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Cyclophosphamide 50 mg Capsule, 100-count — NDC 46708-0619-31 package photo
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Cyclophosphamide 50 mg Capsule, 100-count — NDC 46708-619-31 (Billing 46708-0619-31)

by Alembic Pharmaceuticals Limited · 100 CAPSULE in 1 BOTTLE

This is a package of 100 capsules of Cyclophosphamide 50 mg Capsule from Alembic Pharmaceuticals Limited, marketed since Nov 2022 and currently FDA-listed. It is this product's only package size.

NDC 46708-0619-31
🏷️ FDA NDC (as labeled) 46708-619-31 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 →

This page is curated, coded, and maintained by

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

⚠️
Other active recalls for Cyclophosphamide (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Sep 5, 2025 — cGMP deviations: Temperature excursion during transportation. (Sandoz Inc) · FDA recall D-0651-2025
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 46708-619-31
Product NDC 46708-619
11-digit billing NDC 46708061931
RxCUI 1437968, 1437969
UNII 8N3DW7272P
UPC 0346708618315
Application # ANDA215892
SPL Set ID 9e699cf7-860e-4c03-9760-0c24d56df2de
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-11-23
Route ORAL
Dosage form CAPSULE
Substance CYCLOPHOSPHAMIDE
TE code (Orange Book) AB · RLD · RS
Quick answers
  • RxCUI (RxNorm): 1437968
Why two NDCs? The FDA registers this code as 46708-619-31 — 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 → 46708-0619-31. 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

📗 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $3.00 $300.26 / 100 capsules
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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
46708-0619-31 You're viewing this Main listing 100 CAPSULE in 1 BOTTLE 2022-11-23 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Cyclophosphamide 50 mg 00054-0383-25 Hikma 100 capsules $1.671 AB Availability likely —
Cyclophosphamide 50 mg 62332-0619-31 Alembic 100 capsules $1.671 AB Availability likely —
Cyclophosphamide 50 mg 69097-0517-07 Cipla 100 capsules $1.671 AB Availability likely —
Cyclophosphamide 50 mgthis 46708-0619-31 Alembic 100 capsules — AB FDA listed —
Cyclophosphamide 50 mg 70301-2015-01 OPKO 100 capsules — AB 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

🏛️
2022
On the market since
Nov 2022
📍
2026
Currently FDA-listed
4 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 H3R47K3TBD
    FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
  • UNII PN2ZH5LOQY
    A synthetic red dye approved by the FDA for use in foods, medicines, and cosmetics. It serves as a colorant to make tablets, capsules, and liquids visually distinctive for product identification.
  • UNII XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • UNII 2G86QN327L
    Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
  • UNII WZH3C48M4T
    Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
  • UNII 46N107B71O
    Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
  • UNII 7CV7WJK4UI
    Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.
  • UNII O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

9 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

LabelerAlembic Pharmaceuticals Limited
Application holderALEMBIC PHARMACEUTICALS LTD
FDA applicationANDA215892 (ANDA)
Labeler code46708
First marketedNov 2022
Product typeHuman Prescription Drug
Portfolio502 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.
🎯 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 📄 Package Label / Principal Display Panel
🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Cyclophosphamide is an alkylating drug indicated for treatment of: Malignant Diseases : malignant lymphomas: Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma (1.1) Minimal Change Nephrotic Syndrome in Pediatric Patients : biopsy proven minimal change nephrotic syndrome in pediatric patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy (1.2) Limitations of Use: The safety and effectiveness for the treatment of nephrotic syndrome in adults or other renal disease has not been established.

1.1Malignant Diseases Cyclophosphamide capsules are indicated for the treatment of: • malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin’s disease, 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 capsules, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs.

1.2Minimal Change Nephrotic Syndrome in Pediatric Patients Cyclophosphamide capsules are indicated for the treatment of biopsy proven minimal change nephrotic syndrome in pediatric patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy. Limitations of Use: The safety and effectiveness of cyclophosphamide capsules for the treatment of nephrotic syndrome in adults or other renal disease has not been established.

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION During or immediately after the administration, administer adequate amounts of fluid to reduce the risk of urinary tract toxicity (2.1). Malignant Diseases: Adult and Pediatric Patients (2.2) Oral: Usually 1 mg per kg per day to 5 mg per kg orally once daily for both initial and maintenance dosing. Minimal Change Nephrotic Syndrome in Pediatric Patients (2.3) Recommended oral dose: 2 mg per kg once daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg).

Treatment beyond 90 days increases the probability of sterility in males.

2.1Hydration and Important Administration Instructions During or immediately after the administration of cyclophosphamide capsules, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity. Therefore, cyclophosphamide capsules should be taken in the morning. Cyclophosphamide capsules should be swallowed whole.

The capsules should not be opened, chewed, or crushed. Cyclophosphamide capsules are a cytotoxic drug. Follow applicable special handling and disposal procedures.

1 Exposure to broken capsules should be avoided. If contact with broken capsules occurs, wash hands immediately and thoroughly.

2.2Recommended Dosage for Malignant Diseases Adults and Pediatric Patients The recommended dosage of cyclophosphamide capsules is in the range of 1 mg per kg to 5 mg per kg orally once daily for both initial and maintenance dosing. Other regimens of intravenous and oral cyclophosphamide have been reported. Dosages should be adjusted based on evidence of antitumor activity, myelosuppression, or other severe adverse reactions [see WARNINGS and PRECAUTIONS (5)] .

When cyclophosphamide is included in combined cytotoxic regimens, it may be necessary to reduce the dose of cyclophosphamide, as well as that of the other drugs.

2.3Recommended Dosage for Minimal Change Nephrotic Syndrome in Pediatric Patients The recommended dosage of cyclophosphamide capsules are 2 mg per kg orally once daily for 8 to 12 weeks (maximum cumulative dose 168 mg per kg). Treatment beyond 90 days increases the probability of sterility in males [see USE IN SPECIFIC POPULATIONS (8.4)].

💊 Dosage Forms and Strengths 109 words ▾

3 DOSAGE FORMS AND STRENGTHS Capsules: • 25 mg capsule for oral administration contains 25 mg of cyclophosphamide USP. It is a blue opaque cap / blue opaque body size ‘3’ hard gelatin capsule shells radially imprinted with “A” on cap and “346” on body in black ink filled with white to off-white powder. • 50 mg capsule for oral administration contains 50 mg of cyclophosphamide USP. It is a blue opaque cap / blue opaque body size ‘1’ hard gelatin capsule shells radially imprinted with “A” on cap and “347” on body in black ink filled with white to off-white powder.

Capsules: 25 mg and 50 mg (3)

⛔ Contraindications 67 words ▾

4 CONTRAINDICATIONS Cyclophosphamide capsules are contraindicated in patients with: • A history of severe hypersensitivity reactions to cyclosphosphamide, 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. • In patients with urinary outflow obstruction [see WARNINGS AND PRECAUTIONS (5.2)]. • Hypersensitivity to cyclophosphamide (4) • Urinary outflow obstruction (4)

⚠️ Warnings and Cautions ~2 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.

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 (5.5) Veno-occlusive Liver Disease - Fatal outcome can occur.

(5.6) Embryo-Fetal Toxicity - Can cause fetal harm. Advise patients of potential risk to the fetus and to use effective contraception. (5.7, 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 should not be administered to patients with neutrophils ≤1,500/mm 3 and platelets <50,000/mm 3 . Cyclophosphamide 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 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 tract obstructions [see CONTRAINDICATIONS (4)] . Urinary sediment should be checked regularly for the presence of erythrocytes and other signs of urotoxicity and/or nephrotoxicity. Cyclophosphamide should be used with caution, if at all, in patients with active urinary tract infections.

Aggressive hydration with forced diuresis and frequent bladder emptying can reduce the frequency and severity of bladder toxicity. Mesna has been used to prevent severe bladder toxicity.

5.3Cardiotoxicity Myocarditis, myopericarditis, pericardial effusion including cardiac tamponad… [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)] • Infertility [see Warnings and Precautions (5.8) and Use in Specific Populations (8.3 and 8.4)] • Impaired Wound Healing [see Warnings and Precautions (5.9)] • Hyponatremia [see Warnings and Precautions (5.10)] Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.

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

6.1Common Adverse Reactions Hematopoietic system Neutropenia occurs in patients treated with cyclophosphamide. The degree of neutropenia is particularly important because it correlates with a reduction in resistance to infections. Fever without documented infection has been reported in neutropenic patients.

Gastrointestinal system Nausea and vomiting occur with cyclophosphamide therapy. Anorexia and, less frequently, abdominal discomfort or pain and diarrhea may occur. There are isolated reports of hemorrhagic colitis, oral mucosal ulceration and jaundice occurring during therapy.

Skin and its structures Alopecia occurs in patients treated with cyclophosphamide. Skin rash occurs occasionally in patients receiving the drug. Pigmentation of the skin and changes in nails can occur.

6.2Postmarketing Experience The following adverse reactions have been identified from clinical trials or post-marketing surveillance. Because they are reported from a population from unknown size, precise estimates of frequency cannot be made. 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. General Disorders and Administrative Site Conditions: multiorgan failure, general physical deterioration, influenza-like illness, pyrexia, edema, chest pain, mucosal inflammation, asthenia, pain, chills, fatigue, malaise, headache.

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, (in… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Cyclophosphamide is a pro-drug that is activated by cytochrome P450s [see CLINICAL PHARMACOLOGY (12.3)] . An increase of the concentration of cytotoxic metabolites may occur with: • Protease inhibitors: Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites. Use of protease inhibitor-based regimens was found to be associated with a higher incidence of infections and neutropenia in patients receiving cyclophosphamide, doxorubicin, and etoposide (CDE) than use of a Non-Nucleoside Reverse Transcriptase Inhibitor-based regimen.

Combined or sequential use of cyclophosphamide and other agents with similar toxicities can potentiate toxicities. • Increased hematotoxicity and/or immunosuppression may result from a combined effect of cyclophosphamide and, for example: • ACE inhibitors: ACE inhibitors can cause leukopenia. • Natalizumab • Paclitaxel: Increased hematotoxicity has been reported when cyclophosphamide was administered after paclitaxel infusion. • Thiazide diuretics • Zidovudine • Increased cardiotoxicity may result from a combined effect of cyclophosphamide and, for example: • Anthracyclines • Cytarabine • Pentostatin • Radiation therapy of the cardiac region • Trastuzumab • Increased pulmonary toxicity may result from a combined effect of cyclophosphamide and, for example: • Amiodarone • G-CSF, GM-CSF (granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor): Reports suggest an increased risk of pulmonary toxicity in patients treated with cytotoxic chemotherapy that includes cyclophosphamide and G-CSF or GMCSF. • Increased nephrotoxicity may result from a combined effect of cyclophosphamide and, for example: • Amphotericin B • Indomethacin: Acute water intoxication has been reported with concomitant use of indomethacin • Increase in other toxicities: • Azathioprine: Increased risk of hepatotoxicity (liver necrosis) • Busulfan: Increased incidence of hepatic veno-occlusive disease and mucositis has been reported. • Protease inhibitors: Increased incidence of mucositis • Increased risk of hemorrhagic cystitis may result from a combined effect of cyclophosphamide and past or concomitant radiation treatment.

Etanercept: In patients with Wegener’s granulomatosis, the addition of etanercept to standard treatment, including cyclophosphamide, was associated with a higher incidence of non-cutaneous malignant solid tumors. Metronidazole: Acute encephalopathy has been reported in a patient receiving cyclophosphamide and metronidazole. Causal association is unclear.

In an animal study, the combination of cyclophosphamide with metronidazole was associated with increased cyclophosphamide toxicity. Tamoxifen: Concomitant use of tamoxifen and chemotherapy may increase the risk of thromboembolic complications. Coumarins: Both increased and decreased warfarin effect have been reported in patients receiving warfarin and cyclophosphamide.

Cyclosporine: Lower serum concentrations of cyclosporine have been observed in patients receiving a combination of cyclophosphamide and cyclosporine than in patients receiving only cyclosporine. This interaction may result in an increased incidence of graft-versus-host disease. Depolarizing muscle relaxants: Cyclophosphamide treatment causes a marked and persistent inhibition of cholinesterase activity.

Prolonged apnea may occur with concurrent depolarizing muscle relaxants (e.g., succinylcholine). If a patient has been treated with cyclophosphamide within 10 days of general anesthesia, alert the anesthesiologist.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. (8.2) Females and Males of Reproductive Potential: Verify pregnancy status prior to initiation of cyclophosphamide capsules. May impair fertility. (8.3) 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 capsules 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 from cyclophosphamide capsules, advise lactating women not to breastfeed during the treatment and for 1 week after the last dose.

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of cyclophosphamide capsules [see USE IN SPECIFIC POPULATIONS (8.1)] . Contraception Females Cyclophosphamide capsules can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment with cyclophosphamide capsules for up to 1 year after completion of therapy [ see USE IN SPECIFIC POPULATIONS (8.1) ].

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 capsules and for 4 months after completion of therapy [see USE IN SPECIFIC POPULATIONS (8.1) and 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 fol… [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 capsules 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 104 words ▾

8.4Pediatric Use Pre-pubescent girls treated with cyclophosphamide generally develop secondary sexual characteristics normally and have regular menses. Ovarian fibrosis with apparently 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 118 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 ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action is thought to involve cross-linking of tumor cell DNA.

12.2Pharmacodynamics Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells.

12.3Pharmacokinetics Following IV administration, elimination half-life (t ½ ) ranges from 3 to 12 hours with total body clearance (CL) values of 4 to

5.6L/h. Pharmacokinetics are linear over the dose range used clinically. When cyclophosphamide was administered at 4 g/m 2 over a 90 minutes infusion, saturable elimination in parallel with first-order renal elimination describe the kinetics of the drug.

Absorption After oral administration, peak concentrations of cyclophosphamide occurred at one hour. Area under the curve ratio for the drug after oral and IV administration (AUC po : AUC iv ) ranged from 0.87 to 0.96. Distribution Approximately 20% of cyclophosphamide is protein bound, with no dose dependent changes.

Some metabolites are protein bound to an extent greater than 60%. Volume of distribution approximates total body water (30 to 50 L). Metabolism The liver is the major site of cyclophosphamide activation.

Approximately 75% of the administered dose of cyclophosphamide is activated by hepatic microsomal cytochrome P450s including CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18 and 2C19, with 2B6 displaying the highest 4-hydroxylase activity. Cyclophosphamide is activated to form 4-­hydroxycyclophosphamide, which is in equilibrium with its ring-open tautomer aldophosphamide. 4­hydroxycyclophosphamide 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. Less than 5% of cyclophosphamide may be directly detoxified by side chain oxidation, leading to the formation of inactive metabolites 2-dechloroethylcyclophosphamide.

At high doses, the fraction of parent compound cleared by 4-hydroxylation is reduced resulting in non-linear elimination of cyclophosphamide in patients. Cyclophosphamide appears to induce its own metabolism. Auto-induction results in an increase in the total clearance, increased formation of 4-hydroxyl metabolites and shortened t ½ values following repeated administration at 12- to 24-hour interval.

Elimination Cyclophosphamide is primarily excreted as metabolites. 10 to 20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration. Special Populations Renal Impairment The pharmacokinetics of cyclophosphamide were determined following one-hour intravenous infusion to renally impaired patients.

The results demonstrated that the systemic exposure to cyclophosphamide increased as the renal function decreased. Mean dose-corrected AUC increased by 38% in the moderate renal group, (Creatinine clearance CrCl of 25 to 50 mL/min), by 64% in the severe renal group (CrCl of 10 to 24 mL/min) and by 23% in the hemodialysis group (CrCl of <10 mL/min) compared to the control group. The increase in exposure was significant in the severe group (p>0.05); thus, patients with severe renal impairment should be closely monitored for toxicity [see USE IN SPECIFIC POPULATIONS (8.6)] .

The dialyzability of cyclophosphamide was investigated in four patients on long-term hemodialysis. Dialysis clearance calculated by arterial-venous difference and actual drug recovery in dialysate averaged 104 mL/min, which is in the range of the metabolic clearance of 95 mL/min for the drug. A mean of 37% of the administered dose of cyclophosphamide was removed during hemodialysis.

The elimination half-life (t ½ ) was 3.3 hours in patients during hemodialysis… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 17 words ▾

12.1Mechanism of Action The mechanism of action is thought to involve cross-linking of tumor cell DNA.

📦 How Supplied / Storage and Handling 132 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Cyclophosphamide Capsules 25 mg capsules: Blue opaque cap / blue opaque body size ‘3’ hard gelatin capsule shells radially imprinted with “A” on cap and “346” on body in black ink filled with white to off-white powder. Bottle of 100 capsules with child resistant closure, NDC 46708-618-31 50 mg capsules: Blue opaque cap / blue opaque body size ‘1’ hard gelatin capsule shells radially imprinted with “A” on cap and “347” on body in black ink filled with white to off-white powder. Bottle of 100 capsules with child resistant closure, NDC 46708-619-31 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

Cyclophosphamide is an antineoplastic product. Follow special handling and disposal procedures. 1

📋 Description 127 words ▾

11 DESCRIPTION Cyclophosphamide, USP 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 has a 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.

Each capsule for oral administration contains 25 mg or 50 mg cyclophosphamide (anhydrous, USP) and the following inactive ingredients: pregelatinized starch and sodium stearyl fumarate. Each hard gelatin capsule shell contains FD&C Blue 1, FD&C Red 3, gelatin and titanium dioxide. The empty gelatin capsule shells are printed with edible black ink containing shellac, iron oxide black and potassium hydroxide. cyclophosphamide-str.jpg

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient of the following: Myelosuppression, Immunosuppression, 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 • Advise patients to contact a health care 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)]. 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 (5.7) 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 WARNINGS AND PRECAUTIONS (5.7) and USE IN SPECIFIC POPULATIONS (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 (5.7) and USE IN SPECIFIC POPULATIONS (8.1, 8.3)].

Lactation • Advise lactating women not to breastfeed during treatment and for 1 week after the last dose of cyclophosphamide capsules [see USE IN SPECIFIC POPULATIONS (8.2)]. Infertility • Cyclophosphamide capsules may impair fertility in males and females of reproductive potential [see WARNINGS AND PRECAUTIONS (5.8) 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, 6.2)]. Hydration and Important Administration Instructions • Advise the patient 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)]. • Instruct the patient to swallow cyclophosphamide capsules whole. Do not open, chew, or crush capsules [see DOSAGE AND ADMINISTRATION (2.1)]. • Advise caregivers to wear gloves when handling cyclophosphamide containers and capsules and to avoid exposure to broken capsules.

If contact with broken capsules occurs, wash hands immediately and thoroughly [see DOSAGE AND ADMINISTRATION (2.1)]. Manufactured by: Alembic Pharmaceuticals Limited Formulation Division II, Survey No. 84, 87 And 88, Panelav, Taluka-Halol, Panchmahal- 389350, Gujarat, India.

Revised: 11/2022

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Following IV administration, elimination half-life (t ½ ) ranges from 3 to 12 hours with total body clearance (CL) values of 4 to

5.6L/h. Pharmacokinetics are linear over the dose range used clinically. When cyclophosphamide was administered at 4 g/m 2 over a 90 minutes infusion, saturable elimination in parallel with first-order renal elimination describe the kinetics of the drug.

Absorption After oral administration, peak concentrations of cyclophosphamide occurred at one hour. Area under the curve ratio for the drug after oral and IV administration (AUC po : AUC iv ) ranged from 0.87 to 0.96. Distribution Approximately 20% of cyclophosphamide is protein bound, with no dose dependent changes.

Some metabolites are protein bound to an extent greater than 60%. Volume of distribution approximates total body water (30 to 50 L). Metabolism The liver is the major site of cyclophosphamide activation.

Approximately 75% of the administered dose of cyclophosphamide is activated by hepatic microsomal cytochrome P450s including CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18 and 2C19, with 2B6 displaying the highest 4-hydroxylase activity. Cyclophosphamide is activated to form 4-­hydroxycyclophosphamide, which is in equilibrium with its ring-open tautomer aldophosphamide. 4­hydroxycyclophosphamide 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. Less than 5% of cyclophosphamide may be directly detoxified by side chain oxidation, leading to the formation of inactive metabolites 2-dechloroethylcyclophosphamide.

At high doses, the fraction of parent compound cleared by 4-hydroxylation is reduced resulting in non-linear elimination of cyclophosphamide in patients. Cyclophosphamide appears to induce its own metabolism. Auto-induction results in an increase in the total clearance, increased formation of 4-hydroxyl metabolites and shortened t ½ values following repeated administration at 12- to 24-hour interval.

Elimination Cyclophosphamide is primarily excreted as metabolites. 10 to 20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration. Special Populations Renal Impairment The pharmacokinetics of cyclophosphamide were determined following one-hour intravenous infusion to renally impaired patients.

The results demonstrated that the systemic exposure to cyclophosphamide increased as the renal function decreased. Mean dose-corrected AUC increased by 38% in the moderate renal group, (Creatinine clearance CrCl of 25 to 50 mL/min), by 64% in the severe renal group (CrCl of 10 to 24 mL/min) and by 23% in the hemodialysis group (CrCl of <10 mL/min) compared to the control group. The increase in exposure was significant in the severe group (p>0.05); thus, patients with severe renal impairment should be closely monitored for toxicity [see USE IN SPECIFIC POPULATIONS (8.6)] .

The dialyzability of cyclophosphamide was investigated in four patients on long-term hemodialysis. Dialysis clearance calculated by arterial-venous difference and actual drug recovery in dialysate averaged 104 mL/min, which is in the range of the metabolic clearance of 95 mL/min for the drug. A mean of 37% of the administered dose of cyclophosphamide was removed during hemodialysis.

The elimination half-life (t ½ ) was 3.3 hours in patients during hemodialysis, a 49% reduction of the 6.5 hours to t ½ reported in uremic patients. Reduction in t ½ , larger dialysis clearance than metabolic clearance, high extraction efficiency, and significant drug removal during dialysis, suggest that cyclophosphamide is dialyzable. Hepatic Impairment Total body clearance (CL) of cyclophosphamide is decreased by 40% in patients with severe hepatic impairment… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 32 words ▾

12.2Pharmacodynamics Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function microsomal oxidase system. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells.

🧪 Nonclinical Toxicology 166 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 163 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 10 words ▾

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

📄 Package Label / Principal Display Panel 58 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 25 mg NDC 46708-618-31 Cyclophosphamide Capsules 25 mg CYTOTOXIC AGENT Wear gloves when handling container and capsules. Rx only 100 Capsules Alembic 100 capsules

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 50 mg NDC 46708-619-31 Cyclophosphamide Capsules 50 mg CYTOTOXIC AGENT Wear gloves when handling container and capsules. Rx only 100 Capsules Alembic 100 capsules

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

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
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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
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“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 Alembic Pharmaceuticals Limited. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Alembic Pharmaceuticals Limited 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.
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.
← 46708-0618-31 · Alembic 46708-0620-05 · Alembic →
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.