Adverse reactions : תופעות לוואי

8      ADVERSE REACTIONS

8.1    Adverse Reaction Overview
As with other penicillins, it may be expected that untoward reactions will be related to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and cephalosporins and in those with a history of allergy, asthma, hay fever or urticaria.

8.2    Clinical Trial Adverse Reactions

The following adverse reactions have been reported as associated with the use of Moxypen Forte:

Gastrointestinal ‐ Nausea, vomiting and diarrhea, hemorrhagic and pseudomembranous colitis.
Clostridium difficile‐associated disease (CDAD) has been reported with use of many antibacterial agents, including amoxicillin. Glossitis, black "hairy" tongue and stomatitis, mucocutaneous candidiasis, tooth discoloration (brown, yellow or gray staining); most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Hypersensitivity Reactions ‐ Skin rashes have been reported frequently. Less commonly, a few cases of serum sickness like reactions including urticaria, erythema, erythema multiforme, angioneurotic edema, pruritus have been reported. Rarely, Stevens‐Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, exfoliative dermatitis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis have been reported.

Anaphylaxis is the most serious reaction experienced and has usually been associated with the parenteral dosage form.

NOTE: Urticaria, other skin rashes, and serum sickness‐like reactions may be controlled with antihistamines and if necessary, systemic corticosteroids. Whenever such reactions occur, Moxypen Forte (amoxicillin) should be discontinued unless, in the opinion of the physician, the condition being treated is life threatening and amenable only to amoxicillin therapy. Serious anaphylactic reactions require the immediate use of epinephrine, oxygen and intravenous steroids.

Hepatobiliary ‐ A moderate rise in serum glutamic oxaloacetic transaminase (SGOT) has been noted, particularly in infants, but the significance of this finding is not known. Transient increases in serum alkaline phosphatase and lactic dehydrogenase levels have also been observed but they returned to normal on discontinuation of amoxicillin. Reports have also been seen of hepatic dysfunction including cholestatic jaundice, hepatic cholestasis, acute cytolytic hepatitis, 
Hemic and Lymphatic Systems ‐ Anemia thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, neutropenia and agranulocytosis have been reported during therapy with the penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be a hypersensitivity phenomena. Reports have also been seen of anemia including hemolytic anemia.

Central Nervous System ‐ As with other penicillins, acute and chronic toxicity is not a clinical problem. Although penicillins do not normally cross the blood‐brain barrier to any substantial extent, if massive doses are given (several grams per day) to elderly patients, patients with inflamed meninges or patients with impaired renal function, toxic reactions are likely to occur. At extremely high doses, convulsions can occur. When penicillin reaches a high concentration in the cerebrospinal fluid, neurotoxic symptoms consisting of myoclonia, convulsive seizures and depressed consciousness may occur. Unless administration of the drug is stopped or its dosage reduced, the syndrome may progress to coma and death. Dizziness, hyperkinesias, hyperactivity, agitation, anxiety, insomnia, confusion, and behavioural changes have also been reported.

Skin and Appendages ‐ erythematous maculopapular rash.

Renal ‐ Crystalluria. Interstitial nephritis (oliguria, proteinuria, hematuria, hyaline casts, pyuria) and nephropathy are infrequent and usually associated with high doses of parenteral penicillins; however, this has occurred with all of the penicillins. Such reactions are hypersensitivity responses and are usually associated with fever, skin rash and eosinophilia. Elevations of creatinine or blood urea nitrogen may occur.

8.3    Post‐Marketing Adverse Reactions

Central Nervous System: Amoxicillin can lead to cases of aseptic meningitis of unknown frequency.
Other immune system disorders: Kounis syndrome
8.4     Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il