Klatsid CP
Active material: Clarithromycin
When ATH: J01FA09
CCF: Macrolide antibiotics
ICD-10 codes (testimony): A46, J01, J02, J03, J04, J15, J20, J31, J32, J35.0, J37, J42, L02, L03, L08.0, L73.9
At KFU: 06.07.01
Manufacturer: ABBOTT LABORATORIES Ltd. (Great Britain)
Pharmaceutical form, composition and packaging
Sustained-release tablets, coated yellow color, Oval; in cross section showed two layers: the kernel is almost white, surrounded by a yellow film.
| 1 tab. | |
| clarithromycin | 500 mg |
Excipients: citric acid anhydrous hydrogen phosphate, sodium alginate, sodium calcium alginate, lactose, povidone K30, talc, stearic acid, magnesium stearate.
The composition of the shell: gipromelloza, polyethylene glycol 400, polyethylene glycol 8000, Titanium dioxide, quinoline yellow dye (E104), sorbic acid.
5 PC. – blisters (1) – packs cardboard.
5 PC. – blisters (2) – packs cardboard.
7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
Pharmacological action
Macrolide antibiotics. Clarithromycin inhibits protein synthesis in microbial cells, interacting with the 50S ribosomal subunit of bacteria.
Clarithromycin demonstrated high in vitro activity against standard and isolated bacterial cultures. Highly effective against many aerobic and anaerobic gram-positive and gram-negative microorganisms. Research, carried out in vitro, confirm high efficiency clarithromycin against Legionella pneumophila and Mycoplasma pneumoniae.
The drug is also active against aerobic grampolaugitionah microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes; Aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parainftuenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella pneumophilis; other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis, mycobacteria Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium avium complex (MAC): Mycobacterium avium, Mycobacterium intracellulare.
To clarithromycin insensitive Enterobacteriaceae, Pseudomonas spp., as well as other, non-lactose-degrading gram-negative bacteria.
β-lactamase production does not affect the activity of clarithromycin. Most strains of staphylococci, resistant to methicillin and oxacillin, is also resistant to clarithromycin.
Clarithromycin is effective in vitro and against most strains of the following microorganisms (however, the safety and effectiveness of clarithromycin in clinical practice has not been confirmed by clinical studies, and the practical significance remains unclear): Aerobic gram-positive microorganisms: Streptococcus agalactiae, streptokokki (Group C,F,G), Viridans group streptococci; Aerobic gram-negative microorganisms: Bordeteila pertussis, Pasteurella multocida; anaerobic gram-positive microorganisms: Сlostridium perfringens, Peptococcus niger, Propionibacterium acnes; anaerobic gram-negative microorganisms: Bacteroides melaninogenicus; Borrelia burgdorferi, Treponema pale, Campylobacter jejuni.
The main metabolite of clarithromycin in the human body is the microbiologically active metabolite 14-hydroxyclarithromycin. The microbiological activity of the metabolite is the same, like the original substance, or in 1-2 times weaker against most microorganisms. The exception is Naemophilus influenzae, in relation to which the effectiveness of the metabolite in 2 times higher. The parent substance and its main metabolite have either additive, or a synergistic effect against Haemophilus influenzae in vitro and in vivo, depending on the bacterial culture.
Extended-release tablets are a homogeneous crystalline base, when passing through the gastrointestinal tract, a long-term release of the active substance is ensured.
Pharmacokinetics
Absorption and distribution
After taking the drug orally, the absolute bioavailability is 50%. No accumulation was detected with repeated doses of the drug..
When taking Klacida SR at a dose 500 mg equilibrium maximum concentrations of clarithromycin and 14-hydroxyclarithromycin are 1.3 ug / ml 0.48 ug / ml, respectively.
When taking Klacida SR at a dose 1 г Cssmax clarithromycin and 14-hydroxyclarithromycin is 2.4 ug / ml 0.67 ug / ml, respectively.
When taking the drug in doses 500 mg 1 g/day time to reach Cmax in the blood plasma is about 6 no.
Clarithromycin binds to plasma proteins at 70% in concentration from 0.45 to 4.5 ug / ml. At concentration 45 µg/ml the degree of binding decreases to 41%, probably as a result of saturation of binding sites. This is observed only at concentrations, many times higher than therapeutic.
Clarithromycin and 14-hydroxyclarithromycin are widely distributed in tissues and body fluids. After oral administration, the content of clarithromycin in tissues is usually several times higher than its content in the blood serum.. After oral administration, the concentration of clarithromycin in the cerebrospinal fluid remains low. (in patients with an intact BBB is 1-2% concentration in blood plasma).
Metabolism and excretion
Clarithromycin is metabolized by the cytochrome P system450 with the participation of the CYP3A isoenzyme. The main metabolite of clarithromycin is the microbiologically active metabolite 14-hydroxyclarithromycin. With repeated doses of the drug, the nature of metabolism in the human body did not change.
At steady state, the concentration of 14-hydroxyclarithromycin does not increase, a T1/2 clarithromycin and its metabolite increases with increasing dose of the drug, which indicates the nonlinearity of metabolism when taken in high doses.
About 40% the dose is excreted in the urine, about 30% – through the intestine.
When taking Klacida SR at a dose 500 mg T1/2 clarithromycin and 14-hydroxyclarithromycin are respectively 5.3 and h 7.7 no.
When taking Klacida SR at a dose 1 г t1/2 clarithromycin and 14-hydroxyclarithromycin are respectively 5.8 and h 8.9 no.
Pharmacokinetics in special clinical situations
In patients with moderate to severe liver dysfunction, but with preserved renal function Css and systemic clearance of clarithromycin do not differ from these indicators in healthy patients. Css 14-hydroxyclarithromycin in people with impaired liver function below, than in healthy volunteers.
In patients with impaired renal function, Cmax increasesmax and Cmin plasma, T1/2, AUC of clarithromycin and 14-hydroxyclarithromycin. Elimination constant and urinary excretion decrease. The degree of change in these parameters depends on the degree of renal dysfunction.
Elderly patients had higher blood levels of clarithromycin and 14-hydroxyclarithromycin, and elimination is slower, than younger people. Think, that changes in pharmacokinetics in elderly patients are associated, Firstly, with changes in CK and functional state of the kidneys, and not with the age of the patients.
Testimony
- Infections of the lower respiratory tract (such, like bronchitis, pneumonia);
- Infections of the upper respiratory tract (such, like pharyngitis, sinusitis);
- Infections of the skin and soft tissues (such, like folliculitis, mug).
Dosage regimen
Adults Klacid SR is prescribed according to 500 mg (1 tab.) 1 time / day. At severe infections increase the dose to 1 g (2 tab.) 1 time / day.
The tablets should be taken with food, swallowing whole, without breaking or chewing.
Side effect
Cardio-vascular system: rarely – ventricular arrhythmia, including ventricular tachycardia (with increasing QT interval).
From the digestive system: nausea, stomach ache, vomiting, diarrhea, gastralgia, pancreatitis, glossitis, stomatitis, oral candidiasis, discoloration of the tongue and teeth; rarely — pseudomembranous enterocolitis. Tooth discoloration is reversible and can usually be restored with professional cleaning by a dentist.. Liver dysfunction has been reported rarely, incl. increased liver enzyme activity, hepatic cell and/or cholestatic hepatitis with or without jaundice. These liver dysfunctions can be severe, but they are usually reversible. Very rare cases of liver failure and death have been observed, mainly due to severe concomitant diseases and/or concomitant drug therapy.
CNS: transient headaches, dizziness, anxiety, insomnia, nightmares, tinnitus, depersonalization, hallucinations, convulsions, a sense of fear; rarely – psychosis, confusion; in some cases – hearing loss (hearing was restored when clarithromycin was stopped), change in smell (usually accompanied by distortions of taste sensations).
Allergic reactions: hives, dermahemia, itching, anaphylaxis, Stevens-Johnson syndrome.
From the hematopoietic system: leukopenia, thrombocytopenia.
From the laboratory parameters: increase in blood creatinine; rarely – gipoglikemiâ (while taking hypoglycemic drugs).
Other: development of resistance of microorganisms.
Contraindications
- Expressed by the human kidney (at least QC 30 ml / min); such patients are prescribed immediate-release clarithromycin;
- simultaneous use of astemizole, cisapride, pimozida, Terfenadine;
- Porphyria;
- Pregnancy;
- Lactation (breast-feeding);
- Hypersensitivity to macrolide antibiotics.
Pregnancy and lactation
The safety of clarithromycin during pregnancy and lactation has not been studied..
Known, that clarithromycin is excreted in breast milk.
Therefore, Klacid SR should be used during pregnancy and lactation only in those cases, When there is a safer alternative, and the risk, associated with the disease itself, exceeds the possible harm to the mother and fetus.
Cautions
With care prescribe a drug to patients with impaired hepatic function. If you have chronic liver disease should be carried out regular monitoring of serum enzymes.
The drug should also be prescribed with caution to patients with mild to moderate renal impairment.. In case of severe renal dysfunction (CC less than 30 ml / min) immediate release clarithromycin should be prescribed (tablets 250 mg or 500 mg).
In case of co-administration with warfarin or other indirect anticoagulants, it is necessary to monitor the prothrombin time.
Overdose
Symptoms: nausea, vomiting, stomach ache, diarrhea. In one patient with a history of bipolar disorder, after taking clarithromycin at a dose 8 d changes in mental state appeared, paranoidalynoe behavior, hypokalemia and hypoxemia.
Treatment: the unabsorbed drug should be removed from the gastrointestinal tract and symptomatic therapy should be carried out. Hemodialysis and peritoneal dialysis do not have a significant effect on clarithromycin serum levels, which is also typical for other macrolide drugs.
Drug Interactions
Simultaneous use of clarithromycin with drugs, metabolized with the participation of the cytochrome P isoenzyme CYP3A450, may lead to increased plasma concentrations of such drugs, like alprazolam, astemizol, Carbamazepine, cilostazol, cisapride, cyclosporine, disopyramide, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (eg warfarin), pimozid, quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, terfenadine, triazolam, vynblastyn. A similar mechanism of interaction is observed when using drugs, metabolized by another isoenzyme of the cytochrome P system450, – phenytoin, theophylline and valproate. With the simultaneous use of theophylline and carbamazepine with clarithromycin, moderate, but reliable (p<0.05) increased levels of theophylline and carbamazepine in blood plasma.
When taking clarithromycin concomitantly with HMG-CoA reductase inhibitors (eg, lovastatin and simvastatin) Rare cases of rhabdomyolysis have been described.
Increased concentrations of cisapride were observed with concomitant use of clarithromycin and cisapride.. This may cause a prolongation of the QT interval, aritmiju, ventricular tachycardia, fibrillation and flutter-fibrillation of the ventricles. Similar effects have been observed in patients, taking clarithromycin concomitantly with pimozide.
Macrolide drugs affect the metabolism of terfenadine. Terfenadine blood levels increase, which may be accompanied by an increase in the QT interval, development of arrhythmia, Ventricular tachycardia, fibrillation and ventricular fibrillation. The content of acid metabolites of terfenadine increases in 2-3 times, QT interval increases, however, it does not cause any clinical manifestations. The same picture was observed when taking astemizole simultaneously with drugs from the macrolide group..
There are reports of the development of ventricular flutter-fibrillation with simultaneous use of clarithromycin with quinidine and disopyramide. When prescribing these drugs simultaneously, monitoring their concentrations in the blood is required..
With simultaneous use of clarithromycin with digoxin, an increase in serum digoxin levels was observed. Serum digoxin levels should be monitored in these patients..
With simultaneous oral administration of clarithromycin and zidovudine in HIV-infected patients, a decrease in the steady-state concentration of zidovudine was observed. Because clarithromycin interferes with the absorption of zidovudine, taking these two drugs should be separated in time.
Ritonavir significantly slows down the metabolism of clarithromycin when taken concomitantly. In this case, the value of Cmax == increases by 31%, Cmin – on 182%, AUC – on 77%. There is a significant slowdown in the formation of 14-hydroxyclarithromycin. In this case, in patients without renal impairment, there is no need to adjust the dose of clarithromycin. If CC 60-30 ml/min the dose of clarithromycin should be reduced by 50% up to a maximum dose of 500 mg (1 extended release tablet) 1 time / day. When taking ritonavir, do not simultaneously prescribe a dose of clarithromycin greater than 1 g / day.
Cross-resistance may develop between clarithromycin and other macrolide drugs, and lincomycin and clindamycin.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored in the dark, inaccessible to children at temperature not exceeding 30 ° C. Shelf life – 3 year.
