Clarithromycin

When ATH:
J01FA09

Characteristic.

Semi-synthetic macrolide antibiotic.

White or almost white crystalline powder, soluble in acetone, It is soluble in methanol, ethanol, acetonitrile and virtually nerastvorim water. Molecular weight 747,96.

Pharmacological action.
Antibacterial, bacteriostatic, bactericide.

Application.

Bacterial infections, caused by susceptible microorganisms: upper respiratory tract infection (laringit, pharyngitis, tonsillitis, sinusitis), lower respiratory tract infection (bronchitis, incl. exacerbation of chronic bronchitis, pneumonia, SARS), skin and soft tissue (folliculitis, furunculosis, impetigo, wound infection), otitis media; gastric ulcer and duodenal ulcer (éradikaciâ Helicobacter pylori in a combination therapy), mikobakterioz (incl. atypical, in conjunction with jetambutolom and rifabutinom), Chlamydia.

Contraindications.

Hypersensitivity (incl. to erythromycin and other macrolides), porphyria, simultaneous reception cisapride, pimozida, astemizola, Terfenadine (cm. "Interaction").

Restrictions apply.

Renal and / or hepatic insufficiency, newborns and babies up to 6 Months (safety have not been established).

Pregnancy and breast-feeding.

When pregnancy is possible only in cases, When the expected effect of therapy outweighs the potential risk to the fetus in the absence of suitable alternative therapy (adequate and well-controlled studies of the safety of use in pregnant women were not conducted). If the pregnancy occurred during treatment, clarithromycin, the patient must be warned about the potential risk to the fetus. At the time of treatment should stop breastfeeding (clarithromycin and its active metabolite infiltrating breast milk, safety of breastfeeding is not installed).

Side effects.

From the nervous system and sensory organs: headache, dizziness, anxiety, fear, insomnia, nightmares, noise in ears, change in taste; REER - disorientation, hallucinations, psychosis, depersonalization, confusion; in a few cases, hearing loss, following the abolition of the HP; There are reports of rare cases of paraesthesia.

From the digestive tract: dysfunction of the gastrointestinal tract (nausea, vomiting, gastralgia/abdominal discomfort, diarrhea), stomatitis, glossitis, transient increase in liver transaminases, cholestatic jaundice; rarely — pseudomembranous enterocolitis; There are reports of rare cases of hepatitis development; in exceptional cases there was liver failure.

Cardio-vascular system and blood (hematopoiesis, hemostasis): seldom-B19 (unusual bleeding, hemorrhage), leukopenia; very rarely is the elongation QT interval, ventricular arrhythmia, incl. ventricular tachicardia, Atrial/ventricular blinking.

With the genitourinary system: There are reports of rare cases, increasing the concentration of creatinine in the serum, development of interstitial nephritis, renal failure.

Allergic reactions: skin rash, itch, malignant exudative erythema (Syndrome Stevens - Johnson), anaphylactoid reactions.

Other: development of resistance of microorganisms; in rare cases, hypoglycemia (treatment with oral gipoglikemicakimi means and insulin).

Cooperation.

Together with the admission cizapridom, pimozidom, astemizolom, terfenadine possible extension QT interval, development of cardiac arrhythmias (ventricular tachicardia, fibrillation, Atrial/ventricular blinking). Simultaneous use of ergotamine and digidroergotamina or clarithromycin caused some patients acute jergotaminovuju intoxication, through peripheral vazospazmom and dizesteziej. Klaritromicin increases concentration in the blood (enhances the effects of) PM, metaboliziruthan in the liver, with the participation of zitohroma P450 enzymes: warfarin and other indirect anticoagulants (There are individual postmarketing reports that, that, in the case of combination with clarithromycin oral antikoagulyantami can potenzirovti effect, in the case of a joint application, you must carefully monitor the MF), karʙamazepina, teofillina, astemizola, cisapride, triazolama, midazolama, cyclosporine, digoksina, phenytoin, alkaloids lpv, etc. (together with the application it is recommended to measure their concentration in the blood). While receiving inhibitors of HMG-CoA reductase inhibitors (lovastatin, simvastatin) possible rhabdomyolysis. Clarithromycin lowers klirens triazolama (enhances its pharmacological effects, with the development of sleepiness and confusion).

While applying inward == and zidovudine to HIV-infected adult patients decreased equilibrium concentration of zidovudine. At reception 500 mg clarithromycin twice a day the AUC of zidovudine in equilibrium decreased on average by 12% (n=4). Individual values ranged from a decline of 34% to improve on the 14%. Limited data, received from 24 patients, who took 2-4 for clarithromycin hour before intake of zidovudine, show, that equilibrium concentration of zidovudine (C_max) was increased approximately 2 times, without changing AUC. The simultaneous use of == and didanosine at 12 HIV-infected patients does not lead to statistically significant changes in the pharmacokinetics of didanosine.

While admission == and ritonavir (n=22) increased AUC == (on 77%) and decreased the AUC 14-IT == (on 100%). In this regard, clarithromycin can be used in normal doses (but not above 1 g / day) in patients with normal renal function, receiving ritonavir. However, in patients with renal insufficiency dose == reduce the Cl creatinine 30-60 ml/min at 50%, less 30 mL/min-on 75%.

The simultaneous use of 200 mg of fluconazole every day and 500 mg clarithromycin 2 times a day 21 healthy volunteer caused increase of equilibrium (C)_min and AUC == to 33 and 18% respectively, When this equilibrium concentration 14-IT == unchanged.

It is possible to develop cross resistance between klaritromitinom and other antibiotics from the macrolides, as well as linkozamidov (Lincomycin and clindamycin).

Daily admission 500 mg clarithromycin every 8 h in combination with omeprazole 40 mg in healthy volunteers increased values farmakokineticeskih parameters of omeprazole in equilibrium: plasma concentration (C_max) - On 30%, AUC_0–24 - On 89%, T_1/2 - On 34%. The value of pH in the stomach during the 24 h was 5,2 When taking one of omeprazole and 5,5 When omeprazole to clarithromycin. When increased plasma levels of clarithromycin and its active metabolita-for ==: C_max - On 10%, C_min - On 27%, AUC_0-8 - On 15%, for 14-IT ==: C_max - On 45%, C_min - On 57%, AUC_0-8 - On 45%; clarithromycin concentration in tissues and mucosa of the stomach while admission also raised.

Joint application of ranitidine bismuth citrate and clarithromycin resulted in increased plasma concentrations of ranitidine (on 57%), bismuth (on 48%) and 14-IT == (on 31%), These effects were not clinically significant.

Overdose.

Symptoms: dysfunction of the gastrointestinal tract (nausea, vomiting, diarrhea, abdominal pain), headache, confusion.

Treatment: gastric lavage, simptomaticheskaya therapy. Hepatology and peritonealny dialysis is not effective.

Dosing and Administration.

Inside, I /. The dosage regimen and duration of treatment are determined individually taking into account the indications, severity of infection, susceptibility. Inside, adults and children over 12 years are 250-500 mg 2 once a day; the course of treatment is 6-14 days. In the treatment of infections, caused Mycobacterium avium, Sinus, severe infections, incl. caused Haemophilus influenzae, -for 500-1000 mg 2 once a day; the maximum daily dose 2 g. Children up 12 years — from the calculation 7,5 mg / kg of body weight every 12 no; the maximum daily dose 500 mg. In patients with renal insufficiency (if Cl creatinine less than 30 mL/min or concentration of whey creatinine more than 3,3 mg / 100ml) dose should be reduced in 2 times. Maximum duration of treatment in patients of this group is no more 14 days.

B / drip, 1000 mg / day 2 introduction.

Precautions.

Be wary appoint amidst preparations, metabolized in the liver (It recommended to measure their concentration in the blood).

Clarithromycin modified release is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min), such patients appoint klaritromicin in quick-release tablets.

It is necessary to take into account the possibility of cross resistance between klaritromitinom and other antibiotics from the macrolides, Lincomycin and clindamycin. With prolonged or repeated use of the drug may develop superinfection (the growth of sensitive bacteria and fungi). In case of severe, prolonged diarrhea, which may indicate development psevdomembranoznogo colitis, you need to stop taking the drug and consult your doctor.

Cooperation