NAPLEX Review: REMS Programs and Boxed Warnings

FDA Guidance on Boxed Warnings

• A boxed warning is issued in three scenarios: serious adverse reaction proportionate to potential benefit, preventable/reducible serious adverse reaction, and FDA-approved drug with restricted use.
• Boxed warnings consider patient selection, careful monitoring, avoiding concomitant therapy, and managing patients in a specific manner.

FDA Guidance on REMS Programs

• REMS (Risk Evaluation and Mitigation Strategy) programs are determined by the FDA for specific drugs.
• REMS programs can require: Medication Guides, communication plans, safe disposal technologies, and Elements To Assure Safe Use (ETASU).

Elements To Assure Safe Use (ETASU)

• Healthcare providers must have particular training/experience.
• Pharmacies/practitioners/healthcare settings must be specially certified.
• Drugs can only be dispensed in certain healthcare settings or with evidence of safe use conditions (e.g., lab results).
• Patients must be subject to monitoring or enrolled in a registry.

Medications with an Active REMS Program

• As of 4/17/24, there are 69 medications with REMS programs.

REMS – Neuro/Psych/Pain/Substance Abuse Medications

• Loxapine: risk of bronchospasm.
• Buprenorphine: risk of serious death or harm with IV administration and risk of abuse/overdose.
• Clozapine: risk of severe neutropenia.
• Sodium oxybate: risk of CNS depression and abuse/misuse.
• Opioid Analgesics: risk of abuse/misuse (ensures provider and patient education).
• Phentermine/topiramate: risk of embryo-fetal toxicity.
• Esketamine: risk of sedation/dissociation (must be administered by a healthcare provider).
• Vigabatrin: risk of vision loss.
• Olanzapine (Zyprexa Relprevv): risk of post-injection sedation/delirium syndrome.

REMS – Cardiovascular Medications

• Endothelin Receptor Antagonists: risk of embryo-fetal toxicity and hepatotoxicity (bosentan only).
• Mavacamten: risk of heart failure due to systolic dysfunction.
• Riociguat: risk of embryo-fetal toxicity.

REMS – Immunological Medications

• Alemtuzumab: risk of autoimmunity, infusion reactions, and malignancy.
• Thalidomide/lenalidomide: risk of embryo-fetal toxicity.
• Mycophenolate: risk of embryo-fetal toxicity.
• Brodalumab: risk of suicidal ideation.
• Eculizumab: risk of meningococcal infection.
• Natalizumab: risk of progressive multifocal leukoencephalopathy (PML).

REMS – Miscellaneous Medications

• Alvimopan: ensuring short-term use only.

This quiz covers FDA guidance on boxed warnings, scenarios for issuing boxed warnings, and REMS programs. It is a part of the NAPLEX review.