Pedmarqsi: Uses, Dosage & Side Effects

What Is Pedmarqsi and What Is It Used For?

The active substance in Pedmarqsi is sodium thiosulfate, an inorganic salt (Na₂S₂O₃) that has been used in medicine for more than a century as an antidote for cyanide poisoning and as a treatment for calciphylaxis. In paediatric oncology, its role is entirely different: it acts as a targeted chemoprotectant, a medicine given alongside cisplatin chemotherapy to protect healthy tissues from a specific toxic side effect – in this case, irreversible damage to the sensory hair cells of the inner ear. Pedmarqsi is classified under the ATC code V03AF, which covers detoxifying agents used in antineoplastic treatment, the same broad class as mesna and dexrazoxane.

Cisplatin is one of the most widely used and effective chemotherapy drugs in paediatric oncology, forming the backbone of treatment for many childhood cancers including hepatoblastoma, osteosarcoma, neuroblastoma, germ cell tumours, and medulloblastoma. Although cisplatin is curative for the majority of children with these diseases, it causes dose-dependent, progressive, and permanent sensorineural hearing loss in up to 60–90% of treated children depending on cumulative dose, age, and concurrent treatments. The hearing loss typically begins in the high frequencies that are essential for speech discrimination, language development, and academic performance, and even mild audiometric changes can have profound lifelong consequences for a developing child. Until the approval of Pedmarqsi, there was no licensed pharmacological option to prevent this toxicity, and clinicians relied only on dose modification, audiological monitoring, and hearing aids or cochlear implants after damage had occurred.

Pedmarqsi changes this paradigm by offering, for the first time, an evidence-based pharmacological means of reducing the incidence and severity of cisplatin-induced ototoxicity when administered according to a precisely timed protocol. The medicine received orphan designation in both the European Union and the United States because of the rarity of the conditions in which it is used, and it is marketed under the name Pedmarqsi in Europe (centralised authorisation granted by the European Medicines Agency in 2023) and under the name Pedmark in the United States (approved by the U.S. Food and Drug Administration in September 2022).

How Does Sodium Thiosulfate Protect the Inner Ear?

The exact mechanism by which sodium thiosulfate reduces cisplatin-induced ototoxicity is not fully understood, but two complementary mechanisms are supported by preclinical and clinical evidence. First, sodium thiosulfate is a potent nucleophile that reacts rapidly with platinum ions in the bloodstream to form stable, biologically inactive platinum-thiosulfate complexes. By binding residual unbound cisplatin circulating in plasma at the time of sodium thiosulfate administration, it reduces the amount of free drug available to enter cochlear hair cells. Second, sodium thiosulfate is a reducing agent and radical scavenger, and one of the central mechanisms of cisplatin-induced cochlear damage is the generation of reactive oxygen species (ROS) and oxidative stress within the stria vascularis, outer hair cells, and spiral ganglion. By neutralising these free radicals, sodium thiosulfate helps protect the delicate structures of the inner ear from oxidative injury.

A critical aspect of the protective strategy is the 6-hour delay between the end of cisplatin infusion and the start of sodium thiosulfate. Cisplatin's cytotoxic antitumour effect is driven by rapid intracellular platinum-DNA adduct formation, which occurs during and shortly after the infusion when cisplatin levels are at their peak. By the 6-hour timepoint, intracellular cisplatin binding has largely stabilised and tumour cells have already received the full cytotoxic hit, while the inner ear continues to experience ongoing damage from circulating platinum and secondary oxidative stress. Administering sodium thiosulfate during this window therefore preserves antitumour activity while mitigating late-phase cochlear damage. Administering sodium thiosulfate earlier – or simultaneously with cisplatin – risks directly inactivating cisplatin systemically and reducing anticancer efficacy, which is why the timing must be strictly adhered to.

Approved Indication

Pedmarqsi is approved for the reduction of the risk of ototoxicity induced by cisplatin chemotherapy in paediatric patients aged 1 month to less than 18 years with localised, non-metastatic solid tumours. The indication is deliberately restricted to localised disease because the pivotal trials that demonstrated benefit were conducted in this population, and there remains uncertainty about whether sodium thiosulfate could reduce the anticancer efficacy of cisplatin in patients with disseminated (metastatic) disease. Pedmarqsi is not indicated for adults or for patients with metastatic tumours, and it is not intended for use with carboplatin or other platinum-containing chemotherapies outside of cisplatin regimens.

The tumour types in which cisplatin is most commonly used in children – and therefore the paediatric populations most likely to benefit from Pedmarqsi – include hepatoblastoma (the most common primary liver cancer in children), osteosarcoma (a bone cancer with peak incidence in adolescence), neuroblastoma, germ cell tumours of the gonads or central nervous system, and medulloblastoma. Treatment decisions regarding the use of Pedmarqsi are made by paediatric oncology specialists as part of a multidisciplinary protocol that typically includes surgery, other chemotherapy agents, and often radiation therapy.

Pivotal Clinical Trials

Regulatory approval of Pedmarqsi was supported by two landmark independent clinical trials in children receiving cisplatin. The SIOPEL 6 trial, conducted by the International Childhood Liver Tumours Strategy Group and published in the New England Journal of Medicine in 2018 (Brock et al.), randomised 114 children with standard-risk hepatoblastoma to receive cisplatin alone or cisplatin followed 6 hours later by sodium thiosulfate 20 g/m². The incidence of clinically meaningful hearing loss (Brock grade ≥1) was 63% in the cisplatin-only group compared with 33% in the sodium thiosulfate group, representing an absolute risk reduction of 30 percentage points and a relative risk reduction of approximately 48%. Critically, 3-year event-free survival was 82% in both arms and overall survival was 98% with sodium thiosulfate versus 92% without, confirming that the protective intervention did not compromise cancer control.

The second supporting trial, Children's Oncology Group study ACCL0431, published in the Lancet Oncology in 2017 (Freyer et al.), enrolled 125 children with a broader range of malignancies including hepatoblastoma, osteosarcoma, neuroblastoma, medulloblastoma, and germ cell tumours. In the overall population, sodium thiosulfate reduced the incidence of hearing loss from 56% to 29%. Subgroup analysis revealed that the protective effect was preserved in children with localised disease, while there was a numerical (non-significant) trend toward poorer survival in children with metastatic disease receiving sodium thiosulfate, which is the primary reason the approved indication is restricted to localised tumours. A pooled analysis and long-term follow-up of these trials have continued to confirm the durability of the hearing-protective effect and the acceptability of the safety profile.

What Should You Know Before Your Child Receives Pedmarqsi?

Because Pedmarqsi is administered exclusively to children with cancer receiving cisplatin chemotherapy, the treatment decision is made jointly by paediatric oncologists, pharmacists, audiologists, and the family. This section summarises the key safety considerations that the medical team will discuss with you, so that caregivers understand the precautions taken to protect the child before and during treatment. Pedmarqsi is always given in a hospital or specialised paediatric oncology clinic under close clinical monitoring; it is not intended for home administration.

Contraindications

There are specific situations in which Pedmarqsi must not be administered. Your child's oncologist will review the medical history and current condition carefully to rule out these contraindications before starting treatment.

• Hypersensitivity: Pedmarqsi must not be given to any patient with a known hypersensitivity (allergy) to sodium thiosulfate or to any of the excipients in the formulation. Although hypersensitivity reactions are uncommon, severe allergic reactions have been reported and can include angioedema, bronchospasm, and anaphylaxis.
• Metastatic disease: Pedmarqsi is not indicated, and its use is not recommended, in children with metastatic (disseminated) cancer. This restriction reflects observations from the COG ACCL0431 trial, in which there was a numerical signal of reduced survival in the metastatic subgroup receiving sodium thiosulfate. Until further data are available, the risk-benefit profile is considered acceptable only for localised, non-metastatic tumours.
• Outside the approved age range: Safety and efficacy have not been established in infants younger than 1 month or in adults, and Pedmarqsi is not licensed for these populations.

Warnings and Precautions

Talk to your child's oncologist before each Pedmarqsi dose if any of the following apply:

• Electrolyte abnormalities: Sodium thiosulfate delivers a substantial sodium load and can cause hypernatraemia (high blood sodium). It also promotes urinary loss of potassium and magnesium, which may worsen pre-existing hypokalaemia (low potassium) or hypomagnesaemia (low magnesium) – conditions that are themselves common during cisplatin chemotherapy because cisplatin damages the kidney tubules. Serum sodium, potassium, and magnesium should be measured and abnormalities corrected before each dose, and electrolytes should be rechecked after each administration.
• Heart failure and fluid overload: Because Pedmarqsi delivers a meaningful volume of fluid and a high sodium content, it can precipitate fluid overload, peripheral oedema, and worsening heart failure in children with pre-existing cardiac dysfunction or on restricted fluid or sodium intake.
• Kidney impairment: Sodium thiosulfate is cleared renally. In children with pre-existing renal impairment or cisplatin-induced nephrotoxicity, clearance may be reduced and the risk of electrolyte disturbance increased. Your child's oncologist will assess kidney function before each dose and may adjust fluids or monitoring accordingly.
• Hypertension: The sodium load and fluid volume may transiently increase blood pressure, and pre-existing hypertension should be controlled before administration.
• Sodium-restricted diet: Each 20 ml vial of Pedmarqsi 80 mg/ml contains approximately 280 mg (12.2 mmol) of sodium. This should be taken into account for patients on controlled-sodium diets.

During and after each Pedmarqsi infusion, inform your doctor or nurse immediately if your child experiences:

• Severe nausea, vomiting, or abdominal pain that does not respond to standard anti-emetics
• Shortness of breath, unusually rapid breathing, or persistent cough
• Swelling of the face, lips, tongue, or throat (possible allergic reaction)
• Rash, hives, flushing, or itching
• Unusual tiredness, confusion, muscle cramps, or twitching (possible electrolyte imbalance)
• Palpitations, dizziness, or fainting
• Pain, redness, or swelling at the infusion site

Use in Adolescents, Pregnancy and Breastfeeding

Pedmarqsi is used in children up to the age of 18 years, and adolescents of reproductive potential may be treated within this population. Human data regarding use during pregnancy are limited. Animal studies have not identified major teratogenic risks with sodium thiosulfate, but as with any medicine given during cisplatin chemotherapy, the overall treatment regimen (particularly cisplatin itself) is contraindicated in pregnancy because of the known fetal toxicity of platinum compounds. Sexually active adolescents receiving cisplatin-based chemotherapy must use effective contraception throughout treatment and for the duration recommended by their oncologist.

Breastfeeding is typically contraindicated during cisplatin chemotherapy itself, and this restriction extends to the entire treatment regimen including Pedmarqsi. Lactating patients should discuss feeding options with their care team.

Monitoring During Treatment

Audiological assessment is a cornerstone of care for any child receiving cisplatin. Baseline audiometry should be performed before starting cisplatin and repeated before each cisplatin cycle, at the end of treatment, and during survivorship follow-up. Standardised scales such as the Brock, SIOP Boston, or ASHA grading systems are used to classify the severity of any hearing changes. Pedmarqsi reduces but does not eliminate the risk of hearing loss, and audiometric monitoring therefore remains essential throughout treatment. In very young children who cannot cooperate with behavioural audiometry, auditory brainstem response (ABR) or distortion-product otoacoustic emissions (DPOAE) testing may be used.

Driving and Operating Machinery

For older paediatric patients, Pedmarqsi has not been specifically studied for effects on driving or operating machinery. However, the underlying cancer and cisplatin chemotherapy commonly cause fatigue, nausea, and dizziness, and patients should not drive or operate machinery while affected by these symptoms.

Important Information About Ingredients

Pedmarqsi contains sodium chloride, boric acid, water for injection, and sodium hydroxide or hydrochloric acid (for pH adjustment) in addition to the active substance sodium thiosulfate pentahydrate. Each 20 ml vial delivers approximately 12.2 mmol (280 mg) of sodium, which needs to be considered for patients on a controlled-sodium diet. It also contains boron-containing buffer (boric acid); however, the quantity is within safe limits for paediatric use at the recommended dose. The preparation is preservative-free and intended for single use only.

How Does Pedmarqsi Interact with Other Drugs?

Sodium thiosulfate is a small, hydrophilic inorganic molecule that is cleared rapidly and predominantly unchanged in urine. It does not undergo significant hepatic metabolism, is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes, and is not appreciably bound to plasma proteins. As a result, traditional pharmacokinetic drug-drug interactions mediated by CYP enzymes or protein binding displacement are not expected. The clinically important interactions instead relate to pharmacodynamics and to electrolyte and fluid balance.

Because children receiving Pedmarqsi are simultaneously exposed to several other antineoplastic and supportive medicines, your child's oncologist will carefully review the full medication list before each treatment cycle. This includes prescription medicines, over-the-counter products, vitamins, and any complementary or herbal remedies, all of which should be disclosed to the medical team.

Major Interactions

Minor Interactions

Interactions with other components of multi-agent paediatric chemotherapy regimens (for example, vincristine in SIOPEL protocols or doxorubicin and methotrexate in osteosarcoma regimens) have not shown clinically meaningful pharmacokinetic interference with sodium thiosulfate. However, cumulative toxicities – particularly bone marrow suppression, nephrotoxicity, and ototoxicity – are additive across regimens and must be balanced by the treating oncology team. Always inform your child's medical team about every medicine the child is taking, including short courses of antibiotics, antifungals, and over-the-counter pain relievers.

What Is the Correct Dosage of Pedmarqsi?

Pedmarqsi is always administered by trained healthcare professionals in a hospital or specialised paediatric oncology unit. The dose is individualised based on the child's body weight, and the schedule is tightly coordinated with the cisplatin infusion schedule to preserve the essential 6-hour delay. The paediatric oncology pharmacist prepares each dose by diluting the appropriate volume of Pedmarqsi 80 mg/ml concentrate into a suitable intravenous infusion bag, most commonly sodium chloride 0.9% or dextrose 5%.

Weight-Based Dosing

The approved dosing schedule is stratified by body weight, which reflects the pharmacokinetic differences between younger and older children and ensures adequate plasma concentrations while minimising sodium and fluid load in smaller patients.

Standard Schedule in Relation to Cisplatin

A typical clinical workflow for a cisplatin cycle with Pedmarqsi might look like this: the child receives cisplatin over a 1–6 hour infusion with adequate hydration and anti-emetic prophylaxis. The cisplatin end-of-infusion time is documented. Six hours later, the Pedmarqsi infusion is started and runs over 15 minutes. The child is monitored for blood pressure, heart rate, respiratory rate, temperature, and any infusion-related reactions during and for at least 30–60 minutes after the infusion. Electrolytes are rechecked the following day.

Dose Adjustments

Dose reduction of Pedmarqsi is generally not required for mild or moderate side effects, because the therapeutic effect is tied to adequate plasma concentrations. Instead, supportive measures such as correction of electrolytes, anti-emetics, and fluid management are used. However, in the event of severe hypersensitivity, clinically significant fluid overload, or severe electrolyte disturbances, the treating oncologist may temporarily withhold, dose-reduce, or permanently discontinue Pedmarqsi.

• Cisplatin dose delay or omission: If a cisplatin dose is delayed or skipped, the corresponding Pedmarqsi dose is also withheld. Pedmarqsi is not given as a standalone treatment in the absence of cisplatin.
• Cisplatin dose reduction: The Pedmarqsi dose is based on body weight, not cisplatin dose, so dose reduction of cisplatin does not automatically require Pedmarqsi adjustment.
• Electrolyte disturbances: Pre-dose hypokalaemia, hypomagnesaemia, or hypernatraemia must be corrected before the next Pedmarqsi dose.
• Hypersensitivity reaction: If a mild to moderate hypersensitivity reaction occurs, the infusion may be slowed or temporarily stopped and supportive care given. For severe reactions, Pedmarqsi should be permanently discontinued.

Children and Age Groups

Pedmarqsi is approved for children aged 1 month to less than 18 years. Safety and efficacy in neonates younger than 1 month and in children weighing less than 5 kg have not been established, and use in this group requires individual clinical judgement in consultation with a paediatric oncology pharmacologist. The medicine is not indicated for adults.

Missed Dose

Because Pedmarqsi is administered in a highly controlled inpatient or day-hospital setting, missed doses are rare. If the 6-hour post-cisplatin window is missed for logistical reasons, the medical team will decide whether to administer Pedmarqsi at a later time within an acceptable window or to defer the dose. Caregivers should never attempt to administer Pedmarqsi at home or to reschedule without medical supervision.

Overdose

There is no specific antidote for sodium thiosulfate overdose. Signs of overdose may include severe hypernatraemia with neurologic symptoms (confusion, seizures, coma), volume overload with pulmonary oedema, and severe electrolyte disturbances. Treatment is supportive and includes careful fluid balance, correction of electrolytes, and intensive monitoring; in severe cases, haemodialysis may be considered. Because Pedmarqsi is prepared and administered by trained hospital staff, the risk of clinically relevant overdose is very low.

What Are the Side Effects of Pedmarqsi?

Pedmarqsi is given alongside cisplatin chemotherapy, which itself causes many significant side effects, so distinguishing the effects of each medicine can be challenging. In the pivotal SIOPEL 6 and COG ACCL0431 clinical trials, the overall safety profile of sodium thiosulfate was consistent across both studies, and the side effects considered attributable to Pedmarqsi itself (rather than to cisplatin or the underlying disease) are summarised below.

Side effects are listed by frequency according to the standard MedDRA convention used in European summaries of product characteristics: very common (may affect more than 1 in 10 people), common (up to 1 in 10), uncommon (up to 1 in 100), rare (up to 1 in 1,000), and very rare (up to 1 in 10,000). Most side effects reported with Pedmarqsi are mild to moderate, reversible, and manageable with standard supportive care and electrolyte monitoring.

How Should Pedmarqsi Be Stored?

Proper storage of Pedmarqsi is essential to maintain its stability, sterility, and efficacy. As a hospital-administered medicine, storage is managed by pharmacy staff, but caregivers and families may find the storage requirements useful to understand.

• Unopened vials: Store in a refrigerator at 2–8°C (36–46°F). Keep the vial in the outer carton to protect from light.
• Do not freeze: Freezing can damage the integrity of the solution and must be avoided.
• After dilution: Once diluted into an intravenous infusion bag, the prepared infusion should preferably be used immediately. If not used immediately, in-use storage time and conditions are the responsibility of the user and should follow the detailed instructions in the full Summary of Product Characteristics; typically, storage should not exceed 24 hours refrigerated (2–8°C), protected from light.
• Appearance: The solution is clear and colourless to pale yellow. Do not use if the solution is discoloured, contains visible particles, or if the vial appears damaged.
• Expiry date: Do not use Pedmarqsi after the expiry date printed on the carton and vial (labelled EXP). The expiry date refers to the last day of the stated month.
• Keep out of sight and reach of children outside the clinical setting.

Any unused medicine or waste material should be disposed of in accordance with local regulations for pharmaceutical waste. Healthcare staff are responsible for proper disposal of unused Pedmarqsi.

What Does Pedmarqsi Contain?

Understanding the composition of Pedmarqsi is important for identifying potential allergens, managing sodium intake in children on restricted diets, and ensuring safe administration in the hospital setting.

• Active substance: Sodium thiosulfate (as pentahydrate, Na₂S₂O₃·5H₂O). Each millilitre of solution contains 80 mg of sodium thiosulfate expressed as anhydrous weight; each 20 ml vial delivers 1,600 mg.
• Excipients:
  • Sodium chloride (for tonicity)
  • Boric acid (buffer)
  • Sodium hydroxide and/or hydrochloric acid (for pH adjustment)
  • Water for injection
• Sodium content: Each 20 ml vial contains approximately 12.2 mmol (about 280 mg) of sodium, which is relevant for patients on a controlled-sodium diet.
• Preservatives: Pedmarqsi is preservative-free and intended for single use only.

Appearance: Pedmarqsi is a clear, colourless to slightly yellow solution supplied in a single-use glass vial. The solution should be inspected visually for particulate matter and discoloration prior to administration; any solution that appears abnormal must not be used.

Pack size: Each carton contains one 20 ml single-use vial of Pedmarqsi 80 mg/ml solution for injection.

Marketing authorisation holder: Fennec Pharmaceuticals (through its European and United States subsidiaries). The medicine is marketed under the brand name Pedmarqsi in the European Union and Pedmark in the United States; the active ingredient, strength, and formulation are identical.

Regulatory Status

Pedmarqsi holds orphan drug designation in both the European Union and the United States because of the rarity of childhood cancers treated with cisplatin. It was granted priority review and breakthrough therapy designation by the FDA prior to its September 2022 approval, reflecting the unmet medical need for effective ototoxicity prevention. The European Commission granted centralised marketing authorisation in 2023 following a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the EMA. Post-marketing surveillance and long-term audiological and survival outcomes are being followed through registry studies to confirm the durability of the hearing benefit and to monitor rare adverse effects.