Clarithromycin SR 500mg 14 tablets long

Pharmacological group: Macrolides and azalides 

Pharmacological action: 

Clarithromycin is a semi-synthetic broad-spectrum macrolide antibiotic. Antibacterial action of clarithromycin by inhibition of protein synthesis due to binding to 50s-subunit of bacterial ribosomes. Clarithromycin is active in a wide range of aerobic and anaerobic gram-positive and gram-negative organisms. Minimum overwhelming concentration of clarithromycin (IPC) is less than half that erythromycin for most microorganisms.

14-hydroxy metabolite of clarithromycin also has antimicrobial activity. The minimum inhibitory concentrations of this metabolite are equal to or greater than MPC clarithromycin, with respect to H. influenzae 14-hydroxymetabolite twice as active as clarithromycin.

Claritromicin shows activity in vitro against the following organisms – gram-positive aerobic bacteria: Staphylococcus aureus (sensitive to methicillin), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus viridans and Listeria monocytogenes, aerobic gram-negative bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoea, Legionella pneumophila, Bordetella pertussis, Helicobacter pylori, Campylobacter jejuni, predominantly intracellular organisms: Mycoplasma pneumonia, Ureaplasma urealyticum, Chlamydia trachomatis, Chlamydia pneumonia, Mycobacterium avium, Mycobacterium leprae, M. kansaii, M. chelonae, M. marinum, M. fortitum, anaerobic microorganisms: Bacteroides fragilis, Clostridium perfringens, Propionibacterium acnes, Peptococcus species, Peptostreptococcus species. In addition, the drug is active against Toxoplasma species.

Bactericidal activity clarithromycin has against some bacterial strains: Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, Helicobacter pylori and Campylobacter spp.

Pharmacokinetics: 

Clarithromycin is rapidly and well absorbed from the digestive tract after ingestion. Microbiologically active metabolite 14-hydroxyclarithromycin is formed after the first passage through the liver. Eating does not affect the bioavailability of clarithromycin, however, slightly slows the beginning of absorption of clarithromycin and the formation of 14-hydroxymetabolite. The pharmacokinetics of clarithromycin is non-linear, while the equilibrium concentration is reached 2 days after starting this drug.

Clarithromycin is excreted in the urine, as well as in the feces, mainly through bile. When taking 250 mg of clarithromycin 2 times/day. 15-20% of the administered dose is excreted unchanged in the urine. At the dose of 500 mg 2 times/day. urinary excretion is about 36%. 14-hydroxyclarithromycin-the main metabolite found in urine, it accounts for about 10-15%.

When taking 500 mg of clarithromycin 3 times/day. clarithromycin concentration in plasma is higher than when taking this dose 2 times/day.

The content of clarithromycin in the tissues, including glandular and lung tissue is several times higher than in circulating blood. In therapeutic concentrations of clarithromycin is 80% bound to plasma proteins.

Clarithromycin penetrates into gastric mucus. Levels of clarithromycin in the mucus and tissues of the stomach increases with combination therapy with omeprazole. Clarithromycin passes into breast milk.

Indications: 

Infections, caused by susceptible to clarithromycin microorganisms:

• infections of the lower respiratory tract (including acute and chronic bronchitis, pneumonia), 
• infection of the upper respiratory tract (including sinusitis and pharyngitis), 
• infections of the skin and soft tissues, 
• duodenal ulcer for Helicobacter pylori eradication (as part of complex therapy with proton pump inhibitors).

Dosage regimen:

Inside. 

Adults: the usual dose is 250 mg 2 times / for 7 days, if necessary, the dose can be increased to 500 mg 2 for a period of up to 14 days in severe infections.

Children 12 years and older: the dosage for adults.

For the treatment of duodenal ulcer caused by H. pylori (adult):

Triple therapy regimen (1-14 days): clarithromycin 500 mg 2 times/day., lansoprazole 30 mg 2 times / day., amoxicillin 1000 mg 2 times / day.

Triple therapy regimen (7 days): clarithromycin 500 mg 2 times/day., lansoprazole 30 mg 2 times / day., metronidazole 400 mg 2 times / day.

Diagram of triple therapy (7 days): clarithromycin 500 mg 2 times/day., omeprazole 40 mg / day., amoxicillin 1000 mg 2 times / day. or metronidazole 400 mg 2 times / day.

Triple therapy regimen (10 days): clarithromycin 500 mg 2 times/day. it is prescribed amoxicillin 100 mg 2 times/day. and omeprazole 20 mg / day.

Double therapy regimen (14 days): clarithromycin 500 mg 3ki, omeprazol inside 40 mg 1 time/day.

In case of renal impairment, dose adjustment is usually not required, except for patients with severe kidney lesions (CC < 30 ml/min), but if necessary, the total daily dose should be reduced by half, i.e. 250 mg 1 time/day. or 250 mg 2 times / day. with more severe infections.

While taking ritonavir for patients with impaired renal function recommended dose adjustment according to the following scheme: for patients with CC 30-60 ml/min clarithromycin dose should be reduced by 50%. For patients with KK less 30 ml/min the dose of clarithromycin should be reduced by 75%. In a joint application of clarithromycin and ritonavir should not be applied doses of clarithromycin in excess of 1 g/day.

In case of kidney function lesions, dose correction is usually not required, except for patients with severe kidney lesions (CC < 30 ml/min), but if necessary, the total daily dose should be reduced by half, i.e. 250 mg 1 time/ or 250 mg 2 with more severe infections.

While taking ritonavir for patients with impaired renal function recommended dose adjustment according to the following scheme: for patients with CC 30-60 ml/min clarithromycin dose should be reduced by 50%. For patients with KK less 30 ml/min the dose of clarithromycin should be reduced by 75%. In a joint application of clarithromycin and ritonavir should not be applied doses of clarithromycin in excess of 1 g/

Side effect: 

Clarithromycin is usually well tolerated by patients.

From the digestive tract: nausea, vomiting, dyspepsia, diarrhea, abdominal pain, stomatitis, glossitis, pancreatitis, oral candidiasis, discoloration of the tongue and teeth, rarely — pseudomembranous enterocolitis. Teeth discoloration is reversible and usually restored by special treatment in a dental clinic. As with other antibiotics from the group of macrolides, liver function may be impaired, including increased activity of liver enzymes, hepatic-cellular and/or cholestatic hepatitis with or without jaundice. These liver disorders can be severe, but they are usually reversible. Very rarely there have been cases of liver failure and fatal outcome mainly due to severe comorbidities and/or concomitant drug therapy.

From the blood system: in exceptional cases-leukopenia and thrombocytopenia, increased serum creatinine.

In the Central and peripheral nervous system: paresthesia, headache, disorders of smell, change in taste, dizziness, agitation, insomnia, nightmares, anxiety, tinnitus, confusion, disorientation, hallucinations, psychosis, depersonalization, reversible hearing loss, convulsions.

From the cardiovascular system: as with other macrolides Qt prolongation, ventricular tachycardia, polymorphic ventricular tachyarrhythmia (torsades de pointes).

From the side of musculoskeletal system: arthralgia, myalgia.

From the urinary system: isolated cases of increased creatinine in blood plasma, interstitial nephritis, renal failure.

Allergic reactions: urticaria, angioneurotic edema, anaphylactic shock, in rare cases, Stevens – Johnson syndrome, toxic necrolysis epidermally.

Other: rarely-hypoglycemia in patients taking oral hypoglycemic drugs or insulin.

Contraindications: 

• co-administration with ergot derivatives, 
• coadministration of the following drugs: cisapride, pimozide, terfenadine, 
• children under 12 years of age, 
• pregnancy and lactation.
• hypersensitivity to antibiotics of the macrolide group.

* Caution: patients with impaired liver and kidney function.

Use of the drug during pregnancy and breast-feeding: 

Security claritromicina during pregnancy and lactation has not been studied.

The drug passes into breast milk. If necessary, use during lactation should stop breastfeeding.

Application for violations of liver function: 

Caution: patients with impaired liver function.

Application for violations of renal function: 

In case of renal impairment, dose adjustment is usually not required, except for patients with severe kidney lesions (CC < 30 ml/min), but if necessary, the total daily dose should be reduced by half, i.e. 250 mg 1 time/day. or 250 mg 2 times / day. with more severe infections.

Use in children: 

Contraindications: children under 12 years old.

Special instruction: 

Taking clarithromycin tablets in children under 12 years is not recommended.

With the simultaneous appointment of clarithromycin and warfarin should be regularly monitored prothrombin time.

With the simultaneous appointment of clarithromycin and digoxin, the level of digoxin concentration in the blood serum should be monitored.

Overdose: 

* Symptoms: symptoms from the digestive tract, one of the patients with 8 g clarithromycin was a case of mental disorders, paranoid behavior, hypoglycemia, hypoxemia.

* Treatment: gastric lavage, maintenance therapy. Hemodialysis or peritoneal dialysis is ineffective, as for other macrolides.

Drug interaction: 

When concomitant administration of clarithromycin with cisapride, pimozide and terfenadine in plasma are elevated concentrations of these drugs that may cause QT prolongation and arrhythmias, including ventricular tachycardia, ventricular fibrillation arrhythmia, and torsade de pointes, similar to the effects observed with concomitant administration of astemizole and other macrolides.

Clarithromycin does not interact with oral contraceptives.

How and when taking other macrolide antibiotics, concomitant use of clarithromycin and other drugs metabolized by the cytochrome P450 (warfarin, ergot alkaloids, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporine and tacrolimus) may be accompanied by increased concentrations of the medications listed above in the serum.

With simultaneous use of clarithromycin and HMG-KoA reductase inhibitors (lovastatin, simvastatin), the development of rhabdomyolysis is possible.

With simultaneous appointment clarithromycin and theophylline increases the concentration of theophylline in serum and its toxicity.

Simultaneous administration of clarithromycin and warfarin or digoxin may be accompanied by an increase in the severity of their effects.

With the simultaneous appointment of clarithromycin and carbamazepine, the effect of carbamazepine may increase due to a decrease in the rate of excretion of carbamazepine.

In concomitant administration of clarithromycin and zidovudine (by mouth) to HIV-infected adult patients may reduce the equilibrium concentration of zidovudine, this can largely be avoided by increasing the interval between doses of clarithromycin and zidovudine to 1-2 hours For children such interaction was observed.

While taking ritonavir and clarithromycin for the latter increase the values of pharmacokinetic parameters: AUC, Cmax, Cmin. For patients with normal renal function dose adjustment is usually not required due to the wide therapeutic range of clarithromycin doses.

While the use of clarithromycin and omeprazole, clarithromycin and lansoprazole, clarithromycin and ranitidine may increase the concentration of drugs in blood plasma, but usually dose adjustment is not required.

With simultaneous use of clarithromycin and hypoglycemic agents, including insulin, in rare cases, the development of hypoglycemia.

Conditions and storage: 

Store at a temperature not exceeding 25°C, out of reach of children. 

Do not use after expiry date.