Klacid (Clarithromycin) tablets, ampoules, powder

Composition and form of issue:

Klacid SR

Tablets coated with a film coating, prolonged action. 1 tablet contains active substance:

clarithromycin 500 mg

excipients: citric acid anhydrous sodium calcium sodium alginate lactose alginate povidone-C30 talc stearic acid magnesium stearate 

film coating: hypromellose macrogol 400 macrogol 8000 titanium dioxide dye yellow (quinoline yellow) sorbic acid 

in blister 5, 7, 10 or 14 PCs.in a pack of cardboard 1 or 2 blisters.

Klacid

Powder for preparation of suspension for oral administration. 5 ml contains active substance:

clarithromycin 125 or 250 mg

excipients: carbomer (carbopol 974P) povidone K90 these phthalate castor oil silicon dioxide maltodextrin sucrose titanium dioxide xanthan gum flavor fruity (dosage 125 mg/5 ml) fruit flavor (dosage 250 mg/5 ml) potassium sorbate citric acid anhydrous 

in bottles of 60 (for a dosage of 125 mg/5 ml) or 100 ml (for a dosage of 250 mg / 5 ml) complete with a dosage spoon or dosing syringe in a pack of cardboard 1 bottle.

Tablets, film-coated. 1 tablet contains active substance:

clarithromycin 250 or 500 mg

excipients, the core for tablets of 250 mg: croscarmellose sodium MCC starch pregelatinized silicon dioxide povidone stearic acid magnesium stearate talc quinoline yellow E104 

film coating for tablets of 250 mg: gipromelloza propylene glycol sorbitan monoleate titanium dioxide sorbic acid vanillin quinoline yellow E104 

excipients, core for tablets of 500 mg: croscarmellose MCC silicon dioxide povidone magnesium stearate stearic acid talc 

film coating for tablets of 500 mg: hypromellose hydroxypropyl cellulose propylene glycol sorbitan monoleate titanium dioxide sorbic acid vanillin quinoline yellow E104 

in blister 7, 10 or 14 PCs. in a pack of cardboard 1, 2 or 3 blisters.

Description of dosage form:

Klacid SR

Yellow oval tablets covered with a film cover.

Klacid

Powder for preparation of oral suspension 125 mg / 5 ml — white or almost white, granular, with a fruity aroma. When shaking with water — white or almost white opaque suspension with a fruity aroma.

Powder for the preparation of a suspension for oral administration 250 mg / 5 ml — granules of white or almost white, having a fruity aroma. When water is added, a white or almost white opaque suspension with a fruity aroma is formed.

Yellow pills (250 mg) or light yellow ( 500 mg) are oval, film coated.

Pharmacokinetics:

Klacid SR

Clarithromycin is metabolized in the liver cytochrome p4503a (CYP3A) system. The absolute bioavailability is about 50%. With repeated administration of the drug cumulation is not found, the nature of metabolism in the human body has not changed.

In vitro

In vitro studies showed that, on average, about 70% of clarithromycin binds to proteins of human serum at concentrations of the drug 0, 45-4, 5 µg/ml. While increasing the concentration to 45 mg/ml the binding of clarithromycin was reduced to 41%, which may indicate saturation of binding. This phenomenon was observed only at concentrations significantly higher than therapeutic.

Healthy volunteer

In patients who took 500 mg of the drug Klacid SR 1 time a day, Cmax clarithromycin and the main metabolite clarithromycin-14 (R)-hydroxyclarithromycin (14-on-clarithromycin) in blood plasma was 1, 3 and 0, 48 µg/ml, respectively. T1 / 2 of the original drug and metabolite were 5, 3 and 7, 7 h, respectively. When receiving a single dose of Closesr 1000 mg (2x 500 mg) Cmax of clarithromycin and its hydroxylated metabolite were achieved for 2, 4 and 0, 67 µg/ml, respectively. T1/2 of clarithromycin, when taken at a dose of 1000 mg was 5, 8 h, whereas the same indicator for 14-Oh-clarithromycin was 8, 9 a.m. Tmax when taken as 500 and 1000 mg was approximately 6 h. the Cmax of the 14-Oh-clarithromycin were not increased in proportion to dose of clarithromycin, while T1/2 of clarithromycin and its hydroxylated metabolite tended to increase with increasing dose. This nonlinear pharmacokinetics of clarithromycin combined with a decrease in the formation of 14-hydroxylated and N-demethylated products at high dosages indicates a nonlinear metabolism of clarithromycin.

The news is about 40% of the intake of clarithromycin. About 30% is excreted by the intestine.

Patient

Clarithromycin and its 14-on-metabolite rapidly penetrate the body’s tissues and fluids. Limited data obtained in tests involving a small number of patients indicate that the concentration of clarithromycin in the spinal fluid after oral administration is negligible. Concentrations in tissues are usually several times higher than in blood serum.

Liver disease

In a comparative study, it was shown that in patients with moderate and severe hepatic impairment of renal function, dosage adjustment is not required.

Kidney disease

In people with kidney disease, plasma concentrations of T1 / 2, Cmax and Cmin clarithromycin and its 14-on-metabolite were higher than in people with normal kidney function. In patients with impaired renal function AUC was greater, and the constant elimination and excretion kidneys-less. The degree of these differences correlated with the severity of kidney disease: the more pronounced the violation of kidney function, the greater the differences.

Older people

In the elderly, plasma levels of clarithromycin and its 14-ON-metabolite are higher, and the excretion is slower than in the young. However, the main effect on the pharmacokinetic parameters of clarithromycin has kidney function, not age.

Klacid

The first data on pharmacokinetics were obtained in the study of clarithromycin tablets. The drug is rapidly absorbed into the digestive tract. Absolute bioavailability of clarithromycin tablets of 50 mg is about 50%. The food somewhat delayed the beginning of absorption and the formation of an active metabolite of 14-ON-clarithromycin, but did not affect the bioavailability of the drug.

In vitro

In vitro studies, the binding of clarithromycin to plasma proteins averaged about 70% at clinically significant concentrations from 0, 45 to 4, 5 µg / ml.

Healthy volunteer

Bioavailability and pharmacokinetics of clarithromycin suspension were studied in healthy adults and children. Once taken in adults, the bioavailability of the suspension was equivalent to that of tablets (in both cases, the dose was 250 mg) or slightly higher. As in the case of tablets, the food somewhat delayed absorption of clarithromycin suspension, but did not affect the overall bioavailability of the drug. Cmax, AUC and T1 / 2 clarithromycin when taking children’s suspension (after eating) were 0, 95 mcg / ml, 6, 5 mcg / ml * h and 3, 7 h, respectively, and when taking the pill 250 mg on an empty stomach-1, 1 mcg/ ml 6, 3 mcg * h / ml and 3, h.

When applying clarithromycin suspension at a dose of 250 mg every 12 h in adults, the equilibrium blood levels were almost reached to the reception of the fifth dose. The parameters of pharmacokinetics were as follows: Cmax-1, 98 µg / ml, AUC-11, 5 µg / ml * h, Tmax-2, 8 h and T1 / 2-3, 2 h – for clarithromycin and respectively— 0, 67 5, 33 2, 9 and 4, 9 for 14 on clarithromycin. In healthy people serum concentrations reached a peak within 2 hours after ingestion. Equilibrium Cmax of the main metabolite, 14-Oh-clarithromycin is about 0, 6 mg/ml, and T1/2 when using the drug in a dose 250 mg every 12 hours is equal to 5-6 h. in the appointment of clarithromycin in a dose of 500 mg every 12 h equilibrium Cmax14-Oh-clarithromycin is slightly higher (up to 1 µg/ml) and T1/2 is about 7 hours When using both doses of the equilibrium concentration of metabolite is usually achieved within 2-3 days. In the appointment of clarithromycin in a dose of 250 mg every 12 hours, approximately 20% of the dose appears kidneys in an unmodified form. When applied in a dose of 500 mg every 12 hours, in unchanged form by the kidneys excreted about 30% of the dose. Renal clearance of clarithromycin does not significantly depend on the dose and approaches the normal glomerular filtration rate. The main metabolite found in urine is 14-on-clarithromycin, which accounts for 10-15% of the dose (250 or 500 mg every 12 hours).

Patients taking clarithromycin, according to the testimony

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

Table 1

Concentrations at a dose of 250 mg every 12 hours

In children in need of oral antibiotic treatment, clarithromycin is highly bioavailable. At the same time, the profile of its pharmacokinetics was similar to those of adults who took the same suspension. The drug is rapidly and well absorbed in children. Food slightly delays the absorption of clarithromycin, but does not have a significant impact on its bioavailability or pharmacokinetic properties.

The equilibrium parameters of the pharmacokinetics of clarithromycin reached after 5 days (ninth dose) were as follows: Cmax-4, 60 µg/ ml, AUC-15, 7 µg / ml * h and Tmax-2, 8 h corresponding values for 14-ON metabolite: 1, 64 µg / ml 6, 69 µg / ml * h and 2, 7 hours Calculated T1 / 2 clarithromycin and its metabolite — 2, 2 and 4, respectively, 3 hours.

Patients with otitis media in 2, 5 hours after receiving the fifth dose (7, 5 mg/kg 2 times daily) mean concentrations of clarithromycin and 14-Oh-metabolite in the middle ear were 2, 53 and 1, 27 g/g. Concentration of the drug and its metabolite in 2 times higher than their serum levels.

Impairment of liver function

The equilibrium concentrations of clarithromycin in patients with impaired liver function do not differ from those in healthy people, while the levels of 14-on-clarithromycin were lower. The decrease in the formation of 14-on-clarithromycin in patients with impaired liver function was at least partially offset by an increase in the renal clearance of clarithromycin compared with those in healthy people.

Impaired renal function

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

Older people

In a comparative study in elderly healthy people, receiving clarithromycin re-inside at a dose of 500 mg, revealed an increase in plasma levels and slowing down the excretion compared with those in young healthy people. However, the difference between the two groups was reversed when the creatinine clearance was adjusted. It was concluded that the changes in the pharmacokinetics of clarithromycin reflect kidney function, not the age of the patient.

Patients with Mycobacterium infections

The equilibrium concentrations of clarithromycin and 14-on-clarithromycin in patients with HIV infection who received clarithromycin in normal doses (500 mg 2 times a day) in the form of tablets in adults and suspensions in children, were similar to those in healthy people. However, when using clarithromycin in higher doses, which may be required for the treatment of Mycobacterium infections, antibiotic concentrations can significantly exceed the usual.

In children with HIV infection who were taking clarithromycin in the form of suspension for the reception inside in a dose of 15-30 mg/kg/day in 2 admission, the equilibrium value Cmax typically ranged from 8 to 20 µg/ml. However, in children with HIV infection treated with a suspension of clarithromycin in a dose of 30 mg/kg/day in 2 divided doses, Cmax were 23 µg/ml.

When using the drug in higher doses, an elongation of the half-life period was noted in comparison with that in healthy people who received clarithromycin in conventional doses. The increase in plasma concentrations and the duration of the half-life period in the appointment of clarithromycin in higher doses is consistent with the known nonlinearity of the drug pharmacokinetics.

Combined treatment with omeprazole

Clarithromycin at a dose of 500 mg 3 times a day in combination with omeprazole at a dose of 40 mg/day increases the half–life and AUC0-24 omeprazole. In patients receiving combination therapy, compared with patients receiving one omeprazole, there was an increase of 89% AUC0–24 and 34% T1/2 omeprazole. In clarithromycin Cmax, Cmin and AUC0–8 increased by 10, 27 and 15%, respectively, compared to data when only clarithromycin without omeprazole was used. In an equilibrium state, the concentration of clarithromycin in the gastric mucosa after 6 h after administration in the group receiving the combination, 25 times higher than those obtained in comparison with one clarithromycin. The concentration of clarithromycin in the tissues of the stomach 6 h after administration of the two drugs in 2 times exceeded the data obtained in the group of patients treated with clarithromycin alone.

Description of the pharmacological action:

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

Clarithromycin is highly effective in vitro against standard and isolated bacterial cultures. It is highly active against a wide range of aerobic and anaerobic, gram-positive and gram-negative microorganisms.

Studies in vitro have shown that clarithromycin is highly active against Legionella pneumophila, Mycoplasma pneumoniae and Helicobacter pylori, but Enterobacteriaceae, Pseudomonas spp. and other lactose non-fermenting gram-negative microorganisms impervious to the action of clarithromycin.

It has been shown that clarithromycin has antibacterial action against the following pathogens: aerobic gram-positive microorganisms-Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes aerobic gram-negative microorganisms: Haemophilus influenzae, Haemophilus parftuenzae, Moraxella Legion, catachan, pneumophila, Neisseria gonorrhoeae other microorganisms — Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), Chlamydia trachomatis mycobacteria — Mycobacterium avium complex (MAC) — the complex includes: Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum.

Beta-lactamases do not affect the activity of clarithromycin.

Clarithromycin in vitro is active against most strains of the following microorganisms:

• aerobic gram-positive microorganisms-Streptococcus agalactiae Streptococcus spp. groups C, F, G Streptococcus spp. Viridans groups
• 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 is Campylobacter jejuni.

The main metabolite of clarithromycin in the human body is microbiologically active metabolite 14-hydroxyclarithromycin (14-on-clarithromycin). Microbiological activity of the metabolite is the same as that of the original substance, or 1-2 times weaker against most microorganisms. The exception is H. influenzae, in respect of which the efficiency of the metabolite is 2 times higher. The initial compound (clarithromycin) and its metabolite in combination can have both additive and synergistic effects on H. influenzae in vitro and in vivo, depending on the strain of the bacterium.

Sensitivity studies

Quantitative methods that require measurement of microbial growth inhibition zone diameter provide the most accurate assessment of bacteria sensitivity to antimicrobial agents. One of the recommended sensitivity determination procedures uses discs impregnated with 15 µg clarithromycin (Kirby-Bauer diffusion test). the test results are interpreted depending on the diameter of the growth inhibition zone of the micro-organism and the value of the IPC clarithromycin. The value of IPC is determined by the method of dilution of the medium or diffusion in agar. Laboratory tests give one of three results:

1) “sustainable” – can be considered, that infection not amenable to treatment data drug

2) “sensitive” – the therapeutic effect is ambiguous, and may increase the dosage may lead to sensitivity

3)” sensitive ” — can be considered, that infection amenable to treatment clarithromycin.

Klacid SR

Prolonged-action tablets have a homogeneous basis, which ensures long-term release of the active substance when it passes through the digestive tract.

MPC clarithromycin for most pathogens is less than MPC erythromycin.

Indications:

Klacid SR (tablet, coated), Klacid suspension

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug, including:

• infections of the lower respiratory tract, including bronchitis, pneumonia
• infections of the upper respiratory tract and ENT-organs, including pharyngitis, sinusitis
• infections of the skin and soft tissues, including folliculitis, inflammation of the subcutaneous tissue, erysipelas.

Only for Klacid (coated tablets), Klacid suspension

• common or localized Mycobacterium infections caused by Mycobacterium avium and Mycobacterium intracellulare
• localized infections caused by Mycobacterium chelonae, Mycobacterium fortuitum and Mycobacterium kansasii
• the elimination of N.pylori and decrease the frequency of recurrences of duodenal ulcers.

Only For Klacid of coated tablets:

• prevention of the spread of infection due to Mycobacterium avium complex (MAC), HIV-infected patients with CD4 lymphocytes (T-helper lymphocytes) no more than 100 in 1 mm3
• odontogenic infections.

Contraindications:

Common drugs Klacid SR Klacid and

• hypersensitivity to the drug components and other macrolides
• severe renal insufficiency-creatinine Cl-less than 30 ml/min (Klacid SR, Klacid, suspension)
• concomitant administration of clarithromycin with the following drugs: astemizole, cisapride, pimozide, terfenadine, ergotamine, dihydroergotamine (see ” Interaction» )
• porphyria.

Klacid SR

• simultaneous administration with the following drugs: alprazolam, midazolam, triazolam (oral dosage forms)
• children under 18 years (effectiveness and safety have not been established)
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

With caution

• liver and kidney function disorders
• myasthenia gravis (possible exacerbation of symptoms)
• simultaneous administration with drugs that are metabolized by the liver (see. “Interaction”).

Klacid

• pregnancy
• lactation
• children under 3 years of age (for the dosage form in the form of tablets — see “Special instructions”).

Caution: impaired liver and kidney function.

For additional tablets:

Clarithromycin is excreted mainly by the liver. In this regard, caution should be exercised when prescribing an antibiotic to patients with impaired liver function. Caution should be observed in the treatment of clarithromycin patients with moderate and severe renal insufficiency. In clinical practice, cases of colchicine toxicity when combined with clarithromycin, particularly in elderly people. Some of these cases were observed in patients with renal insufficiency have been several reported cases of death in these patients (See. “Interaction with other drugs” — Colchicine).

Cross-resistance between clarithromycin and other macrolides, as well as lincomycin and clindamycin, should be considered.

Application for pregnancy and breastfeeding:

Klacid SR

Safety of clarithromycin in pregnant and lactating women has not been studied.

Use during pregnancy (especially in the I trimester) is possible only if the potential benefit to the mother exceeds the potential risk to the fetus and/or there is no safer alternative therapy.

If pregnancy occurs during the use of the drug, the patient should be warned about the possible risks to the fetus.

It is known that clarithromycin is excreted in breast milk. During lactation should decide on the abolition of breastfeeding.

Klacid

Safety of clarithromycin in pregnant and lactating women has not been studied. It is known that clarithromycin is excreted in breast milk. Therefore, the use of clarithromycin during pregnancy and lactation is recommended only in cases where there is no safer alternative, and the risk associated with the disease itself exceeds the possible harm to the mother and fetus.

Side effect:

Klacid SR

Side effects are presented depending on the impact on the organs and systems of organs. For cases with frequency read: often >1%, <10 %, rarely <1%, including individual cases.

Cardiovascular system: rarely-ventricular tachycardia, including “pirouette” type, ventricular flutter and flicker, QT interval increase on ECG.

From the digestive system: often-dyspepsia, nausea, abdominal pain, vomiting, diarrhea, gastralgia, acute pancreatitis, glossitis, stomatitis, candidiasis of the oral mucosa, discoloration of the tongue and teeth, pseudomembranous enterocolitis. Liver function disorders, including frequent-increased activity of liver enzymes, hepatocellular and cholestatic hepatitis, cholestatic jaundice. In very rare cases, fatal liver failure has been reported, mainly due to severe comorbidities and/or concomitant drug therapy.

From the nervous system: headaches (frequent) dizziness, anxiety, insomnia, disorders of dreams (“the nightmare” of dreaming), ringing in the ears, depersonalization, hallucinations, seizures, psychotic disorders, confusion, disorientation, depression.

From the side of musculoskeletal system: myalgia.

From the urinary system: interstitial nephritis.

From the sensory organs: often — the distortion or loss of taste deafness, change of smell.

Allergic reactions: anaphylactic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, skin hyperemia, itching, rash.

Changes in laboratory parameters: leukopenia, thrombocytopenia, an increase in the content of creatinine in the blood, hypoglycemia — rarely (including while taking hypoglycemic drugs).

Klacid

Klacid suspension for safety is comparable to tablets of 250 mg in adults. Most often, there were undesirable phenomena from the digestive tract, including diarrhea, vomiting, abdominal pain and nausea. Pseudomembranous enterocolitis was rarely observed. Other adverse reactions included headache, taste disturbance, and transient increase in liver enzymes. As with other antibiotics of the macrolide group, the development of resistance of microorganisms can be noted.

Post-marketing experience

In the treatment of clarithromycin, as well as other macrolides, infrequently there were violations of liver function, including increased activity of liver enzymes, and hepatocellular and/or cholestatic hepatitis, accompanied or not accompanied by jaundice. Hepatic dysfunction may be severe and is usually reversible. In very rare cases, deaths from liver failure have been reported, and these have generally been observed in the presence of serious comorbidities and/or concomitant use of other drugs.

Some cases of serum creatinine level increase are described, but their relationship with the drug has not been established.

When used orally, clarithromycin describes allergic reactions, which ranged from urticaria and small rashes to anaphylaxis and Stevens-Johnson syndrome/toxic epidermal necrolysis. There are reports of transient effects on the Central nervous system, including dizziness, anxiety, insomnia, bad dreams, tinnitus, confusion, disorientation, hallucinations, psychosis and depersonalization causal their relationship to drug not established. In the treatment of clarithromycin describes cases of hearing loss after discontinuing treatment hearing is usually restored. Also known cases of violation of smell, which usually combined with taste perversion.

In the treatment of clarithromycin describes glossitis, stomatitis, thrush and changing the color of the tongue. There are cases of tooth color changes in patients receiving clarithromycin (these changes are usually reversible and can be eliminated by the dentist).

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

In the treatment of clarithromycin, as well as other macrolides, rarely noted elongation of THE Qt interval, ventricular tachycardia and ventricular tachycardia type “pirouette”.

Rare cases of pancreatitis and seizures are described.

There are reports of the development of interstitial nephritis in the treatment of clarithromycin. In clinical practice, cases of colchicine toxicity when combined with clarithromycin, particularly in elderly people. Some of them were observed in patients with renal insufficiency reported several deaths in similar patients (See paras. “Interaction with other drugs” — Colchicine).

Children with a depressed immune system. In patients with AIDS and other immunodeficiency, receiving clarithromycin in higher doses for a long time to treat Mycobacterium infections, it is often difficult to differentiate the undesirable effects of the drug from the symptoms of HIV infection or intercurrent diseases.

In a limited number of children with AIDS, clarithromycin was used to treat Mycobacterium infections. The main adverse events not related to the main disease were tinnitus, deafness, vomiting, nausea, abdominal pain, purpura, pancreatitis and increased amylase activity. In this study, significant deviations of the laboratory indicators from the normative values (sharp increase or decrease) were recorded. Based on these criteria, one child with AIDS who received clarithromycin at a dose of <15 mg/kg/day showed a significant increase in the level of total bilirubin among patients taking clarithromycin at a dose of 15-25 mg/kg/day, one case was reported of a significant increase in ALT levels, residual urea nitrogen and a decrease in platelet count. In patients receiving clarithromycin at the maximum dose (>25 mg/kg/day), significant changes in these laboratory parameters were not revealed.

The main adverse events in patients taking clarithromycin orally at a dose of 1 g were nausea, vomiting, taste perversion, abdominal pain, diarrhea, rash, bloating, headache, hearing impairment, constipation, increased ACT and ALT. Less often dyspnoea, insomnia and dry mouth were also noted.

In this group of patients with suppressed immunity, significant deviations of laboratory parameters from the normative values in specific tests (sharp increase or decrease) were recorded. On the basis of this, approximately 2-3% of patients taking clarithromycin orally at a dose of 1 g/day, there were significant deviations from normal laboratory parameters, such as increased ACT, ALT and a decrease in the number of leukocytes and platelets. A smaller number of patients, there was also an increase in the level of nitrogen of urea of blood.

Drug interaction:

The use of the following drugs in conjunction with clarithromycin is contraindicated due to the possibility of serious side effects:

Cisapride and pimozide

When combined use may increase the concentration of cisapride, QT interval increase, the appearance of cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, ventricular tachycardia type “pirouette”.

Terfenadine and astemizole

When combined, it is possible to increase the concentration of terfenadine/astemizole in the blood, increase THE Qt interval, the occurrence of cardiac arrhythmias, ventricular tachycardia, ventricular fibrillation and tachycardia of the “pirouette”type.

Ergotamine / dihydroergotamine

When used together, the following effects may be associated with acute poisoning drugs ergotamine group: vascular spasm, limb ischemia and other tissues, including the Central nervous system.

The effect of other drugs on clarithromycin

The following drugs have a proven or suspected effect on the concentration of clarithromycin in the case of their co-administration with clarithromycin may require dose adjustment or transition to alternative treatment.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin

Strong inducers of cytochrome P450 system, such as efavirenz, nevirapine, rifampicin, rifabutin and rifapentin can accelerate the metabolism of clarithromycin and thus lower the plasma levels of clarithromycin, weaken the therapeutic effect, and at the same time increase the level of 14-OH-clarithromycin — a metabolite that is also microbiologically active.