azacitidine

a-za-SYE-ti-deen

Therapeutic Classification: antineoplastics

Pharmacologic Classification: nucleoside analogues

High Alert

IV: SC: Myelodysplastic syndromes, including:
- Some refractory anemias,
- Chronic myelomonocytic leukemia.
IV: Newly diagnosed juvenile myelomonocytic leukemia.
PO: Continued treatment of patients with acute myeloid leukemia who achieved first complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy.

Inhibits DNA synthesis.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Absorption: IV administration results in complete bioavailability; 89% absorbed following SUBQ administration; bioavailability of oral administration 11% relative to SUBQ administration.

Distribution: Widely distributed to extravascular tissues.

Metabolism/Excretion: 85% excreted in urine; some hepatic metabolism may occur. <1% fecal elimination.

Half-Life: IV or SUBQ: 4 hr; Oral: 30 min.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
SUBQ/IV	unknown	30 min	unknown
PO	unknown	1 hr	unknown

Contraindicated in:

Hypersensitivity;
Advanced malignant hepatic tumors (IV or SUBQ only);
Myelodysplastic syndromes (oral only) (↑ risk of mortality);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment;
Hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children <18 yr (PO or SUBQ) or <1 mo (IV);
Geri: ↑risk of toxicity in older adults due to age-related ↓ in renal function.

Derm: acute febrile neutrophilic dermatosis, ecchymosis

F and E: hypokalemia

GI: abdominal pain, constipation, diarrhea, nausea, vomiting, HEPATOTOXICITY

GU: ↓fertility, NEPHROTOXICITY, renal tubular acidosis

Hemat: anemia, neutropenia, thrombocytopenia

Local: injection site erythema

Metab: ↓appetite

MS: arthralgia

Neuro: dizziness, fatigue

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), TUMOR LYSIS SYNDROME

Drug-drug:

Additive bone marrow depression may occur with other antineoplastics.

Do NOT interchange/substitute parenteral product with oral formulation.

Myelodysplastic Syndromes

SC IV (Adults ): 75 mg/m² once daily on Days 1–7 of each 28-day cycle; if no beneficial effect occurs after two cycles and if no toxicity other than nausea or vomiting has occurred, may ↑ to 100 mg/m² once daily on Days 1–7 of each 28-day cycle. Continue for as long as patient benefits (minimum of 4–6 cycles recommended).

Juvenile Myelomonocytic Leukemia

IV (Children ≥1 yr and ≥10 kg): 75 mg/m² once daily on Days 1–7 of each 28-day cycle. Continue for ≥3 cycles and a maximum of 6 cycles (as long as patient continues to benefit).
IV (Children ≥1 mo–<1 yr or <10 kg): 2.5 mg/kg once daily on Days 1–7 of each 28-day cycle. Continue for ≥3 cycles and a maximum of 6 cycles (as long as patient continues to benefit).

Acute Myeloid Leukemia

PO (Adults ): 300 mg once daily on Days 1–14 of each 28-day cycle; continue until disease progression or unacceptable toxicity.

(Generic available)

Lyophilized powder for injection (Vidaza): 100 mg/vial
Tablets (Onureg): 200 mg; 300 mg

Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, stools, urine, emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for ↑ fatigue, dyspnea, and orthostatic hypotension.
Assess for nausea and vomiting during therapy. Premedicate patient before each dose. For PO doses: If Grade 3 or 4 nausea or vomiting of diarrhea occurs: Hold dose until nausea and vomiting has resolved to ≤Grade 1. If symptoms reoccur, hold dose until resolved to ≤Grade 1. Resume at ↓ dose of 200 mg once daily. If symptoms continue after dose ↓, ↓ the treatment duration by 7 days. If symptoms continue or reoccur after dose and schedule ↓, discontinue azacitidine.
Monitor for signs of anaphylaxis (facial edema, wheezing, dizziness, fainting, tachycardia, hypotension). Discontinue medication immediately and report symptoms. Epinephrine and resuscitation equipment should be readily available.

Lab Test Considerations:

Verify negative pregnancy status prior to starting therapy.
Monitor CBC with differential and platelet count prior to each dosing cycle. For PO doses: If ANC <0.5 × 10⁹/L on Day 1 of a cycle, do not administer azacitidine until ANC ≥0.5 × 10⁹/L. If neutrophils <1 × 10⁹/L and 1st occurrence, hold therapy until neutrophils ≥1 × 10⁹/L. If occurs in 2 consecutive cycles, hold therapy until neutrophils ≥1 × 10⁹/L; then resume at ↓ dose of 200 mg once daily. If febrile neutropenia continues after dose ↓, ↓ treatment duration by 7 days. If febrile neutropenia reoccurs after dose and schedule ↓, discontinue azacitidine. If platelets <50 × 10⁹/L and 1st occurrence, hold therapy until platelets ≥50 × 10⁹/L. If occurs in 2 consecutive cycles, hold therapy until platelets ≥50 × 10⁹/L; then resume at ↓ dose of 200 mg once daily. If thrombocytopenia with bleeding continues after dose ↓, ↓ the treatment duration by 7 days. If thrombocytopenia with bleeding reoccurs after dose and schedule ↓, discontinue azacitidine. For IV or SUBQ doses: If baseline WBC ≥3 × 10⁹/L, ANC ≥1.5 × 10⁹/L, and platelets ≥75 × 10⁹/L, then adjust dose based on nadir counts for each cycle. If ANC <0.5 × 10⁹ and platelets <25 × 10⁹, then ↓ dose by 50%. If ANC is 0.5–1.5 × 10⁹ and platelets are 25–50 × 10⁹, then ↓ dose to 67% in next course. If ANC >1.5 × 10⁹ and platelets >50 × 10⁹, then 100% of dose can be given in subsequent cycle. If baseline WBC <3 × 10⁹/L, ANC <1.5 × 10⁹/L, or platelets <75 × 10⁹/L, adjust dose based on nadir counts and bone marrow biopsy cellularity at time of nadir for each cycle. If WBC or platelet nadir ↓ 50–75% in counts from baseline and bone marrow biopsy cellularity is 30–60% at time of nadir, give 100% of dose next course. If WBC or platelet nadir ↓ 50–75% in counts from baseline and bone marrow biopsy cellularity is 15–30% at time of nadir, give 50% of dose next course. If WBC or platelet nadir ↓ 50–75% in counts from baseline and bone marrow biopsy cellularity is <15% at time of nadir, give 33% of dose next course. If WBC or platelet nadir ↓ >75% in counts from baseline and bone marrow biopsy cellularity is 30–60% at time of nadir, give 75% of dose next course. If WBC or platelet nadir ↓ >75% in counts from baseline and bone marrow biopsy cellularity is 15–30% at time of nadir, give 50% of dose next course. If WBC or platelet nadir ↓ >75% in counts from baseline and bone marrow biopsy cellularity is <15% at time of nadir, give 33% of dose next course. Administer next course 28 days after start of preceding course, if both WBC and platelet counts are >25% above nadir and rising. If >25% ↑ above nadir is not seen by Day 28, reassess counts every 7 days. If a 25% ↑ is not seen by Day 42, ↓ scheduled dose by 50%.
- Obtain liver chemistries prior to initiation of therapy and before each cycle.
- Monitor serum creatinine and electrolytes prior to starting therapy and before each cycle. If serum bicarbonate <20 mEq/L,↓ dose by 50% in next course. If unexplained ↑ in BUN or serum creatinine occur, delay next cycle until values return to normal or baseline and ↓ dose by 50% in next course.
- May cause hypokalemia.

Premedicate for nausea and vomiting before each dose. For PO doses, administer antiemetic 30 min before each cycle for 1st 2 cycles; may be omitted if no nausea and vomiting occurs.
Do not confuse azacitidine with azathioprine.
Do not substitute PO form for IV or SUBQ azacitidine; may result in fatal adverse reactions.
PO: Administer once daily at the same time each day without regard to food on Days 1–14 of each 28-day cycle. DNC: Swallow tablet whole; do not crush, break, or chew.
Wear gloves, gown, and mask while handling medication.
SC: Use double gloves and a protective gown to prepare and administer. If possible, prepare in a biological safety cabinet or a compounding aseptic containment isolator; eye, face, and respiratory protection may be needed. Prepare and administer in a closed system drug transfer device. During administration, if there is a potential that the substance could splash or if the patient may resist, use eye and face protection. Reconstitution: Add 4 mL of sterile water for injection slowly into the vial. Concentration: 25 mg/mL. Vigorously shake or roll until suspension is uniform. Suspension will be cloudy. Withdraw the appropriate volume of drug from the vial into syringe making sure to purge any air trapped within the syringe. The syringe with needle should then be removed from the vial and the needle disposed of. A fresh SUBQ needle (25-gauge) should then be attached to the syringe. Do not purge the needle prior to injection to reduce the incidence of local injection site reactions. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers. Reconstituted suspension should be administered within 45 min. If time to administration exceeds 45 min, reconstituted suspension can be refrigerated for up to 8 hr. Allow suspension to come to room temperature for 30 min before administration
- Divide doses greater than 4 mL equally into two syringes and administer into separate sites. Rotate sites (thigh, abdomen, upper arm) with new injections at least one inch from old site. Do not use site that is bruised, tender, red, or hard. Invert syringe 2–3 times and roll syringe gently between palms immediately prior to administration to mix suspension. Discard unused portion.

IV Administration:

Intermittent Infusion: Use double gloves and a protective gown to prepare and administer. If possible, prepare in a biological safety cabinet or a compounding aseptic containment isolator; eye, face, and respiratory protection may be needed. Prepare and administer in a closed-system drug-transfer device. During administration, if there is a potential that the substance could splash or if the patient may resist, use eye and face protection. Reconstitution: Reconstitute each vial with 10 mL sterile water for injection. Shake vigorously or roll vial until all solids are dissolved. Solution should be clear; do not administer solutions that are not clear or contain particulate matter. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers. Concentration: 10 mg/mL. Diluent: Withdraw solution from required number of vials and inject into 50–100 mL of 0.9% NaCl or LR. Solution is stable for 1 hr at room temperature.
Rate: Infuse over 10–40 min. Infusion must be completed within 1 hr of reconstitution. Discard unused portions.
Solution Incompatibility:
- solutions containing dextrose
- hetastarch
- solutions containing bicarbonate

Explain the purpose and side effects of azacitidine to patient. Instruct patient to take as directed at the same time each day. Take missed doses as soon as remembered in same day; do not take two doses in dame day. If a dose is vomited, do not take another dose on the same day; resume normal scheduling the following day. Do not stop receiving drug without consulting health care professional. If an appointment is missed, contact health care professional as soon as possible to reschedule. Advise patient to read Medication Guidebefore starting, periodically during therapy, and with each Rx refill in case of changes.
Instruct patient to notify health care professional promptly if fever; chills; cough; body aches; unusual headaches; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; ↑ fatigue or weakness; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional if they have underlying liver or renal disease.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for ≥6 mo after last dose and to avoid breastfeeding during therapy and for 1 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during therapy and for ≥3 mo after last dose. May impair male and female fertility. Advise female patients to notify health care professional promptly if pregnancy is planned or suspected.

Improved bone marrow and blood counts.

Onureg, Vidaza

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Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆