Because OH-clarithromycin has reduced activity against Mycobacterium avium complex MACoverall activity against this pathogen may be altered; therefore alternatives to clarithromycin should be considered for the treatment of MAC.
The reactions considered at least possibly related to clarithromycin are displayed by system organ class and frequency using the following convention: In several reports, tablet residues have occurred in the context of diarrhoea.
Concomitant administration with ticagrelor or ranolazine is contraindicated. Summary of the safety profile The most frequent and common adverse reactions related to clarithromycin therapy for both adult and paediatric populations are abdominal pain, diarrhoea, nausea, vomiting and taste perversion.
Klaricid XL mg tablets PIL. Sign up to bookmark this SPC already have an account? Find medicines with the same active ingredients. Find medicines from the same company. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Klaricid XL mg Tablets are indicated for treatment of infections caused by susceptible organisms.
Lower respiratory tract infections for example, acute and chronic bronchitis, and pneumonia see section 4. Klaricid XL mg Tablets are also indicated in skin and soft tissue infections of mild to moderate severity, for example folliculitis, cellulitis and erysipelas see section 4. The usual recommended dosage of Klaricid XL mg Tablets in adults is one mg modified-release tablet daily to be taken with food.
In more severe infections, the dosage can be increased to two mg modified-release tablets daily. The usual duration of treatment is 6 to 14 days. Clarithromycin immediate release tablets may be utilized in this patient population see section 4. The dosage of clarithromycin should be reduced by one-half, i. Treatment should not be continued beyond 14 days in these patients. Children younger than 12 years: Use of Klaricid XL mg Tablets are not recommended for children younger than 12 years.
Clinical trials have been conducted using clarithromycin peadiatric suspension in children 6 months to 12 years of age. Therefore, children under 12 years of age should use clarithromycin peadiatric suspension granules for oral suspension. All other formulations may be used in this patient population.
Concomitant administration of clarithromycin and ergot alkaloids e. Concomitant administration of clarithromycin and oral midazolam is contraindicated see section 4. Concomitant administration of clarithromycin and any of the following drugs is contraindicated: Clarithromycin should not be given to patients with history of QT prolongation congenital or documented acquired QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes see sections 4.
Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors statins that are extensively metabolized by CYP3A4, lovastatin or simvastatindue to the increased risk of myopathy, including rhabdomyolysis.
As with other strong CYP3A4 inhibitors, Clarithromycin should not be used in patients taking colchicine see sections 4. Clarithromycin should not be given to patients with hypokalaemia risk of prolongation of QT-time.
Clarithromycin should not be used in patients who suffer from severe hepatic failure in combination with renal impairment. The physician should not prescribe clarithromycin to pregnant women without carefully weighing the benefits against risk; particularly during the first three months of pregnancy see section 4.
Clarithromycin is principally excreted by the liver. Therefore, caution should be exercised in administering this antibiotic to patients with impaired hepatic function.
Caution should also be exercised when administering clarithromycin to patients with moderate to severe renal impairment. Cases of fatal hepatic failure see section 4. Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products.
Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop, such as anorexia, jaundice, dark urine, pruritus, or tender abdomen. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening.
Clostridium difficile- associated diarrhoea CDAD has been reported with use of nearly all antibacterial agents including clarithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. CDAD must be considered in all patients who present with diarrhoea following antibiotic use.
Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. Therefore, discontinuation of clarithromycin therapy should be considered regardless of the indication. Microbial testing should be performed and adequate treatment initiated. Drugs inhibiting peristalsis should be avoided. There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency.
Deaths have been reported in some such patients see section 4. Concomitant administration of clarithromycin and colchicine is contraindicated see section 4.
Caution is advised regarding concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam, and intravenous or oromucosal midazolam see section 4.
Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointeshave been seen in treatment with macrolides including clarithromycin see section 4. Therefore as the following situations may lead to an increased risk for ventricular arrhythmias including torsades de pointesclarithromycin should be used with caution in the following patients. Clarithromycin must not be given to patients with hypokalaemia see section 4.
Clarithromycin must not be used in patients with congenital or documented acquired QT prolongation or history of ventricular arrhythmia see section 4. In view of the emerging resistance of Streptococcus pneumoniae to macrolides, it is important that sensitivity testing be performed when prescribing clarithromycin for community-acquired pneumonia.
In hospital-acquired pneumonia, clarithromycin should be used in combination with additional appropriate antibiotics. Skin and soft tissue infections of mild to moderate severity: These infections are most often caused by Staphylococcus aureus and Streptococcus pyogenesboth of which may be resistant to macrolides. Therefore, it is important that sensitivity testing be performed.
In cases where beta —lactam antibiotics cannot be used e. Currently, macrolides are only considered to play a role in some skin and soft tissue infections, such as those caused by Corynebacterium minutissimumacne vulgaris, and erysipelas and in situations where penicillin treatment cannot be used. In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and DRESS, clarithromycin therapy should be discontinued immediately and appropriate treatment should be urgently initiated.
Clarithromycin should be used with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme see section 4. HMG-CoA Reductase Inhibitors statins: Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated see section 4. Caution should be exercised when prescribing clarithromycin with other statins. Rhabdomyolysis has been reported in patients taking clarithromycin and statins. Patients should be monitored for signs and symptoms of myopathy.
In situations where the concomitant use of clarithromycin with statins cannot be avoided, it is recommended to prescribe the lowest registered dose of the statin. Use of a statin that is not dependent on CYP3A metabolism e. Careful monitoring of glucose is recommended see section 4. There is a risk of serious haemorrhage and significant elevations in International Normalized Ratio INR and prothrombin time when clarithromycin is co-administered with warfarin see section 4.
INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.
Long-term use may, as with other antibiotics, result in colonisation with increased numbers of non-susceptible bacteria and fungi. If superinfections occur, appropriate therapy should be instituted. Attention should also be paid to the possibility of cross resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin. Klaricid Modified Release contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take these medicines.
Klaricid XL mg Tablets contain If patients receive two Modified Release tablets once daily, the resulting sodium amount in total The use of the following drugs is strictly contraindicated due to the potential for severe drug interaction effects: Elevated cisapride levels have been reported in patients receiving clarithromycin and cisapride concomitantly.
This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and torsades de pointes. Similar effects have been observed in patients taking clarithromycin and pimozide concomitantly see section 4. Macrolides have been reported to alter the metabolism of terfenadine resulting in increased levels of terfenadine which has occasionally been associated with cardiac arrhythmias, such as QT prolongation, ventricular tachycardia, ventricular fibrillation and torsades de pointes see section 4.
In one study in 14 healthy volunteers, the concomitant administration of clarithromycin and terfenadine resulted in 2- to 3-fold increase in the serum level of the acid metabolite of terfenadine and in prolongation of the QT interval which did not lead to any clinically detectable effect. Similar effects have been observed with concomitant administration of astemizole and other macrolides.
Post-marketing reports indicate that co-administration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm, and ischaemia of the extremities and other tissues including the central nervous system.
Concomitant administration of clarithromycin and ergot alkaloids is contraindicated see section 4. When midazolam was co-administered with clarithromycin tablets mg twice dailymidazolam AUC was increased 7-fold after oral administration of midazolam.
Concomitant administration of oral midazolam and clarithromycin is contraindicated. Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated see 4. Reports of rhabdomyolysis have been received for patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment. Caution should be exercised when prescribing clarithromycin with statins.
Effects of Other Medicinal Products on Clarithromycin. Drugs that are inducers of CYP3A e. This may result in sub-therapeutic levels of clarithromycin leading to reduced efficacy. Furthermore, it might be necessary to monitor the plasma levels of the CYP3A inducer, which could be increased owing to the inhibition of CYP3A by clarithromycin see also the relevant product information for the CYP3A4 inhibitor administered.
Concomitant administration of rifabutin and clarithromycin resulted in an increase in rifabutin, and decrease in clarithromycin serum levels together with an increased risk of uveitis.
The following drugs are known or suspected to affect circulating concentrations of clarithromycin; clarithromycin dosage adjustment or consideration of alternative treatments may be required. Strong inducers of the cytochrome P metabolism system such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine may accelerate the metabolism of clarithromycin and thus lower the plasma levels of clarithromycin, while increasing those of OH-clarithromycin, a metabolite that is also microbiologically active.
Since the microbiological activities of clarithromycin and OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers, alginate de sodium инструкция.
Clarithromycin exposure was decreased by etravirine; however, concentrations of the active metabolite, OH-clarithromycin, were increased.
Because OH-clarithromycin has reduced activity against Mycobacterium avium complex MACoverall activity against this pathogen may be altered; therefore alternatives to clarithromycin should be considered for the treatment of MAC. Steady state concentrations of the active metabolite OH-clarithromycin were not significantly affected by concomitant administration of fluconazole. No clarithromycin dose adjustment is necessary. A pharmacokinetic study demonstrated that the concomitant administration of ritonavir mg every eight hours and clarithromycin mg every 12 hours resulted in a marked inhibition of the metabolism of clarithromycin.
An essentially complete inhibition of the formation of OH-clarithromycin was noted. Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. However, for patients with renal impairment, the following dosage adjustments should be considered: Similar dose adjustments should be considered in patients with reduced renal function when ritonavir is used as a pharmacokinetic enhancer with other HIV protease inhibitors including atazanavir and saquinavir see section below, Bi-directional drug interactions.
Effect of Clarithromycin on Other Medicinal Products. Co-administration of clarithromycin, known to inhibit CYP3A, and a drug primarily metabolised by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug. Clarithromycin should be used with caution in patients receiving treatment with other drugs known to be CYP3A enzyme substrates, especially if the CYP3A substrate has a narrow safety margin e.
Dosage adjustments may be considered, and when possible, serum concentrations of drugs primarily metabolised by CYP3A should be monitored closely in patients concurrently receiving clarithromycin.
The following drugs or drug classes are known or suspected to be metabolised by the same CYP3A isozyme: Drugs interacting by similar mechanisms through other isozymes within the cytochrome P system include phenytoin, theophylline and valproate. There have been post-marketed reports of torsades de pointes occurring with the concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QT prolongation during co-administration of clarithromycin with these drugs.
Serum levels of quinidine and disopyramide should be monitored during clarithromycin therapy. There have been post marketing reports of hypoglycemia with the concomitant administration of clarithromycin and disopyramide. Therefore blood glucose levels should be monitored during concomitant administration of clarithromycin and disopyramide.
With certain hypoglycemic drugs such as nateglinide, and repaglinide, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypolgycemia when used concomitantly. Careful monitoring of glucose is recommended. Clarithromycin mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. The mean hour gastric pH value was 5.
Each of these phosphodiesterase inhibitors is metabolised, at least in part, by CYP3A, and CYP3A may be inhibited by concomitantly administered clarithromycin. Co-administration of clarithromycin with sildenafil, tadalafil or vardenafil would likely result in increased phosphodiesterase inhibitor exposure. Reduction of sildenafil, tadalafil and vardenafil dosages should be considered when these drugs are co-administered with clarithromycin. Dose reduction may need to be considered.
The primary route of metabolism for tolterodine is via the 2D6 isoform of cytochrome P CYP2D6. However, in a subset of the population devoid of CYP2D6, the identified pathway of metabolism is via CYP3A.
In this population subset, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. A reduction in tolterodine dosage may be necessary in the presence of CYP3A inhibitors, such as clarithromycin in the CYP2D6 poor metaboliser population. When midazolam was co-administered with clarithromycin tablets mg twice dailymidazolam AUC was increased 2. If intravenous midazolam is co-administered with clarithromycin, the patient must be closely monitored to allow dose adjustment.
Drug delivery of midazolam via oromucosal route, which could bypass pre-systemic elimination of the drug, will likely result in a similar interaction to that observed after intravenous midazolam rather than oral administration. The same precautions should also apply to other benzodiazepines that are metabolised by CYP3A, including triazolam and alprazolam.
For benzodiazepines which are not dependent on CYP3A for their elimination temazepam, nitrazepam, lorazepama clinically important interaction with clarithromycin is unlikely. There have been post-marketing reports of drug interactions and central nervous system CNS effects e.
Monitoring the patient for increased CNS pharmacological effects is suggested. Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein Pgp. Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. Digoxin is thought to be a substrate for the efflux transporter, P-glycoprotein Pgp. Clarithromycin is known to inhibit Pgp.
When clarithromycin and digoxin are administered together, inhibition of Pgp by clarithromycin may lead to increased exposure to digoxin. Elevated digoxin serum concentrations in patients receiving clarithromycin and digoxin concomitantly have also been reported in post marketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Serum digoxin concentrations should be carefully monitored while patients are receiving digoxin and clarithromycin simultaneously.
Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. Because clarithromycin appears to interfere with the absorption of simultaneously administered oral zidovudine, this interaction can be largely avoided by staggering the doses of clarithromycin and zidovudine to allow for a 4-hour interval between each medication.
This interaction does not appear to occur in paediatric HIV-infected patients taking clarithromycin suspension with zidovudine or dideoxyinosine. This interaction is unlikely when clarithromycin is administered via intravenous infusion.
There have been spontaneous or published reports of interactions of CYP3A inhibitors, including clarithromycin with drugs not thought to be metabolised by CYP3A e. Serum level determinations are recommended for these drugs when administered concomitantly with clarithromycin. Increased serum levels have been reported. Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction.
Doses of clarithromycin greater than mg per day should not be co-administered with protease inhibitors. Caution is advised regarding the concomitant administration of clarithromycin and calcium channel blockers metabolized by CYP3A4 e. Plasma concentrations of clarithromycin as well as calcium channel blockers may increase due to the interaction.
Hypotension, bradyarrhythmias and lactic acidosis have been observed in patients taking clarithromycin and verapamil concomitantly. Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, leading to a bidirectional drug interaction. Clarithromycin may increase the plasma levels of itraconazole, while itraconazole may increase the plasma levels of clarithromycin.
Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged pharmacologic effect. Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction.
Observations from drug interaction studies using the soft gelatin capsule formulation may not be representative of the effects seen using the saquinavir hard gelatin capsule. When saquinavir is co-administered with ritonavir, consideration should be given to the potential effects of ritonavir on clarithromycin see section 4. The safety of clarithromycin for use during pregnancy has not been established. Based on variable results obtained from studies in mice, rats, rabbits and monkeys, the possibility of adverse effects on embryofoetal development cannot be excluded.
Therefore, use during pregnancy is not advised without carefully weighing the benefits against risk. The safety of clarithromycin for using during breast-feeding of infants has not been established. Clarithromycin is excreted into human breast milk. There are no data on the effect of clarithromycin on the ability to drive or use machines.
The potential for dizziness, vertigo, confusion and disorientation, which may occur with the medication, should be taken into account before patients drive or use machines. The most frequent and common adverse reactions related to clarithromycin therapy for both adult and paediatric populations are abdominal pain, diarrhoea, nausea, vomiting and taste perversion.
These adverse reactions are usually mild in intensity and are consistent with the known safety profile of macrolide antibiotics see section b of section 4. There was no significant difference in the incidence of these gastrointestinal adverse reactions during clinical trials between the patient population with or without pre-existing mycobacterial infections.
The following table displays adverse reactions reported in clinical trials and from post-marketing experience with clarithromycin immediate-release tablets, granules for oral suspension, powder for solution for injection, extended-release tablets and modified-release tablets. The reactions considered at least possibly related to clarithromycin are displayed by system organ class and frequency using the following convention: Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness when the seriousness could be assessed.
Cellulitis 1candidiasisgastroenteritis 2infection 3vaginal infection. Leukopenia, neutropenia 4thrombocythaemia 3eosinophilia 4. Anaphylactoid reaction 1hypersensitivity.
Anxiety, nervousness 3. Psychotic disorder, confusional state 5depersonalisation, depression, disorientation, hallucination, abnormal dreams, mania. Dysgeusia, headache, taste perversion. Loss of consciousness 1dyskinesia 1dizziness, somnolence 5tremor. Vertigo, hearing impaired, tinnitus. Cardiac arrest 1atrial fibrillation 1electrocardiogram QT prolonged, extrasystoles 1palpitations. Asthma 1epistaxis 2pulmonary embolism 1. Diarrhoea, vomiting, dyspepsia, nausea, abdominal pain.
Oesophagitis 1gastrooesophageal reflux disease 2gastritis, proctalgia 2stomatitis, glossitis, abdominal distension 4constipation, dry mouth, eructation, flatulence. Liver function test abnormal. Cholestasis 4hepatitis 4alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased 4. Dermatitis bullous 1pruritus, urticaria, rash maculo-papular 3. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms DRESSacne.
Muscle spasms 3musculoskeletal stiffness 1myalgia 2. Blood creatinine increased 1blood urea increased 1. Injection site pain 1injection site inflammation 1. Malaise 4pyrexia 3asthenia, chest pain 4chills 4fatigue 4. Albumin globulin ratio abnormal 1blood alkaline phosphatase increased 4blood lactate dehydrogenase increased 4.
Patient exposure is estimated to be greater than 1 billion patient treatment days for clarithromycin. Injection site phlebitis, injection site pain, and injection site inflammation are specific to the clarithromycin intravenous formulation.
In some of the reports of rhabdomyolysis, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol see section 4.
Monitoring the patient for increased CNS pharmacological effects is suggested see section 4. There have been rare reports of clarithromycin ER tablets in the stool, many of which have occurred in patients with anatomic including ileostomy or colostomy or functional gastrointestinal disorders with shortened GI transit times.
In several reports, tablet residues have occurred in the context of diarrhoea. It is recommended that patients who experience tablet residue in the stool and no improvement in their condition should be switched to a different clarithromycin formulation e. Clinical trials have been conducted using clarithromycin paediatric suspension in children 6 months to 12 years of age.
Therefore, children under 12 years of age should use clarithromycin paediatric suspension. Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. In AIDS and other immunocompromised patients treated with the higher doses of clarithromycin over long periods of time for mycobacterial infections, it was often difficult to distinguish adverse events possibly associated with clarithromycin administration from underlying signs of Human Immunodeficiency Virus HIV disease or intercurrent illness.
In adult patients, the most frequently reported adverse reactions by patients treated with total daily doses of mg and mg of clarithromycin were: Additional low-frequency events included dyspnoea, insomnia and dry mouth.
The incidences were comparable for patients treated with mg and mg, but were generally about 3 to 4 times as frequent for those patients who received total daily doses of mg of clarithromycin. In these immunocompromised patients, evaluations of laboratory values were made by analysing those values outside the seriously abnormal level i.
A lower percentage of patients in these two dosage groups also had elevated Blood Urea Nitrogen levels. Slightly higher incidences of abnormal values were noted for patients who received mg daily for all parameters except White Blood Cell.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: Reports indicate that the ingestion of large amounts of clarithromycin can be expected to produce gastro-intestinal symptoms.
One patient who had a history of bipolar disorder ingested 8 grams of clarithromycin and showed altered mental status, paranoid behaviour, hypokalaemia and hypoxaemia. Adverse reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum levels are not expected to be appreciably affected by haemodialysis or peritoneal dialysis.
Clarithromycin is an antibiotic belonging to the macrolide antibiotic group. It exerts its antibacterial action by selectively binding to the 50s ribosomal sub-unit of susceptible bacteria preventing translocation of activitate amino acids.
It inhibits the intracellular protein synthesis of susceptible bacteria. The R -hydroxy metabolite of clarithromycin, a product of parent drug metabolism also has antimicrobial activity. The metabolite is less active than the parent compound for most organisms, including mycobacterium spp.
An exception is Haemophilus influenza where the hydroxy metabolite is two-fold more active than the parent compound. Staphylococcus aureus methicillin susceptible ; Streptococcus pyogenes Group A beta-hemolytic streptococci ; alpha-hemolytic streptococci viridans group ; Streptococcus Diplococcus pneumoniae; Streptococcus agalactiae; Listeria monocytogenes. Haemophilus influenza; Haemophilus parainfluenza; Moraxella Branhamella catarrhalis; Neisseria gonorrhoeae; Legionella pneumophila; Bordetella pertussis; Campylobacter jejuni.
Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae; Mycobacterium kansasii; Mycobacterium chelonae; Mycobacterium fortuitum; Mycobacterium intracellularis; Chlamydia pneumoniae. Clostridium perfringens ; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes. Clarithromycin has bactericidal activity against several bacterial strains. The organisms include Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella Branhamella catarrhalis; Neisseria gonorrhoeae and Campylobacter spp.
The following breakpoints have been established by the European Committee for Antimicrobial Susceptibility Testing EUCAST. The kinetics of orally administered modified-release clarithromycin have been studied in adult humans and compared with clarithromycin mg and mg immediate release tablets. The extent of absorption was found to be equivalent when equal total daily doses were administered. Little or no unpredicted accumulation was found and the metabolic disposition did not change in any species following multiple dosing.
Based upon the finding of equivalent absorption the following in vitro and in vivo data are applicable to the modified-release formulation. Clarithromycin levels in all tissues, except the central nervous system, were several times higher than the circulating drug levels. The highest concentrations were found in the liver and lung tissue, where the tissue to plasma ratios reached 10 to The pharmacokinetic behaviour of clarithromycin is non-linear.
In fed patients given mg clarithromycin modified-release daily, the peak steady state plasma concentration of clarithromycin and 14 hydroxy clarithromycin were 1. When the dosage was increased to mg daily, these steady-state values were 2.
Elimination half-lives of the parent drug and metabolite were approximately 5. The apparent half-lives of both clarithromycin and its hydroxylated metabolite tended to be longer at higher doses. In repeated dose studies, clarithromycin toxicity was related to dose and duration of treatment. The primary target organ was the liver in all species, with hepatic lesions seen after 14 days in dogs and monkeys. No evidence of mutagenic potential of clarithromycin was seen during a range of in vitro and in vivo tests.
Fertility and reproduction studies in rats have shown no adverse effects. Teratogenicity studies in rats Wistar p. No other toxicological findings considered to be of relevance to the dose level recommended for patient treatment have been reported.
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Klaricid XL mg tablets. Patient Information print SPC this link will open a new window Bookmark This Medicine check related medicine report side effect. Find medicines with the same active ingredients Find medicines from the same company. Name of the medicinal product 2. Qualitative and quantitative composition 3. Marketing authorisation holder 8. Marketing authorisation number s 9.
Date of revision of the text. Name of the medicinal product. A yellow, ovaloid tablet containing mg clarithromycin in a modified-release preparation. Klaricid XL mg Tablets are indicated in adults and children 12 years and older.
Upper respiratory tract infections for example, sinusitis and pharyngitis. Children older than 12 years: Do not crush or chew Klaricid XL mg Tablets. Hypersensitivity to macrolide antibiotic drugs or to any of its excipients see section 6. Concomitant administration with ticagrelor or ranolazine is contraindicated. Caution is advised in patients with severe renal insufficiency see section 4.
Prolongation of the QT Interval Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointeshave been seen in treatment with macrolides including clarithromycin see section 4. Excipients Klaricid Modified Release contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take these medicines Klaricid XL mg Tablets contain Cisapride, pimozide, astemizole and terfenadine: Oral Midazolam When midazolam was co-administered with clarithromycin tablets mg twice dailymidazolam AUC was increased 7-fold after oral administration of midazolam.
HMG-CoA Reductase Inhibitors statins Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated see 4. Effects of Other Medicinal Products on Clarithromycin Drugs that are inducers of CYP3A e.
Efavirenz, nevirapine, rifampicin, rifabutin and rifapentine Strong inducers of the cytochrome P metabolism system such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine may accelerate the metabolism of clarithromycin and thus lower the plasma levels of clarithromycin, while increasing those of OH-clarithromycin, a metabolite that is also microbiologically active.
Etravirine Clarithromycin exposure was decreased by etravirine; however, concentrations of the active metabolite, OH-clarithromycin, were increased. Ritonavir A pharmacokinetic study demonstrated that the concomitant administration of ritonavir mg every eight hours and clarithromycin mg every 12 hours resulted in a marked inhibition of the metabolism of clarithromycin.
Effect of Clarithromycin on Other Medicinal Products CYP3A-based interactions Co-administration of clarithromycin, known to inhibit CYP3A, and a drug primarily metabolised by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug. Antiarrhythmics There have been post-marketed reports of torsades de pointes occurring with the concurrent use of clarithromycin and quinidine or disopyramide.
Omeprazole Clarithromycin mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. Sildenafil, tadalafil and vardenafil Each of these phosphodiesterase inhibitors is metabolised, at least in part, by CYP3A, and CYP3A may be inhibited by concomitantly administered clarithromycin.
Tolterodine The primary route of metabolism for tolterodine is via the 2D6 isoform of cytochrome P CYP2D6. Other drug interactions Colchicine Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein Pgp. Digoxin Digoxin is thought to be a substrate for the efflux transporter, P-glycoprotein Pgp.
Zidovudine Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. Phenytoin and Valproate There have been spontaneous or published reports of interactions of CYP3A inhibitors, including clarithromycin with drugs not thought to be metabolised by CYP3A e. Bi-directional drug interactions Atazanavir Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction.
Calcium Channel Blockers Caution is advised regarding the concomitant administration of clarithromycin and calcium channel blockers metabolized by CYP3A4 e. Itraconazole Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, leading to a bidirectional drug interaction. Saquinavir Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction.
Clarithromycin has been shown not to interact with oral contraceptives. Pregnancy The safety of clarithromycin for use during pregnancy has not been established. Breast-feeding The safety of clarithromycin for using during breast-feeding of infants has not been established. Summary of the safety profile The most frequent and common adverse reactions related to clarithromycin therapy for both adult and paediatric populations are abdominal pain, diarrhoea, nausea, vomiting and taste perversion.
Tabulated summary of adverse reactions The following table displays adverse reactions reported in clinical trials and from post-marketing experience with clarithromycin immediate-release tablets, granules for oral suspension, powder for solution for injection, extended-release tablets and modified-release tablets.
Description of selected adverse reactions Injection site phlebitis, injection site pain, and injection site inflammation are specific to the clarithromycin intravenous formulation. Adverse Reactions in Immunocompromised Patients see section e. Paediatric populations Clinical trials have been conducted using clarithromycin paediatric suspension in children 6 months to 12 years of age. Other special populations Immunocompromised patients In AIDS and other immunocompromised patients treated with the higher doses of clarithromycin over long periods of time for mycobacterial infections, it was often difficult to distinguish adverse events possibly associated with clarithromycin administration from underlying signs of Human Immunodeficiency Virus HIV disease or intercurrent illness.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. Antibacterial for systemic use, macrolide ATC-Code: J01FA09 Mode of Action: Clarithromycin is usually active against the following organisms in vitro: Mycoplasma pneumoniae; Ureaplasma urealyticum. Breakpoints The following breakpoints have been established by the European Committee for Antimicrobial Susceptibility Testing EUCAST.
Tablet Core Citric acid Sodium alginate Sodium calcium alginate Lactose Povidone Talc Stearic acid Magnesium stearate Coating Solution Hypromellose Polyethylene glycol Titanium dioxide Quinoline Yellow E aluminium lake Sorbic acid. Not all pack sizes may be marketed. Mylan Products Ltd 20 Station Close Potters Bar Herts EN6 1TL UK. POM - Prescription Only Medicine. Find out more here. Convulsion, ageusia, parosmia, anosmia, paraesthesia. Torsades de pointes, ventricular tachycardia, Ventricular fibrillation.
Respiratory, thoracic and mediastinal disorder. Pancreatitis acute, tongue discolouration, tooth discolouration. Hepatic failure, jaundice hepatocellular. Musculoskeletal and connective tissue disorders. General disorders and administration site conditions. Injection site phlebitis 1. International normalised ratio increased, prothrombin time prolonged, urine colour abnormal. Streptococcus A, B, C and G.
Таблица Международных Непатентованных Наименований Лекарств (МНН)
Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointeshave been seen in treatment with macrolides including clarithromycin see section 4. Ботулинический токсин типа А-гемагглютинин комплекс. Алтея лекарственного de инструкции экстракт. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. Расторопши пятнистой плодов экстракт. Not all pack sizes may be marketed. Цимицифуги кистевидной корневищ экстракт. Clarithromycin may increase the plasma levels of itraconazole, while itraconazole may increase the plasma levels of clarithromycin. Drug delivery of midazolam via oromucosal route, which could bypass pre-systemic elimination of the drug, will likely result in a similar interaction to that observed after intravenous midazolam rather than oral administration.
Reports of rhabdomyolysis have been received for patients taking clarithromycin concomitantly with these statins. Therefore, caution should be exercised in administering this antibiotic to patients with impaired hepatic function. Staphylococcus aureus methicillin susceptible ; Streptococcus pyogenes Group A beta-hemolytic streptococci ; alpha-hemolytic streptococci viridans group ; Streptococcus Diplococcus pneumoniae; Streptococcus agalactiae; Listeria monocytogenes. Convulsion, ageusia, parosmia, anosmia, paraesthesia.
Dose reduction may need to be considered.
Klaricid XL mg tablets - Summary of Product Characteristics (SPC) - (eMC)
Children older than 12 years: Concomitant administration of clarithromycin and any of the following drugs is contraindicated: Omeprazole Clarithromycin mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects.
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms DRESS , acne. Please check that this is the correct company before contacting them. Adverse Reactions in Immunocompromised Patients see section e. Klaricid Modified Release contains lactose. Patients should be monitored for signs and symptoms of myopathy. The extent of absorption was found to be equivalent when equal total daily doses were administered.
The metabolite is less active than the parent compound for most organisms, including mycobacterium spp. Clostridium perfringens ; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes. Рыбий жир из печени тресковых рыб.
Дидецилдиметиламмония бромида клатрат с мочевиной. Clarithromycin should not be given to patients with history of QT prolongation congenital or documented acquired QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes see sections 4. Because clarithromycin appears to interfere with the absorption of simultaneously administered oral zidovudine, this interaction can be largely avoided by staggering the doses of clarithromycin and zidovudine to allow for a 4-hour interval between each medication.
Therefore, use during pregnancy is not advised without carefully weighing the benefits against risk. The physician should not prescribe clarithromycin to pregnant women without carefully weighing the benefits against risk; particularly during the first three months of pregnancy see section 4.
Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C.
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