Adverse reactions : תופעות לוואי

4.8. Undesirable effects

Undesirable effects are ranked according to body system and frequency according to the following classification:

Very common (≥1/10)
Common (≥1/100to <1/10)
Uncommon (≥1/1,000to <1/100)
Rare (≥1/10,000to <1/1,000)
Very rare (<1/10,000)

Not known (cannot be estimated from available data)
Blood and lymphatic system disorders
Very rare:
Eosinophilia, leukopenia, neutropenia, granulocytopenia, agranulocytosis, pancytopenia, hemolytic anemia, coagulation disorders
not known:
Prolongation of the bleeding time and prothrombin time, thrombocytopenia (see section 4.4) 

Immune system disorders
Uncommon:
Allergic reactions: urticaria, erythema multiforme, exfoliative dermatitis, fever arthralgia, anaphylaxis or anaphylactoid reactions (asthma, purpura, gastrointestinal symptoms). Para- allergic reactions may occur in patients with dermatomycoses, as there may be common antigenic between penicillins and metabolic products of dermatophytes.
Not known:
Serum sickness, Jarisch-Herxheimer reaction in association with spirochete infections (syphilis and Lyme disease), angioedema

Metabolism and nutrition disorders
Rare:
Electrolyte imbalances may occur upon rapid infusion of more than 10 MU.

Nervous system disorders
Rare:
Neuropathy. Convulsive reactions may occur upon infusion of high doses (in adults more than 20 MU); this should be particularly borne in mind in patients with severely impaired renal function, epilepsy, meningitis, cerebral oedema or during cardiopulmonary bypass.

Not known :
Metabolic encephalopathy

Gastrointestinal disorders
Uncommon:
Stomatitis, glossitis, black hairy tongue (lingua villosa nigra), nausea, vomiting If diarrhea develops during treatment, the possibility of pseudomembranous colitis should be considered (see section 4.4).

Rare :
Diarrhoea caused by Clostridium difficile

Hepato biliary disorders
Not known:
Hepatitis, cholestasis

Skin and subcutaneous tissue disorders
Not known: pemphigoid, Acute generalised
exanthematous pustulosis (AGEP), Pruritus,
Maculo papular rash, Rash morbilliform, Erythema.

Renal and urinary disorders
Rare:
Nephropathy (after intravenous administration of more than 10 MU Penicillin G-Sodium), albuminuria, cylindruria and hematuria
Oliguria or anuria which can rarely occur during high-dose penicillin therapy generally disappears within 48 hours upon discontinuation of treatment. Diuresis can also be stimulated with 10% mannitol solution.

General disorders and administration site conditions
Rare:
Severe local reactions during intramuscular administration to infants.

Investigations
Common:
•    Positive direct Coomb's test
•    False-positive urinary protein determination using precipitation techniques (Folin- Ciocalteu-Lowry method, Biuret method)
•    False-positive urinary amino acid determination (ninhydrin method)
•    falsification of pseudobisalbuminemia when using electrophoresis methods to determine albumin.
•    False-positive non-enzymatic urinary glucose detection and urobilinogen detection
•    increased values when determining of 17-ketosteroids in urine (using the Zimmermann reaction) (see section 4.5)

Description of selected adverse reactions
Severe cutaneous adverse reactions SCARs (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis) have been reported with beta-lactam antibiotics, including penicillins (see section 4.4).


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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/