Cytarabine

{{DrugProjectFormSinglePage |authorTag=Alberto Plate [1] |genericName=Cytarabine |aOrAn=an |drugClass=antineoplastic agent |indicationType=treatment |indication=acute non-lymphocytic leukemia of adults and children, acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. Intrathecal administration of cytarabine injection is indicated for the prophylaxis and treatment of meningeal leukemia |hasBlackBoxWarning=Yes |adverseReactions=thrombophlebitis, rash, hyperuricemia, anal inflammation, diarrhea, loss of apetite, nauseas, stomatitis, mouth ulceration, vomiting, decreased reticulocyte count, megaloblastic anemia, decreased liver function and fever. |blackBoxWarningTitle=Black Box Warning: |blackBoxWarningBody=ConditionName:

Only physicians experienced in cancer chemotherapy should use Cytarabine Injection.

For induction therapy patients should be treated in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The main toxic effect of cytarabine is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration and hepatic dysfunction.

The physician must judge possible benefit to the patient against known toxic effects of this drug in considering the advisability of therapy with cytarabine. Before making this judgment or beginning treatment, the physician should be familiar with the following text.

|fdaLIADAdult=====Acute Non-Lymphocytic Leukemia====

• Induction: 100 mg/m2/day by continuous IV infusion (Days 1-7) or 100 mg/m2 IV every 12 hours (Days 1-7).

Meningeal Leukemia

• Dosage: doses ranging from 5 mg/m2 to 75 mg/m2 of body surface area. The frequency of administration varied from once a day for 4 days to once every 4 days. The most frequently used dose was 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment.

|offLabelAdultGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Cytarabine in adult patients. |offLabelAdultNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Cytarabine in adult patients. |offLabelPedGuideSupport=There is limited information regarding Off-Label Guideline-Supported Use of Cytarabine in pediatric patients. |offLabelPedNoGuideSupport=There is limited information regarding Off-Label Non–Guideline-Supported Use of Cytarabine in pediatric patients. |contraindications=Cytarabine is contraindicated in those patients who are hypersensitive to the drug. |warnings=*Cytarabine is a potent bone marrow suppressant. Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression. Patients receiving this drug must be under close medical supervision and, during induction therapy, should have leukocyte and platelet counts performed daily. 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). One case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported. This occurred immediately after the intravenous administration of cytarabine.

• Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) has been reported following some of the experimental cytarabine dose schedules. These reactions include reversible corneal toxicity, and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia, bowel necrosis; and necrotizing colitis. Rarely, severe skin rash, leading to desquamation has been reported. Complete alopecia is more commonly seen with experimental high dose therapy than with standard cytarabine treatment programs. If experimental high dose therapy is used, do not use a cytarabine injection containing benzyl alcohol.

• Cases of cardiomyopathy with subsequent death has been reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation.

• A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients. The outcome of this syndrome can be fatal.

• Benzyl alcohol is contained in this product. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants.

• Two patients with childhood acute myelogenous leukemia who received intrathecal and intravenous cytarabine at conventional doses (in addition to a number of other concomitantly administered drugs) developed delayed progressive ascending paralysis resulting in death in one of the two patients.

|clinicalTrials=====Hematological Effects====

• Anemia
• Leukopenia
• Thrombocytopenia
• Megaloblastosis
• Reduced reticulocytes

Infections

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.

Cytabarine Syndrome

• Fever
• Myalgia
• Bone pain
• Occasionally chest pain
• Maculopapular rash
• Conjunctivitis and malaise

Cardiovascular effects

• Cardiomyopathy
• Cardiovascular finding
• Pericarditis: < 0.1% of patients develop this adverse effect, between 2 - 3 days after initiating the therapy, symptoms lasting for 1-6 weeks . Symptoms include:
• Chest pain
• Dyspnea
• Pericardial effusion
• Pericardial friction rub
• Pulsus paradoxus
• Right ventricular diastolic collapse
• ST-Segment elevation on EKG
• Vasculitis: high-dose cytarabine causes small vessel necrotizing vasculitis.

Dermatological effects

• Alopecia
• Dermatological finding
• Dermatologic toxicity
• Severe Henoch-Schönlein purpura
• Rash
• Skin finding
• Toxic epidermal necrolysis

Endocrine/metabolic Effects

• Disorder of fluid and/or electrolyte: hypokalemia and hypocalcemia, specially when [[diarrhea] is present.
• Hyperuricemia: is a result of tumor lysis syndrome
• Increased body temperature

Gastrointestinal Effects

• Gastrointestinal tract finding: nausea and vomiting are common agh high-dosis. GI bleeding has also been reported..
• Pancreatitis
• Parotitis
• Pseudomembranous enterocolitis

Hepatic Effects

Hepatotoxicity Liver finding

Musculoeskeletal Effects

• Musculoskeletal finding
• Rhabdomyolysis

Neurologic Effects

• Arachnoiditis
• Aseptic meningitis
• Cranial nerve disorder
• Neurological finding
• Neuropathy
• Neurotoxicity
• Paraplegia
• Paresthesia
• Parkinsonism
• Pseudotumor cerebri

Ophthalmic Effects

• Conjunctivitis
• Disorder of cornea
• Disorder of vision
• Eye / vision finding

Urinary Tract Effects

• Cystitis
• Kidney disease
• Renal failure
• Urinary retention

Respiratory Effects

• Acute respiratory distress syndrome
• Pulmonary edema
• Pulmonary toxicity
• Respiratory finding

Other

• Summary
• Hypersensitivity reaction
• Sepsis

|PD=s |alcohol=Alcohol-Cytarabine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. }}