FOLOTYN Solution for injection Ref.[10174] Active ingredients: Pralatrexate

2.1 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 [see Warnings and Precautions (5.1, 5.2)].

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 (5.1, 5.2)].

2.2 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.

2.3 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 [see Use in Specific Populations (8.6)].
• 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 [see Warnings and Precautions (5.6), Use in Specific Populations (8.6)].

2.4 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.

2.4.101 SPL UNCLASSIFIED SECTION

Recommended Dosage Modifications

• 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 Dose Modifications for Mucositis:

^a Based National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0)

Table 2. FOLOTYN Dosage Modifications for Myelosuppression:

G-CSF=granulocyte colony-stimulating factor; GM-CSF=granulocyte macrophage colony-stimulating factor

Table 3. FOLOTYN Dosage Modifications for All Other Adverse Reactions:

^a Based on NCI CTCAE version 3.0

2.5 Preparation and Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use any vials exhibiting particulate matter or discoloration.

FOLOTYN is a hazardous drug. Follow applicable special handling and disposal procedures.¹ If FOLOTYN comes in contact with the skin, immediately and thoroughly wash with soap and water. If FOLOTYN
comes in contact with mucous membranes, flush thoroughly with water.

Aseptically withdraw the calculated dose from the appropriate number of vial(s) into a syringe for immediate use. Do not dilute FOLOTYN.

Administer undiluted FOLOTYN intravenously over 3-5 minutes via the side port of a free-flowing 0.9% Sodium Chloride Injection.

After withdrawal of dose, discard vial(s) including any unused portion.

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 healthcare provider. Based on FOLOTYN’s mechanism of action, consider the prompt administration of leucovorin.

Store refrigerated at 2-8°C (36-46°F) [see USP Controlled Cold Temperature] in original carton to protect from light.

FOLOTYN is a hazardous drug. Follow applicable special handling and disposal procedures.¹