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
Not known: hypotension (at doses >850 mg/m2).
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        Uncommon site conditions                              Flu-like symptoms

Rare
Application site irritation
Investigations                              Rare
Hepatic enzymes increased (e.g. alkaline phosphatase, ASAT, ALAT), blood lactate dehydrogenase (LOH) 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 Section 4.4).

Application site irritations and some of the systemic adverse reactions are thought to result from formation of photo-degradation 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/