azacitidine


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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

an antineoplastic hormone.
indication This drug is used to treat myelodysplastic syndrome.
contraindications Pregnancy, advanced malignant hepatic tumors, and known hypersensitivity to this drug or mannitol prohibit its use.
adverse effects Adverse effects of this drug include anxiety, depression, dizziness, fatigue, headache, cardiac murmur, hypotension, tachycardia, nausea, vomiting, anorexia, constipation, abdominal pain, abdominal distension or tenderness, hemorrhoids, mouth hemorrhage, tongue ulceration, stomatitis, dyspepsia, dysuria, urinary tract infection, ecchymosis, irritation at injection site, rash, sweating, pyrexia, and hypokalemia. Life-threatening side effects include diarrhea, hepatotoxicity, hepatic coma, renal failure, renal tubular acidosis, leukopenia, anemia, thrombocytopenia, and neutropenia.

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.

azacitidine

Vidaza® Hematology A nucleoside analogue that may be used to treat β-thalassemia as it stimulates fetal globin production and myelodysplastic syndrome Side effects Neutropenia, thrombocytopenia, renal failure, liver failure
References in periodicals archive ?
Rigosertib is also being evaluated in an expanded Phase 2 combination study with Azacitidine in MDS patients.
The company is using a clinical trial assay to identify AML and MDS patients with elevated levels of RARA and IRF8 mRNA for inclusion in a Phase 2 clinical trial assessing the safety and efficacy of SY-1425 in combination with azacitidine, a hypomethylating agent, and in combination with daratumumab, an anti-CD38 therapeutic antibody.
Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, today announced that the European Medicines Agency (EMA) has granted Orphan Drug Designation to pracinostat, an investigational drug candidate currently in a Phase 3 study in combination with azacitidine for the treatment of acute myeloid leukemia (AML) in adult patients unfit to induction chemotherapy.
The European Medicines Agency (EMA) has granted Helsinn Group and MEI Pharma Inc (NASDAQ: MEIP) Orphan Drug Designation for the investigational drug candidate pracinostat, which is currently in a Phase 3 study in combination with azacitidine for the treatment of acute myeloid leukaemia (AML) in adult patients unfit to induction chemotherapy, the Swiss pharmaceutical group disclosed on Thursday.
It also took a hit from competition in the US for key products such as Valganciclovir, Decitabine and Azacitidine.
Following FDA approval it launched Azacitidine injection, a generic of Celgene's (CELG) Vidaza injection.
Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias.
Decitabine and azacitidine are DNA methyltransferase inhibitors used in AML, MDS, and other malignancies.
The company has also introduced Azacitidine for Injection, 100 mg/ vial, which is a generic version of Celgene's Vidaza Injection, 100 mg/ vial.
The epigenetics drugs market report estimates the market size (Revenue USD million - 2013 to 2020) for key market segments based on the drug type (ChIP technology, DNA methylation), and their mechanism of action such as DNMT inhibitors - Azacitidine (vidaza) and Decitabine (dacogen); and HDAC inhibitors or HDIs - Romidepsin (istodax), Vorinostat (zolinza), and forecasts growth trends (CAGR% - 2016 to 2020).
GlobalData expects, by the end of the forecast period, new branded therapies Vyxeos, volasertib and CC-486 will dominate the market along with generic azacitidine.
In patients who are at intermediate or high risk for complications, low-intensity chemotherapy with azacitidine (Vidaza[R], ecitabine (Dacogen[R]), or lenalidomide (Revlimid[R]) can improve blood counts, decrease transfusion requirements, reduce the risk for AML, and improve quality of life.