Folotyn

Folotyn (pralatrexate injection) is an antineoplastic (anti-cancer) drug used to treat T-cell lymphoma that has spread throughout the body. Folotyn is given for relapsed T-cell lymphoma, or after other medications have been tried without successful treatment.

Common side effects of Folotyn include:

• redness or sores of the mouth/lips/throat
• nausea
• vomiting
• loss of appetite
• diarrhea
• constipation
• tired feeling
• fatigue
• cough
• swelling
• mild rash or itching
• constipation
• fever
• swelling
• anemia
• low platelet count.

Serious skin reactions can occur. Tell your doctor if you develop rash, peeling, sores or blisters on the skin while using Folotyn. Tell your doctor if you have unlikely but serious side effects of Folotyn including:

• signs of infection (such as fever, cough, sore throat, chills),
• easy bleeding or bruising,
• dehydration,
• feeling weak,
• looking pale, or
• shortness of breath.

Important Dosing Information

Pretreatment Vitamin Supplementation

Folic Acid

Instruct patients to take folic acid 1 to 1.25 mg orally once daily beginning 10 days before the first dose of Folotyn. Continue folic acid during treatment with Folotyn and for 30 days after the last dose.

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.

Recommended Dosage

The recommended dosage of Folotyn is 30 mg/m² intravenously over 3-5 minutes once weekly for 6 weeks in 7-week cycles until progressive disease or unacceptable toxicity.

Dosage Modifications for Renal Impairment and End Stage Renal Disease

• Severe renal impairment (eGFR 15 to 29 mL/min/1.73 m² by MDRD): Reduce the Folotyn dose to 15 mg/m².
• End stage renal disease (ESRD: eGFR less than 15 mL/min/1.73 m² by MDRD) with or without dialysis: Avoid administration. If the potential benefit of administration justifies the potential risk, monitor renal function and reduce the Folotyn dose based on adverse reactions.

Monitoring and Dosage Modifications for Adverse Reactions

Monitoring

Monitor complete blood cell counts and severity of mucositis 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.

Recommended Dosage Modifications

Do not administer Folotyn until:

• Mucositis Grade 1 or less.
• Platelet of 100,000/mcL or greater for first dose and 50,000/mcL or greater for all subsequent doses.
• Absolute neutrophil count (ANC) of 1,000/mcL or greater. Dosage modifications for adverse reactions are provided in Tables 1, 2, and 3.

Table 1 : Folotyn Dosage Modifications for Mucositis

Table 2 : Folotyn Dosage Modifications for Myelosuppression

Table 3 : Folotyn Dosage Modifications for All Other Adverse Reactions

Effects of Other Drugs on Folotyn

Coadministration of Folotyn with probenecid increased pralatrexate plasma concentrations, which may increase the risk of adverse reactions. Avoid coadministration with probenecid or nonsteroidal anti-inflammatory drugs. If coadministration is unavoidable, monitor for increased risk of adverse reactions.

• Based on findings from animal studies and its mechanism of action, Folotyn can cause fetal harm when administered to a pregnant woman.
• There are insufficient data on Folotyn use in pregnant women to evaluate for a drug-associated risk.
• Folotyn was embryotoxic and fetotoxic in rats and rabbits when administered during organogenesis at doses about 1.2% (0.012 times) of the clinical dose on a mg/m² basis.
• Advise pregnant women of the potential risk to a fetus.
• There is no data on the presence of pralatrexate in human milk or its effects on the breastfed child or milk production.
• Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with Folotyn and for 1 week after the last dose.