Azacitidine Seacross 100 mg/vial

/ A.L. Medi-Market LTD,

Do not substitute this medical product for oral azacitidine. The indications and dosing regimen for this medical product differ from that of oral azacytidine.
First Treatment Cycle
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. Premedicate patients for nausea and vomiting.
Obtain complete blood counts, liver chemistries and serum creatinine prior to the first dose.
Subsequent Treatment Cycles
Repeat cycles 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.
Monitor patients for hematologic response and renal toxicities, and delay or reduce dosage if necessary.
See prescribing information for full details.
Instructions for Subcutaneous Administration
Reconstitute this medical product aseptically with 4 mL Water for Injections to obtain a concentration of 25 mg/ml.
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. The product may be held at room temperature for up to 45 minutes, but must be administered within 45 minutes after reconstitution.
Instructions for Intravenous Administration
Reconstitute each vial with 10 mL Water for Injections.
Withdraw the required amount of the solution to deliver the desired dose and inject into a 50 – 100 mL infusion bag of either 0.9% Sodium Chloride solution or Lactated Ringer’s solution. Administer the total dose over a period of 10 – 40 minutes. The administration must be completed within 45 minutes of reconstitution.

Myelodysplastic Syndromes (MDS)
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).

* Advanced Malignant Hepatic Tumors
* Hypersensitivity to Azacitidine or Mannitol

Risks of Substitution with Other Azacitidine Products
The recommended dose and schedule for this medical product are different from those of oral azacitidine products.
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.
Hepatotoxicity in Patients with Severe Pre-existing Hepatic Impairment
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. Monitor liver chemistries prior to initiation of therapy and with each cycle.
Renal Toxicity
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 non-MDS 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. Monitor serum creatinine and electrolytes prior to initiation of therapy and with each cycle. If unexplained reductions in serum bicarbonate <20 mEq/L or elevations of BUN or serum creatinine occur, reduce or hold the dose.
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.
Tumor Lysis Syndrome
Azacitidine 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.
Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals, Azacitidine can cause fetal harm when administered to a pregnant woman.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.
See prescribing information for full details.

Most Commonly Occurring Adverse Reactions (Subcutaneous or Intravenous Route) in patients with MDS: 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.
See prescribing information for full details.

No formal clinical drug interaction studies with azacitidine have been conducted.
See prescribing information for full details.

Pregnancy: Based on its mechanism of action and findings in animals, Azacitidine can cause fetal harm when administered to a pregnant woman. There are no data on the use of azacitidine in pregnant women.
Lactation: 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 and the potential for serious adverse reactions in nursing infants from Azacitidine, advise patients not to breastfeed during treatment with Azacitidine and for 1 week after the last dose.
See prescribing information for full details.

One case of overdose with this medical product was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single intravenous dose of approximately 290 mg/m², 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.