Vidaza

azacitidine

Vidaza

Pharmacologic class: Pyrimidine antimetabolite

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Unclear. Thought to exert antineoplastic effect by causing DNA hypomethylation and direct cytotoxicity on abnormal hematopoietic bone marrow cells. Cytotoxicity causes death of rapidly growing cells, including cancer cells no longer responsive to normal growth control mechanisms.

Availability

Powder for injection (lyophilized): 100-mg single-use vials

Indications and dosages

Treatment of the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusion), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia

Adults: For first treatment cycle: 75 mg/m2 subcutaneously or I.V. daily for 7 days; for subsequent treatment cycles, repeat cycle every 4 weeks. Dosage may be increased to 100 mg/m2 if beneficial effect doesn't occur after two cycles and no toxicity (other than nausea and vomiting) develops. Patient should be treated for at least four cycles. Continue therapy as long as patient benefits from it.

Dosage adjustment

• Based on hematologic response (after administration of recommended dosage for first cycle)
• Unexplained serum bicarbonate reduction below 20 mEq/L
• Unexplained blood urea nitrogen or serum creatinine elevation

Off-label uses

• Acute myeloid leukemia

Contraindications

• Hypersensitivity to drug or mannitol
• Advanced malignant hepatic tumor

Precautions

Use cautiously in:
• impaired renal or hepatic function, myelodysplastic syndrome
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Obtain CBC, liver function tests, and serum creatinine level before starting drug.
• For subcutaneous administration, reconstitute with 4 ml sterile water for injection. Inject diluent slowly into vial; invert vial two or three times and rotate gently until uniform suspension appears. Resulting suspension (which will be cloudy) contains azacitidine 25 mg/ml.
• Invert syringe two to three times and gently roll between palms for 30 seconds immediately before administration.
• When giving subcutaneously, divide doses above 4 ml equally in two syringes, and inject subcutaneously in separate sites.
• Administer within 1 hour after reconstitution.
• When giving subcutaneously, rotate sites for each injection (thigh, abdomen, or upper arm). Give new injection at least 1″ from old site and never into tender, bruised, red, or hard area.
• For I.V. administration, reconstitute each vial with 10 ml sterile water for injection. Vigorously shake or roll bottle until all solids have dissolved.
• Prepare I.V. solution by adding reconstituted drug to 50- to 100-ml infusion bag of normal saline solution injection or lactated Ringer's injection.
• Administer I.V. solution over 10 to 40 minutes; administration must be completed within 1 hour of vial reconstitution.

Adverse reactions

CNS: fatigue, headache, confusion, dizziness, anxiety, depression, insomnia, lethargy, weakness, rigors, malaise, hypoesthesia, cerebral hemorrhage

CV: chest pain, cardiac murmur, tachycardia, hypotension, peripheral edema, syncope

EENT: rhinorrhea, epistaxis, sinusitis, nasopharyngitis, pharyngitis, postnasal drip, eye hemorrhage

GI: nausea, vomiting, diarrhea, constipation, anorexia, abdominal pain or tenderness, abdominal distention, dyspepsia, hemorrhoids, dysphagia, gingival bleeding, oral mucosal petechiae, stomatitis, tongue ulcers, mouth hemorrhage

GU: dysuria, urinary tract infection

Hematologic: anemia, thrombocytopenia, leukopenia, neutropenia, febrile neutropenia, lymphadenopathy, aggravated anemia, postprocedural hemorrhage, pancytopenia, bone marrow failure

Musculoskeletal: myalgia, muscle cramps, arthralgia, limb pain, back pain

Respiratory: cough (possibly productive), dyspnea, exertional or exacerbated dyspnea, upper respiratory tract infection, pneumonia, crackles, wheezing, decreased breath sounds, pleural effusion, rhonchi, atelectasis

Skin: lesion, rash, pruritus, herpes simplex, increased sweating, urticaria, dry skin, skin nodule, erythema, pallor, cellulitis

Other: decreased appetite, weight loss, fever, pitting edema, hematoma, night sweats, peripheral swelling, injection-site reactions, tumor lysis syndrome, Sweet's syndrome (acute febrile neutrophilic dermatosis) transfusion reaction, chest-wall pain, postprocedural or other pain, neutropenic sepsis, septic shock

Interactions

Drug-diagnostic tests.Potassium: decreased

Patient monitoring

• Monitor CBC during therapy.
• Monitor liver function tests and serum creatinine frequently.
• Watch for renal tubular acidosis (serum bicarbonate level below 20 mEq/L associated with alkaline urine and hypokalemia, and serum potassium level below 3 mEq/L).
• Monitor patient for signs and symptoms of tumor lysis syndrome (such as irregular heartbeat, shortness of breath, high potassium level, high uric acid level, impaired mental ability, kidney failure).

Patient teaching

Instruct patient to call prescriber immediately if shortness of breath, high potassium level, impaired mental ability, rash, easy bruising or bleeding, or respiratory symptoms develop.
• Advise male patient not to father a child during therapy.
• Caution female of childbearing potential to avoid pregnancy and breastfeeding during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions, especially those related to the tests mentioned above.

azaCITIDine

(a-za-sye-ti-deen) ,

Vidaza

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: nucleoside analogues
Pregnancy Category: D

Indications

Myelodysplastic syndromes including:
  • some refractory anemias,
  • chronic myelomonocytic leukemia.

Action

Inhibits DNS synthesis.

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: Rapidly absorbed following subcutaneous administration; 89% bioavailable.
Distribution: Unknown.
Metabolism and Excretion: 85% excreted in urine; some hepatic metabolism may occur. Less than 1% fecal elimination.
Half-life: 4 hr.

Time/action profile (effects on bone marrow)

ROUTEONSETPEAKDURATION
Subcutunknownunknownunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Advanced malignant hepatic tumors; Obstetric: Potential for congenital anomalies; Lactation: Potential for serious side effects in infants.
Use Cautiously in: Renal impairment;Liver disease; Obstetric: Patients with child-bearing potential (male and female) due to potential fetal harm; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Genitourinary

  • nephrotoxicity
  • renal tubular acidosis

Dermatologic

  • acute febrile neutrophilic dermatosis
  • ecchymosis

Fluid and Electrolyte

  • hypokalemia

Hematologic

  • anemia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Local

  • injection site erythema (most frequent)

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • fever (most frequent)

Interactions

Drug-Drug interaction

Additive bone marrow depression may occur with other antineoplastics.

Route/Dosage

Subcutaneous Intravenous (Adults) 75 mg/m2/day for 7 days every 4 wk; may be ↑ to 100 mg/m2/day for 7 days every 4 wk if no beneficial effect occurs after 2 cycles. Continue for as long as patient benefits.

Availability

Suspension for injection (requires reconstitution): 100 mg/vial

Nursing implications

Nursing assessment

  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, stools, urine, and 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 increased fatigue, dyspnea, and orthostatic hypotension.
  • Assess patient for nausea and vomiting during therapy. Premedicate patient before each dose.
  • 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: Monitor CBC with differential and platelet count prior to each dosing cycle. If baseline WBC is more than 3 x 109/L, ANC is more than 1.5 x 109/L, and platelets are more than 75 x 109/L, then dose is adjusted based on nadir counts for each cycle. If ANC is less than 0.5 x 109 and platelets are less than 25 x 109 then decrease dose by 50%. If ANC is 0.5–1.5 x 109 and platelets are 25–50 x 109 then decrease dose to 67% in next course. If ANC is greater than 1.5 x 109 and platelets are greater than 50, then 100% of dose can be given in subsequent cycle.
    • Obtain liver chemistries and serum creatinine prior to initiation of therapy.
    • Monitor renal function during therapy. If serum bicarbonate is <20 mEq/L, reduce 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 decrease dose by 50% in next course.
    • May cause hypokalemia.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Risk for injury (Adverse Reactions)

Implementation

  • Do not confuse azacitidine with azathioprine.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. If powder or solution comes in contact with skin or mucosa, wash thoroughly with soap and water. Discard equipment in specially designated containers (see ).
  • Subcutaneous: Reconstitute by adding 4 mL of sterile water for injection slowly into the azacitadine vial for a concentration of 25 mg/mL. Invert vial 2–3 times and rotate gently until suspension is uniform. Suspension will be cloudy. Stable for up to 1 hr at room temperature; must be administered within 1 hr of reconstitution. Suspension may also be refrigerated for up to 8 hr; may be allowed to equilibrate to room temperature for up to 30 min. Invert syringe 2–3 times and roll syringe gently between palms immediately prior to administration to mix suspension.
    • Divide doses greater than 4 mL equally into 2 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.
  • Intravenous Administration
  • Intermittent Infusion: 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. 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.
  • Solution Incompatibility: D5W, hespan, solutions containing bicarbonate

Patient/Family Teaching

  • Instruct patient to notify health care professional promptly if fever; chills; cough; 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; increased fatigue; 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.
  • Advise both male and female patients of the need for contraception during therapy.

Evaluation/Desired Outcomes

  • Improved bone marrow and blood counts.

Vidaza

a trademark for azacitidine.

azacitidine

A nucleoside analogue that may be used to treat beta-thalassemia, as it stimulates foetal globin production and myelodysplastic syndromes.

Adverse effects
Neutropaenia, thrombocytopaenia, liver failure, renal failure.
Mentioned in ?
References in periodicals archive ?
There you see individual revenue forecasts to 2024 for these products: - Vidaza - Dacogen - Zolinza - Istodax And you gain predictions for these expected treatments: - Beleodaq - Faridak There you explore drugs and years with highest predicted sales.
In a phase 3 trial, patients with higher-risk MDS were randomly assigned to receive either Vidaza or conventional care (which could be best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomization).
LONDON, March 2 /PRNewswire/ -- The Myelodysplastic Syndromes (MDS) Foundation is pleased to support the licensed use of VIDAZA in the United Kingdom and Ireland to treat a subset of patients with intermediate-2 and higher-risk MDS, chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML with 20-30% blasts).
Vidaza, generic name azacitidine, can be used to treat sufferers of high-risk myelodysp lastics yndrome (MDS), chronic myelomonocytic leukaemia (CMML) or acute myeloid leukaemia.
New drug Vidaza will be available privately following a global clinical trial which included patients at the Queen Elizabeth Hospital in Edgbaston.
Datamonitor forecasts Dacogen sales to grow in line with Vidaza over the forecast period of 2007 to 2017, Ms.
The Aplastic Anemia & MDS International Foundation (AA&MDSIF) recently announced that the FDA has expanded the label for VIDAZA (azacitidine) to include data from the AZA-001 trial, which found that Vidaza is the only agent that extends survival in MDS (myelodysplastic syndromes) patients.
today announced the completion of an exclusive license agreement for development and commercialization rights to Vidaza in Japan.
McKesson Specialty, a subsidiary of McKesson Corporation, joins Pharmion's exclusive specialty distribution network created to ensure Vidaza is available to physicians and the more than 10,000 patients diagnosed with MDS every year in the United States.
Comment: In a randomized, controlled trial and two nonrandomized trials of 268 patients, about 15% of patients had complete or partial responses to Vidaza, eliminating the need for red blood cell and platelet transfusions.