Approved Drug Label (PDF)
5
Warnings and Precautions
5.4 Depressive Disorders
Additions and/or revisions underlined:
When VOCABRIA is Used for
Treatment HIV-1 Infection
![]()
Depressive disorders (including depressed mood, depression, mood
altered, mood swings, suicidal ideation, suicide attempt) have been
reported with VOCABRIA when used with EDURANT for treatment of HIV-1 infection [see
Adverse Reactions (6.1)]. Promptly evaluate patients with depressive symptoms
to assess whether the symptoms are related to VOCABRIA and to determine whether
the risks of continued therapy outweigh the benefits.
When VOCABRIA is Used for
HIV-1 PrEP
![]()
Depressive disorders (including depression, depressed mood, persistent
depressive disorder, suicidal ideation, suicide attempt) have been
reported with VOCABRIA [see Adverse Reactions (6.1)]. Promptly evaluate individuals
with depressive symptoms to assess whether the symptoms are related to VOCABRIA
and to determine whether the risks of continued therapy outweigh the benefits.
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
…
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).
8
Use in Specific Populations
8.2 Lactation
Additions and/or revisions underlined:
Risk Summary
There are no data on the presence of cabotegravir in human milk, the effects on the breastfed
infant, or the effects on milk production. Cabotegravir is
present in animal milk (see Data).
When a drug is present in
animal milk, it is likely that the drug will be present in human milk.
Potential risks of breastfeeding
include: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing
viral resistance (in HIV-1–positive infants), and (3) adverse reactions in a
breastfed infant similar to those seen in adults
In HIV-1–uninfected
mothers, the developmental and health benefits of breastfeeding and the
mother’s clinical need for VOCABRIA for HIV-1 PrEP should be considered along
with any potential adverse reactions on the breastfed child from VOCABRIA and
the risk of HIV-1 acquisition due to nonadherence and subsequent mother to
child transmission. Mothers should not breastfeed if acute HIV-1 infection is suspected
because of the risk of HIV-1 transmission to the infant.
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or revisions underlined:
…
Depressive Disorders
Inform patients that depressive disorders (including
depressed mood, depression, mood altered, mood swings, suicidal ideation,
suicide attempt) have been reported with VOCABRIA for treatment of HIV-1.
Inform patients that depressive disorders (including depression, depressed
mood, persistent depressive disorder, suicidal ideation, suicide attempt)
have been reported with VOCABRIA for HIV-1 PrEP. Promptly evaluate patients
with severe depressive symptoms to assess whether the symptoms are related to
VOCABRIA and to determine whether the risks of continued therapy outweigh the
benefits [see Warnings and Precautions
(5.4), Adverse Reactions (6.1)].
…
Lactation
Inform individuals with HIV-1
infection that the potential risks of breastfeeding include: (1) HIV-1
transmission (in HIV-1–negative infants), (2) developing viral resistance (in
HIV-1-positive infants), and (3) adverse reactions in
a breastfed infant similar to those seen in adults.
In HIV-1–uninfected mothers, the benefits and risks of
VOCABRIA while breastfeeding should be evaluated, including the risk of HIV-1
acquisition due to medication nonadherence and subsequent mother to child
transmission. Instruct mothers not to
breastfeed if acute HIV-1 infection is suspected because of the risk
of passing the HIV-1 virus to the baby [see Use in Specific Populations (8.2)].
…
PATIENT
INFORMATION
Additions
and/or revisions underlined:
…
Before
taking VOCABRIA, tell your healthcare provider about all your medical conditions,
including if you:
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Risk of Adverse Reactions, Loss of Virologic Response, or Reduced Concentration Due to Drug Interactions
Additions and/or revisions
underlined:
… loss of
virologic protection from VOCABRIA when used for treatment of HIV-1 infection
or HIV-1 PrEP, and possible development of viral resistance [see Contraindications (4), Drug
Interactions (7.2, 7.3)].
… Consider the
potential for drug interactions prior to and during use of VOCABRIA; review
concomitant medications during use of VOCABRIA [see Drug Interactions (7.3)].
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or
revisions underlined:
Adverse Reactions
of VOCABRIA in Clinical Trials for the Treatment of HIV-1 Infection
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, which 590 of 1,182 subjects received oral lead-in, from the pivotal
trials FLAIR and ATLAS (pooled analysis) and 655 of 1,045 subjects received
oral lead-in, from ATLAS-2M [see Clinical
Studies (14.1)] …
… The most common
adverse reactions during the oral lead-in period for FLAIR and ATLAS were
headache, nausea, abnormal dreams, anxiety, and insomnia, all of which occurred
in at least 3 subjects with an incidence less than or equal to 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 less than or equal to 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 (less than or equal to 1%)
subjects discontinued due to adverse events, including asthenia, skin lesion,
fatigue, transaminases increased, and depression.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or
revisions for references have been underlined:
Hepatoxicity
… Inform individuals
that clinical and laboratory monitoring should be considered and APRETUDE
should be discontinued if hepatoxicity is confirmed when VOCABRIA is used for
HIV-1 PrEP [see Warnings and Precautions
(5.3)].
Drug Interactions
… advise patients
to report to their healthcare provider the use of any other prescription or
nonprescription medication or herbal products [see Contraindications (4), Warnings and Precautions (5.5), Drug
Interactions (7.2, 7.3)].
PATIENT INFORMATION
The most common
side effects of VOCABRIA for HIV-1 treatment include:
Newly added:
Fatigue
Diarrhea
Dizziness
Stomach pain
Stomach bloating
Weakness
Approved Drug Label (PDF)
4
Contraindications
Additions and/or revisions underlined:
Treatment of HIV-1
Infection
VOCABRIA is contraindicated in patients:
with previous hypersensitivity reaction to cabotegravir [see Warnings and Precautions (5.2)].
receiving the following coadministered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase (UGT1A1) enzyme induction, which may result in loss of virologic
response [see Drug Interactions (7.2, 7.3), Clinical Pharmacology (12.3)]:
Prior to initiation of VOCABRIA, note that use of CABENUVA with rifabutin is contraindicated.
Since VOCABRIA
is taken in combination with EDURANT tablets, the prescribing information for EDURANT
should be consulted for additional contraindications.
HIV-1 Pre-Exposure Prophylaxis VOCABRIA
is contraindicated in individuals:
- with previous hypersensitivity reaction
to cabotegravir [see Warnings and Precautions (5.2)]
receiving
the following coadministered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to UGT1A1 enzyme induction, which may result in loss of virologic response [see Drug Interactions (7.2, 7.3), Clinical Pharmacology (12.3)]:
Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
Antimycobacterials: Rifampin, rifapentine
5
Warnings and Precautions
5.1 Comprehensive
Management to Reduce
the Risk of HIV-1 Infection
When VOCABRIA is Used for HIV-1 Pre-Exposure Prophylaxis
Newly added
subsection; please refer to label
5.2 Hypersensitivity Reactions
Additions and/or
revisions underlined:
Serious or severe hypersensitivity reactions have been reported
in association with other integrase inhibitors and could occur with VOCABRIA
[see Adverse Reactions (6)].
Administration of oral lead-in dosing was used in clinical
studies to help identify participants who may be at risk of a hypersensitivity reaction. Remain vigilant
and discontinue VOCABRIA if a hypersensitivity reaction is suspected [see Dosage
and Administration (2.2),
Contraindications (4), Adverse Reactions (6)].
Discontinue
VOCABRIA 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.
5.3 Hepatotoxicity
Additions and/or
revisions underlined:
Hepatotoxicity has been reported in a limited
number of patients receiving
cabotegravir with or without known pre-existing hepatic disease
or identifiable risk factors [see Adverse
Reactions (6.1)].
When VOCABRIA is Used f or Treatment
HIV-1 Inf ection
Patients with underlying liver disease or marked elevations in transaminases prior to treatment
with VOCABRIA may be at increased risk for worsening or development of transaminase elevations.
When VOCABRIA is Used f or HIV-1 PrEP
Clinical and laboratory monitoring should be considered and VOCABRIA
should be
discontinued if hepatotoxicity is suspected and individuals managed
as clinically indicated.
5.4 Depressive Disorders
Additions and/or
revisions underlined:
When VOCABRIA
is Used f or Treatment
HIV-1 Infection
Depressive
disorders (including depressed mood, depression, mood altered,
mood swings) have been reported with VOCABRIA when used with EDURANT
for treatment of HIV-1 infection [see Adverse Reactions
(6.1)]. Promptly evaluate
patients with depressive symptoms to assess whether the symptoms are related to VOCABRIA
and to determine whether the risks of
continued
therapy outweigh
the benefits. When VOCABRIA
is Used f or HIV-1 PrEP
Depressive
disorders (including depression, depressed mood, persistent depressive disorder and suicide attempt) have been reported with VOCABRIA
[see Adverse Reactions (6.1)]. Promptly evaluate individuals with depressive symptoms to assess whether the symptoms are related to VOCABRIA
and to determine whether the risks of continued therapy
outweigh the benefits.
5.5 Risk of Adverse Reactions, Loss of Virologic Response, or Reduced
Concentration Due to Drug Interactions
Additions and/or
revisions underlined:
The concomitant use of VOCABRIA
and other drugs may result in known or potentially significant drug interactions, some of which may lead to adverse events, loss of virologic
protection from VOCABRIA when used for treatment
of HIV-1 infection or HIV-1 PrEP, and possible development of viral resistance [see Contraindications (4), Drug Interactions (7.3)].
See Table 1 for steps to prevent or manage these possible
and known significant drug
interactions, including dosing
recommendations. Consider
the potential for drug interactions prior to and during use of VOCABRIA; review concomitant medications during
use of VOCABRIA.
5.6 Risks Associated with Rilpivirine Treatment
Additions and/or
revisions underlined:
VOCABRIA is indicated for use in combination with EDURANT
for treatment of HIV-1 infection [see Indications and Usage
(1.1), Dosage
and Administration (2.1)]. Review the prescribing information for EDURANT
for information on rilpivirine prior to initiation of VOCABRIA
in combination with rilpivirine.
6
Adverse Reactions
6.1 Clinical Trials Experience
Extensive changes; please refer to
label
7
Drug Interactions
7.1 Concomitant Use with Other Antiretroviral Medicines
Additions and/or
revisions underlined:
VOCABRIA in combination with EDURANT
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
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.
7.3 Established and Other Potentially Significant Drug Interactions
Changes to table 1; please refer to
label
7.4 Drugs without Clinically Significant Interactions with Cabotegravir
Additions and/or
revisions underlined:
Based on drug interaction study results, the following drugs can be coadministered with cabotegravir without a dose adjustment: etravirine, midazolam, oral contraceptives containing levonorgestrel and ethinyl
estradiol, rifabutin, and rilpivirine [see Clinical
Pharmacology (12.3)].
Prior to initiating oral therapy, note that use of CABENUVA with rifabutin is contraindicated for the treatment of HIV-1 infection. Dosage modification is recommended when APRETUDE is
used
with rifabutin for HIV-1 PrEP.
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or
revisions underlined:
Risk Summary
There are insufficient human data on the use of VOCABRIA
during pregnancy to adequately assess a drug-associated risk of birth defects and miscarriage. While there are insufficient human data to assess the risk of
neural tube defects (NTDs)
with exposure to VOCABRIA
duringpregnancy, NTDs were associated with dolutegravir, another integrase
inhibitor. Healthcare providers
should discuss the benefit-risk of using VOCABRIA with individuals of childbearing potential or during pregnancy.
The APR has been established to monitor for birth defects following
prenatal exposure
to antiretrovirals. The rate of miscarriage is not reported in the APR. The background risk for major birth
defects and miscarriage for the indicated population is unknown.
The background rate for major birth defects in a
U.S. reference population of the Metropolitan Atlanta
Congenital Defects Program (MACDP) is 2.7%...
Data
Human Data: Data from a birth outcome surveillance study in Botswana showed that dolutegravir, another integrase
inhibitor, was associated
with increased risk of NTDs when administered at the time of conception
and in early pregnancy. Data from clinical trials are insufficient to address this risk with cabotegravir.
8.2 Lactation
Additions and/or
revisions underlined:
Risk Summary
The Centers for Disease
Control and Prevention recommends that HIV-1–infected mothers in the United States (U.S.) not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.
It is not known if cabotegravir is present in human breast
milk, affects human milk production, or has effects on the breastfed infant. When administered to lactating rats, cabotegravir was present in milk (see Data).
Because
of the potential
for (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) adverse reactions in a breastfed
infant similar
to those seen in adults, instruct HIV-1–infected mothers not to breastfeed if they are receiving VOCABRIA
for the treatment of HIV-1 infection.
For uninfected mothers receiving VOCABRIA
for HIV-1 PrEP, assess the benefit-risk of using VOCABRIA to the infant while
breastfeeding.
8.4 Pediatric Use
Additions and/or
revisions underlined:
Treatment of HIV-1
Infection
The safety and efficacy
of VOCABRIA have not been established in pediatric patients
with HIV-1 infection.
HIV-1 Pre-Exposure Prophylaxis
The safety and effectiveness of VOCABRIA for HIV-1 PrEP in at-risk adolescents weighing at least 35 kg is supported by data from 2 adequate
and well-controlled trials of VOCABRIA
for HIV-1 PrEP in adults with additional safety and pharmacokinetic data from studies in HIV-1 infected adults who were administered CABENUVA
and in HIV-1 infected
pediatric subjects
who were administered separate
components of CABENUVA in addition to their current antiretroviral therapy [see Dosage
and Administration (2.5), Adverse Reactions (6.1), Clinical
Pharmacology (12.3), Clinical Studies
(14.2)].
APRETUDE
for HIV-1 PrEP is being evaluated in 2 open-label
multicenter clinical
trials in adolescent individuals. Fifty-nine adolescents have been enrolled. Of these, 54 adolescent participants received one or more injections after receiving VOCABRIA. In adolescents
receiving
VOCABRIA and APRETUDE
for HIV-1 PrEP, the safety data were comparable to the safety data reported in adults receiving
APRETUDE for HIV-1 PrEP.
While using APRETUDE,
HIV-1 testing should be conducted prior to initiating APRETUDE (with or without an oral lead-in
with oral cabotegravir) and prior to each injection of APRETUDE. Adolescents may benefit from more frequent
visits and counseling to support adherence to the dosing schedule [see Dosage and Administration (2.2),
Warnings and Precautions
(5.1)].
The safety, efficacy,
and pharmacokinetics of VOCABRIA in pediatric participants younger than 12 years of age or weighing
<35 kg have not been established.
8.6 Renal
Impairment
Additions and/or
revisions underlined:
No dosage adjustment
of VOCABRIA is necessary
for patients with mild to moderate
(creatinine clearance equal to 30 mL/min
to <90 mL/min) or severe renal impairment (creatinine clearance<30 mL/min) [see Clinical
Pharmacology (12.3)]. The effect of end-stage renal disease
(creatinine clearance <15 mL/min) on the pharmacokinetics of cabotegravir is unknown. As cabotegravir is >99% protein bound, dialysis is not expected to alter exposures
of cabotegravir.
Since VOCABRIA
is taken in combination with EDURANT for the treatment of HIV-1 infection,
the prescribing information for EDURANT
should be consulted for additional recommendations in patients
with severe impairment or end-stage
renal disease.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
Extensive changes; please refer to
label
Patient Information
Extensive changes; please refer to label
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