Cytarabine – Uses, Dosage, Side Effects, Interactions

Cytarabine liposome injection is a sustained-release formulation of the active ingredient cytarabine designed for direct administration into the cerebrospinal fluid (CSF). Cytarabine is a cell cycle phase-specific antineoplastic agent, affecting cells only during the S-phase of cell division. Intracellularly, cytarabine is converted into cytarabine-5′-triphosphate (ara-CTP), which is the active metabolite. The mechanism of action is not completely understood, but it appears that ara-CTP acts primarily through inhibition of DNA polymerase. Incorporation into DNA and RNA may also contribute to cytarabine cytotoxicity. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture.

Use in Cancer

Cytarabine is approved to be used with other drugs to treat:

• Acute non-lymphocytic leukemia in adults and children.

Cytarabine is also approved to prevent and treat:

• Meningeal leukemia (leukemia that has spread to the meninges). It is given as intrathecal therapy.

Cytarabine may also be used to treat:

• Acute lymphoblastic leukemia (ALL).
• Chronic myelogenous leukemia (CML) in the blastic phase.

Cytarabine is also being studied in the treatment of other types of cancer.

Cytarabine is also available in a different form, combined with Daunorubicin Hydrochloride

Contraindications

• Cytarabine is contraindicated in patients who have had a hypersensitivity reaction to it or any of the fundamental ingredients used in the preparation of the drug. With active meningeal infections, liposomal cytarabine is also contraindicated.

Dosage

Dosage Forms

• Solution, Injection: 10 mg/ml, 20 mg/mL (25 mL), 100 mg/ml
• Intrathecal injection, liposomal: 50 mg/5ml

Administration – Rapid intravenous infusion, infuse over 1 to 3 hours intravenously or subcutaneously or intrathecally.

Storage – Store at room temperature.

Dosing: Adult

1. Acute lymphoblastic leukemia (off-label dosing):

   • Induction regimen, relapsed or refractory- Administer 3,000 mg/sq.meter of cytarabine over 3 hours by intravenous infusion daily for five days in combination with idarubicin for three days.[rx]
   • Dose-intensive regimen- 3,000 mg/sq.meter of cytarabine over 2 hours by intravenous infusion. This dose is to be given every 12 hours on days 2 and 3 (4 doses/cycle) of even-numbered cycles in combination with methotrexate.[rx]
2. Acute myeloid leukemia (remission induction chemotherapy):

   • Administer standard dose 100 mg/sq.meter/day of cytarabine by continuous intravenous infusion for 7 days or give 200 mg/sq.meter/day by continuous intravenous infusion for 7 days(as 100 mg/m2 over 12 hours every 12 hours).[rx]
3. Acute myeloid leukemia consolidation therapy (off-label use):

   • 5+2 regimen: Administer 100 mg/sq.meter/day of cytarabine for five days by intravenous infusion in combination with daunorubicin or idarubicin, or mitoxantrone.[rx][rx]
4. Acute myeloid leukemia salvage treatment (off-label use):

   • CLAG-M regimen: Administer 2,000 mg/sq.meter/day of cytarabine by intravenous infusion over 4 hours for five days in combination with cladribine, G-CSF, and mitoxantrone.[rx]
5. Acute promyelocytic leukemia consolidation therapy (off-label use):

   • First consolidation course: Administer 200 mg/sq.meter/day of cytarabine by intravenous infusion for seven days in combination with daunorubicin.[rx]
   • Second consolidation course:

     • If age is ≤60 years and low risk (WBC <10,000/cubic mm), then administer 1,000 mg/sq.meter of cytarabine every 12 hours for four days (8 doses) by intravenous infusion.
     • If age is <50 years and high risk (WBC ≥10,000/cubic mm), then administer 2,000 mg/sq.meter of cytarabine every 12 hours for five days (10 doses) by intravenous infusion.
     • If age is 50 to 60 years and high risk (WBC ≥10,000/cubic mm), then administer 1500 mg/sq.meter of cytarabine every 12 hours for five days (10 doses) by intravenous infusion.
     • If age is >60 years and high risk (WBC ≥10,000/cubic mm) then administer 1,000 mg/sq.meter every 12 hours for four days (8 doses) by intravenous infusion.
6. Acute promyelocytic leukemia induction (off-label dosing):

   • Administer 200 mg/sq.meter/day of cytarabine by continuous intravenous infusion for seven days, beginning on the third day of treatment in combination with tretinoin and daunorubicin.[rx][rx]

Usual Adult Dose for

Acute Nonlymphocytic Leukemia

Induction as part of combination chemotherapy:

• 100 mg/m2/day by continuous IV infusion (Days 1 through 7) or 100 mg/m2 IV every 12 hours (Days 1 through 7)

Meningeal Leukemia

• The dose ranges from 5 mg/m2 to 75 mg/m2 intrathecally once a day for 4 days to once every 4 days (30 mg/m2 every 4 days until cerebrospinal fluid findings are normal, followed by one additional treatment is the most frequently used dose)

Usual Pediatric Dose for

Acute Nonlymphocytic Leukemia

Induction as part of combination chemotherapy:

• 100 mg/m2/day by continuous IV infusion (Days 1 through 7) or 100 mg/m2 IV every 12 hours (Days 1 through 7)
  

Acute Lymphocytic Leukemia

• The literature and/or local protocol should be consulted.

Meningeal Leukemia

• The dose ranges from 5 mg/m2 to 75 mg/m2 intrathecally once a day for 4 days to once every 4 days (30 mg/m2 every 4 days until cerebrospinal fluid findings are normal, followed by one additional treatment is the most frequently used dose)

Side Effects

The Most Common

• ongoing pain that begins in the stomach area but may spread to the back
• redness, pain, swelling, or burning at the site where the injection was given
• nausea
• vomiting
• diarrhea
• stomach pain
• loss of appetite
• sores in the mouth and throat
• hair loss
• muscle or joint pain
• tiredness
• sore or red eyes

More Common

• pale skin
• fainting
• dizziness
• fast or irregular heartbeat
• rash
• hives
• itching
• difficulty breathing or swallowing
• chest pain
• yellowing of the skin or eyes
• dark-colored urine or decreased urination
• shortness of breath
• sudden change or loss of vision
• seizures
• confusion
• numbness, burning, or tingling in the hands, arms, feet, or legs

Rare

• Headache
• Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This can put you at risk for infection, anemia and/or bleeding. Nadir: White blood cells: 7-10 days, platelets: 12-15 days.
• Nausea and vomiting
• Mouth sores (usually occur 7-10 days after therapy).
• Increases in blood tests measuring liver function. These return to normal once treatment is discontinued. More often associated with high-dose regimens.
• Diarrhea
• Loss of appetite
• Skin rash, redness and itching
• Flu-like symptoms (fever, chills, generalized aches and pains) within the first few days of treatment.
• Pain, redness and skin peeling of the palms of hands and soles of feet (hand-foot syndrome) may occur with high-dose therapy (rare). Use of steroid creams or moisturizers may be helpful.
• Blood test abnormalities: Increase in blood level of uric acid. A medication called allopurinal may be given to decrease these levels.
• Temporary hair loss (uncommon, but thinning may occur).
• Eye pain, tearing, sensitivity to light and blurred vision may occur with high-dose therapy. Often steroid drops or ointment to the eyes are used to prevent or relieve this condition.
• Dizziness, headache, excessive sleepiness, confusion, loss of balance may occur in up to 10% of patients receiving high dose therapy. Onset is usually 5 days after treatment and may last up to 1 week. More often these toxicities are mild and reversible.

Drug interactions

Pregnancy and Lactation

When To Contact Your Doctor or Health Care Provider:

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Fever of 100.4°F (38°C) or higher or chills (possible signs of infection).
• Chest pain or heart palpitations
• Inability to pass urine

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

• Diarrhea (4-6 episodes in a 24 hour period)
• Nausea (unable to drink fluids and unrelieved with prescription medication).
• Vomiting (more than 4-5 times in a 24 hour period)
• Unusual bleeding or bruising
• Black or tarry stools, or blood in your stools or urine
• Extreme fatigue (unable to carry on self-care activities)
• Mouth sores (painful redness, swelling or ulcers)
• Cough and/or shortness of breath
• Excessive sleepiness or confusion
• Changes in balance and coordination
• Yellowing of the skin or eyes
• Changes in vision or burning/or tearing of eyes
• Swelling, redness and pain in one leg or arm and not the other
• Stomach pains

Always inform your health care provider if you experience any unusual symptoms.

Precautions:

• Before starting cytarabine treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take aspirin, products containing aspirin unless your doctor specifically permits this.
• Do not receive any kind of immunization or vaccination without your doctor’s approval while taking cytarabine.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (cytarabine may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus).
• For both men and women: Use contraceptives, and do not conceive a child (get pregnant) while taking cytarabine. Barrier methods of contraception, such as condoms, are recommended.

Self-Care Tips:

• Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
• You may be at risk of infection so try to avoid crowds or people with colds, and report fever or any other signs of infection immediately to your health care provider.
• Wash your hands often.
• To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times a day with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed with 8 ounces of water.
• Use an electric razor and a soft toothbrush to minimize bleeding.
• Avoid contact sports or activities that could cause injury.
• To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals.
• Keeps palms of hands and soles of feet moist using emollients such as Aveeno®, Udder Cream, Lubriderm® or Bag Balm®.
• Avoid sun exposure. Wear SPF 30 (or higher) sunblock and protective clothing.
• In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. You should discuss this with your doctor.
• Get plenty of rest.
• Maintain good nutrition.
• If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

References