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| {{DrugProjectFormSinglePage
| | #REDIRECT [[Azacytidine]] |
| |authorTag={{AV}}
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| |aOrAn=a
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| |indication=Myelodysplastic Syndromes (MDS)
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| VIDAZA® 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
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| |hasBlackBoxWarning=Yes
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| |adverseReactions=<!--Black Box Warning-->
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| |blackBoxWarningTitle=Title
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| |blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
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| * Content
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| <!--Adult Indications and Dosage-->
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| <!--FDA-Labeled Indications and Dosage (Adult)-->
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| |fdaLIADAdult======Myelodysplastic Syndromes (MDS)=====
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| *VIDAZA® 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]]
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| =====Dosing Information=====
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| ======First Treatment Cycle======
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| *The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days. Patients should be premedicated for [[nausea and vomiting]].
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| *Complete blood counts, liver chemistries and [[serum creatinine]] should be obtained prior to first dose.
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| ======Subsequent Treatment Cycles======
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| *Cycles should be repeated every 4 weeks. The dose may be increased to 100 mg/m2 if no beneficial effect is seen after 2 treatment cycles and if no toxicity other than [[nausea and vomiting]] has occurred. 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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| *Patients should be monitored for hematologic response and renal toxicities, and dosage delay or reduction as described below may be necessary.
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| ======Dosage Adjustment Based on Hematology Laboratory Values======
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| *For patients with baseline (start of treatment) WBC ≥3.0 x109/L, ANC ≥1.5 x109/L, and platelets ≥75.0 x109/L, adjust the dose as follows, based on nadir counts for any given cycle:
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| table02
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| *For patients whose baseline counts are WBC <3.0 x109/L, ANC<1.5 x109/L, or platelets <75.0 x109/L, dose adjustments should be based on nadir counts and bone marrow biopsy cellularity at the time of the nadir as noted below, unless there is clear improvement in differentiation (percentage of mature granulocytes is higher and ANC is higher than at onset of that course) at the time of the next cycle, in which case the dose of the current treatment should be continued.
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| table03
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| *If a nadir as defined in the table above has occurred, the next course of treatment should be given 28 days after the start of the preceding course, provided that both the WBC and the platelet counts are >25% above the nadir and rising. If a >25% increase above the nadir is not seen by day 28, counts should be reassessed every 7 days. If a 25% increase is not seen by day 42, then the patient should be treated with 50% of the scheduled dose.
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| ======Dosage Adjustment Based on Serum Electrolytes and Renal Toxicity======
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| *If unexplained reductions in serum bicarbonate levels to <20 mEq/L occur, the dosage should be reduced by 50% on the next course. Similarly, if unexplained elevations of [[BUN]] or [[serum creatinine]] occur, the next cycle should be delayed until values return to normal or baseline and the dose should be reduced by 50% on the next treatment course.
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| ======Use in Geriatric Patients======
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| *Azacitidine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
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| ======Preparation of VIDAZA======
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| *VIDAZA is a cytotoxic drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing VIDAZA suspensions [see How Supplied/Storage and Handling (16)].
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| *If reconstituted VIDAZA comes into contact with the skin, immediately and thoroughly wash with soap and water. If it comes into contact with mucous membranes, flush thoroughly with water.
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| *The VIDAZA vial is single-use and does not contain any preservatives. Unused portions of each vial should be discarded properly . Do not save any unused portions for later administration.
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| ======Instructions for Subcutaneous Administration======
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| *VIDAZA should be reconstituted aseptically with 4 mL sterile water for injection. The diluent should be injected slowly into the vial. Vigorously shake or roll the vial until a uniform suspension is achieved. The suspension will be cloudy. The resulting suspension will contain azacitidine 25 mg/mL. Do not filter the suspension after reconstitution. Doing so could remove the active substance.
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| *Preparation for Immediate Subcutaneous Administration: Doses greater than 4 mL should be divided equally into 2 syringes. The product may be held at room temperature for up to 1 hour, but must be administered within 1 hour after reconstitution.
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| *Preparation for Delayed Subcutaneous Administration: The reconstituted product may be kept in the vial or drawn into a syringe. Doses greater than 4 mL should be divided equally into 2 syringes. The product must be refrigerated immediately. When VIDAZA is reconstituted using water for injection that has not been refrigerated, the reconstituted product may be held under refrigerated conditions (2ºC - 8ºC, 36ºF - 46ºF) for up to 8 hours. When VIDAZA is reconstituted using refrigerated (2ºC - 8ºC, 36ºF - 46ºF) water for injection, the reconstituted product may be stored under refrigerated conditions (2ºC - 8ºC, 36ºF - 46ºF) for up to 22 hours. After removal from refrigerated conditions, the suspension may be allowed to equilibrate to room temperature for up to 30 minutes prior to administration.
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| ======Subcutaneous Administration======
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| *To provide a homogeneous suspension, the contents of the dosing syringe must be re-suspended immediately prior to administration. To re-suspend, vigorously roll the syringe between the palms until a uniform, cloudy suspension is achieved.
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| *VIDAZA suspension is administered subcutaneously. Doses greater than 4 mL should be divided equally into 2 syringes and injected into 2 separate sites. Rotate sites for each injection (thigh, abdomen, or upper arm). New injections should be given at least one inch from an old site and never into areas where the site is tender, bruised, red, or hard.
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| *Suspension Stability: VIDAZA reconstituted with non-refrigerated water for injection for subcutaneous administration may be stored for up to 1 hour at 25°C (77°F) or for up to 8 hours between 2°C and 8°C (36°F and 46°F); when reconstituted with refrigerated (2ºC - 8ºC, 36ºF - 46ºF) water for injection, it may be stored for 22 hours between 2°C and 8°C (36°F and 46°F).
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| ====== Instructions for Intravenous Administration======
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| *Reconstitute the appropriate number of VIDAZA vials to achieve the desired dose. Reconstitute each vial with 10 mL sterile water for injection. Vigorously shake or roll the vial until all solids are dissolved. The resulting solution will contain azacitidine 10 mg/mL. The solution should be clear. Parenteral drug product should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
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| *Withdraw the required amount of VIDAZA solution to deliver the desired dose and inject into a 50 -100 mL infusion bag of either 0.9% Sodium Chloride Injection or Lactated Ringer's Injection.
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| ======Intravenous Solution Incompatibility======
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| *VIDAZA is incompatible with 5% Dextrose solutions, Hespan, or solutions that contain bicarbonate. These solutions have the potential to increase the rate of degradation of VIDAZA and should therefore be avoided.
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| ======Intravenous Administration======
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| *VIDAZA solution is administered intravenously. Administer the total dose over a period of 10 - 40 minutes. The administration must be completed within 1 hour of reconstitution of the VIDAZA vial.
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| *Solution Stability: VIDAZA reconstituted for intravenous administration may be stored at 25°C (77°F), but administration must be completed within 1 hour of reconstitution.
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| <!--Off-Label Use and Dosage (Adult)-->
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| <!--Guideline-Supported Use (Adult)-->
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| |offLabelAdultGuideSupport======Condition1=====
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| * Developed by:
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| * Class of Recommendation:
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| * Strength of Evidence:
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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| <!--Non–Guideline-Supported Use (Adult)-->
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| |offLabelAdultNoGuideSupport======Condition1=====
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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| <!--Pediatric Indications and Dosage-->
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| <!--FDA-Labeled Indications and Dosage (Pediatric)-->
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| |fdaLIADPed======Condition1=====
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Off-Label Use and Dosage (Pediatric)-->
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| <!--Guideline-Supported Use (Pediatric)-->
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| |offLabelPedGuideSupport======Condition1=====
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| * Developed by:
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| * Class of Recommendation:
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| * Strength of Evidence:
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Non–Guideline-Supported Use (Pediatric)-->
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| |offLabelPedNoGuideSupport======Condition1=====
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| * Dosing Information
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| :* Dosage
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| =====Condition2=====
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| There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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| <!--Contraindications-->
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| |contraindications======Advanced Malignant Hepatic Tumors=====
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| *VIDAZA is contraindicated in patients with advanced malignant hepatic tumors.
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| =====Hypersensitivity to Azacitidine or Mannitol=====
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| *VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol.
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| <!--Warnings-->
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| |warnings======Anemia, Neutropenia and Thrombocytopenia======
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| *VIDAZA causes anemia, neutropenia and thrombocytopenia. Monitor complete blood counts frequently for response and/or toxicity, at a minimum, prior to each dosing cycle. After administration of the recommended dosage for the first cycle, adjust dosage for subsequent cycles based on nadir counts and hematologic response .
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| =====VIDAZA Toxicity in Patients with Severe Pre-existing Hepatic Impairment=====
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| *Because azacitidine is potentially hepatotoxic in patients with severe pre-existing hepatic impairment, caution is needed in patients with liver disease. Patients with extensive tumor burden due to metastatic disease have been reported to experience progressive hepatic coma and death during azacitidine treatment, especially in such patients with baseline albumin <30 g/L. Azacitidine is contraindicated in patients with advanced malignant hepatic tumors.
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| *Safety and effectiveness of VIDAZA in patients with MDS and hepatic impairment have not been studied as these patients were excluded from the clinical trials.
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| =====Renal Toxicity=====
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| *Renal toxicity ranging from elevated serum creatinine to renal failure and death have been reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for nonMDS conditions. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to <20 mEq/L in association with an alkaline urine and hypokalemia (serum potassium <3 mEq/L) developed in 5 patients with CML treated with azacitidine and etoposide. If unexplained reductions in serum bicarbonate <20 mEq/L or elevations of BUN or serum creatinine occur, the dosage should be reduced or held [see Dosage and Administration (2.4)].
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| *Patients with renal impairment may be at increased risk for renal toxicity. Also, azacitidine and its metabolites are primarily excreted by the kidney. Therefore, these patients should be closely monitored for toxicity [see Dosage and Administration (2.4, 2.5)]. Patients with MDS and renal impairment were excluded from the clinical studies.
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| =====Use in Pregnancy=====
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| *VIDAZA may cause fetal harm when administered to a pregnant woman. Azacitidine caused congenital malformations in animals. Women of childbearing potential should be advised to avoid pregnancy during treatment with VIDAZA. There are no adequate and well-controlled studies in pregnant women using VIDAZA. If this drug is used during pregnancy or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].
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| 5.5 Use in Males
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| Men should be advised to not father a child while receiving treatment with VIDAZA. In animal studies, pre-conception treatment of male mice and rats resulted in increased embryofetal loss in mated females
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| ====Precautions====
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| * Description
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| <!--Adverse Reactions-->
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| <!--Clinical Trials Experience-->
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| |clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
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| =====Body as a Whole=====
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| =====Cardiovascular=====
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| =====Digestive=====
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| =====Endocrine=====
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| =====Hematologic and Lymphatic=====
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| =====Metabolic and Nutritional=====
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| =====Musculoskeletal=====
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| =====Neurologic=====
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| =====Respiratory=====
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| =====Skin and Hypersensitivy Reactions=====
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| =====Special Senses=====
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| =====Urogenital=====
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| =====Miscellaneous=====
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| <!--Postmarketing Experience-->
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| |postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
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| =====Body as a Whole=====
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| =====Cardiovascular=====
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| =====Digestive=====
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| =====Endocrine=====
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| =====Hematologic and Lymphatic=====
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| =====Metabolic and Nutritional=====
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| =====Musculoskeletal=====
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| =====Neurologic=====
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| =====Respiratory=====
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| =====Skin and Hypersensitivy Reactions=====
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| =====Special Senses=====
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| =====Urogenital=====
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| =====Miscellaneous=====
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| <!--Drug Interactions-->
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| |drugInteractions=* Drug
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| :* Description
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| <!--Use in Specific Populations-->
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| |useInPregnancyFDA=* '''Pregnancy Category'''
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| |useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
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| There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
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| |useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
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| |useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
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| |useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
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| |useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
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| |useInGender======Use in Males=====
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| *Men should be advised to not father a child while receiving treatment with VIDAZA. In animal studies, pre-conception treatment of male mice and rats resulted in increased embryofetal loss in mated females
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| .
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| |useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
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| |useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
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| |useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
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| |useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
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| |useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
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| <!--Administration and Monitoring-->
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| |administration=* Oral
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| * Intravenous
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| |monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
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| * Description
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| <!--IV Compatibility-->
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| |IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
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| <!--Overdosage-->
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| |overdose====Acute Overdose===
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| ====Signs and Symptoms====
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| * Description
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| ====Management====
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| * Description
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| ===Chronic Overdose===
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| There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
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| <!--Pharmacology-->
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| <!--Drug box 2-->
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| |drugBox=<!--Mechanism of Action-->
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| |mechAction=*
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| <!--Structure-->
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| |structure=*
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| : [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
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| <!--Pharmacodynamics-->
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| |PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
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| <!--Pharmacokinetics-->
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| |PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
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| <!--Nonclinical Toxicology-->
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| |nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
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| <!--Clinical Studies-->
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| |clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
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| <!--How Supplied-->
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| |howSupplied=*
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| <!--Patient Counseling Information-->
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| |fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
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| <!--Precautions with Alcohol-->
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| |alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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| <!--Brand Names-->
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| |brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
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| <!--Look-Alike Drug Names-->
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| |lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
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| <!--Drug Shortage Status-->
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| |drugShortage=
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| }}
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| {{PillImage
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| |fileName=No image.jpg
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| }}
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| {{LabelImage
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| |fileName={{PAGENAME}}11.png
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| }}
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| {{LabelImage
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| |fileName={{PAGENAME}}11.png
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| }}
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| <!--Pill Image-->
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| <!--Label Display Image-->
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| <!--Category-->
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| [[Category:Drug]]
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