Cytarabine (Conventional)

• Tell all of your health care providers that you take cytarabine. This includes your doctors, nurses, pharmacists, and dentists.
• You may have more of a chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Some infections have been very bad and even deadly.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• You may be given another drug to lower certain side effects of this medicine.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Some products have benzyl alcohol. Do not give a product that has benzyl alcohol in it to a newborn. Talk with the doctor to see if this product has benzyl alcohol in it.
• Talk with your doctor before getting any vaccines. Use with cytarabine may either raise the chance of an infection or make the vaccine not work as well.
• If you are taking digoxin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this medicine.
• Patients with cancer who take cytarabine may be at a greater risk of getting a bad health problem called tumor lysis syndrome (TLS). Sometimes, this has been deadly. Call your doctor right away if you have a fast heartbeat or a heartbeat that does not feel normal; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, loose stools, or not able to eat; or feel sluggish.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust to prevent pregnancy while taking this medicine.
• If you are pregnant or you get pregnant while taking cytarabine, call your doctor right away.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• It is given as a shot into a vein, the fatty part of the skin, or into the spine.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• Antineoplastic Agent, Antimetabolite
• Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)

There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended:

Aronoff, 2007 (cytarabine 100 to 200 mg/m2): Children and Adults: No adjustment necessary

Kintzel, 1995 (high-dose cytarabine 1 to 3 g/m2):

CrCl 46 to 60 mL/minute: Administer 60% of dose

CrCl 31 to 45 mL/minute: Administer 50% of dose

CrCl <30 mL/minute: Consider use of alternative drug

Smith, 1997 (high-dose cytarabine; ≥2 g/m2/dose):

Serum creatinine 1.5 to 1.9 mg/dL or increase (from baseline) of 0.5 to 1.2 mg/dL: Reduce dose to 1 g/m2/dose

Serum creatinine ≥2 mg/dL or increase (from baseline) of >1.2 mg/dL: Reduce dose to 0.1 g/m2/day as a continuous infusion

Hemodialysis: In 4 hour dialysis sessions (with high flow polysulfone membrane) 6 hours after cytarabine 1 g/m2 over 2 hours, 63% of the metabolite ARA-U was extracted from plasma (based on a single adult case report) (Radeski, 2011)

American Society of Clinical Oncology (ASCO) Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).

American Society for Blood and Marrow Transplantation (ASBMT) practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight (full weight) for calculation of body surface area in cytarabine dosing for hematopoietic stem cell transplant conditioning regimens in pediatrics and adults (Bubalo, 2014).

IV: Infuse standard dose therapy for AML (100 to 200 mg/m2/day) as a continuous infusion. Infuse high-dose therapy (off-label) over 1 to 3 hours (usually). Other rates have been used, refer to specific reference.

In adults, doses >1000 mg/m2 are associated with a moderate emetic potential (Basch, 2011; Roila, 2010). In pediatrics, doses >200 mg/m2 are associated with a moderate emetic potential and 3000 mg/m2 is associated with a high emetic potential (Dupuis, 2011); antiemetics are recommended to prevent nausea and vomiting.

Intrathecal: Intrathecal doses should be administered as soon as possible after preparation.

May also be administered SubQ.

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Flucytosine: Cytarabine (Conventional) may diminish the therapeutic effect of Flucytosine. Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Frequency not always defined. CNS, gastrointestinal, ophthalmic, and pulmonary toxicities are more common with high-dose regimens.

Cardiovascular: Angina pectoris, chest pain, hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease), local thrombophlebitis, pericarditis

Central nervous system: Aseptic meningitis, cerebral dysfunction, dizziness, headache, neuritis, neurotoxicity, paralysis (intrathecal and IV combination therapy), reversible posterior leukoencephalopathy syndrome

Dermatologic: Acute generalized exanthematous pustulosis, alopecia, dermal ulcer, ephelis, pruritus, skin rash, urticaria

Endocrine & metabolic: Hyperuricemia

Gastrointestinal: Abdominal pain, anal fissure, anorexia, diarrhea, esophageal ulcer, esophagitis, increased serum amylase, increased serum lipase, intestinal necrosis, mucositis, nausea, pancreatitis, sore throat, toxic megacolon, vomiting

Genitourinary: Urinary retention

Hematologic & oncologic: Anemia, bone marrow depression, hemorrhage, leukopenia, megaloblastic anemia, neutropenia (onset: 1 to 7 days; nadir [biphasic]: 7 to 9 days and at 15 to 24 days; recovery [biphasic]: 9 to 12 days and at 24 to 34 days), reticulocytopenia, thrombocytopenia (onset: 5 days; nadir: 12 to 15 days; recovery 15 to 25 days)

Hepatic: Hepatic insufficiency, increased serum transaminases (acute), jaundice

Hypersensitivity: Allergic edema, anaphylaxis

Infection: Sepsis

Local: Cellulitis at injection site, inflammation at injection site (SC injection), local inflammation (anus), pain at injection site (SC injection)

Neuromuscular & skeletal: Rhabdomyolysis

Ophthalmic: Conjunctivitis

Renal: Renal insufficiency

Respiratory: Acute respiratory distress, dyspnea, interstitial pneumonitis

Miscellaneous: Drug toxicity (cytarabine syndrome; chest pain, conjunctivitis, fever, maculopapular rash, malaise, myalgia, ostealgia), fever

Adverse events associated with high-dose cytarabine

Cardiovascular: Cardiomegaly, cardiomyopathy (in combination with cyclophosphamide)

Central nervous system: Neurotoxicity (patients with renal impairment: ≤55%), coma, drowsiness, neurocerebellar toxicity, peripheral neuropathy (motor and sensory), personality changes

Dermatologic: Alopecia (complete), desquamation, skin rash (severe)

Gastrointestinal: Gastrointestinal ulcer, necrotizing enterocolitis, pancreatitis, peritonitis, pneumatosis cystoides intestinalis

Hepatic: Hepatic abscess, hepatic injury, hyperbilirubinemia

Infection: Sepsis

Ophthalmic: Corneal toxicity, hemorrhagic conjunctivitis

Respiratory: Acute respiratory distress, pulmonary edema

Adverse events associated with intrathecal cytarabine administration

Central nervous system: Aphonia, leukoencephalopathy (necrotizing; with concurrent cranial irradiation, intrathecal methotrexate, and intrathecal hydrocortisone), nerve palsy (accessory nerve), neurotoxicity, paraplegia

Gastrointestinal: Dysphagia, nausea, vomiting

Ophthalmic: Blindness (with concurrent systemic chemotherapy and cranial irradiation), diplopia

Respiratory: Cough, hoarseness

Miscellaneous: Fever

Only physicians experienced in cancer chemotherapy should use cytarabine.

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.