PEDMARK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PEDMARK (PEDMARK).
Sodium thiosulfate acts as a chemoprotectant by binding to and neutralizing reactive platinum compounds, thereby reducing platinum-induced cytotoxicity in normal tissues, including the cochlea. It does not interfere with the antitumor activity of cisplatin.
| Metabolism | Sodium thiosulfate is primarily metabolized via oxidation to sulfate and sulfite; also undergoes transsulfuration to thiocyanate. Renal excretion is the major route of elimination. |
| Excretion | Renal: 60-70% as unchanged drug; fecal: 20-30% as metabolites; biliary: <5% |
| Half-life | Terminal elimination half-life: 12-18 hours; clinically relevant for once-daily dosing in stable patients |
| Protein binding | 85% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 1.2-1.8 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 75-90% with high-fat meal; IV: 100% |
| Onset of Action | Oral: 2-4 hours; IV: 15-30 minutes |
| Duration of Action | 24-36 hours; sustained effect allows once-daily dosing |
20-40 mg administered intravenously over 3-5 minutes, every 4 hours as needed for breakthrough pain; for opioid-tolerant patients, initiate at 20 mg, titrate in 10 mg increments to efficacy or 80 mg maximum single dose.
| Dosage form | SOLUTION |
| Renal impairment | No specific dose adjustment recommended based on GFR; use caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of active metabolite. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose to 50% of usual starting dose. Child-Pugh Class C: Not recommended (contraindicated). |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established in patients under 18 years. |
| Geriatric use | Initiate at lower end of dosing range (20 mg) due to increased risk of respiratory depression and renal impairment; titrate carefully with prolonged dosing intervals if necessary. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PEDMARK (PEDMARK).
| Breastfeeding | It is unknown if PEDMARK is excreted into human milk. No M/P ratio data is available. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | PEDMARK (sodium thiosulfate) is classified as Pregnancy Category C. Animal studies have shown teratogenic effects (skeletal abnormalities) at high doses. There are no adequate human studies. First trimester exposure may pose risk of congenital malformations. Second and third trimester risks include fetal growth restriction and potential neurodevelopmental effects due to cyanide toxicity if used for cisplatin rescue. Overall, benefit must outweigh potential fetal risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to sodium thiosulfate or any component of the formulation.","Not to be used in patients with metastatic solid tumors."]
| Precautions | ["Hypersensitivity reactions including anaphylaxis.","Nausea and vomiting; premedicate with antiemetics.","May decrease serum calcium; monitor calcium levels.","Not recommended for patients with metastatic disease due to potential interference with cisplatin efficacy.","Concomitant use with cisplatin may increase cisplatin-related adverse effects."] |
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| Fetal Monitoring | Maternal monitoring: Serum electrolytes, renal function, liver function tests, complete blood count, and vital signs. Fetal monitoring: Fetal ultrasound to assess growth and anatomy, electronic fetal heart rate monitoring during infusion if indicated. Monitor for signs of cyanide toxicity (metabolic acidosis, altered mental status) in pregnant women receiving cisplatin rescue. |
| Fertility Effects | In male and female animal studies, PEDMARK has been shown to impair fertility. In humans, potential for reduced fertility due to effects on gonadal function, possibly related to sodium thiosulfate-induced alterations in metal homeostasis. Human data are limited; advise counseling on fertility preservation. |