KLAX 500 mg Film Tablet

Transcription

1 KLAX 500 mg Film Tablet FORMULA Each film coated tablet contains 500 mg clarithromycin. Excipients: Quinoline yellow, titanium dioxide, vanillin, sorbic acid PHARMACOLOGICAL PROPERTIES Clarithromycin is a macrolide group semisynthetic antibiotic. The property of O-methyl substitution of clarithromycin, which is a 14 carboniferius macrolide, unlike erythromycin, strengthens the molecule s stability against gastric acid as well as affecting favourably the molecule s antimicrobial and pharmacokinetic properties. Clarithromycin takes effect, as a result of bonding of the ribosomes of sensitive microorganisms with the submit of 50S, by inhibiting protein synthesis. It has usually bacteriostatical effect like the other macrolides. It has bactericidal affect against helicobacter pylori. (This effect is stronger for neutral PH) Clarithromycin has a wide spectrum; many aerobes and anaerobes are sensitive to Gram negative and positive bacteria. 14-OH Clarithromycin is the metabolite of Clarithromycin has antibacterial activity. For example, 14-OH metabolite is twice effective against Haemophilus influenza when compared to clarithromycin. Clarithromycin is not affected by β-lactamase group enzymes released by bacteria. Clarithromycin is indicated to be effective against the following bacteria either in vitro, or in vivo for the clinical infections: Gram-Positive aerobes : Staphylococcus aureus; Streptococcus pneumoniae and Streptococcus pyogenes Gram-Negative aerobes : Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and Helicobacter pylori Other aerobes : Mycoplasma pneumoniae Mycobacterium group bacteria: Mycobacterium avium complex (MAC) which is composed of Mycobacterium avium and Mycobacterium intracellulare; Mycobacterium kansasii, Mycobacterium chelonae and Mycobacterium fortuitum Clarithromycin has been found effective against the following bacteria under in vitro conditions, however the meaning of such microbiological effectiveness is not known clinically. Gram-Positive aerobes : Streptococcus agalactiae; C, F and G group Streptococcus, Viridans group streptococcus and Listeria monocytogenes Gram-Negative aerobes : Bordetella pertussis, Campylobacter jejuni, Legionella pneumophila, Neisseria gonorrhoeae and Pasteurella multocida Other aerobe bacteria : Chlamydia trachomatis Gram-Positive anaerobe bacteria: Clostridium perfringens, Peptococcus niger and Propionibacterium acnes Gram-Negative anaerobe bacteria: Bacteroides melaninogenicus Clarithromycin is absorbed quickly if taken orally. Bioavailability rate is approximately 50%. If taken with a full stomach, its absorption and 14-OH metabolite synthesis might delay, but the rate of bioavailability does not change. Therefore, it could be taken with an empty or with full stomach. The maximum plasma concentration (C max) is reached within 2 hours. In recommended doses, stable plasma concentrations (1 mcg/ml through 250 mg application two times a day; 2-3 mcg/ml through 500 mg application two times a day) are reached by the 2nd 3rd day of

2 treatment. Since Clarithromycin is a lypophilic molecule and it can penetrate into the tissues at very high concentrations, Clarithromycin reaches intracellular concentrations in high amounts. Tissue concentrations of drug are generally over the plasma level. For example if 250 mg is taken at every 12 hours, its concentration in tonsillar tissue becomes 2 times higher than in plasma, its concentration in lung tissue becomes 5 times higher than in plasma. The penetration of Clarithromycin into gastric mucosa is good as well. Stomach mucosa thickens and Clarithromycin concentration in mucus increases when they are used together with a proton pump inhibitor. Sufficient clinical data is not available about the passage of Clarithromycin into cerebrospinal fluid (CSF). Clarithromycin, binds to serum proteins at rates of approximately 50-70%, end is metabolized in the liver. 14-OH Clarithromycin metabolite has antibacterial effectiveness as well. Half life of Clarithromycin is an average of 3-4 hours. Half-life of 14-OH metabolite is longer to a degree (5-6 hours). Approximately 20-40% of the dose taken is eliminated through the urinary tract, and the rest is eliminated quantity through feces. INDICATIONS KLAX is indicated in infections caused by sensitive microorganisms: Upper respiratory tract infections ( Pharyngitis, tonsillitis, sinusitis otitis media etc) Lower respiratory tract infections ( Bronchitis, pneumonia) Skin and soft tissue infections ( folliculitis, cellulites, impetigo etc) Disseminated myco bacterial infections caused by Mycobacterium avium and Mycobacterium intracellulare and other local micro bacterial infections caused by other myco bacteria. Helicobacter pylori eradication (Clarithromycin is indicated for Helicobacter pylori eradication in the presence of acid suppression; decreases the risk of duodenal ulcer recurrences) CONTRAINDICATONS KLAX is contraindicated for those who are known hypersensitive to Clarithromycin or any substance of its composition or to a macrolide group antibiotic. Besides, it should not be used for cardiac patients with arrhythmia, ischemic heart disease, congestive heart failure etc. under terfenadine treatment and for those with electrolyte imbalance. CAUTIONS/PRECAUTIONS Clarithromycin is eliminated either through the kidneys or the liver. In case of liver failure when the renal functions are normal, it is reported that no dose adjustment is required. However, for those with serious renal failure, whether or not a liver failure exists, it might be necessary to dose adjustment either lower the dose or to extend the dose interval. Crossresistance possibility of Clarithromycin with other macrolide antibiotics should be taken into consideration. Almost every antibiotic, including macrolides, might cause pseudomembranous colitis. Therefore it should be aware by patients with diarrhoea during antibiotic treatment. In insignificant cases, it is enough to stop the antibiotic treatment. In serious cases, necessary precautions should be taken and an antibiotic effective against Clostridium difficile should be administered also. Pregnancy Category C. Use by pregnant women and nursing mothers: Clarithromycin should not be used in pregnant women unless it is required certainly. Clarithromycin is passes to breast milk. Therefore Clarithromycin should not be used in nursing women unless it is required certainly. Use by elders: The effectivity and reliability profile of Clarithromycin for elders do not show a marked difference compared to adults. A dose adjustment might be required for patients with renal failure.

3 SIDE EFFECTS/ADVERSE EFFECTS Clarithromycin is a well tolerated drug. Side effects are mostly insignificant and temporary. Most frequent side effects are related to gastrointestinal tract. Diarrhoea, nausea, dyspepsia, taste disorders in the mouth and stomachache have been reported. Headache is likely to appear as well. It has been stated that only 1% of side effects seen during clinical researches lead to cessation of the treatment. For patients with immune system disorders, generally it is difficult to distinguish the adverse effects which have arisen due to high dosage and long-term usage microbial infections from those symptoms seen in the course of HIV infections. Allergic reactions varying from urticaria and intermediate skin eruption to anaphylaxis and Steven-Johnson syndrome may arise due to Clarithromycin. Temporary central nervous system symptoms, including dizziness, insomnia, hallucinations, night terrors and confusion, might appear, as well. Increase in SGPT, SGOT, GGT, Alkaline Phosphotase, LDH and total bilirubin values is not likely for patients using clarithromycin. Seldom leucopenia and elevated prothrombin time have been reported. Increase in the level of BUN (4%) and increase in serum creatinin levels have been reported, as well. When clarithromycin was used in combination with omeprazole in clinical researches, colour variations on the tongue have been observed. Hearing loss, which was recovered as a result of quitting the treatment, was also reported during clarithromycin treatment. Tooth discoloration has occurred on patients under clarithromycin treatment. Discoloration has been removed by professional tooth cleansing. Seldom hypoglycaemia cases, some of which appeared on patients under hypoglycaemic agent and insulin treatment have been reported Isolated thrombocytopenia cases have been reported. DRUG INTERACTIONS AND OTHER INTERACTIONS Theophylline: When clarithromycin is used together with theophylline, serum concentration of theophylline might increase. Therefore, if it is required to take both drugs alongside, the serum concentration of theophylline should be monitored. Carbamazepine: When clarithromycin is used alongside with carbamazepine, due to the fact that serum concentration of carbamazepine might increase, it should be monitored. Terfenadine: When clarithromycin is used alongside with terfenadine, it has been determined that serum concentration of terfenadine active metabolite triples on average. Patients using terfenadine should be monitored of Clarithromycin use. (See contraindications) Zidovudine: In case clarithromycin is administered to AIDS patients alongside with zidovudine, fixed plasma concentrations of zidovudine decrease. Sisapride: Increased sisapride levels have been observed when used together with sisapride. Ritonavir: When clarithromycin is used together with ritonavir, the area of clarithromycin under the curve (AUC) increases. Due to the fact that clarithromycin therapeutic margins have a broad interval, there is no need to adjust the dose for those with normal renal functions. In events of renal failures, if both drugs will be used alongside, the dose of clarithromycin should be reduced at a rate of 50% in cases when creatinine clearance is between ml/minute and at a rate of 75% in case when it is lower than 30 ml/minute. Daily Clarithromycin doses exceeding 1 g should not be used together with ritonavir. Eventhough it is not encountered in researches held to date on clarithromycin, mentioned interactions above should be considered for erythromycin as well, which is chemically a similar molecule. When erythromycin is used together with digoxin, serum concentration of digoxin increases; when applied with oral anticoagulants, anticoagulant effect increases; when used with triazolam, the excretion of triazolam slows down and its pharmacological effects might increase. In case of ergotamine or dihydroergotamine administration to patients using erythromycin, it has been reported that ergot toxication might appear in some patients. Erythromycin might further lead to an increase in serum concentrations of the drugs such as

4 carbamazepine, cyclosporine, hexobarbital, phenytoin, which are metabolized by the CPY450 system. No teratogenic, mutagenic, carcinogenic or fertility destructive effect have been observed in toxicity researches made on animals. IN CASE OF AN UNEXPECTED EFFECT, CONSULT TO PHYSICIAN DOSE AND ADMINISTRATION KLAX may be taken with empty or full stomach. Skin and soft tissue infections through respiratory tract: Recommended dosage for adults and for children older than 12 years is 250 mg at intervals of 12 hours. In serious infections, the dosage may be doubled (500 mg at intervals of 12 hours). Average treatment duration is 7-14 days for such infections. In infections due to streptococci, treatment should not be ceased before 10 days in order to minimize complication risk. Infections connected with micro bacteria: Recommended initial dosage for adults is 500 mg at intervals of 12 hours. If there is no response to such doses within 3-4 weeks, the dosage may be doubled (1000 mg at intervals of 12 hours). Treatment should proceed until clinical and microbiological response is received. It is recommended to use clarithromycin in combination with other antimicrobacterials. Helicobacter pylori eradication: Recommended clarithromycin dosage for adults is 500mg, 2 times daily during 14 days (Together with a preparate preventing acid secretion). Once the combination treatment has been ceased, it should be continued for 14 more days with an acid secretion preventing agent, such as a proton pump inhibitor used in combination (Total treatment duration is 28 days) OVERDOSE There is no sufficient data available on clarithromycin overdose. Overdose symptoms specific to macrolides are hearing loss, serious nausea, vomiting and diarrhoea. If it is necessary, the stomach of the patient should be irrigated and other supportive therapy should be done. STORAGE CONDITIONS: Keep under 30 C (room temperature), and do not expose to light. KEEP IN PLACES OUT OF REACH OF CHILDREN AND KEEP IN ITS PACKAGE TRADE FORM AND PACKAGE CONTENT: In a package of 14 tablets, each film coated tablet containing 500 mg clarithromycin as an active substance.

5 OTHER PHARMACOLOGICAL DOSAGE FORMS KLAX 250 mg film tablet: In a blister package of 14 tablets, each film coated tablet containing 250 mg clarithromycin KLAX 125 mg/5 ml Suspension: In a glass bottle of the capacity of 70ml, each 5 ml cup containing 125 mg clarithromycin KLAX 250 mg/5 ml Suspension: In a glass bottle of the capacity of 50 ml & 100 ml, each 5 ml cup containing 250 mg clarithromycin License No : 22/07/ /89 License Owner : Toprak İlaç ve Kimyevi Mad.San. ve Tic.A.Ş. Toprak Center, Ihlamur Yıldız Cad. No: Beşiktaş/İSTANBUL Producer :Toprak İlaç ve Kimyevi Mad.San. ve Tic.A.Ş. Tem Otoyolu Adapazarı Çıkışı, Kandaklar Mevkii Adapazarı SAKARYA PRESCRIPTION DRUG