FOLOTYN

What it is

FOLOTYN is pralatrexate solution for intravenous infusion injection. Each 1 mL of solution contains 20 mg of pralatrexate. Pralatrexate solution for infusion is a preservative-free, sterile, isotonic, non-pyrogenic clear yellow aqueous parenteral solution. Pralatrexate is an antineoplastic folate analogue that inhibits dihydrofolate reductase, resulting in disruption of DNA synthesis and subsequent tumour cell death.

Approved indications

— Adult patients with peripheral T-cell lymphoma (nodal, extranodal, and leukaemic/disseminated) who have progressed after at least one prior therapy.

Dosing overview

The recommended starting dose of FOLOTYN is 30 mg/m² administered as an intravenous infusion over 3–5 minutes, once weekly for six weeks, followed by a one week rest period (7-week treatment cycle), until progressive disease or unacceptable toxicity. Patients should take low-dose (1.0–1.25 mg) oral folic acid on a daily basis, initiated during the 10-day period preceding the first dose of FOLOTYN, and dosing should continue during the full course of therapy and for 30 days after the last dose. Patients should also receive a vitamin B₁₂ (1 mg) intramuscular injection no more than 10 weeks prior to the first dose of FOLOTYN and every 8–10 weeks thereafter.

Key safety warnings

Pralatrexate can suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anaemia. Folic acid and vitamin B₁₂ supplementation is recommended to reduce the risk of haematological toxicity. Full blood cell counts and severity of mucositis should be monitored weekly for all patients receiving FOLOTYN. Treatment with pralatrexate can cause mucosal inflammation. Monitor for mucosal inflammation weekly and if ≥ Grade 2 mucosal inflammation is observed, omit and/or reduce the dose. FOLOTYN can cause severe dermatological reactions, which may result in death. Dermatological reactions with FOLOTYN have ranged from alopecia, pruritus and rash, to serious or fatal skin exfoliation, ulceration, toxic epidermal necrolysis. There have been a small number of fatal dermatological reactions both within the clinical trials and post-marketing setting with pralatrexate. Pneumonitis has been reported in patients treated with FOLOTYN. Across clinical studies, pneumonitis was reported in 9 patients (1.3%), including 7 patients with PTCL. Most cases were considered causally related to pralatrexate. Tumour lysis syndrome has been reported in patients with lymphoma receiving pralatrexate. Patients should be monitored closely and treated for complications.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. Pregnancy or breast-feeding.

PBS listing

FOLOTYN 20 mg in 1 mL solution for intravenous infusion has 4 PBS items listed with authority required restriction at an ex-manufacturer price of A$1035.50.

Regulatory history

The TGA initially rejected the submission on 17 May 2013. However, following an appeal to the Administrative Appeals Tribunal (AAT), the drug was approved on 23 December 2014, leading to its entry onto the ARTG on 26 February 2015. In November 2017, FOLOTYN was recommended by the PBAC for authority required listing for relapsed or refractory peripheral T-cell lymphoma under Section 100 (Efficient Funding of Chemotherapy – Public and Private Hospital).