Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Frequencies
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)
The most commonly reported ADRs are gastrointestinal disorders (anorexia, nausea and vomiting) and blood and lymphatic system disorders such as anaemia, leukopenia and thrombocytopenia. The latter are dose-dependent and delayed, with the nadirs often only occurring after 3 to 4 weeks.
Infections and infestations                  Uncommon
Infections
Blood and lymphatic system disorders         Common
Anaemia, leukopenia, thrombocytopenia

Rare
Pancytopenia, agranulocytosis

Immune system disorders                      Rare
Anaphylactic reactions
Nervous system disorders                     Rare
Headaches, impaired vision, confusion, lethargy,
convulsions, facial paraesthesia
Vascular disorders                           Rare
Facial flushing
Gastrointestinal disorders                Common
Anorexia, nausea, vomiting
Rare
Diarrhoea
Hepatobiliary disorders                   Rare
Hepatic necrosis due to veno-occlusive disease
(VOD) of the liver, Budd-Chiari syndrome (with potentially fatal outcome)
Renal and urinary disorders               Rare
Impaired renal function
Skin and subcutaneous tissue disorders Uncommon
Alopecia, hyperpigmentation, photosensitivity
Rare
Erythema, maculopapular exanthema, urticaria
General disorders and administration site Uncommon conditions                                  Flu-like symptoms
Rare
Application site irritation
Investigations                            Rare
Hepatic enzymes increased (e.g. alkaline phosphatase, ASAT, ALAT), blood lactate dehydrogenase (LDH) increased, blood creatinine increased, blood urea increased

Description of selected adverse reactions

Changes in blood counts often observed (anaemia, leukopenia, thrombocytopenia) are dose-dependent and delayed, with the nadirs often only occurring after 3 to 4 weeks.

Flu-like symptoms with exhaustion, chills, fever, and muscular pain are occasionally observed during or often only days after dacarbazine administration. These disturbances may recur with the next infusion.

Rarely liver necrosis due to occlusion of intrahepatic veins (veno-occlusive disease of the liver) has been observed after administration of dacarbazine in monotherapy or in combined treatment modalities. In general, the syndrome occurred during the second cycle of therapy. Symptoms included fever, eosinophilia, abdominal pain, enlarged liver, jaundice and shock which worsened rapidly over a few hours or days. As fatal outcome has been described special care has to be taken (see sections 4.2 and 4.4).

Application site irritations and some of the systemic adverse reactions are thought to result from formation of photodegradation products.
Facial paraesthesia and flushing may occur shortly after injection.

Allergic reactions of the skin in the form of erythema, maculopapular exanthema or urticaria are observed rarely.

Inadvertent paravenous injection is expected to cause local pain and necrosis.

Reporting 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.