Clarithromycin, 250 mg 14 pcs

Pharmacotherapeutic group: antibiotic-macrolide.

Code ATX: J01FA09

Pharmacological properties

Pharmacodynamics

. Clarithromycin is a semisynthetic antibiotic of the macrolide group and has an antibacterial effect by interacting with the 50S ribosomal subunit and inhibiting the protein synthesis of bacteria susceptible to it.

Clarithromycin has demonstrated high in vitro activity against both standard laboratory strains of bacteria and those isolated from patients in clinical practice. It shows high activity against many aerobic and anaerobic gram-positive and gram-negative microorganisms. Minimum inhibitory concentrations (MIC) of clarithromycin for most pathogens are lower than MIC of erythromycin on average by one log2 dilution.

Clarithromycin in vitro is highly active against Legionella pneumophila, Mycoplasma pneumoniae. It has a bactericidal effect against Helicobacter pylori, this activity of clarithromycin is higher at neutral pH than at acidic pH.

In addition, in vitro and in vivo data indicate that clarithromycin is active against clinically relevant mycobacterial species. Enterobacteriaceae and Pseudomonas spp. also other non-lactose-fermenting gram-negative bacteria are not sensitive to clarithromycin.

The activity of clarithromycin against most strains of the following microorganisms has been proven both in vitro and in clinical practice for the diseases listed under “Indications for use”.

Aerobic Gram-positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes.

Aerobic Gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophila.

Other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR). Mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC) – complex including: Mycobacterium avium, Mycobacterium intracellulare.

The production of beta-lactamase has no effect on clarithromycin activity. Most staphylococcal strains resistant to methicillin and oxacillin are also resistant to clarithromycin.

Helicobacter pylori

The sensitivity of H.pylori to clarithromycin was studied on isolates of H. pylori isolated from 104 patients before starting therapy with the drug. Clarithromycin-resistant H.pylori strains were isolated in 4 patients, 2 patients had moderate resistance strains, and the remaining 98 patients had clarithromycin-sensitive H.pylori isolates.

Clarithromycin has in vitro action against most strains of the following microorganisms (but the safety and effectiveness of clarithromycin in clinical practice has not been confirmed by clinical studies, and the practical value remains unclear):

• aerobic gram-positive microorganisms: Streptococcus agalactiae, Streptococci

(groups C, F, G)., Viridans group streptococci;

• aerobic gram-negative microorganisms: Bordetella pertussis, Pasteurella
• anaerobic gram-positive microorganisms: Clostridium perfringens, Peptococcus niger, Propionibacterium acnes;
• anaerobic gram-negative microorganisms: Bacteroides melaninogenicus;
• Spirochetes: Borrelia burgdorferi, Treponema pallidum;
• Campylobacter: Campylobacter

The main metabolite of clarithromycin in humans is the microbiologically active metabolite 14-hydroxyclarithromycin (14-OH-clarithromycin). The microbiological activity of the metabolite is the same as that of the parent substance, or 1-2 times weaker against most microorganisms. The exception is H. influenzae, against which the effectiveness of the metabolite is twice as high. The parent substance and its main metabolite have either additive or synergistic effect against H.influenzae under conditions in vitro and in vivo depending on the bacterial strain.

Sensitivity test

Quantitative methods, which require measuring the diameter of the growth suppression zone, provide the most accurate estimates of the sensitivity of bacteria to antimicrobial agents. One recommended technique for sensitivity testing uses discs impregnated with 15 µg of clarithromycin (Kirby-Bauer disc-diffusion method); the diameters of the growth-suppression zones correlate with the IPC values of clarithromycin when interpreting the test. IPC values are determined by dilution in broth or agar.

When using these techniques, a report from the laboratory that the strain is “sensitive” indicates that the infectious agent is likely to respond to treatment. A “resistant” response indicates that the pathogen will probably not respond to treatment. A response of “intermediate sensitivity” suggests that the therapeutic effect of the drug may be ambiguous, or the microorganism may be sensitive using higher doses of the drug (intermediate sensitivity is also called “moderate sensitivity”).

Pharmacokinetics

absorption

The drug is easily and quickly absorbed in the gastrointestinal tract. Absolute bioavailability is about 50%. No cumulation was found when multiple doses of the drug were administered, and the metabolic pattern in the human body was not altered. Eating immediately before taking the drug increased the bioavailability of the drug by 25% on average. Overall, this increase is insignificant and should have little clinical significance with the recommended dosing regimens. Therefore, clarithromycin can be used regardless of food intake.

Distribution, metabolism and excretion In vitro

The in vitro studies showed that clarithromycin binds to plasma proteins by 70% at concentrations ranging from 0.45 to 4.5 µg/mL. At a concentration of 45.0 µg/ml, the binding decreases to 41%, probably as a result of saturation of the binding sites. This is observed only at concentrations many times greater than the therapeutic concentration.

In vivo

in vivo animal studies have shown that clarithromycin is present in all tissues except the central nervous system at concentrations several times greater than plasma. The highest concentrations (10-20 times higher than plasma concentrations) were found in the liver and lungs.

Health

. When clarithromycin was administered at a dose of 250 mg 2 times daily, the maximum equilibrium concentration (Cmax) of clarithromycin and 14-OH-clarithromycin in plasma was reached after 2-3 days and was 1 µg/mL and 0.6 µg/mL, respectively. The half-life (T1/2) of clarithromycin and its main metabolite was 3-4 hours and 5-6 hours, respectively.

When clarithromycin was administered at a dose of 500 mg twice daily, the Cmax of clarithromycin and 14-OH-clarithromycin in plasma was reached after the 5th dose. After the 5th and 7th dose, the Cmax of clarithromycin and 14-OH-clarithromycin in plasma averaged 2.7-2.9 mcg/mL and 0.88-0.83 mcg/mL, respectively. The T1/2 of clarithromycin and its main metabolite was 4.5-4.8 hours and 6.9-8.7 hours, respectively.

The cmax of 14-OH clarithromycin did not increase in proportion to the clarithromycin dose, whereas the T1/2 of both clarithromycin and its hydroxylated metabolite tended to increase with increasing dose.

This nonlinear pharmacokinetics of clarithromycin combined with decreased formation of 14-hydroxylated and N-demethylated products at high doses indicates a nonlinear metabolism of clarithromycin that becomes more pronounced at higher doses.

The kidneys excreted about 37.9% after oral clarithromycin doses of 250 mg and 46.0% after clarithromycin doses of 1200 mg; the intestines excreted about 40.2% and 29.1% (including subjects with only one stool sample containing 14.1%), respectively.

Patients

Clarithromycin and its metabolite 14-OH-clarithromycin penetrate rapidly into tissues and body fluids. There is limited evidence that the concentration of clarithromycin in cerebrospinal fluid during oral administration is negligible (i.e., only 1-2% of the serum concentration with normal blood-brain barrier permeability). Concentrations in tissues are usually several times higher than in blood serum.

The table gives examples of tissue and serum concentrations:

LiverLiver function disorders

In patients with moderate to severe hepatic impairment but with preserved renal function, clarithromycin dose adjustment is not necessary. Equilibrium plasma concentration and systemic clearance of clarithromycin do not differ between patients in this group and healthy patients. Equilibrium concentration of 14-OH clarithromycin is lower in people with hepatic impairment than in healthy subjects. Kidney dysfunction

In impaired renal function, the Cmax and minimum concentration (Cmin) of clarithromycin in plasma, the elimination half-life and the area under the pharmacokinetic concentration-time curve (AUC) of clarithromycin and its metabolite 14-OH-clarithromycin increase. The elimination constant and renal excretion decreases. The degree of change in these parameters depends on the degree of renal impairment.

Elderly patients

Elderly patients had higher blood concentrations of clarithromycin and its metabolite 14-OH-clarithromycin and slower excretion than the younger group. However, after adjustment for renal creatinine clearance, there were no differences in the two groups. Thus, the main influence on the pharmacokinetic parameters of clarithromycin is renal function, not age.

Patients with mycobacterial infections

. Equilibrium concentrations of clarithromycin and 14-OH clarithromycin in patients with HIV infection who received clarithromycin at conventional doses (500 mg twice daily) were similar to those in healthy subjects. However, when clarithromycin is used in higher doses that may be necessary to treat mycobacterial infections, concentrations of the antibiotic may be significantly higher than usual. In HIV-infected patients taking clarithromycin at a dose of 1000 mg/day or 2000 mg/day in two doses, equilibrium Cmax values were typically 2-4 mcg/ml and 5-10 mcg/ml, respectively. When using the drug in higher doses, a prolongation of the T1/2 was observed compared to that in healthy subjects receiving clarithromycin in usual doses. The increased plasma concentrations and prolongation of the elimination half-life when using clarithromycin at higher doses are due to the non-linear pharmacokinetics of the drug.

Combined treatment with omeprazole

Clarithromycin 500 mg 3 times daily in combination with omeprazole at a dose of 40 mg/day helps to increase the T1/2 and AUC0-24 of omeprazole. There was an 89% increase in AUC0-24 and 34% increase in T1/2 of omeprazole in all patients receiving combination therapy compared to those receiving omeprazole alone. Clarithromycin had Cmax, Cmin, and AUC0-8 increases of 10%, 27%, and 15%, respectively, compared with data when clarithromycin alone was used without omeprazole. At equilibrium, clarithromycin concentrations in gastric mucosa were 25 times higher 6 h after administration in the group receiving the combination compared with those receiving clarithromycin alone. Clarithromycin concentrations in gastric tissue 6 hours after the 2-drug regimen were twice as high as in the clarithromycin alone group.

Indications

Infectious inflammatory diseases caused by clarithromycin-sensitive microorganisms in adults and children over 12 years of age:

Active ingredient

Composition

1 film-coated tablet contains:

the active substance: clarithromycin in terms of 100% anhydrous 250 mg or 500 mg;

excipients: potato starch 46.0 mg or 92.0 mg, microcrystalline cellulose 75.0 mg or 150.0 mg, povidone (polyvinylpyrrolidone low molecular weight medical) 40,0 mg or 80.0 mg, pregelatinized starch (starch-1500) 30.0 mg or 60.0 mg, colloidal silica (aerosil) 4.5 mg or 9.0 mg, magnesium stearate 4.5 mg or 9.0 mg;

coating: Opadray II (polyvinyl alcohol, partially hydrolyzed 8.0 mg or 16.0 mg, macrogol (polyethylene glycol) 3350 4.040 mg or 8.080 mg, talc 2.960 mg or 5.920 mg, E171 titanium dioxide 4.374 mg or 8.748 mg, E104 quinoline yellow aluminum varnish 0,602 mg or 1,204 mg, iron oxide (II) dye E172 0.006 mg or 0.012 mg, sunset yellow aluminum varnish E110 0.014 mg or 0.028 mg, indigo carmine aluminum varnish E132 0.004 mg or 0.008 mg).

How to take, the dosage

For oral administration regardless of meals.

Adults and children over 12 years of age – 1 tablet (250 mg) 2 times a day.

In case of more severe infections, the dose is increased to 500 mg twice a day. Usual duration of treatment is from 5 to 14 days.

The exceptions are community-acquired pneumonia and sinusitis, which require 6 to 14 days of treatment.

Dosages for treatment of mycobacterial infections other than tuberculosis

The recommended dose for mycobacterial infections is clarithromycin 500 mg twice daily.

The treatment of disseminated MAC infections in patients with AIDS should be continued as long as there is clinical and microbiological efficacy. Clarithromycin should be administered in combination with other antimicrobials active against these pathogens. The duration of treatment of other non-tuberculous mycobacterial infections is determined by the physician.

For the prevention of infections caused by MAC

The recommended dose of clarithromycin for adults is 500 mg twice daily.

For odontogenic infections

The dose of clarithromycin is 250 mg (1 tablet) 2 times daily for 5 days.

For eradication of Helicobacter pylori

In patients with peptic ulcer disease caused by Helicobacter pylori infection, clarithromycin may be prescribed 500 mg twice daily in combination with other antimicrobials and proton pump inhibitors for 7-14 days, according to national and international guidelines for the treatment of Helicobacter pylori infection.

Patients with renal impairment

Patients with creatinine clearance less than 30 ml/min are prescribed half the usual dose of clarithromycin, i.e.i.e. 250 mg (1 tablet) once daily or, for more severe infections, 1 tablet (250 mg) 2 times daily. Treatment of such patients is continued for no more than 14 days.

Application in children younger than 12 years

The use of clarithromycin tablets in children younger than 12 years has not been studied.

Interaction

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

Cyzapride pimozide terfenadine astemizole

The use of the following drugs with clarithromycin is contraindicated due to the potential for serious side effects. When clarithromycin is coadministered with cisapride/pimozide/terfenadine/astemizole, the plasma concentrations of the latter may be increased and may lead to prolonged QT interval and cardiac arrhythmias including ventricular fibrillation ventricular pirouette tachycardia (see Contraindications). See Contraindications).

Extreme ergot alkaloids

Combined use of clarithromycin with ergotamine or dihydroergotamine can cause acute poisoning with ergotamine-group products: vascular spasm, ischemia of the extremities and other tissues including the central nervous system. Concomitant use of clarithromycin and ergot alkaloids is contraindicated (see “Contraindications”)

The effect of other drugs on clarithromycin

The following drugs have a proven or suspected effect on clarithromycin concentrations. If they are used together with clarithromycin, doses may need to be adjusted and alternative treatment may be necessary.

Drugs that are CYP3A isoenzyme inducers (e.g., rifampicin phenytoin carbamazepine phenobarbital St. John’s wort) may induce the metabolism of clarithromycin. This can lead to subtherapeutic concentrations of clarithromycin, resulting in reduced efficacy. In addition, plasma concentrations of CYP3A-inducers should be monitored which may increase due to inhibition of the CYP3A isoenzyme by clarithromycin.

Efavirenz nevirapine rifampicin rifabutin rifapentin

Strong cytochrome P430 inducers such as efavirenz nevirapine rifampicin rifabutin and rifapentine can metabolize clarithromycin and so decrease the blood concentration of clarithromycin and impair the therapeutic effect and increase the concentration of 14-(R)-hydroxyclarithromycin.

Etravirin

The concentration of clarithromycin is decreased with etravirin but the concentration of the active metabolite 14-(R)-hydroxyclarithromycin is increased.

Fluconazole

The co-administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g/day increases the minimum mean equilibrium concentration of clarithromycin (Cmin) and the area under the concentration-time curve of clarithromycin by 33% and 18% respectively. No clarithromycin dose adjustment is required for concomitant administration of fluconazole.

Ritonavir

The co-administration of ritonavir at a dose of 600 mg/day and clarithromycin 1 g/day results in decreased metabolism of clarithromycin. When ritonavir was coadministered, the maximum equilibrium concentration (Cmax) of clarithromycin increased by 31% Cmin increased by 182% and the area under the concentration-time curve increased by 77%. There was complete suppression of 14-(R)-hydroxyclarithromycin formation. In patients with chronic renal insufficiency a dose adjustment is necessary: in creatinine clearance 30-60 ml/min the dose of clarithromycin should be reduced by 50% in creatinine clearance less than 30 ml/min by 75%. Doses of clarithromycin greater than 1 g/day should not be used with ritonavir.

Oral hypoglycemic drugs/insulin

The co-administration of clarithromycin and oral hypoglycemic drugs and/or insulin may cause significant hypoglycemia. Close monitoring of glucose levels is recommended.

Effects of clarithromycin on other medicinal products

Antirhythmic drugs

Ventricular pirouette tachycardia may occur when using clarithromycin and antiarrhythmic drugs (quinidine procainamide) together. If clarithromycin is coadministered with these drugs, electrocardiograms should be monitored regularly for QT interval prolongation and serum concentrations of these drugs should be monitored.

CYP3A isoenzyme interactions

The co-administration of clarithromycin and drugs primarily metabolized by CYP3A isoenzymes may increase or prolong both therapeutic and adverse effects. Clarithromycin should be used with caution in patients receiving drugs that are substrates of CYP3A isoenzyme, especially if these drugs have a narrow therapeutic range (e.g. carbamazepine) and/or are extensively metabolized by this enzyme, if necessary the dose of the drug taken with clarithromycin should be adjusted. Serum concentrations of drugs primarily metabolized by the CYP3A isoenzyme should also be monitored if possible.

3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) inhibitors (statins)

Clarithromycin increases concentrations of HMG-CoA reductase inhibitors (e.g. lovastatin simvastatin). Co-administration of clarithromycin with lovastatin or simvastatin is contraindicated (see section “Contraindications”) due to the fact that these statins are largely metabolized by the CYP3A4 isoenzyme and co-administration with clarithromycin increases their serum concentrations resulting in increased risk of myopathy. If clarithromycin is required, lovastatin or simvastatin should be discontinued during therapy.

Indirect anticoagulants

The co-administration of warfarin and clarithromycin may cause bleeding with increased INR and prothrombin time. If combined with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored.

Omeprazole

Concomitant administration of clarithromycin and omeprazole increases plasma levels of clarithromycin and its metabolite. Concentrations of clarithromycin in tissues and gastric mucosa are also increased with concomitant administration.

Sildenafil tadalafil vardenafil

The co-administration of clarithromycin with sildenafil tadalafil or vardenafil (phosphodiesterase 5 inhibitors) may lead to increased inhibitory effects on phosphodiesterase. It may be necessary to reduce the dose of sildenafil tadalafil and vardenafil.

Theophylline carbamazepine

The combined use of clarithromycin and theophylline or carbamazepine may increase concentrations of these drugs in the systemic blood stream.

Tolterodine

In co-administration of clarithromycin with tolterodine in patients with low CYP2D6 isoenzyme activity it may be necessary to decrease the dose of tolterodine in the presence of clarithromycin (CYP3A isoenzyme inhibitor).

Benzodiazepines (e.g., alprazolam midazolam triazolam)

The co-administration of clarithromycin (1 g/day) with midazolam (oral) showed a 7-fold increase in the area under the concentration-time curve of midazolam. Oral co-administration of clarithromycin and midazolam should be avoided. Dose adjustment may be required when using midazolam (intravenous) and clarithromycin.

The same precautions should be applied to other benzodiazepines that are metabolized by CYP3A isoenzymes including triazolam alprazolam. For benzodiazepines whose excretion is not dependent on CYP3A isoenzyme (temazepam nitrazepam lorazepam) a clinically significant interaction with clarithromycin is unlikely.

When clarithromycin and triazolam are used together, central nervous system (CNS) effects such as drowsiness and confusion are possible. Therefore, it is recommended to monitor for CNS disturbances when used together.

Interaction with other drugs

Colchicine

The effects of colchicine may be increased if clarithromycin and colchicine are taken together. The possible development of clinical symptoms of colchicine poisoning must be monitored especially in elderly patients and patients with chronic renal failure (some cases have been reported to be fatal).

In patients with normal renal and hepatic function, the dose of colchicine should be reduced when used concomitantly with clarithromycin.

The concomitant use of clarithromycin and colchicine is contraindicated in patients with impaired hepatic and renal function (see Contraindications).

Digoxin

The co-administration of digoxin and clarithromycin may lead to increased serum concentrations of digoxin in patients. If clarithromycin and digoxin are coadministered, serum digoxin concentrations should be closely monitored (digoxin concentrations may increase and potentially cause detailed arrhythmias).

Zidovudine

The concomitant administration of clarithromycin and zidovudine in HIV-infected adults may decrease the equilibrium concentration of zidovudine. Because clarithromycin affects the absorption of zidovudine when taken orally, the interaction can be largely avoided by taking clarithromycin and zidovudine at 4-hour intervals.

Phenytoin and valproic acid

When phenytoin or valproic acid are used with clarithromycin it is recommended that their serum concentrations be determined as there are reports of elevated concentrations.

Bidirectional drug interactions

Atazanavir

Co-administration of clarithromycin (1 g/day) and atazanavir (400 mg/day) may result in a twofold increase in exposure to clarithromycin and a 70% decrease in exposure to 14-(R)-hydroxyclarithromycin with a 28% increase in the area under the concentration-time curve of atazanavir.

In patients with normal renal function, clarithromycin dose reduction is not required.

In patients with moderate renal impairment (creatinine clearance 30-60 ml/min), the dose of clarithromycin should be reduced by 50%.

In patients with creatinine clearance less than 30 mL/min, the dose of clarithromycin should be reduced by 75%. Clarithromycin in doses greater than 1 g/day should not be used with protease inhibitors.

Slow calcium channel blockers

Care should be taken with clarithromycin concomitantly with slow calcium channel blockers that are metabolized by CYP3A (e.g., verapamil amlodipine diltiazem) as there is a risk of arterial hypotension. Plasma concentrations of clarithromycin as well as slow calcium channel blockers may increase with concomitant use. Arterial hypotension, bradyarrhythmia and lactoacidosis are possible with concomitant use of clarithromycin and verapamil.

Itraconazole

The co-administration of clarithromycin and itraconazole may lead to increased plasma concentrations. Patients taking itraconazole and clarithromycin concomitantly should be closely monitored for symptoms of increased or prolonged duration of pharmacological effects of these drugs.

Saquinavir

Combined use of clarithromycin (1 g/day) and saquinavir (in soft gelatin capsules 1200 mg 3 times daily) may increase area under “concentration-time” curve and Cmax of saquinavir by 177% and 187%, respectively, and clarithromycin by 40%. No dose adjustments are required when the two drugs are used together for a limited time at the doses indicated above.

Special Instructions

Prolonged use of antibiotics can lead to the formation of colonies with increased numbers of insensitive bacteria and fungi. In case of superinfection, appropriate therapy should be prescribed.

Prescribing clarithromycin to pregnant women should be done with careful risk-benefit assessment, especially during the first three months of pregnancy.

Hepatic dysfunction (increased hepatic enzyme activity in blood, hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with clarithromycin. Liver dysfunction can be severe, but is usually reversible.

There have been cases of fatal hepatic failure, mostly related to the presence of serious comorbidities and/or concomitant use of other medications. In case of signs and symptoms of hepatitis, such as anorexia, jaundice, darkened urine, itching, abdominal pain on palpation, clarithromycin therapy should be stopped immediately.

In the presence of chronic liver disease, serum enzymes should be monitored regularly.

When treated with virtually all antibacterials, including clarithromycin, there have been cases of pseudomembranous colitis, the severity of which may vary from mild to life-threatening. Cases of Clostridium difficile-associated diarrhea, the severity of which may range from mild to life-threatening colitis, have been described with virtually all antibiotic treatments, including clarithromycin. Antibiotic drugs can alter normal gut microflora, which can lead to the growth of Clostridium difficile.

Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who develop diarrhea after using antibiotics. After a course of antibiotic therapy, careful medical follow-up of the patient is necessary. Cases of pseudomembranous colitis have been described 2 months after antibiotic treatment.

When treated with macrolides, including clarithromycin, prolongation of cardiac repolarization and the QT interval have been observed, causing a risk of cardiac arrhythmias and ventricular pirouette tachycardia (see section “Adverse effects”). Because the following situations may increase the risk of ventricular arrhythmias (including pirouette ventricular tachycardia), clarithromycin should not be used in the following patient categories:

Contraindications).

Clarithromycin should be used with caution in the following patient categories:

Contraindications

Side effects

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

Allergic reactions: Frequent – rash; infrequent – anaphylactoid reaction1, hypersensitivity, bullous dermatitis1, itching, urticaria, maculopapular rash3; frequency unknown – anaphylactic reaction, angioneurotic edema, serious skin adverse reactions (e.g., acute generalized exanthematous pustulosis), Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).

Nervous system disorders: frequent – headache, insomnia; infrequent – loss of consciousness1, dyskinesia1, dizziness, somnolence, tremor, anxiety, increased excitability3; frequency unknown- seizures, psychotic disorders, confusion, depersonalization, depression, disorientation, hallucinations, dream disorders (“nightmare” dreams), paresthesia, mania.

Side skin coat: often – intense sweating; frequency unknown – acne. Since the urinary system: frequency unknown – renal failure, interstitial nephritis.

Metabolism and nutrition: infrequent – anorexia, decreased appetite.

Musculoskeletal system disorders: Infrequent – muscle spasm3, musculoskeletal stiffness1, myalgia2; frequency unknown – rhabdomyolysis3, myopathy.

From the digestive system: Frequent – diarrhea, vomiting, dyspepsia, nausea, abdominal pain; infrequent – esophagitis1, gastroesophageal reflux disease2gastritis, proctalgia2, stomatitis, glossitis, bloating4, constipation, dry mouth, belching, flatulence, cholestasis4, hepatitis including.including cholestatic or hepatocellular4; frequency unknown – acute pancreatitis, discoloration of tongue and teeth, liver failure, cholestatic jaundice.

Respiratory system: Infrequent – asthma1, nasal bleeding2, pulmonary embolism1.

Sensory organs: frequent – dysgeusia; infrequent – vertigo, hearing impairment, tinnitus; frequency unknown – deafness, agueusia (loss of taste), parosmia, anosmia.

Cardiovascular system: Frequent – vasodilation1; infrequent – cardiac arrest1, atrial fibrillation1, QT interval prolongation on electrocardiogram, extrasystole1, palpitations; frequency unknown – ventricular tachycardia, including pirouette type, ventricular fibrillation, bleeding.

Laboratory findings: Frequent – abnormality in hepatic sample; infrequent – increased creatinine1 concentration, increased urea1 concentration, change in albumin-globulin ratio1, leukopenia, neutropenia4, eosinophilia4, thrombocythemia3, increased activity: alanine aminotransferase (ALT), aspartate aminotransferase (ACT), gammaglutamyltransferase (GGTP)4, alkaline phosphatase4, lactate dehydrogenase (LDH)4; frequency unknown – agranulocytosis, thrombocytopenia, increased international normalized ratio (INR) value, prolongation of prothrombin time, change in urine color, increased blood bilirubin concentration.

General disorders: very common – phlebitis at the injection site1; common – pain at the injection site1, inflammation at the injection site1; infrequent – malaise4, hyperthermia3, asthenia, chest pain4, chills4, fatigue4.

Infectious and parasitic diseases: infrequent – cellulitis1, candidiasis, gastroenteritis2, secondary infections3 (including vaginal); frequency unknown – pseudomembranous colitis, rye.

The incidence, type, and severity of adverse reactions in children are presumed to be the same as in adults.

Patients with suppressed immunity: In patients with AIDS and other immunodeficiencies who receive clarithromycin at higher doses for longer periods to treat mycobacterial infections, it is often difficult to distinguish adverse effects of the drug from symptoms of HIV infection or a concomitant disease.

The most common adverse events in patients taking a daily dose of clarithromycin equal to 1000 mg were: nausea, vomiting, perversion of taste, abdominal pain, diarrhea, rash, flatulence, headache, constipation, hearing disorders, and increased ACT and ALT activity in blood. Adverse events with low frequency of occurrence, such as dyspnea, insomnia, and dry mouth, have also been reported.

In patients with suppressed immunity, laboratory values were evaluated by analyzing their significant deviations from the norm (sharp increase or decrease). Based on this criterion, 2-3% of patients who received clarithromycin at a dose of 1000 mg daily registered a significant increase in ACT and ALT activity in the blood, as well as a decrease in leukocyte and platelet counts. A small number of patients also registered an increase in residual urea nitrogen concentration.

* In some reports of rhabdomyolysis, clarithromycin has been taken in conjunction with other drugs known to be associated with the development of rhabdomyolysis (statins, fibrates, colchicine or allopurinol).

1 – The reports of these adverse reactions have only been reported with clarithromycin, in the dosage form (DF) lyophilisate for preparation of infusion solution.

2 – The reports of these adverse reactions have only been reported with clarithromycin, in LF sustained-release film-coated tablets.

3 – The reports of these adverse reactions have only been reported with clarithromycin, in LF oral suspension pellets.

4 – Reports of these adverse reactions have only been reported with clarithromycin, in LF film-coated tablets.

Overdose

Pregnancy use

Similarities