Cytarabine Pfizer Adverse Reactions

Summary of Safety Profile (see also PRECAUTIONS): Haematological: Myelosuppression: Cytarabine is a potent bone marrow suppressant and anaemia, leucopenia, thrombocytopenia, reduced reticulocytes and megaloblastosis can be expected. The severity of these effects is dose and schedule dependent. Cellular changes in the morphology of bone marrow and peripheral smears can be expected. Following 5-day constant infusions or acute injections of 50 mg/m² to 600 mg/m², white cell depression follows a biphasic course. Regardless of initial count, dosage level, or schedule, there is an initial fall starting the first 24 hours with a nadir at days 7-9. This is followed by a brief rise which peaks around the twelfth day. A second and deeper fall reaches nadir at days 15-24. Then there is a rapid rise to above baseline in the next 10 days. Platelet depression is noticeable at 5 days with a peak depression occurring between days 12-15. Thereupon, a rapid rise to above baseline occurs in the next 10 days.
Gastrointestinal: Nausea and vomiting are common and are more severe following rapid intravenous infusion.
Cytarabine (Ara-C) Syndrome: A cytarabine syndrome characterised by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise has been reported. It usually occurs 6 - 12 hours following drug administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are deemed treatable, corticosteroids should be contemplated as well as continuation of therapy with cytarabine.
Infectious Complications: Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body, may be associated with the use of cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity. These infections may be mild, but can be severe and at times fatal.
Tabulated Summaries of Adverse Effects: The reported adverse reactions are listed below by System Organ Class and by frequency. Frequencies are defined as: Very common (>10%), Common (>1%, ≤10%), Uncommon (>0.1%, ≤1%), Rare (>0.01%, ≤0.1%), and Frequency not known (cannot be estimated from available data). (See Table 1 and Table 2.)

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Other Adverse Reactions: Experimental Dose Schedule: A syndrome of sudden respiratory distress, rapidly progressing to pulmonary oedema and a radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia; fatal outcome has been reported.
Intermediate Dose Schedule: A diffuse interstitial pneumonitis without clear cause that may have been related to cytarabine was reported in patients treated with experimental intermediate doses of cytarabine (1 g/m²) with and without other chemotherapeutic agents (meta-AMSA, daunorubicin, VP-16).
Intrathecal Administration: The most frequently reported adverse reactions after intrathecal administration were nausea, vomiting and fever; these reactions are mild and self-limiting. Paraplegia has been reported. Necrotising leucoencephalopathy with or without convulsion has also been reported; in some cases patients had also been treated with intrathecal methotrexate and/or hydrocortisone, as well as by central nervous system radiation. Isolated neurotoxicity has been reported. Blindness occurred in two patients in remission whose treatment consisted of combination systemic chemotherapy, prophylactic central nervous system radiation and intrathecal cytarabine. Delayed progressive ascending paralysis resulting in death has been reported in children with acute myelogenous leukaemia (AML) following intrathecal and intravenous cytarabine at conventional doses in combination with other drugs.