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sorafenib 200 mg Tablet, Film Coated, 120-count — NDC 43598-0458-04 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

sorafenib 200 mg Tablet, Film Coated, 120-count — NDC 43598-458-04 (Billing 43598-0458-04)

by Dr.Reddys Laboratories Inc · 120 TABLET, FILM COATED in 1 BOTTLE

This is a package of 120 tablets of sorafenib 200 mg Tablet, Film Coated from Dr.Reddys Laboratories Inc, marketed since Jun 2022 and currently FDA-listed. It is the main listing for this product, which comes in 2 package sizes.

NDC 43598-0458-04
🏷️ FDA NDC (as labeled) 43598-458-04 billing pads the product segment with a zero
This package
Contains120-count Pack sizes2 compare ↓
Also priced by: Part D plans $94.87/unit — full pricing hub ↓
Main listing for product 43598-458 · Also comes in: 360 tablets 43598-458-36
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

NDC database record

One package, one record: these facts belong to NDC 43598-458-04 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
43598 labeler · 458 product · 04 package
Package marketed since
Jun 8, 2022
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
120 EA per package
Barcode (UPC)
0343598458045
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 43598-458-04
Product NDC 43598-458
11-digit billing NDC 43598045804
NCPDP billing unit EA — each (per item)
RxCUI 597747
UNII 5T62Q3B36J
UPC 0343598458045
Application # ANDA216073
SPL Set ID 93f9c3b2-d4c5-80d3-5421-8b4c29fbf8a6
Established class (EPC) Kinase Inhibitor
Mechanism of action Protein Kinase Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-06-08
Route ORAL
Dosage form TABLET, FILM COATED
Substance SORAFENIB TOSYLATE
TE code (Orange Book) AB · RLD · RS

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

GPI-14 21533060400320
GPI class SORAfenib Tosylate
GCN Seq No 060199
GCN 26263
HICL code 033400
Ingredient (HICL) Sorafenib Tosylate
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1Q
Therapeutic class — specific (HIC3) Antineoplastic Systemic Enzyme Inhibitors
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name SORAFENIB 200 MG TABLET
FDB brand name Sorafenib
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 060199
  • GCN: 26263
  • GPI-14 (Medi-Span): 21533060400320
  • HICL (First Databank): 033400
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 597747
Why two NDCs? The FDA registers this code as 43598-458-04 — 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 → 43598-0458-04. 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 Kinase Inhibitor class.

Pharmacologic class Kinase Inhibitor
Drug family (ATC) Other protein kinase inhibitors
How it works Protein Kinase Inhibitors
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 SORAFENIB 200 MG TABLET Ingredient Sorafenib Tosylate
📖 What it is MedlinePlus · NLM

Sorafenib is used to treat advanced renal cell carcinoma (RCC; a type of cancer that begins in the kidneys). Sorafenib is also used to treat hepatocellular carcinoma (a type of liver cancer) that cannot be treated with surgery and a certain type of thyroid cancer that has spread to other parts of the body and cannot be treated with radioactive iodine. Sorafenib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Sorafenib — sold as the brand Nexavar or as a generic — is approved for three specific cancers: liver cancer that can't be surgically removed (hepatocellular carcinoma), advanced k...
  • What cancers does sorafenib actually treat?
  • Yes — it really does. You should take sorafenib on an empty stomach, at least 1 hour before eating or 2 hours after a meal. A high-fat meal can reduce how much of the medicine your...
  • Does it matter if I take sorafenib with food?
📖 Read our full Sorafenib guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

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

Price systemPer 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 $94.87 $11,384.92 / 120 tablets
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
43598-0458-04 You're viewing this Main listing 120 TABLET, FILM COATED in 1 BOTTLE 2022-06-08 — Active
43598-0458-36 43598-458-36 360 TABLET, FILM COATED in 1 BOTTLE 2022-06-08 — Active

You're viewing the smallest of 2 pack sizes for this product.

Pack size FAQ

What quantity is in this package?
This is a 120-count package — 120 tablet, film coated in 1 bottle.
How does this package differ from NDC 43598-0458-36?
Both are sorafenib 200 mg Tablet, Film Coated — the drug itself is identical. This page's package is the 120-count one, while NDC 43598-0458-36 is the 360 tablets package.
What NDC number is used to bill for this package of sorafenib 200 mg Tablet, Film Coated?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Sorafenib Tosylate 200 mg 00378-1201-78 Mylan 120 tablets — AB FDA listed —
Sorafenib 200 mg 00480-5425-89 Teva 120 tablets — AB FDA listed —
Sorafenib 200 mg 13668-0682-12 Torrent 120 tablets — AB FDA listed —
sorafenib 200 mg 24979-0715-04 Upsher-Smith 60 tablets — AB FDA listed —
sorafenib 200 mgthis 43598-0458-04 Dr.Reddys 120 tablets — AB FDA listed —
Nexavar 200 mg 50419-0488-58 Bayer 120 tablets — AB FDA listed —
Nexavar 200 mg 50419-0489-01 Bayer 120 tablets — AB FDA listed —
sorafenib 200 mg 51407-0760-12 Golden 120 tablets — AB FDA listed —
sorafenib 200 mg 51990-0201-06 Yabao 60 tablets — 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
Jun 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.

What it looks like

Color Yellow
ShapeRound
ImprintI
Size1 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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 OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • UNII R75537T0T4
    Hypromellose 2910 is a plant-derived thickening agent made from cellulose. It serves as a binder that holds tablet ingredients together, a film-coating for pills, and a viscosity controller in liquids.
  • UNII 0WZ8WG20P6
    Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII 30IQX730WE
    Polyethylene glycol 6000 is a synthetic polymer made from ethylene glycol units. It acts as a binder, filler, and solubilizer in medicines to help hold ingredients together, add bulk, and improve how well active drugs dissolve and absorb.
  • UNII 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • 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.

10 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

LabelerDr.Reddys Laboratories Inc
Application holderDR REDDYS LABORATORIES LTD
FDA applicationANDA216073 (ANDA)
Labeler code43598
First marketedJun 2022
Product typeHuman Prescription Drug
Portfolio74 products on file

More NDCs from Dr.Reddys Laboratories Inc labeler code 43598

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 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 113 words ▾

1 INDICATIONS AND USAGE Sorafenib is a kinase inhibitor indicated for the treatment of • Unresectable hepatocellular carcinoma ( 1.1 ) • Advanced renal cell carcinoma ( 1.2 ) • Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment ( 1.3 )

1.1Hepatocellular Carcinoma Sorafenib tablets are indicated for the treatment of patients with unresectable hepatocellular carcinoma (HCC).

1.2Renal Cell Carcinoma Sorafenib tablets are indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

1.3Differentiated Thyroid Carcinoma Sorafenib tablets are indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION The recommended dosage is 400 mg orally twice daily without food. ( 2.1 )

2.1Recommended Dosage The recommended dosage of sorafenib tablets is 400 mg orally twice daily without food (at least 1 hour before or 2 hours after a meal) until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity.

2.2Dosage Modifications for Adverse Reactions Recommended Dosage Modifications The recommended dosage modifications for adverse reactions are provided in Tables 1, 2, and 3. Table 1: Recommended Dose Reductions for Adverse Reactions Dose Reduction Hepatocellular Carcinoma and Renal Cell Carcinoma Differentiated Thyroid Carcinoma First Dose Reduction 400 mg orally once daily 400 mg orally in the morning and 200 mg orally in the evening about 12 hours apart OR 200 mg orally in the morning and 400 mg orally in the evening about 12 hours apart Second Dose Reduction 200 mg orally once daily OR 400 every other day 200 mg orally twice daily Third Dose Reduction None 200 mg orally once daily Table 2: Recommended Dosage Modifications of Sorafenib Tablets for Adverse Reactions Adverse Reaction Severity 1 Sorafenib Tablets Dosage Modification Cardiovascular Events [see Warnings and Precautions ( 5.1 )] Cardiac Ischemia and/or Infarction Grade 2 and above Permanently discontinue.

Congestive Heart Failure Grade 3 Interrupt 2 until Grade 1 or less, resume at reduced dose by 1 dose level. 3 Grade 4 Permanently discontinue. Hemorrhage [see Warnings and Precautions ( 5.2 ) ] Grade 2 and above requiring medical intervention Permanently discontinue.

Hypertension [see Warnings and Precautions ( 5.3 )] Grade 2 (symptomatic/persistent) OR Grade 2 symptomatic increase by greater than 20 mm Hg (diastolic) or greater than 140/90 mm Hg if previously within normal limits OR Grade 3 Interrupt until symptoms resolve and diastolic blood pressure less than 90 mm Hg, then resume at reduced dose by 1 dose level. 3 If needed, reduce another dose level. 3 Grade 4 Permanently discontinue.

Gastrointestinal Perforation [see Warnings and Precautions ( 5.5 )] Any grade Permanently discontinue. QT Interval Prolongation [see Warnings and Precautions ( 5.9 )] Greater than 500 milliseconds OR Increase from baseline of 60 milliseconds or greater Interrupt and correct electrolyte abnormalities (magnesium, potassium, calcium). Use medical judgement before restarting.

Drug-Induced Liver Injury [see Warnings and Precautions ( 5.10 )] Grade 3 ALT or higher in the absence of another cause 4 OR AST/ALT greater than 3 × upper limit normal (ULN) with bilirubin greater than 2 × ULN in the absence of another cause 4 Permanently discontinue. Non-hematological toxicities [see Adverse Reactions ( 6.1 )] Grade 2 Continue treatment at reduced dose by 1 dose level. Grade 3 1st occurrence Interrupt until Grade 2 or less, then resume at reduced dose by 1 dose level.

No improvement within 7 days OR 2 nd or 3 rd occurrence Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels. 4 th occurrence Interrupt until Grade 2 or less, then resume at reduced dose by 2 dose levels for HCC and RCC or 3 dose levels for DTC. Grade 4 Permanently discontinue.

1 Adverse reactions graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0). 2 If no recovery after 30 day interruption, discontinue treatment unless the patient is deriving clinical benefit. 3 If more than 2 dose reductions are required, permanently discontinue treatment.

4 In addition, any grade increased alkaline phosphatase in the absence of known bone pathology and Grade 2 or worse increased bilirubin; any 1 of the following: INR of 1.5 or greater, ascites and/or encephalopathy in the absence of underlying cirrhosis or other organ failure considered to be due to drug-induced liver injury. Table 3: Recommended Dosage Modifications for Dermatologic Toxicities Dermatologic Toxicity Grade Occurrence Sorafenib Ta… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 43 words ▾

3 DOSAGE FORMS AND STRENGTHS Sorafenib tablets USP, 200 mg are light yellow to yellow colour, round, biconvex, film-coated tablets debossed with ‘I’ on one side and plain on the other side and free from physical defects. Tablets: 200 mg ( 3 )

⛔ Contraindications 90 words ▾

4 CONTRAINDICATIONS • Sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. • Sorafenib tablets in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer [see Warnings and Precautions ( 5.8 )]. • Sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. ( 4 ) • Sorafenib in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer.

( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Cardiovascular Events : Consider temporary or permanent discontinuation of sorafenib tablets. ( 2.2 , 5.1 ) • Hemorrhage : Discontinue sorafenib tablets if needed. ( 5.2 ) • Hypertension: Monitor blood pressure weekly during the first 6 weeks and periodically thereafter.

Consider temporary or permanent discontinuation for severe or persistent hypertension despite antihypertensive therapy. ( 5.3 ) • Dermatologic Toxicities : Interrupt and/or decrease dose. Discontinue for severe or persistent reactions, or if Stevens-Johnson syndrome and toxic epidermal necrolysis is suspected.

( 5.4 ) • Gastrointestinal Perforation: Discontinue sorafenib tablets. ( 5.5 ) • Risk of Impaired Wound Healing : Withhold sorfenib tablets for at least 10 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing.

The safety of resumption of sorafenib tablets after resolution of wound healing complications has not been established. ( 5.7 ) • QT Prolongation : Monitor electrocardiograms and electrolytes in patients at increased risk for ventricular arrhythmias. Correct electrolytes.

Interrupt if QTc greater than 500 msec or increases greater than 60 msec from baseline. ( 2.2 , 5.9 , 12.2 ) • Drug-Induced Liver Injury : Monitor liver function tests regularly; discontinue for unexplained transaminase elevations. ( 5.10 ) • Embryo-Fetal Toxicity: Sorafenib may cause fetal harm.

Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.11 , 8.1 , 8.3 ) • Impairment of Thyroid Stimulating Hormone Suppression (TSH) in DTC : Monitor TSH monthly and adjust thyroid replacement therapy in patients with thyroid cancer. ( 5.12 )

5.1Cardiovascular Events In the SHARP (HCC) study, the incidence of cardiac ischemia/infarction was 2.7% in sorafenib-treated patients compared with 1.3% in those receiving placebo; in the TARGET (RCC) study, the incidence of cardiac ischemia/infarction was higher in the sorafenib-treated group (2.9%) compared with patients receiving placebo (0.4%), and in the DECISION (DTC) study, the incidence of cardiac ischemia/infarction was 1.9% in the sorafenib-treated group compared with 0% in patients receiving placebo. Patients with unstable coronary artery disease or recent myocardial infarction were excluded from this study.

In multiple clinical trials, congestive heart failure has been reported in 1.9% of sorafenib-treated patients (N=2276) [see Adverse Reactions ( 6.2 )] . Consider temporary or permanent discontinuation of sorafenib tablets in patients who develop cardiovascular events [see Dosage and Administration ( 2.2 )].

5.2Hemorrhage An increased risk of bleeding may occur following sorafenib tablets administration. In the SHARP (HCC) study, the rates of bleeding from esophageal varices (2.4% and 4%) and of bleeding with a fatal outcome from any site (2.4% and 4%) were similar in sorafenib-treated patients and those receiving placebo, respectively. In the TARGET (RCC) study, bleeding was reported in 15.3% of patients in the sorafenib-treated group and 8.2% of patients receiving placebo.

The incidence of Grade 3 and 4 bleeding was 2% and 0%, respectively, in sorafenib-treated patients, and 1.3% and 0.2%, respectively, in those receiving placebo. There was one fatal hemorrhage in each treatment group in the TARGET (RCC) study. In the DECISION (DTC) study, bleeding was reported in 17.4% of sorafenib-treated patients and 9.6% of those receiving placebo; however, the incidence of Grade 3 bleeding was similar (1% and 1.4%) in sorafenib-treated patients and in those receiving placebo.

If any bleeding necessitates medical intervention, consider permanent discontinuation of sorafenib tablets [see Dosage and Administration ( 2.2 )] . Due to the potential risk of bleeding, treat tracheal, bronchial, and esophageal infiltration with local therapy prior to administering sorafenib tablets in patients with DTC.

5.3Hyperten… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in the labeling: • Cardiovascular events [see Warnings and Precautions ( 5.1 )] • Hemorrhage [see Warnings and Precautions ( 5.2 )] • Hypertension [see Warnings and Precautions ( 5.3 )] • Dermatologic toxicities [see Warnings and Precautions ( 5.4 )] • Gastrointestinal perforation [see Warnings and Precautions ( 5.5 )] • QT interval prolongation [see Warnings and Precautions ( 5.9 ) and Clinical Pharmacology ( 12.2 )] • Drug-induced liver injury [see Warnings and Precautions ( 5.10 )] • Impairment of TSH suppression in DTC [see Warnings and Precautions ( 5.12 )] The most common adverse reactions (≥20%) are diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, hypertension, and hemorrhage.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described reflect exposure to sorafenib in 955 patients who participated in placebo-controlled studies in hepatocellular carcinoma (N=297), advanced renal cell carcinoma (N=451), or differentiated thyroid carcinoma (N=207).

The most common adverse reactions (≥20%), which were considered to be related to sorafenib, in patients with HCC, RCC or DTC are diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, hypertension, and hemorrhage. Hepatocellular Carcinoma Table 4 shows the percentage of patients in the SHARP (HCC) study experiencing adverse reactions that were reported in at least 10% of patients and at a higher rate in the sorafenib-treated group than in those receiving placebo.

Table 4: Adverse Reactions Reported in at Least 10% of Patients and at a Higher Rate in Sorafenib Arm than the Placebo Arm – SHARP (HCC) Sorafenib N=297 Placebo N=302 Adverse Reaction 1 All Grades % Grade 3 % Grade 4 % All Grades % Grade 3 % Grade 4 % Any Adverse Reaction 98 39 6 96 24 8 Gastrointestinal Diarrhea 55 10 <1 25 2 0 Anorexia 29 3 0 18 3 <1 Nausea 24 1 0 20 3 0 Vomiting 15 2 0 11 2 0 Constipation 14 0 0 10 0 0 Constitutional symptoms Fatigue 46 9 1 45 12 2 Weight loss 30 2 0 10 1 0 Pain Pain, abdomen 31 9 0 26 5 1 Dermatology/skin Hand-foot skin reaction 21 8 0 3 <1 0 Rash/desquamation 19 1 0 14 0 0 Alopecia 14 0 0 2 0 0 Pruritus 14 <1 0 11 <1 0 Dry skin 10 0 0 6 0 0 Hepatobiliary/pancreas Liver dysfunction 11 2 1 8 2 1 1 Adverse reactions graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v3.0).

Hypertension was reported in 9% of patients treated with sorafenib and 4% of those receiving placebo. Grade 3 hypertension was reported in 4% of sorafenib-treated patients and 1% of those receiving placebo. Hemorrhage/bleeding was reported in 18% of those receiving sorafenib and 20% of patients receiving placebo.

The rates of Grade 3 and 4 bleeding were also higher in patients receiving placebo (Grade 3 – 3% sorafenib and 5% placebo and Grade 4 – 2% sorafenib and 4% placebo). Bleeding from esophageal varices was reported in 2.4% in sorafenib-treated patients and 4% of patients receiving placebo. Renal failure was reported in <1% of patients treated with sorafenib and 3% of patients receiving placebo.

Clinical pancreatitis was reported in 1 of 297 sorafenib-treated patients (Grade 2). The rate of adverse reactions (including those associated with progressive disease) resulting in permanent discontinuation was similar in both the sorafenib-treated patients and those… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 207 words ▾

7 DRUG INTERACTIONS • Strong CYP3A Inducers: Avoid strong CYP3A4 inducers. ( 7.1 )

7.1Effect of Other Drugs on Sorafenib Strong CYP3A4 Inducers The concomitant use of sorafenib with rifampin, a strong CYP3A4 inducer decreased the mean AUC of sorafenib, which may decrease the antitumor activity [see Clinical Pharmacology ( 12.3) ] . Avoid concomitant use of sorafenib with strong CYP3A4 inducers, when possible, because these drugs can decrease the systemic exposure to sorafenib. Neomycin The concomitant use of sorafenib with neomycin decreased the mean AUC of sorafenib, which may decrease the antitumor activity.

Avoid concomitant use of sorafenib with neomycin. The effects of other antibiotics on the pharmacokinetics of sorafenib have not been studied [see Clinical Pharmacology ( 12.3 )] .

7.2Concomitant Use of Warfarin The concomitant use of sorafenib and warfarin may increase the risk of bleeding or increased the INR. Monitor INR and for clinical bleeding episodes in patients taking warfarin while receiving sorafenib tablets [see Warnings and Precautions ( 5.6 )].

7.3Drugs That Prolong the QT Interval Sorafenib is associated with QTc interval prolongation. Avoid coadministration of sorafenib tablets with medicinal products with a known potential to prolong QT/QTc interval [see Warnings and Precautions (5.9), Clinical Pharmacology ( 12.2 )].

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Lactation: Advise women not to breastfeed. ( 8.2 )

8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [ see Clinical Pharmacology ( 12.1 )] , sorafenib may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral administration of sorafenib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than human exposures at the recommended dose of 400 mg twice daily (see Data) .

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The 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 and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In animal reproduction studies, sorafenib was teratogenic and induced embryo-fetal toxicity (including increased post-implantation loss, resorptions, skeletal retardations, and retarded fetal weight) when administered orally to pregnant rats and rabbits during the period of organogenesis. The effects occurred at doses considerably below the recommended human dose of 400 mg twice daily (approximately 500 mg/m 2 /day on a body surface area basis). Adverse intrauterine development effects were seen at doses >0.2 mg/kg/day (1.2 mg/m 2 /day) in rats and ≥0.3 mg/kg/day (≥3.6 mg/m 2 /day) in rabbits.

These doses result in exposures (AUC) that are approximately 0.008 times the AUC in patients at the recommended dose.

8.2Lactation Risk Summary There are no data on the presence of sorafenib or its metabolites in human milk, or its effects on the breast-fed child or on milk production. Sorafenib was present in milk of lactating rats (see Data) . Because of the potential for serious adverse reactions in a breastfed child from sorafenib, advise women not to breastfeed during treatment with sorafenib tablets and for 2 weeks after the last dose.

Data Animal Data Following administration of radiolabeled sorafenib to lactating Wistar rats, approximately 27% of the radioactivity was secreted into milk. The milk to plasma AUC ratio was approximately 5:1.

8.3Females and Males of Reproductive Potential Sorafenib may 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 sorafenib. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of sorafenib tablets.

Males Based on genotoxicity and findings in animal reproduction studies, advise males with female partners of reproductive potential and pregnant partners to use effective contraception during treatment with sorafenib tablets and for 3 months following the last dose of sorafenib tablets [see Use in Specific Populations ( 8.1) , Nonclinical Toxicology ( 13.1 )] . Infertility Males Based on findings in animal studies, sorafenib may impair fertility in males of reproductive potential [see Nonclinical Toxicology ( 13.1 )].

8.4Pediatric Use The safety and effectiveness of sorafenib have not been established in pediatric patients. Juvenile Animal Toxicity Data Repeat dosing of sorafenib to young and growing dogs resulted in irregular thickening of the femoral growth plate at daily sorafenib doses ≥600 mg/m 2 (approximately 0.3 times the AUC at the recommended human dose), hypocellularity of the bone marrow adjoining the growth plate at 200 mg/m 2 /day (approximately 0.1 times the AUC at the recommended human dose), and alterations of the dentin composition at 600 mg/m 2 /day.

Similar effects were not observed in adult… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [ see Clinical Pharmacology ( 12.1 )] , sorafenib may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral administration of sorafenib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than human exposures at the recommended dose of 400 mg twice daily (see Data) .

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. The 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 and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In animal reproduction studies, sorafenib was teratogenic and induced embryo-fetal toxicity (including increased post-implantation loss, resorptions, skeletal retardations, and retarded fetal weight) when administered orally to pregnant rats and rabbits during the period of organogenesis. The effects occurred at doses considerably below the recommended human dose of 400 mg twice daily (approximately 500 mg/m 2 /day on a body surface area basis). Adverse intrauterine development effects were seen at doses >0.2 mg/kg/day (1.2 mg/m 2 /day) in rats and ≥0.3 mg/kg/day (≥3.6 mg/m 2 /day) in rabbits.

These doses result in exposures (AUC) that are approximately 0.008 times the AUC in patients at the recommended dose.

🧒 Pediatric Use 105 words ▾

8.4Pediatric Use The safety and effectiveness of sorafenib have not been established in pediatric patients. Juvenile Animal Toxicity Data Repeat dosing of sorafenib to young and growing dogs resulted in irregular thickening of the femoral growth plate at daily sorafenib doses ≥600 mg/m 2 (approximately 0.3 times the AUC at the recommended human dose), hypocellularity of the bone marrow adjoining the growth plate at 200 mg/m 2 /day (approximately 0.1 times the AUC at the recommended human dose), and alterations of the dentin composition at 600 mg/m 2 /day.

Similar effects were not observed in adult dogs when dosed for 4 weeks or less.

🧓 Geriatric Use 86 words ▾

8.5Geriatric Use In total, 59% of HCC patients treated with sorafenib were age 65 years or older and 19% were 75 and older. In total, 32% of RCC patients treated with sorafenib were age 65 years or older and 4% were 75 and older. No differences in safety or efficacy were observed between older and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

🆘 Overdosage 61 words ▾

10 OVERDOSAGE The adverse reactions observed at a dose of 800 mg twice daily (2 times the recommended dose) were primarily diarrhea and dermatologic. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals. In cases of suspected overdose, withhold sorafenib tablets and institute supportive care.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro . Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, RET/PTC, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis.

Sorafenib inhibited tumor growth of HCC, RCC, and DTC human tumor xenografts in immunocompromised mice. Reductions in tumor angiogenesis were seen in models of HCC and RCC upon sorafenib treatment, and increases in tumor apoptosis were observed in models of HCC , RCC, and DTC.

12.2Pharmacodynamics Cardiac Electrophysiology The effect of sorafenib 400 mg twice daily on the QTc interval was evaluated in a multi-center, open-label, non-randomized trial in 53 patients with advanced cancer. No large changes in the mean QTc intervals (that is, >20 ms) from baseline were detected in the trial. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval, 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2 [see Warnings and Precautions ( 5.9 ), Drug Interactions ( 7.3 )].

12.3Pharmacokinetics Multiple doses of sorafenib for 7 days resulted in a 2.5- to 7-fold accumulation compared to a single dose. Steady-state plasma sorafenib concentrations were achieved within 7 days, with a peak-to-trough ratio of mean concentrations of less than 2. The steady-state concentrations of sorafenib following administration of sorafenib 400 mg twice daily were evaluated in DTC, RCC and HCC patients.

Patients with DTC have mean steady-state concentrations that are 1.8-fold higher than patients with HCC and 2.3-fold higher than those with RCC. The reason for increased sorafenib concentrations in DTC patients is unknown. Mean C max and AUC increased less than proportionally beyond oral doses of 400 mg administered twice daily.

Absorption After administration of sorafenib tablets, the mean relative bioavailability was 38 to 49% when compared to an oral solution. Following oral administration, sorafenib reached peak plasma levels in approximately 3 hours. Effects of Food With a moderate-fat meal (30% fat; 700 calories), bioavailability was similar to that in the fasted state.

With a high-fat meal (50% fat; 900 calories), bioavailability was reduced by 29% compared to that in the fasted state. Distribution In vitro binding of sorafenib to human plasma proteins was 99.5%. Elimination The mean elimination half-life of sorafenib was approximately 25 to 48 hours.

Metabolism Sorafenib undergoes oxidative metabolism by hepatic CYP3A4, as well as glucuronidation by UGT1A9. Excretion Sorafenib accounted for approximately 70 to 85% of the circulating analytes in plasma at steady-state. Eight metabolites of sorafenib have been identified, of which 5 have been detected in plasma.

The main circulating metabolite of sorafenib, the pyridine N-oxide that comprises approximately 9 to 16% of circulating analytes at steady-state, showed in vitro potency similar to that of sorafenib. Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96% of the dose was recovered within 14 days, with 77% of the dose excreted in feces and 19% of the dose excreted in urine as glucuronidated metabolites. Unchanged sorafenib, accounting for 51% of the dose, was found in feces but not in urine.

Specific Populations A study of the pharmacokinetics of sorafenib indicated that the mean AUC of sorafenib in Asians (N=78) was 30% lower than in Whites (N=40). Sex and age do not have a clinically meaningful effect on the pharmacokinetics of sorafenib. Patients with Renal Impairment Mild (CLcr 50 to 80 mL/min), moderate (CLcr 30 to <50 mL/min), and severe (CLcr <30 mL/min) renal impairment do not affect the pharmacokinetics of sorafenib [see Use in Specific Populations ( 8.6 )].

Pati… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 103 words ▾

12.1Mechanism of Action Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro . Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, RET/PTC, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis.

Sorafenib inhibited tumor growth of HCC, RCC, and DTC human tumor xenografts in immunocompromised mice. Reductions in tumor angiogenesis were seen in models of HCC and RCC upon sorafenib treatment, and increases in tumor apoptosis were observed in models of HCC , RCC, and DTC.

📦 How Supplied / Storage and Handling 78 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Sorafenib tablets USP, 200 mg are supplied as light yellow to yellow colour, round, biconvex, film-coated tablets debossed with ‘I’ on one side and plain on the other side and free from physical defects. Bottles of 120 tablets NDC 43598-458-04 Bottles of 360 tablets NDC 43598-458-36 Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store in a dry place.

📋 Description 152 words ▾

11 DESCRIPTION Sorafenib, a kinase inhibitor, is the tosylate salt of sorafenib. Sorafenib tosylate, USP has the chemical name 4-(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N2-methylpyridine-2-carboxamide 4-methylbenzenesulfonate. The molecular formula of sorafenib tosylate, USP is C 21 H 16 ClF 3 N 4 O 3 .C 7 H 8 O 3 S and the molecular weight of sorafenib tosylate, USP is 637.03 grams/mole.

Its structural formula is: Sorafenib tosylate, USP is a white or slightly yellowish or brownish powder. Sorafenib tosylate, USP is soluble in polyethylene glycol 400, slightly soluble in ethanol, and practically insoluble in aqueous media (i.e. water) and in heptane. Sorafenib tablets, USP for oral use are supplied as film-coated tablets containing 200 mg of sorafenib equivalent to 274 mg sorafenib tosylate, USP and the following inactive ingredients: croscarmellose sodium, hypromellose, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium lauryl sulphate, talc and titanium dioxide.

FDA approved dissolution test specifications differ from USP.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read FDA-approved patient labeling (Patient Information). Cardiovascular Events Discuss with patients that cardiac ischemia and/or infarction and congestive heart failure, have been reported during sorafenib treatment, and that they should immediately report any episodes of chest pain or other symptoms of cardiac ischemia or congestive heart failure [ see Warnings and Precautions ( 5.1 )] . Bleeding Inform patients that sorafenib tablets can increase the risk of bleeding and that they should promptly report any episodes of bleeding [see Warnings and Precautions ( 5.2 )].

Inform patients that bleeding or elevations in the International Normalized Ratio (INR) have been reported in some patients taking warfarin while on sorafenib tablets and that their INR should be monitored regularly [see Warnings and Precautions ( 5.6 )]. Hypertension Inform patients that hypertension can develop during sorafenib tablets treatment, especially during the first six weeks of therapy, and that blood pressure should be monitored regularly during treatment [see Warnings and Precautions ( 5.3 )]. Skin Reactions Advise patients of the possible occurrence of hand-foot skin reaction and rash during sorafenib tablets treatment and appropriate counter measures [see Warnings and Precautions ( 5.4 )].

Gastrointestinal Perforation Advise patients that cases of gastrointestinal perforation have been reported in patients taking sorafenib tablets [see Warnings and Precautions ( 5.5 )]. Risk of Impaired Wound Healing Advise patients that sorafenib tablets may impair wound healing. Advise patients to inform their healthcare provider of any planned surgical procedure [see Warnings and Precautions ( 5.7 )].

QT Interval Prolongation Inform patients with a history of prolonged QT interval that sorafenib tablets can worsen the condition [ see Warnings and Precautions ( 5.9 ) and Clinical Pharmacology ( 12.2 )]. Drug-Induced Liver Injury Inform patients that sorafenib tablets can cause hepatitis which may result in hepatic failure and death. Advise patients that liver function tests should be monitored regularly during treatment and to report signs and symptoms of hepatitis [see Warnings and Precautions ( 5.10 )].

Embryo-Fetal Toxicity Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to a fetus and potential loss of pregnancy [see Use in Specific Populations ( 8.1 )]. Advise females of reproductive potential to use effective contraception during treatment with sorafenib tablets and for 6 months after the last dose.

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment with sorafenib tablets and for 3 months after receiving the last dose of sorafenib tablets [see Warnings and Precautions ( 5.11 ), Use in Specific Populations ( 8.1, 8.3 )]. Lactation Advise patients not to breastfeed while taking sorafenib tablets and for 2 weeks after receiving the last dose of sorafenib tablets [see Use in Specific Populations ( 8.2 ) ]. Missed Doses Instruct patients that if a dose of sorafenib tablets is missed, the next dose should be taken at the regularly scheduled time, and not double the dose.

Instruct patients to contact their healthcare provider immediately if they take too much sorafenib tablets. Rx only Distributor: Dr. Reddy’s Laboratories Inc., Princeton, NJ 08540 Made in India Revised: 12/2024

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Multiple doses of sorafenib for 7 days resulted in a 2.5- to 7-fold accumulation compared to a single dose. Steady-state plasma sorafenib concentrations were achieved within 7 days, with a peak-to-trough ratio of mean concentrations of less than 2. The steady-state concentrations of sorafenib following administration of sorafenib 400 mg twice daily were evaluated in DTC, RCC and HCC patients.

Patients with DTC have mean steady-state concentrations that are 1.8-fold higher than patients with HCC and 2.3-fold higher than those with RCC. The reason for increased sorafenib concentrations in DTC patients is unknown. Mean C max and AUC increased less than proportionally beyond oral doses of 400 mg administered twice daily.

Absorption After administration of sorafenib tablets, the mean relative bioavailability was 38 to 49% when compared to an oral solution. Following oral administration, sorafenib reached peak plasma levels in approximately 3 hours. Effects of Food With a moderate-fat meal (30% fat; 700 calories), bioavailability was similar to that in the fasted state.

With a high-fat meal (50% fat; 900 calories), bioavailability was reduced by 29% compared to that in the fasted state. Distribution In vitro binding of sorafenib to human plasma proteins was 99.5%. Elimination The mean elimination half-life of sorafenib was approximately 25 to 48 hours.

Metabolism Sorafenib undergoes oxidative metabolism by hepatic CYP3A4, as well as glucuronidation by UGT1A9. Excretion Sorafenib accounted for approximately 70 to 85% of the circulating analytes in plasma at steady-state. Eight metabolites of sorafenib have been identified, of which 5 have been detected in plasma.

The main circulating metabolite of sorafenib, the pyridine N-oxide that comprises approximately 9 to 16% of circulating analytes at steady-state, showed in vitro potency similar to that of sorafenib. Following oral administration of a 100 mg dose of a solution formulation of sorafenib, 96% of the dose was recovered within 14 days, with 77% of the dose excreted in feces and 19% of the dose excreted in urine as glucuronidated metabolites. Unchanged sorafenib, accounting for 51% of the dose, was found in feces but not in urine.

Specific Populations A study of the pharmacokinetics of sorafenib indicated that the mean AUC of sorafenib in Asians (N=78) was 30% lower than in Whites (N=40). Sex and age do not have a clinically meaningful effect on the pharmacokinetics of sorafenib. Patients with Renal Impairment Mild (CLcr 50 to 80 mL/min), moderate (CLcr 30 to <50 mL/min), and severe (CLcr <30 mL/min) renal impairment do not affect the pharmacokinetics of sorafenib [see Use in Specific Populations ( 8.6 )].

Patients with Hepatic Impairment Mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment do not affect the pharmacokinetics of sorafenib [see Use in Specific Populations ( 8.7 )] . Drug Interactions Studies Effect of Strong CYP3A4 Inhibitors on Sorafenib: Ketoconazole, a strong inhibitor of CYP3A4 and P-glycoprotein, administered at a dose of 400 mg once daily for 7 days did not alter the mean AUC of a single oral dose of sorafenib 50 mg in healthy subjects. Effect of Strong CYP3A4 Inducers on Sorafenib: Concomitant use of sorafenib with rifampin administered at a dose of 600 mg once daily for 5 days with a single oral dose of sorafenib 400 mg in healthy volunteers resulted in a 37% decrease in the mean AUC of sorafenib.

Effect of Neomycin on Sorafenib: Neomycin administered as an oral dose of 1 gram three times daily for 5 days decreased the mean AUC of sorafenib by 54% in healthy subjects administered a single oral dose of sorafenib 400 mg. Effect of Sorafenib on Other Drugs : Sorafenib 400 mg twice daily for 28 days did not increase the systemic exposure of concomitantly administered midazolam (CYP3A4 substrate), dextromethorphan (CYP2D6 substrate), and omeprazole (CYP2C19 substrate) [see Clinical Pharmacology ( 12.3 )]. Drugs that Increase Ga… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 96 words ▾

12.2Pharmacodynamics Cardiac Electrophysiology The effect of sorafenib 400 mg twice daily on the QTc interval was evaluated in a multi-center, open-label, non-randomized trial in 53 patients with advanced cancer. No large changes in the mean QTc intervals (that is, >20 ms) from baseline were detected in the trial. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval, 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2 [see Warnings and Precautions ( 5.9 ), Drug Interactions ( 7.3 )].

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Hepatocellular Carcinoma The SHARP (HCC) study (NCT00105443) was an international, multicenter, randomized, double blind, placebo-controlled trial in patients with unresectable hepatocellular carcinoma. Overall survival was the primary endpoint. A total of 602 patients were randomized; 299 to sorafenib 400 mg twice daily and 303 to matching placebo.

All 602 randomized subjects were included in the ITT population for the efficacy analyses. Demographics and baseline disease characteristics were similar between the sorafenib and placebo arms with regard to age, gender, race, performance status, etiology (including hepatitis B, hepatitis C and alcoholic liver disease), TNM stage (stage I: <1% vs. <1%; stage II: 10.4% vs. 8.3%; stage III: 37.8% vs.

43.6%; stage IV: 50.8% vs. 46.9%), absence of both macroscopic vascular invasion and extrahepatic tumor spread (30.1% vs. 30%), and Barcelona Clinic Liver Cancer stage (stage B: 18.1% vs.

16.8%; stage C: 81.6% vs. 83.2%; stage D: <1% vs. 0%).

Liver impairment by Child-Pugh score was comparable between the sorafenib and placebo arms (Class A: 95% vs. 98%; B: 5% vs. 2%).

Only one patient with Child-Pugh class C was entered. Prior treatments included surgical resection procedures (19.1% vs. 20.5%), locoregional therapies (including radiofrequency ablation, percutaneous ethanol injection and transarterial chemoembolization; 38.8% vs.

40.6%), radiotherapy (4.3% vs. 5%) and systemic therapy (3% vs. 5%).

The trial was stopped for efficacy following a pre-specified second interim analysis for survival showing a statistically significant advantage for sorafenib over placebo for overall survival (HR: 0.69, p=0.00058) (see Table 10 and Figure 1). This advantage was consistent across all subsets analyzed. Final analysis of time to tumor progression (TTP) based on data from an earlier time point (by independent radiologic review) also was significantly longer in the sorafenib arm (HR: 0.58, p=0.000007) (see Table 10).

Table 10: Efficacy Results from SHARP (HCC) Efficacy Parameter Sorafenib (N=299) Placebo (N=303) Overall Survival Number of Events 143 178 Median, months 10.7 7.9 (95% CI) (9.4, 13.3) (6.8, 9.1) Hazard Ratio 1 (95% CI) 0.69 (0.55, 0.87) P-value (log-rank test 2 ) 0.00058 Time to Progression 3 Number of Events 107 156 Median, months 5.5 2.8 (95% CI) (4.1, 6.9) (2.7, 3.9) Hazard Ratio 1 (95% CI) 0.58 (0.45, 0.74) P-value (log-rank test 2 ) 0.000007 CI=Confidence interval 1 Hazard ratio, sorafenib/placebo, stratified Cox model 2 Stratified log rank (for the interim analysis of survival, the stopping boundary one-sided alpha = 0.0077) 3 The time-to-progression (TTP) analysis, based on independent radiologic review, was based on data from an earlier time point than the survival analysis Figure 1: Kaplan-Meier Curve of Overall Survival in SHARP (HCC) (Intent-to-Treat Population)

14.2Renal Cell Carcinoma The safety and efficacy of sorafenib in the treatment of advanced renal cell carcinoma (RCC) were studied in the following two randomized controlled clinical trials. TARGET TARGET (NCT00073307) was an international, multicenter, randomized, double blind, placebo-controlled trial in patients with advanced renal cell carcinoma who had received one prior systemic therapy. Primary study endpoints included overall survival and progression-free survival (PFS).

Tumor response rate was a secondary endpoint. The PFS analysis included 769 patients, per protocol, stratified by MSKCC (Memorial Sloan Kettering Cancer Center) prognostic risk category (low or intermediate) and country and randomized to sorafenib 400 mg twice daily (N=384) or to placebo (N=385). Table 11 summarizes the demographic and disease characteristics of the study population analyzed.

Baseline demographics and disease characteristics were well balanced for both treatment groups. The median time from initial diagnosis of RCC to randomization was 1.6 and 1.9 years for the sorafenib and placebo arms, respectively… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been performed with sorafenib. Sorafenib was clastogenic when tested in an in vitro mammalian cell assay (Chinese hamster ovary) in the presence of metabolic activation. Sorafenib was not mutagenic in the in vitro Ames bacterial cell assay or clastogenic in an in vivo mouse micronucleus assay.

One intermediate in the manufacturing process, which is also present in the final drug substance (<0.15%), was positive for mutagenesis in an in vitro bacterial cell assay (Ames test) when tested independently. No specific studies with sorafenib have been conducted in animals to evaluate the effect on fertility. However, results from the repeat-dose toxicity studies suggest there is a potential for sorafenib to impair reproductive function and fertility.

Multiple adverse effects were observed in male and female reproductive organs, with the rat being more susceptible than mice or dogs. Typical changes in rats consisted of testicular atrophy or degeneration, degeneration of epididymis, prostate, and seminal vesicles, central necrosis of the corpora lutea and arrested follicular development. Sorafenib-related effects on the reproductive organs of rats were manifested at daily oral doses ≥5 mg/kg (30 mg/m 2 ).

This dose results in an exposure (AUC) that is approximately 0.5 times the AUC in patients at the recommended human dose. Dogs showed tubular degeneration in the testes at 30 mg/kg/day (600 mg/m 2 /day). This dose results in an exposure that is approximately 0.3 times the AUC at the recommended human dose.

Oligospermia was observed in dogs at 60 mg/kg/day (1,200 mg/m 2 /day) of sorafenib.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been performed with sorafenib. Sorafenib was clastogenic when tested in an in vitro mammalian cell assay (Chinese hamster ovary) in the presence of metabolic activation. Sorafenib was not mutagenic in the in vitro Ames bacterial cell assay or clastogenic in an in vivo mouse micronucleus assay.

One intermediate in the manufacturing process, which is also present in the final drug substance (<0.15%), was positive for mutagenesis in an in vitro bacterial cell assay (Ames test) when tested independently. No specific studies with sorafenib have been conducted in animals to evaluate the effect on fertility. However, results from the repeat-dose toxicity studies suggest there is a potential for sorafenib to impair reproductive function and fertility.

Multiple adverse effects were observed in male and female reproductive organs, with the rat being more susceptible than mice or dogs. Typical changes in rats consisted of testicular atrophy or degeneration, degeneration of epididymis, prostate, and seminal vesicles, central necrosis of the corpora lutea and arrested follicular development. Sorafenib-related effects on the reproductive organs of rats were manifested at daily oral doses ≥5 mg/kg (30 mg/m 2 ).

This dose results in an exposure (AUC) that is approximately 0.5 times the AUC in patients at the recommended human dose. Dogs showed tubular degeneration in the testes at 30 mg/kg/day (600 mg/m 2 /day). This dose results in an exposure that is approximately 0.3 times the AUC at the recommended human dose.

Oligospermia was observed in dogs at 60 mg/kg/day (1,200 mg/m 2 /day) of sorafenib.

📄 Patient Package Insert ~3 min read ▾

Patient Information Sorafenib (soe raf' e nib) Tablets, USP oral What is sorafenib tablet? Sorafenib tablet is a prescription medicine used to treat: • a type of liver cancer called hepatocellular carcinoma (HCC) that cannot be removed by surgery • a type of kidney cancer called renal cell carcinoma (RCC) • a type of thyroid cancer called differentiated thyroid carcinoma (DTC) that can no longer be treated with radioactive iodine and is progressing It is not known if sorafenib tablets are safe and effective in children.

Do not take sorafenib tablets if you: • are allergic to sorafenib or any of the other ingredients in sorafenib tablets. See the end of this leaflet for a complete list of ingredients in sorafenib tablets. • have squamous cell lung cancer and receive carboplatin and paclitaxel. Before taking sorafenib tablets, tell your healthcare provider about all of your medical conditions including if you: • have heart problems including a condition called “congenital long QT syndrome” • have chest pain have abnormal magnesium, potassium, or calcium blood levels • have bleeding problems • have high blood pressure • plan to have surgery or have had a recent surgery.

You should stop taking sorafenib tablets at least 2 weeks before planned surgery. See “What are the possible side effects of sorafenib tablets?” • are pregnant or plan to become pregnant. Sorafenib may harm your unborn baby.

Tell your healthcare provider right away if you become pregnant during treatment with sorafenib tablets. For females who are able to become pregnant: • Your healthcare should do a pregnancy test before you start treatment with sorafenib tablets. • Use effective birth control (contraception) during your treatment with sorafenib tablets and for 6 months after the last dose of sorafenib tablets. For males with female partners who are able to become pregnant: • Use effective birth control (contraception) during your treatment with sorafenib tablets and for 3 months after the last dose of sorafenib tablets. • are breastfeeding or plan to breastfeed.

It is not known if sorafenib passes into your breast milk. Do not breastfeed during treatment with sorafenib tablets and for 2 weeks after receiving the last dose of sorafenib tablets. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Especially tell your healthcare provider if you take the medicine warfarin. How should I take sorafenib tablets? • Take sorafenib tablets exactly as your healthcare provider tells you to take it. • Take sorafenib tablets 2 times a day. Your healthcare provider may change your dose, temporarily stop treatment or completely stop treatment with sorafenib tablets if you have side effects. • Take sorafenib tablets without food (at least 1 hour before or 2 hours after a meal). • If you miss a dose of sorafenib tablets, skip the missed dose, and take your next dose at your regular time.

Do not double your dose of sorafenib tablets. • If you take too much sorafenib tablets call your doctor or go to the nearest hospital emergency room right away. What are the possible side effects of sorafenib tablets? Sorafenib tablets may cause serious side effects, including: • decreased blood flow to the heart, heart attack and heart failure.

Get emergency help right away if you get symptoms such as chest pain, shortness of breath, racing heartbeat, swelling in lower legs, feet and abdomen, feel lightheaded or faint, tiredness, nausea, vomiting, or sweat a lot. • increased risk of bleeding. Bleeding is a common side effect of sorafenib tablets that can be serious and can lead to death. Tell your healthcare provider right away if you have any signs of bleeding during treatment with sorafenib tablets: • vomiting blood or if your vomit looks like coffee-grounds • heavier than normal menstrual cycle • pink or brown urine • unusual vaginal bleeding • red or black (looks like tar) stools • frequent… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 28 words ▾

PACKAGE LABEL PRINCIPAL DISPLAY PANEL SECTION Sorafenib Tablets, 200 mg - 120's Count Container Label Unvarnished Area Consists of: 2D Barcode, Lot Number, Expiry Date and Serial Number

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 Sorafenib — the program that covers self-administered drugs. 5 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 Sorafenib. 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
$3.4M
Claims incl. refills
592
Beneficiaries
285
Spend / beneficiary
$11,930.60
Spend / claim
$5,743.62
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 ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“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 Dr.Reddys Laboratories Inc. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 360 tablets (43598-0458-36). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Dr.Reddys Laboratories 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.
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.
← 43598-0457-30 · Dr.Reddys 43598-0459-01 · Dr.Reddys →
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.