POTELIGEO

POTELIGEO- mogamulizumab injection
Kyowa Kirin, Inc.

1 INDICATIONS AND USAGE

POTELIGEO is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

The recommended dose of POTELIGEO is 1 mg/kg administered as an intravenous infusion over at least 60 minutes. Administer on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of each subsequent 28-day cycle until disease progression or unacceptable toxicity.

Administer POTELIGEO within 2 days of the scheduled dose. If a dose is missed, administer the next dose as soon as possible and resume dosing schedule.

Do not administer POTELIGEO subcutaneously or by rapid intravenous administration.

Recommended Premedications

Administer premedication with diphenhydramine and acetaminophen for the first POTELIGEO infusion.

2.2 Dose Modifications for Toxicity

Dermatologic Toxicity

• Permanently discontinue POTELIGEO for life-threatening (Grade 4) rash or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) [see Warnings and Precautions (5.1) ]. If SJS or TEN is suspected, stop POTELIGEO and do not resume unless SJS or TEN has been excluded and the cutaneous reaction has resolved to Grade 1 or less.
• If moderate or severe (Grades 2 or 3) rash occurs, interrupt POTELIGEO and administer at least 2 weeks of topical corticosteroids. If rash improves to Grade 1 or less, POTELIGEO may be resumed [see Warnings and Precautions (5.1) ].
• If mild (Grade 1) rash occurs, consider topical corticosteroids.

Infusion Reactions

• Permanently discontinue POTELIGEO for a life-threatening (Grade 4) infusion reaction [see Warnings and Precautions (5.2) ].
• Temporarily interrupt the infusion of POTELIGEO for mild to severe (Grades 1 to 3) infusion reactions and treat symptoms. Reduce the infusion rate by at least 50% when restarting the infusion after symptoms resolve. If reaction recurs and is unmanageable, discontinue infusion. [see Warnings and Precautions (5.2) ].
• If an infusion reaction occurs, administer premedication (such as diphenhydramine and acetaminophen) for subsequent POTELIGEO infusions.

2.3 Preparation and Administration

Preparation

• Visually inspect drug product solution for particulate matter and discoloration prior to administration. POTELIGEO is a clear to slightly opalescent colorless solution. Discard the vial if cloudiness, discoloration, or particulates are observed.
• Calculate the dose (mg/kg) and number of vials of POTELIGEO needed to prepare the infusion solution based on patient weight.
• Aseptically withdraw the required volume of POTELIGEO into the syringe and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP. The final concentration of the diluted solution should be between 0.1 mg/mL to 3.0 mg/mL.
• Mix diluted solution by gentle inversion. Do not shake.
• Discard any unused portion left in the vial.

The diluted solution is compatible with polyvinyl chloride (PVC) or polyolefin (PO) infusion bags.

Administration

• Administer infusion solution over at least 60 minutes through an intravenous line containing a sterile, low protein binding, 0.22 micron (or equivalent) in-line filter.
• Do not mix POTELIGEO with other drugs.
• Do not co-administer other drugs through the same intravenous line.

Storage of Diluted Solution

After preparation, infuse the POTELIGEO solution immediately, or store under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from the time of infusion preparation.

Do not freeze. Do not shake.

3 DOSAGE FORMS AND STRENGTHS

Injection: 20 mg/5 mL (4 mg/mL) as a clear to slightly opalescent colorless solution in a single-dose vial.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Dermatologic Toxicity

Fatal and life-threatening skin adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have occurred in recipients of POTELIGEO. Rash (drug eruption) is one of the most common adverse reactions associated with POTELIGEO. In Trial 1, 25% (80/319) of patients treated with POTELIGEO had an adverse reaction of drug eruption, with 18% of these cases being severe (Grade 3) and 82% of these cases being Grade 1 or 2. Of 528 patients treated with POTELIGEO in clinical trials, Grade 3 skin adverse reactions were reported in 3.6%, Grade 4 skin adverse reactions in <1%, and SJS in <1%.

The onset of drug eruption is variable, and the affected areas and appearance vary. In Trial 1, the median time to onset was 15 weeks, with 25% of cases occurring after 31 weeks. The more common presentations reported included papular or maculopapular rash, lichenoid, spongiotic or granulomatous dermatitis, and morbilliform rash. Other presentations included scaly plaques, pustular eruption, folliculitis, non-specific dermatitis, and psoriasiform dermatitis.

Monitor patients for rash throughout the treatment course. Management of dermatologic toxicity includes topical corticosteroids and interruption or permanent cessation of POTELIGEO [see Dosage and Administration (2.2) ]. Consider skin biopsy to help distinguish drug eruption from disease progression.

Discontinue POTELIGEO permanently for SJS or TEN or for any life-threatening (Grade 4) reaction. For possible SJS or TEN, interrupt POTELIGEO and do not restart unless SJS or TEN is ruled out and the cutaneous reaction has resolved to Grade 1 or less.

5.2 Infusion Reactions

Fatal and life-threatening infusion reactions have been reported in patients treated with POTELIGEO. In Trial 1, infusion reactions occurred in 35% (112/319) of patients treated with POTELIGEO, with 8% of these reactions being severe (Grade 3). Most reactions (approximately 90%) occur during or shortly after the first infusion. Infusion reactions can also occur with subsequent infusions. The most commonly reported signs include chills, nausea, fever, tachycardia, rigors, headache, and vomiting.

Consider premedication (such as diphenhydramine and acetaminophen) for the first infusion of POTELIGEO in all patients. Whether premedication reduces the risk or severity of these reactions is not established. In Trial 1, infusion reactions occurred in 42% of patients without premedication and 32% of patients with premedication. Monitor patients closely for signs and symptoms of infusion reactions and interrupt the infusion for any grade reaction and treat promptly [see Dosage and Administration (2.2) ].

5.3 Infections

Fatal and life-threatening infections have occurred in patients treated with POTELIGEO, including sepsis, pneumonia, and skin infection. In Trial 1, 18% (34/184) of patients randomized to POTELIGEO had Grade 3 or higher infection or an infection-related serious adverse reaction. Monitor patients for signs and symptoms of infection and treat promptly.

5.4 Autoimmune Complications

Fatal and life-threatening immune-mediated complications have been reported in recipients of POTELIGEO. Grade 3 or higher immune-mediated or possibly immune-mediated reactions have included myositis, myocarditis, polymyositis, hepatitis, pneumonitis, glomerulonephritis and a variant of Guillain-Barré syndrome. Use of systemic immunosuppressants for immune-mediated reactions was reported in 1.9% (6/319) of recipients of POTELIGEO in Trial 1, including for a case of Grade 2 polymyalgia rheumatica. New-onset hypothyroidism (Grade 1 or 2) was reported in 1.3% of patients and managed with observation or levothyroxine. Interrupt or permanently discontinue POTELIGEO as appropriate for suspected immune-mediated adverse reactions. Consider the benefit/risk of POTELIGEO in patients with a history of autoimmune disease.

5.5 Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) after POTELIGEO

Increased risks of transplant complications have been reported in patients who receive allogeneic HSCT after POTELIGEO including severe (Grade 3 or 4) acute graft-versus-host disease (GVHD), steroid-refractory GVHD, and transplant-related death. Among recipients of pre-transplantation POTELIGEO, a higher risk of transplant complications has been reported if POTELIGEO is given within a shorter time frame (approximately 50 days) before HSCT. Follow patients closely for early evidence of transplant-related complications.