PEDMARK
Generic: SODIUM THIOSULFATE
Basic Information
Manufacturer
Fennec Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
f98c7076-2a7b-4fd7-ab90-eed5e9137bae
Indications & Usage
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.
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.
Adverse Reactions
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.
6.1 Clinical 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 3.6 Nausea 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 3.6 General 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 ACCL0431.
Table 4.
Adverse Reactions (≥10%) in Patients Who Received PEDMARK and Cisplatin with a Difference Between Arms of >5% Compared to Cisplatin Alone in COG ACCL0431 Adverse Reaction PEDMARK + Cisplatin (N = 59) Cisplatin Alone (N = 64) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Metabolism and nutrition disorders Hypokalemia 27 27 20 20 Hypophosphatemia 20 20 11 11 Hyponatremia 14 12 6 6 Hypernatremia 12 0 6 0 Gastrointestinal disorders Stomatitis 14 14 6 6 6.2 Postmarketing Experience/Spontaneous Reports The following adverse reactions have been identified from spontaneous reports based on medical literature.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiovascular Disorders: hypertension, hypotension Metabolic and Nutritional Disorders: metabolic acidosis, hypocalcemia
( 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.
6.1 Clinical 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 3.6 Nausea 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 3.6 General 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 ACCL0431.
Table 4.
Adverse Reactions (≥10%) in Patients Who Received PEDMARK and Cisplatin with a Difference Between Arms of >5% Compared to Cisplatin Alone in COG ACCL0431 Adverse Reaction PEDMARK + Cisplatin (N = 59) Cisplatin Alone (N = 64) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Metabolism and nutrition disorders Hypokalemia 27 27 20 20 Hypophosphatemia 20 20 11 11 Hyponatremia 14 12 6 6 Hypernatremia 12 0 6 0 Gastrointestinal disorders Stomatitis 14 14 6 6 6.2 Postmarketing Experience/Spontaneous Reports The following adverse reactions have been identified from spontaneous reports based on medical literature.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiovascular Disorders: hypertension, hypotension Metabolic and Nutritional Disorders: metabolic acidosis, hypocalcemia