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FOLOTYN is a brand name for Pralatrexate, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: FOLOTYN® (pralatrexate injection) is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Approval is based on response rates demonstrated in a single-arm trial [see Clinical Trials]. Prolongation of progression-free survival (PFS), overall survival (OS) and…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations FOLOTYN® is for intravenous use only. It should be administered under the supervision of a qualified physician experienced in the use of antineoplastic agents. 2 Recommended Dose and Dosage Adjustment. Monitor complete blood cell counts and severity of mucosal inflammation at baseline and weekly.
2 Recommended Dose and Dosage Adjustment]. Prior to administering any dose of FOLOTYN®: Mucosal inflammation should be ≤ Grade 1. Platelet count should be ≥ 100 x 109/L for first dose and ≥ 50 x 109/L for all subsequent doses. Absolute neutrophil count (ANC) should be ≥ 1 x 109/L.
25 mg orally once daily beginning 10 days before the first dose of FOLOTYN®. Continue folic acid during the full course of therapy and for 30 days after the last dose of FOLOTYN® [see Warnings and Precautions].
Vitamin B12:
Administer vitamin B12 1 mg intramuscularly within 10 weeks prior to the first dose of FOLOTYN® and every 8-10 weeks thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with FOLOTYN® [see Warnings and Precautions].
9% Sodium Chloride Injection, intravenous line once weekly for 6 weeks in 7-week cycles until progressive disease or unacceptable toxicity. The calculated dose of FOLOTYN® should be aseptically withdrawn into a syringe for immediate use.
Do not dilute FOLOTYN®. 73m2), the recommended dose of FOLOTYN® is 15 mg/m2. Health Canada has not authorized an indication for pediatric use. Dose Adjustment Doses may be omitted or reduced based on patient tolerance. Omitted doses should not be made up at the end of the cycle; once a dose reduction occurs for toxicity, do not re-escalate.
For dose modifications and omissions, use the guidelines in Tables 1, 2, and 3. 9% Sodium Chloride Injection. Do not dilute FOLOTYN®. Single use vial. Discard unused portion. 4 Missed Dose Missed/omitted doses should not be made up at the end of the cycle.
2 Clinical Trial Adverse Reactions]. Serious Adverse Events Forty-four percent of patients (n = 49) experienced a serious adverse event while on study or within 30 days after their last dose of FOLOTYN® in the PROPEL study. The most common serious adverse events (≥3%), were pyrexia (7%), febrile neutropenia (5%), sepsis (5%), dehydration (4%), dyspnea (4%), mucosal inflammation (4%), herpes zoster (3%), neutropenia (3%), pneumonia (3%), and thrombocytopenia (3%).
NNOOCC//cc FOLOTYN® (pralatrexate injection) Product Monograph Page 13 of 35 One death from cardiopulmonary arrest in a patient with mucositis and febrile neutropenia was reported in this trial. 2% of patients treated on all FOLOTYN® trials at doses ranging from 30 to 325 mg/m2.
Discontinuations Twenty-three percent of patients (n = 25) in the PROPEL study discontinued treatment with FOLOTYN® due to adverse reactions. The adverse reactions reported most frequently as the reason for discontinuation of treatment were mucosal inflammation (6%, n = 7) and thrombocytopenia (5%, n = 5).
Dose Modifications The target dose of FOLOTYN® was 30 mg/m2 once weekly for 6 weeks in 7-week cycles. Sixty- nine percent (69%, n = 77) of patients in the PROPEL study remained at the target dose for the duration of treatment. Overall, 85% of scheduled doses were administered.
A total of 76 (38%) patients required at least one dose omission mainly due to mucosal inflammation (n = 46; 41%), thrombocytopenia (n = 28; 25%) and neutropenia (n = 14; 13%). Thirty five (32%) patients required a dose reduction; the most common cause was mucosal inflammation (n = 25; 23%).
Other reasons for dose reduction occurring in 2 or more patients were liver function abnormality, thrombocytopenia and fatigue (each n = 2; 2%). 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
General Fatigue was commonly reported in clinical trials with FOLOTYN® but was generally mild to moderate in intensity. If affected, patients should be instructed not to drive cars, use machines or perform hazardous tasks [see Adverse Reactions and Drug Interactions, Drug-Lifestyle Interactions].
Carcinogenesis and Mutagenesis Carcinogenicity studies have not been performed with pralatrexate [see Non-Clinical Toxicology]. Dermatologic Reactions FOLOTYN® can cause severe dermatologic reactions, which may result in death. 1%]) and post marketing experience, and have included skin exfoliation, ulceration, and toxic epidermal necrolysis (TEN).
Serious and potentially life-threatening dermatological reactions have occurred, including fatal cases occurring after the first dose. Patients with extensive skin disease or a history of adverse skin reactions appear to be at higher risk of developing theses severe reactions, with onset occurring early in the course of therapy in most cases.
They may be progressive and increase in severity with further treatment, and may involve skin and subcutaneous sites of known lymphoma. Monitor patients with dermatologic reactions closely, and if severe, withhold or discontinue FOLOTYN® [see Adverse Reactions and Special Populations].
Embryo-Fetal Toxicity FOLOTYN® should not be used during pregnancy, as it can cause fetal harm when administered to a pregnant woman. FOLOTYN® was embryotoxic and fetotoxic in rats and rabbits. If the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the fetus [see Special Populations].
Hepatic Toxicity FOLOTYN® can cause hepatic toxicity and liver function test abnormalities. Persistent liver function test abnormalities may be indicators of hepatic toxicity and require dose modification or discontinuation. Monitor liver function tests.
FOLOTYN® (pralatrexate injection) is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.
FOLOTYN® (pralatrexate injection) is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), has been issued marketing authorization with conditions, pending the results of trials to verify its clinical benefit.
Patients should be advised of the nature of the authorization. For further information for FOLOTYN® please refer to Health Canada’s Notice of Compliance with conditions - drug products web site. NNOOCC//cc NNOOCC//cc FOLOTYN® (pralatrexate injection) Product Monograph Page 6 of 35
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. The safety of FOLOTYN® was evaluated in an open-label, single-arm, multi-center, international trial in 111 patients with relapsed or refractory peripheral T-cell lymphoma.
Patients received a starting dose of 30 mg/m2 once weekly for 6 weeks in 7-week cycles [see Clinical Trials]. The median duration of treatment was 70 days (range 1-540 days). Table 5 - Adverse Events Occurring in ≥10% of Patients in pivotal study PROPEL Adverse Events PROPEL Study (n = 111) Total n (%) Grade 3 n (%) Grade 4 n (%) Any Adverse Events 111 (100) 48 (43) 34 (31) Blood and Lymphatic System Disorders Thrombocytopenia* 45 (41) 15 (14) 21 (19) Anaemia* 38 (34) 17 (15) 2 (2) Neutropenia* 27 (24) 14 (13) 8 (7) Leucopenia* 12 (11) 3 (3) 4 (4) Cardiac Disorders Tachycardia 11 (10) 0 (0) 0 (0) FOLOTYN® (pralatrexate injection) Product Monograph Page 14 of 35 Table 5 - Adverse Events Occurring in ≥10% of Patients in pivotal study PROPEL Adverse Events PROPEL Study (n = 111) Total n (%) Grade 3 n (%) Grade 4 n (%) Gastrointestinal Disorders Nausea 44 (40) 4 (4) 0 (0) Constipation 37 (33) 0 (0) 0 (0) Vomiting 28 (25) 2 (2) 0 (0) Diarrhea 23 (21) 2 (2) 0 (0) Abdominal Pain 13 (12) 4 (4) 0 (0) General Disorders Mucosal Inflammation* 78 (70) 19 (17) 4 (4) Fatigue 40 (36) 5 (5) 2 (2) Pyrexia 36 (32) 1 (1) 1 (1) Oedema* 33 (30) 1 (1) 0 (0) Asthenia 11 (10) 1 (1) 0 (0) Infections and Infestations Upper Respiratory Tract Infection 11 (10) 1 (1) 0 (0) Investigations Liver Function Test Abnormal* 14 (13) 6 (5) 0 (0) Metabolism and Nutrition Disorders Anorexia* 17 (15) 3 (3) 0 (0) Hypokalaemia* 17 (15) 4 (4) 1 (1) Musculoskeletal and Connective Tissue Disorders Pain in Extremities 13 (12) 0 (0) 0 (0) Back Pain 12 (11) 3 (3) 0 (0) Respiratory, Thoracic and Mediastinal Disorders Cough 31 (28) 1 (1) 0 (0) Epistaxis 29 (26) 0 (0) 0 (0) Dyspnoea 21 (19) 8 (7) 0 (0) Pharyngolaryngeal Pain 15 (14) 1 (1) 0 (0) Skin and Subcutaneous Disorders Rash 17 (15) 0 (0) 0 (0) Pruritus* 16 (14) 2 (2) 0 (0) Night Sweats 12 (11) 0 (0) 0 (0) *Grouped preferred terms for the following: Thrombocytopenia (including Platelet Count Decreased) Anaemia (including Haemoglobin Decreased) Oedema (including Oedema Peripheral and Pitting Oedema) FOLOTYN® (pralatrexate injection) Product Monograph Page 15 of 35 Neutropenia (including Neutrophil Count Deceased) Anorexia (including Decreased Appetite) Hypokalaemia (including Blood Potassium Decreased) Pruritus (including Pruritus Generalised) Liver Function Test Abnormal (including Alanine Aminotransferase Increased, Alanine Aminotransferase, Aspartate Aminotransferase Increased, Aspartate Aminotransferase and Transaminases Increased) Leucopenia (including White Blood Cell Count Decreased) Mucosal Inflammation (including Stomatitis Anal Inflammation, Vaginal Inflammation, Rectal Mucositis, Oesophagitis, Mouth Ulceration, Oral Mucosal Erythema, Pharyngeal Inflammation and Pharyngitis) Description of selected Adverse Events in the pivotal PROPEL study Mucosal Inflammation Under the grouped term of mucosal inflammation, 78 patients (70%) had an event, which was the most frequently occurring AE when analyzed by grouping similar preferred terms.
The median time to onset for ≥ Grade 3 […]
Omit dose until recovery, adjust or discontinue therapy based on the severity of the hepatic toxicity [see Dosage and Administration and Special Populations]. NNOOCC//cc FOLOTYN® (pralatrexate injection) Product Monograph Page 10 of 35 Hematologic FOLOTYN® can cause bone marrow suppression, manifested by thrombocytopenia, neutropenia, and/or anemia.
Fatal cases have been reported. 2 Recommended Dose and Dosage Adjustment - Tables 1, 2 and 3. Administer vitamin B12 and instruct patients to take folic acid to reduce the risk of treatment- related hematological toxicity [see Dosage and Administration and Adverse Reactions].
Infection Serious adverse events such as pneumonia, sepsis, septic shock, herpes zoster (including fatal outcomes) have been reported in clinical trials and in the post-market setting with FOLOTYN®. Patients should be carefully monitored during treatment for the emergence of possible infections [see Adverse Reactions].
Monitoring and Laboratory Tests Management of severe or intolerable adverse reactions may require dose omission, reduction, or discontinuation of FOLOTYN® therapy. Monitor complete blood cell counts and severity of mucosal inflammation at baseline and weekly.
Perform serum chemistry tests, including renal and hepatic function, prior to the start of the first and fourth dose of each cycle, or more often if required. Mucosal inflammation FOLOTYN® can cause mucosal inflammation. Fatal cases have been reported.
2 Recommended Dose and Dosage Adjustment - Table 1. Administer vitamin B12 and instruct patients to take folic acid to reduce the risk of mucosal inflammation [see Dosage and Administration and Adverse Reactions]. Renal Acute kidney injury and renal failure have been reported with FOLOTYN® treatment in clinical trials and in the post-market setting.
Monitor renal function tests. Patients with moderate to severe renal function impairment may be at greater risk for increased exposure and toxicity. 2 Recommended Dose and Dosage Adjustment-Tables 1-3. Serious adverse drug reactions including toxic epidermal necrolysis and mucositis were reported in patients with end stage renal disease (ESRD) undergoing dialysis who were administered FOLOTYN® therapy.
Avoid FOLOTYN® use in patients with end stage renal disease including those undergoing dialysis unless the potential benefit justifies the potential risk [see Dosage and Administration, Adverse Reactions, Special Populations, and Clinical Pharmacology].
Respiratory Cases of pulmonary toxicity (including pneumonitis, respiratory failure, and acute respiratory distress syndrome), some with fatal outcomes, have been reported in patients treated with FOLOTYN®. 3%), including 7 patients with PTCL.
Four (4) of the study reports were non-serious. Most cases were considered causally related to pralatrexate. FOLOTYN® (pralatrexate injection) Product Monograph Page 11 of 35 Sexual health Female Patients: Females of childbearing potential must be informed of the potential hazard to the fetus which includes potential birth defects and fetal death (embryotoxicity).
Due to the potential hazard to the fetus, females of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with FOLOTYN®. Adequate contraception should be used while receiving FOLOTYN® and up to 8 weeks after ending treatment.
Male Patients:
It is not known if pralatrexate is present in semen. Male patients must take appropriate precautions to avoid fathering a child during FOLOTYN® treatment. Male patients should use condoms with […]