Retifanlimab-dlwr

Retifanlimab-dlwr
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rithish Nimmagadda,MBBS.[2]

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Overview

Retifanlimab-dlwr is an humanized anti-programmed death receptor-1 (anti-PD-1) monoclonal antibody that is FDA approved for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma .

Indication approved under accelerated approval based on tumor response rate and duration of response; continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.. Common adverse reactions include Adverse effects (≥10%): fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia, nausea.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

-IV Administration

Administer by IV infusion. Dilute prior to administration. Available as a single-dose vial containing retifanlimab-dlwr 500 mg/20 mL (25 mg/mL) solution.

Do not administer using a polyurethane infusion set.

Administer diluted solution through a polyvinylchloride (PVC) with di-2-ethylhexyl phthalate (DEHP) IV line containing a sterile, non-pyrogenic, low-protein binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2–5 micron in-line or add-on filter, or 15 micron mesh in-line or add-on filter. Do not coadminister other drugs through the same infusion line.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and efficacy not established in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Contraindications

None

Warnings

-Immune-mediated Adverse Reactions

Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue. Reactions may occur at any time, generally during treatment but may also occur after drug is discontinued.

Early identification and management needed to ensure safe use.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Assess liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.

If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection).

Medically manage immune-mediated adverse reactions promptly; refer for specialty consultation as appropriate. Withhold or permanently discontinue depending on nature and severity of the reaction.

If treatment interruption or discontinuation required, administer systemic corticosteroids (1–2 mg/kg per day prednisone or equivalent) until improvement to grade 1 or less; upon improvement, initiate corticosteroid taper and continue to taper over ≥1 month. Consider administration of other systemic immunosuppressants if reaction not controlled with corticosteroid therapy.

Immune-mediated adverse reactions described in following sections may not be inclusive of all possible severe and fatal reactions.

Pneumonitis

Immune-mediated pneumonitis, sometimes fatal, reported.

In patients treated with other PD-1/PD-L1 blocking monoclonal antibodies, incidence of pneumonitis higher in patients with history of prior thoracic radiation.

Colitis

Immune-mediated colitis reported.

Cytomegalovirus infection/reactivation reported in patients with corticosteroid-refractory immune-mediated colitis treated with anti-PD-1/PD-L1 monoclonal antibodies. In patients with corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Hepatitis

Immune-mediated hepatitis reported.

Endocrinopathies

Immune-mediated endocrinopathies, including adrenal insufficiency, hypophysitis, thyroid dysfunction (i.e., hyperthyroidism, hypothyroidism, thyroiditis), and type 1 diabetes, reported.

Primary and secondary adrenal insufficiency reported. For grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement therapy as clinically indicated. Withhold or permanently discontinue depending on severity.

Immune-mediated hypophysitis reported; may present with acute symptoms associated with mass effect (e.g., headache, photophobia, visual field cuts). May lead to hypopituitarism. If hypophysitis occurs, initiate hormone replacement therapy as clinically indicated. Withhold or permanently discontinue depending on severity. [ref]

Immune-mediated thyroid disorders, including thyroiditis, hyperthyroidism, and hypothyroidism, reported. [ref] Thyroiditis may present with or without endocrinopathy. Hypothyroidism may follow hyperthyroidism. [ref] Initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue depending on severity.

Type 1 diabetes reported. Monitor patients for hyperglycemia or other signs and symptoms of diabetes mellitus. Initite insulin therapy as clinically indicated. Withhold retifanlimab depending on severity.

Nephritis with Renal Dysfunction

Immune-mediated nephritis reported.

Dermatologic Adverse Reactions

Immune-mediated rash or dermatitis reported. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), reported with anti-PD-1/PD-L1 monoclonal antibodies.

For treatment of mild to moderate non-exfoliative rashes, topical emollients and/or topical corticosteroids may be adequate. Withhold or permanently discontinue depending on severity.

Other Immune-mediated Adverse Reactions

Other immune-mediated adverse reactions reported rarely; in some instances, reactions were severe or fatal.

Specific reactions included cardiac/vascular disorders (myocarditis, pericarditis, vasculitis); GI disorders (pancreatitis, gastritis, duodenitis); musculoskeletal disorders (myositis/polymyositis, rhabdomyolysis and associated sequelae, arthritis, polymyalgia rheumatica); neurologic disorders (meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis [including exacerbation], Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy); hypoparathyroidism; ocular disorders (uveitis, iritis, other ocular inflammatory toxicities); and other hematologic/immune disorders (hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis], sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection).

Some cases of ocular toxicity may be associated with retinal detachment. [ref] Various grades of visual impairment (including blindness) can occur. [ref] If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome. [ref]

Infusion-related Reactions

Severe infusion-related reactions reported. [ref]

Monitor for signs and symptoms. [ref]

Slow infusion rate, interrupt infusion, or permanently discontinue based on severity. [ref]

Consider premedication with an antipyretic, antihistamine, or both in patients who have had previous systemic reactions to infusions of therapeutic proteins. [ref]

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Serious or fatal complications can occur in patients who receive allogeneic HSCT before or after treatment with anti-PD-1/PD-L1 antibodies. [ref] Complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome without an identified infectious cause. [ref]

Closely monitor patients for evidence of transplant-related complications and intervene promptly. Weigh benefits versus risks of therapy prior to or after allogeneic HSCT.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm based on findings from animal studies and mechanism of action.

Perform pregnancy testing in females of reproductive potential prior to starting retifanlimab-dlwr.

Advise pregnant women of potential risk to fetus.

Advise females of reproductive potential to use effective contraception during treatment with retifanlimab and for 4 months after the last dose.

Immunogenicity

Potential for immunogenicity. Development of anti-drug antibodies and neutralizing antibodies to retifanlimab-dlwr reported. Effects of these antibodies on safety, efficacy, pharmacokinetics, and pharmacodynamics of retifanlimab unknown.

Effects of antibodies on safety, efficacy, pharmacokinetics, and pharmacodynamics of retifanlimab unknown.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Retifanlimab-dlwr Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Retifanlimab-dlwr Postmarketing Experience in the drug label.

Drug Interactions

No formal drug interaction studies to date

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): May cause fetal harm based on findings from animal studies and mechanism of action
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Retifanlimab-dlwr in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Retifanlimab-dlwr during labor and delivery.

Nursing Mothers

Unknown whether retifanlimab distributes into human milk; effects on milk production or the breast-fed infant also unknown. Maternal IgG known to be distributed into human milk

Pediatric Use

There is no FDA guidance on the use of Retifanlimab-dlwr in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Retifanlimab-dlwr in geriatric settings.

Gender

There is no FDA guidance on the use of Retifanlimab-dlwr with respect to specific gender populations.

Race

There is no FDA guidance on the use of Retifanlimab-dlwr with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Retifanlimab-dlwr in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Retifanlimab-dlwr in patients with hepatic impairment.

Females of Reproductive Potential and Males

Perform pregnancy testing in females of reproductive potential prior to treatment initiation. Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.

Immunocompromised Patients

There is no FDA guidance one the use of Retifanlimab-dlwr in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Retifanlimab-dlwr Administration in the drug label.

Monitoring

There is limited information regarding Retifanlimab-dlwr Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Retifanlimab-dlwr and IV administrations.

Overdosage

There is limited information regarding Retifanlimab-dlwr overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Retifanlimab-dlwr Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Retifanlimab-dlwr Mechanism of Action in the drug label.

Structure

There is limited information regarding Retifanlimab-dlwr Structure in the drug label.

Pharmacodynamics

There is limited information regarding Retifanlimab-dlwr Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Retifanlimab-dlwr Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Retifanlimab-dlwr Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Retifanlimab-dlwr Clinical Studies in the drug label.

How Supplied

There is limited information regarding Retifanlimab-dlwr How Supplied in the drug label.

Storage

There is limited information regarding Retifanlimab-dlwr Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Retifanlimab-dlwr Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Retifanlimab-dlwr interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

Zynyz®

Look-Alike Drug Names

There is limited information regarding Retifanlimab-dlwr Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.