Pharmacotherapeutic group
Antibiotic, macrolide
ATX code: J01FA09
Pharmacodynamics:
Clarithromycin is a semisynthetic antibiotic of the macrolide group and has antibacterial action by interacting with the 50S ribosomal subunit and inhibiting protein synthesis of bacteria sensitive to it.
Clarithromycin has shown high in-vitro activity against both standard laboratory strains of bacteria and those isolated from patients in clinical practice. It shows high activity against many aerobic and anaerobic gram-positive and gram-negative microorganisms. Minimum inhibitory concentrations (MIC) of clarithromycin for most pathogens are lower than MIC of erythromycin on average by one log2 dilution.
Clarithromycin is highly active against LegionellapneumophilaMycoplasmapneumoniae. It has a bactericidal effect against Helicobacterpylori this activity of clarithromycin is higher at neutral pH than at acidic pH.
In addition, in-vitro and in-vivo data indicate that clarithromycin is active against clinically relevant mycobacterial species. Enterobacteriaceae and Pseudomonasspp. as well as other non-lactose-fermenting gram-negative bacteria are not sensitive to clarithromycin.
The activity of clarithromycin against most strains of the microorganisms listed below has been demonstrated both in vitro and in clinical practice for the conditions listed under “Indications for use”.
Aerobic Gram-positive microorganisms
Staphylococcusaureus
Streptococcus pneumoniae
Streptococcus pyogenes
Listeria monocytogenes
Aerobic Gram-negative microorganisms
p> Haemophilusinfluenzae
Haemophilus parainfluenzae
Moraxella catarrhalis
Neisseria gonorrhoeae
Legionella pneumophila
Other microorganisms/p>
Mycoplasma pneumoniae
Chlamydia pneumoniae (TWAR)
Mycobacteria
/p>
Mycobacterium leprae
Mycobacterium kansasii
Mycobacterium chelonae
/p>
Mycobacterium fortuitum
Mycobacterium avium complex (MAC) – a complex including: Mycobacterium avium
MycobacteriumintracellulareThe production of beta-lactamase has no effect on clarithromycin activity. Most staphylococcal strains that are resistant to methicillin and oxacillin are also resistant to clarithromycin.
Helicobacter pylori
Sensitivity of H.pylori to clarithromycin was studied in H.pylori isolates isolated from 104 patients before initiation of therapy with the drug. Clarithromycin-resistant H.pylori strains were isolated in 4 patients, 2 patients had moderate resistance strains, and the remaining 98 patients had clarithromycin-sensitive H.pylori isolates.
Clarithromycin also has activity against most strains of the following microorganisms (but the safety and efficacy of clarithromycin in clinical practice has not been confirmed by clinical studies and the practical value remains unclear):
Aerobic Gram-positive microorganisms
Streptococcusagalactiae
Streptococci (Group C FG)
Viridansgroupstreptococci
Aerobic gram-negative microorganisms
/p>
Bordetellapertussis
Pasteurellamultocida
Anaerobic gram-positive microorganisms
/p>
Clostridim perfringens
Peptococcus niger
Propionibacterium acnes
/p>
Anaerobic Gram-negative microorganisms
Bacteroides melaninogenicus
p> Spirochetes
Borrelia burgdorferi
Treponema pallidum
Campylobacter
/p>
Campilobacterjejuni
The main metabolite of clarithromycin in humans is the microbiologically active metabolite 14-hydroxyclarithromycin (14-OH-clarithromycin). The microbiological activity of the metabolite is the same as that of the parent substance or 1-2 times weaker against most microorganisms. The exception is H.influenzae against which the effectiveness of the metabolite is twice as high. The parent substance and its main metabolite have either additive or synergistic effect against H.influenzae under in-vitro and in-vivo conditions depending on the bacterial strain.
Sensitivity test
Quantitative methods requiring measurement of the diameter of the growth suppression zone provide the most accurate estimates of bacterial sensitivity to antimicrobials. One recommended technique for sensitivity testing uses 15-µg clarithromycin-impregnated disks (Kirby-Bauer disco-diffusion method); in interpreting the test, zona diameters of growth suppression correlate with the IPC values of clarithromycin. IPC values are determined by dilution in broth or agar. Using these techniques, a report from the laboratory that the strain is “sensitive” indicates that the infectious agent is likely to respond to treatment. A “resistant” response indicates that the pathogen will probably not respond to treatment. An “intermediate sensitivity” response suggests that the therapeutic effect of the drug may be ambiguous or that the microorganism may be sensitive with higher doses of the drug. (Intermediate sensitivity is also called “moderate sensitivity.)
Pharmacokinetics:
Intake
The drug is easily and quickly absorbed in the gastrointestinal tract. Absolute bioavailability is about 50%. No cumulation was found when multiple doses of the drug were administered and the metabolism did not change in the human body. Eating immediately before taking the drug increased the bioavailability of the drug by 25% on average. Overall, this increase is insignificant and should have little clinical significance with the recommended dosing regimens. Therefore, clarithromycin can be used regardless of food intake.
Distribution metabolism and excretion
Invitro studies have shown that clarithromycin binds to plasma proteins by 70% at concentrations from 045 to 45 µg/ml. At a concentration of 450 µg/ml, the binding decreases to 41% probably as a result of saturation of the binding sites. This is observed only at concentrations many times greater than the therapeutic concentration.
Invivo studies on animals have shown that clarithromycin is present in all tissues except the central nervous system at concentrations several times greater than plasma concentrations. The highest concentrations (10-20 times higher than plasma concentrations) were found in the liver and lungs.
Health
When clarithromycin was administered at a dose of 250 mg twice daily, the maximum equilibrium concentration (Cmax) of clarithromycin and 14-OH-clarithromycin in plasma was reached after 2-3 days and was 1 µg/ml and 06 µg/ml, respectively. The half-life (T1/2) of clarithromycin and its main metabolite were 3-4 hours and 5-6 hours, respectively.
When clarithromycin was administered at a dose of 500 mg twice daily, the Cmax of clarithromycin and 14-OH clarithromycin in plasma was reached after the 5th dose. After the 5th and 7th dose, the Cmax of clarithromycin and 14-OH-clarithromycin in plasma averaged 27 to 29 mcg/mL and 088 to 083 mcg/mL, respectively. The T1/2 of clarithromycin and its main metabolite were 45 – 48 hours and 69 – 87 hours, respectively.
The cmax of 14-OH clarithromycin did not increase in proportion to the clarithromycin dose, whereas the elimination half-life of both clarithromycin and its hydroxylated metabolite tended to increase with increasing dose. This nonlinear pharmacokinetics of clarithromycin combined with decreased formation of 14-hydroxylated and N-demethylated products at high doses indicates a nonlinear metabolism of clarithromycin that becomes more pronounced at higher doses.
The urinary excretion is about 379% after oral clarithromycin doses of 250 mg and 460% after clarithromycin doses of 1200 mg; the intestinal excretion is about 402% and 291% (including subjects with only one stool sample containing 141%), respectively.
Patients
Clarithromycin and its metabolite 14-OH-clarithromycin penetrate rapidly into tissues and body fluids. There is limited evidence that the oral concentration of clarithromycin in cerebrospinal fluid is negligible (i.e., only 1-2% of the serum concentration with normal blood-brain barrier permeability). Concentrations in tissues are usually several times higher than in blood serum.
The table shows examples of tissue and serum concentrations:
Concentrations (250 mg every 12 hours) /td> | |||
Tissue type | Tissue (µg/g) < | Serum (µg/mL) | |
My tonsils | 16 | 08 /td> | |
Lung | 88 | 17 |
Liver function disorders
/p>
In patients with moderate to severe hepatic impairment but with preserved renal function, clarithromycin dose adjustment is not necessary. Equilibrium plasma concentration and systemic clearance of clarithromycin do not differ between patients in this group and healthy patients. The equilibrium concentration of 14-OH clarithromycin is lower in people with hepatic impairment than in healthy patients.
In impaired renal function, the Cmax and minimum plasma concentration (Cmin) of clarithromycin and its metabolite 14-OH clarithromycin increase in the elimination half-life. The elimination constant and renal excretion decreases. The degree of change in these parameters depends on the degree of renal impairment.
Elderly patients
Elderly patients had higher blood concentrations of clarithromycin and its metabolite 14-OH clarithromycin and slower excretion than the younger group. However, after adjustment for renal creatinine clearance there were no differences in the two groups. Thus, the main influence on the pharmacokinetic parameters of clarithromycin is renal function and not age.
Patients with mycobacterial infections
The equilibrium concentrations of clarithromycin and 14-OH clarithromycin in patients with HIV infection receiving clarithromycin at conventional doses (500 mg twice daily) were similar to those in healthy subjects. However, when clarithromycin is used in higher doses that may be necessary to treat mycobacterial infections, concentrations of the antibiotic may be significantly higher than usual. In HIV-infected patients taking clarithromycin at a dose of 1000 mg/day or 2000 mg/day in two doses, equilibrium Cmax values were typically 2-4 mcg/ml and 5 – 10 mcg/ml, respectively. Longer half-life was observed at higher doses than in healthy subjects receiving clarithromycin at normal doses. The increased plasma concentrations and prolonged half-life when using clarithromycin at higher doses are due to the non-linear pharmacokinetics of the drug.
Combination therapy with omeprazole
Clarithromycin 500 mg 3 times daily in combination with omeprazole at a dose of 40 mg/day helps to increase T1/2 and AUC0-24 of omeprazole. In all patients receiving combined therapy compared to those receiving omeprazole alone there was an 89% increase in AUC0-24 and 34% increase in T1/2 of omeprazole. In clarithromycin Cmax Cminn AUC0-8 were increased by 10% 27% and 15% respectively compared to data when clarithromycin alone was used without omeprazole. At equilibrium concentrations of clarithromycin in gastric mucosa 6 hours after administration were 25 times higher in the group receiving the combination compared to those receiving clarithromycin alone. Concentrations of clarithromycin in gastric tissue 6 hours after the administration of 2 drugs were twice as high as in the group of patients receiving clarithromycin alone.
Indications
Infectious inflammatory diseases caused by clarytromycin-sensitive microorganisms in adults and children over 12 years:
– Lower respiratory tract infections (such as bronchitis pneumonia);
– Upper respiratory tract infections (such as pharyngitis sinusitis);
– skin and soft tissue infections (such as folliculitis inflammation of the hypodermis of mumps);
– disseminated or localized mycobacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare; localized infections caused by Mycobacterium chelonae Mycobacterium fortuitum and Mycobacterium kansasii;
Prevention of spread of infection caused by Mycobacterium avium complex (MAC) in HIV-infected patients with the content of CD4 lymphocytes (T-helper lymphocytes) not exceeding 100 in 1 mm3.
– eradication of H.pylori and reduction of duodenal ulcer recurrence rate.
Active ingredient
Composition
1 film-coated tablet contains:
The active ingredient: clarithromycin – 500.00 mg.
Auxiliary substances: kernel: croscarmellose sodium – 65.60 mg; microcrystalline cellulose – 183.90 mg; silicon dioxide – 12.00 mg; povidone (K 29 – 32) – 25.50 mg; stearic acid – 21.00 mg; magnesium stearate – 12.60 mg; talc – 29.40 mg;
Film coating: Hypromellose (hydroxypropyl methylcellulose) – 22.10 mg; hyprolose – 1.70 mg; propylene glycol – 14.62 mg; sorbitan oleate – 1.70 mg; titanium dioxide – 5.10 mg; sorbic acid -0.94 mg; vanillin – 0.94 mg; quinoline yellow dye E-104 – 0.07 mg.
How to take, the dosage
The average oral dose for adults is 250 mg 2 times a day. If necessary, 500 mg 2 times a day may be prescribed.
The duration of treatment course is 6-14 days.
For the treatment of infections caused by Mycobacterium avium, Clacid is prescribed orally – 1 g 2 times a day. The duration of treatment may be 6 months or more.
Interaction
The following drugs are contraindicated with clarithromycin due to the possibility of serious side effects:
Cisapride pimozide terfenadine and astemizole
When clarithromycin is coadministered with cisapride pimozide terfenadine or astemizole, an increase in plasma concentrations of the latter has been reported that can lead to prolonged QT interval and cardiac arrhythmias including ventricular fibrillation and pirouette-type ventricular tachycardia (see Contraindications. See Contraindications).
After-marketing studies have shown that the following effects related to acute poisoning with ergotamine or dihydroergotamine can occur when clarithromycin is coadministered: vasospasm, ischemia of the extremities and other tissues including the central nervous system. Concomitant use of clarithromycin with ergot alkaloids is contraindicated (see section “Contraindications”).
Special Instructions
Prolonged use of antibiotics can lead to the formation of colonies with increased numbers of insensitive bacteria and fungi. In case of superinfection, appropriate therapy should be prescribed.
Prescribing clarithromycin to pregnant women should be done with careful risk-benefit assessment especially during the first three months of pregnancy.
Hepatic dysfunction (increased hepatic enzyme activity in the blood hepatocellular and/or cholestatic hepatitis with or without jaundice) has been reported with clarithromycin. Liver dysfunction can be severe but is usually reversible. There are cases of hepatic failure with fatal outcome mainly related to the presence of serious comorbidities and/or concomitant use of other drugs. If signs and symptoms of hepatitis occur, such as anorexia jaundice darkened urine itching abdominal pain on palpation, clarithromycin therapy should be stopped immediately.
In the presence of chronic liver disease, serum enzymes should be monitored regularly.
When treated with virtually all antibacterial agents including clarithromycin there have been cases of pseudomembranous colitis the severity of which can vary from mild to life-threatening. Cases of Clostridium difficile-associated diarrhea have been reported with virtually all antibacterials, including clarithromycin, and the severity of diarrhea can range from mild to life-threatening colitis.
Antibiotic drugs can alter normal gut microflora, which can lead to growth of C.difficile. Pseudomembranous colitis caused by Clostridium difficile should be suspected in all patients who develop diarrhea after using antibiotics. After a course of antibiotic therapy, careful medical follow-up of the patient is necessary. Cases of pseudomembranous colitis have been described 2 months after antibiotic treatment.
When treated with macrolides including clarithromycin, prolongation of cardiac repolarization and QT interval have been observed, causing a risk of cardiac arrhythmias and pirouette-type ventricular tachycardia (see section “Adverse effects”). Because the following situations may increase the risk of ventricular arrhythmias (including pirouette ventricular tachycardia), clarithromycin should not be used in the following patient categories:
– in patients with hypokalemia (see “Contraindications” section);
– simultaneous administration of clarithromycin with astemizole cisapride pimozide and terfenadine is contraindicated (see
Patients with a history of congenital or acquired registered QT interval prolongation or ventricular arrhythmias are contraindicated (see Contraindications).
– Clarithromycin should be used with caution in the following patient categories:
– in patients with coronary heart disease (CHD) severe heart failure conduction abnormalities or clinically significant bradycardia;
– in patients with electrolyte disturbances such as hypomagnesemia;
– in patients concomitantly taking other medications associated with QT interval prolongation (see
Patients concomitantly taking other drugs associated with QT interval prolongation (see section “Interaction with other medicinal products”).
Epidemiologic studies on the risk of adverse cardiovascular outcomes with the use of macrolides have had mixed results. Some observational studies have found a short-term risk of myocardial infarction and cardiovascular death associated with macrolide use, including clarithromycin. When prescribing clarithromycin, the anticipated benefits of the drug should be weighed against these risks.
Cross-resistance to clarithromycin and other macrolide antibiotics and to lincomycin and clindamycin may develop.
Given the increasing resistance of Streptococcuspneumoniae to macrolides, it is important to perform sensitivity testing when prescribing clarithromycin to patients with community-acquired pneumonia. In hospital pneumonia, clarithromycin should be used in combination with appropriate antibiotics. Skin and soft tissue infections of mild to moderate severity are most often caused by Staphylococcusaureus and Streptococcuspyogenes. Both pathogens may be resistant to macrolides. Therefore, it is important to test for sensitivity. Macrolides can be used for infections caused by Corynebacteriumminutissimum diseases of acne vulgaris and rye as well as in situations where penicillin cannot be used.
In case of acute hypersensitivity reactions such as anaphylactic reactions severe cutaneous drug reactions (e.g., acute generalized exanthematous pustulosis) Stevens-Johnson syndrome toxic epidermal necrolysis and drug rash with eosinophilia and systemic symptoms (DRESS syndrome), clarithromycin should be stopped immediately and appropriate therapy started.
In case of co-administration with warfarin or other indirect anticoagulants, the INR and prothrombin time should be monitored (see section “Interaction with other medicinal products”).
There are no data concerning the effect of clarithromycin on driving and operating ability.
Perhaps caution should be exercised when driving vehicles and operating machinery due to the potential for dizziness, vertigo, confusion, and disorientation that may occur with this drug.
Contraindications
For oral administration. Regardless of food intake.
The usual recommended dose of clarithromycin in adults and children over 12 years of age is 250 mg 2 times daily (in which case Clacid® film-coated tablets 250 mg may be used).
Clarithromycin 500 mg 2 times a day is used for more severe infections.
The usual duration of treatment is 5 to 14 days.
The exceptions are community-acquired pneumonia and sinusitis, which require 6 to 14 days of treatment.
Doses for treatment of mycobacterial infections other than tuberculosis:
In mycobacterial infections, a dose of clarithromycin 500 mg twice daily is recommended.
The treatment of disseminated MAC infections in patients with AIDS should be continued as long as there is clinical and microbiological efficacy. Clarithromycin should be used in combination with other antimicrobials active against these pathogens.
The duration of treatment for other non-tuberculous mycobacterial infections is determined by the physician.
For the prevention of infections caused by MAC:
The recommended dose of clarithromycin for adults is 500 mg twice daily.
For eradication of H. pylori.
In patients with peptic ulcer disease caused by H. pylori infection, clarithromycin may be given 500 mg 2 times daily in combination with other antimicrobial agents and proton pump inhibitors for 7-14 days according to the national and international recommendations for treatment of H. pylori infection.
Patients with renal failure
Patients with a creatinine clearance of less than 30 mL/min are half the usual dose of clarithromycin (in this case the dose of 250 mg is used). These patients are not treated for more than 14 days.
The use in children younger than 12 years of age
The use of clarithromycin tablets in children younger than 12 years has not been studied.
– Moderate to severe renal failure.
– Moderate to severe hepatic insufficiency.
– Concomitant administration of clarithromycin with benzodiazepines such as alprazolam triazolam midazolam for intravenous use or for application to the oral mucosa (see “Interaction with other medicinal products”).
– Concomitant use with drugs that are metabolized by CYP3A isoenzymes such as carbamazepine cilostazol cyclosporine disopyramide methylprednisolone omeprazole indirect anticoagulants (e.g. warfarin) quinidine rifabutin sildenafil tacrolimus vinblastine (see section “Interaction with other medicinal products”).
– Concomitant use with drugs that induce CYP3A4 isoenzyme such as rifampicin phenytoin carbamazepine phenobarbital St. John’s wort (see section “Interaction with other medicinal products”).
– Concomitant use of clarithromycin with statins not dependent on CYP3A isoenzyme metabolism (e.g., fluvastatin) (see section “Interaction with other medicinal products”).
– Concomitant use with “slow” calcium channel blockers that are metabolized by CYP3A4 isoenzyme (e.g., verapamil amlodipine diltiazem).
Patients with coronary heart disease (CHD) severe heart failure hypomagnesemia impaired conduction or clinically significant bradycardia as well as patients taking concurrent Class 1A (quinidine procainamide) and Class III (dofetilide amiodarone sotalol) antiarrhythmic drugs.
Pregnancy.
Side effects
Classification of adverse reactions by frequency of development (number of reported cases/number of patients): very common (â¥1/10) common (â¥1/100 < 1/10) infrequent (â¥1/1000 < 1/100) frequency unknown (adverse effects from post-marketing experience; frequency cannot be estimated based on available data).
Allergic reactions
Often: rash.
Infrequent: anaphylactoid reaction1 hypersensitivity dermatitis bullosa1 pruritus urticaria maculopapular rash3.
Frequency unknown: anaphylactic reaction angioedema serious skin adverse reactions (e.g., acute generalized exanthematous pustulosis) Stevens-Johnson syndrome toxic epidermal necrolysis drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).
Nervous system disorders
Often: headache insomnia.
Infrequent: loss of consciousness1 dyskinesia1 dizziness somnolence tremor anxiety hyperexcitability3.
Prevalence unknown: seizures psychotic disorders confusion depersonalization depression disorientation hallucinations dream disorders (“nightmares” dreams) paresthesia mania.
Skin disorders
Often: intense sweating.
Prevalence unknown: acne.
Urinary system disorders
Often unknown: renal failure interstitial nephritis.
Metabolism and nutrition disorders
Infrequent: anorexia decreased appetite.
Musculoskeletal disorders
Infrequent: muscle spasm3 musculoskeletal stiffness1 myalgia2.
Infrequent unknown: rhabdomyolysis2* myopathy.
Digestive system disorders
Often: diarrhea vomiting dyspepsia nausea abdominal pain.
Infrequent: esophagitis1 gastroesophageal reflux disease2 gastritis proctalgia2 stomatitis glossitis bloating4 constipation dry mouth belching flatulence cholestasis4 hepatitis including cholestatic or hepatocellular4.
Frequency unknown: acute pancreatitis discoloration of tongue and teeth liver failure cholestatic jaundice.
Respiratory system disorders
Infrequent: asthma1 nasal bleeding2 pulmonary embolism1.
Sensory system disorders
Often: dysgeusia.
Infrequent: vertigo impaired hearing tinnitus.
Frequent unknown: deafness agueusia (loss of taste sensation) parosmia anosmia.
Cardiovascular system disorders
Often: vasodilation1.
Infrequent: cardiac arrest1 atrial fibrillation1 prolongation of QT interval on electrocardiogram extrasystole1 palpitations.
Frequency unknown: ventricular tachycardia including pirouette-type ventricular fibrillation bleeding.
Laboratory indices
Often: abnormality in liver function test.
Infrequent: increased creatinine concentration1 increased urea concentration1 albumin-globulin ratio change1 leukopenia neutropenia4 eosinophilia4 thrombocythemia3 increased activity: alanine aminotransferase (ALT) aspartate aminotransferase (ACT) gammaglutamyltransferase (GGTP)4 alkaline phosphatase4 lactate dehydrogenase (LDH)4.
Frequency unknown: agranulocytosis thrombocytopenia increased international normalized ratio (INR) prolongation of prothrombin time urine color changes increased blood bilirubin concentration.
General disorders
Very common: phlebitis at the injection site1.
Often: pain at the injection site1 inflammation at the injection site1.
Infrequent: malaise4 hyperthermia3 asthenia chest pain4 chills4 fatigue4.
Infectious and parasitic diseases
Infrequent: cellulitis1 candidiasis gastroenteritis2 secondary infections3 (including vaginal).
Infrequent unknown: pseudomembranous colitis rye.
The incidence of type and severity of adverse reactions in children is thought to be the same as in adults.
Patients with suppressed immunity
In patients with AIDS and other immunodeficiencies who receive clarithromycin at higher doses for long term treatment of mycobacterial infections, it is often difficult to distinguish adverse effects of the drug from symptoms of HIV infection or a concomitant disease.
The most common adverse effects in patients taking a daily dose of clarithromycin equal to 1000 mg were: nausea, vomiting, taste disorder abdominal pain diarrhea rash flatulence headache constipation hearing disorders increased ACT and ALT activity in blood. Adverse events with low frequency of occurrence have also been reported. Such as shortness of breath insomnia and dry mouth.
In patients with suppressed immunity, laboratory parameters were evaluated by analyzing their significant deviations from the norm (sharp increase or decrease). Based on this criterion, 2 to 3% of patients who received clarithromycin at a dose of 1,000 mg daily had a significant increase in ACT and ALT activity in the blood and a decrease in leukocyte and platelet counts. A small number of patients also registered an increase in residual urea nitrogen concentration.
* In some reports of rhabdomyolysis, clarithromycin has been taken together with other medications known to be associated with rhabdomyolysis (statins fibrates colchicine or allopurinol).
1 These adverse reactions have only been reported with Clacid® lyophilizate for preparation of solution for infusion.
2 These adverse reactions have only been reported with Clacid® SR sustained release film-coated tablets.
3 These adverse reactions have only been reported with oral Clacid® suspension granules.
4 These adverse reactions have only been reported with Clacid® film-coated tablets.
Overdose
Pregnancy use
The safety of clarithromycin use during pregnancy and breastfeeding has not been established.
The use of clarithromycin in pregnancy (especially in the first trimester) is possible only if there is no alternative therapy and the potential benefit to the mother exceeds the potential risk to the fetus.
Clarithromycin is excreted with the breast milk. Breast-feeding must be discontinued if it is necessary during lactation.
Similarities
Weight | 0.026 kg |
---|---|
Shelf life | 1 year |
Conditions of storage | In a light-protected place, at a temperature not exceeding 30 °C |
Manufacturer | AbbVi S.r.l., Italy |
Medication form | pills |
Brand | AbbVi S.r.l. |
Other forms…
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