VOXELOTOR Drug Interactions: What You Need to Know

INTERACTIONS

• Sensitive CYP3A4 Substrates: Avoid coadministration of sensitive CYP3A4 substrates with a narrow therapeutic index. ( 7.2 )
• Strong or moderate CYP3A4 Inducers: Avoid coadministration with strong or moderate CYP3A4 inducers. If unavoidable, increase the dose of OXBRYTA. ( 2.5 , 2.6 , 7.1 )

7.1 Effect of Other Drugs on Voxelotor Strong or Moderate CYP3A4 Inducers Coadministration of strong or moderate CYP3A4 inducers may decrease voxelotor plasma and whole blood concentrations and may lead to reduced efficacy. Avoid coadministration of OXBRYTA with strong or moderate CYP3A4 inducers. Increase the OXBRYTA dosage when coadministration with a strong or moderate CYP3A4 inducer is unavoidable <span class="opacity-50 text-xs">[see Dosage and Administration (2.5 , 2.6) and Clinical Pharmacology (12.3) ]</span>.

7.2 Effect of Voxelotor on Other Drugs Voxelotor increased the systemic exposure of midazolam (a sensitive CYP3A4 substrate) <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>. Avoid coadministration of OXBRYTA with sensitive CYP3A4 substrates with a narrow therapeutic index. If concomitant use is unavoidable, consider dose reduction of the sensitive CYP3A4 substrate(s).

7.3 Laboratory Test Interference OXBRYTA administration may interfere with measurement of Hb subtypes (HbA, HbS, and HbF) by HPLC <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span>. If precise quantitation of Hb species is required, chromatography should be performed when the patient has not received OXBRYTA therapy in the immediately preceding 10 days.

OXBRYTA is contraindicated in patients with a history of serious drug hypersensitivity reaction to voxelotor or excipients. Clinical manifestations may include generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ]. Prior drug hypersensitivity to voxelotor or excipients. ( 4 )

AND PRECAUTIONS

• Hypersensitivity Reactions: Observe for signs and symptoms and manage promptly. ( 5.1 )
• Laboratory Test Interference: Perform quantification of hemoglobin species when patient is not receiving OXBRYTA. ( 5.2 )

5.1 Hypersensitivity Reactions Serious hypersensitivity reactions after administration of OXBRYTA have occurred in &lt;1% of patients treated. Clinical manifestations may include generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in postmarketing experience with OXBRYTA <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> . Patients who develop a combination of skin rash, fever, peripheral eosinophilia, and internal systemic organ involvement (e.g., hepatic, renal, pulmonary) while receiving OXBRYTA should undergo medical evaluation. Advise patients of the signs and symptoms of severe hypersensitivity reactions, including DRESS. If hypersensitivity reactions occur, discontinue OXBRYTA and administer appropriate medical therapy. Do not reinitiate OXBRYTA in patients who experience these symptoms with previous use.

5.2 Laboratory Test Interference OXBRYTA administration may interfere with measurement of Hb subtypes (HbA, HbS, and HbF) by high-performance liquid chromatography (HPLC) <span class="opacity-50 text-xs">[see Drug Interactions (7.3) ]</span>. If precise quantitation of Hb species is required, chromatography should be performed when the patient has not received OXBRYTA therapy in the immediately preceding 10 days.