Clarithromycin Stella Adverse Reactions

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. These adverse reactions are usually mild in intensity and are consistent with the known safety profile of macrolide antibiotics.
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.
Tabulated summary of adverse reactions: The reactions considered at least possibly related to clarithromycin are displayed by system organ class and frequency using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and not known* (adverse reactions from post-marketing experience; cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness when the seriousness could be assessed.
* Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Patient exposure is estimated to be greater than 1 billion patient treatment days for clarithromycin.
Infections and infestations: Uncommon: Candidiasis, vaginal infection.
Not known: Pseudomembranous colitis, erysipelas.
Blood and lymphatic system: Uncommon: Leukopenia, neutropenia, eosinophilia.
Not known: Agranulocytosis, thrombocytopenia.
Immune system disorders: Uncommon: Hypersensitivity.
Not known: Anaphylactic reaction, angioedema.
Metabolism and nutrition disorders: Uncommon: Anorexia, decreased appetite.
Psychiatric disorders: Common: Insomnia.
Uncommon: Anxiety.
Not known: Psychotic disorder, confusional state, depersonalisation, depression, disorientation, hallucination, abnormal dreams, mania.
Nervous system disorders: Common: Dysgeusia, headache, taste perversion.
Uncommon: Dizziness, somnolence, tremor.
Not known: Convulsion, ageusia, parosmia, anosmia, paraesthesia.
Ear and labyrinth disorders: Uncommon: Vertigo, hearing impaired, tinnitus.
Not known: Deafness.
Cardiac disorders: Uncommon: Electrocardiogram QT prolonged, palpitations.
Not known: Torsades de pointes, ventricular tachycardia, ventricular fibrillation.
Vascular disorders: Not known: Haemorrhage.
Gastrointestinal disorders: Common: Diarrhoea, vomiting, dyspepsia, nausea, abdominal pain.
Uncommon: Gastritis, stomatitis, glossitis, abdominal distension, constipation, dry mouth, eructation, flatulence.
Not known: Pancreatitis acute, tongue discolouration, tooth discolouration.
Hepatobiliary disorders: Common: Liver function test abnormal.
Uncommon: Cholestasis, hepatitis, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased.
Not known: Hepatic failure, jaundice hepatocellular.
Skin and subcutaneous tissue disorders: Common: Rash, hyperhidrosis.
Uncommon: Pruritus, urticaria.
Not known: Severe cutaneous adverse reactions (SCAR) (e.g. Acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), acne).
Musculoskeletal and connective tissue disorders: Not known: Rhabdomyolysis, myopathy.
Renal and urinary disorders: Not known: Renal failure, nephritis interstitial.
General disorders and administration site conditions: Uncommon: Malaise, asthenia, chest pain, chills, fatigue.
Investigations: Uncommon: Blood alkaline phosphatase increased, blood lactate dehydrogenase increased.
Not known: International normalised ratio increased, prothrombin time prolonged, urine color abnormal.
Description of selected adverse reactions: In some of the reports of rhabdomyolysis, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol.
There have been post-marketing reports of drug interactions and central nervous system (CNS) effects (e.g. somnolence and confusion) with the concomitant use of clarithromycin and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested.
Special population: 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.
In adult patients, the most frequently reported adverse reactions by patients treated with total daily doses of 1000 mg and 2000 mg of clarithromycin were: nausea, vomiting, taste perversion, abdominal pain, diarrhoea, rash, flatulence, headache, constipation, hearing disturbance, Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvate Transaminase (SGPT) elevations. Additional low-frequency events included dyspnoea, insomnia and dry mouth. The incidences were comparable for patients treated with 1000 mg and 2000 mg, but were generally about 3 to 4 times as frequent for those patients who received total daily doses of 4000 mg of clarithromycin.
In these immunocompromised patients, evaluations of laboratory values were made by analysing those values outside the seriously abnormal level (i.e. the extreme high or low limit) for the specified test. On the basis of these criteria, about 2% to 3% of those patients who received 1000 mg or 2000 mg of clarithromycin daily had seriously abnormal elevated levels of SGOT and SGPT, and abnormally low white blood cell and platelet counts. 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 4000 mg daily for all parameters except White Blood Cell.