Folotyn

Name: Folotyn

Folotyn Drug Class

Folotyn is part of the drug class:

  • Folic acid analogues

Folotyn Overdose

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Uses of Folotyn

  • It is used to treat a type of lymphoma.
  • It may be given to you for other reasons. Talk with the doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
  • Feeling very tired or weak.
  • Shortness of breath.
  • Pale skin.
  • Swelling.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Use in specific populations

Pregnancy

Pregnancy Category D [see Warnings and Precautions (5.7)]

Embryo-Fetal Toxicity

Folotyn can cause fetal harm when administered to a pregnant woman. Pralatrexate was embryotoxic and fetotoxic in rats at IV doses of 0.06 mg/kg/day (0.36 mg/m2/day or about 1.2% of the clinical dose on a mg/m2 basis) given on gestation days 7 through 20. Treatment with pralatrexate caused a dose-dependent decrease in fetal viability manifested as an increase in late, early, and total resorptions. There was also a dose-dependent increase in post-implantation loss. In rabbits, IV doses of 0.03 mg/kg/day (0.36 mg/m2/day) or greater given on gestation days 8 through 21 also caused abortion and fetal lethality. This toxicity manifested as early and total resorptions, post-implantation loss, and a decrease in the total number of live fetuses. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Nursing Mothers

It is not known whether pralatrexate is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from this drug, a decision should be made whether to discontinue nursing or to discontinue Folotyn, taking into account the importance of Folotyn to the mother.

Pediatric Use

Pediatric patients were not included in clinical studies with Folotyn. The safety and effectiveness of Folotyn in pediatric patients have not been established.

Geriatric Use

In the PTCL efficacy study, 36% of patients (n = 40) were 65 years of age and over. No overall differences in efficacy and safety were observed in patients based on age (< 65 years compared with ≥ 65 years). Due to the contribution of renal excretion to overall clearance of pralatrexate (approximately 34%), age-related decline in renal function may lead to a reduction in clearance and a commensurate increase in plasma exposure. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Since elderly patients may be at higher risk, monitor more closely. Omit dose and subsequently adjust or discontinue therapy for exposure related toxicity [see Dosage and Administration (2.2), Warnings and Precautions (5.5, 5.6), Use in Specific Populations (8.6, 8.7), and Clinical Pharmacology (12.3)].

Hepatic Impairment

The safety, efficacy and pharmacokinetics of Folotyn have not been evaluated in patients with hepatic impairment. Patients with the following laboratory values were excluded from the pralatrexate lymphoma clinical trials: total bilirubin > 1.5 mg/dL; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN); and AST or ALT > 5 × ULN if documented hepatic involvement with lymphoma. Treatment with Folotyn can cause hepatic toxicity and liver function test abnormalities [see Dosage and Administration (2.2) and Warnings and Precautions (5.6)].

Renal Impairment

For patients with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m2), the recommended dose of Folotyn is 15 mg/m2. For patients with mild to moderate renal impairment, dose reduction is not necessary.

Serious adverse drug reactions, including TEN and mucositis have been reported in patients with ESRD undergoing dialysis. Monitor patients for renal function and for systemic toxicity due to increased drug exposure and adjust dosing accordingly. Avoid the use of Folotyn in patients with end stage renal disease undergoing dialysis unless the potential benefit justifies the potential risk [see Dosage and Administration (2.1, 2.2), Warnings and Precautions (5.3, 5.6), Adverse Reactions (6.2), and Clinical Pharmacology (12.3)].

Overdosage

No specific information is available on the treatment of overdosage of Folotyn. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician. Based on Folotyn's mechanism of action, consider the prompt administration of leucovorin.

Folotyn Description

Folotyn (pralatrexate injection) contains pralatrexate, which is an antineoplastic folate analog. Pralatrexate has the chemical name (2S)-2-[[4-[(1RS)-1-[(2, 4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic acid. The structural formula is as follows:

Pralatrexate is a 1:1 racemic mixture of S- and R- diastereomers at the C10 position (indicated with *).

The molecular formula is C23H23N7O5 and the molecular weight is 477.48 g/mol.

Pralatrexate is an off-white to yellow solid. It is soluble in aqueous solutions at pH 6.5 or higher. Pralatrexate is practically insoluble in chloroform and ethanol. The pKa values are 3.25, 4.76, and 6.17.

Folotyn is supplied as a preservative-free, sterile, isotonic, non-pyrogenic clear yellow aqueous parenteral solution contained in a single-dose clear glass vial (Type I) for intravenous administration. Each 1 mL of solution contains 20 mg of pralatrexate, sufficient sodium chloride to achieve an isotonic (280-300 mOsm) solution, and sufficient sodium hydroxide, and hydrochloric acid if needed, to adjust and maintain the pH at 7.5-8.5. Folotyn is supplied as either 20 mg (1 mL) or 40 mg (2 mL) single-dose vials at a concentration of 20 mg/mL.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies have not been performed with pralatrexate.

Mutagenesis

Pralatrexate did not cause mutations in the Ames test or the Chinese hamster ovary cell chromosome aberration assay. Nevertheless, these tests do not reliably predict genotoxicity for this class of compounds. Pralatrexate did not cause mutations in the mouse micronucleus assay.

Impairment of Fertility

No fertility studies have been performed.

Important information

Before you receive Folotyn, tell your doctor if you have kidney disease.

Folotyn can lower blood cells that help your body fight infections and help your blood to clot. You may get an infection or bleed more easily. Call your doctor if you have unusual bruising or bleeding, or signs of infection (fever, chills, body aches).

Do not use Folotyn if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. You should not breast-feed a baby while you are being treated with Folotyn. You may be required to take oral folic acid supplements and receive vitamin B12 injections to help prevent some of the side effects of Folotyn. Follow your doctor's medication instructions very closely.

Folotyn side effects

Get emergency medical help if you have any signs of an allergic reaction to Folotyn: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • bone marrow suppression--fever, chills, cold or flu symptoms, pale skin, easy bruising or bleeding, red or pink urine, painful mouth sores, cough, trouble breathing, feeling light-headed, rapid heart rate;

  • dehydration--feeling very thirsty or hot, are unable to urinate, and have heavy sweating or hot and dry skin;

  • low potassium--confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling);

  • severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common Folotyn side effects may include:

  • nausea, vomiting, loss of appetite, diarrhea, constipation;

  • tired feeling;

  • swelling; or

  • mild rash or itching.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For Healthcare Professionals

Applies to pralatrexate: intravenous solution

Gastrointestinal

Very common (10% or more): Mucositis (70%), nausea (40%), constipation (33%), vomiting (25%), diarrhea (21%), anorexia (15%)[Ref]

Hematologic

Very common (10% or more): Thrombocytopenia (41%), anemia (34%), neutropenia (24%), leukopenia (11%)
Common (1% to 10%): Febrile neutropenia, pancytopenia[Ref]

General

The most common side effects observed in patients with peripheral T-cell lymphoma (PTCL) were mucositis, thrombocytopenia, nausea, and fatigue.[Ref]

Cardiovascular

Very common (10% or more): Edema (30%), tachycardia (10%)
Uncommon (0.1% to 1%): Cardiopulmonary arrest[Ref]

Respiratory

Very common (10% or more): Cough (28%), epistaxis (26%), dyspnea (19%), upper respiratory tract infection (10%)

Metabolic

Very common (10% or more): Hypokalemia (15%)
Common (1% to 10%): Dehydration

Dermatologic

Very common (10% or more): Rash (15%), pruritus (14%)
Frequency not reported: Skin exfoliation, ulceration, toxic epidermal necrolysis

Other

Very common (10% or more): Fatigue (36%), pyrexia (32%), pharyngolaryngeal pain (14%), abdominal pain (12%), pain in extremity (12%), back pain (11%), night sweats (11%), asthenia (10%)

Hepatic

Very common (10% or more): Abnormal liver function tests (13%)

Immunologic

Common (1% to 10%): Sepsis

Some side effects of Folotyn may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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