Pharmaceutical form(s)/strength: Capsules, 200mg, 400mg, Oral suspensions, 90mg/5ml, 180mg/5ml, 36 mg/ml SI/H/PSUR/0002/002 Date of FAR:

Transcription

1 0BCore Safety Profile Active substance: Ceftibuten Pharmaceutical form(s)/strength: Capsules, 200mg, 400mg, Oral suspensions, 90mg/5ml, 180mg/5ml, 36 mg/ml P-RMS: SI/H/PSUR/0002/002 Date of FAR:

2 4.3 Contraindications TRADEMARK must not be administered in patients with known serious or acute hypersensitivity reactions (anaphylaxis) to penicillins or other betalactam antibiotics. Experience in children below three months of age is insufficient to establish the safety of ceftibuten for this patient population. 4.4 Special warnings and precautions for use Renal impairment The dosage of TRADEMARK may require adjustment in patients with marked renal insufficiency as well as patients undergoing dialysis. TRADEMARK is readily dialyzable. Dialysis patients should be monitored carefully, and their TRADEMARK administration should be timed to occur immediately following dialysis. Formatiert: Unterstrichen Gastrointestinal TRADEMARK should be prescribed with caution in individuals with a history of complicated gastrointestinal disease, particularly chronic colitis. Clostridium difficile During therapy with TRADEMARK and other broad-spectrum antibiotics, alteration of the intestinal flora may result in antibiotic-associated diarrhea, including pseudomembranous colitis due to Clostridium difficile toxin. Patients may experience moderate to severe or lifethreatening diarrhea, with or without dehydration, either during or after treatment with the associated antibiotic. It is important to consider this diagnosis in any patient noted to have persistent diarrhea while taking or up to two months after the administration of TRADEMARK or any broad-spectrum antibiotic. Hypersensitivity Cephalosporin antibiotics should be administered with extreme caution in patients with known or suspected allergy to penicillins. Approximately 5% of patients with documented penicillin allergy experience crossreactivity to the cephalosporin antibiotics. Serious acute hypersensitivity reactions (anaphylaxis) have been reported also in individuals receiving both penicillins and cephalosporins, and cross-hyperreactivity with anaphylaxis has been known to occur. If an allergic reaction to TRADEMARK occurs, discontinue use and administer appropriate therapy. Serious anaphylaxis requires appropriate emergency treatment as indicated clinically. Special caution should also be exercised when using TRADEMARK in patients with allergic reactions of any kind (e.g. hay fever or bronchial asthma), as these patients are at increased risk of serious hypersensitivity reactions. If seizures or allergic shock occur during TRADEMARK treatment, immediate discontinuation of TRADEMARK treatment is required, and appropriate medical treatment may need to be initiated immediately. Formatiert: Unterstrichen Haematology Cephalosporins, including ceftibuten, may reduce prothrombin activity in rare cases. This causes prolongation of thromboplastin time, especially in patients previously stabilized on oral anticoagulant therapy. Thromboplastin time or the INR (International Normalized Ratio) should be monitored; if indicated, vitamin K should be administered to these patients. General TRADEMARK oral suspension should be taken on an empty stomach. TRADEMARK capsules may be taken without regard to food. 2 / 5 Formatiert: Unterstrichen, Englisch (Großbritannien)

3 Excipients TRADEMARK oral suspension contains saccharose. Patients with rare hereditary problems of fructose intolerance, a saccharose-isomaltase deficiency or glucose/galactose malabsorption, should not take this medicine. 4.5 Interaction with other medicinal products and other forms of interaction (see also section 4.4) DRUG INTERACTIONS Drug interaction studies have been conducted with TRADEMARK and each of the following: high-dose aluminum-magnesium hydroxide antacid, ranitidine, and single dose intravenous theophylline. No significant drug interaction occurred 47,48. The effect of TRADEMARK on the plasma levels or pharmacokinetics of theophylline administered orally is not known. Cephalosporins, including ceftibuten, can rarely affect prothrombin activity leading to prolonged prothrombin time, especially in patients previously stabilized on oral anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous Vitamin K administered as indicated. INTERFERENCE WITH LABORATORY TESTS No known chemical or laboratory test interactions have been noted with TRADEMARK except for a false positive direct Coombs test has been reported during the use of other cephalosporins. However, the results of assays using red cells of healthy persons to test the ability of TRADEMARK to cause direct Coombs in vitro reactions, showed no positive reactions even at concentrations as high as 40 μg/ml. OTHER RELEVANT SAFETY INFORMATION No other data available. 4.6 Pregnancy and lactation There are no adequate and controlled studies in pregnant women or during labor and delivery. Because animal reproduction studies are not always predictive of human response, administration of TRADEMARK during such clinical situations should be weighed in terms of potential risk and benefit to both mother and fetus. Ceftibuten is excreted in the breast milk. Breastfed infants may therefore develop changes in the intestinal flora with diarrhea and yeast colonization, possibly necessitating interruption of lactation. The possibility of sensitization should also be taken into account TRADEMARK should be used during lactation only if the benefits clearly outweigh the risks. 4.7 Effects on ability to drive and use machines TRADEMARK has no influence on the ability to drive and use machines. 3 / 5

4 4.8 Undesirable effects Summary of the safety profile In clinical trials in approximately 3000 patients, the most frequently reported adverse effects were nausea (3%), diarrhoea (3 %) (see section 4.4), and headache (2 %). Tabulated list of adverse reactions Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: common ( 1/100 to <1/10); uncommon ( 1/1,000 to <1/100); rare ( 1/10,000 to <1/1,000); very rare (<1/10,000); not known. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Adverse reactions reported during clinical trials or through post-marketing surveillance in patients treated with TRADEMARK System Organ Class Adverse Reactions Infections and infestations Candidiasis (oral), vaginal infection Clostridium difficile colitis Superinfection Blood and lymphatic system disorders Eosinophilia, Coombs direct test positive*, hemoglobin decreased, prothrombin time prolonged, international normalised ratio increased Leukopenia, thrombocythaemia, aplastic anaemia, haemolytic anemia, haemorrhagic disorder, pancytopenia, neutropenia, agranulocytosis Immune system disorders Serum sickness; Hypersensitivity reactions including anaphylactic reaction, bronchospasm, rash, urticaria, photosensitivity reaction, pruritus, angioedema, Stevens-Johnson syndrome, erythema multiforme, and toxic epidermal necrolysis Metabolism and nutrition disorders Anorexia Psychiatric disorders In children: agitation, insomnia Psychotic disorder Nervous System Headache Dysgeusia Convulsions Paraesthesia, somnolence in children: hyperkinesia Aphasia Ear and labyrinth disorders Vertigo Respiratory, thoracic and mediastinal disorders Nasal congestion, dyspnoea 4 / 5

5 Gastro-intestinal disorders Hepatobiliary disorders Nausea, diarrhoea Gastritis, vomiting, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, faecal incontinence Melaena Hyperbilirubinaemia*, aspartate aminotransferase increased, alanine aminotransferase increased Blood lactate dehydrogenase increased Hepatobiliary disease, jaundice Skin and subcutaneous tissue disorders In children: dermatitis diaper Renal and urinary disorders Dysuria In children: hematuria Renal impairment*, nephropathy toxic*, renal glycosuria*, ketonuria* General disorders and administration site conditions Fatigue In children: irritability, chills * observed with other cephalosporins and may occur with TRADEMARK. 4.9 Overdose No toxic manifestations have been seen following accidental overdosage with TRADEMARK Gastric lavage may be indicated, otherwise no specific antidote exists. Significant quantities of TRADEMARK can be removed from the circulation by hemodialysis. Effective removal by peritoneal dialysis has not been determined. In healthy adult volunteers receiving single doses of up to 2 grams of TRADEMARK, no serious adverse reactions were observed and all clinical and laboratory findings were within normal range. 5 / 5