Adverse reactions : תופעות לוואי

4.8. Undesirable effects
Summary of the Safety profile
The most common adverse reactions are phlebitis, pseudo-allergic reactions and flushing of the upper body (“red-neck syndrome”) in connection with too rapid intravenous infusion of vancomycin.
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) have been reported in association with vancomycin treatment (see section 4.4).
The absorption of vancomycin from the gastrointestinal tract is negligible. However, in severe inflammation of the intestinal mucosa, especially in combination with renal insufficiency, adverse reactions that occur when vancomycin is administered parenterally may appear.


Tabulated List of Adverse reactions
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The adverse reactions listed below are defined using the following MedDRA convention and system organ class database:
Very common (≥ 1/10); 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 (cannot be estimated from the available data).
 System organ class
Frequency          Adverse reaction

Blood and the lymphatic system disorders
Rare                 Reversible neutropenia1, agranulocytosis, eosinophilia, thrombocytopenia, pancytopenia.
Immune system disorders:
Rare                 Hypersensitivity reactions, anaphylactic reactions2 Ear and labyrinth disorders:
Uncommon             Transient or permanent loss of hearing4
Rare                 Vertigo, tinnitus3, dizziness
Cardiac disorders
Very rare            Cardiac arrest
Vascular disorders:
Common               Decrease in blood pressure
Rare                 Vasculitis
Respiratory, thoracic and mediastinal disorders:
Common               Dyspnoea, stridor
Gastrointestinal disorders
Rare                 Nausea
Very rare            Pseudomembranous enterocolitis
Not known            Vomiting, Diarrhoea
Skin and subcutaneous tissue disorders:
Common               Flushing of the upper body (“red man syndrome”), exanthema and mucosal inflammation, pruritus, urticaria
Very rare            Exfoliative dermatitis, Stevens-Johnson syndrome, Toxic epidermal necrolysis (TEN), Linear IgA bullous dermatosis
Not known            Eosinophilia and systemic symptoms (DRESS syndrome (drug-induced hypersensitivity syndrome))
AGEP (Acute Generalized Exanthematous Pustulosis)
Renal and urinary disorders:
Common               Renal insufficiency manifested primarily by increased serum creatinine and serum urea
Rare                 Interstitial nephritis, acute renal failure.
Not known            Acute tubular necrosis
General disorders and administration site conditions:
Common               Phlebitis, redness of the upper body and face.
Rare                 Drug fever, shivering, pain and muscle spasm of the chest and back muscles 
Description of selected adverse drug reactions
1Reversible  neutropenia usually starting one week or more after onset of intravenous therapy or after total dose of more than 25 g.
2During  or shortly after rapid infusion anaphylactic/anaphylactoid reactions including wheezing may occur. The reactions abate when administration is stopped, generally between 20 minutes and 2 hours.
Vancomycin should be infused slowly (see sections 4.2 and 4.4). Necrosis may occur after intramuscular injection.
3Tinnitus,   possibly preceding onset of deafness, should be regarded as an indication to discontinue treatment.
4Ototoxicity has primarily been reported in patients given high doses, or in those on concomitant treatment with other ototoxic medicinal product like aminoglycoside, or in those who had a pre-existing reduction in kidney function or hearing.
Paediatric population
The safety profile is generally consistent among children and adult patients. Nephrotoxicity has been described in children, usually in association with other nephrotoxic agents such as aminoglycosides.
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/ and by email to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com