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 class Frequency             Adverse effects
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 cysts                following long-term use.
and polyps)
Blood and lymphatic system       common         Anaemia disorders                        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.
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).
2
Gastrointestinal disorders      very common emetogenic potential: >250 mg/m high; ≤ 250 mg/m high-moderate
2
 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