Chemical formula: C₉H₁₃N₃O₅ Molecular mass: 243.217 g/mol PubChem compound: 6253
Cytarabine interacts in the following cases:
GI absorption of oral digoxin tablets may be substantially reduced in patients receiving combination chemotherapy regimens (including regimens containing cytarabine), possibly as a result of temporary damage to intestinal mucosa caused by the cytotoxic agents. Reversible decreases in steady-state plasma digoxin concentrations and renal glycoside excretion were observed in patients receiving beta-acetyldigoxin and chemotherapy regimens containing cyclophosphamide, vincristine and prednisone with or without cytarabine or procarbazine. Limited data suggest that the extent of GI absorption of digitoxin is not substantially affected by concomitant administration of combination chemotherapy regimens known to decrease absorption of digoxin. Steady-state plasma digitoxin concentrations did not appear to change. Therefore, monitoring of plasma digoxin levels may be indicated in patients receiving similar combination chemotherapy regimens. The utilization of digitoxin for such patients may be considered as an alternative.
Due to the immunosuppresive action of cytarabine, 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.
Fertility studies to assess the reproductive toxicity of cytarabine have not been conducted. Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking cytarabine therapy, especially in combination with alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Given that cytarabine has a mutagenic potential which could induce chromosomal damage in the human spermatozoa, males undergoing cytarabine treatment and their partner should be advised to use a reliable contraceptive method.
One in vitro study indicates that cytarabine may antagonise the activity of gentamicin against Klebsiella pneumoniae. In patients on cytarabine being treated with gentamicin for a K.pneumoniae infection, a lack of a prompt therapeutic response may indicate the need for re-evaluation of antibacterial therapy.
There is evidence of pharmacodynamic interaction between methotrexate and cytarabine leading to encephalopathy.
Cytarabine is a potent bone marrow suppressant. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients receiving the drug should be kept under close medical supervision. Leucocyte, and platelet counts should be performed frequently and daily during induction. Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood.
Facilities should be available for management of complications, possibly fatal, of bone marrow suppression (infection resulting from granulocytopenia and other impaired body defenses, and hemorrhage secondary to thrombocytopenia).
5-Fluorocytosine should not be administered with cytarabine as the therapeutic efficacy of 5-Fluorocytosine has been shown to be abolished during such therapy.
Cytarabine is teratogenic in some animal species. It should not be used in pregnant women (especially during the first trimester) or in those who may become pregnant, unless the possible benefits outweigh the potential risks. Women who are, or who may become, pregnant during treatment with cytarabine should be informed of the risks.
Men and women have to use effective contraception during and up to 6 months after treatment.
It is not known if cytarabine or its metabolite is distributed into breast milk, and it should not be used in mothers who are breastfeeding.
Fertility studies to assess the reproductive toxicity of cytarabine have not been conducted. Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking cytarabine therapy, especially in combination with alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Given that cytarabine has a mutagenic potential which could induce chromosomal damage in the human spermatozoa, males undergoing cytarabine treatment and their partner should be advised to use a reliable contraceptive method.
No documented effect on ability to drive or operate machinery.
Nevertheless, patients receiving chemotherapy may have an impaired ability to drive or operate machinery and should be warned of the possibility and advised to avoid such tasks if so affected.
The following adverse events have been reported in association with cytarabine therapy.
Frequencies are defined using the following convention: 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).
Undesirable effects from cytarabine are dose-dependent. Most common are gastrointestinal undesirable effects. Cytarabine is toxic to the bone marrow, and causes haematological undesirable effects.
Uncommon: Sepsis (immunosuppression)
Uncommon: Lentigo
Common: Anaemia, megaloblastosis, leucopenia, thrombocytopenia
Not known: Reticulocytopenia, neutropenia, febrile neutropenia
These appear to be more evident after high doses and continuous infusions; the severity depends on the dose of the drug and schedule of administration
Common: Anorexia, hyperuricaemia
Common: At high doses cerebellar or cerebral influence with deterioration of the level of consciousness, dysarthria, nystagmus
Uncommon: Headache, peripheral neuropathy and paraplegia at intrathecal administration
Not known: Dizziness, neuritis or neural toxicity and pain, neurotoxicity rash
Common: Reversible haemorrhagic conjunctivitis (photophobia, burning, visual disturbance, increased lacrimation), keratitis
Not known: Conjunctivitis
Uncommon: Pericarditis
Very rare: Arrhythmia
Not Known: Sinus bradycardia
Uncommon: Pneumonia, dyspnea, sore throat
Common: Dysphagia, abdominal pain, nausea, vomiting, diarrhea, oral/anal inflammation or ulceration
Uncommon: Oesphagitis, oesophageal ulceration, pneumatosis cystoides intestinalis, necrotising colitis, peritonitis
Not known: Gastrointestinal haemorrhage
Nausea and vomiting may occur and are generally more frequent following rapid intravenous administration than with continuous intravenous infusion of the drug.
Common: Reversible effects on the liver with increased enzyme levels
Not known: Hepatic dysfunction, jaundice
Common: Reversible undesirable effects to the skin, such as erythema, bullous dermatitis, urticaria, vasculitis, alopecia,
Uncommon: skin ulceration, pruritus, burning pain of palms and soles
Very rare: Neutrophilic eccrine hidradenitis
Not known: Rash, freckling, skin bleeding
Uncommon: Myalgia, joint pain
Common: Renal impairment, urinary retention
Not known: Renal dysfunction
Common: Fever, thrombophlebitis at the injection site, cellulitis at injection site
Not known: Irritation or sepsis at the injection site, chest pain and mucosal bleeding
A cytarabine syndrome (immunoallergic effect) is characterised by fever, myalgia, bone pain, occasionally chest pain, exanthema, maculopapular rash, conjunctivitis, nausea and malaise. It usually occurs 6-12 hours after administration. Corticosteroids have been shown to be beneficial in treating or preventing this syndrome. If the symptoms of the syndrome are serious enough to warrant treatment, corticosteroids should be contemplated. If treatment is effective, therapy with cytarabine may be continued.
Adverse effects due to high dose cytarabine treatment, other than those seen with conventional doses include:
Blood and lymphatic system disorders: Hematological toxicity has been seen as profound pancytopenia which may last 15-25 days along with more severe bone marrow aplasia than that observed at conventional doses.
Nervous system disorders: After treatment with high doses of cytarabine, symptoms of cerebral or cerebellar influence like personality changes, affected alertness, dysarthria, ataxia, tremor, nystagmus, headache, confusion, somnolence, dizziness, coma, convulsions, etc. appear in 8-37% of treated patients. The incidence in elderly (>55 years) may be even higher. Other predisposing factors are impaired liver and renal function, previous CNS treatment (e.g. radiotherapy) and alcohol abuse. CNS disturbances are in the most cases reversible.
The risk of CNS toxicity increases if the cytarabine treatment – given as high dose i.v. is combined with another CNS toxic treatment such as radiation therapy or high dose of a cytotoxic agent
Eye disorders: Reversible corneal lesion and haemorrhagic conjunctivitis have been described. These phenomena can be prevented or decreased by installation of corticosteroid eye drops.
Gastrointestinal disorders: Especially in treatment with high doses of cytarabine, more severe reactions may appear in addition to common symptoms. Intestinal perforation or necrosis with ileus and peritonitis have been reported. Pancreatitis has also been observed after high-dose therapy.
Hepatobiliary disorders: Liver abscesses, hepatomegaly, Budd-Chiari-syndrome (hepatic venous thrombosis), and hyperbilirubinaemia have been observed after high-dose therapy.
Respiratory, thoracic and mediastinal disorders: Clinical signs as present in pulmonary oedema/ARDS may develop, particularly in high-dose therapy. The reaction is probably caused by an alveolar capillary injury. It is difficult to make an assessment of frequencies (stated as 10-26% in different publications), since the patients usually have been in relapse where other factors may contribute to this reaction.
Reproductive system and breast disorders: Amenorrhoea and azoospermia.
Others: Following cytarabine therapy, cardiomyopathy and rhabdomyolysis have been reported.
The gastrointestinal undesirable effects are reduced if cytarabine is administered as infusion. Local glucocorticoids are recommended as prophylaxis of haemorrhagic conjunctivitis.
One case of anaphylaxis that resulted in cardiopulmonary arrest and necessitated resuscitation has been reported.
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