Klacid Special Precautions

Film-coated tablet and Granules for oral suspension: 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 Use in Pregnancy & Lactation).
Clarithromycin is principally metabolised 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 (see Dosage & Administration).
Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been reported with clarithromycin. This hepatic dysfunction may be severe and is usually reversible. Cases of fatal hepatic failure (see Adverse Reactions) have been reported. 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.
Clostridioides 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. difficile. 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 Interactions). Concomitant administration of clarithromycin and colchicine is contraindicated (see Contraindications).
Caution is advised regarding concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam, and intravenous or oromucosal midazolam (see Interactions).
Cardiovascular Events: Prolongation of the QT interval, reflecting effects on cardiac repolarisation imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in patients treated with macrolides including clarithromycin (see Adverse Reactions). Due to increased risk of QT prolongation and ventricular arrhythmias (including torsades de pointes), the use of clarithromycin is contraindicated in patients taking any of astemizole, cisapride, domperidone, pimozide and terfenadine; in patients who have electrolyte disturbances such as hypomagnesaemia or hypokalaemia; and in patients with a history of QT prolongation or ventricular cardiac arrhythmia (see Contraindications).
Carefully consider the balance of benefits and risks before prescribing clarithromycin for any patients taking hydroxychloroquine or chloroquine, because of the potential for an increased risk of cardiovascular events and cardiovascular mortality (see Interactions).
Furthermore, clarithromycin should be used with caution in the following: Patients with coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia; Patients concomitantly taking other medicinal products associated with QT prolongation other than those which are contraindicated.
Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results. Some observational studies have identified a rare short-term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including clarithromycin. Consideration of these findings should be balanced with treatment benefits when prescribing clarithromycin.
Pneumonia: 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 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.
In the event of severe acute hypersensitivity reactions, such as anaphylaxis, severe cutaneous adverse reactions (SCAR) (e.g. Acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome, toxic epidermal necrolysis and drug rash with eosinophilia and systemic symptoms (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 Interactions).
HMG-CoA Reductase Inhibitors (statins): Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see Contraindications). 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.g. fluvastatin) can be considered (see Interactions).
Oral hypoglycaemic agents/Insulin: The concomitant use of clarithromycin and oral hypoglycaemic agents (such as sulphonylureas) and/or insulin can result in significant hypoglycaemia. Careful monitoring of glucose is recommended (see Interactions).
Oral anticoagulants: 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 Interactions). INR and prothrombin times should be frequently monitored while patients are receiving clarithromycin and oral anticoagulants concurrently.
Caution should be exercised when clarithromycin is co-administered with direct acting oral anticoagulants such as dabigatran, rivaroxaban and apixaban, particularly to patients at high risk of bleeding (see Interactions).
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.
Excipients: Patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrase-isomaltase insufficiency should not take Klacid granules for oral susp 125 mg/5 ml. When prescribing to diabetic patients, the sucrose content should be taken into account.
Film-coated tablet: Use of any antimicrobial therapy, such as clarithromycin, to treat H. pylori infection may select for drug-resistant organisms.
Modified-release tablet: 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 Use in Pregnancy & Lactation).
Patients with hepatic function disorders: Clarithromycin is principally metabolized by the liver. Therefore, caution should be exercised in administering the antibiotic to patients with impaired hepatic function. In patients with suspected hepatic function disorders, the serum concentrations of transaminases (AST, ALT), γ-GT and alkaline phosphatase, as well as serum bilirubin, should be carefully monitored (see Contraindications).
Hepatic function disorders, including elevated liver enzymes values, and hepatocellular damage and/or cholestatic hepatitis with or without jaundice, have been reported in connection with clarithromycin. This hepatic function disorder may be severe but is usually reversible. In some cases, hepatic failure with fatal outcome has been reported, which was associated with serious underlying diseases and/or other hepatotoxic medications. Discontinue using clarithromycin immediately if signs and symptoms of hepatitis such as anorexia, jaundice, dark urine, pruritus, or tender abdomen occur.
Patients with renal function disorders: Caution is advised in patients with severe renal impairment. If severe renal impairment exists (creatinine clearance <30 ml/min), this medicinal product should be used only under close medical supervision (see Dosage & Administration).
When taking other macrolide antibiotics as well as lincomycin and clindamycin: Attention should be paid to the possibility of cross-resistance of pathogens to clarithromycin and other macrolide antibiotics (e.g. erythromycin), as well as lincomycin and clindamycin. Concomitant administration of several preparations from this substance group therefore seems inadvisable.
Colchicine: There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly. Some of the colchicine toxicity occurred in patients with renal function disorders. Deaths have been reported in some of such patients (see Interactions). Concomitant administration of clarithromycin and colchicine is contraindicated (see Contraindications).
Caution is advised regarding concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam, and intravenous or oromucosal midazolam (see Interactions).
Cardiovascular events: Prolongation of the QT interval has been observed in patients treated with macrolides including clarithromycin, which reflects cardiac repolarization. This is associated with the risk of developing cardiac arrhythmia and torsades de pointes (see Adverse Reactions). Given the increased risk of prolongation of QT intervals and ventricular arrhythmias (including torsade de pointes), clarithromycin is contraindicated in patients taking astemizole, cisapride, domperidone, pimozide and terfenadine, in patients with hypokalaemia and in those with a history of prolongation of the QT interval or ventricular arrhythmia (see Contraindications).
Clarithromycin should be used with caution in the following patients: Patients with coronary artery disease, severe cardiac insufficiency, conduction disturbances or clinically relevant bradycardia; Patients with hypomagnesaemia; Patients concomitantly taking other medicinal products which prolong the QT interval and are contraindicated as such.
Epidemiological studies to assess the risk of adverse cardiovascular reactions following administration of macrolides have highlighted various results. A rare, short-term risk of arrhythmias, myocardial infarction and cardiovascular mortality has been noted during some observational studies following administration of macrolides including clarithromycin. These correlations should be considered in the benefit-risk context when prescribing clarithromycin.
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 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. because of allergies), other antibiotics, such as clindamycin, may be the drugs 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 cases where penicillin treatment cannot be used.
In the case of severe acute hypersensitivity reactions, such as anaphylaxis, severe cutaneous adverse reactions (SCAR) (e.g. acute generalized exanthematous pustulosis [AGEP], Stevens-Johnson Syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms [DRESS syndrome], clarithromycin treatment should be discontinued immediately and appropriate treatment should be urgently initiated.
Persistent and severe diarrhoea and colic: Like almost all antibacterial agents including macrolides, pseudomembranous colitis has been reported, which may range from mild to life-threatening. Clostridium difficile-associated diarrhoea (CDAD) has been reported with use of nearly all antibiotics, including clarithromycin, which can occur in the form of mild diarrhoea progressing to fatal colitis. Treatment with antibiotics alters the normal flora of the colon, which may lead to overgrowth of C. difficile. Therefore, in patients with diarrhoea which occurred during or following therapy with antibacterial agents, CDAD must be considered. CDAD may also occur 2 months after the end of the therapy. A careful medical history is therefore necessary.
Depending on the indication, discontinuation of Klacid MR therapy should be considered and, if necessary, appropriate treatment should be initiated immediately (e.g. appropriate antibiotics/chemotherapeutic agents, the clinical efficacy of which has been established in these indications). Drugs that inhibit peristalsis should not be used.
Long-term use may, as with other antibiotics, result in colonization with non-susceptible bacteria and fungi. If a superinfection occurs, appropriate therapy should be instituted.
Clarithromycin should be used with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme (see Interactions).
Oral antidiabetic agents/Insulin: Concomitant administration of clarithromycin and oral hypoglycemic agents (such as sulphonylureas) and/or insulin can result in significant hypoglycemia. Careful monitoring of blood glucose level is recommended (see Interactions).
Oral Anticoagulants: There is a risk of serious hemorrhage and significant elevations of the INR values and prothrombin time when clarithromycin is co-administered with warfarin. INR and prothrombin times should be regularly monitored while patients are taking clarithromycin and oral anticoagulants concurrently.
HMG-CoA Reductase Inhibitors (statins): Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated (see Contraindications). Caution should be exercised when prescribing clarithromycin with statins at the same time. Rhabdomyolysis have been reported in patients taking clarithromycin and statins concomitantly. Patients should be monitored for signs and symptoms of myopathy.
In cases where the concomitant use of clarithromycin with statins cannot be avoided, it is recommended to prescribe the lowest permitted dose of the statin. Use of another statin that is not dependent on CYP3A metabolism (e.g. fluvastatin) can be considered (see Interactions).
Patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose-malabsorption should not take Klacid MR.
Effects on ability to drive and use machines: 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.