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Arsenic trioxide 1 mg/mL Injection, Solution — NDC 68382-0997-10 package photo
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Arsenic trioxide 1 mg/mL Injection, Solution — NDC 68382-997-10 (Billing 68382-0997-10)

by Zydus Pharmaceuticals USA Inc. · 10 VIAL in 1 CARTON / 10 mL in 1 VIAL

This is a package of Arsenic trioxide 1 mg/mL Injection, Solution from Zydus Pharmaceuticals USA Inc., marketed since Nov 2018 and currently FDA-listed. It is this product's only package size.

NDC 68382-0997-10
🏷️ FDA NDC (as labeled) 68382-997-10 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

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Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68382-997-10
Product NDC 68382-997
11-digit billing NDC 68382099710
NCPDP billing unit ML — per mL (volume)
RxCUI 829926
UNII S7V92P67HO
Application # ANDA206228
SPL Set ID e9d27f88-de82-4379-b143-4b94b3dd8bbe
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2018-11-14
Route INTRAVENOUS
Dosage form INJECTION, SOLUTION
Substance ARSENIC TRIOXIDE
TE code (Orange Book) AP · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 21700008102020
GPI class Arsenic Trioxide
GCN Seq No 053975
GCN 21764
HICL code 021734
Ingredient (HICL) Arsenic Trioxide
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1F
Therapeutic class — specific (HIC3) Antineoplastics,Miscellaneous
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name ARSENIC TRIOXIDE 10 MG/10ML VL
FDB brand name Arsenic Trioxide
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 053975
  • GCN: 21764
  • GPI-14 (Medi-Span): 21700008102020
  • HICL (First Databank): 021734
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 829926
Why two NDCs? The FDA registers this code as 68382-997-10 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 68382-0997-10. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Other antineoplastic agents class.

Drug family (ATC) Other antineoplastic agents
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name ARSENIC TRIOXIDE 10 MG/10ML VL Ingredient Arsenic Trioxide
📖 What it is MedlinePlus · NLM

Arsenic trioxide is used in combination with tretinoin to treat acute promyelocytic leukemia (APL; a type of cancer in which there are too many immature blood cells in the blood and bone marrow) in certain people as a first treatment. It is also used to treat APL in certain people who have not been helped by other types of chemotherapy or whose condition has improved but then worsened following treatment with a retinoid and other types of chemotherapy treatment(s). Arsenic trioxide is in a class of medications called anti-neoplastics. It works by slowing or stopping the growth of cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats acute promyelocytic leukemia (APL). It is used with tretinoin in adults with newly diagnosed low-risk APL, and also for APL that has relapsed or not responded to earlier...
  • It is given through an IV by your healthcare team, once daily in treatment cycles. You won't take it at home. Your team will set the schedule and check your blood and heart often.
  • Arsenic trioxide can affect your heart rhythm, electrolytes, and liver. Regular ECGs and labs help catch problems early. Keep every appointment.
  • Why do I need so many heart tests and blood tests?
📖 Read our full Arsenic Trioxide guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $26.18 $2,618.12 / 100 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9017 $5.069 / J9017 unit —
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Billing & reimbursement

FDA NDC (as labeled)68382-997-10
11-digit billing NDC68382-0997-10
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9017
DescriptorINJECTION, ARSENIC TRIOXIDE, 1 MG
Billing units / pkg1 units
How the units are derivedThis package is 10 ML; the HCPCS unit is 1 MG, so one package = 1 billing unit.
Medicare Part B spend (2026 (Q1))$53,002 · 453 claims · $117.00 per claim (all NDCs under J9017)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
68382-0997-10 You're viewing this Main listing 10 VIAL in 1 CARTON / 10 mL in 1 VIAL 2018-11-14 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Arsenic Trioxide 1 mg/mL 14789-0600-10 Nexus 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 23155-0869-41 Heritage 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 25021-0226-10 Sagent 10 vials — AP FDA listed —
Arsenic trioxide 1 mg/mL 49315-0005-10 Zydus 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 50742-0438-10 Ingenus 1 vial — AP FDA listed —
Arsenic Trioxide 1 mg/mL 63323-0637-10 Fresenius 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 68083-0535-10 Gland 10 vials — AP FDA listed —
Arsenic trioxide 1 mg/mLthis 68382-0997-10 Zydus 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 69918-0720-02 Nordic 2 vials — AP Discontinued —
Arsenic Trioxide 1 mg/mL 70121-1483-07 Amneal 10 vials — AP FDA listed —
Arsenic trioxide 1 mg/mL 70710-1895-06 Zydus 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 72205-0171-07 Novadoz 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 72603-0339-10 Northstar 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 81607-0005-11 Orbicular 10 vials — AP FDA listed —
Arsenic Trioxide 1 mg/mL 83090-0009-01 Sintetica 1 vial — AP FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2018
On the market since
Nov 2018
📍
2026
Currently FDA-listed
8 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

3 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerZydus Pharmaceuticals USA Inc.
Application holderZYDUS PHARMACEUTICALS USA INC
FDA applicationANDA206228 (ANDA)
Labeler code68382
First marketedNov 2018
Product typeHuman Prescription Drug
Portfolio454 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~2 min read ▾

BOXED WARNING WARNING: DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES AND ENCEPHALOPATHY INCLUDING WERNICKE'S Differentiation Syndrome: Patients with acute promyelocytic leukemia (APL) treated with arsenic trioxide have experienced differentiation syndrome, which may be life-threatening or fatal. Signs and symptoms may include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy, and multi-organ dysfunction, in the presence or absence of leukocytosis.

If differentiation syndrome is suspected, immediately initiate high-dose corticosteroids and hemodynamic monitoring until resolution. Temporarily withhold arsenic trioxide [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.1 )]. Cardiac Conduction Abnormalities: Arsenic trioixde can cause QTc interval prolongation, complete atrioventricular block and torsade de pointes, which can be fatal.

Before administering arsenic trioxide, assess the QTc interval, correct electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer arsenic trioxide to patients with a ventricular arrhythmia or prolonged QTc interval. Withhold arsenic trioxide until resolution and resume at reduced dose for QTc prolongation [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.2 )].

Encephalopathy: Serious encephalopathy, including Wernicke's, has occurred with arsenic trioxide. Wernicke's is a neurologic emergency. Consider testing thiamine levels in patients at risk for thiamine deficiency.

Administer parenteral thiamine in patients with or at risk for thiamine deficiency. Monitor patients for neurological symptoms and nutritional status while receiving arsenic trioxide. If Wernicke's encephalopathy is suspected, immediately interrupt arsenic trioxide and initiate parenteral thiamine.

Monitor until symptoms resolve or improve and thiamine levels normalize [see Warnings and Precautions ( 5.3 )]. WARNING: DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES, and ENCEPHALOPATHY INCLUDING WERNICKE'S See full prescribing information for complete boxed warning. • Patients with acute promyelocytic leukemia (APL) treated with arsenic trioxide have experienced symptoms of differentiation syndrome, which may be life-threatening or fatal. If differentiation syndrome is suspected, immediately initiate high-dose corticosteroids and hemodynamic monitoring until resolution.

Temporarily withhold arsenic trioxide. (2.3, 5.1) • Arsenic trioxide can cause QTc interval prolongation, complete atrioventricular block and torsade de pointes, which can be fatal. Before administering arsenic trioxide, assess the QTc interval, correct electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval.

Do not administer arsenic trioxide to patients with ventricular arrhythmia or prolonged QTc interval. Withhold arsenic trioxide until resolution and resume at reduced dose for QTc prolongation. (2.3, 5.2) • Serious encephalopathy, including Wernicke's, has occurred with arsenic trioxide.

If Wernicke's encephalopathy is suspected, immediately interrupt arsenic trioxide and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize. (5.3)

🎯 Indications and Usage 172 words ▾

1 INDICATIONS AND USAGE Arsenic trioxide injection is an arsenical indicated: In combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. ( 1.1 ) For induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

( 1.2 )

1.1Newly-Diagnosed Low-Risk APL Arsenic trioxide injection is indicated in combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

1.2Relapsed or Refractory APL Arsenic trioxide injection is indicated for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Newly-diagnosed low-risk APL: Induction: Administer 0.15 mg/kg/day intravenously daily in combination with tretinoin until bone marrow remission. Do not exceed 60 days. ( 2.1 ) Consolidation: Administer 0.15 mg/kg/day intravenously daily for 5 days per week during weeks 1-4 of each 8-week cycle for a total of 4 cycles in combination with tretinoin.

( 2.1 ) Relapsed or refractory APL: Induction: Administer 0.15 mg/kg/day intravenously daily until bone marrow remission. Do not exceed 60 days. ( 2.2 ) Consolidation: Administer 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks.

( 2.2 )

2.1Recommended Dosage for Newly-Diagnosed Low-Risk Acute Promyelocytic Leukemia (APL) A treatment course for patients with newly-diagnosed low-risk APL consists of 1 induction cycle and 4 consolidation cycles. For the induction cycle, the recommended dosage of arsenic trioxide is 0.15 mg/kg/day intravenously daily in combination with tretinoin until bone marrow remission but not to exceed 60 days (see Table 1). For the consolidation cycles, the recommended dosage of arsenic trioxide is 0.15 mg/kg/day intravenously daily 5 days per week during weeks 1 to 4 of each 8-week cycle for a total of 4 cycles in combination with tretinoin (see Table 1).

Omit tretinoin during weeks 5 to 6 of the fourth cycle of consolidation. Table 1 Recommended Dosage of arsenic trioxide in Combination with Tretinoin Induction (1 cycle) Arsenic trioxide 0.15 mg/kg once daily intravenously until marrow remission but not to exceed 60 days Tretinoin a 22.5 mg/m 2 twice daily orally until marrow remission but not to exceed 60 days Consolidation (4 cycles) a Rounded to the nearest 10 mg increment b Omitted during the 4th cycle of consolidation. Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Arsenic trioxide 0.15 mg/kg once daily intravenously Days 1 to 5 Days 1 to 5 Days 1 to 5 Days 1 to 5 -- -- -- -- Tretinoin a 22.5 mg/m 2 twice daily orally Days 1 to 7 Days 1 to 7 -- -- Days b 1 to 7 Days b 1 to 7 -- -- Differentiation syndrome prophylaxis consisting of prednisone 0.5 mg/kg daily from day 1 until the end of induction cycle with arsenic trioxide and tretinoin is recommended.

2.2Recommended Dosage for Relapsed or Refractory APL A treatment course for patients with relapsed or refractory APL consists of 1 induction cycle and 1 consolidation cycle [see Clinical Studies ( 14.2 )] . For the induction cycle, the recommended dosage of arsenic trioxide is 0.15 mg/kg/day intravenously daily until bone marrow remission or up to a maximum of 60 days. For the consolidation cycle, the recommended dosage of arsenic trioxide is 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks.

Begin consolidation 3 to 6 weeks after completion of induction cycle.

2.3Monitoring and Dosage Modifications for Adverse Reactions During induction, monitor coagulation studies, blood counts, and chemistries at least 2-3 times per week through recovery. During consolidation, monitor coagulation studies, blood counts, and chemistries at least weekly. Table 2 shows the dosage modifications for adverse reactions due to arsenic trioxide when used alone or in combination with tretinoin.

Table 2 Dosage Modifications for Adverse Reactions of Arsenic Trioxide Adverse Reaction Dosage Modification Differentiation syndrome, defined by the presence of 2 or more of the following: - Unexplained fever - Dyspnea - Pleural and/or pericardial effusion - Pulmonary infiltrates - Renal failure - Hypotension - Weight gain greater than 5 kg [see Warnings and Precautions ( 5.1 )] Temporarily withhold arsenic trioxide. Consider holding tretinoin if symptoms are severe. Administer dexamethasone 10 mg intravenously every 12 hours until the resolution of signs and symptoms for a minimum of 3 days.

Resume treatment when the clinical condition improves and reduce the dose of the withheld drug(s) by 50%. Increase the dose of the withheld drug(s) to the r… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 39 words ▾

3 DOSAGE FORMS AND STRENGTHS Arsenic trioxide injection is an injectable solution for intravenous administration supplied as 10 mg/10 mL of arsenic trioxide in single-dose vials. Injection: 10 mg/10 mL of arsenic trioxide in single-dose vial ( 3 )

⛔ Contraindications 18 words ▾

4 CONTRAINDICATIONS Arsenic trioxide is contraindicated in patients with hypersensitivity to arsenic. Hypersensitivity to arsenic. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Hepatotoxicity: Elevated aspartate aminotransferase (AST), alkaline phosphatase and serum bilirubin have occurred in patients with newly-diagnosed low-risk APL treated with arsenic trioxide in combination with tretinoin. Monitor hepatic function tests at least twice weekly during induction and at least once weekly during consolidation. Withhold arsenic trioxide for certain elevations in AST, alkaline phosphatase and bilirubin and resume at reduced dose upon resolution.

( 2.3 , 5.4 ) Carcinogenesis: Arsenic trioxide is a human carcinogen. Monitor patients for the development of second primary malignancies. ( 5.5 ) Embryo-Fetal Toxicity: Can cause fetal harm.

Advise of potential risk to a fetus and use of effective contraception. ( 5.6 , 8.1 , 8.3 )

5.1Differentiation Syndrome Differentiation syndrome, which may be life-threatening or fatal, has been observed in patients with acute promyelocytic leukemia (APL) treated with arsenic trioxide. In clinical trials, 16% to 23% of patients treated with arsenic trioxide for APL developed differentiation syndrome. Signs and symptoms include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusion, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy and multi-organ dysfunction.

Differentiation syndrome has been observed with and without concomitant leukocytosis, and it has occurred as early as day 1 of induction to as late as the second month induction therapy. When arsenic trioxide is used in combination with tretinoin, prophylaxis with prednisone is recommended during the induction cycle [see Dosage and Administration ( 2.1 )]. If differentiation syndrome is suspected, temporarily withhold arsenic trioxide and immediately initiate dexamethasone 10 mg intravenously every 12 hours and hemodynamic monitoring until resolution of signs and symptoms for a minimum of 3 days [see Dosage and Administration ( 2.3 )].

5.2Cardiac Conduction Abnormalities Patients treated with arsenic trioxide can develop QTc prolongation, torsade de pointes, and complete atrioventricular block. In the clinical trials of patients with newly-diagnosed low-risk APL treated with arsenic trioxide in combination with tretinoin, 11% experienced QTc (Framingham formula) prolongation > 450 msec for men and > 460 msec for women throughout the treatment cycles. In the clinical trial of patients with relapsed or refractory APL treated with arsenic trioxide monotherapy, 40% had at least one ECG tracing with a QTc interval greater than 500 msec.

A prolonged QTc was observed between 1 and 5 weeks after start of arsenic trioxide infusion, and it usually resolved by 8 weeks after arsenic trioxide infusion. There are no data on the effect of arsenic trioxide on the QTc interval during the infusion of the drug. The risk of torsade de pointes is related to the extent of QTc prolongation, concomitant administration of QTc prolonging drugs, a history of torsade de pointes, pre-existing QTc interval prolongation, congestive heart failure, administration of potassium-wasting diuretics, or other conditions that result in hypokalemia or hypomagnesemia.

The risk may be increased when arsenic trioxide is coadministered with medications that can lead to electrolyte abnormalities (such as diuretics or amphotericin B) [see Drug Interactions ( 7 )] . Prior to initiating therapy with arsenic trioxide, assess the QTc interval by electrocardiogram, correct pre-existing electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer arsenic trioxide to patients with a ventricular arrhythmia or prolonged QTc.

If possible, discontinue drugs that are known to prolong the QTc interval. If it is not possible to discontinue the interacting drug, perform cardiac monitoring frequently [see Drug Interactions ( 7 )]. During arsenic trioxide therapy, maintain potassium concentrations above 4 mEq/L and… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling.: Differentiation Syndrome [see Warnings and Precautions ( 5.1 )] Cardiac Conduction Abnormalities [see Warnings and Precautions ( 5.2 )] Encephalopathy [see Warnings and Precautions ( 5.3 )] Hepatotoxicity [see Warnings and Precautions ( 5.4 )] Carcinogenesis [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (> 30%) are nausea, cough, fatigue, pyrexia, headache, abdominal pain, vomiting, tachycardia, diarrhea, dyspnea, hypokalemia, leukocytosis, hyperglycemia, hypomagnesemia, insomnia, dermatitis, edema, QTc prolongation, rigors, sore throat, arthralgia, paresthesia, and pruritus ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Newly-Diagnosed Low-Risk APL The safety of arsenic trioxide in combination with tretinoin was evaluated in Study APL0406, a randomized trial comparing arsenic trioxide plus tretinoin (n=129) versus chemotherapy plus tretinoin (n=137) in patients with newly-diagnosed APL [see Clinical Studies (14.1)].

In the arsenic trioxide /tretinoin group, 98% of patients completed induction therapy and 89% completed at least three consolidation cycles. In the chemotherapy/tretinoin group, 96% completed induction therapy and 87% patients completed all three courses of consolidation therapy. Serious adverse reactions were reported in 25% of patients on the arsenic trioxide /tretinoin arm and 24% on the chemotherapy/tretinoin arm.

The serious adverse reactions reported in ≥ 2% of patients who received arsenic trioxide /tretinoin were abnormal liver tests, differentiation syndrome, dyspnea, pneumonia, and other infections. Fatal adverse reactions were reported in 1 (1%) patient on the arsenic trioxide /tretinoin arm and 8 (6%) patients on the chemotherapy/tretinoin arm. Arsenic trioxide /tretinoin was discontinued due to toxicity in 1 patient during induction and in 4 patients during the first three consolidation courses, whereas chemotherapy/tretinoin was discontinued due to toxicity in 4 patients during induction and in 6 patients during consolidation.

Selected hematologic and nonhematologic toxicities that occurred during induction or consolidation are presented in Table 4. Table 4 Select Adverse Reactions of Arsenic trioxide in Combination with Tretinoin in Patients with Newly-Diagnosed APL in Study APL0406 *Mostly cases of reversible peripheral neuropathy Adverse Reaction Induction n (%) First Consolidation n (%) Second Consolidation n (%) Third Consolidation n (%) Thrombocytopenia > 15 days (Grade 3-4) arsenic trioxide /tretinoin Chemotherapy/tretinoin 74 (58%) 120 (88%) 6 (5%) 17 (14%) 6 (5%) 77 (63%) 8 (7%) 26 (22%) Neutropenia >15 days (Grade 3-4) arsenic trioxide /tretinoin Chemotherapy/tretinoin 61 (48%) 109 (80%) 8 (7%) 40 (32%) 7 (6%) 90 (73%) 5 (4%) 28 (24%) Hepatic toxicity (Grade 3-4) arsenic trioxide /tretinoin Chemotherapy/tretinoin 51 (40%) 4 (3%) 5 (4%) 1 (1%) 1 (1%) 0 (0%) 0 (0%) 0 (0%) Infection and fever of unknown origin arsenic trioxide /tretinoin Chemotherapy/tretinoin 30 (23%) 75 (55%) 10 (8%) 8 (6%) 4 (3%) 46 (38%) 2 (2%) 2 (2%) Hypertriglyceridemia arsenic trioxide /tretinoin Chemotherapy/tretinoin 29 (22%) 29 (22%) 22 (18%) 19 (15%) 17 (14%) 10 (8%) 16 (14%) 13 (11%) Hypercholesterolemia arsenic trioxide /tretinoin Chemotherapy/tretinoin 14 (10%) 12 (9%) 19 (16%) 12 (10%) 19 (16%) 12 (10%) 16 (14%) 11 (9%) QT prolongation arsenic trioxide /tretinoin Chemotherapy/tretinoin 11 (9%) 1 (1%) 3 (2%) 0 (0%) 3 (2%) 0 (0%) 2 (2%) 0 (0%) Gastrointestinal toxicity (Grad… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 193 words ▾

7 DRUG INTERACTIONS Drugs That Can Prolong the QT/QTc Interval Concomitant use of these drugs and arsenic trioxide may increase the risk of serious QT/QTc interval prolongation [see Warnings and Precautions ( 5.1 )]. Discontinue or replace with an alternative drug that does not prolong the QT/QTc interval while the patient is using arsenic trioxide. Monitor ECGs more frequently in patients when it is not feasible to avoid concomitant use.

Drugs That Can Lead to Electrolyte Abnormalities Electrolyte abnormalities increase the risk of serious QT/QTc interval prolongation [see Warnings and Precautions ( 5.1 )]. Avoid concomitant use of drugs that can lead to electrolyte abnormalities. Monitor electrolytes more frequently in patients who must receive concomitant use of these drugs and arsenic trioxide.

Drugs That Can Lead to Hepatotoxicity Concomitant use of these drugs and arsenic trioxide particularly when given in combination with tretinoin, may increase the risk of serious hepatotoxicity [see Warnings and Precautions ( 5.4 )]. Discontinue or replace with an alternative drug that does not cause hepatotoxicity while the patient is using arsenic trioxide. Monitor liver function tests more frequently in patients when it is not feasible to avoid concomitant use.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Renal Impairment: Monitor patients with severe renal impairment (creatinine clearance less than 30 mL/min) for toxicity when treated with arsenic trioxide; dose reduction may be warranted. ( 8.6 ) Hepatic Impairment: Monitor patients with severe hepatic impairment (Child-Pugh Class C) for toxicity when treated with arsenic trioxide. ( 8.7 )

8.1Pregnancy Risk Summary Based on the mechanism of action [see Clinical Pharmacology ( 12.1 )] and findings in animal studies, arsenic trioxide can cause fetal harm when administered to a pregnant woman. Arsenic trioxide was embryolethal and teratogenic in rats when administered on gestation day 9 at a dose approximately 10 times the recommended human daily dose on a mg/m 2 basis (see Data) . A related trivalent arsenic, sodium arsenite, produced teratogenicity when administered during gestation in mice at a dose approximately 5 times the projected human dose on a mg/m 2 basis and in hamsters at an intravenous dose approximately equivalent to the projected human daily dose on a mg/m 2 basis.

There are no studies with the use of arsenic trioxide in pregnant women, and limited published data on arsenic trioxide use during pregnancy are insufficient to inform a drug-associated risk of major birth defects and miscarriage. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

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% to 4% and 15% to 20%, respectively. Data Human Data One patient was reported to deliver a live infant with no reported congenital anomalies after receiving arsenic trioxide during the first five months of pregnancy.

A second patient became pregnant three months after discontinuing arsenic trioxide and was reported to have a normal pregnancy outcome. A third patient was a pregnant healthcare provider who experienced dermal contact with liquid arsenic trioxide and had a normal pregnancy outcome after treatment and monitoring. A fourth patient who became pregnant while receiving arsenic trioxide had a miscarriage.

Animal Data Studies in pregnant mice, rats, hamsters, and primates have shown that inorganic arsenicals cross the placental barrier when given orally or by injection. An increase in resorptions, neural-tube defects, anophthalmia and microphthalmia were observed in rats administered 10 mg/kg of arsenic trioxide on gestation day 9 (approximately 10 times the recommended human daily dose on a mg/m 2 basis). Similar findings occurred in mice administered a 10 mg/kg dose of a related trivalent arsenic, sodium arsenite (approximately 5 times the projected human dose on a mg/m 2 basis), on gestation days 6, 7, 8, or 9.

Intravenous injection of 2 mg/kg sodium arsenite (approximately equivalent to the projected human daily dose on a mg/m 2 basis) on gestation day 7 (the lowest dose tested) resulted in neural-tube defects in hamsters.

8.2Lactation Risk Summary Arsenic trioxide is excreted in human milk. There are no data on the effects of arsenic trioxide on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with arsenic trioxide and for 2 weeks after the final dose.

8.3Females and Males of Reproductive Potential Arsenic trioxide can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )]. Pregnancy Testing Conduct pregnancy testing in females of reproductive potential prior to initiation of arsenic trioxide. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with arsenic trioxide and for 6 months… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Based on the mechanism of action [see Clinical Pharmacology ( 12.1 )] and findings in animal studies, arsenic trioxide can cause fetal harm when administered to a pregnant woman. Arsenic trioxide was embryolethal and teratogenic in rats when administered on gestation day 9 at a dose approximately 10 times the recommended human daily dose on a mg/m 2 basis (see Data) . A related trivalent arsenic, sodium arsenite, produced teratogenicity when administered during gestation in mice at a dose approximately 5 times the projected human dose on a mg/m 2 basis and in hamsters at an intravenous dose approximately equivalent to the projected human daily dose on a mg/m 2 basis.

There are no studies with the use of arsenic trioxide in pregnant women, and limited published data on arsenic trioxide use during pregnancy are insufficient to inform a drug-associated risk of major birth defects and miscarriage. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

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% to 4% and 15% to 20%, respectively. Data Human Data One patient was reported to deliver a live infant with no reported congenital anomalies after receiving arsenic trioxide during the first five months of pregnancy.

A second patient became pregnant three months after discontinuing arsenic trioxide and was reported to have a normal pregnancy outcome. A third patient was a pregnant healthcare provider who experienced dermal contact with liquid arsenic trioxide and had a normal pregnancy outcome after treatment and monitoring. A fourth patient who became pregnant while receiving arsenic trioxide had a miscarriage.

Animal Data Studies in pregnant mice, rats, hamsters, and primates have shown that inorganic arsenicals cross the placental barrier when given orally or by injection. An increase in resorptions, neural-tube defects, anophthalmia and microphthalmia were observed in rats administered 10 mg/kg of arsenic trioxide on gestation day 9 (approximately 10 times the recommended human daily dose on a mg/m 2 basis). Similar findings occurred in mice administered a 10 mg/kg dose of a related trivalent arsenic, sodium arsenite (approximately 5 times the projected human dose on a mg/m 2 basis), on gestation days 6, 7, 8, or 9.

Intravenous injection of 2 mg/kg sodium arsenite (approximately equivalent to the projected human daily dose on a mg/m 2 basis) on gestation day 7 (the lowest dose tested) resulted in neural-tube defects in hamsters.

🧒 Pediatric Use 121 words ▾

8.4Pediatric Use The safety and efficacy of arsenic trioxide in combination with tretinoin in pediatric patients has not been established. The safety and efficacy of arsenic trioxide as a single agent for treatment of pediatric patients with relapsed or refractory APL is supported by the pivotal phase 2 study in 40 patients with relapsed or refractory APL. Five patients below the age of 18 years (age range: 5 years to 16 years) were treated with arsenic trioxide at the recommended dose of 0.15 mg/kg/day.

A literature review included an additional 17 patients treated with arsenic trioxide for relapsed or refractory APL, with ages ranging from 4 years to 21 years. No differences in efficacy and safety were observed by age.

🧓 Geriatric Use 178 words ▾

8.5Geriatric Use Use of arsenic trioxide in combination with tretinoin in newly-diagnosed adult patients with low-risk APL is supported by a randomized, controlled trial that included 16 patients between the ages of 60 years and 70 years. No overall differences in safety or effectiveness were observed between these patients and younger patients. A literature review included an additional 77 patients aged 60 years to 84 years who were treated with arsenic trioxide in combination with tretinoin as part of induction and consolidation therapy for low-and high-risk APL.

These studies showed lower survival rates in older patients. Monitor elderly patients frequently during treatment with arsenic trioxide. Use of arsenic trioxide as monotherapy in patients with relapsed or refractory APL is supported by the open-label, single-arm trial that included 6 patients aged 65 and older (range: 65 to 73 years).

A literature review included an additional 4 patients aged 69 to 72 years who were treated with arsenic trioxide for relapsed or refractory APL. No overall differences in safety or effectiveness were observed between these patients and younger patients.

🆘 Overdosage 84 words ▾

10 OVERDOSAGE Manifestations Manifestations of arsenic trioxide (arsenic trioxide) overdosage include convulsions, muscle weakness, and confusion. Management For symptoms of arsenic trioxide overdosage, immediately discontinue arsenic trioxide and consider chelation therapy. A conventional protocol for acute arsenic intoxication includes dimercaprol administered at a dose of 3 mg/kg intramuscularly every 4 hours until immediate life-threatening toxicity has subsided.

Thereafter, penicillamine at a dose of 250 mg orally, up to a maximum frequency of four times per day (≤ 1 g per day), may be given.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action of arsenic trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-alpha.

12.2Pharmacodynamics Cardiac Electrophysiology In a single-arm trial of arsenic trioxide (0.15 mg/kg daily), 16 of 40 patients (40%) had a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after arsenic trioxide infusion, and then returned towards baseline by the end of 8 weeks after arsenic trioxide infusion.

12.3Pharmacokinetics The inorganic, lyophilized form of arsenic trioxide, when placed into solution, immediately forms the hydrolysis product arsenious acid (As III ). As III is the pharmacologically active species of arsenic trioxide. Monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) are the main pentavalent metabolites formed during metabolism, in addition to arsenic acid (As V ) a product of As III oxidation.

The pharmacokinetics of arsenical species ([As III ], [As V ], [MMA V ], [DMA V ]) were determined in 6 APL patients following once-daily doses of 0.15 mg/kg for 5 days per week. Over the total single-dose range of 7 mg to 32 mg (administered as 0.15 mg/kg), systemic exposure (AUC) appears to be linear. Peak plasma concentrations of arsenious acid (As III ), the primary active arsenical species were reached at the end of infusion (2 hours).

Plasma concentration of As III declined in a biphasic manner with a mean elimination half-life of 10 hours to 14 hours and is characterized by an initial rapid distribution phase followed by a slower terminal elimination phase. The daily exposure to As III (mean AUC 0-24h ) was 194 ng·hr/mL (n=5) on Day 1 of Cycle 1 and 332 ng·hr/mL (n=6) on Day 25 of Cycle 1, which represents an approximate 2-fold accumulation. The primary pentavalent metabolites, MMA V and DMA V , are slow to appear in plasma (approximately 10 hours to 24 hours after first administration of arsenic trioxide), but, due to their longer half-life, accumulate more upon multiple dosing than does As III .

The mean estimated terminal elimination half-lives of the metabolites MMA V and DMA V are 32 hours and 72 hours, respectively. Approximate accumulation ranged from 1.4- to 8-fold following multiple dosing as compared to single-dose administration. As V is present in plasma only at relatively low levels.

Distribution The volume of distribution (V ss ) for As III is large (mean 562 L, N=10) indicating that As III is widely distributed throughout body tissues. V ss is also dependent on body weight and increases as body weight increases. Elimination Metabolism Much of the As III is distributed to the tissues where it is methylated to the less cytotoxic metabolites, monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ) by methyltransferases primarily in the liver.

The metabolism of arsenic trioxide also involves oxidation of As III to As V , which may occur in numerous tissues via enzymatic or nonenzymatic processes. As V is present in plasma only at relatively low levels following administration of arsenic trioxide. Excretion Approximately 15% of the administered arsenic trioxide dose is excreted in the urine as unchanged As III .

The methylated metabolites of As III (MMA V , DMA V ) are primarily excreted in the urine. The total clearance of As III is 49 L/h and the renal clearance is 9 L/h. Clearance is not dependent on body weight or dose administered over the range of 7 mg to 32 mg.

Specific Populations Patients with Renal Impairment The effect of renal impairment on the pharmacokinetics of As III , As V , and the pentavalent metabolites MMA V and DMA V was evaluated in 20 patients with advanced malignancies. Patients were classified as… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 51 words ▾

12.1Mechanism of Action The mechanism of action of arsenic trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-alpha.

📦 How Supplied / Storage and Handling 82 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Arsenic trioxide injection is supplied as a sterile, clear, colorless solution in 10 mL glass, single-dose vials. NDC Strength Pack Style 68382-997-10 10 mg per 10 mL single-dose vials 10 vials per carton Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Do not freeze.

Arsenic trioxide is a hazardous drug. Follow applicable special handling and disposal procedures. 1

📋 Description 131 words ▾

11 DESCRIPTION Arsenic trioxide injection is a sterile injectable solution of arsenic trioxide. The molecular formula of arsenic trioxide in the solid state is As 2 O 3 , with a molecular weight of 197.8 and the following structural formula: Arsenic trioxide injection is available in 10 mL, single-dose vials containing 10 mg of arsenic trioxide. Arsenic trioxide injection is formulated as a sterile, nonpyrogenic, clear solution of arsenic trioxide in water for injection using sodium hydroxide and dilute hydrochloric acid to adjust to pH 8.

Arsenic trioxide injection is preservative-free. Arsenic trioxide, the active ingredient, is present at a concentration of 1 mg/ mL. Inactive ingredients and their respective approximate concentrations are sodium hydroxide (1.2 mg/mL) for solubilization and hydrochloric acid for pH adjustment to pH 7.5 to 8.5.

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💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Differentiation Syndrome Advise patients that symptoms of APL differentiation syndrome include fever, sudden weight gain, dizziness/lightheadedness, labored breathing, and accumulation of fluid in the lungs, heart, and chest. This syndrome is managed by immediate treatment with high-dose corticosteroids. Advise patients to immediately report any of these symptoms [see Warnings and Precautions ( 5.1 )].

Cardiac Conduction Abnormalities Advise patients that arsenic trioxide may cause ECG abnormalities, including QT prolongation. If extreme, this prolongation has the potential to cause fainting, irregular heartbeat, or more serious side effects. Advise patients to immediately report any of these symptoms.

Advise patients to provide a complete list of current medications as caution should be taken when arsenic trioxide is coadministered with other medications that can cause QT prolongation or lead to electrolyte abnormalities [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7 )]. Encephalopathy and Wernicke's Encephalopathy (WE) Advise patients that symptoms of encephalopathies include neurological symptoms such as confusion, decreased level of consciousness, seizures, cognitive deficits, ataxia, visual symptoms and ocular motor dysfunction.

Advise patients and caregivers to closely monitor for neurological symptoms and immediately report them to their healthcare provider [see Warnings and Precautions ( 5.3 )]. Advise patients at risk for thiamine deficiency (e.g., chronic alcohol use, malabsorption, nutritional deficiency, concomitant use of furosemide) that Wernicke's encephalopathy is a neurologic emergency that can be prevented and treated with thiamine supplementation, and to immediately report any neurological symptoms to their healthcare provider [see Warnings and Precautions ( 5.3 )].

Embryo-Fetal Toxicity Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.5 ) and Use in Specific Populations ( 8.1 )]. Advise females of reproductive potential to use effective contraception during treatment with arsenic trioxide and for 6 months after the last dose [see Use in Specific Populations ( 8.3 )].

Advise males with female partners of reproductive potential to use effective contraception during treatment with arsenic trioxide for 3 months after the last dose [see Use in Specific Populations ( 8.3 )]. Lactation Advise women not to breastfeed during treatment with arsenic trioxide and for 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )]. Infertility Advise males of reproductive potential that arsenic trioxide may impair fertility [see Use in Specific Population ( 8.3 )].

Other Adverse Reactions Advise patients of the expected adverse reactions of arsenic trioxide. Most patients in clinical trials experienced some drug-related toxicity, most commonly leukocytosis, gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, and dizziness. Advise patients to call their healthcare provider at the onset of any adverse reactions [see Adverse Reactions ( 6.1 )].

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics The inorganic, lyophilized form of arsenic trioxide, when placed into solution, immediately forms the hydrolysis product arsenious acid (As III ). As III is the pharmacologically active species of arsenic trioxide. Monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) are the main pentavalent metabolites formed during metabolism, in addition to arsenic acid (As V ) a product of As III oxidation.

The pharmacokinetics of arsenical species ([As III ], [As V ], [MMA V ], [DMA V ]) were determined in 6 APL patients following once-daily doses of 0.15 mg/kg for 5 days per week. Over the total single-dose range of 7 mg to 32 mg (administered as 0.15 mg/kg), systemic exposure (AUC) appears to be linear. Peak plasma concentrations of arsenious acid (As III ), the primary active arsenical species were reached at the end of infusion (2 hours).

Plasma concentration of As III declined in a biphasic manner with a mean elimination half-life of 10 hours to 14 hours and is characterized by an initial rapid distribution phase followed by a slower terminal elimination phase. The daily exposure to As III (mean AUC 0-24h ) was 194 ng·hr/mL (n=5) on Day 1 of Cycle 1 and 332 ng·hr/mL (n=6) on Day 25 of Cycle 1, which represents an approximate 2-fold accumulation. The primary pentavalent metabolites, MMA V and DMA V , are slow to appear in plasma (approximately 10 hours to 24 hours after first administration of arsenic trioxide), but, due to their longer half-life, accumulate more upon multiple dosing than does As III .

The mean estimated terminal elimination half-lives of the metabolites MMA V and DMA V are 32 hours and 72 hours, respectively. Approximate accumulation ranged from 1.4- to 8-fold following multiple dosing as compared to single-dose administration. As V is present in plasma only at relatively low levels.

Distribution The volume of distribution (V ss ) for As III is large (mean 562 L, N=10) indicating that As III is widely distributed throughout body tissues. V ss is also dependent on body weight and increases as body weight increases. Elimination Metabolism Much of the As III is distributed to the tissues where it is methylated to the less cytotoxic metabolites, monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ) by methyltransferases primarily in the liver.

The metabolism of arsenic trioxide also involves oxidation of As III to As V , which may occur in numerous tissues via enzymatic or nonenzymatic processes. As V is present in plasma only at relatively low levels following administration of arsenic trioxide. Excretion Approximately 15% of the administered arsenic trioxide dose is excreted in the urine as unchanged As III .

The methylated metabolites of As III (MMA V , DMA V ) are primarily excreted in the urine. The total clearance of As III is 49 L/h and the renal clearance is 9 L/h. Clearance is not dependent on body weight or dose administered over the range of 7 mg to 32 mg.

Specific Populations Patients with Renal Impairment The effect of renal impairment on the pharmacokinetics of As III , As V , and the pentavalent metabolites MMA V and DMA V was evaluated in 20 patients with advanced malignancies. Patients were classified as having normal renal function (creatinine clearance [CLcr] > 80 mL/min, n=6), mild renal impairment (CLcr 50 mL/min to 80 mL/min, n=5), moderate renal impairment (CLcr 30 mL/min to 49 mL/min, n=6), or severe renal impairment (CLcr < 30 mL/min, n=3). Following twice-weekly administration of 0.15 mg/kg over a 2-hour infusion, the mean AUC 0-INF for As III was comparable among the normal, mild and moderate renal impairment groups.

However, in the severe renal impairment group, the mean AUC 0-INF for As III was approximately 48% higher than that in the normal group. Systemic exposure to MMA V and DMA V tended to be larger in patients with renal impairment; however, the clinical consequences of this increased exposure are not known. As V plasma levels were genera… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 57 words ▾

12.2Pharmacodynamics Cardiac Electrophysiology In a single-arm trial of arsenic trioxide (0.15 mg/kg daily), 16 of 40 patients (40%) had a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after arsenic trioxide infusion, and then returned towards baseline by the end of 8 weeks after arsenic trioxide infusion.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Newly-Diagnosed Low-Risk APL Arsenic trioxide in combination with tretinoin was investigated in Study APL0406 (NCT00482833), a multicenter, randomized, open-label trial in patients with newly-diagnosed low-risk APL (white blood cell count at diagnosis ≤10 Gi/L). The patients were randomized 1:1 to receive arsenic trioxide /tretinoin for induction and consolidation or chemotherapy/tretinoin for induction, consolidation, and maintenance. Patients in the arsenic trioxide/tretinoin group received induction treatment with arsenic trioxide 0.15 mg/kg intravenously once daily in combination with tretinoin 22.5 mg/m 2 (rounded to the nearest 10 mg increment) orally twice daily until hematologic complete remission (CR) or for a maximum of 60 days.

Patients in this group who achieved a CR during induction received four 8-week cycles of consolidation treatment with arsenic trioxide 0.15 mg/kg intravenously once daily for 5 days every week during weeks 1 to 4 of the 8-week cycle, in combination with tretinoin 22.5 mg/m 2 (rounded to the nearest 10 mg increment) orally twice daily during weeks 1 to 2 and 5 to 6 of the 8-week cycle. Tretinoin was omitted during weeks 5 to 6 of the last cycle. Patients in the chemotherapy/tretinoin group received idarubicin 12 mg/m 2 intravenously once daily on days 2, 4, 6 and 8 in combination with tretinoin 22.5 mg/m 2 (rounded to the nearest 10 mg increment) orally twice daily, starting on day 1, until hematologic CR or for a maximum of 60 days.

Patients in this group who achieved a CR during induction received consolidation and maintenance treatment with tretinoin in combination with chemotherapy. The trial enrolled 162 patients with a morphologic diagnosis of APL. The median age of patients was 45 years in the arsenic trioxide /tretinoin arm and 47 years in the chemotherapy/tretinoin arm, and 52% and 46% were male in the arsenic trioxide /tretinoin and chemotherapy/tretinoin arms, respectively.

Baseline characteristics were balanced between treatment arms, including median WBC count, platelet count, PML-RARA isoform, and FLT3-ITD status. Efficacy was based on event-free survival (EFS) rate at 2 years. EFS was defined as the time from randomization to the occurrence of treatment failure, defined as no achievement of CR or CRi after induction therapy, no achievement of molecular remission after 3 consolidation courses, molecular relapse, hematologic relapse, or death.

The primary analysis of EFS was based on the difference between the two treatment arms in patients achieving EFS at 2 years. With a median follow-up of 34.4 months, the 2 year EFS rate of the modified ITT (mITT) population (patients who received at least one dose of the assigned treatment) was 94% in the arsenic trioxide /tretinoin arm (n=77) versus 82% in the chemotherapy/tretinoin arm (n=79), a treatment difference of 11% (95% CI: 1, 22; p-value 0.048). Overall survival (OS) for the mITT population was 99% (95% CI: 93, 100) in the arsenic trioxide /tretinoin arm versus 91% (95% CI: 86, 97) in the chemotherapy/tretinoin arm.

The difference in 2-year OS rate between the arms was 8% (95% CI: 0, 16). Figure 1 Event-Free Survival for Newly-Diagnosed APL The number of patients in the plot is based on the mITT population.

14.2Relapsed or Refractory APL Arsenic trioxide was investigated in Study PLRXAS01, an open-label, single-arm trial in 40 patients with relapsed or refractory APL who were previously treated with an anthracycline and a retinoid regimen. Patients received arsenic trioxide 0.15 mg/kg/day intravenously over 1 to 2 hours until the bone marrow was cleared of leukemic cells or for a maximum of 60 days. The CR (absence of visible leukemic cells in bone marrow and peripheral recovery of platelets and white blood cells with a confirmatory bone marrow ≥ 30 days later) rate in this population of previously treated patients was 28 of 40 (70%).

Among the 22 patients who had relapsed less than one year after treatmen… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with arsenic trioxide [see Warnings and Precautions ( 5.6 )]. Arsenic trioxide and trivalent arsenite salts have not been demonstrated to be mutagenic to bacteria, yeast, or mammalian cells. Arsenite salts are clastogenic in vitro (human fibroblast, human lymphocytes, Chinese hamster ovary cells, Chinese hamster V79 lung cells).

Trivalent arsenic was genotoxic in the chromosome aberrations assay and micronucleus bone marrow assay in mice. The effect of arsenic on fertility has not been adequately studied in humans. Decreased testicular weight and impaired spermatogenesis have been reported in animal studies.

Male Wistar rat pups were administered 1.5 mg/kg sodium arsenite solution via the intraperitoneal route from postnatal days 1 to 14 and testes were collected for evaluation on postnatal days 15, 21, and 50. Results of this study revealed an altered morphology of the seminiferous tubules along with degeneration of spermatogenic cells, increased number of sperm with abnormal morphology, and decreased sperm counts. In beagle dogs administered intravenous arsenic trioxide for 90 days, reduced inner cell layers within seminiferous tubules and significantly decreased numbers of spermatocytes, spermatozoa, and sperm cells were observed at doses of 1 mg/kg/day and higher.

The 1 mg/kg/day dose is approximately 3 times the recommended human daily dose on a mg/m 2 basis.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 218 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been conducted with arsenic trioxide [see Warnings and Precautions ( 5.6 )]. Arsenic trioxide and trivalent arsenite salts have not been demonstrated to be mutagenic to bacteria, yeast, or mammalian cells. Arsenite salts are clastogenic in vitro (human fibroblast, human lymphocytes, Chinese hamster ovary cells, Chinese hamster V79 lung cells).

Trivalent arsenic was genotoxic in the chromosome aberrations assay and micronucleus bone marrow assay in mice. The effect of arsenic on fertility has not been adequately studied in humans. Decreased testicular weight and impaired spermatogenesis have been reported in animal studies.

Male Wistar rat pups were administered 1.5 mg/kg sodium arsenite solution via the intraperitoneal route from postnatal days 1 to 14 and testes were collected for evaluation on postnatal days 15, 21, and 50. Results of this study revealed an altered morphology of the seminiferous tubules along with degeneration of spermatogenic cells, increased number of sperm with abnormal morphology, and decreased sperm counts. In beagle dogs administered intravenous arsenic trioxide for 90 days, reduced inner cell layers within seminiferous tubules and significantly decreased numbers of spermatocytes, spermatozoa, and sperm cells were observed at doses of 1 mg/kg/day and higher.

The 1 mg/kg/day dose is approximately 3 times the recommended human daily dose on a mg/m 2 basis.

📚 References 8 words ▾

15 REFERENCES 1. "OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

📄 Package Label / Principal Display Panel 80 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL PRINCIPAL DISPLAY PANEL - Vial Label NDC 68382-997-01 Arsenic Trioxide Injection 10 mg/10 mL (1 mg/mL) NEW CONCENTRATION For Intravenous Use Only Cytotoxic Agent 10 mL Single-Dose Vial Rx only Zydus Pharmaceuticals PRINCIPAL DISPLAY PANEL - Carton Label NDC 68382-997-10 Arsenic Trioxide Injection 10 mg/10 mL (1 mg/mL) NEW CONCENTRATION For Intravenous Use Only 10 X 10 mL Single-Dose Vials Rx only Zydus Pharmaceuticals arsenic trioxide injection, 1 mg/mL-Vial label Arsenic trioxide Injection 1 mg/mL-carton label

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
398
Units reimbursed last 4 qtrs
4.5K
Gross reimbursed last 4 qtrs
$117.6K
Avg / prescription
$295.36
Avg / unit
$26.1832
Latest quarter Q1 2026
82Rx
Fee-for-service vs managed care ⓘ
47% FFS 53% MCO
Fee-for-service · 189 Rx Managed care · 209 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 1,430 units · 7.3 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 2,103 units · 5.4 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 637 units · 5.9 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: 320 units · 6.3 per 100k residents AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
5.47.3
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 New York 7.3 /100k
2 Alabama 6.3 /100k
3 North Carolina 5.9 /100k
4 California 5.4 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Zydus Pharmaceuticals USA Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Zydus Pharmaceuticals USA Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J9017 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 68382-0984-05 · Zydus 68382-0998-01 · Zydus →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.