potential effect of ritonavir on clarithromycin.

Special instructions:

There are reports of a violation of liver function in the form of increasing the activity of "hepatic" enzymes to hepatitis (with cholestasis and without cholestasis). Dysfunction of the liver can be pronounced, but, as a rule, they are reversible.In some cases, with serious concomitant diseases or simultaneous intake of other drugs, fatal liver failure may develop. Symptoms of hepatitis include anorexia, jaundice, darkening of the urine, skin itching, abdominal pain. If there is evidence of hepatitis, the use of clarithromycin should be stopped immediately. In the presence of chronic liver diseases it is necessary to carry out regular monitoring of serum enzymes.

When clarithromycin was used, there were cases of prolongation of the QT interval on the electrocardiogram and cases of arrhythmia development, including "pirouette" ventricular tachycardia. Risk factors for arrhythmia include severe heart failure, coronary heart disease, uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia (less than 50 beats per minute), simultaneous use of antiarrhythmic agents of class IA (quinidine, disopyramide, procainamide) and Class III (dofetilide, amiodarone, sotalol). The tendency to prolong the QT interval on an electrocardiogram in connection with taking medications is especially characteristic for elderly patients.Clarithromia should be used with caution in coronary heart disease, severe heart failure, hypomagnesemia, severe bradycardia, and concomitant administration of antiarrhythmic agents of IA and III class, as well as in elderly patients. With these conditions and with the simultaneous administration of clarithromycin with these drugs, the electrocardiogram should be monitored regularly to increase the QT interval. Clarithromycin contraindicated in patients with congenital or acquired lengthening of the QT interval, hypokalemia, and with episodes of ventricular arrhythmia in the anamnesis.

When used simultaneously with cisapride, pimozide, astemizole or terfenadine, the QT interval is prolonged, the development of cardiac arrhythmias, including ventricular paroxysmal tachycardia, ventricular fibrillation and flutter or ventricular fibrillation. Simultaneous use of clarithromycin with cisapride, pimozide, astemizole or terfenadine is contraindicated.

Caution is prescribed against the background of drugs metabolized by the liver (it is recommended to measure their concentration in the blood).

With the joint administration of oral anticoagulants (eg, warfarin) and clarithromycin, bleeding is possible, a marked increase in the international normalized ratio (MNO) and prothrombin time. In the case of co-administration with warfarin or other indirect anticoagulants, it is necessary to monitor the indices of INR and prothrombin time.

It is necessary to pay attention to the possibility of cross-resistance between clarithromycin and other antibiotics from the macrolide group, as well as lincomycin and clindamycin.

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

In the treatment of almost all antibacterial agents, including clarithromycin, cases of pseudomembranous colitis are described, the severity of which varies from mild to life-threatening. Antibiotic drugs can change the normal intestinal microflora, which can lead to growth Clostridium difficile. Pseudomembranous colitis caused by Clostridium difficile, it is necessary to suspect in all patients with diarrhea, developed after the use of antibacterial agents.After the course of antibiotic therapy, careful medical supervision of the patient is necessary. Cases of pseudomembranous colitis after 2 months after taking antibiotics were described. In mild cases, it is sufficient to cancel the treatment and apply ion-exchange resins (colestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole. Do not use drugs that inhibit the intestinal motility.

Given the growing resistance Streptococcus pneumoniae to macrolides, it is important to conduct sensitivity testing in the appointment of clarithromycin to patients with community-acquired pneumonia. With hospital pneumonia clarithromycin should be used in combination with appropriate antibiotics.

Infections of the skin and soft tissues of mild and moderate severity are most often caused Staphylococcus aureus and Streptococcus pyogenes. In this case, both pathogens can be resistant to macrolides. Therefore, it is important to carry out a sensitivity test.

In the case of acute hypersensitivity reactions, such as an anaphylactic reaction, Stevens-Johnson syndrome,toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptomatology (DRESS-syndrome), it is necessary to immediately stop taking clarithromycin and begin appropriate therapy.

If you need to reduce the dose by 75%, you can use the drug form "Klabaks - granules for the preparation of a suspension - 125 mg / ml."

Effect on the ability to drive transp. cf. and fur:

Not studied.

Form release / dosage:Film-coated tablets, 250 and 500 mg.

Packaging:

Tablets, film-coated 250 mg: 4 tablets in a blister of aluminum foil and PVC; 1, 3 or 10 blisters in a cardboard box with instructions for use. 14 tablets in a blister of aluminum foil and PVC; 1 blister in a cardboard box with instructions for use.

Film-coated tablets 500 mg: 10 or 14 tablets in a blister of aluminum foil and PVC; 1 blister in a cardboard box with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012083 / 01

Date of registration:28.09.2011 / 17.03.2016

Expiration Date:Unlimited

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp11.01.2018

Illustrated instructions

Instructions

Klabaks® (Klabax®)