Cabotegravir and rilpivirine - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Serious or severe hypersensitivity reactions have been reported with cabotegravir- and rilpivirine-containing regimens.

Reactions associated with cabotegravir include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

Reactions associated with rilpivirine-containing regimens include cases of drug reaction with eosinophilia and systemic symptoms (DRESS).

Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. • Serious post-injection reactions with rilpivirine were reported.

Monitor and treat as clinically indicated. • Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine.

Monitoring of liver chemistries is recommended.

Discontinue CABENUVA if hepatotoxicity is suspected. • Depressive disorders have been reported with CABENUVA.

Prompt evaluation is recommended for depressive symptoms. • Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients up to 12 months or longer.

It is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injections of CABENUVA when dosed monthly and no later than 2 months after the final injections when dosed every 2 months.

If virologic failure is suspected, prescribe an alternative regimen as soon as possible.

5.1 Hypersensitivity Reactions Serious or severe hypersensitivity reactions have been reported with cabotegravir- and rilpivirine-containing regimens.

Reactions associated with cabotegravir include Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) [see Adverse Reactions ] .

Reactions associated with rilpivirine-containing regimens include cases of drug reaction with eosinophilia and systemic symptoms (DRESS) [see Adverse Reactions ( 6.1 , 6.2 )] .

While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries.

Administration of cabotegravir and rilpivirine oral lead-in dosing was used in clinical studies to help identify patients who may be at risk of a hypersensitivity reaction [see Dosage and Administration , Contraindications ] .

Remain vigilant and discontinue CABENUVA if a hypersensitivity reaction is suspected [see Contraindications , Adverse Reactions ] .

Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, mucosal involvement [oral blisters or lesions], conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing).

Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated.

For information regarding the long-acting properties of CABENUVA, [see Warnings and Precautions ] .

Administer oral lead-in dosing prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction [see Dosage and Administration , Contraindications ] .

5.2 Post-Injection Reactions In clinical trials, serious post-injection reactions were reported within minutes after the injection of rilpivirine.

These events included symptoms such as dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest).

These events were reported in <1% of participants and began to resolve within minutes after the injection, with some patients receiving supportive care.

These events may have been associated with accidental intravenous administration during the intramuscular injection procedure [see Adverse Reactions ] .

Carefully follow the Instructions for Use when preparing and administering CABENUVA.