Clerimed pills 500mg, 14pcs

Composition

Active ingredient:  

• clarithromycin 500 mg;

excipients:  

• microcrystalline cellulose 178,5 mg,

• silicon dioxide colloid 2.0 mg,

• croscarmellose sodium salt and 74.0 mg,

• povidone 35,0 mg,

• stearic acid 12.5 mg,

• talc 15,0 mg,

• magnesium stearate 7.5 mg;

shell: hypromellose 13,0 mg,8.6 mg propylene glycol, sorbitan monooleate 1.0 mg, vanilla flavoring 0,550 mg, titanium dioxide E 171 3.0 mg, quinoline yellow E 104 varnish 1.1 mg, hydroxypropyl cellulose 1.0 mg, Corbicula acid 0,55 mg.

Pharmacological action

Clarithromycin is a semi-synthetic broad-spectrum macrolide antibiotic. Disrupts microbial protein synthesis by binding to the 50S subunit of the microbial cell ribosome membrane. It has mainly bacteriostatic action, in high doses – bactericidal. It has an antibacterial effect against a wide range of sensitive microorganisms. It acts on extracellularly and intracellularly located pathogens. The activity of clarithromycin against most strains of the following microorganisms has been proven both in vitro and in clinical practice: aerobic gram – positive microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes; aerobic gram – negative microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Legionella pneumophila; other microorganisms: Mycoplasma pneumoniae, Chlamydia pneumoniae; Mycobacteria: Mycobacterium avium complex (MAC) – a complex that includes: Mycobacterium avium, Mycobacterium intracellulare; Helicobacter pylori. Beta-lactamases do not affect the activity of clarithromycin. Clarithromycin activity in vitro – aerobic gram-positive microorganisms: Listeria monocytogenes; Streptococcus agalactiae; Streptococci of groups C, F, G; Streptococci of groups viridans; aerobic gram-negative microorganisms: Neisseria gonorrhoeae, 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; Mycobacteria: Mycobacterium leprae, Mycobacterium chelonae; Campylobacteria: Campylobacter jejuni. Clarithromycin exhibits bactericidal activity against Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Campylobacter jejuni, and Helicobacter pylori. The microbiologically active metabolite of clarithromycin,14 (R) – hydroxyclarithromycin, is twice as active as the parent compound against Haemophilus influenza. For other sensitive microorganisms, the minimum inhibitory concentration(MPC) of 14 (R)-hydroxyclarithromycin is equal to or 1-2 times weaker than the MPC of the starting substance. Most strains of staphylococci that are resistant to methicillin and oxacillin are resistant to clarithromycin. The IPC of clarithromycin for most sensitive microorganisms is 2 times lower than the IPC of erythromycin. Clarithromycin is superior to roxithromycin in its activity against streptococcus and hemophilic bacillus. The antibacterial activity of clarithromycin is several times higher in a slightly alkaline or neutral medium than in an acidic one. Pharmacokinetics: After oral use, it is rapidly and completely absorbed from the gastrointestinal tract. Food slows down absorption without significantly affecting bioavailability. Bioavailability of 250 mg tablets is 50%. Plasma protein binding is 70-80%. After a single dose, two peaks of maximum concentration (Cmax) are recorded. The second peak is due to the ability of the drug to accumulate in the gallbladder, followed by gradual or rapid entry into the intestine and absorption. TSMAKH when taking 250 mg – 1-3 hours. In therapeutic concentrations, it accumulates in the lungs, skin, and soft tissues (where the tissue concentration is 10 times higher than the level of the drug in the blood serum). It is found in the tonsils, liver, and middle ear fluid. Clarithromycin penetrates well into the walls of the stomach, and its level in smooth muscles and gastric mucosa is higher when combined with omeprazole than without it. No more than 1-2% of the drug level in the blood plasma penetrates through the intact blood-brain barrier. Penetrates well into breast milk. Undergoes biotransformation in the liver (the “first pass” effect). After oral use,20% of the dose is rapidly hydroxylated in the liver by cytochrome P 450 isoenzymes (CYP3A4, CYP3A5, and CYP3A7) to form the main metabolite,14(R) – hydroxyclarithromycin, which has a pronounced antimicrobial activity against Haemophilus influenza. It is an inhibitor of the isoenzymes CYP3A4, CYP3A5 and CYP3A7. The steady-state concentration (Css)of clarithromycin and its main metabolite is established within 2 days after starting the drug. With regular intake of 250 mg per day, the Css for the unchanged drug and its metabolite is 1.0 and 0.6 mcg / ml, respectively; the half-life (T 1/2) is 3-4 hours and 5-6 hours, respectively. When the dose is increased to 500 mg/day, the Css of the unchanged drug and its metabolite in plasma is 2.7-2.9 and 0.83-0.88 mcg / ml, respectively; T 1/2 – 4,8-5 hours and 6.9-8.7 hours, respectively. The concentration of clarithromycin in blood plasma when taking 500 mg 3 times a day is higher than that when taking 500 mg twice a day. Excreted by the kidneys and intestines: 20-30% – unchanged, the rest – in the form of metabolites. With a single dose of 250 mg,37.9% is excreted by the kidneys and 40.2% by the intestines, respectively. The main metabolite – 14-hydroxyclarithromycin in the urine accounts for 10-15% of the dose taken. In chronic renal failure, the TMAX, Cmax, and AUC of clarithromycin and its metabolite are increased. In patients with impaired liver function, the steady-state concentration of clarithromycin did not differ from that in patients with normal liver function, while the steady-state concentration of 14(R) – hydroxyclarithromycin in patients with impaired liver function was significantly lower. A decrease in the elimination of the drug in the form of 14 (R) – hydroxyclarithromycin with impaired liver function is partially compensated by an increase in the excretion of clarithromycin by the kidneys, as a result, the Css value of clarithromycin changes slightly and no dose adjustment is required. In elderly patients, the pharmacokinetics do not change significantly.

Indications

Infectious and inflammatory diseases caused by sensitive microflora.

For adults:

– pharyngitis, tonsillitis, acute maxillary sinusitis;

chronic bronchitis in acute, community-acquired pneumonia (including those caused by atypical pathogens: Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila);

– uncomplicated infections of skin and subcutaneous tissue;

– disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare;

– in combination with amoxicillin and omeprazole/lansoprazole in the form of triple therapy in infections caused by Helicobacter pylori, including gastric ulcer and duodenal ulcer. In combination with omeprazole or ranitidine bismuth citrate as a triple therapy for the treatment of acute duodenal ulcers caused by Helicobacter pylori.

Children over 12 years of age (or with a body weight of more than 33 kg):

– pharyngitis, tonsillitis, acute sinusitis, acute otitis media;

– community-acquired pneumonia;

– uncomplicated skin and subcutaneous tissue infections;

– disseminated infection caused by Mycobacterium avium and Mycobacterium intracellulare.

Use during pregnancy and lactation

Clarithromycin is contraindicated in the first trimester of pregnancy.

In the second and third cases, the drug is prescribed only if there are clear indications, if the intended benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to prescribe during lactation, the question of stopping breastfeeding should be decided.

Contraindications

• Hypersensitivity to clarithromycin, auxiliary substances of the drug or other antibiotics from the group of macrolides;
• porphyria;
• simultaneous reception of astemizole, cisapride, pimozide, terfenadina, ergot alkaloids (ergotamine, dihydroergotamine and other), midazolam for oral use, alprazolama, triazolam;
• children up to age 12 years or weighing less than 33 kg (for this dosage form);
• first trimester of pregnancy;
• lactation.

With caution: Renal or hepatic insufficiency, myasthenia gravis, concomitant use of drugs metabolized by the liver, concomitant use of colchicine, pregnancy of the II-III trimester.

Side effects

From the central nervous system: headache, dizziness, anxiety, insomnia, “nightmare” dreams, seizures, depression, disorientation, hallucinations, psychosis, depersonalization, confusion.

From the digestive system:  dyspepsia (loss of appetite, bloating), nausea, vomiting, gastralgia (stomach ache), diarrhoea (diarrhea), flatulence, stomatitis, glossitis, candidiasis of the mucous membrane of the mouth, change the color of the tongue or teeth (marked when used together with omeprazole), acute pancreatitis, transient increase in activity of “hepatic” transaminases, hepatocellular and cholestatic hepatitis, intrahepatic cholestasis, cholestatic jaundice;

rarely – pseudomembranous colitis, hepatic failure with fatal outcome, mainly on the background of severe comorbidities and/or concomitant drug therapy.Discoloration of teeth is reversible and usually recovers with professional dental cleaning.

From the cardiovascular system: ventricular tachycardia, including the “pirouette” type, flutter or flicker of the ventricles, prolongation of the Q-T interval on the ECG.

From the side of the senses: noise, ringing in the ears, perversion of taste sensations (dysgeusia), hearing loss; in isolated cases – hearing loss that passes after discontinuation of the drug, impaired sense of smell (insomnia).

Hematopoietic and hemostatic disorders: thrombocytopenia (unusual bleeding, hemorrhage).

From the urinary system: interstitial nephritis, renal failure.

From the musculoskeletal system: arthralgia, myalgia.

Laboratory parameters: leukopenia, eosinophilia, hypercreatininemia, hypoglycemia (including when taking hypoglycemic drugs at the same time). Allergic reactions: skin rash, pruritus, urticaria, skin hyperemia, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, anaphylactic reactions; rarely-anaphylactic shock, angioedema, bronchospasm.

Other services: increased body temperature, superinfections (development of resistance of microorganisms), candidiasis.

If an adverse reaction occurs, you should stop taking the drug and consult a doctor as soon as possible. If any of the side effects listed in the instructions get worse or you notice any other side effects that are not listed in the Instructions, tell your doctor.

Interaction

When clarithromycin is co-administered with drugs primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which can increase or prolong both therapeutic and side effects. Concomitant use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam is contraindicated. Use with caution with carbamazepine, cilostazol, cyclosporine, disopyramide, lovastatin, simvastatin, methylprednisolone, ranitidine, indirect anticoagulants (for example, warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, phenytoin, theophylline, valproic acid, cilostazol (metabolized through other drugs). cytochrome P450 isoenzymes), as this may lead to an increase in the plasma concentration of the latter. It is necessary to adjust the dose of the drug and monitor the concentration of these drugs in the blood plasma. Concomitant use of clarithromycin with cisapride, pimozide, terfenadine, astemizole, quinidine, disopyramide leads to an increase in the plasma level of these drugs (2-3 times) in the blood, which can be accompanied by prolongation of the QT interval, the development of life-threatening ventricular arrhythmias: ventricular tachycardia, including the “pirouette” type, ventricular fibrillation and flutter. ECG and serum concentrations of these drugs should be monitored. When combined with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group (vascular spasm, ischemia of the extremities and other tissues, including the central nervous system) is possible. Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin (cytochrome P450 inducers) reduce the concentration of clarithromycin in plasma and weaken its therapeutic effect, and, at the same time, increase the concentration of 14(R)-hydroxyclarithromycin. Concomitant use of fluconazole 200 mg daily and clarithromycin 1 g daily may increase the steady-state concentration (Css) and area under the concentration-time curve (AUC) of clarithromycin by 33% and 18%, respectively. No dose adjustment of clarithromycin is required. Concomitant use of ritonavir 600 mg / day and clarithromycin 1 g / day significantly slows down the metabolism of clarithromycin: Cmax of clarithromycin increases by 31%, Css-by 181%, AUC-by 77%; significantly slows down the formation of 14-hydroxyclarithromycin. For patients with CRF, clarithromycin dose adjustment is necessary: with a creatinine clearance of 30 to 60 ml / min, the clarithromycin dose should be reduced by 50%, and with a creatinine clearance of less than 30 ml/min – by 75%. Ritonavir should not be taken together with clarithromycin in a dose exceeding 1 g per day. When using clarithromycin with omeprazole, ranitidine: despite the possibility of increasing their plasma concentration, there is no need to reduce the doses of omeprazole or ranitidine. So, when taking clarithromycin and omeprazole, Cmax, AUC and T 1/2 of omeprazole can increase by 30%,89% and 34%, respectively. The average pH value in the stomach for 24 hours was 5.2 when taking omeprazole alone and 5.7 when taking omeprazole together with clarithromycin. When using clarithromycin with sildenafin, taladafil or vardenafil (phosphodiesterase-5 inhibitors), it is possible to increase the inhibitory effect on phosphodiesterase. It may be necessary to reduce the dose of phosphodiesterase-5 inhibitors. When clarithromycin is co-administered with theophylline, carbamazepine: the elimination of theophylline and carbamazepine slows down, the concentration of the latter in the systemic circulation may increase and theophylline intoxication may develop; carbamazepine effects may increase. When using clarithromycin with tolterodine in patients with low activity of the CYP2D6 isoenzyme, it may be necessary to reduce the dose of tolterodine in the presence of clarithromycin (an inhibitor of CYP3A isoenzymes). If clarithromycin (1 g/day) is co-administered with midazolam (orally), the AUC of midazolam may increase by 7 times. Concomitant oral use of clarithromycin and midazolam, as well as other benzodiazepines that are metabolized by the CYP3A isoenzyme (triazolam and alprazolam), should be avoided. When using clarithromycin and midazolam (IV), dose adjustment may be required. The same precautions should be applied to other benzodiazepines that are metabolized by the CYP3A isoenzyme. For benzodiazepines whose elimination does not depend on the CYP3A isoenzyme (temazepam, nitrazepam, lorazepam), a clinically significant interaction with clarithromycin is unlikely. When using clarithromycin with colchicine: clarithromycin, like other macrolides, inhibiting CYP3A and P-glycoprotein, can enhance the effect of colchicine. It is necessary to monitor the possible development of clinical symptoms of colchicine intoxication, especially in elderly patients and patients with CRF (fatal cases have been reported). Concomitant use of clarithromycin and digoxin may increase the concentration of digoxin in the blood, which can lead to increased therapeutic and side effects of digoxin, including the development of potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored. Concomitant use of clarithromycin and zidovudine in adult HIV-infected patients may lead to a decrease in the steady-state concentration and Css of zidovudine in the blood. Since clarithromycin affects the absorption of zidovudine, these two drugs should be separated in time at intervals of 1-2 hours. The dosage of clarithromycin and zidovudine should be selected. Concomitant use of clarithromycin (1 g / day) and atazanavir (400 mg/day) may increase the AUC of atazanavir by 28%, clarithromycin by 2 times, and decrease the AUC of 14-hydroxyclarithromycin by 70%. In patients with a creatinine clearance of 30-60 ml/min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g / day should not be administered together with protease inhibitors. When taking clarithromycin and itraconazole together, a mutual increase in the concentration of drugs in plasma is possible. Patients taking itraconazole and clarithromycin concomitantly should be closely monitored for possible increased or prolonged pharmacological effects of these drugs. Concomitant use of clarithromycin (1 g / day) and saquinavir (in soft gelatin capsules,1200 mg 3 times a day) may increase the AUC and Css of saquinavir by 177% and 187%, respectively, and clarithromycin by 40%. When these two drugs are co-administered for a limited time in the doses and dosage forms indicated above, no dose adjustment is required. When taken together with verapamil, it is possible to reduce blood pressure, bradyarrhythmia and lactic acidosis. Clarithromycin increases the concentration of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (lovastatin, simvastatin or others): rare cases of rhabdomyolysis are described. When clarithromycin is co-administered with warfarin (or other indirect anticoagulants), the effect of warfarin may increase; prothrombin time should be monitored periodically. When used with hypoglycemic drugs, including insulin, hypoglycemia may develop in rare cases. Interaction with oral contraceptives was not detected.

How to take it, course of use and dosage

Inside, regardless of food intake.Adults and children over 12 years of age (with a body weight of more than 33 kg):- for pharyngitis and tonsillitis caused by S. Pyogenes,250 mg every 12 hours for 10 days;- for acute sinusitis-500 mg every 12 hours for 14 days;- in case of exacerbation of chronic bronchitis caused by H. Influenza-500 mg every 12 hours for 7-14 days, caused by H. Parainfluenzae-500 mg every 12 hours for 7 days, caused by M. catarrhalis, S. pneumoniae-250 mg every 12 hours for 7-14 days;- for community-acquired pneumonia caused by H. influenzae-250 mg every 12 hours for 7 days, caused by S. pneumoniae, C. pneumoniae, M. Pneumonia-250 mg every 12 hours for 7-14 days;- for uncomplicated skin and subcutaneous tissue infections caused by S. aureus, S. pyogenes-250 mg every 12 hours for 7-14 days;For the purpose of eradication of Helicobacter pylori in combination with other drugs:- clarithromycin-500 mg, lansoprazole-30 mg, amoxicillin-1000 mg, all medications 2 times a day for 10-14 days;- clarithromycin-500 mg, omeprazole-20 mg, amoxicillin-1000 mg, all medications 2 times a day for 10 days; for patients who had an ulcer at the time of starting therapy, it is recommended to continue taking omeprazole 20 mg per day for the next 18 days;- clarithromycin-500 mg 3 times a day, omeprazole-40 mg / day for 14 days, followed by the appointment of omeprazole for 14 days at a dose of 20 mg / day. In the treatment and prevention of infections caused by the Mycobacterium avium and Mycobacterium intracellulare complex,500 mg 2 times a day is prescribed orally. The maximum daily dose is 1000 mg. The duration of treatment is 6 months or more. In patients with chronic renal insufficiency (creatinine clearance < 30 ml / min or serum creatinine concentration > 3.3 mg / 100 ml): the dose is reduced twice, or the interval between injections is doubled-250 mg every 24 hours. The maximum duration of treatment for patients in this group is 14 days. In patients with hepatic insufficiency, caution should be exercised: with normal renal function, no dose adjustment is usually required; in patients with hepatic insufficiency with concomitant severe renal insufficiency (creatinine clearance 30 ml/min), the dose is reduced twice, or the interval between injections is doubled.

Overdose

Symptoms: abdominal pain, nausea, vomiting, diarrhea, headache, confusion. A case of overdose in a patient (with a history of bipolar disorder) after taking 8 g of clarithromycin is described – there were mental disorders, paranoid behavior, hypokalemia and hypoxemia.

Treatment: Gastric lavage and symptomatic therapy are recommended. It is not removed during hemodialysis or peritoneal dialysis. There is no specific antidote.

Special instructions

In the presence of chronic liver diseases, it is necessary to regularly monitor the activity of” liver ” enzymes in blood serum.

With caution, it is prescribed against the background of drugs that are metabolized by the liver (it is recommended to measure their concentration in the blood). In the case of co-use with warfarin and other indirect anticoagulants, prothrombin time should be monitored.

If a secondary infection develops, adequate therapy should be prescribed.

If severe or prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and appropriate treatment.

It is possible to develop cross-resistance between clarithromycin and other macrolide antibiotics, as well as lincosamides (lincomycin and clindamycin). With long-term therapy, drug resistance of the microflora may develop.

Influence on the ability to drive vehicles and mechanisms:

Given the likelihood of developing side effects from the central nervous system, during treatment, care should be taken when driving vehicles and during potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Clarithromycin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets