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Cyclophosphamide 1000 mg/10mL Injection, Solution, Concentrate — NDC 00781-3529-10 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Cyclophosphamide 1000 mg/10mL Injection, Solution, Concentrate — NDC 0781-3529-10 (Billing 00781-3529-10)

by Sandoz Inc · 1 VIAL, MULTI-DOSE in 1 CARTON / 10 mL in 1 VIAL, MULTI-DOSE

This is a package of Cyclophosphamide 1000 mg/10mL Injection, Solution, Concentrate from Sandoz Inc, marketed since Apr 2024 and currently FDA-listed. It is this product's only package size.

NDC 00781-3529-10
🏷️ FDA NDC (as labeled) 0781-3529-10 billing pads the labeler segment with a zero
Rx only Brand 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 →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 0781-3529-10 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
0781 labeler · 3529 product · 10 package
Package marketed since
Apr 8, 2024
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 0781352910 1
Medicaid fills, this package
25 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026
🚨
Active recall for this product.
Class II · Sep 5, 2025 — cGMP deviations: Temperature excursion during transportation. (Sandoz Inc) · FDA recall D-0651-2025
Lots / codes: Only the following 6 GTN Numbers for Lot # 110459 exp. date 02/28/2027: (01)00307813528104(21)10686040629319 (01)00307813528104(21)10687281435306 (01)00307813528104(21)10687409963168 (01)00307813528104(21)10701200331212 (01)00307813528104(21)10687325644911 (01)00307813528104(21)10687661160169 · reported Sep 24, 2025
Check your lot/expiration against the official notice — look up the recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0781-3529-10
Product NDC 0781-3529
11-digit billing NDC 00781352910
NCPDP billing unit ML — per mL (volume)
RxCUI 2679073
UNII 8N3DW7272P
Application # NDA217150
SPL Set ID cf2f4b95-0327-499a-a5a3-51b1bdef68c5
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2024-04-08
Route INTRAVENOUS
Dosage form INJECTION, SOLUTION, CONCENTRATE
Substance CYCLOPHOSPHAMIDE

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

GPI-14 21101020002010
GCN Seq No 085308
GCN 54762
HICL code 003893
Ingredient (HICL) Cyclophosphamide
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1A
Therapeutic class — specific (HIC3) Antineoplastic - Alkylating Agents
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name CYCLOPHOSPHAMIDE 1 GM/10 ML VL
FDB brand name Cyclophosphamide
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 085308
  • GCN: 54762
  • GPI-14 (Medi-Span): 21101020002010
  • HICL (First Databank): 003893
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 2679073
Why two NDCs? The FDA registers this code as 0781-3529-10 — a 4-4-2 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 labeler segment → 00781-3529-10. 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 Alkylating Drug class.

Pharmacologic class Alkylating Drug
Drug family (ATC) Nitrogen mustard analogues
How it works Alkylating Activity
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 CYCLOPHOSPHAMIDE 1 GM/10 ML VL Ingredient Cyclophosphamide
📖 What it is MedlinePlus · NLM

Cyclophosphamide is used to treat Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's lymphoma (types of cancer that begin in a type of white blood cells that normally fights infection); mycosis fungoides (a type of blood cancer that first appears as skin rashes); multiple myeloma (a type of cancer of the bone marrow); and certain types of leukemia (cancer of the white blood cells), including chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML, ANLL), and acute lymphoblastic leukemia (ALL). It is also used to treat retinoblastoma (cancer in...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It is mainly a chemotherapy drug for cancers such as lymphomas, multiple myeloma, leukemias and breast and ovarian cancer. Some oral and injection products are also approved for ch...
  • It may be given into a vein or taken by mouth, depending on your product. Drink plenty of fluids and empty your bladder often to protect it. The label says morning dosing is best....
  • Common ones are low white blood cell counts, fever, hair loss, nausea, vomiting and diarrhea. Your blood counts will be checked regularly. Call right away for fever or infection si...
  • Tell us about everything you take. Protease inhibitors, warfarin, cyclosporine, tamoxifen and metronidazole can interact. Also tell any surgeon or anesthesiologist if you had cyclo...
📖 Read our full Cyclophosphamide guide →
1
Nutrient depletion considerations

Cyclophosphamide may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Cyclophosphamide nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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 $81.08 $810.76 / 10 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9074 $3.438 / J9074 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)0781-3529-10
11-digit billing NDC00781-3529-10
Format4-4-2 as registered → padded to 5-4-2 for billing (zero added to the labeler segment)
HCPCS J-codeJ9074
Descriptor5 MG
Billing units / pkg200 units
How the units are derivedThis package is 10; the HCPCS unit is 5 MG, so one package = 200 billing units.
Medicare Part B spend (2026 (Q1))$344,032 · 432 claims · $796.37 per claim (all NDCs under J9074)
Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk
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
00781-3529-10 You're viewing this Main listing 1 VIAL, MULTI-DOSE in 1 CARTON / 10 mL in 1 VIAL, MULTI-DOSE 2024-04-08 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Cyclophosphamide 500 mg/5mL 00781-3528-10 Sandoz 1 vial — — FDA listed —
Cyclophosphamide 1000 mg/10mLthis 00781-3529-10 Sandoz 1 vial — — FDA listed —
Cyclophosphamide 2000 mg/20mL 00781-3530-10 Sandoz 1 vial — — FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
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

🏛️
2024
On the market since
Apr 2024
📍
2026
Currently FDA-listed
2 years listed
🔒
·
Generic approved (availability unconfirmed)
see note
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

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 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.

2 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

LabelerSandoz Inc
Application holderSANDOZ INC
FDA applicationNDA217150 (NDA)
Labeler code00781
First marketedApr 2024
Product typeHuman Prescription Drug
Portfolio391 products on file

More NDCs from Sandoz Inc labeler code 00781

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.
🎯 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 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Malignant Diseases Cyclophosphamide Injection is indicated for the treatment of adult patients with: • malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin’s lymphoma, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma • multiple myeloma • leukemias: Chronic lymphocytic leukemia, chronic granulocytic leukemia (it is usually ineffective in acute blastic crisis), acute myelogenous and monocytic leukemia, acute lymphoblastic (stem-cell) leukemia (cyclophosphamide given during remission is effective in prolonging its duration) • mycosis fungoides (advanced disease) • neuroblastoma (disseminated disease) • adenocarcinoma of the ovary • retinoblastoma • carcinoma of the breast Cyclophosphamide, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs.

Limitations of Use This cyclophosphamide product is not indicated for use in pediatric patients due to the to the alcohol and propylene glycol content in this product. If treatment with cyclophosphamide is indicated in a pediatric patient, use a different cyclophosphamide product [see Warnings and Precautions ( 5.7 ), Use in Specific Populations ( 8.4 ), and Description ( 11 )] . Cyclophosphamide Injection is an alkylating drug indicated for treatment of adult patients with: Malignant Diseases: malignant lymphomas: Hodgkin’s lymphoma, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma.

( 1 ) Limitations of Use This cyclophosphamide product is not indicated for use in pediatric patients due to the alcohol and propylene glycol content in this product. If treatment with cyclophosphamide is indicated in a pediatric patient, use a different cyclophosphamide product. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION During or immediately after Cyclophosphamide Injection administration, administer adequate amounts of fluid to reduce the risk of urinary tract toxicity ( 2.1 ). Malignant Diseases: Adult Patients ( 2.2 ) • Intravenous: Initial course for patients with no hematologic deficiency: 40 mg/kg to 50 mg/kg in divided doses over 2 to 5 days. Other regimens include 10 mg/kg to 15 mg/kg given every 7 to 10 days or 3 mg/kg to 5 mg/kg twice weekly.

( 2.2 ) • See full prescribing information for instructions on preparation, handling, and administration. ( 2.3 )

2.1Important Administration Information During or immediately after the administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, Cyclophosphamide Injection should be administered in the morning.

2.2Recommended Dosage for Malignant Diseases Intravenous Use When used as the only oncolytic drug therapy, the recommended dosage for the initial course of Cyclophosphamide Injection for patients with no hematologic deficiency is 40 mg per kg to 50 mg per kg given intravenously in divided doses over a period of 2 to 5 days. Other intravenous regimens include 10 mg per kg to 15 mg per kg given every 7 to 10 days or 3 mg per kg to 5 mg per kg twice weekly. Adjust the dosage of Cyclophosphamide Injection based on the specific regimen administered, response to treatment, myelosuppression or other adverse reactions, and patient risk factors [see Warnings and Precautions ( 5 )] .

2.3Preparation, Handling and Administration Cyclophosphamide Injection is a hazardous drug. Follow applicable special handling and disposal procedures 1 . Caution should be exercised when handling and preparing Cyclophosphamide Injection.

To minimize the risk of dermal exposure, always wear gloves when handling vials containing Cyclophosphamide Injection. Cyclophosphamide Injection Intravenous Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use Cyclophosphamide Injection vials if there are signs of particulate matter.

Cyclophosphamide Injection does not contain any antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Use aseptic technique. For Direct Intravenous Injection Aseptically withdraw the prescribed dose from the vial and dilute to a concentration of 20 mg/mL by using any of the following diluents: • 5% Dextrose Injection • 0.45% Sodium Chloride Injection • 0.9% Sodium Chloride Injection For Intravenous Infusion Aseptically withdraw the prescribed dose from the vial and dilute to a concentration of 2 mg/mL by using any of the following diluents: • 0.9% Sodium Chloride Injection • 0.45% Sodium Chloride Injection • 5% Dextrose Injection To reduce the likelihood of adverse reactions that appear to be administration rate dependent (e.g., facial swelling, headache, nasal congestion, scalp burning), Cyclophosphamide Injection should be injected or infused very slowly.

Duration of the infusion also should be appropriate for the volume and type of carrier fluid to be infused. Each vial is recommended for no more than a total of eight (8) dose withdrawals. Storage of Diluted Cyclophosphamide Injection Solution: If the diluted solution is not used immediately, store at room temperature at 68°F to 77°F (20°C to 25°C) for up to 24 hours or refrigerated at 36°F to 46°F (2°C to 8°C) for up to 6 days.

Storage of Undiluted Cyclophosphamide Injection Solution: After first use, the partially used vial should be stored in the refrigerator in the original carton at 2°C to 8°C (36ºF to 46°F) up to 28 days. Discard unused portion after 28 days.

💊 Dosage Forms and Strengths 60 words ▾

3 DOSAGE FORMS AND STRENGTHS Cyclophosphamide Injection is a 100 mg/mL sterile, clear, colorless to pale-yellow solution in a multiple-dose vial available in the following presentations: • 500 mg/5 mL • 1,000 mg/10 mL • 2,000 mg/20 mL Injection: 500 mg/5 mL (100 mg/mL), 1,000 mg/10 mL (100 mg/mL), 2,000 mg/20 mL (100 mg/mL) in multiple-dose vials ( 3 )

⛔ Contraindications 82 words ▾

4 CONTRAINDICATIONS Severe Hypersensitivity Cyclophosphamide Injection is contraindicated in patients who have a history of severe hypersensitivity reactions to cyclophosphamide, any of its metabolites, or to other components of the product. Anaphylactic reactions including death have been reported with cyclophosphamide. Cross-sensitivity with other alkylating agents can occur.

Urinary Outflow Obstruction Cyclophosphamide Injection is contraindicated in patients with urinary outflow obstruction [see Warnings and Precautions ( 5.2 )]. • Severe hypersensitivity to cyclophosphamide ( 4 ) • Urinary outflow obstruction ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections: Severe immunosuppression may lead to serious and sometimes fatal infections. Close hematological monitoring is required. ( 5.1 ) • Urinary Tract and Renal Toxicity: Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria can occur.

Urotoxicity can be fatal. Exclude or correct any urinary tract obstructions prior to treatment. ( 5.2 ) • Cardiotoxicity: Myocarditis, myopericarditis, pericardial effusion, arrythmias and congestive heart failure, which may be fatal, have been reported.

Monitor patients, especially those with risk factors for cardiotoxicity or pre-existing cardiac disease. ( 5.3 ) • Pulmonary Toxicity: Pneumonitis, pulmonary fibrosis and pulmonary veno-occlusive disease leading to respiratory failure may occur. Monitor patients for signs and symptoms of pulmonary toxicity.

( 5.4 ) • Secondary Malignancies: Have been reported in patients treated with cyclophosphamide containing regimens. ( 5.5 ) • Veno-occlusive Liver Disease: Fatal outcome can occur. ( 5.6 ) • Alcohol Content: This product is not indicated for use in pediatric patients.

The alcohol content in a dose of Cyclophosphamide Injection may affect the central nervous system. This may include impairment of a patient's ability to drive or use machines immediately after infusion. ( 5.7 ) • Embryo-Fetal Toxicity: Can cause fetal harm.

Advise females of reproductive potential of potential risk to a fetus and to use effective contraception. Advise males with female partners of reproductive potential to use effective contraception ( 5.8 , 8.1 , 8.3 )

5.1Myelosuppression, Immunosuppression, Bone Marrow Failure and Infections Cyclophosphamide can cause myelosuppression (leukopenia, neutropenia, thrombocytopenia and anemia), bone marrow failure, and severe immunosuppression which may lead to serious and sometimes fatal infections, including sepsis and septic shock. Latent infections can be reactivated [see Adverse Reactions ( 6.2 )]. Antimicrobial prophylaxis may be indicated in certain cases of neutropenia at the discretion of the managing physician.

In case of neutropenic fever, antibiotic therapy is indicated. Antimycotics and/or antivirals may also be indicated. Monitoring of complete blood counts is essential during cyclophosphamide treatment so that the dose can be adjusted, if needed.

Cyclophosphamide Injection should not be administered to patients with neutrophils ≤1,500/mm3 and platelets < 50,000/mm 3 . Cyclophosphamide Injection treatment may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop a serious infection. G-CSF may be administered to reduce the risks of neutropenia complications associated with cyclophosphamide use.

Primary and secondary prophylaxis with G-CSF should be considered in all patients considered to be at increased risk for neutropenia complications. The nadirs of the reduction in leukocyte count and thrombocyte count are usually reached in weeks 1 and 2 of treatment. Peripheral blood cell counts are expected to normalize after approximately 20 days.

Bone marrow failure has been reported. Severe myelosuppression may be expected particularly in patients pretreated with and/or receiving concomitant chemotherapy and/or radiation therapy.

5.2Urinary Tract and Renal Toxicity Hemorrhagic cystitis, pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide. Medical and/or surgical supportive treatment may be required to treat protracted cases of severe hemorrhagic cystitis. Discontinue Cyclophosphamide Injection therapy in case of severe hemorrhagic cystitis.

Urotoxicity (bladder ulceration, necrosis, fibrosis, contracture and secondary cancer) may require interruption of cyclophosphamide treatment or cystectomy. Urotoxicity can be fatal. Urotoxicity can occur with short-term or long-term use of cyclophosphamide.

Before starting treatment, exclude or correct any urinary t… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling. • Hypersensitivity [see Contraindications ( 4 )] • Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections [see Warnings and Precautions ( 5.1 )] • Urinary Tract and Renal Toxicity [see Warnings and Precautions ( 5.2 )] • Cardiotoxicity [see Warnings and Precautions ( 5.3 )] • Pulmonary Toxicity [see Warnings and Precautions ( 5.4 )] • Secondary Malignancies [see Warnings and Precautions ( 5.5 )] • Veno-occlusive Liver Disease [see Warnings and Precautions ( 5.6 )] • Alcohol Content [see Warnings and Precautions ( 5.7 )] • Infertility [see Warnings and Precautions ( 5.9 ) ] • Impaired Wound Healing [see Warnings and Precautions ( 5.10 )] • Hyponatremia [see Warnings and Precautions ( 5.11 )] The most common adverse reactions are neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials and Postmarketing Experience The following adverse reactions associated with the use of cyclophosphamide were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions were neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.

Cardiac: cardiac arrest, ventricular fibrillation, ventricular tachycardia, cardiogenic shock, pericardial effusion (progressing to cardiac tamponade), myocardial hemorrhage, myocardial infarction, cardiac failure (including fatal outcomes), cardiomyopathy, myocarditis, pericarditis, carditis, atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, bradycardia, tachycardia, palpitations, QT prolongation. Congenital, Familial and Genetic : intra-uterine death, fetal malformation, fetal growth retardation, fetal toxicity (including myelosuppression, gastroenteritis).

Ear and Labyrinth: deafness, hearing impaired, tinnitus. Endocrine: water intoxication. Eye: visual impairment, conjunctivitis, lacrimation.

Gastrointestinal: gastrointestinal hemorrhage, acute pancreatitis, colitis, enteritis, cecitis, stomatitis, constipation, parotid gland inflammation, nausea, vomiting, diarrhea. General Disorders and Administrative Site Conditions: multiorgan failure, general physical deterioration, influenza-like illness, injection/infusion site reactions (thrombosis, necrosis, phlebitis, inflammation, pain, swelling, erythema), pyrexia, edema, chest pain, mucosal inflammation, asthenia, pain, chills, fatigue, malaise, headache, febrile neutropenia.

Hematologic: myelosuppression, bone marrow failure, disseminated intravascular coagulation and hemolytic uremic syndrome (with thrombotic microangiopathy). Hepatic: veno-occlusive liver disease, cholestatic hepatitis, cytolytic hepatitis, hepatitis, cholestasis; hepatotoxicity with hepatic failure, hepatic encephalopathy, ascites, hepatomegaly, blood bilirubin increased, hepatic function abnormal, hepatic enzymes increased. Immune: immunosuppression, anaphylactic shock and hypersensitivity reaction.

Infections: The following manifestations have been associated with myelosuppression and immunosuppression caused by cyclophosphamide: increased risk for and severity of pneumonias (including fatal outcomes), other bacterial, fungal, viral, protozoal, and parasitic infections; reactivation of latent infections, (including viral hepatitis, tuberculosis), pneumocystis jiroveci , herpes zoster, strongyloides , sepsis and septic shock. Investigations: blood lactate dehydrogenase increased, C-reactive protein increased. Metabolism and Nutrition: hyponatremia, fluid retention, blood glucose increased, blood glucos… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS

7.1Effect of Other Drugs on Cyclophosphamide Exposure Protease Inhibitors Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites and may enhance the toxicities of cyclophosphamide, including higher incidence of infections, neutropenia, and mucositis. Monitor for increased toxicities in patients receiving protease inhibitors.

7.2Drugs that Potentiate Cyclophosphamide Toxicities Radiation therapy or drugs with similar toxicities to Cyclophosphamide Injection can potentiate toxicities for cyclophosphamide. Monitor for increased toxicities in patients receiving radiation therapy or drugs known to cause: • Myelosuppression and/or immunosuppression [see Warnings and Precautions ( 5.1 )] • Nephrotoxicity including hemorrhagic cystitis [see Warnings and Precautions ( 5.2 )] • Cardiotoxicity [see Warnings and Precautions ( 5.3 )] • Pulmonary toxicity [see Warnings and Precautions ( 5.4 )] • Secondary malignancies [see Warnings and Precautions ( 5.5 )] • Hepatotoxicity including liver necrosis and VOD [see Warnings and Precautions ( 5.6) ]

7.3Effect of Cyclophosphamide on Other Drugs Metronidazole Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. Monitor for neurologic toxicities in patients receiving metronidazole. Tamoxifen Concomitant use of tamoxifen and a cyclophosphamide-containing chemotherapy regimen may increase the risk of thromboembolic complications.

Monitor for signs and symptoms of thromboembolic events in patients receiving tamoxifen. Coumarins Both increased and decreased warfarin effect have been reported in patients receiving warfarin and cyclophosphamide. Monitor anticoagulant activity closely in patients receiving warfarin or other coumarins.

Cyclosporine Concomitant administration of cyclophosphamide may decrease serum concentrations of cyclosporine. This interaction may result in an increased incidence of graft-versus-host disease. Monitor for signs and symptoms of graft-versus-host disease in patients receiving cyclosporine.

Depolarizing muscle relaxants If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, alert the anesthesiologist. Cyclophosphamide causes a marked and persistent inhibition of cholinesterase activity. Prolonged apnea may occur with concurrent depolarizing muscle relaxants (e.g., succinylcholine).

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Lactation: Advise not to breastfeed. ( 8.2 ) • Renal Impairment: Monitor for toxicity in patients with moderate and severe renal impairment. ( 8.6 , 12.3 )

8.1Pregnancy Risk Summary Based on its mechanism of action and published reports of effects in pregnant patients or animals, Cyclophosphamide Injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 ) and Nonclinical Toxicology ( 13.1 )] . Exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn [see Data] . Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys [see Data] .

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Data Human Data Malformations of the skeleton, palate, limbs and eyes as well as miscarriage have been reported after exposure to cyclophosphamide in the first trimester. Fetal growth retardation and toxic effects manifesting in the newborn, including leukopenia, anemia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis have been reported after exposure to cyclophosphamide. Animal Data Administration of cyclophosphamide to pregnant mice, rats, rabbits, and monkeys during the period of organogenesis at doses at or below the dose in patients based on body surface area resulted in various malformations, which included neural tube defects, limb and digit defects and other skeletal anomalies, cleft lip and palate, and reduced skeletal ossification.

8.2Lactation Risk Summary Cyclophosphamide is present in breast milk. Neutropenia, thrombocytopenia, low hemoglobin, and diarrhea have been reported in infants breast fed by women treated with cyclophosphamide. Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during the treatment and for 1 week after the last dose.

8.3Females and Males of Reproductive Potential Cyclophosphamide Injection can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of Cyclophosphamide Injection. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with Cyclophosphamide Injection and for up to 1 year after therapy.

Males Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment with Cyclophosphamide Injection for 4 months after therapy [see Nonclinical Toxicology ( 13.1 )] . Infertility Females Amenorrhea, transient or permanent, associated with decreased estrogen and increased gonadotropin secretion develops in a proportion of women treated with cyclophosphamide. Affected patients generally resume regular menses within a few months after cessation of therapy.

The risk of premature menopause with cyclophosphamide increases with age. Oligomenorrhea has also been reported in association with cyclophosphamide treatment. Animal data suggest an increased risk of failed pregnancy and malformations may persist after discontinuation of cyclophosphamide as long as oocytes/follicles exist that were exposed to cyclophosphamide during any of their maturation phases.

The exact duration of follicular development in humans is not known but may be longer than 12 months [see Nonclinical Toxicology ( 13.1 )] . Males Men treated with cyclophosphamide may develop oligospermia or azoospermia which are normally as… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on its mechanism of action and published reports of effects in pregnant patients or animals, Cyclophosphamide Injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 ) and Nonclinical Toxicology ( 13.1 )] . Exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn [see Data] . Cyclophosphamide is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys [see Data] .

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Data Human Data Malformations of the skeleton, palate, limbs and eyes as well as miscarriage have been reported after exposure to cyclophosphamide in the first trimester. Fetal growth retardation and toxic effects manifesting in the newborn, including leukopenia, anemia, pancytopenia, severe bone marrow hypoplasia, and gastroenteritis have been reported after exposure to cyclophosphamide. Animal Data Administration of cyclophosphamide to pregnant mice, rats, rabbits, and monkeys during the period of organogenesis at doses at or below the dose in patients based on body surface area resulted in various malformations, which included neural tube defects, limb and digit defects and other skeletal anomalies, cleft lip and palate, and reduced skeletal ossification.

🧒 Pediatric Use 200 words ▾

8.4Pediatric Use This cyclophosphamide product is not indicated for use in pediatric patients due to the alcohol and propylene glycol content in this product. If treatment with cyclophosphamide is indicated in a pediatric patient, use a different cyclophosphamide product. Since propylene glycol and alcohol are both metabolized by the same enzymes, co-administration of these excipients may raise systemic exposure to alcohol, particularly in pediatric patients. [see Indications and Usage ( 1 ), Warnings and Precautions ( 5.7 ), and Description ( 11 )] .

Other cyclophosphamide products may have a different amount of alcohol or no alcohol. Pre-pubescent girls treated with cyclophosphamide generally develop secondary sexual characteristics normally and have regular menses. Ovarian fibrosis with apparent complete loss of germ cells after prolonged cyclophosphamide treatment in late pre-pubescence has been reported.

Girls treated with cyclophosphamide who have retained ovarian function after completing treatment are at increased risk of developing premature menopause. Pre-pubescent boys treated with cyclophosphamide develop secondary sexual characteristics normally but may have oligospermia or azoospermia and increased gonadotropin secretion. Some degree of testicular atrophy may occur.

Cyclophosphamide induced azoospermia is reversible in some patients, though the reversibility may not occur for several years after cessation of therapy.

🧓 Geriatric Use 70 words ▾

8.5Geriatric Use There is insufficient data from clinical studies of cyclophosphamide available for patients 65 years of age and older to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac functioning, and of concomitant disease or other drug therapy.

🆘 Overdosage 122 words ▾

10 OVERDOSAGE No specific antidote for cyclophosphamide is known. Overdosage should be managed with supportive measures, including appropriate treatment for any concurrent infection, myelosuppression, or cardiac toxicity should it occur. Serious consequences of overdosage include manifestations of dose dependent toxicities such as myelosuppression, urotoxicity, cardiotoxicity (including cardiac failure), veno-occlusive hepatic disease, and stomatitis [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 and 5.6 )] .

Patients who received an overdose should be closely monitored for the development of toxicities, and hematologic toxicity in particular. Cyclophosphamide and its metabolites are dialyzable. Therefore, rapid hemodialysis is indicated when treating any suicidal or accidental overdose or intoxication.

Cystitis prophylaxis with mesna may be helpful in preventing or limiting urotoxic effects with cyclophosphamide overdose.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action has not been fully characterized. However, cross-linking of tumor cell DNA may be involved. The active alkylating metabolites of cyclophosphamide interfere with the growth of susceptible rapidly proliferating malignant cells.

12.2Pharmacodynamics Cyclophosphamide exposure-response relationships and the time course of pharmacodynamic response have not been fully characterized.

12.3Pharmacokinetics Cyclophosphamide is a prodrug. Cyclophosphamide pharmacokinetics are linear over the approved recommended dose range. Distribution The volume of distribution of cyclophosphamide is 30 to 50 L.

Cyclophosphamide is approximately 20% protein bound, with no dose dependent changes. Some metabolites are greater than 60% protein bound. Elimination The elimination half-life (t½) of cyclophosphamide ranges from 3 to 12 hours, and clearance (CL) ranges from 4 to

5.6L/h. When cyclophosphamide was administered at 4 g/m 2 (approximately 2 times the approved recommended dosage) over a 90-minutes infusion, concentration-time data demonstrate saturable elimination in parallel with first-order renal elimination. Metabolism Cyclophosphamide is metabolized by cytochrome P450s including CYP2A6, 2B6, 3A, 2C9, and 2C19.

Cyclophosphamide is activated to form 4-hydroxycyclophosphamide, which is in equilibrium with its ring-open tautomer aldophosphamide. 4-hydroxycyclophosphamide and aldophosphamide can undergo oxidation by aldehyde dehydrogenases to form the inactive metabolites 4-ketocyclophosphamide and carboxyphosphamide, respectively. Aldophosphamide can undergo β-elimination to form active metabolites phosphoramide mustard and acrolein.

This spontaneous conversion can be catalyzed by albumin and other proteins. At high doses, the fraction of parent compound cleared by 4-hydroxylation is reduced resulting in non-linear elimination of cyclophosphamide. Cyclophosphamide appears to induce its own metabolism.

This auto-induction results in an increase in CL, increased formation of active 4-hydroxycyclophosphamide and shortened t½ following multiple doses administered at 12-to-24-hour interval. Excretion Cyclophosphamide and its metabolites are eliminated by hepatic and renal pathways. Cyclophosphamide is primarily excreted as metabolites.

Ten to 20% is excreted unchanged in the urine. A small percentage of cyclophosphamide may be eliminated unchanged in bile. Specific Populations Renal Impairment Following one-hour intravenous infusion, cyclophosphamide AUC increased by 38% in patients with CLcr of 25 to 50 mL/min, by 77% in patients with CLcr of 10 to 24 mL/min and by 23% in the hemodialysis group (CLcr of < 10 mL/min) compared to the control group (CLcr≥ 80 mL/min).

Cyclophosphamide is dialyzable. Dialysis clearance averaged 104 mL/min, which is similar to the metabolic clearance of 95 mL/min for cyclophosphamide. A mean of 37% of the administered dose of cyclophosphamide was removed during a 4-hour hemodialysis period.

The t½ was 3.3 hours in patients during hemodialysis, a 49% reduction compared to t½ of 6.5 hours in uremic patients. Hepatic Impairment Cyclophosphamide CL is decreased by 40% (45 ±

8.6L/kg) and t½ is prolonged by 64% (12.5 ± 1 hours) in patients with hepatic impairment with a mean bilirubin 3.5 mg/dL and mean AST 90 IU/L compared to patients with normal hepatic function (mean bilirubin 0.5 mg/dL, mean AST 10 IU/L).

🧬 Mechanism of Action 38 words ▾

12.1Mechanism of Action The mechanism of action has not been fully characterized. However, cross-linking of tumor cell DNA may be involved. The active alkylating metabolites of cyclophosphamide interfere with the growth of susceptible rapidly proliferating malignant cells.

📦 How Supplied / Storage and Handling 86 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Cyclophosphamide Injection, 100 mg/mL is a sterile ready-to-dilute, clear, colorless to pale-yellow solution in a multiple-dose vial available in the following strengths: Strength NDC Number Volume 500 mg/5 mL 0781-3528-10 Carton of one 5 mL Multiple-Dose Vial 1,000 mg/10 mL 0781-3529-10 Carton of one 10 mL Multiple-Dose Vial 2,000 mg/20 mL 0781-3530-10 Carton of one 20 mL Multiple-Dose Vial Store vials refrigerated at 2°C to 8°C (36°F to 46°F). Cyclophosphamide is a hazardous product.

Follow special handling and disposal procedures. 1

📋 Description 188 words ▾

11 DESCRIPTION Cyclophosphamide is an alkylating drug. It is a synthetic antineoplastic drug chemically related to the nitrogen mustards. The chemical name for cyclophosphamide is 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate, and has the following structural formula: Cyclophosphamide is a white crystalline powder with the molecular formula C 7 H 15 Cl 2 N 2 O 2 P•H 2 O and a molecular weight of 279.1.

Cyclophosphamide is soluble in water and freely soluble in alcohol. Cyclophosphamide Injection, 100 mg/mL is a sterile ready-to-dilute, clear, colorless to pale-yellow solution in a multiple-dose vial available as 500 mg/5 mL, 1,000 mg/10 mL, and 2,000 mg/20 mL strengths. • 500 mg vial contains 534.5 mg cyclophosphamide monohydrate equivalent to 500 mg cyclophosphamide, 2.92 g dehydrated alcohol (equivalent to 73.9 % v/v) and 0.96 g propylene glycol. • 1,000 mg vial contains 1,069 mg cyclophosphamide monohydrate equivalent to 1,000 mg cyclophosphamide, 5.85 g dehydrated alcohol (equivalent to 73.9 % v/v) and 1.92 g propylene glycol. • 2,000 mg vial contains 2,138 mg cyclophosphamide monohydrate equivalent to 2,000 mg cyclophosphamide, 11.69 g dehydrated alcohol (equivalent to 73.9 % v/v) and 3.84 g propylene glycol. chemical-structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient of the following: Myelosuppression, Immunosuppression, Bone Marrow Failure, and Infections • Inform patients of the possibility of myelosuppression, immunosuppression, and infections. Explain the need for routine blood cell counts. Instruct patients to monitor their temperature frequently and immediately report any occurrence of fever [see Warnings and Precautions ( 5.1 )] .

Urinary Tract and Renal Toxicity • Advise the patient to report urinary symptoms (patients should report if their urine has turned a pink or red color) and the need for increasing fluid intake and frequent voiding [see Warnings and Precautions ( 5.2 )] . Cardiotoxicity • Inform patients of the possibility of cardiotoxicity (which may be fatal). • Advise patients to contact a healthcare professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Warnings and Precautions ( 5.3 )] .

Pulmonary Toxicity • Warn patients of the possibility of developing non-infectious pneumonitis. Advise patients to report promptly any new or worsening respiratory symptoms [see Warnings and Precautions ( 5.4 )] . Alcohol Content • Explain to patients the possible effects of the alcohol content in Cyclophosphamide Injection, including possible effects on the central nervous system.

Patients in whom alcohol should be avoided or minimized should consider the alcohol content of Cyclophosphamide Injection. Alcohol could impair their ability to drive or use machines immediately after infusion [see Warnings and Precautions ( 5.7 )] . Secondary Malignancies • Inform patients that there is an increased risk of secondary malignancies with Cyclophosphamide Injection [see Warnings and Precautions (5.5)].

Embryo-Fetal Toxicity • Inform female patients of the risk to a fetus and potential loss of the pregnancy. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.1 )] . • Advise females of reproductive potential to use effective contraception during treatment and for up to 1 year after completion of therapy [see Warning and Precautions ( 5.8 ) and Use in Specific Population ( 8.1 , 8.3 )] . • Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after completion of therapy [see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.1 , 8.3 )] .

Lactation • Advise women not to breastfeed during treatment and for 1 week after the last dose of Cyclophosphamide Injection [see Use in Specific Populations ( 8.2 )] . Infertility • Advise patients that Cyclophosphamide Injection may impair fertility in males and females of reproductive potential [see Warnings and Precautions ( 5.9 ) and Use in Specific Populations ( 8.3 , 8.4 )] . Common Adverse Reactions • Explain to patients that side effects such as nausea, vomiting, stomatitis, impaired wound healing, amenorrhea, premature menopause, sterility, and hair loss may be associated with cyclophosphamide administration.

Other undesirable effects (including, e.g., dizziness, blurred vision, visual impairment) could affect the ability to drive or use machines [see Adverse Reactions ( 6.1 )] . Hydration and Important Administration Instructions • Advise the patients that during or immediately after the administration, adequate amounts of fluid are required to reduce the risk of urinary tract toxicity [see Dosage and Administration ( 2.1 )] . Manufactured by FAREVA Unterach GmbH for Sandoz Inc., Princeton, NJ 08540

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Cyclophosphamide is a prodrug. Cyclophosphamide pharmacokinetics are linear over the approved recommended dose range. Distribution The volume of distribution of cyclophosphamide is 30 to 50 L.

Cyclophosphamide is approximately 20% protein bound, with no dose dependent changes. Some metabolites are greater than 60% protein bound. Elimination The elimination half-life (t½) of cyclophosphamide ranges from 3 to 12 hours, and clearance (CL) ranges from 4 to

5.6L/h. When cyclophosphamide was administered at 4 g/m 2 (approximately 2 times the approved recommended dosage) over a 90-minutes infusion, concentration-time data demonstrate saturable elimination in parallel with first-order renal elimination. Metabolism Cyclophosphamide is metabolized by cytochrome P450s including CYP2A6, 2B6, 3A, 2C9, and 2C19.

Cyclophosphamide is activated to form 4-hydroxycyclophosphamide, which is in equilibrium with its ring-open tautomer aldophosphamide. 4-hydroxycyclophosphamide and aldophosphamide can undergo oxidation by aldehyde dehydrogenases to form the inactive metabolites 4-ketocyclophosphamide and carboxyphosphamide, respectively. Aldophosphamide can undergo β-elimination to form active metabolites phosphoramide mustard and acrolein.

This spontaneous conversion can be catalyzed by albumin and other proteins. At high doses, the fraction of parent compound cleared by 4-hydroxylation is reduced resulting in non-linear elimination of cyclophosphamide. Cyclophosphamide appears to induce its own metabolism.

This auto-induction results in an increase in CL, increased formation of active 4-hydroxycyclophosphamide and shortened t½ following multiple doses administered at 12-to-24-hour interval. Excretion Cyclophosphamide and its metabolites are eliminated by hepatic and renal pathways. Cyclophosphamide is primarily excreted as metabolites.

Ten to 20% is excreted unchanged in the urine. A small percentage of cyclophosphamide may be eliminated unchanged in bile. Specific Populations Renal Impairment Following one-hour intravenous infusion, cyclophosphamide AUC increased by 38% in patients with CLcr of 25 to 50 mL/min, by 77% in patients with CLcr of 10 to 24 mL/min and by 23% in the hemodialysis group (CLcr of < 10 mL/min) compared to the control group (CLcr≥ 80 mL/min).

Cyclophosphamide is dialyzable. Dialysis clearance averaged 104 mL/min, which is similar to the metabolic clearance of 95 mL/min for cyclophosphamide. A mean of 37% of the administered dose of cyclophosphamide was removed during a 4-hour hemodialysis period.

The t½ was 3.3 hours in patients during hemodialysis, a 49% reduction compared to t½ of 6.5 hours in uremic patients. Hepatic Impairment Cyclophosphamide CL is decreased by 40% (45 ±

8.6L/kg) and t½ is prolonged by 64% (12.5 ± 1 hours) in patients with hepatic impairment with a mean bilirubin 3.5 mg/dL and mean AST 90 IU/L compared to patients with normal hepatic function (mean bilirubin 0.5 mg/dL, mean AST 10 IU/L).

🧬 Pharmacodynamics 17 words ▾

12.2Pharmacodynamics Cyclophosphamide exposure-response relationships and the time course of pharmacodynamic response have not been fully characterized.

🧪 Nonclinical Toxicology 170 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Cyclophosphamide administered by different routes, including intravenous, subcutaneous or intraperitoneal injection, or in drinking water, caused tumors in both mice and rats. In addition to leukemia and lymphoma, benign and malignant tumors were found at various tissue sites, including urinary bladder, mammary gland, lung, liver, and injection site [see Warnings and Precautions ( 5.5 )] . Cyclophosphamide was mutagenic and clastogenic in multiple in vitro and in vivo genetic toxicology studies.

Cyclophosphamide is genotoxic in male and female germ cells. Animal data indicate that exposure of oocytes to cyclophosphamide during follicular development may result in a decreased rate of implantations and viable pregnancies, and in an increased risk of malformations. Male mice and rats treated with cyclophosphamide show alterations in male reproductive organs (e.g., decreased weights, atrophy, changes in spermatogenesis), and decreases in reproductive potential (e.g., decreased implantations and increased post-implantation loss) and increases in fetal malformations when mated with untreated females [see Use in Specific Populations ( 8.3 )] .

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 167 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Cyclophosphamide administered by different routes, including intravenous, subcutaneous or intraperitoneal injection, or in drinking water, caused tumors in both mice and rats. In addition to leukemia and lymphoma, benign and malignant tumors were found at various tissue sites, including urinary bladder, mammary gland, lung, liver, and injection site [see Warnings and Precautions ( 5.5 )] . Cyclophosphamide was mutagenic and clastogenic in multiple in vitro and in vivo genetic toxicology studies.

Cyclophosphamide is genotoxic in male and female germ cells. Animal data indicate that exposure of oocytes to cyclophosphamide during follicular development may result in a decreased rate of implantations and viable pregnancies, and in an increased risk of malformations. Male mice and rats treated with cyclophosphamide show alterations in male reproductive organs (e.g., decreased weights, atrophy, changes in spermatogenesis), and decreases in reproductive potential (e.g., decreased implantations and increased post-implantation loss) and increases in fetal malformations when mated with untreated females [see Use in Specific Populations ( 8.3 )] .

📚 References 9 words ▾

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

📄 Recent Major Changes 7 words ▾

Dosage and Administration ( 2.2 ) 12/2024

📄 Package Label / Principal Display Panel 99 words ▾

PRINCIPAL DISPLAY PANEL – 5 mL Carton NDC 0781-3528-10 Sterile Cyclophosphamide Injection 500 mg/5 mL (100 mg/mL) Must Dilute Before Intravenous Use Hazardous Drug Rx Only One 5 mL Multiple-Dose Vial SANDOZ 5ml-carton

PRINCIPAL DISPLAY PANEL – 10 mL Carton NDC 0781-3529-10 Sterile Cyclophosphamide Injection 1,000 mg/10 mL (100 mg/mL) Must Dilute Before Intravenous Use Hazardous Drug Rx Only One 10 mL Multiple-Dose Vial SANDOZ 10ml-carton

PRINCIPAL DISPLAY PANEL – 20 mL Carton NDC 0781-3530-10 Sterile Cyclophosphamide Injection 2,000 mg/20 mL (100 mg/mL) Must Dilute Before Intravenous Use Hazardous Drug Rx Only One 20 mL Multiple-Dose Vial SANDOZ 20ml-carton

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
25
Units reimbursed last 4 qtrs
280
Gross reimbursed last 4 qtrs
$22.7K
Avg / prescription
$908.05
Avg / unit
$81.2068
Latest quarter Q1 2026
13Rx
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 25 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: 280 units · 2.8 per 100k residents MI New York: no data reported 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: no data reported 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: no data reported 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: no data reported 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
2.82.8
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 Michigan 2.8 /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.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Cyclophosphamide — the program that covers self-administered drugs. 11 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Cyclophosphamide. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$490.1K
Claims incl. refills
1.4K
Beneficiaries
699
Spend / beneficiary
$701.16
Spend / claim
$342.02
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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 Sandoz Inc. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Sandoz 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 J9074 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.
← 00781-3528-10 · Sandoz 00781-3530-10 · Sandoz →
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.