Arsenic Trioxide Medac: Uses, Dosage & Side Effects
An antineoplastic and differentiating agent for the treatment of acute promyelocytic leukemia (APL), administered as an intravenous infusion
Arsenic Trioxide Medac is a hospital-administered intravenous medication containing the active substance arsenic trioxide (1 mg/ml), manufactured by medac GmbH. It is used to treat acute promyelocytic leukemia (APL), a rare but potentially curable subtype of acute myeloid leukemia characterized by the PML-RARα fusion gene. The drug works by inducing differentiation of immature leukemic promyelocytes into normal mature blood cells, while also triggering programmed cell death (apoptosis) in these cancerous cells. Arsenic Trioxide Medac is approved for newly diagnosed low-to-intermediate risk APL in combination with all-trans retinoic acid (ATRA), as well as for relapsed or refractory APL when previous treatments have failed. Treatment requires close medical supervision including regular ECG monitoring and blood tests due to potential cardiac and metabolic risks.
Quick Facts: Arsenic Trioxide Medac
Key Takeaways
- Arsenic Trioxide Medac is a targeted therapy for acute promyelocytic leukemia (APL) that works by inducing cancer cell differentiation and apoptosis through degradation of the PML-RARα oncoprotein.
- For newly diagnosed low-to-intermediate risk APL, it is combined with all-trans retinoic acid (ATRA) in a chemotherapy-free regimen that achieves cure rates exceeding 90% in clinical trials.
- Differentiation syndrome is a potentially life-threatening complication requiring immediate medical attention — symptoms include fever, breathing difficulty, weight gain, and fluid retention.
- QT prolongation and cardiac arrhythmias are serious risks; ECG monitoring and electrolyte correction (potassium, magnesium, calcium) are mandatory before and during treatment.
- Both women and men of reproductive potential must use effective contraception during treatment and for 6 months (women) or 3 months (men) after the last dose; breastfeeding is contraindicated.
What Is Arsenic Trioxide Medac and What Is It Used For?
Arsenic Trioxide Medac contains the active substance arsenic trioxide (chemical formula As2O3), manufactured by medac GmbH, a German pharmaceutical company specializing in oncology and autoimmune disease medications. Although arsenic has been recognized as a toxin for centuries, its therapeutic potential in leukemia was first explored in traditional Chinese medicine and later validated through rigorous clinical trials that revolutionized the treatment of acute promyelocytic leukemia. Today, arsenic trioxide is considered one of the most important advances in hematology, having transformed APL from one of the most lethal forms of acute leukemia into one of the most curable.
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) that accounts for approximately 5–8% of all AML cases. APL is characterized by the accumulation of immature white blood cells called promyelocytes in the bone marrow and blood. In virtually all cases, APL is driven by a specific chromosomal abnormality — the translocation t(15;17)(q24;q21) — which creates the PML-RARα fusion gene. This abnormal gene produces a fusion protein that blocks the normal differentiation of promyelocytes, trapping them in an immature state and causing them to proliferate uncontrollably. APL often presents with life-threatening coagulopathy (a tendency toward both bleeding and clotting), making early diagnosis and prompt initiation of treatment critical.
Arsenic trioxide exerts its anti-leukemic effects through multiple complementary mechanisms. Its primary action is the direct targeting and degradation of the PML-RARα oncoprotein. By binding to cysteine residues in the PML moiety of the fusion protein, arsenic trioxide promotes its SUMOylation (a type of protein modification), ubiquitination, and subsequent degradation by the proteasome. This removal of the oncogenic driver allows the previously blocked promyelocytes to resume their normal differentiation pathway, maturing into functional granulocytes. Additionally, arsenic trioxide induces apoptosis (programmed cell death) in APL cells through several pathways, including increased generation of reactive oxygen species (ROS), activation of caspases, disruption of mitochondrial membrane potential, and modulation of pro-apoptotic and anti-apoptotic proteins.
Arsenic Trioxide Medac is approved for use in the following clinical scenarios:
- Newly diagnosed low-to-intermediate risk APL: Arsenic trioxide is used in combination with all-trans retinoic acid (ATRA) as first-line therapy. This ATRA+ATO (arsenic trioxide) regimen represents a groundbreaking chemotherapy-free approach to APL treatment. The landmark APL0406 trial by Lo-Coco et al., published in the New England Journal of Medicine, demonstrated that ATRA+ATO was non-inferior to traditional ATRA plus chemotherapy (AIDA protocol) in low-to-intermediate risk patients, with superior event-free survival and overall survival. Long-term follow-up data have confirmed cure rates exceeding 90% with the ATRA+ATO combination. Risk stratification in APL is primarily based on the initial white blood cell (WBC) count at diagnosis: low risk is defined as WBC ≤10 × 109/L.
- Relapsed or refractory APL: For patients whose APL has not responded to or has returned after other treatments (including ATRA and/or chemotherapy), arsenic trioxide is used as salvage therapy. In the pivotal clinical trials that led to its initial approval, arsenic trioxide achieved complete remission rates of 85–87% in relapsed APL, including molecular remission (negative PML-RARα by PCR) in the majority of responding patients. This established arsenic trioxide as the single most effective agent available for relapsed APL.
APL is a medical emergency at diagnosis because of the severe coagulopathy that accompanies it. Disseminated intravascular coagulation (DIC), hyperfibrinolysis, and proteolytic enzyme release from leukemic promyelocytes can cause fatal hemorrhage, particularly intracranial bleeding. Early mortality (death within the first 30 days) remains the greatest challenge in APL management and is most commonly caused by hemorrhagic complications before or shortly after treatment initiation. Current international guidelines from organizations including the European LeukemiaNet (ELN), NCCN, and ESMO emphasize that treatment with ATRA should begin immediately upon clinical suspicion of APL, even before genetic confirmation, and that arsenic trioxide should be started as soon as the diagnosis is confirmed.
Arsenic trioxide is one of the most successful examples of targeted therapy in oncology. Before its introduction, APL had a 5-year survival rate of approximately 35–45% with chemotherapy alone. With the introduction of ATRA in the 1990s, outcomes improved dramatically. The addition of arsenic trioxide has pushed cure rates for low-to-intermediate risk APL above 90%, making it one of the most curable cancers in adults when diagnosed and treated promptly. The 2018 Nobel Prize in Physiology or Medicine was awarded in part for the discovery of arsenic trioxide as a treatment for APL.
What Should You Know Before Taking Arsenic Trioxide Medac?
Contraindications
There are specific situations in which Arsenic Trioxide Medac must not be used. Understanding these absolute contraindications is essential before treatment begins, and your healthcare team will verify these before administering the first dose.
- Hypersensitivity: Do not receive Arsenic Trioxide Medac if you are allergic to arsenic trioxide or any of the other ingredients in the product (sodium hydroxide, hydrochloric acid for pH adjustment, and water for injections). Allergic reactions can range from mild skin reactions to severe anaphylaxis.
Warnings and Precautions
Tell your doctor or nurse immediately if you experience difficulty breathing, cough, chest pain, or fever during treatment with arsenic trioxide. These may be signs of differentiation syndrome (previously called APL differentiation syndrome or retinoic acid syndrome), a serious condition in which leukemia cells release inflammatory cytokines as they differentiate. Without prompt treatment (typically with high-dose corticosteroids such as dexamethasone), differentiation syndrome can be fatal. It occurs in approximately 25–30% of patients receiving ATRA+ATO combination therapy, usually during the first few weeks of treatment.
Before and during treatment with Arsenic Trioxide Medac, your doctor will take the following precautions and you should inform them if any of these conditions apply to you:
- Cardiac monitoring: An electrocardiogram (ECG) must be performed before the first dose to assess your baseline heart rhythm, particularly the QT interval. Arsenic trioxide can cause QT prolongation, which increases the risk of potentially fatal cardiac arrhythmias, including torsade de pointes. ECGs are then performed twice weekly throughout the treatment course. If the QTc interval exceeds 500 milliseconds, treatment may need to be interrupted until electrolyte imbalances are corrected and the QTc returns to acceptable levels. Patients with pre-existing QT prolongation, congestive heart failure, or those taking other QT-prolonging medications are at particularly high risk.
- Electrolyte monitoring: Blood tests for potassium, magnesium, calcium, and creatinine are required before the first dose and are repeated regularly during treatment. Electrolyte imbalances, particularly low potassium (hypokalemia) and low magnesium (hypomagnesemia), significantly increase the risk of QT prolongation and cardiac arrhythmias. Your doctor will correct any electrolyte abnormalities before starting treatment and will maintain potassium levels above 4.0 mEq/L and magnesium levels above 1.8 mg/dL throughout treatment.
- Kidney function: If you have impaired kidney function, inform your doctor. Since arsenic and its metabolites are primarily excreted through the kidneys, reduced kidney function may lead to accumulation of arsenic in the body and increased toxicity. Kidney function tests (creatinine) are monitored before and during treatment.
- Liver function: If you have any liver problems, tell your doctor. Arsenic trioxide can cause hepatotoxicity (liver damage), manifesting as elevated liver enzymes (transaminases and bilirubin). Liver function tests are performed regularly during treatment. Grade 3 or higher liver toxicity may require treatment interruption.
- Vitamin B1 (thiamine) deficiency: Patients at risk of vitamin B1 deficiency (such as those with poor nutrition, chronic alcohol use, or prolonged parenteral nutrition) should be monitored for cognitive function and mobility. Arsenic trioxide may worsen or precipitate Wernicke encephalopathy, a serious neurological condition caused by thiamine deficiency, presenting with confusion, difficulty walking, and eye movement abnormalities.
- Secondary malignancies: Your doctor may monitor your health during and after treatment because arsenic trioxide may be associated with an increased risk of developing other types of cancer. Report any new or unusual symptoms to your doctor at every visit.
- Leukocytosis: During treatment, the white blood cell count may rise significantly (hyperleukocytosis) as leukemia cells undergo differentiation. This can contribute to differentiation syndrome and may require management with hydroxyurea or temporary interruption of arsenic trioxide.
Children and Adolescents
Arsenic Trioxide Medac is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of arsenic trioxide in pediatric patients have not been established in adequate controlled trials. Pediatric APL is managed according to specific pediatric protocols, typically involving ATRA in combination with chemotherapy, under the guidance of pediatric hematology-oncology specialists. Some pediatric oncology cooperative groups have conducted studies using arsenic trioxide in children with relapsed APL, but data remain limited and the drug does not have a formal pediatric indication.
Pregnancy and Breastfeeding
Arsenic trioxide is expected to cause serious harm to the developing fetus. It has demonstrated reproductive toxicity and teratogenicity in animal studies. Women of childbearing potential must use effective contraception during treatment and for at least 6 months after the last dose. Men receiving Arsenic Trioxide Medac must also use effective contraception and are advised not to father a child during treatment and for 3 months after the last dose. If you are pregnant or become pregnant during treatment, inform your doctor immediately to discuss the risks and options.
Breastfeeding: Arsenic passes into breast milk and may cause harm to a nursing infant. Women must not breastfeed during treatment with Arsenic Trioxide Medac and for at least two weeks after the final dose. Discuss alternative feeding options with your healthcare team before starting treatment.
Driving and Using Machines
Arsenic Trioxide Medac is expected to have no or negligible effect on the ability to drive and use machines under normal circumstances. However, if you experience side effects such as dizziness, confusion, or fatigue after receiving an infusion, wait until these symptoms resolve completely before driving or operating machinery. Given that this medication is administered in a hospital setting, most patients will not be driving immediately after treatment.
Arsenic Trioxide Medac contains less than 1 mmol of sodium (23 mg) per dose, meaning that it is essentially “sodium-free.” This is relevant for patients on sodium-restricted diets.
How Does Arsenic Trioxide Medac Interact with Other Drugs?
Arsenic trioxide has clinically significant interactions primarily related to its ability to prolong the QT interval on the electrocardiogram. When combined with other QT-prolonging medications, the risk of potentially fatal cardiac arrhythmias, including torsade de pointes, is substantially increased. Additionally, drugs that deplete electrolytes (particularly potassium and magnesium) can indirectly worsen QT prolongation and should be used with extreme caution.
The following table summarizes the most important drug interactions. However, this is not an exhaustive list. Always inform your doctor, pharmacist, or nurse about all medications you are taking, have recently taken, or might take, including over-the-counter and herbal products.
Major Interactions
| Drug / Drug Class | Examples | Interaction Mechanism | Clinical Significance |
|---|---|---|---|
| Class I/III Antiarrhythmics | Quinidine, amiodarone, sotalol, dofetilide | Additive QT prolongation | High risk of torsade de pointes; avoid combination if possible |
| Antipsychotics | Thioridazine, haloperidol, pimozide | Additive QT prolongation | Increased arrhythmia risk; close ECG monitoring required |
| Tricyclic Antidepressants | Amitriptyline, nortriptyline, imipramine | Additive QT prolongation | Enhanced cardiac risk; ECG monitoring recommended |
| Certain Antibiotics | Erythromycin, sparfloxacin, moxifloxacin | Additive QT prolongation | Choose alternative antibiotics when possible |
| Electrolyte-Depleting Drugs | Amphotericin B, loop diuretics, thiazides | Reduces potassium/magnesium levels, worsening QT prolongation | Aggressive electrolyte monitoring and replacement needed |
| Older Antihistamines | Terfenadine, astemizole | Additive QT prolongation | Avoid; use non-QT-prolonging alternatives (cetirizine, loratadine) |
| Prokinetic Agents | Cisapride | Additive QT prolongation | Contraindicated; use alternative GI medications |
Additional Considerations
If you are taking or have recently taken any medication that may affect your liver, inform your doctor. Although arsenic trioxide is not extensively metabolized by hepatic cytochrome P450 enzymes, hepatotoxic medications may increase the risk of liver damage when used concurrently.
There are no known food or drink restrictions during treatment with Arsenic Trioxide Medac. However, maintaining adequate nutrition and hydration is important to support electrolyte balance and overall health during cancer treatment.
Herbal supplements and traditional medicines should be discussed with your healthcare team, as some may have QT-prolonging properties or affect electrolyte levels. Products containing St. John’s wort, licorice root (which can deplete potassium), and certain dietary supplements should be reviewed before treatment.
The risk of cardiac complications with arsenic trioxide increases when multiple QT-prolonging drugs are combined. Even if a medication is not listed above, it may still interact with arsenic trioxide. Always provide your medical team with a complete, up-to-date list of all medications, supplements, and herbal products you are using.
What Is the Correct Dosage of Arsenic Trioxide Medac?
Arsenic Trioxide Medac is administered exclusively by intravenous infusion in a supervised healthcare setting. The drug comes as a concentrate (1 mg/ml) that must be diluted in 100–250 ml of 5% glucose (dextrose) solution or 0.9% sodium chloride solution before infusion. PVC-free infusion bags should be used. The prepared solution is administered over 1–2 hours; however, the infusion time may be extended to up to 4 hours if vasomotor reactions (such as flushing or dizziness) occur. A central venous catheter is not required. Arsenic Trioxide Medac must not be mixed with or administered through the same intravenous line as other medications.
Adults — Newly Diagnosed APL
Induction Phase
Arsenic trioxide 0.15 mg/kg per day as an intravenous infusion, administered daily. Treatment continues until complete remission is achieved, or for a maximum of 60 days in the first treatment cycle, whichever comes first. During induction, arsenic trioxide is given concurrently with ATRA (all-trans retinoic acid).
Consolidation Phase
Following achievement of complete remission, patients receive 4 additional consolidation cycles. Each cycle consists of 20 doses given 5 days per week (Monday through Friday) for 4 weeks, followed by a 4-week treatment-free interval. ATRA is administered concurrently during each consolidation cycle according to the treatment protocol.
Adults — Relapsed or Refractory APL
Induction Phase
Arsenic trioxide 0.15 mg/kg per day as an intravenous infusion, administered daily. Treatment continues until complete remission is achieved (typically bone marrow remission), or for a maximum of 50 days in the first treatment cycle, whichever comes first.
Consolidation Phase
Beginning 3–6 weeks after completion of induction, patients receive 1 additional consolidation cycle of 25 doses given 5 days per week for 5 weeks.
Children and Adolescents
Arsenic Trioxide Medac is not recommended for use in patients under 18 years of age due to insufficient data on safety and efficacy in this population.
Elderly Patients
No specific dose adjustment is recommended for elderly patients based on age alone. However, older patients may be more susceptible to electrolyte imbalances, cardiac toxicity, and other adverse effects. Careful monitoring of cardiac function, electrolytes, and renal function is particularly important in this population. Dose modifications may be necessary based on individual tolerance and comorbidities.
Patients with Renal Impairment
Since arsenic trioxide and its metabolites are primarily eliminated through the kidneys, patients with renal impairment require particularly careful monitoring. There are limited pharmacokinetic data in patients with severe renal impairment. Dose adjustments may be necessary, and your doctor will carefully assess the benefit-risk balance before initiating treatment. More frequent monitoring of renal function, electrolytes, and arsenic-related toxicities is recommended in these patients.
Missed Dose
Since Arsenic Trioxide Medac is administered in a hospital or clinic setting by healthcare professionals, missed doses are managed by your medical team. If a scheduled infusion is missed, your doctor will adjust the treatment schedule accordingly. Do not attempt to compensate by receiving a double dose.
Overdose
Overdose with arsenic trioxide can cause seizures, muscle weakness, and confusion. If an overdose is suspected or occurs, treatment must be stopped immediately and supportive care should be initiated. The specific antidote for acute arsenic poisoning is dimercaprol (BAL, British Anti-Lewisite), which chelates arsenic and facilitates its excretion. Your medical team will provide appropriate management, which may include cardiac monitoring, electrolyte correction, and supportive intensive care.
| Setting | Phase | Dose | Schedule | Duration |
|---|---|---|---|---|
| Newly diagnosed APL | Induction | 0.15 mg/kg/day IV | Daily | Until remission (max 60 days) |
| Newly diagnosed APL | Consolidation | 0.15 mg/kg/day IV | 5 days/week × 4 weeks | 4 cycles (4-week breaks) |
| Relapsed/refractory APL | Induction | 0.15 mg/kg/day IV | Daily | Until remission (max 50 days) |
| Relapsed/refractory APL | Consolidation | 0.15 mg/kg/day IV | 5 days/week × 5 weeks | 1 cycle (25 doses) |
What Are the Side Effects of Arsenic Trioxide Medac?
Like all medicines, Arsenic Trioxide Medac can cause side effects, although not everybody gets them. Some side effects can be serious and require immediate medical attention. Your healthcare team will monitor you closely throughout treatment to detect and manage side effects as early as possible.
Tell your doctor or nurse immediately if you notice any of the following, as these may be signs of differentiation syndrome, which can be fatal: difficulty breathing, cough, chest pain, fever. Also tell your doctor immediately about signs of an allergic reaction: difficulty breathing, fever, sudden weight gain, fluid retention, fainting, or palpitations (strong heartbeats you can feel in your chest).
Side effects are categorized below by frequency according to standard medical conventions:
Very Common
May affect more than 1 in 10 patients
- Fatigue (tiredness), pain, fever, headache
- Nausea, vomiting, diarrhea
- Dizziness, muscle pain, numbness or tingling (paresthesia)
- Rash or itching
- Elevated blood sugar (hyperglycemia), edema (swelling due to fluid retention)
- Shortness of breath (dyspnea), rapid heartbeat (tachycardia), abnormal ECG readings
- Decreased potassium or magnesium in the blood
- Abnormal liver function tests (elevated bilirubin, elevated gamma-glutamyltransferase)
Common
May affect up to 1 in 10 patients
- Decreased blood cell counts (platelets, red blood cells, and/or white blood cells), increased white blood cells
- Chills, weight gain
- Febrile neutropenia (fever with low white blood cell count), herpes zoster (shingles) infection
- Chest pain, lung hemorrhage, hypoxia (low oxygen levels), fluid around the heart (pericardial effusion) or lungs (pleural effusion)
- Low blood pressure (hypotension), abnormal heart rhythm (arrhythmia)
- Seizures, joint or bone pain, inflammation of blood vessels (vasculitis)
- Elevated sodium or magnesium, ketoacidosis, abnormal kidney function tests, renal failure
- Abdominal pain, facial flushing, facial swelling, blurred vision
Uncommon
May affect up to 1 in 100 patients
- Pancreatitis (inflammation of the pancreas)
- Peripheral neuropathy (nerve damage causing weakness, numbness, or pain in hands and feet)
- Severe skin reactions
- Torsade de pointes (a specific type of dangerous heart rhythm disturbance)
Not Known
Frequency cannot be estimated from available data
- Lung infection (pneumonia), bloodstream infection (sepsis)
- Lung inflammation causing chest pain and shortness of breath (pneumonitis), heart failure
- Dehydration, confusion
- Brain disease (encephalopathy), including Wernicke encephalopathy with difficulty using limbs, speech disorders, and confusion
Long-Term Considerations
Patients who have completed arsenic trioxide treatment should be aware of potential long-term effects. While the acute side effects typically resolve after treatment completion, some patients may experience persistent peripheral neuropathy (numbness or tingling in the extremities) that can take months to resolve. Long-term cardiac monitoring may be recommended, particularly for patients who experienced QT prolongation during treatment. There is a theoretical risk of secondary malignancies associated with arsenic exposure, and regular follow-up with your hematologist is important for ongoing surveillance.
The liver function abnormalities seen during treatment are generally reversible upon discontinuation, but patients with pre-existing liver disease may require extended monitoring. Your healthcare team will schedule appropriate follow-up appointments to monitor your recovery and detect any late-onset effects.
Reporting Side Effects
It is important to report suspected side effects after a medicine has been approved. This allows ongoing monitoring of the medicine’s benefit-risk balance. Healthcare professionals and patients can report suspected adverse reactions to their national pharmacovigilance authority (such as the FDA MedWatch program in the United States, the Yellow Card Scheme in the United Kingdom, or the EMA EudraVigilance system in Europe).
How Should You Store Arsenic Trioxide Medac?
As Arsenic Trioxide Medac is administered in a hospital or clinic setting, storage is managed by healthcare professionals. However, understanding the storage requirements provides important context about the medication’s stability and handling.
- Keep out of sight and reach of children. Although this medication is handled exclusively in healthcare settings, standard precautions apply.
- Shelf life: Do not use after the expiry date stated on the vial label and carton. The expiry date refers to the last day of the stated month.
- Unopened vials: Store below 25°C. Do not freeze.
- After opening: The medication must be used immediately after the vial is opened. It does not contain preservatives.
- After dilution: From a microbiological perspective, the product should be used immediately. If not used immediately, in-use storage should normally not exceed 24 hours at 2–8°C, unless dilution took place under controlled and validated aseptic conditions.
- Visual inspection: Do not use the solution if it contains visible particles or if the solution is discolored. The solution should be clear and colorless.
- Disposal: Unused medicine and waste should be disposed of in accordance with local regulations for cytotoxic drugs. Arsenic trioxide must not be disposed of via household waste or wastewater.
What Does Arsenic Trioxide Medac Contain?
Understanding the composition of Arsenic Trioxide Medac is important for healthcare professionals preparing the infusion and for patients who may have allergies or sensitivities to specific ingredients.
Active Substance
The active substance is arsenic trioxide (As2O3). Each milliliter of concentrate contains 1 mg of arsenic trioxide. Each glass vial contains 10 ml of concentrate, providing a total of 10 mg of arsenic trioxide per vial.
Other Ingredients (Excipients)
- Sodium hydroxide — used to adjust the pH of the solution
- Hydrochloric acid (concentrated) — used for pH adjustment
- Water for injections — the solvent
The product does not contain any preservatives. This is why the vial must be used immediately after opening, and strict aseptic technique must be maintained throughout preparation and administration.
Appearance and Pack Sizes
Arsenic Trioxide Medac is a concentrate for solution for infusion supplied in Type I glass vials with bromobutyl rubber stoppers and aluminium flip-off caps. The concentrate is a clear, colorless aqueous solution. Each carton contains 1 or 10 vials. Not all pack sizes may be marketed in every country.
Preparation Instructions (for Healthcare Professionals)
Arsenic Trioxide Medac must be diluted before administration. Strict aseptic technique is mandatory throughout handling because the product contains no preservative. Healthcare staff must be trained in handling cytotoxic drugs and must wear appropriate protective clothing including gloves, gowns, and eye protection. The contents of the vial are withdrawn using a syringe and immediately diluted with 100–250 ml of glucose 50 mg/ml (5%) solution or sodium chloride 9 mg/ml (0.9%) solution. PVC-free plastic infusion bags should be used. Any unused solution remaining in the vial must be discarded appropriately. The product is for single use only.
Marketing Authorization
Arsenic Trioxide Medac is manufactured and marketed by medac Gesellschaft für klinische Spezialpräparate mbH, based in Wedel, Germany. medac is a pharmaceutical company specializing in oncology, autoimmune diseases, and urology. The product is authorized in multiple European Union member states and other countries worldwide. As a generic product, it contains the same active substance at the same concentration as the reference product and has been shown to be bioequivalent through appropriate pharmaceutical studies.
Frequently Asked Questions
Arsenic Trioxide Medac is used to treat acute promyelocytic leukemia (APL), a specific subtype of acute myeloid leukemia. It is approved for newly diagnosed low-to-intermediate risk APL (typically in combination with all-trans retinoic acid, ATRA) and for relapsed or refractory APL when other treatments have failed. APL is characterized by the PML-RARα fusion gene resulting from the t(15;17) chromosomal translocation. With modern ATRA+ATO therapy, cure rates for low-to-intermediate risk APL exceed 90%.
Arsenic Trioxide Medac is given as an intravenous (IV) infusion over 1 to 2 hours (up to 4 hours if vasomotor reactions occur) in a hospital or clinic setting by a healthcare professional. The concentrate is first diluted in glucose 5% or sodium chloride 0.9% solution. A central venous catheter is not required. It is not available in oral form. The drug must not be mixed with or administered through the same IV line as other medications.
Differentiation syndrome (formerly called APL differentiation syndrome or retinoic acid syndrome) is a potentially life-threatening complication that occurs when leukemia cells rapidly differentiate in response to treatment with arsenic trioxide and/or ATRA. Symptoms include fever, breathing difficulty, cough, chest pain, weight gain, fluid retention around the lungs or heart, and sometimes kidney problems. It occurs in approximately 25–30% of patients receiving ATRA+ATO. Treatment involves immediate initiation of high-dose corticosteroids (typically dexamethasone 10 mg IV twice daily) and temporary interruption of arsenic trioxide and/or ATRA if symptoms are severe.
Arsenic trioxide can prolong the QT interval on the electrocardiogram (ECG), which increases the risk of dangerous heart rhythm disturbances, including torsade de pointes — a form of ventricular tachycardia that can degenerate into ventricular fibrillation and sudden cardiac death. This is why an ECG is required before starting treatment and is performed twice weekly during treatment. Electrolytes (potassium, magnesium, calcium) must also be monitored and corrected because imbalances worsen the QT prolongation risk. If the QTc interval exceeds 500 ms, treatment may need to be temporarily stopped.
No. Arsenic trioxide is expected to cause serious harm to the developing fetus based on its mechanism of action and animal reproductive toxicity data. Women of childbearing potential must use effective contraception during treatment and for at least 6 months after the last dose. Men receiving treatment must also use effective contraception and should not father a child during treatment and for 3 months afterward. Breastfeeding is contraindicated because arsenic passes into breast milk; women must not breastfeed during treatment and for at least 2 weeks after the final dose.
Arsenic Trioxide Medac, manufactured by medac GmbH, contains the same active substance (arsenic trioxide 1 mg/ml) as other approved arsenic trioxide products such as Trisenox and Arsenic Trioxide Accord. These products are therapeutically equivalent, meaning they deliver the same drug at the same concentration and are used for the same indications. The choice between products is typically made by hospitals based on availability, pricing, and procurement agreements. All approved arsenic trioxide products must meet the same rigorous quality, safety, and efficacy standards established by regulatory authorities such as the EMA and FDA.
References
- European Medicines Agency (EMA). Arsenic Trioxide Medac — Summary of Product Characteristics. Last updated 2024. Available at: www.ema.europa.eu
- U.S. Food and Drug Administration (FDA). Trisenox (arsenic trioxide) injection — Prescribing Information. Revised 2024. Available at: www.fda.gov
- Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111–121. doi:10.1056/NEJMoa1300874
- Platzbecker U, Avvisati G, Cicconi L, et al. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017;35(6):605–612. doi:10.1200/JCO.2016.67.1982
- Burnett AK, Russell NH, Hills RK, et al. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16(13):1295–1305. doi:10.1016/S1470-2045(15)00193-X
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia (Version 1.2025). Available at: www.nccn.org
- Sanz MA, Fenaux P, Tallman MS, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019;133(15):1630–1643. doi:10.1182/blood-2019-01-894980
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd list, 2023. Arsenic trioxide listed as an essential medicine for acute promyelocytic leukemia. Available at: www.who.int
- Cicconi L, Platzbecker U, Avvisati G, et al. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: final report of the randomized APL0406 trial. Leukemia. 2020;34(9):2465–2473. doi:10.1038/s41375-020-0791-7
- British National Formulary (BNF). Arsenic trioxide — Indications, dose, contra-indications, side-effects. Available at: bnf.nice.org.uk
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iMedic Medical Editorial Team — Specialists in Hematology-Oncology and Clinical Pharmacology
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iMedic Medical Review Board — Independent panel of medical experts following international guidelines
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Last reviewed: | Published: | Guidelines: WHO, EMA, FDA, NCCN, ELN, BNF