Cytarabine

Cytarabine may be found in some form under the following brand names:

• Cytosar-U

• Depocyt

• Tarabine PFS

Cytarabine is part of the drug class:

• Pyrimidine analogues

Serious side effects have been reported with cytarabine including the following:

• neurotoxicity. This occurs when the exposure to cytarabine disrupts or even kills neurons, cells that send signals in the brain and other parts of the nervous system. If patients develop neurotoxicity, future doses of cytarabine should be decreased, and cytarabine should be stopped if toxicity persists. Tell your healthcare provider right away if you experience any signs or symptoms of neurotoxicity:
  • limb weakness or numbness
  • memory loss
  • vision loss
  • loss of thinking capacity
  • headache
  • changes in behavior
• lowered blood counts. This is medically known as bone marrow suppression. Your doctor will want to monitor for this, as bone marrow suppression can lead to thrombocytopenia, anemia, and leukopenia.
  • thromobocytopenia. This is a condition in which your blood has a lower than normal number of blood cell fragments called platelets. Tell your healthcare provider right away if you have the following signs and symptoms of thrombocytopenia:
    • mild to serious bleeding
    • purple, brown, and red bruises (purpura)
    • small red or purple dots on your skin (petechiae)
    • prolonged bleeding, even from minor cuts
    • bleeding or oozing from the mouth or nose, especially nosebleeds or bleeding from brushing your teeth
    • abnormal vaginal bleeding (especially heavy menstrual flow)
    • blood in the urine or stool or bleeding from the rectum. Blood in the stool can appear as red blood or as a dark, tarry color. Taking iron supplements also can cause dark, tarry stools.
    • headaches and other neurological symptoms. These problems are very rare, but you should discuss them with your doctor.
  • anemia. This is a condition in which your blood has a lower than normal number of red blood cells. Tell your healthcare provider right away if you have the following signs and symptoms of anemia:
    • shortness of breath
    • dizziness
    • headache
    • coldness in the hands and feet
    • pale skin
    • chest pain
  • leukopenia. This is a condition when there are a low number of white blood cells in your body. These cells help fight infections. You may become more susceptible to infections and even to negative reactions of live vaccines if you are taking cytarabine. Tell your healthcare provider if you are feeling “under the weather” or are running a fever. Also, let your healthcare provider know if you are scheduled to receive a vaccination, as live vaccinations can make you sick.
  • Benzyl alcohol is contained in the non-liposome formulation. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants.

Do not take cytarabine if you:

• are allergic to any of its ingredients
• have a meningeal infection

DO NOT USE CYTARABINE INJECTION (which contains benzyl alcohol) INTRATHECALLY (into the brain or spinal cord). Only the liposome formulation may be given intrathecally.

If you take too much cytarabine call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If cytarabine is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Call your doctor for instructions if you miss an appointment for your cytarabine injection.

Cytarabine is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Cytarabine is used to treat certain types of leukemia (blood cancers). Cytarabine is also used to treat leukemia associated with meningitis.

Cytarabine will not treat an active meningitis infection that has already developed in the body.

Cytarabine may also be used for purposes not listed in this medication guide.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Do not receive a "live" vaccine while using cytarabine. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Acute Myeloid Leukemia (AML)

Conventional cytarabine: Remission induction (in combination with other antineoplastic agents) in AML (acute nonlymphocytic leukemia) in children and adults.237 a b c j

Conventional cytarabine and either idarubicin or daunorubicin (with or without thioguanine) are currently preferred components of induction regimens.g h However, various regimens have been used in combination therapy, and comparative efficacy is continually being evaluated.g

Conventional cytarabine: Has been used with other antineoplastic agents in regimens of consolidation following induction of a complete remission†; 239 242 243 f g role of such therapy in prolonging remissions and optimal dosage, schedules, and duration of consolidation chemotherapy regimens not established.g

Conventional cytarabine: Has been used with other antineoplastic agents in the treatment of erythroleukemia.f

Conventional cytarabine: Also has been used alone in high-dose† regimens to induce remissions in some patients with refractory AML or with secondary AML.f

Acute Lymphocytic Leukemia (ALL)

Conventional cytarabine: Has been used alone or with other antineoplastic agents for remission induction in ALL;237 a b c j however, combinations containing other antineoplastic agents are more effective.f h

Conventional cytarabine: Generally has been limited to use with other antineoplastics for remission induction in some patients who do not achieve a complete remission with combinations containing other agents or who relapse during maintenance therapy.f

Conventional cytarabine: Also has been used occasionally in regimens of consolidation and/or maintenance therapy following induction of a complete remission by combinations containing other agents.f h

Conventional cytarabine: Has been used alone in high-dose† regimens to induce remissions in some patients with refractory ALL.f

Meningeal Leukemia and Other Meningeal Neoplasms

Conventional cytarabine: Has been used effectively alone or with other chemotherapeutic agents in treatment, maintenance, and prophylactic therapy of meningeal leukemia and other meningeal neoplasms (e.g., lymphoma).a c f j

Many clinicians consider intrathecal conventional cytarabine and intrathecal methotrexate to have similar efficacy in the treatment of these conditions; however, intrathecal conventional cytarabine produces less systemic toxicity than intrathecal methotrexate.f

Liposomal cytarabine: Treatment of lymphomatous meningitis.d

Intrathecal liposomal cytarabine appears to have greater efficacy in the treatment of neoplastic meningitis and less systemic toxicity compared with intrathecal conventional cytarabine;i however, further study is needed.d i

Chronic Myelogenous Leukemia (CML)

Conventional cytarabine: Used with other antineoplastic agents (e.g., daunorubicin) in the treatment of accelerated or blast phase of CML;a b c f j however, various regimens have been used in combination therapy, and comparative efficacy is continually being evaluated.237 246 247 253 254

Non-Hodgkin’s Lymphomas†

Conventional cytarabine: Has been used with other antineoplastic agents for maintenance therapy of non-Hodgkin’s lymphoma in children†.f

Conventional cytarabine: Has been used with other antineoplastic agents for remission induction and/or maintenance therapy in adults with non-Hodgkin’s lymphomas, principally advanced diffuse histiocytic lymphoma†.f

Conventional cytarabine: Has been used alone in high-dose† regimens with some success for the treatment of refractory non-Hodgkin’s lymphomas†.f

Storage

Parenteral

25°C (may be exposed to 15–30°C).j

15–30°C.250 251 252 Store in manufacturer’s carton and protect from light.250

2–8°C; avoid freezing and aggressive agitation.d

Single-use vials do not contain preservative; use ≤4 hours after withdrawing dose from vial.d Do not save any unused portions for later administration; properly dispose of vial and any unused contents.d

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Manufacturer recommends that liposomal cytarabine not be mixed with other drugs or diluents.d

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For cytarabine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to cytarabine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Although there is no specific information comparing use of cytarabine in children with use in other age groups, cytarabine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of cytarabine in the elderly with use in other age groups, cytarabine is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking cytarabine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using cytarabine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine

Using cytarabine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adenovirus Vaccine
• Bacillus of Calmette and Guerin Vaccine, Live
• Cholera Vaccine, Live
• Influenza Virus Vaccine, Live
• Poliovirus Vaccine, Live
• Smallpox Vaccine
• Typhoid Vaccine
• Yellow Fever Vaccine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of cytarabine. Make sure you tell your doctor if you have any other medical problems, especially:

• Chickenpox (including recent exposure) or
• Herpes zoster (shingles)—Risk of severe disease affecting other parts of the body

• Gout (history of) or
• Kidney stones (history of)—Cytarabine may increase levels of uric acid in the body, which can cause gout or kidney stones

• Infection—Cytarabine can decrease your body's ability to fight infection

• Kidney disease or
• Liver disease—Effects of cytarabine may be increased because of slower removal from the body

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published.1–7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Applies to cytarabine: injectable powder for injection, injectable solution

Ocular

Very common (10% or more): Hemorrhagic conjunctivitis, corneal disorder
Common (1% to 10%): Photophobia, burning, visual disturbance, increased lacrimation, keratitis
Uncommon (0.1% to 1%): Conjunctivitis
Frequency not reported: Blindness[Ref]

Nervous system

Very common (10% or more): Somnolence
Common (1% to 10%): Decreased level of consciousness, dysarthria, nystagmus
Uncommon (0.1% to 1%): Neurotoxicity, neuritis, dizziness, headache, peripheral neuropathy, paraplegia (with intrathecal administration)
Frequency not reported: Dizziness, neurotoxicity rash, coma, convulsion, peripheral sensory neuropathy, ataxia, tremor, coma, convulsions[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Chest pain
Very rare (less than 0.01%): Arrhythmia
Frequency not reported: Pericarditis, cardiomyopathy[Ref]

Hematologic

Very common (10% or more): Bone marrow failure, thrombocytopenia, anemia, megaloblastic anemia, leukopenia, reticulocyte count decreased
Common (1% to 10%): Bleeding (all sites), thrombophlebitis
Frequency not reported: Reticulocytopenia, neutropenia, febrile neutropenia[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Anaphylactic reaction, allergic edema[Ref]

Immunologic

Very common (10% or more): Sepsis, infection
Frequency not reported: Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body (sometimes fatal)[Ref]

Local

Uncommon (0.1% to 1%): Injection site cellulitis, injection site thrombophlebitis
Frequency not reported: Injection site pain, injection site inflammation, injection site irritation, injection site sepsis[Ref]

Musculoskeletal

Very common (10% or more): Cytarabine syndrome (e.g., fever, myalgia, bone pain, occasionally chest pain, exanthema, maculopapular rash, conjunctivitis, nausea, malaise)
Uncommon (0.1% to 1%): Myalgia, joint pain[Ref]

Metabolic

Common (1% to 10%): Anorexia, hyperuricemia[Ref]

Psychiatric

Frequency not reported: Personality change, confusion[Ref]

Genitourinary

Uncommon (0.1% to 1%): Urinary retention
Frequency not reported: Amenorrhea, azoospermia[Ref]

Hepatic

Very common (10% or more): Hepatic function abnormal
Common (1% to 10%): Liver enzymes increased
Uncommon (0.1% to 1%): Jaundice
Frequency not reported: Liver abscess, hyperbilirubinemia, hepatomegaly, Budd-Chiari-syndrome (hepatic venous thrombosis)[Ref]

Respiratory

Very common (10% or more): Pneumonia, acute respiratory distress syndrome, pulmonary edema
Uncommon (0.1% to 1%): Shortness of breath[Ref]

Other

Very common (10% or more): Pyrexia[Ref]

Renal

Uncommon (0.1% to 1%): Renal dysfunction[Ref]

Dermatologic

Very common (10% or more): Alopecia, rash
Common (1% to 10%): Skin ulceration, erythema, bullous dermatitis, vasculitis
Uncommon (0.1% to 1%): Lentigo, palmar-plantar erythrodysesthesia syndrome, urticaria, pruritus, freckling, burning pain of palms and soles
Very rare (less than 0.01%): Neutrophilic eccrine hidradenitis
Frequency not reported: Skin bleeding[Ref]

Gastrointestinal

Very common (10% or more): Stomatitis, mouth ulceration, anal ulcer, anal inflammation, diarrhea, vomiting, nausea, abdominal pain
Common (1% to 10%): Necrotizing colitis
Uncommon (0.1% to 1%): Sore throat, esophagitis, esophageal ulceration, bowel necrosis
Frequency not reported: Pancreatitis, bowel necrosis, GI ulcer, pneumatosis intestinalis, peritonitis, mucosal bleeding[Ref]

Some side effects of cytarabine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Acute Leukemia Induction:
100 to 200 mg/m2/day or 2 to 6 mg/kg/day as a continuous IV infusion over 24 hours or in divided doses by rapid injection for 5 to 10 days. This course may be repeated approximately every 2 weeks.


For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
2 to 3 g/m2 IV every twelve hours for up to 12 doses. The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.


For chronic granulocytic leukemia / chronic myelogenous leukemia:
20 mg/m2 subcutaneously for 10 days per month for 6 months with interferon alfa.

For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
1 to 3 g/m2 IV every twelve hours for up to 12 doses The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.

The manufacturer has stated that doses ranging from 5 mg/m2 to 75 mg/m2 has been used intrathecally and the frequency of administration has varied from once a day for 4 days to once every 4 days. The manufacturer has further stated that 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment was the therapy most frequently used.

However, some clinicians recommend the following age based dosing:
<1 year: 20 mg
1 to 2 years: 30 mg
2 to 3 years: 50 mg
>3 years: 70 to 75 mg

For intrathecal administration, reconstitute with preservative-free saline and use immediately.