Nelarabine – Uses, Dosage, Side Effects, Interactions

Indications

  • For the treatment of pediatric and adult patients with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.
  • Nelarabine is indicated for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Due to the small patient populations in these disease settings, the information to support these indications is based on limited data
  • Nelarabine is a purine analog and antineoplastic agent used in the therapy of T-cell lymphoblastic leukemia or lymphoma. Nelarabine is associated with a low rate of transient serum enzyme elevations during therapy and has been linked to rare instances of clinically apparent acute liver injury with jaundice.
  • T-cell acute lymphoblastic leukemia (T-ALL)
  • T-cell lymphoblastic lymphoma (T-LBL)

Use in Cancer

Nelarabine is approved to treat adults and children aged 1 year or older with:

  • T-cell acute lymphoblastic leukemia.
  • T-cell lymphoblastic lymphoma.

Nelarabine is used in patients whose cancer has not gotten better with other treatments or has come back after at least two chemotherapy regimens.

Contraindications

  • Hypersensitivity to nelarabine or any component of the formulation
  • Severe neurologic reactions have been reported. Monitor for signs and
  • symptoms of neurologic toxicity.
  • Hematologic Reactions: Complete blood counts including platelets should be monitored regularly.
  • Fetal harm can occur if administered to a pregnant woman. Women should be advised not to become pregnant when taking

Dosage

Strengths: 5 mg/mL

Usual Adult Dose

Acute Lymphoblastic Leukemia

  • 1500 mg/m2 IV over 2 hours on days 1, 3, and 5 repeated every 21 days

Lymphoma

  • 1500 mg/m2 IV over 2 hours on days 1, 3, and 5 repeated every 21 days

Usual Pediatric Dose

Acute Lymphoblastic Leukemia

  • 650 mg/m2 IV over 1 hour daily for 5 consecutive days repeated every 21 days

Lymphoma

  • 650 mg/m2 IV over 1 hour daily for 5 consecutive days repeated every 21 days

Side Effects

The Most Common

  • nausea
  • vomiting
  • diarrhea
  • constipation
  • loss of appetite
  • stomach pain or swelling
  • sores on the mouth or tongue
  • headache
  • dizziness
  • difficulty falling asleep or staying asleep
  • depression
  • pain in your arms, legs, back, or muscles
  • swelling of the hands, arms, feet, ankles, or lower legs
  • blurred vision
  • pale skin
  • shortness of breath
  • fast heartbeat
  • Myelosuppression, somnolence, dizziness, peripheral neurologic disorders,
  • hypoesthesia, headache, paresthesia, fatigue, pyrexia, asthenia, edema, pain, myalgia

More Common

  • chest pain
  • cough
  • wheezing
  • unusual bleeding or bruising
  • nosebleeds
  • small red or purple dots on the skin
  • fever, sore throat, chills, or other signs of infection
  • extreme thirst
  • decreased urination
  • sunken eyes
  • dry mouth and skin

Rare

  • abdominal pain
  • anxiety
  • fever
  • flu and flu-like symptoms (e.g., fatigue, sore throat, headache, fever, chills)
  • symptoms of a chest or lung infection (bronchitis, pneumonia; e.g., shortness of breath, cough, chest pain)
  • symptoms of infection (e.g., unusual fatigue, fever, aches, pain, flu-like symptoms)
  • symptoms of shingles (e.g., “band” of severe pain, blistering rash, headache, burning, tingling, numbness or itchiness of the skin, general feeling of being unwell)
  • symptoms of tuberculosis (e.g., persistent cough, fever, weight loss)
  • vaginal yeast infection (e.g., itching, white, curd-like discharge)

Drug Interactions

Pregnancy and Lactation

Pregnancy Category D

Pregnancy

Based on its mechanism of action and findings in animal studies, this drug can cause fetal harm when administered to a pregnant woman. Administration to pregnant animals during the period of organogenesis resulted in teratogenicity at maternal doses below the recommended human adult dose. Limited available data on pregnant women are insufficient to determine a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the pregnant woman associated with untreated leukemia or lymphoma including anemia, thrombocytopenia, and death.

Breastfeeding

There are no data on the presence of this drug in human or animal milk, the effect on the breastfed child, or the effect on milk production. Because of the potential for serious adverse reactions in the breastfed child such as severe neurological reactions, women should not breastfeed during therapy.

Use should be avoided.
Excreted into human milk: Unknown
Excreted into animal milk: Data not available

What special precautions should I follow?

Before using nelarabine injection,

  • tell your doctor and pharmacist if you are allergic to nelarabine, any other medications, or any of the ingredients in nelarabine injection. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention adenosine deaminase inhibitors such as pentostatin (Nipent). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had kidney or liver disease.
  • tell your doctor if you or your partner are pregnant or plan to become pregnant. If you are female, you will need to take a pregnancy test before you begin receiving nelarabine and should not become pregnant while you are using nelarabine. If you are male, you and your female partner should use birth control during your treatment and for 3 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you or your partner become pregnant while using nelarabine, call your doctor immediately. Nelarabine may harm the fetus.
  • tell your doctor if you are breastfeeding. You should not breastfeed while you are using nelarabine.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are receiving nelarabine.
  • you should know that nelarabine may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
  • do not have any vaccinations during your treatment with nelarabine without talking with your doctor.

When to Contact Your Doctor or Health Care Provider:

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

  • Fever of 100.4 F (38C) or higher, chills (possible signs of infection).
  • Seizures, confusion, extreme sleepiness, numbness/tingling or extreme weakness.
  • Nausea (interferes with the ability to eat and is unrelieved with prescribed medication)
  • Vomiting (vomiting more than 4-5 times in a 24-hour period)
  • Diarrhea (4-6 episodes in a 24-hour period)
  • Extreme fatigue (unable to carry on self-care activities)
  • Constipation unrelieved by laxative use
  • Numbness and tingling in the hands, fingers, feet or toes
  • Problems with fine motor skills such as buttoning clothes
  • Unsteady while walking or increased tripping while walking
  • Weakness when getting out of a chair or walking upstairs
  • Swelling of the feet or ankles. Sudden weight gain.
  • Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst, dry mouth, dark and decreased amount of urine, or dizziness
  • Unable to urinate
  • Unusual bleeding or bruising
  • Black or tarry stools, or blood in your stools
  • Blood in the urine
  • Chest pain or pressure or a fast heartbeat

Always inform your healthcare provider if you experience any unusual symptoms.

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 those not feeling well, and report fever or any other signs of infection immediately to your healthcare provider.
  • Wash your hands often.
  • Use an electric razor and a soft toothbrush to minimize bleeding.
  • Avoid contact sports or activities that could cause injury.
  • This medication causes little nausea. But if you should experience nausea, take anti-nausea medications as prescribed by your doctor, and eat small frequent meals. Sucking on lozenges and chewing gum may also help.
  • Keep your bowels moving. Your healthcare provider may prescribe a stool softener to help prevent constipation that may be caused by this medicine.
  • Avoid sun exposure. Wear SPF 15 (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 healthcare team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.
  • Acetaminophen or ibuprofen may help relieve discomfort from fever, headache, and/or generalized aches and pains. However, be sure to talk with your doctor before taking it.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Nelarabine
  2. https://pubchem.ncbi.nlm.nih.gov/substance/47206859
  3. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fffa5d75-0dba-4ad7-a252-5f60fa28489a
  4. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021877s005lbl.pdf
  5. https://go.drugbank.com/drugs/DB01280
  6. https://www.drugs.com/mtm/nelarabine.html
  7. https://medlineplus.gov/druginfo/meds/a607077.html
  8. ChemIDplus Chemical Information Classification
  9. CompTox Chemicals Dashboard Chemical Lists
  10. (2R,3S,4S,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
    (2R,3S,4S,5R)-2-(2-amino-6-methoxypurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
  11. NCI Thesaurus Tree
  12. LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    NORMAN Suspect List Exchange Classification
  13. LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
  14. PubChem
  15. Therapeutic category of drugs in Japan
    Anatomical Therapeutic Chemical (ATC) classification
  16. NCBI

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