azacitidine

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.

Contraind./Precautions ⬆ ⬇

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.

Adv. Reactions/Side Effects ⬆ ⬇

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

Interactions ⬆ ⬇

Drug-drug:

Additive bone marrow depression may occur with other antineoplastics.

Availability ⬆ ⬇

(Generic available)

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

Route/Dosage ⬆ ⬇

Do NOT interchange/substitute parenteral product with oral formulation.

Myelodysplastic Syndromes

SC IV (Adults ): 75 mg/m²once 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/m²once 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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits DNA synthesis.

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: nucleoside analogues

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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

Patient/Family Teaching ⬆ ⬇

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.

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Indications ⬇