Levoleucovorin
Generic: LEVOLEUCOVORIN
Basic Information
Manufacturer
Hikma Pharmaceuticals USA Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
54f01988-aac2-4b0e-9d20-b7f621a0cd50
Indications & Usage
1 INDICATIONS AND USAGE Levoleucovorin for Injection is indicated for: rescue after high-dose methotrexate therapy in adult and pediatric patients with osteosarcoma.
diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination in adult and pediatric patients.
the treatment of adults with metastatic colorectal cancer in combination with fluorouracil.
Limitations of Use Levoleucovorin for Injection is not indicated for pernicious anemia and megaloblastic anemia secondary to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission.
Levoleucovorin for Injection is a folate analog indicated for: Rescue after high-dose methotrexate therapy in adult and pediatric patients with osteosarcoma.
( 1 ) Diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination in adult and pediatric patients.
( 1 ) Treatment of adults with metastatic colorectal cancer in combination with fluorouracil.
( 1 ) Limitations of Use: Levoleucovorin for Injection is not indicated for the treatment of pernicious anemia and megaloblastic anemia secondary to lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission.
( 1 )
diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination in adult and pediatric patients.
the treatment of adults with metastatic colorectal cancer in combination with fluorouracil.
Limitations of Use Levoleucovorin for Injection is not indicated for pernicious anemia and megaloblastic anemia secondary to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission.
Levoleucovorin for Injection is a folate analog indicated for: Rescue after high-dose methotrexate therapy in adult and pediatric patients with osteosarcoma.
( 1 ) Diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination in adult and pediatric patients.
( 1 ) Treatment of adults with metastatic colorectal cancer in combination with fluorouracil.
( 1 ) Limitations of Use: Levoleucovorin for Injection is not indicated for the treatment of pernicious anemia and megaloblastic anemia secondary to lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypercalcemia [see Warnings and Precautions ( 5.1 )] Increased gastrointestinal toxicities with fluorouracil [see Warnings and Precautions ( 5.2 )] The most common adverse reactions (≥20%) in patients receiving high-dose methotrexate therapy with Levoleucovorin for Injection rescue are stomatitis and vomiting.
( 6.1 ) The most common adverse reactions (>50%) in patients receiving Levoleucovorin for Injection in combination with fluorouracil for metastatic colorectal cancer are stomatitis, diarrhea, and nausea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp.
at 1-877-845-0689 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.
High-Dose Methotrexate Therapy Table 2 presents the frequency of adverse reactions which occurred during the administration of 58 courses of high-dose methotrexate 12 grams/m 2 followed by Levoleucovorin for Injection rescue for osteosarcoma in 16 patients aged 6 to 21 years.
Most patients received Levoleucovorin for Injection 7.5 mg every 6 hours for 60 hours or longer, beginning 24 hours after completion of methotrexate administration.
Table 2 Adverse Reactions with High-Dose Methotrexate Therapy Adverse Reactions Levoleucovorin for Injection n = 16 All Grades (%) Grades 3-4 (%) Gastrointestinal Stomatitis 38 6 Vomiting 38 0 Nausea 19 0 Diarrhea 6 0 Dyspepsia 6 0 Typhlitis 6 6 Respiratory Dyspnea 6 0 Skin and Appendages Dermatitis 6 0 Other Confusion 6 0 Neuropathy 6 0 Renal function abnormal 6 0 Taste perversion 6 0 Combination with Fluorouracil in Colorectal Cancer Table 3 presents the frequency of adverse reaction which occurred in 2 arms of a randomized controlled trial conducted by the North Central Cancer Treatment Group (NCCTG) in patients with metastatic colorectal cancer.
The trial failed to show superior overall survival with fluorouracil + levoleucovorin compared to fluorouracil + d,l -leucovorin.
Patients were randomized to fluorouracil 370 mg/m 2 intravenously and levoleucovorin 100 mg/m 2 intravenously, both daily for 5 days, or to fluorouracil 370 mg/m 2 intravenously and d,l -leucovorin 200 mg/m 2 intravenously, both daily for 5 days.
Treatment was repeated week 4 and week 8, and then every 5 weeks until disease progression or unacceptable toxicity.
Table 3 Adverse Reactions Occurring in ≥ 10% of Patients in Either Arm Adverse Reaction Levoleucovorin/fluorouracil n=318 d,l -Leucovorin/fluorouracil n=307 Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%) Gastrointestinal Disorders Stomatitis 72 12 72 14 Diarrhea 70 19 65 17 Nausea 62 8 61 8 Vomiting 40 5 37 6 Abdominal Pain1 14 3 19 3 General Disorders Asthenia/Fatigue/Malaise 29 5 32 11 Skin Disorders Dermatitis 29 1 28 1 Alopecia 26 0.3 28 1 Metabolism and Nutrition Anorexia/Decreased Appetite 24 4 25 2 1 Includes abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness 6.2 Postmarketing Experience The following adverse reaction have been identified during postapproval use of levoleucovorin products.
Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Dermatologic: pruritus, rash Respiratory: dyspnea Other: temperature change, rigors, allergic reactions
( 6.1 ) The most common adverse reactions (>50%) in patients receiving Levoleucovorin for Injection in combination with fluorouracil for metastatic colorectal cancer are stomatitis, diarrhea, and nausea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp.
at 1-877-845-0689 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.
High-Dose Methotrexate Therapy Table 2 presents the frequency of adverse reactions which occurred during the administration of 58 courses of high-dose methotrexate 12 grams/m 2 followed by Levoleucovorin for Injection rescue for osteosarcoma in 16 patients aged 6 to 21 years.
Most patients received Levoleucovorin for Injection 7.5 mg every 6 hours for 60 hours or longer, beginning 24 hours after completion of methotrexate administration.
Table 2 Adverse Reactions with High-Dose Methotrexate Therapy Adverse Reactions Levoleucovorin for Injection n = 16 All Grades (%) Grades 3-4 (%) Gastrointestinal Stomatitis 38 6 Vomiting 38 0 Nausea 19 0 Diarrhea 6 0 Dyspepsia 6 0 Typhlitis 6 6 Respiratory Dyspnea 6 0 Skin and Appendages Dermatitis 6 0 Other Confusion 6 0 Neuropathy 6 0 Renal function abnormal 6 0 Taste perversion 6 0 Combination with Fluorouracil in Colorectal Cancer Table 3 presents the frequency of adverse reaction which occurred in 2 arms of a randomized controlled trial conducted by the North Central Cancer Treatment Group (NCCTG) in patients with metastatic colorectal cancer.
The trial failed to show superior overall survival with fluorouracil + levoleucovorin compared to fluorouracil + d,l -leucovorin.
Patients were randomized to fluorouracil 370 mg/m 2 intravenously and levoleucovorin 100 mg/m 2 intravenously, both daily for 5 days, or to fluorouracil 370 mg/m 2 intravenously and d,l -leucovorin 200 mg/m 2 intravenously, both daily for 5 days.
Treatment was repeated week 4 and week 8, and then every 5 weeks until disease progression or unacceptable toxicity.
Table 3 Adverse Reactions Occurring in ≥ 10% of Patients in Either Arm Adverse Reaction Levoleucovorin/fluorouracil n=318 d,l -Leucovorin/fluorouracil n=307 Grades 1-4 (%) Grades 3-4 (%) Grades 1-4 (%) Grades 3-4 (%) Gastrointestinal Disorders Stomatitis 72 12 72 14 Diarrhea 70 19 65 17 Nausea 62 8 61 8 Vomiting 40 5 37 6 Abdominal Pain1 14 3 19 3 General Disorders Asthenia/Fatigue/Malaise 29 5 32 11 Skin Disorders Dermatitis 29 1 28 1 Alopecia 26 0.3 28 1 Metabolism and Nutrition Anorexia/Decreased Appetite 24 4 25 2 1 Includes abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness 6.2 Postmarketing Experience The following adverse reaction have been identified during postapproval use of levoleucovorin products.
Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Dermatologic: pruritus, rash Respiratory: dyspnea Other: temperature change, rigors, allergic reactions