Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Vulnerability to Opioid Overdose
Newly
added information:
Patient Access to Naloxone for the
Emergency Treatment of Opioid Overdose
Discuss the availability of naloxone for
the emergency treatment of opioid overdose with the patient and caregiver, at
the initial VIVITROL injection and with each subsequent injection. Because of
the risks for opioid overdose described above, discuss with the patient and
caregiver the importance of having access to naloxone for the emergency
treatment of opioid overdose.
Inform patients and caregivers of the
options for obtaining naloxone as permitted by individual state naloxone
dispensing and prescribing requirements or guidelines (e.g., by prescription,
directly from a pharmacist, or as part of a community-based program). Strongly
consider prescribing naloxone for the emergency treatment of opioid overdose.
Educate patients and caregivers on how to
recognize the signs and symptoms of an opioid overdose and, if naloxone is
prescribed, how to treat with naloxone. Emphasize the importance of calling 911
or getting emergency medical help in all cases of known or suspected opioid
overdose, even if naloxone is administered [see
Patient Counseling Information (17)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
Risk of opioid
overdose
You
or someone close to you should call 911 or get emergency medical help
right away if you:
Talk
to your healthcare provider about naloxone, a medicine that is available to
patients for the emergency treatment of an opioid overdose.
Call
911 or get emergency medical help right away in all cases of known or suspected
opioid overdose, even if naloxone is administered.
PATIENT COUNSELING INFORMATION
VIVITROL for Opioid
Use Disorder:
Additions and/or revisions underlined:
Advise
patients that if they previously used opioids, they may be more sensitive to
lower doses of opioids and at risk of accidental overdose should they use
opioids when their next dose is due, if they miss a dose, or after VIVITROL treatment
is discontinued. It is important that patients inform family members and the
people closest to the patient of this increased sensitivity to opioids and the
risk of overdose. Educate patients and caregivers on how to recognize the
signs and symptoms of an opioid overdose.
Advise
patients that because Vivitrol can block the effects of opioids …
Patient Access to Naloxone for the Emergency Treatment
of Opioid Overdose
Because
of the vulnerability to opioid overdose described above, discuss with the patient
and caregiver the importance of having access to naloxone, and inform them of
options for obtaining it, as permitted by individual state naloxone dispensing
and prescribing requirements or guidelines (e.g., by prescription, directly
from a pharmacist, or as part of a community-based program) [see Warnings and
Precautions (5.1)].
Educate
patients and caregivers on how to recognize the signs and symptoms of an opioid
overdose.
Explain
to patients and caregivers that naloxone’s effects are temporary, and that they
must call 911 or get emergency medical help right away in all cases of known or
suspected opioid overdose, even if naloxone is administered.
If
naloxone is prescribed, also advise patients and caregivers:
How to treat with naloxone in the event of an opioid
overdose
To tell family and friends about their naloxone and to
keep it in a place where family and friends can access it in an emergency
To read the Patient Information (or other educational
material) that will come with their naloxone. Emphasize the importance of doing
this before an opioid emergency happens, so the patient and caregiver will know
what to do.
VIVITROL for All
indications:
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Injection Site Reactions
(Additions and/or revisions are underlined)
VIVITROL must be prepared and administered by a healthcare provider.
VIVITROL injections may be followed by pain, tenderness, induration, swelling, erythema,
bruising,
or
pruritus;
however,
in
some cases injection site reactions may be very severe. In the clinical trials, one patient developed an area of induration that
continued
to
enlarge
after
4 weeks, with subsequent development of necrotic tissue that required surgical excision. In the
postmarketing period, additional cases of injection site
reaction with features including
induration,
cellulitis, hematoma, abscess, sterile abscess, and
necrosis,
have
been
reported. Some
cases
required
surgical
intervention, including debridement of
necrotic
tissue.
Some cases
resulted
in
significant
scarring.
The
reported
cases
occurred
primarily in female patients.
6
Adverse Reactions
6.2 Postmarketing Experience
(Additions
and/or revisions are underlined)
Adverse
Events Following Patient Self-Administration
Adverse
events including injection site reactions and precipitated
opioid withdrawal resulting in serious
outcomes, including hospitalization, have been reported following
patient self- administration of VIVITROL. VIVITROL must be prepared and administered by a healthcare provider.
Hypersensitivity Reactions
Including
Anaphylaxis
Hypersensitivity reactions including anaphylaxis have been reported during postmarketing
surveillance.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions are underlined)
Advise the patient to read the
FDA-Approved
patient
labeling
(Medication
Guide).
Physicians should include the following
issues
in
discussions
with
patients
for
whom they
prescribe
VIVITROL:
Advise patients that if they previously used opioids,
they may be more sensitive to lower doses of opioids and at risk of accidental
overdose should they use opioids when their next dose is due, if they miss a
dose, or after VIVITROL treatment is discontinued. It is important
that patients inform family members
and the people closest to the patient
of this increased sensitivity to opioids and the
risk of overdose.
Advise patients that because VIVITROL can block the effects of opioids,
patients will not perceive any effect
if they attempt to self-administer heroin
or any other opioid drug in small doses while on VIVITROL. Further, emphasize that administration of large
doses of heroin or any other opioid to try to bypass the blockade and get high while
on VIVITROL may lead to serious injury, coma,
or death.
Inform patients
on VIVITROL that they may not experience the expected effects from opioid-containing
analgesic, antidiarrheal, or antitussive medications.
Instruct
patients that VIVITROL must be prepared and administered by a healthcare
provider.
Medication Guide
(Newly added Medication Guide: please refer
to labeling)
Approved Drug Label (PDF)
6
Adverse Reactions
6 ADVERSE REACTIONS
(Subsection
has been revised)
The following clinically significant adverse
reactions are described elsewhere in the labeling:
Accidental Opioid Overdose
Injections Site Reactions
Precipitated Opioid Withdrawal
Hepatotoxicity
Depression
and Suicidality
Eosinophilic
Pneumonia
Hypersensitivity Reactions
6.1 Clinical Trials Experience
(Subsection
title has been revised)
Opioid Dependence
In a controlled trial of 6 months, 2% of opioid-dependent patients treated
with VIVITROL discontinued treatment due to an adverse event,
as compared to 2% of the opioid-dependent patients
treated with placebo.
Common Adverse Reactions
Alcohol Dependence
Table 1 lists
all treatment-emergent clinical adverse reactions, regardless of causality, occurring in 2'5%
of patients with alcohol dependence, for which the incidence
was greater in the combined
VIVITROL group than in the placebo
group. A majority of patients treated
with VIVITROL in clinical studies had adverse
reactions with a maximum
intensity of “mild” or “moderate”.
Table 1: Treatment-emergent Adverse
Reactions (Reactions in 2:5% of patients with alcohol dependence treated with VIVITROL and occurring more
frequently in the combined VIVITROL group than in the placebo
group)
…
Opioid Dependence
In the open-label, long-term safety study conducted
in the US, the commonly
reported adverse reactions among the opioid-dependent patients
in the study were similar to those commonly observed events in the alcohol-dependent populations in VIVITROL clinical
trials as displayed in Table 1,
above. For example, injection site reactions
of all types, nausea and diarrhea occurred
in more than 5% of patients
on VIVITROL in the open-label study.
In contrast, 48% percent, of the
opioid-dependent patients had at least
one adverse event in the “Infections and Infestations” Body System.
Adverse Reactions/Preferred Terms of nasopharyngitis, upper respiratory tract infection, urinary tract infection, and sinusitis were most commonly reported.
In the placebo-controlled study in opioid-dependent patients
conducted in Russia,
the overall frequency of adverse events
was lower than in the U.S. population described
above. Table 2 lists treatment-emergent clinical adverse events, regardless of causality, occurring in 2'2% of patients with opioid dependence, for which the incidence was greater in the VIVITROL group
than in the placebo group. All adverse events
were assessed as having a maximum
intensity of “mild” or “moderate.”
Table 2: Treatment-emergent Clinical Adverse
Events (Events in 2:2% of patients with
opioid dependence treated with
VIVITROL and occurring more frequently in the VIVITROL group than in
the placebo group)
6.2 Postmarketing
Experience
(Subsection
title has been revised)
8
Use in Specific Populations
8.1 Pregnancy
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; additions
and/or revisions are underlined)
Risk Summary
The available data from published
case series with VIVITROL use in pregnant
women are insufficient to identify a drug-associated risk of major
birth defects, miscarriage or adverse maternal or fetal outcomes. There are clinical considerations. Reproduction and developmental animal studies
have not been conducted for VIVITROL. Daily oral administration of naltrexone to female rats and rabbits increased
the incidence of early fetal loss at exposures 2' 11 times and 2' 2 times the human exposure, respectively. Daily oral administration of naltrexone to pregnant rats and rabbits
during the period
of organogenesis did not induce malformation at exposures up to 175 times and 14 times the human exposure, respectively.
The estimated
background risk of major birth defects
and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss,
or other adverse outcomes. In the U.S. general population, the estimated
background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-associated maternal and embryo-fetal risk
Untreated opioid addiction in pregnancy is associated with adverse
obstetrical outcomes such as low birth weight, preterm
birth, and fetal death. In addition,
untreated opioid addiction often results in continued or relapsing
illicit opioid use.
Published studies
have demonstrated that alcohol is
associated with fetal
harm including growth restriction,
facial abnormalities, central nervous
system abnormalities, behavioral
disorders, and impaired
intellectual development.
Data
Animal Data
Reproduction and developmental studies
have not been conducted for VIVITROL. Studies
with naltrexone administered via the oral route have been conducted
in pregnant rats and rabbits.
Daily oral administration of naltrexone has been shown
to increase the incidence of early fetal loss when given to rats at doses 2'30 mg/kg/day
(11 times the human exposure
based on an AUC(0-28d) comparison) and to rabbits
at oral doses 2'60 mg/kg/day (2 times the human exposure based on an AUC(0-28d) comparison).
Daily oral administration of naltrexone to rats and rabbits
during the period
of organogenesis did not induce malformations at doses up to 200 mg/kg/day
(175- and 14-times
the human exposure based on an AUC(0-28d) comparison,
respectively).
8.2 Lactation
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion)
Risk Summary
Naltrexone and its major metabolite, 6P-naltrexol, are present
in human milk. There are no data on the effects on the breastfed
infant or the effects on milk production. The developmental health benefits of breastfeeding should be considered along with the mother’s clinical
need for naltrexone and any potential adverse
effects on the breastfed infant from naltrexone or the mother’s underlying maternal condition.
8.5 Geriatric Use
(Additions and/or revisions are
underlined)
This drug is known to be substantially excreted by the kidney,
and the risk of adverse
reactions to this drug may be greater in patients with impaired
renal function. Because
elderly patients are more likely to have decreased renal function, it may be useful
to monitor renal function.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions are
underlined)
Advise the patient to read the FDA-Approved patient labeling (Medication Guide).
…
- Inform patients
on VIVITROL
that they may not experience the expected effects from opioid-containing analgesic, antidiarrheal, or antitussive medications.
…
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