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PEDMARK SODIUM THIOSULFATE 12.5 g/100mL Injection, Solution — NDC 73077-0010-01 package photo

PEDMARK SODIUM THIOSULFATE 12.5 g/100mL Injection, Solution

by Fennec Pharmaceuticals Inc. · 1 VIAL, SINGLE-DOSE in 1 BOX, UNIT-DOSE (73077-010-01) / 100 mL in 1 VIAL, SINGLE-DOSE
NDC 73077-0010-01
🏷️ FDA NDC (as labeled) 73077-010-01 billing pads the product segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced 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

🆔 Identity & classification

FDA NDC (as labeled) 73077-010-01
Product NDC 73077-010
11-digit billing NDC 73077001001
NCPDP billing unit ML — per mL (volume)
RxCUI 2618749, 2618755
UNII HX1032V43M
Application # NDA212937
SPL Set ID f98c7076-2a7b-4fd7-ab90-eed5e9137bae
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-10-03
Route INTRAVENOUS
Dosage form INJECTION, SOLUTION
Substance SODIUM THIOSULFATE
GPI-14 21757375602020
GCN Seq No 083866
GCN 52939
HICL code 001108
Ingredient (HICL) Sodium Thiosulfate
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1I
Therapeutic class — specific (HIC3) Chemotherapy Rescue/Antidote Agents
AHFS code 91:04.12.00
AHFS class Chemotherapy Antidotes/Protectants
FDB label name PEDMARK 12.5 GRAM/100 ML VIAL
FDB brand name Pedmark
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 73077-010-01 — 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 → 73077-0010-01. 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 Antidotes class.

Drug family (ATC) Antidotes, Gold preparations
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.

🏭 Manufacturer & labeler

LabelerFennec Pharmaceuticals Inc.
Application holderFENNEC PHARMACEUTICALS INC
FDA applicationNDA212937 (NDA)
Labeler code73077
First marketedOct 2022
Product typeHuman Prescription Drug
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.

🩺 Clinical

Label name PEDMARK 12.5 GRAM/100 ML VIAL Ingredient Sodium Thiosulfate
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.

🧪 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 R57ZHV85D4
    Boric acid is a weak acid derived from boron. In medicines, it typically serves as a buffer to help maintain the product's pH level and may act as a preservative in certain formulations.
  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.

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

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

Inactive ingredient FAQ

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

💲 Pricing

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

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo 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 · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J0208 No ASP payment limit on file for J0208 this quarter.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🧾 Billing & reimbursement

FDA NDC (as labeled)73077-010-01
11-digit billing NDC73077-0010-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ0208
DescriptorINJECTION, SODIUM THIOSULFATE, 100 MG
Billing units / pkg1.25 units
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Pedmark 12.5 g/100mLthis 73077-0010-01 Fennec 1 vial — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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
First FDA approval
Sep 2022
📍
2026
Currently FDA-listed
4 years listed
🛡️
2039
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jul 2039. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Sep 20, 2022 RLD RS ⏳ ~12.8 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 11998604 — method of use (U-3952)
US 11992530 — method of use (U-3948)
US 11964018 — method of use (U-3898)
US 10596190 — method of use (U-3443)
US 11617793 — drug product
US 11510984 — drug product
US 11291728 — drug product
Exclusivity ODE-384
2022 2024 2026 2028 2030 2032 2034 2036 2038
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (7)
PatentTypeUse codeExpires
US 11998604 ↗ Method of use U-3952 Jul 1, 2039
US 11992530 ↗ Method of use U-3948 Jul 1, 2039
US 11964018 ↗ Method of use U-3898 Jul 1, 2039
US 10596190 ↗ delist req. Method of use U-3443 Jan 5, 2038
US 11617793 ↗ Drug product — Jul 1, 2039
US 11510984 ↗ Drug product — Jul 1, 2039
US 11291728 ↗ Drug product — Jul 1, 2039
FDA exclusivity
CodeWhat it grantsExpires
ODE-384Orphan Drug Exclusivity (7-year)Sep 20, 2029
Common questions
Is there a generic version of PEDMARK 12.5 GRAM/100 ML VIAL?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for PEDMARK 12.5 GRAM/100 ML VIAL. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jul 2039 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
73077-0010-01 You're viewing this 1 VIAL, SINGLE-DOSE in 1 BOX, UNIT-DOSE (73077-010-01) / 100 mL in 1 VIAL, SINGLE-DOSE 2022-10-03 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) — 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 FDA registers it as 73077-010-01, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 73077-0010-01, written without dashes as 73077001001. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 73077-0010-01, the first segment (73077) is the labeler code FDA assigned to Fennec Pharmaceuticals Inc.; the middle segment (0010) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) identifies this exact package size and type. Together they name one specific package of one specific product.
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 Fennec Pharmaceuticals Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Fennec Pharmaceuticals Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J0208 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. 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 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 145 words ▾

1 INDICATIONS AND USAGE PEDMARK is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. Limitations of Use The safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer than 6 hours. PEDMARK may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred.

PEDMARK is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. ( 1 ) Limitations of Use: The safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer than 6 hours. PEDMARK may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION PEDMARK is not substitutable with other sodium thiosulfate products. ( 2 ) The recommended dose of PEDMARK is based on surface area according to actual body weight. Administer PEDMARK as an intravenous infusion over 15 minutes starting 6 hours after completion of cisplatin infusion.

For multiday cisplatin regimens, administer PEDMARK 6 hours after each cisplatin infusion but at least 10 hours before the next cisplatin infusion. Do not start PEDMARK if less than 10 hours before starting the next cisplatin infusion ( 2 ) Actual Body Weight PEDMARK Dose Less than 5 kg 10 g/m 2 5 to 10 kg 15 g/m 2 Greater than 10 kg 20 g/m 2

2.1Important Dosing Information PEDMARK is not substitutable with other sodium thiosulfate products. Ensure serum sodium level is within normal range prior to initiating PEDMARK [see Warnings and Precautions (5.2) ] .

2.2Recommended Dosage and Administration The recommended dose of PEDMARK is based on surface area according to actual body weight as summarized in Table 1. Table 1. Recommended Dose for PEDMARK Actual Body Weight PEDMARK Dose Less than 5 kg 10 g/m 2 5 to 10 kg 15 g/m 2 Greater than 10 kg 20 g/m 2 Administer PEDMARK as an intravenous infusion over 15 minutes, following cisplatin infusions that are 1 to 6 hours in duration [see Indications and Usage (1) ] .

Infuse PEDMARK as described below to minimize the potential interference with the antitumor activity of cisplatin [see Clinical Pharmacology (12.1) , Clinical Studies (14) ]. Administer PEDMARK 6 hours after completion of a cisplatin infusion. For multiday cisplatin regimens, administer PEDMARK 6 hours after completion of each cisplatin infusion and at least 10 hours before the next cisplatin infusion.

Do not administer PEDMARK if the next cisplatin infusion is scheduled to begin in less than 10 hours [see Clinical Pharmacology (12.3) , Clinical Studies (14) ].

2.3Recommended Premedications Administer antiemetics before each PEDMARK infusion [see Warnings and Precautions (5.3) ] . For patients who experience a hypersensitivity reaction, administer antihistamines and glucocorticoids (if appropriate) before each subsequent PEDMARK infusion [see Warnings and Precautions (5.1) ].

2.4Dosage Modifications for Adverse Reactions The recommended dosage modifications for adverse reactions are provided in Table 2. Table 2. Recommended PEDMARK Dosage Modifications for Adverse Reactions Adverse Reaction Severity Dosage Modification Hypersensitivity [see Warnings and Precautions (5.1) ] Grade 3 or 4 Permanently discontinue PEDMARK.

Hypernatremia [see Warnings and Precautions (5.2) ] >145 mmol/L Withhold PEDMARK until sodium is within normal limits. Resume at the same dose. Hypokalemia [see Warnings and Precautions (5.2) ] Grade 3 or 4 Withhold PEDMARK until potassium is within normal limits.

Resume at the same dose. Other Adverse Reactions [see Adverse Reactions (6.1) ] Grade 3 Withhold until ≤ Grade 1. Resume at the same dose.

Grade 4 Permanently discontinue PEDMARK.

2.5Preparation Calculate the dose (grams) and determine the number of vial(s) needed. Visually inspect the contents of the vial for particulate matter and discoloration. Discard the vial(s) if discolored or contains visible particulates.

Withdraw the calculated dose from the vial(s) into a syringe or transfer the calculated dose into an empty infusion bag. Use immediately after withdrawing into a syringe or transferring to an empty infusion bag. If not used immediately, PEDMARK can be stored in an infusion bag for no more than 18 hours at 20°C to 22°C (68°F to 72°F).

Discard unused portion. No incompatibilities have been observed between PEDMARK with infusion bags made of polyvinyl chloride, ethylene vinyl acetate, or polyolephin.

💊 Dosage Forms and Strengths 29 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 12.5 grams/100 mL (125 mg/mL) clear, colorless solution in a single-dose vial Injection: 12.5 grams/100 mL in a single-dose vial. ( 3 )

⛔ Contraindications 41 words ▾

4 CONTRAINDICATIONS PEDMARK is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or any of its components [see Warnings and Precautions (5.1) ] . History of severe hypersensitivity to sodium thiosulfate or any components. ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Hypersensitivity : Immediately discontinue PEDMARK and institute appropriate care. Administer premedications before each subsequent dose. PEDMARK may contain sodium sulfite; patients with sulfite sensitivity may have hypersensitivity reactions.

( 5.1 ) Hypernatremia and Hypokalemia : PEDMARK is not indicated for use in pediatric patients less than 1 month of age. Monitor serum sodium and potassium at baseline and as clinically indicated. Withhold PEDMARK in patients with serum sodium greater than 145 mmol/L ( 5.2 ) Nausea and Vomiting : Administer antiemetics prior to each PEDMARK administration.

( 5.3 )

5.1Hypersensitivity Hypersensitivity reactions occurred in 8% to 13% of patients in clinical trials [see Adverse Reactions (6.1) ]. PEDMARK is contraindicated in patients with a history of severe hypersensitivity to sodium thiosulfate or its components [see Contraindications (4) ]. Monitor patients for hypersensitivity reactions.

Immediately discontinue PEDMARK and institute appropriate care if a hypersensitivity reaction occurs [see Dosage and Administration (2.4) ] . Administer antihistamines or glucocorticoids (if appropriate) before each subsequent administration of PEDMARK [see Dosage and Administration (2.3) ] . PEDMARK may contain sodium sulfite.

Sulfite exposure can cause hypersensitivity reactions, including anaphylactic symptoms and life-threatening or severe asthma episodes, in patients with sulfite sensitivity. The overall prevalence of sulfite sensitivity in the general population is unknown; sulfite sensitivity is seen more frequently in people with asthma compared to people without asthma.

5.2Hypernatremia and Hypokalemia At the recommended dosage of PEDMARK, a 20 g/m 2 dose delivers a sodium load of 162 mmol/m 2 , a 15 g/m 2 dose delivers a sodium load of 121 mmol/m 2 and a 10 g/m 2 dose delivers a sodium load of 81 mmol/m 2 . Hypernatremia occurred in 12% to 26% of patients in clinical trials, including a single Grade 3 case. Hypokalemia occurred in 15% to 27% of patients in clinical trials, with Grade 3 or 4 occurring in 9% to 27% [see Adverse Reactions (6.1) ].

Pediatric patients younger than 1 month have less well-developed sodium homeostasis compared to other pediatric patients. PEDMARK is not indicated and not recommended for use in pediatric patients younger than 1 month of age. Monitor serum sodium and potassium levels at baseline and as clinically indicated.

Do not initiate PEDMARK infusions in patients with baseline serum sodium greater than 145 mmol/L [see Clinical Pharmacology (12.2) , Dosage and Administration (2.3) ] . Withhold PEDMARK in patients with serum sodium greater than 145 mmol/L [see Clinical Pharmacology (12.2) , Dosage and Administration (2.4) ] . Monitor for signs and symptoms of hypernatremia and hypokalemia.

Provide supportive care and supplementation as appropriate.

5.3Nausea and Vomiting Nausea occurred in 8% to 40% of patients in clinical trials, with Grade 3 or 4 in 3.8 to 8%. Vomiting occurred in 7% to 85% of patients in clinical trials, with Grade 3 or 4 in 7% to 8% [see Adverse Reactions (6.1) ]. Administer antiemetics prior to each PEDMARK administration [see Dosage and Administration (2.3) ] . Provide additional antiemetics and supportive care as appropriate.

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Hypernatremia and Hypokalemia [see Warnings and Precautions (5.2) ] Nausea and Vomiting [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL 6 are vomiting, nausea, decreased hemoglobin, and hypernatremia. ( 6 ) Most common adverse reaction (≥25% with difference between arms of >5% compared to cisplatin alone) in COG ACCL0431 is hypokalemia.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fennec Pharmaceuticals, Inc. at 1-833-336-6321, 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. SIOPEL 6 The safety of PEDMARK was evaluated in SIOPEL 6 [see Clinical Studies (14) ]. Patients received cisplatin-based chemotherapy with or without PEDMARK administered at a dose of 10 g/m 2 , 15 g/m 2 , or 20 g/m 2 (depending on body weight) as an intravenous infusion over 15 minutes starting 6 hours after completion of each cisplatin infusion.

Patients received PEDMARK for a median of 6 cycles (range: 2 to 8 cycles) during a median of 94 days (range: 2.1 to 5.2 months) of cisplatin-based chemotherapy. Serious adverse reactions occurred in 40% of patients who received PEDMARK in combination with cisplatin-based chemotherapy. Serious adverse reactions in >5% of patients who received PEDMARK included infection, decreased neutrophil count, and pyrexia.

PEDMARK was permanently discontinued due to an adverse reaction in 1 patient; this patient discontinued PEDMARK for Grade 2 hypersensitivity. The most common adverse reactions (≥25% with difference between arms of >5% compared to cisplatin alone) were vomiting, nausea, decreased hemoglobin, and hypernatremia. Table 3 summarizes the adverse reactions reported in SIOPEL 6.

Table 3. Adverse Reactions (≥10%) in Patients Who Received PEDMARK and Cisplatin with a Difference Between Arms of >5% Compared to Cisplatin Alone in SIOPEL 6 Adverse Reaction PEDMARK + Cisplatin (N = 53) Cisplatin Alone (N = 56) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Gastrointestinal disorders Vomiting 85 8 54

3.6Nausea 40 3.8 30 5 Investigations Decreased Hemoglobin 34 19 29 16 Metabolism and nutrition disorders Hypernatremia 26 1.9 3.6 0 Hypokalemia 15 9 1.8 0 Hypophosphatemia 15 9 1.8 0 Hypermagnesemia 11 9 5

3.6General disorders Pyrexia 15 0 9 0 COG ACCL0431 The safety of PEDMARK was evaluated in COG ACCL0431 [see Clinical Studies (14) ]. Patients received cisplatin-based chemotherapy with or without PEDMARK, administered at a dose that is bioequivalent to the recommended dose as an intravenous infusion over 15 minutes starting 6 hours after completion of each cisplatin infusion. Patients who received PEDMARK were treated for a median of 3 cycles (range: 1 to 6) during a median of 15 weeks of cisplatin-based chemotherapy.

Serious adverse reactions occurred in 36% of patients who received PEDMARK in combination with cisplatin-based chemotherapy. Serious adverse reactions in >5% of patients who received PEDMARK included febrile neutropenia, decreased neutrophil count, decreased platelet count, decreased white blood cell count, anemia, stomatitis, infections, decreased lymphocyte count, and increased alanine aminotransferase (ALT). PEDMARK was permanently discontinued due to an adverse reaction in 1 patient; this patient discontinued PEDMARK for Grade 2 hypersensitivity.

The most common adverse reaction (≥25% with difference between arms of >5% compared to cisplatin alone) was hypokalemia. Table 4 summarizes the adverse reactions reported in COG…

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS Renal Impairment : Monitor for signs and symptoms of hypernatremia and hypokalemia more closely if the glomerular filtration rate (GFR) falls below 60 mL/min/1.73m 2 . ( 5.2 , 8.6 )

8.1Pregnancy Risk Summary There are no available data on PEDMARK used in pregnant women to evaluate for a drug-associated risk. Oral or intravenous administration of sodium thiosulfate during the period of organogenesis resulted in no signs of malformations or lethality, but at doses and exposures that were lower than those in humans ( see Data ). PEDMARK is administered following cisplatin infusions, which can cause embryo-fetal harm.

Refer to cisplatin prescribing information for additional information. 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 studies, sodium thiosulfate was not embryotoxic or teratogenic in pregnant mice, rats, hamsters, or rabbits at daily (5 to 13 daily doses during the period of organogenesis) oral maternal doses of up to 550, 400, 400, and 580 mg/kg/day (0.08 to 0.35 times the highest clinical dose of 20 g/m 2 based on body surface area [BSA]), respectively, of sodium thiosulfate; exposure in these animals compared to humans may be much lower due to poor oral bioavailability.

Sodium thiosulfate was not embryotoxic or teratogenic in hamsters following a total daily dose of 1500 mg/kg (0.38 times the highest clinical dose of 20 g/m 2 based on BSA). Additionally, an intravenous pharmacokinetic study in gravid ewes indicated that sodium thiosulfate does not cross the placenta.

8.2Lactation There are no data on the presence of sodium thiosulfate in human milk or its effects on the breastfed child or on milk production. PEDMARK is administered in combination with cisplatin. Refer to cisplatin prescribing information for additional information.

8.4Pediatric Use The safety and effectiveness of PEDMARK have been established to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. The safety and effectiveness of PEDMARK have not been established in pediatric patients younger than 1 month old or in pediatric patients with metastatic cancer. PEDMARK is not recommended in pediatric patients younger than 1 month old due to the increased risk of hypernatremia [see Warnings and Precautions (5.2) ] .

8.6Renal Impairment Sodium thiosulfate is substantially excreted by the kidney [see Clinical Pharmacology (12.3) ] . No dose adjustment is recommended for patients with renal impairment or end-stage renal disease. Monitor for signs and symptoms of hypernatremia and hypokalemia more closely if the GFR falls below 60 mL/min/1.73 m 2 [see Warnings and Precautions (5.2) ] .

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary There are no available data on PEDMARK used in pregnant women to evaluate for a drug-associated risk. Oral or intravenous administration of sodium thiosulfate during the period of organogenesis resulted in no signs of malformations or lethality, but at doses and exposures that were lower than those in humans ( see Data ). PEDMARK is administered following cisplatin infusions, which can cause embryo-fetal harm.

Refer to cisplatin prescribing information for additional information. 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 studies, sodium thiosulfate was not embryotoxic or teratogenic in pregnant mice, rats, hamsters, or rabbits at daily (5 to 13 daily doses during the period of organogenesis) oral maternal doses of up to 550, 400, 400, and 580 mg/kg/day (0.08 to 0.35 times the highest clinical dose of 20 g/m 2 based on body surface area [BSA]), respectively, of sodium thiosulfate; exposure in these animals compared to humans may be much lower due to poor oral bioavailability.

Sodium thiosulfate was not embryotoxic or teratogenic in hamsters following a total daily dose of 1500 mg/kg (0.38 times the highest clinical dose of 20 g/m 2 based on BSA). Additionally, an intravenous pharmacokinetic study in gravid ewes indicated that sodium thiosulfate does not cross the placenta.

🧒 Pediatric Use 86 words ▾

8.4Pediatric Use The safety and effectiveness of PEDMARK have been established to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors. The safety and effectiveness of PEDMARK have not been established in pediatric patients younger than 1 month old or in pediatric patients with metastatic cancer. PEDMARK is not recommended in pediatric patients younger than 1 month old due to the increased risk of hypernatremia [see Warnings and Precautions (5.2) ] .

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Cisplatin-induced ototoxicity is caused by irreversible damage to hair cells in the cochlea hypothesized to be due to a combination of reactive oxygen species (ROS) production and direct alkylation of DNA leading to cell death. Sodium thiosulfate interacts directly with cisplatin to produce an inactive platinum species. In addition, sodium thiosulfate can enter cells through the sodium sulfate cotransporter 2 and cause intracellular effects such as the increase in antioxidant glutathione levels and inhibition of intracellular oxidative stress.

Both activities may contribute to the ability of sodium thiosulfate to reduce the risk of ototoxicity. Concurrent incubation of sodium thiosulfate with cisplatin decreased the in vitro cytotoxicity of cisplatin to tumor cells; delaying the addition of sodium thiosulfate to these cultures prevented the protective effect.

12.2Pharmacodynamics Serum Sodium Level A 20 g/m 2 dose delivers a sodium load of 162 mmol/m 2 , a 15 g/m 2 dose delivers a sodium load of 121 mmol/m 2 , and a 10 g/m 2 dose delivers a sodium load of 81 mmol/m 2 . In SIOPEL 6, the recommended dosage resulted in an average transient increase in serum sodium levels of approximately 6 mmol/L at 1 hour after infusion [see Warnings and Precautions (5.2) ] and levels had returned to baseline by 18 hours or 24 hours after administration.

12.3Pharmacokinetics The pharmacokinetics (PK) of thiosulfate was assessed in pediatric patients. At the recommended dosage, the mean (±SD) maximum concentration (C max ) was 13 ± 1.2 mM. The C max of thiosulfate increased proportionally to dose over the range of 4 g/m 2 to 20 g/m 2 .

No accumulation of thiosulfate is expected following administration of PEDMARK on two consecutive days. Distribution Sodium thiosulfate does not bind to human plasma proteins. Sodium thiosulfate is an inorganic salt and thiosulfate anions do not readily cross cell membranes.

The mean volume of distribution of thiosulfate is

0.23L/kg. Elimination The mean half-life (t 1/2 ) of thiosulfate is approximately 20 minutes to 50 minutes. The mean total clearance of thiosulfate is 2.2 mL/min/kg in patients with fully developed renal function (age approximately 1 year).

Renal clearance accounts for approximately 50% of total clearance in patients with fully developed renal function. Metabolism Thiosulfate is an endogenous intermediate product of sulfur-containing amino acid metabolism. Thiosulfate is metabolized through thiosulfate sulfur transferase and thiosulfate reductase to sulfite, which is oxidized to sulfate.

Excretion After administration of sodium thiosulfate, approximately 50% of the administered sodium thiosulfate was excreted unchanged in urine and >95% of the dose excreted in urine occurs within the first 4 hours after administration. Specific Populations Patients with Renal Impairment Thiosulfate C max increased approximately 25% and AUC increased approximately 2-fold in subjects on hemodialysis (GFR 0 to 6 mL/min/1.72 m 2 , estimated by the modification of diet in renal disease [MDRD] equation) compared to subjects with normal renal function (GFR >70 mL/min/1.72 m 2 , MDRD).

Drug Interaction Studies In Vitro Studies Cytochrome P450 Enzymes: Sodium thiosulfate is an inducer of CYP2B6 but not of CYP1A2 or CYP3A4. Sodium thiosulfate is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 at clinically relevant concentrations.

🧬 Mechanism of Action 128 words ▾

12.1Mechanism of Action Cisplatin-induced ototoxicity is caused by irreversible damage to hair cells in the cochlea hypothesized to be due to a combination of reactive oxygen species (ROS) production and direct alkylation of DNA leading to cell death. Sodium thiosulfate interacts directly with cisplatin to produce an inactive platinum species. In addition, sodium thiosulfate can enter cells through the sodium sulfate cotransporter 2 and cause intracellular effects such as the increase in antioxidant glutathione levels and inhibition of intracellular oxidative stress.

Both activities may contribute to the ability of sodium thiosulfate to reduce the risk of ototoxicity. Concurrent incubation of sodium thiosulfate with cisplatin decreased the in vitro cytotoxicity of cisplatin to tumor cells; delaying the addition of sodium thiosulfate to these cultures prevented the protective effect.

📦 How Supplied / Storage and Handling 61 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING PEDMARK (sodium thiosulfate injection) is a clear, colorless, sterile solution in a Type 1 Plus borosilicate glass single-dose vial with rubber stopper and capped with aluminum overseal, supplied as: 12.5 grams/100 mL (125 mg/mL) single-dose vial, NDC 73077-010-01 Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F to 86°F).

📦 Storage and Handling 18 words ▾

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F to 86°F).

📋 Description 147 words ▾

11 DESCRIPTION Sodium thiosulfate anhydrous is an inorganic salt with a molecular formula of Na 2 S 2 O 3 and a molecular weight of 158.11 g/mol. The structural formula is: It is a white to off-white crystalline solid that is soluble in water, but insoluble in alcohol. The aqueous solution has a pH ranging from 6.5 to 8.0.

PEDMARK (sodium thiosulfate injection) is a sterile, preservative-free, clear, colorless solution in a single-dose vial for intravenous use with a pH between 7 and 9. Each vial contains the equivalent of 12.5 grams of sodium thiosulfate pentahydrate (provided as sodium thiosulfate anhydrous 8 grams) in 100 mL solution (125 mg/mL). Each mL contains the equivalent of 125 mg of sodium thiosulfate pentahydrate (provided as sodium thiosulfate anhydrous 80 mg) and 0.25 mg boric acid.

Sodium hydroxide and hydrochloric acid may have been used for pH adjustment. Chemical Structure

💬 Information for Patients 84 words ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Inform patients and caregivers that PEDMARK can cause hypersensitivity reactions [see Warnings and Precautions (5.1) ]. Hypernatremia and Hypokalemia Inform patients and caregivers that PEDMARK can cause hypernatremia and hypokalemia, and to promptly report signs and symptoms consistent with these electrolyte abnormalities [see Warnings and Precautions (5.2) ].

Nausea and Vomiting Inform patients and caregivers that PEDMARK can cause nausea and vomiting [see Warnings and Precautions (5.3) ].

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