Klaz 250/Klaz Suspension

Klaz 250/Klaz Suspension

clarithromycin

Manufacturer:

Amherst Lab

Distributor:

Pediatrica
Full Prescribing Info
Contents
Clarithromycin.
Description
Klaz 250: Each film-coated tablet contains: Clarithromycin 250 mg.
Klaz Suspension: After reconstitution, each 5 mL suspension contains: Clarithromycin 125 mg or 250 mg.
Action
Pharmacology: Pharmacodynamics: Clarithromycin, a semi-synthetic 14-membered ring macrolide, exerts its antibacterial activity by binding to the donor site on the 50s subunit of the bacterial ribosome thus inhibiting protein synthesis. Like other macrolides, clarithromycin penetrates intracellularly and is highly concentrated in the polymorphonuclear leukocytes and tissue macrophages. There is no evidence, however, that clarithromycin has in vivo pharmacologic effect on mammalian cells.
Pharmacokinetics: Film-coated Tablet and Suspension: Clarithromycin is rapidly absorbed and reaches peak serum concentrations approximately 2 hours after oral administration.
Clarithromycin has non-linear, dose-dependent pharmacokinetics due to saturation of metabolic pathways. This nonlinearity is minimal with usual dosages (250 to 500 mg every 8 to 12 hours) but increases disproportionately with single high doses (e.g., 1.2 g) or with multiple clarithromycin doses.
Food delays the onset of clarithromycin absorption and increases peak time (tmax) from 2 to 2.5 hours; the extent of absorption is unaffected.
Administration of a 250 mg clarithromycin dose, either as tablet or suspension to fasting healthy adults, results in average peak serum clarithromycin concentration (Cmax) of 0.6 mcg/mL reached within 1 to 4 hours. After oral administration of clarithromycin 250 mg tablet every 12 hours or clarithromycin 500 mg tablet every 8 to 12 hours, peak steady-state clarithromycin concentrations were achieved within 3 days and averaged about 1 to 2 or 3 to 4 mcg/mL, respectively, while peak steady-state 14-hydroxy (OH) clarithromycin concentrations were achieved within 3 to 4 days and averaged about 0.6 to 1 mcg/mL for both doses. The active metabolite of clarithromycin is 14-hydroxy (OH) clarithromycin.
The overall bioavailability of clarithromycin suspension was equivalent to or slightly greater than the tablet in a single 250 mg dose study in adults. Administration of clarithromycin suspension with food led to a slight delay in the onset of absorption but did not affect the overall bioavailability of clarithromycin. The Cmax, area under the plasma concentration time curve (AUC), and half-life (t1/2) for clarithromycin suspension (non-fasted state) were 0.95 mcg/mL, 6.5 mcg.hr/mL, and 3.7 hours, respectively, and for clarithromycin tablet (fasted state) were 1.1 mcg/mL, 6.3 mcg.hr/mL, and 3.3 hours, respectively.
In a single-dose study in children under fed conditions, clarithromycin suspension 7.5 mg/kg resulted in an increase in Cmax from 3.6 ± 1.5 mcg/mL to 4.6 ± 2.8 mcg/mL and the AUC from 10 ± 5.5 mcg.hr/mL to 14.2 ± 9.4 mcg.hr/mL.
In a multiple dose study in adults, administration of clarithromycin suspension 250 mg every 12 hours resulted in steady state after the fifth dose: Cmax 1.98 mcg/mL, AUC 11.5 mcg.hr/mL, tmax 2.8 hours and t1/2 3.2 hours for clarithromycin, and 0.67 mcg/mL, 5.33 mcg.hr/mL, 2.9 hours and 4.9 hours, respectively, for 14-OH clarithromycin. When a similar formulation was administered in children requiring oral antibiotic treatment, steady-state pharmacokinetic parameters reached after the ninth dose on treatment day 5 were: Cmax 4.6 mcg/mL, AUC 15.7 mcg.hr/mL, tmax 2.8 hours and t1/2 2.2 hours for clarithromycin, and 1.64 mcg/mL, 6.69 mcg.hr/mL, 2.7 hours and 4.3 hours, respectively, for 14-OH clarithromycin.
Data on the penetration of clarithromycin into the middle ear fluid in patients with secretory otitis media were obtained in a study in children receiving clarithromycin 7.5 mg/kg every 12 hours. The mean concentrations of clarithromycin and 14-OH clarithromycin in the middle ear fluid were 2.53 mcg/mL and 1.27 mcg/mL, respectively. These concentrations were generally twice as high as the corresponding concentrations in serum (i.e., 1.7 mcg/mL for clarithromycin and 0.8 mcg/mL for 14-OH clarithromycin).
Clarithromycin and 14-OH clarithromycin are distributed into most body tissues and fluids including lung, tonsil and nasal tissues. Tissue concentrations are higher than serum concentrations because of the drug's high intracellular concentrations. Clarithromycin is also distributed into the cerebrospinal fluid after oral administration but there is no evidence regarding its use in the treatment of meningitis.
At usual therapeutic concentrations, clarithromycin's protein binding is approximately 42% to 72%. It has a high affinity for α1-glycoprotein.
Clarithromycin's t1/2 after a 250 mg dose as conventional tablet given twice a day is about 3 to 4 hours; the t1/2 is 5 to 7 hours with 500 mg twice a day. The elimination t1/2 at steady-state is similar with equivalent clarithromycin doses as tablet or oral suspension. The t1/2 of clarithromycin ER tablet was 6.64 hours.
Clarithromycin is metabolized primarily in the liver via the cytochrome P450 3A (CYP3A) isoenzyme. Although seven metabolites of clarithromycin have been identified, 14-OH clarithromycin is the principal metabolite in the serum and is the only one with substantial antibacterial activity.
About 20-30%, or 40% of a given clarithromycin dose is excreted unchanged in the urine within 12 hours after administration of clarithromycin 250 mg or 500 mg tablet, or 250 mg (125 mg/5 mL) suspension every 12 h ours, respectively. Urinary excretion of clarithromycin ER accounts for about 40% of the clarithromycin dose. Fecal elimination accounts for approximately 30%.
Extended-release Tablet: Administration of clarithromycin extended-release (ER) tablets provides extended absorption of clarithromycin from the gastrointestinal (GI) tract. Although the 24-hour AUCs for clarithromycin and 14-OH clarithromycin following administration of clarithromycin ER tablets are equivalent to the 24-hour AUCs of an equal total daily dose as clarithromycin tablets, clarithromycin ER tablets result in lower and later Cmax of clarithromycin and 14-OH clarithromycin. While the extent of formation of 14-OH clarithromycin following oral administration of clarithromycin 500 mg ER tablets is not affected by food, administration under fasting conditions is associated with approximately 30% lower clarithromycin AUC. Therefore, clarithromycin ER tablets should be taken with meals.
In healthy human subjects under fed conditions, the mean Cmax of 1.797 mcg/mL was achieved 5.58 hours (tmax) following oral administration of clarithromycin 500 mg ER tablet once a day for five consecutive days. The AUC (0-τ) was 20.406 mcg.hr/mL and the AUC(0-∞) was 22.214 mcg.hr/mL.
Clarithromycin and 14-OH clarithromycin are distributed into most body tissues and fluids including lung, tonsil and nasal tissues. Tissue concentrations are higher than serum concentrations because of the drug's high intracellular concentrations. Clarithromycin is also distributed into the cerebrospinal fluid after oral administration but there is no evidence regarding its use in the treatment of meningitis.
At usual therapeutic concentrations, clarithromycin's protein binding is approximately 42% to 72%. It has a high affinity for α1-glycoprotein.
Clarithromycin's t1/2 after a 250 mg dose as conventional tablet given twice a day is about 3 to 4 hours; the t1/2 is 5 to 7 hours with 500 mg twice a day. The elimination t1/2 at steady-state is similar with equivalent clarithromycin doses as tablet or oral suspension. The t1/2 of clarithromycin ER tablet was 6.64 hours.
Clarithromycin is metabolized primarily in the liver via the cytochrome P450 3A (CYP3A) isoenzyme. Although seven metabolites of clarithromycin have been identified, 14-OH clarithromycin is the principal metabolite in the serum and is the only one with substantial antibacterial activity.
About 20-30%, or 40% of a given clarithromycin dose is excreted unchanged in the urine within 12 hours after administration of clarithromycin 250 mg or 500 mg tablet, or 250 mg (125 mg/5 mL) suspension every 12 hours, respectively. Urinary excretion of clarithromycin ER accounts for about 40% of the clarithromycin dose. Fecal elimination accounts for approximately 30%.
Microbiology: Antimicrobial Spectrum of Activity: Clarithromycin has demonstrated activity in vitro and in clinical infections against most strains of the following microorganisms: See Table 1.

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Beta-lactamases have no effect on clarithromycin activity.
Most strains of methicillin-resistant and oxacillin-resistant staphylococci are resistant to clarithromycin.
Omeprazole/clarithromycin dual therapy, ranitidine bismuth citrate/clarithromycin dual therapy, omeprazole/clarithromycin/amoxicillin triple therapy and lansoprazole/clarithromycin/amoxicillin triple therapy have been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections.
Clarithromycin has demonstrated in vitro activity against most strains of the following microorganisms; however, clinical significance is unknown: See Table 2.

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It is suggested to carry out susceptibility tests.
Indications/Uses
For the treatment of the following infections caused by susceptible microorganisms: Upper respiratory tract infections including streptococcal pharyngitis and tonsillitis, acute maxillary sinusitis, and acute otitis media.
Lower respiratory tract infections including bronchitis and pneumonia.
Uncomplicated skin and skin structure infections including impetigo, folliculitis, cellulitis, abscesses (usually require surgical drainage).
Disseminated or localized mycobacterial infections due to Mycobacterium avium or Mycobacterium intracellulare. Localized infections due to Mycobacterium kansasii, Mycobacterium chelonae and Mycobacterium fortuitum (usually in combination with other antimicrobial agents).
Helicobacter pylori infections (in combination with other drugs).
Odontogenic infections.
Prevention of disseminated Mycobacterium avium complex (MAC) infection in patients with advanced HIV infection.
Dosage/Direction for Use
Clarithromycin Tablet: Usual Adult Dose: 250 mg to 500 mg (with or without food) every 12 hours for 5 to 14 days.
In Children ≥12 years old (who can swallow tablets whole): Follow adult dosing: See Table 3.

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Clarithromycin Suspension: Clarithromycin suspension may be given with or without food, or with milk. (See Table 4.)

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 *Clarithromycin should be used in combination with other antimycobacterial drugs.
Dosage in Patients with Renal Impairment (with creatinine clearance <30 mL/min): See Table 5.

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Dosage in Patients with Hepatic Impairment: No dosage adjustment necessary.
Or, as prescribed by a physician.
Overdosage
Clinical features of clarithromycin overdosage may include GI symptoms such as abdominal pain, nausea, vomiting, and diarrhea. One patient who had a history of bipolar disorder ingested 8 g of clarithromycin and showed altered mental status, paranoid behavior, hypokalemia and hypoxemia.
Adverse reactions accompanying overdosage should be treated promptly by elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum concentrations are not expected to be appreciably removed by hemodialysis or peritoneal dialysis.
Contraindications
Known hypersensitivity to clarithromycin, erythromycin or any macrolide antibiotic, or to any component of the product.
Patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin.
Patients with a history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes.
Concomitant administration with cisapride, pimozide, astemizole, terfenadine, and ergotamine or dihydroergotamine which may result in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) leading to death.
Concomitant administration with simvastatin or lovastatin.
Concomitant administration with ticagrelor or ranolazine.
Concomitant administration of clarithromycin and colchicine in patients with renal or hepatic impairment.
Warnings
Clarithromycin should not be used in pregnant women except where no alternative therapy is appropriate, particularly during the first trimester of pregnancy. If the patient becomes pregnant while receiving clarithromycin, the patient should be informed of the potential hazard to the fetus (see Use in Pregnancy & Lactation).
The concomitant use of clarithromycin and drugs metabolized by CYP3A and/or transported by P-glycoprotein (P-gp) may result in significant safety concerns (see Interactions).
Special Precautions
Acute Hypersensitivity Reactions: In the event of severe acute hypersensitivity reactions, such as anaphylaxis, severe cutaneous adverse reactions (SCAR) [e.g., acute generalized exanthematous pustulosis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS)], and Henoch-Schönlein purpura, clarithromycin treatment should be discontinued immediately and appropriate therapy be instituted.
Serious hypersensitivity reactions may require immediate emergency treatment including epinephrine, antihistamines or corticosteroids.
QT Prolongation: Clarithromycin has been associated with QT interval prolongation and infrequent cases of arrhythmia including torsades de pointes. Fatalities have been reported. Due to the risk of QT prolongation, clarithromycin should be avoided in patients with ongoing proarrhythmic conditions such as coronary artery disease, uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving class I (quinidine, procainamide) or class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval.
Hepatotoxicity: Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis (with or without jaundice), has been reported with clarithromycin. The hepatic impairment may be severe and is usually reversible. In some cases, hepatic failure resulting in death has been reported and generally has been associated with serious underlying illnesses and/or concomitant medications.
Clarithromycin should be discontinued immediately if signs and symptoms of hepatitis occur, such as anorexia, jaundice, dark urine, pruritus, or tender abdomen.
Use of Clarithromycin with Other Drugs: Use of Clarithromycin with other drugs may lead to drug-drug interactions.
Atypical Antipsychotics (quetiapine): Due to inhibition of CYP3A by clarithromycin, concomitant use of clarithromycin with quetiapine results in increased quetiapine concentrations. Serious and life-threatening adverse reactions, including malignant neuroleptic syndrome, have been reported. Clarithromycin should not be used in combination with quetiapine unless clinically necessary (see Interactions). Monitoring and dose reductions may be required.
Oral Hypoglycemic Agents/Insulin: The concomitant use of clarithromycin and oral hypoglycemic agents (such as sulfonylureas) and/or insulin can result in significant hypoglycemia. Careful monitoring of glucose is recommended (see Interactions).
Oral Anticoagulants: There is a risk of serious hemorrhage and significant elevations in International Normalized Ratio (INR) and prothrombin time when clarithromycin is concomitantly used with warfarin. INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concomitantly (see Interactions).
HMG-CoA Reductase Inhibitors: Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see Contraindications). Caution should be exercise 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.g., fluvastatin) can be considered (see Interactions).
Triazolobenzodiazepines and Related Benzodiazepines: Caution is advised regarding the concomitant administration of clarithromycin with triazolobenzodiazepines (such as triazolam and alprazolam), or with other benzodiazopenes (such as intravenous midazolam) due to increased risk of central nervous system (CNS) effects (e.g., somnolence and confusion) (see Interactions).
Calcium Channel Blockers: Caution is advised regarding the concomitant administration of clarithromycin and calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine) due to risk of hypotension and acute kidney injury. Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older. Use clarithromycin with caution when administered concomitantly with medications that induce the cytochrome CYP3A4 enzyme (see Interactions).
Colchicine Toxicity: 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 Interactions).
All-Cause Mortality in Patients With Coronary Artery Disease 1 to 10 Years After Clarithromycin: In one clinical trial evaluating treatment with clarithromycin on outcomes in patients with coronary artery disease, an increase in risk of all-cause mortality one year or more after the end of treatment was observed in patients randomized to receive clarithromycin. Clarithromycin for treatment of coronary artery disease is not an approved indication. The cause of the increased risk has not been established. Other epidemiologic studies evaluating this risk have shown variable results. Consider balancing this potential risk with treatment benefits when prescribing clarithromycin in patients who have suspected or confirmed coronary artery disease.
Clostridium difficile-associated diarrhea (CDAD): This has been reported with the use of nearly all antibacterial agents, including clarithromycin, and may range in severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients who present with diarrhea following administration of antibacterial agents.
Myasthenia Gravis: Exacerbation of symptoms of myasthenia gravis and new onset of myasthenic syndrome has been reported in patients receiving clarithromycin.
Patients Infected with Human Immunodeficiency Virus (HIV): Several studies of HIV-positive patients receiving clarithromycin for treatment of MAC infection have shown poorer survival in those patients randomized to receive doses higher than 500 mg twice a day. The explanation for these results has not been determined. Treatment or prophylaxis of MAC infection with clarithromycin should not exceed the approved dose of 500 mg twice a day.
Skin and soft tissue infections of mild to moderate severity: These infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes, both 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.g., allergy), other antibiotics, such as clindamycin, may be the drug of first choice. Currently, macrolides are only considered to play a role in some skin and soft tissue infections, such as those caused by Corynebacterium minutissimum, acne vulgaris, and erysipelas and in situations where penicillin treatment cannot be used.
Pneumonia: In view of the emerging resistance of Streptococcus pneumoniae to macrolides, it is important that susceptibility testing be performed when prescribing clarithromycin for community-acquired pneumonia. In hospital-acquired pneumonia, clarithromycin should be used in combination with additional appropriate antibiotics.
Other Precautions: Use with caution in patients receiving other ototoxic drugs, especially aminoglycosides. Monitoring of vestibular and auditory function should be carried out during and after treatment.
There is a possibility of cross resistance between clarithromycin and other macrolides, as well as lincomycin and clindamycin.
For the eradication of Helicobacter pylori, clarithromycin and amoxicillin should not be administered to patients with renal impairment since the appropriate dosage in this patient population has not yet been established.
Clarithromycin in combination with ranitidine bismuth citrate should not be used in patients with creatinine clearance <25 mL/minute and in those with a history of acute porphyria.
Prescribing clarithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to be beneficial to the patient and increases the risk of the development of drug-resistant microorganisms.
As with other antibacterial drugs, long term or repeated use may result in overgrowth of non-susceptible organisms, including fungi. Use of any antimicrobial therapy, such as clarithromycin, to treat Helicobacter pylori infection may select for drug-resistant organisms.
Effects on the Ability to Drive and 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.
Hepatic Impairment: Formation of 14-OH clarithromycin is reduced in patients with moderate to severe hepatic impairment. However, there is also increased renal clearance of the parent drug that dosage adjustment might not be necessary unless renal function is also impaired.
Renal Impairment: Clarithromycin's serum t1/2 is prolonged in patients with impaired renal function and dosage should be adjusted as necessary.
In general, clarithromycin may be used without dosage adjustment in patients with hepatic impairment and normal renal function. However, in patients with creatinine clearances <30 mL/min with or without hepatic impairment, dosage reduction or prolongation of dosing intervals for clarithromycin may be necessary.
Use in Children: The safety and efficacy of clarithromycin in pediatric patients under 6 months old have not been established. The safety of clarithromycin in children younger than 20 months old with Mycobacterium avium complex infection has not been established.
Use in Elderly: Peak serum concentrations and AUCs of clarithromycin and 14-OH clarithromycin may be increased in elderly patients 65 to 81 years old. This may be due to age-related decrease in renal function. However, increased incidence of adverse event reported in this age group has not been seen in clinical studies. Dosage modification may be required for elderly patients with severe renal impairment.
Elderly patients may be more susceptible to development of torsades de pointes arrhythmias that younger patients.
Use in Pregnancy: Clarithromycin has been associated with adverse effects of pregnancy outcome and/or embryo-fetal development in animals at doses that produced plasma levels 2 to 17 times those achieved with the maximum recommended human doses (see Use in Pregnancy & Lactation).
Use In Pregnancy & Lactation
Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. The benefits against risk, particularly during the first trimester of pregnancy should be carefully weighed by a physician.
500 mg-1000 mg/kg/day dosing: Four studies in mice revealed a variable incidence of cleft palate after oral doses of 1000 mg/kg/day during gestation days 6 to 15. Cleft palate was also seen at 500 mg/kg/day. The 1000 mg/kg/day exposure resulted in plasma levels 17 times the human serum levels. In monkeys, an oral dose of 70 mg/kg/day produced fetal growth retardation at plasma levels 2 times the human serum levels.
125 mg-160 mg/kg/day dosing: Four teratogenicity studies in rats (oral and IV doses up to 160 mg/kg/day administered during the period of major organogenesis) and two in rabbits (at oral doses up to 125 mg/kg/day or IV doses of 30 mg/kg/day administered during gestation days 6 to 18) failed to demonstrate any teratogenicity from clarithromycin. Two additional oral studies in a different rat strain at similar doses and similar conditions demonstrated a low incidence of cardiovascular anomalies at doses of 150 mg/kg/day administered during gestation days 6 to 15. Plasma levels after 150 mg/kg/day were 2 times the human serum levels.
Embryonic loss has been seen in monkeys and rabbits.
Lactation: Since clarithromycin is distributed in human milk, caution should be exercised when the drug is given to breastfeeding women.
Adverse Reactions
The most common adverse events reported with clarithromycin treatment include diarrhea, nausea, vomiting, abnormal taste, dyspepsia, abdominal pain/discomfort, rash and headache. Most of these effects were mild or moderate in severity.
Infections and infestations: Candidiasis, cellulitis, erysipelas, erythrasma, infection, pseudomembranous colitis, rhinitis, vaginal candidiasis, vaginal infection.
Blood and lymphatic system disorders: Anemia, agranulocytosis, eosinophilia, leukopenia, neutropenia, thrombocythemia, thrombocytopenia.
Immune system disorders: Anaphylactic reaction, anaphylactoid reaction, anaphylaxis, angioedema, hypersensitivity, myasthenia gravis.
Metabolism and nutrition disorders: Anorexia, decreased appetite, hypoglycemia.
Psychiatric disorders: Abnormal behavior, acute psychosis, anxiety, behavioral changes, confusion, confusional state, depersonalization, depression, disorientation, hallucination, insomnia, nervousness, mania/manic behavior, nightmare, psychotic behavior/disorder, psychosis, screaming.
Nervous system disorders: Abnormal dreams, ageusia, alteration of sense of smell, anosmia, convulsion, dizziness, dysgeusia, dyskinesia, loss of consciousness, nervousness, paresthesia, parosmia, somnolence, taste perversion, tremor.
Eye disorders: Conjuctivitis, corneal opacities, photophobia, visual disturbance.
Ear and labyrinth disorders: Deafness, ear disorder, hearing loss, hearing impaired, tinnitus, vertigo.
Cardiac disorders: Atrial fibrillation, cardiac arrest, electrocardiogram QT prolonged, extrasystoles, palpitations, torsades de pointes, ventricular arrhythmia/fibrillation/tachycardia.
Vascular disorders: Hemorrhage, vasodilation.
Respiratory, thoracic and mediastinal disorders: Asthma, cough, dyspnea, epistaxis, pharyngitis, pulmonary embolism.
Gastrointestinal disorders: Abdominal distention/pain, constipation, dark stools, dry mouth/thirst, eructation, esophagitis, flatulence, gastritis, gastroenteritis, gastrointestinal disorder, gastroesophageal reflux disease, glossitis, laryngiusmus, oral candidiasis/moniliasis, pancreatitis, proctalgia, rectal itching, stomatitis, tongue/tooth discoloration.
Hepatobiliary disorders: Cholestasis, jaundice (cholestatic and hepatocellular), hepatic failure, hepatic function abnormal, hepatitis, hepatitis cholestatic, hepatomegaly, liver function test abnormal.
Skin and subcutaneous tissue disorders: Acne, acute generalized exanthematous pustulosis, dermatitis, dermatitis bullous, diaper rash, drug rash with eosinophilia and systemic symptoms (DRESS), fixed drug eruption, Henoch-Schönlein purpura, hyperhidrosis, leukocytoclastic vasculitis, maculopapular rash, pruritus, purpuric rash, severe cutaneous adverse reactions (SCAR), Stevens-Johnson syndrome, toxic epidermal necrosis, urticaria.
Musculoskeletal and connective tissue disorder: Back pain, muscle spasms, musculoskeletal stiffness, myalgia, myopathy, nuchal rigidity, rhabdomyolysis.
Renal and urinary disorders: Hematuria, interstitial nephritis, renal failure.
Reproductive system and breast disorders: Dysmenorrhea.
General disorders and administration site conditions: Asthenia, chest pain, chills, fatigue, influenza, malaise, pain, pyrexia.
Investigations: Alanine aminotransferase increased, albumin globulin ratio abnormal, amylase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, blood bilirubin increased, blood creatinine increased, blood urea increased, gamma-glutamyltransferase increased, hemoglobin decreased, international normalized ratio (INR) increased, liver enzymes increased, liver function test abnormal, platelet count decreased, prothrombin time prolonged, urine color abnormal, white blood cell count decreased.
Clinical Trials Experience: All-Cause Mortality in Patients with Coronary Artery Disease 1 to 10 Years Following Clarithromycin Exposure: In one clinical trial evaluating treatment with clarithromycin on outcomes in patients with coronary artery disease, an increase in risk of all-cause mortality was observed in patients randomized to clarithromycin. Clarithromycin for treatment of coronary artery disease is not an approved indication. Patients were treated with clarithromycin or placebo for 14 days and observed for primary outcome events (e.g., all-cause mortality or non-fatal cardiac events) for several years. A numerically higher number of primary outcome events in patients randomized to receive clarithromycin was observed with a hazard ratio of 1.06 (95% confidence interval 0.98 to 1.14). However, at follow-up 10 years post-treatment, there were 866 (40%) deaths in the clarithromycin group and 815 (37%) deaths in the placebo group that represented a hazard ratio for all-cause mortality of 1.10 (95% confidence interval 1.00 to 1.21). The difference in the number of deaths emerged after one year or more after the end of treatment. The cause of the difference in all-cause mortality has not been established. Other epidemiologic studies evaluating this risk have shown variable results (see Precautions).
Drug Interactions
Potentially Hazardous Interactions: Like erythromycin, concurrent use of clarithromycin with drugs metabolized by the cytochrome P-450 system may be associated with elevated serum levels of these drugs. The table as follows describes some of these interactions: See Table 6.

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Interference with Laboratory Tests: Interactions with laboratory tests have not been established.
Caution For Usage
Directions for Reconstitution: See Table 7.

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Storage
Store at temperatures not exceeding 25°C: Clarithromycin (Klaz) 125 mg/5 mL Powder for Suspension, 250 mg/5 mL Granules for Suspension.
Store at temperatures not exceeding 30°C: Clarithromycin (Klaz) 250 mg Tablet.
MIMS Class
ATC Classification
J01FA09 - clarithromycin ; Belongs to the class of macrolides. Used in the systemic treatment of infections.
Presentation/Packing
Klaz 250: FC tab 250 mg (yellow, elliptical-shaped, plain on both sides) x 50's.
Klaz Suspension: Oral susp (white to off-white granules containing granular, red-colored strawberry-flavored specks for reconstitution into a pink, slightly viscous suspension with strawberry odor and flavor) 125 mg/5 mL x 35 mL, 70 mL. 250 mg/5 mL x 35 mL, 70 mL.
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