Vocabria (Page 3 of 7)

6 ADVERSE REACTIONS

The following adverse reactions are described below and in other sections of the labeling:

Hypersensitivity reactions [see Warnings and Precautions (5.2)]
Hepatotoxicity [see Warnings and Precautions (5.3)]
Depressive disorders [see Warnings and Precautions (5.4)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect rates observed in practice. See full prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) for additional safety information. Since VOCABRIA is taken in combination with EDURANT tablets, the prescribing information for EDURANT (rilpivirine) should be consulted for relevant information on rilpivirine.

Adverse Reactions of VOCABRIA in Clinical Trials for the Treatment of HIV-1 Infection

Clinical Trials Experience in Adults: The safety assessment of VOCABRIA for oral lead-in therapy prior to therapy with CABENUVA is based on the analysis of 48-week data from virologically suppressed subjects with HIV-1 infection in 3 international, multicenter, open-label trials, where 590 of 1,182 subjects received oral lead-in within the pivotal trials FLAIR and ATLAS (pooled analysis) and 655 of 1,045 subjects received oral lead-in within ATLAS-2M [see Clinical Studies (14.1)].

Adverse reactions were reported following exposure to VOCABRIA tablets and EDURANT tablets administered in combination as oral lead-in therapy (median time exposure: 5.3 weeks). Adverse reactions included those attributable to the oral formulation of cabotegravir and rilpivirine administered as a combination regimen. Refer to the prescribing information for EDURANT for other adverse reactions associated with oral rilpivirine.

The most common adverse reactions during the oral lead-in period in the pooled analyses of FLAIR and ATLAS at Week 48 were headache, nausea, abnormal dreams, anxiety, and insomnia, all of which occurred in at least 3 subjects with an incidence ≤1%. The most common adverse reactions during the oral lead-in period for ATLAS-2M were fatigue, diarrhea, headache, nausea, dizziness, abdominal discomfort, abdominal distension, insomnia, and asthenia, all of which occurred in at least 3 subjects across both arms, with an incidence ≤2%.

During the oral lead-in period for FLAIR and ATLAS, 6 (1%) subjects discontinued due to adverse events, including asthenia, myalgia, depression suicidal, and headache. During the oral lead-in period for ATLAS-2M, 4 (<1%) subjects discontinued due to adverse events, including asthenia, skin lesion, fatigue, transaminases increased, and depression.

In the extension phase of the FLAIR study at Week 124, the overall safety profile was consistent with that observed at Week 48 and when injection therapy with CABENUVA was initiated directly without the oral lead-in phase.

Clinical Trial Experience in Adolescents: Based on data from the Week 16 analysis of the MOCHA study in 8 adolescents (aged 12 to younger than 18 years and weighing ≥35 kg) receiving background antiretroviral therapy, the safety profile during the oral lead-in period in adolescents was consistent with the safety profile established with cabotegravir in adults.

Adverse Reactions of VOCABRIA in Clinical Trials for HIV-1 PrEP

Clinical Trial Experience in Adults: In trial HPTN 083, adverse reactions were reported while participants were on blinded study product following exposure to VOCABRIA tablets as oral lead-in for HIV-1 PrEP (median time exposure: 4.1 weeks). The most common adverse reactions reported at ≥1% during the oral lead-in period were diarrhea (4% and 4%), nausea (3% and 5%), dizziness (2% and 2%), headache (2% and 2%), fatigue (1% and 2%), and abnormal dreams (1% and 2%) for VOCABRIA and TRUVADA (emtricitabine and tenofovir disoproxil fumarate), respectively. During the oral lead-in period, 24 (1%) participants receiving VOCABRIA discontinued due to adverse events, including increased alanine aminotransferase, increased aspartate aminotransferase, suicide attempt, and dizziness, which were observed in ≥2 participants.

In Trial HPTN 084, adverse reactions were reported while participants were on blinded study product following exposure to VOCABRIA tablets as oral lead-in for HIV-1 PrEP (median time exposure: 4.1 weeks). The most common adverse reactions reported at ≥1% during the oral lead-in period were headache (6% and 7%), nausea (3% and 7%), dizziness (3% and 4%), diarrhea (2% and 4%), upper respiratory tract infection (2% and 2%), somnolence (2% and 1%), fatigue (1% and 2%), abdominal pain (1% and 1%), vomiting (<1% and 3%), decreased appetite (<1% and 2%), and pruritus (<1% and 1%) for VOCABRIA and TRUVADA, respectively. During the oral lead-in period, 4 (<1%) participants receiving VOCABRIA discontinued due to adverse events of increased alanine aminotransferase (n = 3) and sleep disorders (n = 1).

Clinical Trials Experience in Adolescents: In adolescents receiving VOCABRIA for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving VOCABRIA for HIV-1 PrEP [see Use in Specific Populations (8.4)].

Less Common Adverse Reactions

The following select adverse reactions (regardless of severity) occurred in <1% of participants receiving VOCABRIA in clinical trials for the treatment of HIV-1 infection or for HIV-1 PrEP.

Psychiatric Disorders: Suicidal ideation, and suicide attempt (these events were observed primarily in subjects with a pre‑existing history of depression or other psychiatric illness).

6.2 Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of cabotegravir-containing regimens. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders

Hypersensitivity reactions (including angioedema and urticaria) [see Warnings and Precautions (5.2)].

7 DRUG INTERACTIONS

7.1 Concomitant Use with Other Antiretroviral Medicines

VOCABRIA in combination with EDURANT (rilpivirine) is a complete regimen for the treatment of HIV-1 infection. Refer to the prescribing information for EDURANT for relevant information on rilpivirine.

Coadministration of VOCABRIA with other antiretroviral medications for PrEP is not recommended [see Drug Interactions (7.4), Clinical Pharmacology (12.3)].

Prior to initiating dosing with VOCABRIA, the prescribing information for CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) or APRETUDE should be consulted to ensure use of CABENUVA or APRETUDE will be appropriate for either the treatment of HIV-1 infection or HIV-1 PrEP, respectively.

7.2 Potential for Other Drugs to Affect VOCABRIA

Cabotegravir is primarily metabolized by UGT1A1 with some contribution from UGT1A9. Drugs that are strong inducers of UGT1A1 or UGT1A9 are expected to decrease cabotegravir plasma concentrations and may result in loss of efficacy; therefore, coadministration of VOCABRIA with these drugs is contraindicated [see Contraindications (4)].

Coadministration of oral cabotegravir with polyvalent cation-containing products may lead to decreased absorption of cabotegravir [see Drug Interactions (7.3)].

7.3 Established and Other Potentially Significant Drug Interactions

Information regarding potential drug interactions with cabotegravir are provided in Table 1. These recommendations are based on either drug interaction trials or predicted interactions due to the expected magnitude of the interaction and potential for loss of efficacy [see Contraindications (4), Warnings and Precautions (5.5), Clinical Pharmacology (12.3)]. Table 1 includes potentially significant interactions but is not all inclusive.

Refer to the prescribing information for EDURANT (rilpivirine) for established or potentially significant interactions that should be considered during concomitant administration of VOCABRIA and EDURANT for HIV-1 treatment.

Table 1. Drug Interactions with VOCABRIA
↓ = Decrease.
a Rifabutin can be coadministered with cabotegravir; however, it is contraindicated with CABENUVA for HIV-1 treatment. Dosage modification is recommended with APRETUDE for HIV-1 PrEP.

Concomitant Drug Class:

Drug Name

Effect on Concentration

Clinical Comment

Antacids containing polyvalent cations (e.g., aluminum or magnesium hydroxide, calcium carbonate)

↓Cabotegravir

Administer antacid products at least 2 hours before or 4 hours after taking VOCABRIA.

Anticonvulsants:

Carbamazepine

Oxcarbazepine

Phenobarbital

Phenytoin

↓Cabotegravir

Coadministration is contraindicated with VOCABRIA due to potential for loss of efficacy and development of resistance [see Contraindications (4)].

Antimycobacterialsa:

Rifampin

Rifapentine

↓Cabotegravir

Antimycobacterial:

Rifabutin

↓Cabotegravir

Dose modification is not required for VOCABRIA. Dose modification is recommended for APRETUDE for HIV-1 PrEP. Coadministration is contraindicated with CABENUVA for HIV-1 treatment.

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