Adverse reactions : תופעות לוואי

4.8     Undesirable effects

The table includes adverse events that were presented during drug treatment but may not necessarily have a causal relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be clinically important.
When placebo-controlled trials are available, adverse events are included if the incidence is > 5% higher in the treatment group.
High dose is defined as >200 mg/m2
The following table includes adverse effects of carmustine divided by groups according to MedDRA terminology with frequency of occurrence: 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 (frequency cannot be estimated from the available data):

MedDRA system organ              Frequency       Adverse effects class
Clinically important side effects are in italics
Infections and Infestations      Not known       Opportunistic infections (including fatal outcome)
Neoplasms benign, malignant      Common          Acute leukemias, bone marrow dysplasias; and unspecified (including                       following long-term use.
cysts and polyps)
Not known       Secondary malignancies


Blood and lymphatic system       Common          Anaemia.
disorders
Very common Myelosuppression; onset 7-14 days, nadir 21-
35 days, recovery 42-56 days; cumulative,
MedDRA system organ            Frequency      Adverse effects class
Clinically important side effects are in italics dose related, delayed and often biphasic.
Immune system disorders         Not known      Allergic reaction
Metabolism and nutrition        Not known      Electrolyte disorders (hypokalaemia, disorders                                      hypomagnesaemia, and hypophosphataemia)

Nervous system disorders       Very common Ataxia, dizziness, headache.

Common      Encephalopathy (high-dose therapy and dose- limiting).
Not known   Muscular pain, status epilepticus, seizure,
grand mal seizure.
Eye disorders                  Very common Ocular toxicities, transient conjunctival flushing and blurred vision; retinal haemorrhages.
Rare        Neuroretinitis


Cardiac disorders              Very common Hypotension, due to alcohol content of diluent (high-dose therapy)
Not known   Tachycardia, chest pain
Vascular disorders             Very common Phlebitis.

Rare        Veno-occlusive disease (high-dose therapy).
Respiratory, thoracic and      Very common Pulmonary toxicity1,interstitial fibrosis (with mediastinal disorders                      prolonged therapy and cumulative dose > 1400 mg/m2) Pneumonitis (for doses
>450mg/m2).
Rare        Interstitial fibrosis (with lower doses).
Gastrointestinal disorders                 emetogenic potential: >250 mg/m2 high; Very common ≤ 250 mg/m high-moderate
2

Nausea and vomiting, severe; begins within 2-
4 h of administration and lasts for 4-6 h.
Common      Anorexia, constipation, diarrhoea, stomatitis.

Rare           Bleeding in the gastrointestinal tract
Not known      Neutropenic enterocolitis
Hepatobiliary disorders        Common         Hepatotoxicity, reversible, delayed up to 60 days after administration (high-dose therapy and dose-limiting), manifested by:
-    bilirubin, reversible increase
-    alkaline phosphatase, reversible increase
-    SGOT, reversible increase.
Skin and subcutaneous tissue   Not known      extravasation hazard: vesicant disorders
Very common Dermatitis with topical use improves with reduced concentration of compounded product, hyperpigmentation, transient, with accidental skin contact.
Common      Alopecia, flushing (due to alcohol content of diluent; increased with administration times
<1-2 h), injection site reaction.
Renal and urinary disorders    Rare        Renal toxicity (for cumulative doses <1,000 mg/m2).
Reproductive system and           Rare           Gynecomastia.
breast disorders


Not known      Infertility, teratogenesis.

General disorders and              Very rare      Thrombophlebitis administration site conditions
1
Pulmonary toxicity is also manifested as pneumonitis and interstitial lung disease in post- marketing experience


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