Azacitidine STADA Nordic: Uses, Dosage & Side Effects
A hypomethylating agent (pyrimidine nucleoside analogue) used to treat myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia in adults not eligible for stem cell transplantation
Azacitidine STADA Nordic (azacitidine) is a hypomethylating agent belonging to the class of pyrimidine nucleoside analogues. It is used to treat adults with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplantation or intensive chemotherapy. Azacitidine works by reversing abnormal DNA methylation patterns that silence tumor suppressor genes in cancer cells, thereby restoring normal cell growth control and promoting differentiation and death of malignant cells. It is administered as a subcutaneous injection in a hospital or clinic setting and requires a prescription.
Quick Facts: Azacitidine STADA Nordic
Key Takeaways
- Azacitidine STADA Nordic is a hypomethylating agent that works by reversing abnormal DNA methylation, restoring the expression of tumor suppressor genes silenced in myelodysplastic syndromes and related blood cancers.
- It is indicated for adults with intermediate-2 and high-risk MDS, CMML with 10–29% marrow blasts, and AML with 20–30% blasts and multi-lineage dysplasia, as well as AML patients not eligible for transplant or intensive chemotherapy.
- Treatment is given as a subcutaneous injection for 7 consecutive days in 28-day cycles; a minimum of 6 cycles is recommended before assessing full response, and treatment continues as long as clinical benefit is observed.
- The most significant side effects are hematological: neutropenia, thrombocytopenia, and anemia require regular blood count monitoring, with dose adjustments or delays as needed to manage myelosuppression.
- Azacitidine is contraindicated in pregnancy and breastfeeding; both women and men of reproductive potential must use effective contraception during and for several months after treatment completion.
What Is Azacitidine STADA Nordic and What Is It Used For?
Azacitidine STADA Nordic contains the active substance azacitidine, a pyrimidine nucleoside analogue of cytidine. It belongs to a class of anticancer medications known as hypomethylating agents (HMAs), which have revolutionized the treatment landscape for myelodysplastic syndromes and related myeloid neoplasms over the past two decades. Azacitidine was first synthesized in the 1960s and initially investigated as a conventional cytotoxic agent, but its clinical development took a transformative turn when researchers discovered its ability to modulate gene expression through epigenetic mechanisms at lower doses.
The primary mechanism of action of azacitidine involves the inhibition of DNA methyltransferase (DNMT), the enzyme responsible for adding methyl groups to cytosine residues in DNA. In many hematological malignancies, particularly MDS and AML, aberrant hypermethylation of CpG islands in the promoter regions of tumor suppressor genes leads to their silencing. This epigenetic silencing allows cancer cells to proliferate unchecked, evade apoptosis, and resist differentiation. By incorporating into DNA during cell replication and trapping DNA methyltransferase in an irreversible covalent complex, azacitidine causes progressive loss of methylation marks over successive cell divisions. This DNA hypomethylation leads to the re-expression of previously silenced tumor suppressor genes, restoring normal growth control, promoting cellular differentiation, and triggering programmed cell death (apoptosis) in abnormal hematopoietic cells.
In addition to its hypomethylating effects on DNA, azacitidine is also extensively incorporated into RNA, which accounts for approximately 65% of total cellular incorporation. This RNA incorporation disrupts ribosomal assembly and protein synthesis, contributing to the direct cytotoxic effects observed at higher drug concentrations. The dual mechanism—epigenetic modulation at low doses and direct cytotoxicity at higher doses—makes azacitidine a uniquely versatile anticancer agent. At the doses used clinically (75 mg/m²), the hypomethylating effect is considered the predominant therapeutic mechanism.
Azacitidine STADA Nordic is approved by regulatory authorities in the European Union for the treatment of the following conditions in adult patients who are not eligible for hematopoietic stem cell transplantation (HSCT):
- Intermediate-2 and high-risk myelodysplastic syndromes (MDS): According to the International Prognostic Scoring System (IPSS), these are MDS subtypes with a significant risk of progression to AML and poor overall survival. MDS encompasses a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and a propensity to evolve into acute myeloid leukemia. The landmark AZA-001 trial demonstrated that azacitidine significantly prolonged overall survival compared with conventional care regimens (24.5 months vs. 15 months; p=0.0001) in higher-risk MDS patients.
- Chronic myelomonocytic leukemia (CMML): Specifically for CMML patients with 10–29% marrow blasts without a myeloproliferative disorder. CMML is a clonal hematopoietic stem cell disorder that shares features of both myelodysplastic syndromes and myeloproliferative neoplasms, characterized by persistent peripheral blood monocytosis and dysplastic changes in the bone marrow.
- Acute myeloid leukemia (AML) with 20–30% blasts and multi-lineage dysplasia: According to the WHO classification, this represents AML that has evolved from a preceding MDS. These patients often have complex cytogenetic abnormalities and carry a poor prognosis with conventional therapies.
- AML with more than 30% marrow blasts: For patients who are not eligible for HSCT. This indication recognizes that many elderly or comorbid AML patients cannot tolerate intensive induction chemotherapy, and azacitidine provides a meaningful treatment alternative that can improve survival and quality of life.
The AZA-001 study, published in The Lancet Oncology, was the first randomized controlled trial to demonstrate a significant overall survival advantage for any drug treatment in higher-risk MDS. This landmark trial established azacitidine as the standard of care for patients not eligible for transplantation and fundamentally changed the treatment paradigm for these diseases. Subsequent real-world studies and registry analyses have confirmed the survival benefit observed in clinical trials, with response rates of approximately 40–50% and a median overall survival of 18–24 months in treated populations.
Unlike traditional chemotherapy that kills rapidly dividing cells indiscriminately, azacitidine works through an epigenetic mechanism—it modifies how genes are expressed without changing the DNA sequence itself. By removing aberrant methyl groups from DNA, it can “switch on” tumor suppressor genes that the cancer cells have silenced. This mechanism explains why multiple treatment cycles are needed before full response is observed, as the epigenetic changes accumulate gradually over successive cycles of cell division.
What Should You Know Before Taking Azacitidine STADA Nordic?
Contraindications
There are specific situations in which Azacitidine STADA Nordic must not be used. Understanding these absolute contraindications is essential before treatment begins, as they represent conditions where the risks of azacitidine far outweigh any potential benefits.
- Hypersensitivity: Do not receive azacitidine if you are allergic to azacitidine or any of the other ingredients in the product (mannitol and sodium hydroxide used for pH adjustment). Allergic reactions can range from mild skin reactions to severe anaphylaxis.
- Advanced malignant hepatic tumors: Azacitidine is contraindicated in patients with advanced liver cancer (hepatic malignancy). Hepatic coma and death have been reported in these patients, particularly those with extensive tumor burden involving the liver. The hepatic metabolism of azacitidine can be severely compromised in this setting, leading to unpredictable drug accumulation and toxicity.
- Pregnancy and breastfeeding: Azacitidine must not be used during pregnancy. Animal studies have demonstrated teratogenicity and embryotoxicity. Breastfeeding must be discontinued during treatment as it is unknown whether azacitidine or its metabolites are excreted in human milk.
Warnings and Precautions
Azacitidine causes significant myelosuppression (suppression of bone marrow function), leading to neutropenia, thrombocytopenia, and anemia. These effects are dose-limiting and can be life-threatening. Complete blood counts must be performed before each treatment cycle and as clinically indicated. Dose delays, reductions, or treatment discontinuation may be necessary. Febrile neutropenia (fever with severely low white blood cells) requires urgent medical attention and empirical antibiotic therapy.
Before and during treatment with Azacitidine STADA Nordic, your doctor will carefully monitor you for the following potential complications:
- Hematological toxicity: The most common and expected adverse effects of azacitidine are cytopenias (reductions in blood cell counts). Neutropenia increases the risk of bacterial and fungal infections, thrombocytopenia increases the risk of bleeding, and anemia causes fatigue and may require red blood cell transfusions. Blood counts typically reach their lowest point (nadir) between days 10 and 17 of each treatment cycle and usually recover before the next cycle begins.
- Hepatotoxicity: Liver injury has been reported in patients receiving azacitidine, ranging from mild elevations in liver enzymes to severe hepatic failure. Patients with pre-existing liver disease require careful monitoring. Liver function tests should be performed before initiation and periodically during treatment. The drug is contraindicated in patients with advanced malignant hepatic tumors.
- Renal toxicity: Renal abnormalities, including elevations in serum creatinine and renal tubular acidosis (decrease in serum bicarbonate with metabolic acidosis and hypokalemia), have been reported. Renal function should be monitored before and during treatment. Dose reduction may be necessary in patients with renal impairment. If unexplained reductions in serum bicarbonate occur, your doctor should evaluate for possible renal tubular acidosis.
- Tumor lysis syndrome: Patients with a large tumor burden prior to treatment may be at risk for tumor lysis syndrome, a potentially life-threatening condition caused by the rapid breakdown of cancer cells. This can lead to elevated uric acid, potassium, and phosphate levels, with consequent kidney damage, cardiac arrhythmias, and seizures. Adequate hydration and monitoring of electrolytes are recommended.
- Cardiac disorders: Patients with pre-existing cardiac conditions should be monitored closely. Cardiac events including heart failure and cardiac arrest have been reported, though a direct causal relationship has not been established in all cases.
- Infections: Due to the myelosuppressive effects, patients are at increased risk of infections, including serious and potentially fatal bacterial, viral, and fungal infections. Patients should be advised to report any signs of infection (fever, chills, cough, painful urination) promptly. Prophylactic antimicrobial therapy may be considered in high-risk patients.
- Injection site reactions: Subcutaneous injection of azacitidine commonly causes local reactions at the injection site, including redness (erythema), pain, induration (hardening), bruising, swelling, and itching. Rotating injection sites between the thigh, abdomen, and upper arm can help minimize these reactions. Cold compresses applied after injection may provide relief.
- Necrotizing fasciitis: Rare cases of necrotizing fasciitis (a severe, rapidly spreading soft tissue infection), including fatal cases, have been reported at the injection site during azacitidine therapy. Patients should be monitored for any signs of tissue necrosis and treatment should be discontinued if this occurs.
Pregnancy and Breastfeeding
Azacitidine is genotoxic and has been shown to be teratogenic and embryotoxic in animal studies. Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose. Men must use effective contraception during treatment and for 3 months after the last dose. Men are advised to seek counseling on sperm preservation before starting treatment, as azacitidine may impair male fertility. Breastfeeding must be discontinued during azacitidine therapy.
If you are pregnant or think you might be pregnant, inform your doctor immediately before starting treatment. If you or your partner become pregnant during treatment, contact your doctor urgently. The potential risk to the fetus based on the mechanism of action and animal data is considered significant, and azacitidine should only be prescribed to women of childbearing potential when a reliable pregnancy test has been confirmed as negative and effective contraception is in place.
Fertility may be affected by treatment with azacitidine. Both female and male patients should discuss fertility preservation options with their healthcare team before starting therapy. Men should consider sperm cryopreservation, as the drug may affect spermatogenesis. The duration of potential fertility impairment after treatment completion is not fully characterized.
How Does Azacitidine STADA Nordic Interact with Other Drugs?
Formal drug-drug interaction studies with azacitidine have been limited. However, based on its pharmacological properties, mechanism of metabolism, and clinical experience, several important interactions should be considered. Azacitidine is metabolized primarily through spontaneous chemical hydrolysis and enzymatic deamination by cytidine deaminase, rather than through cytochrome P450 (CYP450) enzymes. This means that CYP450-mediated drug interactions are considered unlikely, which is a favorable pharmacokinetic property for patients who typically receive multiple concurrent medications.
However, the following interactions warrant clinical attention and should be discussed with your healthcare provider:
Major Interactions
| Drug / Class | Interaction | Recommendation |
|---|---|---|
| Live vaccines (e.g., MMR, varicella, yellow fever) | Azacitidine-induced immunosuppression may allow vaccine virus replication, potentially causing serious or fatal infections | Avoid all live vaccines during treatment and for at least 3 months after completion |
| Hepatotoxic agents (e.g., methotrexate, valproic acid, statins) | Additive risk of liver damage; azacitidine itself can cause hepatotoxicity | Monitor liver function closely; consider dose adjustments of hepatotoxic co-medications |
| Nephrotoxic agents (e.g., aminoglycosides, NSAIDs, cisplatin) | Additive risk of renal impairment and renal tubular acidosis | Monitor renal function and serum bicarbonate; avoid concurrent use if possible |
| Myelosuppressive agents (other chemotherapy, immunosuppressants) | Increased risk of severe cytopenias, infections, and bleeding | Enhanced blood count monitoring; adjust doses as clinically indicated |
Minor Interactions
| Drug / Class | Interaction | Recommendation |
|---|---|---|
| Anticoagulants (warfarin, DOACs) | Azacitidine-induced thrombocytopenia may increase bleeding risk when combined with anticoagulants | Monitor platelet counts and coagulation parameters closely; adjust anticoagulant dosing as needed |
| Antiplatelet agents (aspirin, clopidogrel) | Additive bleeding risk due to thrombocytopenia | Weigh bleeding risk vs. cardiovascular benefit; hold if platelet count critically low |
| Inactivated vaccines (influenza, pneumococcal) | Reduced immune response due to immunosuppression; vaccines may be less effective | Vaccination may still be given but expected efficacy is reduced; consider timing around treatment cycles |
It is important to tell your doctor or pharmacist about all medications you are currently taking, including prescription and over-the-counter drugs, vitamins, herbal supplements, and dietary products. While azacitidine has a relatively low risk of pharmacokinetic drug interactions due to its unique metabolic pathway, pharmacodynamic interactions—where two drugs have additive or synergistic effects on the same organ system—remain clinically important, particularly with respect to myelosuppression, hepatotoxicity, and nephrotoxicity.
Recent clinical interest has focused on the combination of azacitidine with venetoclax (a BCL-2 inhibitor) for the treatment of newly diagnosed AML in patients ineligible for intensive chemotherapy. This combination, approved by the FDA and EMA, has shown significant improvements in response rates and survival but requires careful management of enhanced myelosuppression. If you are receiving azacitidine as part of a combination regimen, your doctor will provide specific guidance on the interaction profile of the entire treatment protocol.
What Is the Correct Dosage of Azacitidine STADA Nordic?
Azacitidine STADA Nordic is always prescribed and administered under the supervision of a physician experienced in the treatment of hematological malignancies. The dosing is individualized based on body surface area (BSA), which is calculated from the patient’s height and weight. The powder for injection must be reconstituted by a healthcare professional before administration. Patients should be premedicated with anti-emetics (anti-nausea medication) as azacitidine commonly causes nausea and vomiting.
Adults
Standard Dosing Regimen
The recommended starting dose for all indications is 75 mg/m² body surface area, injected subcutaneously, once daily for 7 consecutive days, followed by a rest period of 21 days (total cycle length: 28 days). This cycle is repeated every 28 days. For example, a patient with a BSA of 1.8 m² would receive 135 mg per injection (75 mg/m² × 1.8 m²).
Treatment should be continued for a minimum of 6 cycles. Complete or partial responses may not appear until cycles 4–6, so early discontinuation should be avoided unless there is clear evidence of disease progression or unacceptable toxicity. After the initial 6 cycles, treatment should be continued for as long as the patient continues to show clinical benefit.
Alternative 5-Day Regimen
An alternative dosing schedule of 75 mg/m² daily for 5 consecutive days every 28 days may be used when the standard 7-day regimen is not feasible for logistical or tolerance reasons. While this schedule is sometimes used in clinical practice, the 7-day regimen is the one supported by the pivotal AZA-001 trial data and is generally preferred.
Dose Adjustments for Hematological Toxicity
| Scenario | Nadir Counts | Recommended Action |
|---|---|---|
| WBC ≥ 3.0 × 10&sup9;/L, ANC ≥ 1.5 × 10&sup9;/L, Platelets ≥ 75 × 10&sup9;/L | Adequate recovery | 100% of dose in next cycle |
| ANC 0.5–1.5 × 10&sup9;/L, Platelets 25–75 × 10&sup9;/L | Moderate suppression | 50% dose reduction in next cycle (if recovery not due to disease); delay cycle if counts not recovered |
| ANC < 0.5 × 10&sup9;/L, Platelets < 25 × 10&sup9;/L | Severe suppression | 50% dose reduction in next cycle (if recovery not due to disease); delay cycle if counts not recovered |
If the cytopenias are considered to be due to the underlying disease process rather than azacitidine treatment (i.e., baseline counts were already low before treatment started), the dose should not be reduced. The decision to reduce, delay, or continue treatment at full dose requires careful clinical judgment and is made by the treating hematologist based on the individual patient’s disease status, response to therapy, and overall clinical condition.
Children
Azacitidine STADA Nordic is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of azacitidine in the pediatric population have not been established in adequate clinical studies. MDS and CMML are predominantly diseases of older adults, and the use of azacitidine in pediatric patients remains investigational and limited to clinical trial settings.
Elderly
No specific dose adjustment is recommended based on age alone. However, as MDS and AML primarily affect older adults (median age at diagnosis is approximately 70 years), the majority of clinical experience with azacitidine is in elderly patients. Older patients may have reduced renal function and are more likely to have comorbidities, so careful monitoring of renal function, blood counts, and overall tolerance is particularly important. The AZA-001 trial included patients up to 85 years of age, demonstrating that azacitidine can provide meaningful survival benefit even in very elderly patients when appropriately monitored.
Renal Impairment
No specific dose adjustment is required for patients with mild to moderate renal impairment. However, since azacitidine and its metabolites are excreted primarily by the kidneys, patients with renal impairment should be monitored closely for adverse effects. If unexplained elevations of serum creatinine or BUN occur, the next treatment cycle should be delayed until values return to normal or baseline, and the dose should be reduced by 50% for the following cycle. Azacitidine has not been specifically studied in patients with severe renal impairment (creatinine clearance < 30 ml/min) or patients on dialysis.
Missed Dose
If a dose is missed during the 7-day treatment period, it should be administered as soon as possible, and the treatment schedule should be adjusted accordingly. Since azacitidine is administered in a clinical setting by healthcare professionals, missed doses are relatively uncommon. If the delay is significant, the healthcare team will determine whether to extend the current cycle or adjust the schedule for subsequent cycles. Do not attempt to double doses to make up for missed injections.
Overdose
There is limited clinical experience with azacitidine overdose. In the event of an overdose, the patient should be monitored with appropriate blood counts and should receive supportive treatment as necessary. There is no specific antidote for azacitidine overdose. The expected complications of overdose would primarily involve severe and prolonged myelosuppression (neutropenia, thrombocytopenia, and anemia), along with gastrointestinal toxicity. Management would include supportive care with blood product transfusions, growth factor support (G-CSF for neutropenia), and antimicrobial prophylaxis or treatment as indicated.
What Are the Side Effects of Azacitidine STADA Nordic?
Like all medicines, Azacitidine STADA Nordic can cause side effects, although not everybody experiences them. Some side effects may be serious and require immediate medical attention. The most frequent and clinically significant adverse effects are related to myelosuppression (bone marrow suppression), which is both the primary pharmacological effect and the dose-limiting toxicity of azacitidine. Hematological side effects are expected and manageable with appropriate monitoring and supportive care, but they can occasionally lead to serious complications such as life-threatening infections or hemorrhage.
The side effects are listed below according to their frequency of occurrence, based on clinical trial data and post-marketing surveillance:
Very Common (affects more than 1 in 10 patients)
Frequency: > 10%
- Neutropenia (low white blood cells) – febrile neutropenia
- Thrombocytopenia (low platelets) – increased bleeding risk
- Anemia (low red blood cells) – fatigue, pallor, shortness of breath
- Leukopenia (low total white blood cells)
- Pneumonia and other infections (respiratory tract, urinary tract)
- Nausea, vomiting, diarrhea, constipation
- Abdominal pain
- Injection site reactions (erythema, pain, bruising, induration, itching)
- Fatigue, asthenia (weakness), pyrexia (fever)
- Decreased appetite, weight loss
- Dizziness, headache
- Dyspnea (shortness of breath)
- Arthralgia (joint pain), myalgia (muscle pain)
- Petechiae (small red spots on skin from bleeding)
Common (affects 1 to 10 in 100 patients)
Frequency: 1–10%
- Sepsis (life-threatening blood infection)
- Nasopharyngitis (common cold), cellulitis
- Pancytopenia (reduction of all blood cell types)
- Hypokalemia (low potassium), hyponatremia (low sodium)
- Depression, insomnia, anxiety
- Peripheral neuropathy (numbness, tingling in hands/feet)
- Epistaxis (nosebleeds)
- Cardiac events (atrial fibrillation, cardiac failure)
- Hypotension (low blood pressure)
- Stomatitis (mouth sores), dyspepsia (indigestion)
- Rash, pruritus (itching), ecchymosis (bruising)
- Elevated liver enzymes (ALT, AST, alkaline phosphatase)
- Elevated serum creatinine
- Chest pain, musculoskeletal pain
- Hematoma, injection site hemorrhage
Uncommon (affects 1 to 10 in 1,000 patients)
Frequency: 0.1–1%
- Renal tubular acidosis (metabolic acidosis with low bicarbonate)
- Tumor lysis syndrome
- Hepatic failure, hepatic coma
- Allergic reactions (anaphylactic reactions)
- Interstitial lung disease, pulmonary fibrosis
- Sweet syndrome (acute febrile neutrophilic dermatosis)
- Pyoderma gangrenosum
Rare (affects less than 1 in 1,000 patients)
Frequency: < 0.1%
- Necrotizing fasciitis at injection site (potentially fatal)
- Differentiation syndrome
- Stevens-Johnson syndrome / toxic epidermal necrolysis
Contact your doctor or seek emergency medical care immediately if you experience: fever or chills (possible infection from neutropenia), unusual bleeding or bruising (possible thrombocytopenia), severe abdominal pain, signs of allergic reaction (difficulty breathing, swelling of face/throat, severe rash), confusion or decreased consciousness, severe skin reactions with blistering, or signs of tissue infection (rapidly spreading redness, warmth, and pain) around any injection site.
Most side effects of azacitidine are manageable with supportive care and dose adjustments. Nausea and vomiting can be controlled with anti-emetic medications (ondansetron or similar 5-HT3 receptor antagonists are commonly used). Injection site reactions are typically mild and self-limiting, and can be minimized by rotating injection sites and applying cold compresses. Blood product transfusions (red blood cells and platelets) and growth factor support (G-CSF) are commonly used to manage the hematological side effects.
It is important to remember that many patients experience significant improvement in blood counts and quality of life after several cycles of azacitidine therapy, as the drug begins to restore normal bone marrow function. The early cycles of treatment often produce the most pronounced myelosuppression, with gradual improvement as the malignant clone is suppressed and normal hematopoiesis recovers.
How Should You Store Azacitidine STADA Nordic?
Proper storage of Azacitidine STADA Nordic is essential to maintain the chemical stability, pharmaceutical quality, and therapeutic efficacy of the product. As a powder for suspension for injection, the storage requirements differ between the unopened (unreconstituted) product and the reconstituted suspension ready for injection.
- Unopened vials: Store below 25°C. Keep the vial in the outer carton to protect from light. There is no need for refrigeration of the unreconstituted powder.
- After reconstitution: Chemical and physical in-use stability of the reconstituted suspension has been demonstrated for up to 8 hours at 2–8°C (in the refrigerator). From a microbiological point of view, the product should be used immediately after reconstitution. If not used immediately, in-use storage times and conditions are the responsibility of the user and should not exceed 8 hours at 2–8°C.
- Before injection: If the reconstituted suspension has been stored in the refrigerator, allow it to equilibrate to room temperature for approximately 30 minutes before administration. The suspension should be used within 30 minutes of removal from the refrigerator.
- Do not freeze: The reconstituted suspension should not be frozen.
- Do not use if the suspension contains large particles or is discolored. A uniform cloudy suspension is expected after reconstitution.
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and vial label after “EXP”. The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment, as azacitidine is a cytotoxic substance that requires special handling and disposal in accordance with local guidelines for hazardous pharmaceutical waste.
What Does Azacitidine STADA Nordic Contain?
Understanding the composition of Azacitidine STADA Nordic is important both for clinical practice and for identifying potential allergens or intolerances. The product has a simple formulation designed to provide stability as a lyophilized powder and produce a uniform suspension upon reconstitution.
Active Ingredient
- Azacitidine: 100 mg per vial. After reconstitution with 4 ml of water for injections, the resulting suspension contains approximately 25 mg/ml of azacitidine. Azacitidine (chemical name: 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one) is a pyrimidine nucleoside analogue of cytidine with a molecular weight of 244.2 g/mol. It is a white to off-white powder that is sparingly soluble in water.
Inactive Ingredients (Excipients)
- Mannitol (E421): 100 mg per vial. Mannitol is a sugar alcohol used as a bulking agent and lyoprotectant (protects the active substance during the freeze-drying process). It helps to create the characteristic cake structure of the lyophilized powder and facilitates rapid and complete reconstitution.
- Sodium hydroxide: May be added in small quantities for pH adjustment of the formulation. The amount is minimal and not considered clinically significant.
Reconstitution
The powder should be reconstituted with 4 ml of water for injections. The vial should be vigorously shaken or rolled until a uniform, cloudy suspension is achieved. The reconstituted product will appear as an opaque, homogeneous suspension free from large aggregates. Each ml of the reconstituted suspension contains 25 mg of azacitidine. A single vial will provide slightly more than the 4 ml needed for the full dose to account for the small dead volume retained in the vial and needle during withdrawal.
Azacitidine STADA Nordic does not contain preservatives, latex, or any animal-derived ingredients. Individuals with a known hypersensitivity to mannitol or any other component should inform their doctor before receiving this medication. Healthcare professionals handling the product should follow institutional guidelines for the safe handling of cytotoxic drugs, including wearing protective gloves and avoiding inhalation of the powder or contact with skin or mucous membranes.
Frequently Asked Questions About Azacitidine STADA Nordic
Azacitidine STADA Nordic is used to treat adult patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) with 10–29% marrow blasts, and acute myeloid leukemia (AML) with 20–30% blasts and multi-lineage dysplasia. It is also used for AML patients with more than 30% marrow blasts who are not eligible for stem cell transplantation or intensive chemotherapy. It works as a hypomethylating agent, reversing abnormal DNA methylation to restore expression of tumor suppressor genes.
Azacitidine is given as a subcutaneous (under the skin) injection at 75 mg/m² body surface area once daily for 7 consecutive days, followed by a 21-day rest period (28-day cycle). Treatment should continue for a minimum of 6 cycles, as responses may not appear until cycles 3–6. If the patient is benefiting, treatment typically continues indefinitely until disease progression or unacceptable side effects. An alternative 5-day schedule may be used when appropriate.
Regular complete blood count (CBC) monitoring is essential. Blood counts should be checked before each treatment cycle and as clinically indicated between cycles (typically around day 14–17 when counts reach their nadir). Liver function tests and renal function tests (including serum bicarbonate) should also be monitored periodically. Your doctor may check blood counts more frequently during the first few cycles to establish your individual response pattern.
No. Azacitidine is contraindicated during pregnancy due to demonstrated teratogenicity and embryotoxicity in animal studies. Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose. Men must use effective contraception during treatment and for 3 months after. Men should consider sperm cryopreservation before starting treatment. Breastfeeding must be discontinued during azacitidine therapy.
Both products contain the same active ingredient—azacitidine—at the same concentration (25 mg/ml after reconstitution). Vidaza was the original brand-name product, while Azacitidine STADA Nordic is a generic version manufactured by STADA Arzneimittel. Generic azacitidine products have been approved by regulatory authorities (such as the EMA) after demonstrating equivalent pharmaceutical quality, bioequivalence, and comparable safety and efficacy profiles. They can be used interchangeably for the same indications.
Injection site reactions are very common with subcutaneous azacitidine and include redness, pain, bruising, swelling, and itching. To minimize these: rotate injection sites between the thigh, abdomen, and upper arm; apply a cold compress or ice pack after injection; avoid injecting into areas that are tender, bruised, red, or hard. Most injection site reactions are mild and resolve within a few days. However, if you notice rapidly spreading redness, warmth, or tissue breakdown at an injection site, seek medical attention immediately as rare cases of serious skin infections have been reported.
References
- European Medicines Agency (EMA). Azacitidine Summary of Product Characteristics (SmPC). Last updated 2025. Available from: www.ema.europa.eu
- U.S. Food and Drug Administration (FDA). Vidaza (azacitidine for injection) Prescribing Information. Reference ID: 5106837. Updated 2024. Available from: www.fda.gov
- Fenaux P, Mufti GJ, Hellström-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study (AZA-001). Lancet Oncol. 2009;10(3):223–232. doi:10.1016/S1470-2045(09)70003-8
- Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2002;20(10):2429–2440. doi:10.1200/JCO.2002.04.117
- DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia (VIALE-A). N Engl J Med. 2020;383(7):617–629. doi:10.1056/NEJMoa2012971
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes. Version 1.2025. Available from: www.nccn.org
- Platzbecker U, Middeke JM, Sockel K, et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018;19(12):1668–1679. doi:10.1016/S1470-2045(18)30580-1
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd List (2023). Available from: www.who.int
- British National Formulary (BNF). Azacitidine monograph. National Institute for Health and Care Excellence (NICE). Updated 2025. Available from: bnf.nice.org.uk
- Malcovati L, Hellström-Lindberg E, Bowen D, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943–2964. doi:10.1182/blood-2013-03-492884
Editorial Team
Medical Content
iMedic Medical Editorial Team – Specialists in Hematology-Oncology and Clinical Pharmacology
Medical Review
iMedic Medical Review Board – Independent panel of medical experts reviewing according to EMA, FDA, and WHO guidelines
Evidence Framework
GRADE evidence framework – Level 1A evidence based on systematic reviews and randomized controlled trials
Editorial Standards
Adherence to NCCN, ESMO, and ELN (European LeukemiaNet) clinical practice guidelines for myeloid neoplasms
Last reviewed: | Published: | Editorial Standards | Our Medical Team