AZACITIDINE- azacitidine injection, powder, lyophilized, for solution
BluePoint Laboratories
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use AZACITIDINE FOR INJECTION safely and effectively. See full prescribing information for AZACITIDINE FOR INJECTION.
AZACITIDINE for injection, for subcutaneous or intravenous use Initial U.S. Approval: 2004 INDICATIONS AND USAGEAzacitidine for injection is a nucleoside metabolic inhibitor indicated for the treatment of patients with the following FAB myelodysplastic syndrome (MDS) subtypes: Refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (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). ( 1) DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONSWARNINGS AND PRECAUTIONS
ADVERSE REACTIONSMost common adverse reactions (>30%) by subcutaneous route are: nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia and ecchymosis. Most common adverse reactions by intravenous route also included petechiae, rigors, weakness and hypokalemia ( 6.1). To report SUSPECTED ADVERSE REACTIONS, contact Breckenridge Pharmaceutical, Inc. at 1-800-367-3395 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION. Revised: 5/2021 |
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).
Obtain complete blood counts, liver chemistries and serum creatinine prior to the first dose.
Monitor patients for hematologic response and renal toxicities [see Warnings and Precautions (5.3)] , and delay or reduce dosage if necessary as described below.
Nadir Counts | % Dose in the Next Course | |
---|---|---|
ANC (×10 9/L) | Platelets (×10 9/L) | |
Less than 0.5 |
Less than 25 |
50% |
0.5 –1.5 |
25-50 |
67% |
Greater than 1.5 |
Greater than 50 |
100% |
WBC or Platelet Nadir
% decrease in counts from baseline | Bone Marrow
Biopsy Cellularity at Time of Nadir (%) |
||
---|---|---|---|
30-60 | 15-30 | Less than 15 | |
% Dose in the Next Course |
|||
50 - 75 |
100 |
50 |
33 |
greater than 75 |
75 |
50 |
33 |
If unexplained reductions in serum bicarbonate levels to less than 20 mEq/L occur, reduce the dosage by 50% for the next course. Similarly, if unexplained elevations of BUN or serum creatinine occur, delay the next cycle until values return to normal or baseline and reduce the dose by 50% for the next course [see Warnings and Precautions (5.3)] .
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, select the dose carefully and monitor renal function [see Warnings and Precautions (5.3) and Use in Specific Populations (8.5)] .
Azacitidine for injection is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1
The azacitidine for injection vial is single-dose and does not contain any preservatives. Discard unused portions of each vial properly [see How Supplied/Storage and Handling (16)] . Do not save any unused portions for later administration.
Preparation for Immediate Subcutaneous Administration: For doses requiring more than 1 vial, divide the dose equally between the syringes (e.g., dose 150 mg = 6 mL, 2 syringes with 3 mL in each syringe) and inject into two separate sites. Due to retention in the vial and needle, it may not be feasible to withdraw all of the suspension from the vial. The product may be held at room temperature for up to 1 hour, but must be administered within 1 hour after reconstitution.
Subcutaneous Administration
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.
Azacitidine for injection suspension is administered subcutaneously. 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.
Intravenous Solution Incompatibility
Azacitidine for injection is supplied as lyophilized powder in 100 mg single-dose vials.
Azacitidine for injection is contraindicated in patients with advanced malignant hepatic tumors [see Warnings and Precautions (5.2)] .
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 [see Contraindications (4.1)] .
Monitor liver chemistries prior to initiation of therapy and with each cycle.
Safety and effectiveness of azacitidine in patients with MDS and hepatic impairment have not been studied as these patients were excluded from the clinical trials.
Patients with renal impairment may be at increased risk for renal toxicity. Also, azacitidine and its metabolites are primarily excreted by the kidney. Therefore, monitor these patients closely for toxicity [see Dosage and Administration (2.4, 2.5)] . Patients with MDS and renal impairment were excluded from the clinical studies.
Azacitidine for injection may cause fatal or serious tumor lysis syndrome, including in patients with MDS. Tumor lysis syndrome may occur despite concomitant use of allopurinol. Assess baseline risk and monitor and treat as appropriate.
Advise females with reproductive potential to avoid pregnancy during treatment with azacitidine for injection [see Use in Specific Populations (8.3)] . Men should be advised to not father a child while receiving treatment with azacitidine for injection.
The following adverse reactions are described in other labeling sections:
Most Commonly Occurring Adverse Reactions (Subcutaneous or Intravenous Route): nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia, ecchymosis. The most common adverse reactions by intravenous route also included petechiae, rigors, weakness and hypokalemia.
Adverse Reactions Most Frequently (>2%) Resulting in Clinical Intervention (Subcutaneous or Intravenous Route):
Discontinuation: leukopenia, thrombocytopenia, neutropenia.
Dose Reduced: leukopenia, neutropenia, thrombocytopenia.
In Studies 1, 2 and 3, a total of 268 patients were exposed to azacitidine, including 116 exposed for 6 cycles (approximately 6 months) or more and 60 exposed for greater than 12 cycles (approximately one year). Azacitidine was studied primarily in supportive-care controlled and uncontrolled trials (n=150 and n=118, respectively). The population in the subcutaneous studies (n=220) was 23 to 92 years old (mean 66.4 years), 68% male, and 94% white, and had MDS or AML. The population in the intravenous study (n=48) was 35 to 81 years old (mean 63.1 years), 65% male, and 100% white. Most patients received average daily doses between 50 and 100 mg/m 2.
In Study 4, a total of 175 patients with higher-risk MDS (primarily RAEB and RAEB-T subtypes) were exposed to azacitidine. Of these patients, 119 were exposed for 6 or more cycles, and 63 for at least 12 cycles. The mean age of this population was 68.1 years (ranging from 42 to 83 years), 74% were male, and 99% were white. Most patients received daily azacitidine doses of 75 mg/m 2.
Table 1 presents adverse reactions occurring in at least 5% of patients treated with azacitidine (subcutaneous) in Studies 1 and 2. It is important to note that duration of exposure was longer for the azacitidine-treated group than for the observation group: patients received azacitidine for injection for a mean of 11.4 months while mean time in the observation arm was 6.1 months.
Number (%) of Patients | ||
---|---|---|
System Organ Class
Preferred Term* | All Azacitidine for Injection†
(N=220) | Observation‡
(N=92) |
|
||
Blood and lymphatic system disorders |
||
Anemia |
153 (70) |
59 (64) |
Anemia aggravated |
12 (6) |
5 (5) |
Febrile neutropenia |
36 (16) |
4 (4) |
Leukopenia |
106 (48) |
27 (29) |
Neutropenia |
71 (32) |
10 (11) |
Thrombocytopenia |
144 (66) |
42 (46) |
Gastrointestinal disorders |
||
Abdominal tenderness |
26 (12) |
1 (1) |
Constipation |
74 (34) |
6 (7) |
Diarrhea |
80 (36) |
13 (14) |
Gingival bleeding |
21 (10) |
4 (4) |
Loose stools |
12 (6) |
0 |
Mouth hemorrhage |
11 (5) |
1 (1) |
Nausea |
155 (71) |
16 (17) |
Stomatitis |
17 (8) |
0 |
Vomiting |
119 (54) |
5 (5) |
General disorders and administration site conditions |
||
Chest pain |
36 (16) |
5 (5) |
Injection site bruising |
31 (14) |
0 |
Injection site erythema |
77 (35) |
0 |
Injection site granuloma |
11 (5) |
0 |
Injection site pain |
50 (23) |
0 |
Injection site pigmentation changes |
11 (5) |
0 |
Injection site pruritus |
15 (7) |
0 |
Injection site reaction |
30 (14) |
0 |
Injection site swelling |
11 (5) |
0 |
Lethargy |
17 (8) |
2 (2) |
Malaise |
24 (11) |
1 (1) |
Pyrexia |
114 (52) |
28 (30) |
Infections and infestations |
||
Nasopharyngitis |
32 (15) |
3 (3) |
Pneumonia |
24 (11) |
5 (5) |
Upper respiratory tract infection |
28 (13) |
4 (4) |
Injury, poisoning, and procedural complications |
||
Post procedural hemorrhage |
13 (6) |
1 (1) |
Metabolism and nutrition disorders |
||
Anorexia |
45 (21) |
6 (7) |
Musculoskeletal and connective tissue disorders |
||
Arthralgia |
49 (22) |
3 (3) |
Chest wall pain |
11 (5) |
0 |
Myalgia |
35 (16) |
2 (2) |
Nervous system disorders |
||
Dizziness |
41 (19) |
5 (5) |
Headache |
48 (22) |
10 (11) |
Psychiatric disorders |
||
Anxiety |
29 (13) |
3 (3) |
Insomnia |
24 (11) |
4 (4) |
Respiratory, thoracic and mediastinal disorders |
||
Dyspnea |
64 (29) |
11 (12) |
Skin and subcutaneous tissue disorders |
||
Dry skin |
11 (5) |
1 (1) |
Ecchymosis |
67 (31) |
14 (15) |
Erythema |
37 (17) |
4 (4) |
Rash |
31 (14) |
9 (10) |
Skin nodule |
11 (5) |
1 (1) |
Urticaria |
13 (6) |
1 (1) |
Vascular disorders |
||
Hematoma |
19 (9) |
0 |
Hypotension |
15 (7) |
2 (2) |
Petechiae |
52 (24) |
8 (9) |
Table 2 presents adverse reactions occurring in at least 5% of patients treated with azacitidine in Study 4. Similar to Studies 1 and 2 described above, duration of exposure to treatment with azacitidine was longer (mean 12.2 months) compared with best supportive care (mean 7.5 months).
Number (%) of Patients | ||||
---|---|---|---|---|
Any Grade | Grade 3/4 | |||
System Organ Class
Preferred Term* | Azacitidine for Injection
(N=175) | Best Supportive Care Only
(N=102) | Azacitidine for Injection
(N=175) | Best Supportive Care Only
(N=102) |
|
||||
Blood and lymphatic system disorders | ||||
Anemia |
90 (51) |
45 (44) |
24 (14) |
9 (9) |
Febrile neutropenia |
24 (14) |
10 (10) |
22 (13) |
7 (7) |
Leukopenia |
32 (18) |
2 (2) |
26 (15) |
1 (1) |
Neutropenia |
115 (66) |
29 (28) |
107 (61) |
22 (22) |
Thrombocytopenia |
122 (70) |
35 (34) |
102 (58) |
29 (28) |
Gastrointestinal disorders |
||||
Abdominal pain |
22 (13) |
7 (7) |
7 (4) |
0 |
Constipation |
88 (50) |
8 (8) |
2 (1) |
0 |
Dyspepsia |
10 (6) |
2 (2) |
0 |
0 |
Nausea |
84 (48) |
12 (12) |
3 (2) |
0 |
Vomiting |
47 (27) |
7 (7) |
0 |
0 |
General disorders and administration site conditions |
||||
Fatigue |
42 (24) |
12 (12) |
6 (3) |
2 (2) |
Injection site bruising |
9 (5) |
0 |
0 |
0 |
Injection site erythema |
75 (43) |
0 |
0 |
0 |
Injection site hematoma |
11 (6) |
0 |
0 |
0 |
Injection site induration |
9 (5) |
0 |
0 |
0 |
Injection site pain |
33 (19) |
0 |
0 |
0 |
Injection site rash |
10 (6) |
0 |
0 |
0 |
Injection site reaction |
51 (29) |
0 |
1 (1) |
0 |
Pyrexia |
53 (30) |
18 (18) |
8 (5) |
1 (1) |
Infections and infestations |
||||
Rhinitis |
10 (6) |
1 (1) |
0 |
0 |
Upper respiratory tract infection |
16 (9) |
4 (4) |
3 (2) |
0 |
Urinary tract infection |
15 (9) |
3 (3) |
3 (2) |
0 |
Investigations |
||||
Weight decreased |
14 (8) |
0 |
1 (1) |
0 |
Metabolism and nutrition disorders |
||||
Hypokalemia |
11 (6) |
3 (3) |
3 (2) |
3 (3) |
Nervous system disorders |
||||
Lethargy |
13 (7) |
2 (2) |
0 |
1 (1) |
Psychiatric disorders |
||||
Anxiety |
9 (5) |
1 (1) |
0 |
0 |
Insomnia |
15 (9) |
3 (3) |
0 |
0 |
Renal and urinary disorders |
||||
Hematuria |
11 (6) |
2 (2) |
4 (2) |
1 (1) |
Respiratory, thoracic and mediastinal disorders |
||||
Dyspnea |
26 (15) |
5 (5) |
6 (3) |
2 (2) |
Dyspnea exertional |
9 (5) |
1 (1) |
0 |
0 |
Pharyngolaryngeal pain |
11 (6) |
3 (3) |
0 |
0 |
Skin and subcutaneous tissue disorders |
||||
Erythema |
13 (7) |
3 (3) |
0 |
0 |
Petechiae |
20 (11) |
4 (4) |
2 (1) |
0 |
Pruritus |
21 (12) |
2 (2) |
0 |
0 |
Rash |
18 (10) |
1 (1) |
0 |
0 |
Vascular disorders |
||||
Hypertension |
15 (9) |
4 (4) |
2 (1) |
2 (2) |
In Studies 1, 2 and 4 with subcutaneous administration of azacitidine, adverse reactions of neutropenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, constipation, and injection site erythema/reaction tended to increase in incidence with higher doses of azacitidine for injection.
In clinical studies of either subcutaneous or intravenous azacitidine, the following serious adverse reactions occurring at a rate of < 5% (and not described in Tables 1 or 2) were reported:
Blood and lymphatic system disorders: agranulocytosis, bone marrow failure, pancytopenia splenomegaly.
Eye disorders: eye hemorrhage
Gastrointestinal disorders: diverticulitis, gastrointestinal hemorrhage, melena, perirectal abscess.
Hepatobiliary disorders: cholecystitis.
Immune system disorders: anaphylactic shock, hypersensitivity.
Infections and infestations: abscess limb, bacterial infection, cellulitis, blastomycosis, injection site infection, Klebsiella sepsis, neutropenic sepsis, pharyngitis streptococcal, pneumonia Klebsiella, sepsis, septic shock, Staphylococcal bacteremia, Staphylococcal infection, toxoplasmosis.
Metabolism and nutrition disorders: dehydration.
Musculoskeletal and connective tissue disorders: bone pain aggravated, muscle weakness, neck pain.
Neoplasms benign, malignant and unspecified: leukemia cutis.
Nervous system disorders: cerebral hemorrhage, convulsions, intracranial hemorrhage.
Renal and urinary disorders: loin pain, renal failure.
Skin and subcutaneous tissue disorders: pyoderma gangrenosum, rash pruritic, skin induration.
Surgical and medical procedures: cholecystectomy.
Vascular disorders: orthostatic hypotension.
Risk Summary
The background rate of major birth defects and miscarriage is unknown for the indicated population. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.
Data
Animal Data
Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single IP (intraperitoneal) injection of 6 mg/m 2 (approximately 8% of the recommended human daily dose on a mg/m 2 basis) azacitidine on gestation day 10. Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation day 15 at doses of ~3-12 mg/m 2 (approximately 4%-16% the recommended human daily dose on a mg/m 2 basis).
Risk Summary
There is no information regarding the presence of azacitidine in human milk, the effects of azacitidine on the breastfed infant, or the effects of azacitidine on milk production. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for azacitidine in animal studies [see Nonclinical Toxicology (13.1)] and the potential for serious adverse reactions in nursing infants from azacitidine advise patients not to breastfeed during treatment with azacitidine.
Pregnancy Testing
Contraception
Infertility
Based on animal data, azacitidine could have an effect on male or female fertility [see Nonclinical Toxicology (13.1)] .
Of the total number of patients in Studies 1, 2 and 3, 62% were 65 years and older and 21% were 75 years and older. No overall differences in effectiveness were observed between these patients and younger patients. In addition there were no relevant differences in the frequency of adverse reactions observed in patients 65 years and older compared to younger patients.
Of the 179 patients randomized to azacitidine in Study 4, 68% were 65 years and older and 21% were 75 years and older. Survival data for patients 65 years and older were consistent with overall survival results. The majority of adverse reactions occurred at similar frequencies in patients < 65 years of age and patients 65 years of age and older.
Elderly patients are more likely to have decreased renal function. Monitor renal function in these patients [see Dosage and Administration (2.5) and Warnings and Precautions (5.3)] .
One case of overdose with azacitidine was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single intravenous dose of approximately 290 mg/m 2, almost 4 times the recommended starting dose. The events resolved without sequelae, and the correct dose was resumed the following day. In the event of overdosage, the patient should be monitored with appropriate blood counts and should receive supportive treatment, as necessary. There is no known specific antidote for azacitidine overdosage.
The pharmacokinetics of azacitidine were studied in 6 MDS patients following a single 75 mg/m 2 subcutaneous dose and a single 75 mg/m 2 intravenous dose.
Absorption
Distribution
The bioavailability of subcutaneous azacitidine relative to intravenous azacitidine is approximately 89%, based on area under the curve. Mean volume of distribution following intravenous dosing is 76 ± 26 L. Mean apparent subcutaneous clearance is 167 ± 49 L/hour and mean half-life after subcutaneous administration is 41 ± 8 minutes. The AUC and C max of subcutaneous administration of azacitidine in 21 patients with cancer were approximately dose proportional within the 25 to 100 mg/m 2 dose range. Multiple dosing at the recommended dose regimen does not result in drug accumulation.
Elimination
Published studies indicate that urinary excretion is the primary route of elimination of azacitidine and its metabolites. Following intravenous administration of radioactive azacitidine to 5 cancer patients, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for <1% of administered radioactivity over 3 days. Mean excretion of radioactivity in urine following subcutaneous administration of 14C-azacitidine was 50%. The mean elimination half-lives of total radioactivity (azacitidine and its metabolites) were similar after intravenous and subcutaneous administrations, about 4 hours.
Specific Populations
The effects of hepatic impairment, gender, age, or race on the pharmacokinetics of azacitidine have not been studied.
Drug-Drug Interactions
No formal clinical drug interaction studies with azacitidine have been conducted.
The potential carcinogenicity of azacitidine was evaluated in mice and rats. Azacitidine induced tumors of the hematopoietic system in female mice at 2.2 mg/kg (6.6 mg/m 2, approximately 8% the recommended human daily dose on a mg/m 2 basis) administered IP three times per week for 52 weeks. An increased incidence of tumors in the lymphoreticular system, lung, mammary gland, and skin was seen in mice treated with azacitidine IP at 2.0 mg/kg (6.0 mg/m 2, approximately 8% the recommended human daily dose on a mg/m 2 basis) once a week for 50 weeks. A tumorigenicity study in rats dosed twice weekly at 15 or 60 mg/m 2 (approximately 20%-80% the recommended human daily dose on a mg/m 2 basis) revealed an increased incidence of testicular tumors compared with controls.
Administration of azacitidine to male mice at 9.9 mg/m 2 (approximately 9% the recommended human daily dose on a mg/m 2 basis) daily for 3 days prior to mating with untreated female mice resulted in decreased fertility and loss of offspring during subsequent embryonic and postnatal development. Treatment of male rats 3 times per week for 11 or 16 weeks at doses of 15-30 mg/m 2 (approximately 20% - 40%, the recommended human daily dose on a mg/m 2 basis) resulted in decreased weight of the testes and epididymides, and decreased sperm counts accompanied by decreased pregnancy rates and increased loss of embryos in mated females. In a related study, male rats treated for 16 weeks at 24 mg/m 2 resulted in an increase in abnormal embryos in mated females when examined on day 2 of gestation.
Myelodysplastic Syndromes (MDS)
Of the 191 patients included in the study, independent review (adjudicated diagnosis) found that 19 had the diagnosis of AML at baseline. These patients were excluded from the primary analysis of response rate, although they were included in an intent-to-treat (ITT) analysis of all patients randomized. Approximately 55% of the patients randomized to observation crossed over to receive azacitidine for injection treatment.
Azacitidine for Injection
(N=99) | Observation
(N=92) |
|
---|---|---|
Gender (n%) | ||
Male |
72 (72.7) |
60 (65.2) |
Female |
27 (27.3) |
32 (34.8) |
Race (n%) | ||
White |
93 (93.9) |
85 (92.4) |
Black |
1 (1.0) |
1 (1.1) |
Hispanic |
3 (3.0) |
5 (5.4) |
Asian/Oriental |
2 (2.0) |
1 (1.1) |
Age (years) | ||
N |
99 |
91 |
Mean ± SD |
67.3 ± 10.39 |
68.0 ± 10.23 |
Range |
31 - 92 |
35 - 88 |
Adjudicated MDS diagnosis at study entry (n%) | ||
RA |
21 (21.2) |
18 (19.6) |
RARS |
6 (6.1) |
5 (5.4) |
RAEB |
38 (38.4) |
39 (42.4) |
RAEB-T |
16 (16.2) |
14 (15.2) |
CMMoL |
8 (8.1) |
7 (7.6) |
AML |
10 (10.1) |
9 (9.8) |
Transfusion product used in 3 months before study entry (n%) | ||
Any transfusion product |
70 (70.7) |
59 (64.1) |
Blood cells, packed human |
66 (66.7) |
55 (59.8) |
Platelets, human blood |
15 (15.2) |
12 (13.0) |
Hetastarch |
0 (0.0) |
1 (1.1) |
Plasma protein fraction |
1 (1.0) |
0 (0.0) |
Other |
2 (2.0) |
2 (2.2) |
RA | RARS | RAEB | RAEB-T | CMMoL | ||
---|---|---|---|---|---|---|
Complete Response (CR), duration ≥4 weeks |
Marrow |
<5% blasts | ||||
Peripheral Blood |
Normal CBC if abnormal at baseline
|
|||||
Partial Response (PR), duration ≥4 weeks |
Marrow |
No marrow requirements |
≥50% decrease in blasts
|
|||
Peripheral Blood |
≥50% restoration in the deficit from normal levels of baseline white cells, hemoglobin and platelets if abnormal at baseline
|
Azacitidine for Injection
(N=89) | Observation Before Crossover
(N=83) | ||
---|---|---|---|
Response | n (%) | n (%) | P value |
Overall (CR+PR) |
14 (15.7) |
0 ( 0.0) |
(<0.0001) |
Complete (CR) |
5 ( 5.6) |
0 ( 0.0) |
(0.06) |
Partial (PR) |
9 (10.1) |
0 ( 0.0) |
-- |
Patients in the observation group who crossed over to receive azacitidine for injection treatment (47 patients) had a response rate of 12.8%.
Azacitidine was administered subcutaneously at a dose of 75 mg/m 2 daily for 7 consecutive days every 28 days (which constituted one cycle of therapy). Patients continued treatment until disease progression, relapse after response, or unacceptable toxicity. Azacitidine patients were treated for a median of 9 cycles (range 1 to 39), BSC only patients for a median of 7 cycles (range 1 to 26), low dose cytarabine patients for a median of 4.5 cycles (range 1 to 15), and chemotherapy with cytarabine and anthracycline patients for a median of 1 cycle (range 1 to 3, i.e. induction plus 1 or 2 consolidation cycles).
Kaplan-Meier Curve of Time to Death from Any Cause: (Intent-to-Treat Population)
Key: AZA = azacitidine; CCR = conventional care regimens; CI = confidence interval; HR = Hazard Ratio | ||||||||||||||
Azacitidine treatment led to a reduced need for red blood cell transfusions (see Table 6). In patients treated with azacitidine who were RBC transfusion dependent at baseline and became transfusion independent, the median duration of RBC transfusion independence was 13.0 months.
Efficacy Parameter | Azacitidine plus BSC
(n= 179) | Conventional Care Regimens
(n= 179) |
---|---|---|
|
||
Number and percent of patients who were transfusion dependent at baseline who became transfusion independent on treatment * |
50/111 (45.0%)
|
13/114 (11.4%)
|
Number and percent of patients who were transfusion-independent at baseline who became transfusion-dependent on treatment |
10/68 (14.7%)
|
28/65 (43.1%)
|
How Supplied
Azacitidine for injection is supplied as a lyophilized powder in 100 mg single-dose vials packaged in cartons of 1 vial (NDC 68001-504-54).
Instruct patients to inform their physician about any underlying liver disease [see Warnings and Precautions (5.2)] .
Renal Toxicity
Instruct patients to inform their physician about any underlying renal disease [see Warnings and Precautions (5.3)] .
Embryo-Fetal Risk
Advise pregnant women of the potential risk to a fetus [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1)] .
Advise females of reproductive potential to avoid pregnancy during treatment with azacitidine for injection. Advise males with female sexual partners of reproductive potential to not father a child and to use effective contraception during treatment with azacitidine for injection. Advise patients to report pregnancy to their physicians immediately [see Warnings and Precautions (5.5) and Use in Specific Populations (8.3)] .
Lactation
Advise patients to avoid breastfeeding while receiving azacitidine for injection [see Use in Specific Populations (8.2)] .
AZACITIDINE
azacitidine injection, powder, lyophilized, for solution |
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Labeler - BluePoint Laboratories (985523874) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
---|---|---|---|
Panacea Biotec Pharma, Ltd. | 857979552 | manufacture(68001-504) |