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 areavailable, adverse events are included if the incidence is > 5% higher in the treatmentgroup.
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                  not known        Opportunistic infections (including fatal Infestations                                     outcome)
Neoplasms benign, malignant     common           Acute leukemias, bone marrow dysplasias; and unspecified                                  following long-term use.
(includingcysts and polyps)
Blood and lymphatic             common           Anaemia.
systemdisorders very common      Myelosuppression; onset 7-14 days, nadir 21-
35 days, recovery 42-56 days; cumulative,
dose related, delayed and often biphasic.
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.
MedDRA system organ              Frequency       Adverse effects class
Clinically important side effects are in italics
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       very common     emetogenic potential: >250 mg/m2 high; ≤ 250 mg/m2 high-moderate very common     Nausea and vomiting, severe; begins within 2-
4 h of administration and lasts for 4-6 h.
common          Anorexia, constipation, diarrhoea, stomatitis.
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.
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