Azacitidine

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

Azacitidine is used to treat certain types of bone marrow cancers and blood cell disorders.

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

You should not receive this medicine if you have liver cancer.

You should not receive this medicine if you are allergic to azacitidine or mannitol, or if you have:

• liver cancer.

To make sure azacitidine is safe for you, tell your doctor if you have:

• kidney disease; or
• a history of liver disease.

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

Use birth control to prevent pregnancy while you are receiving azacitidine, whether you are a man or a woman. If a man fathers a baby while using azacitidine, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment, and for at least 4 weeks after your treatment ends.

It is not known whether azacitidine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

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.

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

Do not receive a "live" vaccine while receiving azacitidine, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Other drugs may interact with azacitidine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Azacitidine is injected under the skin, or into a vein through an IV. A healthcare provider will give you this injection.

This medicine is usually given for 7 days in a row every 4 weeks for at least 4 treatment cycles. Your treatment schedule may be different. Follow your doctor's instructions.

You may also be given medications to reduce nausea and vomiting while you are receiving azacitidine.

Tell your caregiver right away if azacitidine accidentally gets on your skin. Wash the area thoroughly with soap and warm water.

Azacitidine can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

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

Azacitidine is a prescription medication used to treat myelodysplastic syndrome. The bone marrow does not make enough healthy blood cells in this type of condition. Azacitidine belongs to a group of drugs called demethylation agents, which work by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow.

This medication is available in an injectable form to be given directly under the skin (subQ) or into the vein (IV) by a healthcare professional.

Common side effects of azacitidine include nausea, vomiting, fever, and constipation.

You should not receive this medicine if you are allergic to azacitidine or mannitol, or if you have:

• liver cancer.

To make sure azacitidine is safe for you, tell your doctor if you have:

• kidney disease; or

• a history of liver disease.

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

Use birth control to prevent pregnancy while you are receiving azacitidine, whether you are a man or a woman. If a man fathers a baby while using azacitidine, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment, and for at least 4 weeks after your treatment ends.

It is not known whether azacitidine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

General

• Consult specialized references for proper handling and disposal of antineoplastics.1

• Pretreatment for nausea and vomiting is recommended by the manufacturer.1 9

Administration

Administer by sub-Q injection or short IV infusion.1

Has been administered by continuous IV infusion† in at least one clinical trial.1 6 10 11

Sub-Q Administration

Administer suspension by sub-Q injection into the thigh, abdomen, or upper arm; rotate injection sites.1

Give new injections ≥2.54 cm (1 inch) from an old site; do not give injections into areas where the skin is tender, bruised, red, or hard.1

If the dose exceeds 4 mL, divide the dose equally into 2 syringes and inject into 2 separate sites.1

Immediately prior to administration, resuspend syringe contents by vigorously rolling the syringe between the palms until a uniform suspension is achieved.1

Handle cautiously; if the reconstituted suspension contacts skin or mucosa, wash the skin immediately and thoroughly with soap and water or flush the mucosa with copious amounts of water.1

Reconstitute vial containing 100 mg of azacitidine with 4 mL of sterile water for injection to provide a suspension containing 25 mg/mL.1 Suspension will be cloudy.1

Vigorously shake or roll the vial until complete dissolution has occurred.1

Do not administer such concentrated suspensions IV.1 14

Vials are intended for single use only; discard any unused portions of the suspension.1

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Infuse IV solution over 10–40 minutes.1 IV administration must be completed within 1 hour of reconstitution.1

The concentrated suspension intended for sub-Q injection must not be administered IV.1 14

Handle cautiously; if the reconstituted solution contacts skin or mucosa, wash the skin immediately and thoroughly with soap and water or flush the mucosa with copious amounts of water.1

Reconstitute vial containing 100 mg of azacitidine with 10 mL of sterile water for injection to provide a solution containing 10 mg/mL.1 Solution should be clear.1

Shake vial vigorously or roll until complete dissolution has occurred.1

Reconstituted solution should be further diluted prior to IV administration.1

Withdraw the desired dose of reconstituted azacitidine solution from the vial and inject into a 50- to 100-mL infusion bag containing 0.9% sodium chloride injection or lactated Ringer’s injection.1

Vials are intended for single use only; discard any unused portions.1

Infuse solution over 10–40 minutes.1

Dosage

Adults

Initially, 75 mg/m2 daily for 7 days every 4 weeks.1 2 6 9

Daily dosage may be increased to 100 mg/m2 if no beneficial effect is observed after 2 treatment cycles and if no toxicity other than nausea and vomiting has occurred.1 9

The manufacturer recommends that patients receive at least 4–6 treatment cycles, although additional treatment cycles may be needed to achieve complete or partial response.1

Continue azacitidine as long as the patient is deriving benefit from therapy.1 9

Monitor for hematologic and renal toxicities (see Hematologic Effects and also Renal Toxicity, under Cautions); delay treatment or reduce dosage accordingly.1 9

Dosage of 75 mg/m2 daily for 7 days every 28 days has been used.10001 10002 10005 10007 10009 In several clinical trials, patients who achieved complete response received 3 additional cycles of the drug; those exhibiting partial response or improvement received the drug until complete response or relapse occurred.10001

Adjust the azacitidine dosage in the next treatment cycle based on nadir ANC and platelet counts observed in the current cycle.1 (See Table 1.)

Base dosage adjustments on nadir blood cell counts and bone marrow biopsy cellularity at the time of the nadir count (see Table 2), unless clear improvement in differentiation (increased percentage of mature granulocytes and higher ANC) is observed at the time of initiation of the subsequent cycle relative to the time of initiation of the previous cycle.1 If such improvement in differentiation is observed, continue the current dosage.1

The next 7-day course of azacitidine should be given 28 days after initiation of the previous course, provided that both the WBC and platelet counts at day 28 exceed the nadir counts by ≥25% and are increasing.1 If an increase in WBC and platelet counts of ≥25% has not occurred by day 28, reassess these blood cell counts every 7 days;1 if increases of ≥25% do not occur by day 42, patients should receive 50% of the scheduled dosage.1

If unexplained elevations of BUN or Scr occur, delay the next cycle until such values return to normal or baseline levels and reduce the dosage of azacitidine in the next treatment cycle by 50%.1

If unexplained decreases in serum bicarbonate concentrations (to <20 mEq/L) occur, reduce the dosage of azacitidine in the next treatment cycle by 50%.1

Special Populations

No special population dosage recommendations at this time.1 9

Storage

Parenteral

Powder: 25°C (may be exposed to 15–30°C).1

Reconstituted suspension for sub-Q injection (in vial or syringe): 25°C for up to 1 hour or 2–8°C for up to 8 hours.1 Refrigerated suspensions may be allowed to equilibrate to room temperature for up to 30 minutes prior to administration.1

Reconstituted solution for IV infusion: 25°C; complete IV administration within 1 hour of reconstitution.1

Compatibility

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

Parenteral

Incompatible with solutions containing sodium bicarbonate.1

• Importance of women informing clinicians immediately if they are or plan to become pregnant.1 Advise women to avoid pregnancy and advise men not to father a child during therapy.1

• Importance of women informing clinicians if they plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., underlying hepatic or renal disease).1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

• It is used to treat a health problem called myelodysplastic syndrome (MDS).
• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
• Chest pain or pressure.
• Shortness of breath.
• Very bad dizziness or passing out.
• Very bad headache.
• Very bad irritation where the shot was given.
• Feeling very tired or weak.
• A very bad skin problem (necrotizing fasciitis) has happened in people taking this medicine. Sometimes, this has been deadly. Call your doctor right away if your skin is warm with red or purple areas of swelling that spread quickly. Call your doctor right away if you have ulcers, blisters, black spots on the skin, or any other skin changes that concern you.

Note: Azacitidine is associated with a moderate emetic potential (Basch 2011; Roila 2010); antiemetics are recommended to prevent nausea and vomiting.

Myelodysplastic syndromes (MDS): IV, SubQ: Initial cycle: 75 mg/m2/day for 7 days. Subsequent cycles: 75 mg/m2/day for 7 days every 4 weeks; dose may be increased to 100 mg/m2/day if no benefit is observed after 2 cycles and no toxicity other than nausea and vomiting have occurred. Patients should be treated for a minimum of 4 to 6 cycles; treatment may be continued as long as patient continues to benefit.

Note: Alternate (off-label) schedules (which have produced hematologic response) have been used for convenience in community oncology centers (Lyons 2009): SubQ:

75 mg/m2/day for 5 days (Mon-Fri), 2 days rest (Sat, Sun), then 75 mg/m2/day for 2 days (Mon, Tues); repeat cycle every 28 days or

50 mg/m2/day for 5 days (Mon-Fri), 2 days rest (Sat, Sun), then 50 mg/m2/day for 5 days (Mon-Fri); repeat cycle every 28 days or

75 mg/m2/day for 5 days (Mon-Fri), repeat cycle every 28 days

Acute myeloid leukemia (AML) (off-label use): SubQ: 75 mg/m2/day for 7 days every 4 weeks for at least 6 cycles; treatment may be continued as long as patient continues to benefit or until disease progression or unacceptable toxicity (Fenaux 2010). Dose reductions and/or therapy interruption may be required for hematologic toxicity.

Dosage adjustment based on serum electrolytes: If serum bicarbonate falls to <20 mEq/L (unexplained decrease): Reduce dose by 50% for next treatment course.

Azacitidine is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Azacitidine is used to treat certain types of bone marrow cancers and blood cell disorders.

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

-First Treatment Cycle: 75 mg/m2/day via subcutaneous injection or IV infusion for 7 days; repeat cycles every 4 weeks.
-Subsequent Cycles: After 2 treatment cycles, may increase dose to 100 mg/m2 if no beneficial effect is seen and if no toxicity other than nausea and vomiting has occurred.
-Duration of Therapy: Minimum of 4 to 6 cycles; may continue treatment as long as the patient continues to benefit.

Comments: Premedicate patients for nausea and vomiting.

Use: Treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome (MDS) subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions; refractory anemia with excess blasts (RAEB); refractory anemia with excess blasts in transformation (RAEB-T); and chronic myelomonocytic leukemia (CMMoL).

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.