AZACITIDINE PACKAGE INSERT PDF

Azacitidine for injection is indicated for treatment of patients with the following French-American-British FAB myelodysplastic syndrome subtypes: refractory anemia RA or refractory anemia with ringed sideroblasts 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. Premedicate patients for nausea and vomiting. Repeat cycles every 4 weeks. It is recommended that patients be treated for a minimum of 4 to 6 cycles. However, complete or partial response may require additional treatment cycles. Treatment may be continued as long as the patient continues to benefit.

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Send the page " " to a friend, relative, colleague or yourself. We do not record any personal information entered above. A pyrimidine nucleoside analog that inhibits RNA and DNA synthesis Used for the treatment of patients with certain myelodysplastic syndrome subtypes Contraindicated in patients with advanced malignant hepatic tumors or hypersensitivity to mannitol.

It is recommended that patients be treated for a minimum of 4 to 6 treatment cycles. Treatment may be continued as long as the patient continues to benefit. All patients should receive antiemetics prior to each azacitidine dose. Therapy interruption or a dose reduction may be necessary if a patient develops severe treatment-related toxicity.

Patients were reassessed after 4 cycles, and those with a complete response CR continued for 3 more cycles, those with a partial response PR or stable disease continued until CR or progressive disease. Quality of life QOL was also assessed in this study. Median time to leukemic transformation was 21 months in the azacitidine arm compared with 13 months in the supportive care arm.

QOL assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially treated with azacitidine. The oral venetoclax dose is increased during a ramp-up phase as follows: mg on day 1; mg on day 2; mg on day 3; and mg once daily on day 4 and beyond. Continue treatment until disease progression.

At a median follow-up was 7. Comorbidities included severe cardiac disease 4. Azacitidine has not been evaluated in patients with myelodysplastic syndrome and hepatic impairment; use is contraindicated in patients with advanced hepatic malignancy. Specific guidelines for dosage adjustments in hepatic impairment are not available.

Baseline renal impairment: No azacitidine dosage adjustment is necessary in cycle 1 in patients with renal impairment. For storage information, see specific product information within the How Supplied section. Observe and exercise usual precautions for handling, preparing, and administering solutions of cytotoxic drugs. If reconstituted azacitidine contacts the skin, wash the skin immediately with soap and water.

If it comes in contact with mucous membranes, flush thoroughly with water. Azacitidine is available as a single-use, mg lyophilized powder vial. Mannitol-containing and mannitol-free formulations have different stability following reconstitution for subcutaneous use.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Shake or roll the vial vigorously until all powder is dissolved; the solution should be clear. Dilute immediately by injecting the calculated amount of azacitidine into a 50 to mL infusion bag of either 0. Storage following reconstitution: The solution is stable at room temperature 25 degrees C or 77 degrees F for up to 1 hour after reconstitution. Intravenous IV Infusion: Administer the azacitidine admixture IV over 10 to 40 minutes; complete the infusion within 1 hour of azacitidine vial reconstitution.

Shake or roll the vial vigorously until a uniform suspension occurs; the suspension will be cloudy. Do not filter the suspension after reconstitution as this may remove the active substance. If the dose requires using more than one mg vial, divide the dose equally between 2 syringes; due to retention in the vial and needle, it may not be feasible to withdraw all of the contents from the vial.

Storage following reconstitution mannitol-containing formulations : The solution is stable at room temperature for up to 1 hour after reconstitution. Under refrigeration 2 to 8 degrees C or 36 to 46 degrees F , the solution in the vial or a syringe is stable for up to 8 hours when reconstituted with Sterile Water for injection that was not refrigerated or for up to 22 hours when reconstituted with Sterile Water for injection that was refrigerated.

Under refrigeration 2 to 8 degrees C or 36 to 46 degrees F , the solution in the vial or a syringe is stable for up to 12 hours when reconstituted with Sterile Water for injection that was not refrigerated or for up to 30 hours when reconstituted with Sterile Water for injection that was refrigerated.

Immediately prior to administration, invert the syringe 2 or 3 times and vigorously roll the syringe between the palms until a uniform, cloudy suspension is achieved. Administer the azacitidine suspension subcutaneously; inject in 2 different sites if 2 syringes are required.

Rotate sites for each injection thigh, abdomen, or upper arm. Give new injections at least one inch from an old site; do not inject in a site that is tender, bruised, red, or hard. Generic: - Discard unused portion.

Do not store for later use. Azacitidine is contraindicated in patients with mannitol hypersensitivity or sensitivity to azacitidine. Azacitidine is contraindicated in patients with advanced hepatic malignancies. Monitor liver function tests prior to starting azacitidine and before each cycle of therapy. Hepatotoxicity may occur in patients with severe hepatic impairment.

Progressive hepatic coma and death have been reported in azacitidine-treated patients with extensive tumor burden due to metastatic disease, particularly in patients with hypoalbuminemia i. Bone marrow suppression including anemia, neutropenia, and thrombocytopenia has been commonly reported.

A dosage adjustment in subsequent cycles may be required based on nadir counts and hematologic response. Nephrotoxicity e. Monitor serum creatinine levels and electrolytes prior to starting azacitidine and prior to each cycle of therapy.

Azacitidine and its metabolites are primarily excreted by the kidney; therefore, use caution in geriatric patients or patients with renal impairment and closely monitor renal function. Patients with MDS and renal impairment were excluded from clinical trials. Tumor lysis syndrome TLS has been reported in patients with myelodysplastic syndrome who received azacitidine. TLS may occur despite prophylaxis with allopurinol. Azacitidine may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies; there are no data on the use of azacitidine in pregnant women.

Females of reproductive potential should avoid pregnancy during treatment with azacitidine. Advise pregnant women of the potential risk to the fetus. Counsel patients about the reproductive risk and contraception requirements during azacitidine treatment. Pregnancy testing should be performed prior to starting azacitidine in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for 6 months after azacitidine therapy.

Women who become pregnant while receiving azacitidine should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during and for 3 months after azacitidine therapy due to the risk of male-mediated teratogenicity. Based on data in animals, infertility may occur in male or females treated with azacitidine.

It is not known if azacitidine or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions including tumorigenicity in nursing infants, women should discontinue breast-feeding during azacitidine therapy and for 1 week after the last dose. Palifermin: Moderate Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.

Penicillamine: Major Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

Azacitidine is a pyrimidine analog for cytosine. Once incorporated into tRNA, azacitidine inhibits tRNA methyltransferases and interferes with tRNA methylation and processing, which leads to inhibition of protein synthesis. Azacitidine inhibition of DNA methyltransferase is dose- and time-dependent. Animal studies have indicated increased response when smaller doses of azacitidine were given over a period of time versus larger doses given less frequently. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis.

Methylation usually suppresses gene transcription and gene deletion. In some cancer cells, hypermethylation blocks the activity of tumor suppressor genes, which regulate cell division and differentiation to prevent malignant transformation.

When suppressor gene activity is blocked, cell division becomes unregulated, leading to the formation of neoplastic cells. Hypermethylation is thought to be an early step in malignant transformation of cells. Hypomethylation may restore normal gene function to those genes critical for differentiation and proliferation.

Azacitidine induces cytotoxicity in rapidly dividing cells that are no longer responsive to normal cell growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine.

Azacitidine is administered as a subcutaneous injection or as an intravenous IV infusion. An in vitro study indicated that it may be metabolized by the liver. The primary route of elimination is urinary excretion. Affected cytochrome P isoenzymes or drug transporters: unknown No formal clinical drug interaction studies have been conducted with azacitidine.

Azacitidine is rapidly absorbed after subcutaneous administration. Multiple dosing at the recommended dose-regimen does not result in drug accumulation. PDR Search. Required field. Your Name Your name is required. Recipient's Email Separate multiple email address with a comma Please enter valid email address Recipient's email is required.

Thank you. Your email has been sent. Jump to Section. Related Drug Information Drug Summary. NOTE: Azacitidine has been designated an orphan drug for this indication. For the treatment of MDS subtypes of refractory anemia or refractory anemia with ringed sideroblasts if accompanied by neutropenia or thrombocytopenia or requiring transfusions , refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.

Subcutaneous dosage. Intravenous dosage.

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