Nelarabine

Nelarabine is a chemotherapy drug used in T-cell acute lymphoblastic leukemia. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity.

Nelarabine® is indicated for the treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.

Nelarabine belongs to the group of medicines called antineoplastics. It is used to treat specific types of cancer called T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL).

Nelarabine interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by Nelarabine, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious, but may cause concern.

Before you begin treatment with Nelarabine, you and your doctor should talk about the good Nelarabine will do as well as the possible risks of using it. Nelarabine is usually given to patients who have already used at least two other cancer medicines first.

Nelarabine is to be administered only by or under the supervision of your doctor.

Nelarabine is available only with your doctor's prescription.

Recommended Dosage

This product is for intravenous use only.

The recommended duration of treatment for adult and pediatric patients has not been clearly established. In clinical trials, treatment was generally continued until there was evidence of disease progression, the patient experienced unacceptable toxicity, the patient became a candidate for bone marrow transplant, or the patient no longer continued to benefit from treatment.

Adult

Dosage: The recommended adult dose of Nelarabine is 1,500 mg/m² administered intravenously over 2 hours on Days 1, 3, and 5 repeated every 21 days. Nelarabine is administered undiluted.

Pediatric

Dosage: The recommended pediatric dose of Nelarabine is 650 mg/m² administered intravenously over 1 hour daily for 5 consecutive days repeated every 21 days. Nelarabine is administered undiluted.

Dosage Modification

Administration of Nelarabine should be discontinued for neurologic adverse reactions of NCI Common Toxicity Criteria Grade 2 or greater. Dosage may be delayed for other toxicity including hematologic toxicity.

Adjustment of Dose in Special Populations

Nelarabine has not been studied in patients with renal or hepatic dysfunction. No dose adjustment is recommended for patients with a creatinine clearance (CLcr) ≥50 mL/min. There are insufficient data to support a dose recommendation for patients with a CLcr <50 mL/min.

Prevention of Hyperuricemia

Appropriate measures (e.g., hydration, urine alkalinization, and prophylaxis with allopurinol) must be taken to prevent hyperuricemia.

Instructions for Handling, Preparation, and Administration

Handling: Nelarabine is a cytotoxic agent. Caution should be used during handling and preparation. Use of gloves and other protective clothing to prevent skin contact is recommended. Proper aseptic technique should be used. Guidelines for proper handling and disposal of anticancer drugs have been published.1-4

Preparation and Administration: Do not dilute Nelarabine prior to administration. The appropriate dose of Nelarabine is transferred into polyvinylchloride (PVC) infusion bags or glass containers and administered as a 2-hour infusion in adult patients and as a 1-hour infusion in pediatric patients.

Prior to administration, inspect the drug product visually for particulate matter and discoloration.

Stability: Nelarabine Injection is stable in polyvinylchloride (PVC) infusion bags and glass containers for up to 8 hours at up to 30° C.

See also:
What is the most important information I should know about Nelarabine?

Nelarabine may cause serious side effects of the central nervous system, such as problems with balance, coordination, or fine motor skills. These symptoms may not go away even after you stop receiving Nelarabine. Talk with your doctor if you have concerns about any possible long-term side effects.

Do not use Nelarabine if you are pregnant. It could harm the unborn baby.

You should not breast-feed while you are using Nelarabine.

Before you receive Nelarabine, tell your doctor if you have liver or kidney disease, a nerve disorder, a history of chemotherapy or radiation treatment of your head, neck, or spinal cord.

Nelarabine can lower blood cells that help your body fight infections and help your blood to clot. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while you are being treated with Nelarabine.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Use Nelarabine as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Nelarabine. Talk to your pharmacist if you have questions about this information.
• Nelarabine is usually given as an injection at your doctor's office, hospital, or clinic.
• If you miss a dose of Nelarabine, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Nelarabine.

Use: Labeled Indications

T-cell acute lymphoblastic leukemia/lymphoma: Treatment of relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma in patients ≥1 year of age following at least 2 chemotherapy regimens

See also:
What other drugs will affect Nelarabine?

Nelarabine and ara-G did not significantly inhibit the activities of the human hepatic cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 in vitro at concentrations of Nelarabine and ara-G up to 100 ?M.

There is in vitro evidence that pentostatin is a strong inhibitor of adenosine deaminase. This may result in a reduction in the conversion of the pro-drug Nelarabine to its active moiety and consequently in a reduction in efficacy of Nelarabine and/or change in adverse event profile of either drug. Administration of Nelarabine in combination with adenosine deaminase inhibitors, such as pentostatin, is not recommended

See also:
What are the possible side effects of Nelarabine?

Applies to Nelarabine: intravenous solution

In addition to its needed effects, some unwanted effects may be caused by Nelarabine (the active ingredient contained in Nelarabine). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking Nelarabine:

More common:

• Abdominal pain or cramps
• anxiety
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• bloody nose
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in walking and balance
• chest pain
• chills
• clumsiness or unsteadiness
• cold sweats
• coma
• convulsions
• cool, pale skin
• cough or hoarseness
• decreased or uncontrolled urination
• difficulty with breathing
• discouragement
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• drowsiness
• dry mouth
• fast or irregular heartbeat
• feeling sad or empty
• feeling unusually cold
• fever
• flushed, dry skin
• fruit-like breath odor
• headache
• incoordination
• increased hunger
• increased thirst
• increased urination
• irritability
• loss of appetite
• loss of interest or pleasure
• lower back, side, or stomach pain
• mood or mental changes
• muscle cramps in hands, arms, feet, legs, or face
• muscle pain
• muscle spasms (tetany) or twitching seizures
• muscle weakness
• nausea or vomiting
• nervousness
• nightmares
• numbness, tingling, pain, or weakness in hands, feet, fingertips, or mouth
• pain or tenderness around the eyes and cheekbones
• painful or difficult urination
• paralysis or severe weakness of legs
• rapid breathing
• seizures
• shakiness and unsteady walk
• shivering
• shortness of breath
• sleepiness or unusual drowsiness
• sleeplessness
• slurred speech
• small red or purple spots on skin
• sneezing
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stuffy or runny nose
• sunken eyes
• sweating
• swelling of hands, ankles, feet, or lower legs
• swollen glands
• tightness in chest
• trouble concentrating
• trouble sleeping
• troubled breathing with exertion
• unable to sleep
• uncontrolled bowel movements
• unexplained weight loss
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual bleeding or bruising
• unusual tiredness or weakness
• wheezing
• wrinkled skin
• yellow eyes or skin

• Change in taste
• loss of memory
• loss of taste
• problems with memory

Minor Side Effects

Some of the side effects that can occur with Nelarabine may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

• Back pain
• diarrhea
• difficulty having a bowel movement (stool)
• difficulty with moving
• full or bloated feeling
• joint pain
• lack or loss of strength
• muscle aching or stiffness
• pain in the arms or legs
• pressure in the stomach
• swelling of the abdomen or stomach area
• swelling or inflammation of the mouth
• swollen joints