Klacid, 125 mg/5 ml, powder for the preparation of suspension for oral administration, 42.3 g, 1 pc.

Klacid, 125 mg/5 ml, powder for the preparation of suspension for oral administration, 42.3 g, 1 pc.

The first data on pharmacokinetics were obtained from the study of clarithromycin tablets. The drug is quickly absorbed into the gastrointestinal tract. The absolute bioavailability of clarithromycin 50 mg tablets is approximately 50%. Food slightly delayed the onset of absorption and the formation of the active metabolite of 14-OH-clarithromycin, but did not affect the bioavailability of the drug.

In vitro

In in vitro studies, clarithromycin binding to plasma proteins averaged approximately 70% at clinically relevant concentrations ranging from 0.45 to 4.5 mcg/ml.

Healthy

The bioavailability and pharmacokinetics of clarithromycin suspension were studied in healthy adults and children. When administered once in adults, the bioavailability of the suspension was equivalent to or slightly greater than that of the tablets (both 250 mg dose). As with tablets, food slightly delayed the absorption of clarithromycin suspension but did not affect the overall bioavailability of the drug. Cmax, AUC and T1/2 of clarithromycin when taking the pediatric suspension (after meals) were 0.95 mcg/ml, 6.5 mcg h/ml and 3.7 hours, respectively, and when taking a 250 mg tablet on an empty stomach - 1.1 µg/ml; 6.3 µg·h/ml and 3.3 h.

When clarithromycin suspension was administered at a dose of 250 mg every 12 hours in adults, steady-state blood levels were practically achieved by the fifth dose. In this case, the pharmacokinetic parameters were as follows: Cmax - 1.98 μg/ml, AUC - 11.5 μg h/ml, Tmax - 2.8 hours and T1/2 - 3.2 hours - for clarithromycin and, accordingly, 0. 67; 5.33; 2.9 and 4.9 for 14-OH-clarithromycin. In healthy subjects, serum concentrations peaked within 2 hours after oral administration. Css of the main metabolite - 14-OH-clarithromycin - is about 0.6 μg/ml, and T1/2 when using the drug at a dose of 250 mg every 12 hours is 5-6 hours. When prescribing clarithromycin at a dose of 500 mg every 12 hours, Css 14-OH-clarithromycin is slightly higher (up to 1 μg/ml), and T1/2 is about 7 hours. When using both doses, equilibrium concentrations of the metabolite are usually achieved within 2–3 days. When clarithromycin is prescribed at a dose of 250 mg every 12 hours, approximately 20% of the dose is excreted unchanged by the kidneys. When used at a dose of 500 mg every 12 hours, approximately 30% of the dose is excreted unchanged by the kidneys. The renal clearance of clarithromycin is not significantly dose-dependent and approaches the normal glomerular filtration rate. The main metabolite found in urine is 14-OH-clarithromycin, which accounts for 10–15% of the dose (250 or 500 mg every 12 hours).

Sick

Clarithromycin and its 14-OH metabolite are well distributed into tissues and body fluids. Tissue concentrations are usually several times higher than serum concentrations. Table 1 provides examples of tissue and serum concentrations.

Table 1

Concentrations when administered at a dose of 250 mg every 12 hours

In children requiring oral antibiotic treatment, clarithromycin has high bioavailability. Moreover, its pharmacokinetic profile was similar to those in adults taking the same suspension. The drug is quickly and well absorbed in children. Food slightly delays the absorption of clarithromycin, but does not significantly affect its bioavailability or pharmacokinetic properties.

The steady-state parameters of clarithromycin pharmacokinetics achieved after 5 days (ninth dose) were as follows: Cmax - 4.6 μg/ml, AUC - 15.7 μg·h/ml and Tmax - 2.8 hours; corresponding values ​​for 14-OH metabolite: 1.64 μg/ml; 6.69 mcg h/ml and 2.7 hours. Estimated T1/2 of clarithromycin and its metabolite are 2.2 and 4.3 hours, respectively.

In patients with otitis, 2.5 hours after taking the fifth dose (7.5 mg/kg 2 times a day), the average concentrations of clarithromycin and 14-OH metabolite in the middle ear were 2.53 and 1.27 μg/g. Concentrations of the drug and its metabolite were 2 times higher than their serum levels.

Liver dysfunction

Steady-state concentrations of clarithromycin in patients with impaired liver function did not differ from those in healthy subjects, while levels of 14-OH-clarithromycin were lower. The decrease in the formation of 14-OH-clarithromycin in patients with impaired liver function was, at least partially, offset by an increase in the renal clearance of clarithromycin compared with that in healthy subjects.

Renal dysfunction

The pharmacokinetics of clarithromycin also changed in patients with impaired renal function who received the drug orally at a dose of 500 mg repeatedly. In such patients, plasma levels, T1/2, Cmax, Cmin and AUC of clarithromycin and its 14-OH metabolite were higher than in healthy people. Deviations in these parameters correlated with the degree of renal failure: with more severe renal dysfunction, the differences were more significant (see “Dosage and Administration”).

Aged people

In a comparative study in elderly healthy subjects receiving repeat oral clarithromycin 500 mg, plasma levels of the drug were increased and elimination was slower compared with those in younger healthy subjects. However, there was no difference between the two groups when adjustment was made for creatinine Cl. It was concluded that changes in the pharmacokinetics of clarithromycin reflect renal function and not the age of the patient.

Patients with mycobacterial infections

Css of clarithromycin and 14-OH-clarithromycin in patients with HIV infection who received clarithromycin in usual doses in the form of tablets in adults and suspension in children were similar to those in healthy people. However, when clarithromycin is used in higher doses, which may be required to treat mycobacterial infections, antibiotic concentrations may be significantly higher than usual.

In children with HIV infection receiving clarithromycin at a dose of 15–30 mg/kg/day in 2 divided doses, steady-state Cmax values ​​typically ranged from 8 to 20 mcg/ml. However, in children with HIV infection who received a clarithromycin suspension at a dose of 30 mg/kg/day in 2 divided doses, Cmax reached 23 mcg/ml.

When using the drug in higher doses, a prolongation of T1/2 was observed compared with that in healthy people receiving clarithromycin in usual doses. The increase in plasma concentrations and T1/2 duration when clarithromycin is prescribed at higher doses is consistent with the known nonlinearity of the pharmacokinetics of the drug.

Indications for use

The use of the drug Klacid is indicated for the following diseases and conditions:

• infectious diseases of the lower respiratory tract: pneumonia , bronchitis , etc.;
• infectious diseases of the upper respiratory tract: sore throat , sinusitis , pharyngitis , etc.;
• infectious lesions of soft tissues, skin: folliculitis , erysipelas , etc.;
• mycobacterial infections caused by Mycobacterium intracellulare and Mycobacterium avium;
• infections caused by Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium kansasii.

It is also practiced to take the drug to prevent infection caused by Mycobacterium avium complex (MAC). Prescribed to reduce the frequency of relapses of duodenal ulcers .

Interaction

Interaction with cytochrome P450

Clarithromycin is metabolized in the liver by the cytochrome P450 3A isoenzyme (CYP3A). This mechanism determines many interactions with other drugs. Clarithromycin may inhibit the biotransformation of other drugs by this system, which may result in increased serum levels. The following drugs are known or suspected to be metabolized by the same CYP3A isoenzyme: alprazolam, astemizole, carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergotamine alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (for example, warfarin), pimozide, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam and vinblastine. Similar mechanisms of interaction, which are mediated by other cytochrome P450 isoenzymes, are characteristic of phenytoin, theophylline and valproic acid.

In clinical studies, when theophylline or carbamazepine was combined with clarithromycin, there was a small but statistically significant (p < 0.05) increase in serum theophylline and carbamazepine levels.

In clinical practice, the following CYP3A-mediated interactions have been reported with the use of erythromycin and/or clarithromycin:

- when clarithromycin was combined with HMG-CoA reductase inhibitors, such as lovastatin and simvastatin, rhabdomyolysis developed in rare cases;

- with simultaneous use of clarithromycin with cisapride, an increase in the levels of the latter was observed. This may lead to prolongation of the QT interval and the development of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsade de pointes (TdP). Similar effects have been reported in patients receiving clarithromycin with pimozide (see "Contraindications").

Macrolides caused disruption of the metabolism of terfenadine, which led to an increase in its plasma levels and was sometimes associated with the development of arrhythmias, incl. prolongation of the QT interval, ventricular tachycardia, ventricular fibrillation and ventricular tachycardia of the “pirouette” type (see “Contraindications”). In one study of 14 healthy volunteers, the combined use of clarithromycin tablets and terfenadine resulted in a 2- to 3-fold increase in serum levels of the acid metabolite terfenadine and a prolongation of the QT interval, which was not associated with any clinical effects. In clinical practice, cases of ventricular tachycardia of the “pirouette” type have been reported when clarithromycin is combined with quinidine or disopyramide. Serum levels of these drugs should be monitored during treatment with clarithromycin.

Ergotamine/dihydroergotamine

In clinical practice, when clarithromycin was combined with ergotamine or dihydroergotamine, cases of acute toxicity of the latter, which is characterized by vasospasm and ischemia of the limbs and other tissues, including the central nervous system, were recorded.

Interaction with other drugs

Digoxin.

In patients receiving clarithromycin tablets in combination with digoxin, an increase in serum concentrations of the latter was observed. Monitoring serum digoxin levels is advisable. Cross-resistance may develop between clarithromycin, lincomycin and clindamycin.

Colchicine.

It is a substrate for CYP3A and P-glycoprotein. Clarithromycin and other macrolides are inhibitors of CYP3A and P-glycoprotein. When colchicine and clarithromycin are coadministered, inhibition of P-glycoprotein and/or CYP3A may result in increased effects of colchicine. Patients should be closely monitored for symptoms of colchicine toxicity.

Interaction with antiretroviral drugs

Zidovudine.

Concomitant oral administration of clarithromycin tablets with zidovudine in HIV-infected adults may result in a decrease in the Css of zidovudine. This interaction was not observed in HIV-infected children taking clarithromycin pediatric suspension with zidovudine or dideoxyinosine.

Ritonavir.

In a pharmacokinetic study, the combined use of ritonavir at a dose of 200 mg every 8 hours and clarithromycin at a dose of 500 mg every 12 hours resulted in a significant suppression of the metabolism of clarithromycin. Cmax of clarithromycin when combined with ritonavir increased by 31%, Cmin by 182%, AUC by 77%. Virtually complete inhibition of the formation of 14-OH-clarithromycin was observed. Given the high therapeutic index of clarithromycin, a dose reduction is not required in patients with normal renal function. However, in patients with impaired renal function, dose adjustment is advisable. In patients with Cl creatinine 30-60 ml/min, the dose of clarithromycin is reduced by 50%, and in patients with Cl creatinine <30 ml/min - by 75%. At doses greater than 1 g/day, clarithromycin should not be used in combination with ritonavir.

Klacida's analogs

Level 4 ATC code matches:
Ecositrin

Azicine

Rovamycin

AzitRus

Safocid

Clarithromycin

Sumamed Forte

Klarbakt

Azithromycin

Azitro Sandoz

Sumamed

ZI-Factor

Azitral

Azimed

Azicide

Spiramycin-vero

Zitrolide

Ecomed

Macropen

Klacid SR

Analogues of Klacid are products that belong to the same group and have an active substance similar to Klacid. These are the medications:

• Klacid SR
• Clubax
• Fromilid
• Klarbakt
• Clerimed
• Clarexide
• Bacticap
• Binocular
• Claricite
• Clarithrosin
• Clarithromycin
• Claromine

You can replace the drug only after the doctor’s approval, since each of these drugs has certain features of use and side effects.

The price of analogues can be either higher or lower. The differences between Klacid and Klacid SR are that the latter drug is a long-acting drug, that is, the active substance is released more slowly.

Compound

Klacida price, where to buy

You can buy this antibiotic at any pharmacy; its cost depends on the form and dosage.

The price of Klacid 250 mg tablets averages 650 rubles per pack of 10 tablets. The price of Klacid 500 mg is from 800 rubles per pack of 14 pcs. The price of granules for preparing Klacid suspension is on average 500 rubles.

• Online pharmacies in RussiaRussia
• Online pharmacies in KazakhstanKazakhstan

ZdravCity

• Klacid granules d/prig.
  susp. for oral administration 125 mg/5 ml vial. 70.7 g No. 1EbbVee S.r.L. RUR 597 order
• Klacid tablets p.p.o. 500mg 14 pcs.Coswell Spa

  RUB 824 order

• Klacid tablets p.p.o. 250 mg 10 pcs. Abbott S.r.L./ Ebbwy S.r.L.

  RUB 667 order

Pharmacy Dialogue

• Klacid (tab. 250 mg No. 10) EbbVi

  RUR 662 order

• Klacid gran. d/prig. susp. 125mg/5ml 100ml (70.7g) EbbVie

  610 rub. order

• Klacid tablets 500 mg No. 14EbbVi

  RUB 811 order

• Klacid (gran. d/prig. suspension 125 mg/5 ml 100 ml (70.7 g) syringe) EbbVi

  640 rub. order

• Klacid (portable d/p. suspension 250 mg/5 ml 49.5 g) EbbVi

  RUB 874 order

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Side effects

Klacid® suspension is comparable in safety to 250 mg tablets in adults. The most common adverse events were from the gastrointestinal tract, incl. diarrhea, vomiting, abdominal pain and nausea. Pseudomembranous enterocolitis has been observed extremely rarely. Other adverse reactions included headache, taste disturbances, and transient increases in liver enzymes. As with the use of other macrolide antibiotics, the development of microbial resistance may occur.

Post-marketing experience

During treatment with clarithromycin, as with other macrolides, liver dysfunction, including increased liver enzyme activity, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported infrequently. Hepatic dysfunction can be severe and is usually reversible. In very rare cases, deaths from liver failure have been reported, which were usually observed in the presence of serious concomitant diseases and/or concomitant use of other drugs.

Isolated cases of increased serum creatinine levels have been described, but their connection with the drug has not been established.

Allergic reactions have been reported with oral administration of clarithromycin, ranging from urticaria and minor rashes to anaphylaxis and Stevens-Johnson syndrome/toxic epidermal necrolysis. There have been reports of transient CNS effects including dizziness, anxiety, insomnia, nightmares, tinnitus, confusion, disorientation, hallucinations, psychosis and depersonalization; their cause-and-effect relationship with the drug has not been established. Cases of hearing loss have been reported during treatment with clarithromycin; after cessation of treatment, hearing was usually restored. There are also cases of disturbance of the sense of smell, which are usually combined with a perversion of taste.

Glossitis, stomatitis, oral thrush and discoloration of the tongue have been described during treatment with clarithromycin. There are known cases of tooth discoloration in patients treated with clarithromycin (these changes are usually reversible and can be corrected by a dentist).

Rare cases of hypoglycemia have been described, some of which were observed in patients receiving oral hypoglycemic agents or insulin. Isolated cases of leukopenia and thrombocytopenia have been reported.

When treating with clarithromycin, as with other macrolides, prolongation of the QT interval, ventricular tachycardia and torsade de pointes (TdP) have been observed in rare cases.

Rare cases of pancreatitis and seizures have been described.

There are reports of the development of interstitial nephritis during treatment with clarithromycin. In clinical practice, cases of toxicity of colchicine when combined with clarithromycin have been described, especially in elderly people. Some of them were observed in patients with renal failure; Several deaths have been reported in similar patients (See Interactions) Colchicine

).

Children with suppressed immunity.

In patients with AIDS and other immunodeficiencies receiving clarithromycin in higher doses over a long period of time for the treatment of mycobacterial infections, it is often difficult to differentiate the undesirable effects of the drug from symptoms of HIV infection or intercurrent illnesses.

In a limited number of children with AIDS, clarithromycin pediatric suspension has been used to treat mycobacterial infections. The main adverse events not related to the underlying disease were tinnitus, deafness, vomiting, nausea, abdominal pain, purpura, pancreatitis and increased amylase activity. In this study, significant deviations of laboratory parameters from normative values ​​(sharp increase or decrease) were recorded. Based on these criteria, one child with AIDS receiving clarithromycin at a dose of <15 mg/kg/day had a significant increase in total bilirubin; Among patients taking clarithromycin at a dose of 15-25 mg/kg/day, one case of significant increases in ALT levels, residual urea nitrogen and a decrease in platelet counts was reported. In patients receiving clarithromycin at the maximum dose (>25 mg/kg/day), no significant changes in these laboratory parameters were detected.

Description of the dosage form

Powder for suspension for oral administration 125 mg/5 ml

- white or almost white, granular powder, with a fruity aroma. When shaken with water - a white or almost white opaque suspension with a fruity aroma.

Powder for suspension for oral administration 250 mg/5 ml

- white or almost white granules with a fruity aroma. When water is added, a white or almost white opaque suspension is formed with a fruity aroma.

special instructions

People with liver disease may experience changes in serum enzyme levels, for which tablets should be prescribed with caution.

It is prescribed with caution to people who are simultaneously taking other medications that are metabolized by the liver.

With prolonged treatment with antibiotics, the formation of colonies with a large number of insensitive fungi and bacteria is possible.

In case of chronic liver diseases, serum enzymes should be regularly monitored.

Pseudomembranous colitis may occur during antibiotic treatment. It is also possible to change the normal intestinal microflora.

The medicine should be prescribed with caution to people with severe heart failure, bradycardia, and hypomagnesemia. It is necessary to constantly monitor the ECG, determining the increase in the QT interval.

of myasthenia gravis may increase in people who take clarithromycin.

The powder for preparing the Klacid suspension contains sucrose, which should be taken into account by people suffering from diabetes .

When treating with clarithromycin, you need to carefully drive vehicles and perform activities that require high concentration.

Pharmacodynamics

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

Clarithromycin has demonstrated high activity in vitro

against standard and isolated bacterial cultures. Highly effective against many aerobic and anaerobic, gram-positive and gram-negative microorganisms.

in vitro studies

Clarithromycin has been shown to be highly active against
Legionella pneumophila
,
Mycoplasma pneumoniae
and
Helicobacter (Campilobacter) pylori.
Enterobacteriaceae, Pseudomonas spp.

, as well as other non-lactose-degrading gram-negative bacteria, are not sensitive to clarithromycin.

Clarithromycin has been shown to have an antibacterial effect against the following pathogens: aerobic gram-positive microorganisms - Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes;

aerobic gram-negative microorganisms -
Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila, Neisseria gonorrhoeae;
other microorganisms -
Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis
;
mycobacteria - Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum; Mycobacterium avium complex (MAC)
- a complex including:
Mycobacterium avium, Mycobacterium intracellulare.
Clarithromycin in vitro

is active against most strains of the following microorganisms (however, the safety and effectiveness of the use of clarithromycin in clinical practice has not been confirmed by clinical studies and the practical significance remains unclear):

— aerobic gram-positive microorganisms — Streptococcus agalactiae; Streptococci

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

— aerobic gram-negative microorganisms — 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

;

- Campylobacter - Campylobacter jejuni.

The main metabolite of clarithromycin in the human body 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

, for which the effectiveness of the metabolite is 2 times higher.
The parent substance and its major metabolite, when combined, have either additive or synergistic effects against H. influenzae in vitro
and
in vivo
, depending on the bacterial culture.