Included as part of the PRECAUTIONS section.
Addiction, Abuse And Misuse
VANTRELA ER contains hydrocodone, a Schedule II
controlled substance. As an opioid, VANTRELA ER exposes users to the risks of
addiction, abuse, and misuse. As extended-release products such as VANTRELA ER
deliver the opioid over an extended period of time, there is a greater risk for
overdose and death due to the larger amount of hydrocodone present [see Drug
Abuse and Dependence].
Although the risk of addiction in any individual is
unknown, it can occur in patients appropriately prescribed VANTRELA ER. Addiction
can occur at recommended dosages and if the drug is misused or abused.
Assess each patient's risk for opioid addiction, abuse,
or misuse prior to prescribing VANTRELA ER, and monitor all patients receiving
VANTRELA ER for the development of these behaviors or conditions. Risks are
increased in patients with a personal or family history of substance abuse
(including drug or alcohol addiction or abuse) or mental illness (e.g., major depression).
The potential for these risks should not, however, prevent the proper
management of pain in any given patient. Patients at increased risk may be
prescribed opioids such as VANTRELA ER, but use in such patients necessitates
intensive counseling about the risks and proper use of VANTRELA ER along with
intensive monitoring for signs of addiction, abuse, and misuse. Abuse or misuse
of VANTRELA ER by crushing, chewing, snorting, or injecting the dissolved
product will result in the uncontrolled delivery of the hydrocodone and can
result in overdose and death [see OVERDOSAGE].
Opioids are sought by drug abusers and people with
addiction disorders and are subject to criminal diversion. Consider these risks
when prescribing or dispensing VANTRELA ER. Strategies to reduce these risks
include prescribing the drug in the smallest appropriate quantity and advising
the patient on the proper disposal of unused drug [see PATIENT INFORMATION]. Contact local state professional licensing board or state
controlled substances authority for information on how to prevent and detect
abuse or diversion of this product.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory
depression has been reported with the use of opioids, even when used as
recommended. Respiratory depression, if not immediately recognized and treated,
may lead to respiratory arrest and death. Management of respiratory depression
may include close observation, supportive measures, and use of opioid
antagonists, depending on the patient's clinical status [see OVERDOSAGE].
Carbon dioxide (CO2) retention from opioid-induced respiratory depression can
exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory
depression can occur at any time during the use of VANTRELA ER, the risk is
greatest during the initiation of therapy or following a dosage increase.
Closely monitor patients for respiratory depression when initiating therapy
with and following dosage increases of VANTRELA ER.
To reduce the risk of respiratory depression, proper
dosing and titration of VANTRELA ER are essential [see DOSAGE AND
ADMINISTRATION]. Overestimating the VANTRELA ER dosage when converting
patients from another opioid product, can result in fatal overdose with the
Accidental ingestion of even one dose of VANTRELA ER,
especially by children, can result in respiratory depression and death due to
an overdose of hydrocodone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of VANTRELA ER during pregnancy can result
in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike
opioid withdrawal syndrome in adults, may be life-threatening if not recognized
and treated, and requires management according to protocols developed by
neonatology experts. Observe newborns for signs of neonatal opioid withdrawal
syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged
period of the risk of neonatal opioid withdrawal syndrome and ensure that
appropriate treatment will be available [see Use in Specific Populations,
Risks Of Concomitant Use Or Discontinuation Of Cytochrome
P450 3A4 Inhibitors And Inducers
Concomitant use of VANTRELA ER with a CYP3A4 inhibitor,
such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents
(e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase
plasma concentrations of hydrocodone and prolong opioid adverse reactions,
which may cause potentially fatal respiratory depression [see Life-Threatening Respiratory Depression], particularly when an inhibitor is added after a stable dose
of VANTRELA ER is achieved. Similarly, discontinuation of a CYP3A4 inducer,
such as rifampin, carbamazepine, and phenytoin, in VANTRELA ER-treated patients
may increase hydrocodone plasma concentrations and prolong opioid adverse
reactions. When using VANTRELA ER with CYP3A4 inhibitors or discontinuing
CYP3A4 inducers in VANTRELA ER-treated patients, monitor patients closely at
frequent intervals and consider dosage reduction of VANTRELA ER until stable
drug effects are achieved [see DRUG INTERACTIONS].
Concomitant use of VANTRELA ER with CYP3A4 inducers or
discontinuation of a CYP3A4 inhibitor could decrease hydrocodone plasma
concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal
syndrome in a patient who had developed physical dependence to hydrocodone.
When using VANTRELA ER with CYP3A4 inducers or discontinuing CYP3A4 inhibitors,
monitor patients closely at frequent intervals and consider increasing the
opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid
withdrawal occur [see DRUG INTERACTIONS].
Risks From Concomitant Use With Benzodiazepines Or Other
Profound sedation, respiratory depression, coma, and
death may result from the concomitant use of VANTRELA ER with benzodiazepines
or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics,
anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics,
other opioids, alcohol). Because of these risks, reserve concomitant
prescribing of these drugs for use in patients for whom alternative treatment
options are inadequate.
Observational studies have demonstrated that concomitant
use of opioid analgesics and benzodiazepines increases the risk of drug-related
mortality compared to use of opioid analgesics alone. Because of similar
pharmacological properties, it is reasonable to expect similar risk with the
concomitant use of other CNS depressant drugs with opioid analgesics [see
If the decision is made to prescribe a benzodiazepine or
other CNS depressant concomitantly with an opioid analgesic, prescribe the
lowest effective dosages and minimum durations of concomitant use. In patients
already receiving an opioid analgesic, prescribe a lower initial dose of the
benzodiazepine or other CNS depressant than indicated in the absence of an
opioid, and titrate based on clinical response. If an opioid analgesic is
initiated in a patient already taking a benzodiazepine or other CNS depressant,
prescribe a lower initial dose of the opioid analgesic, and titrate based on
clinical response. Follow patients closely for signs and symptoms of respiratory
depression and sedation.
Advise both patients and caregivers about the risks of
respiratory depression and sedation when VANTRELA ER is used with
benzodiazepines or other CNS depressants (including alcohol and illicit drugs).
Advise patients not to drive or operate heavy machinery until the effects of concomitant
use of the benzodiazepine or other CNS depressant have been determined. Screen patients
for risk of substance use disorders, including opioid abuse and misuse, and
warn them of the risk for overdose and death associated with the use of
additional CNS depressants including alcohol and illicit drugs [see DRUG
INTERACTIONS, PATIENT INFORMATION].
Life-Threatening Respiratory Depression In Patients With Chronic
Pulmonary Disease And In Elderly, Cachectic, Or Debilitated Patients
The use of VANTRELA ER in patients with acute or severe
bronchial asthma in an unmonitored setting or in the absence of resuscitative
equipment is contraindicated.
Patients With Chronic Pulmonary Disease
VANTRELA ER -treated patients with significant chronic
obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased
respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory
depression are at increased risk of decreased respiratory drive including
apnea, even at recommended dosages of VANTRELA ER [see Life-Threatening Respiratory Depression].
Elderly, Cachectic, Or Debilitated Patients
Life-threatening respiratory depression is more likely to
occur in elderly, cachectic, or debilitated patients because they may have
altered pharmacokinetics or altered clearance compared to younger, healthier
patients [see Life-Threatening Respiratory Depression].
Monitor such patients closely, particularly when
initiating and titrating VANTRELA ER and when VANTRELA ER is given
concomitantly with other drugs that depress respiration [see Life-Threatening Respiratory Depression and Risks from Concomitant Use with Benzodiazepines or Other CNS
Depressants]. Alternatively, consider the use of non-opioid analgesics in these
Cases of adrenal insufficiency have been reported with
opioid use, more often following greater than one month of use. Presentation of
adrenal insufficiency may include non-specific symptoms and signs including
nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic
testing as soon as possible. If adrenal insufficiency is diagnosed, treat with
physiologic replacement doses of corticosteroids. Wean the patient off of the
opioid to allow adrenal function to recover and continue corticosteroid
treatment until adrenal function recovers. Other opioids may be tried as some
cases reported use of a different opioid without recurrence of adrenal
insufficiency. The information available does not identify any particular
opioids as being more likely to be associated with adrenal insufficiency.
VANTRELA ER may cause severe hypotension including
orthostatic hypotension and syncope in ambulatory patients. There is an added
risk to individuals whose ability to maintain blood pressure has been
compromised by a depleted blood volume or concurrent administration of certain
CNS depressants (e.g., phenothiazines or general anesthetics) [see DRUG
INTERACTIONS]. Monitor these patients for signs of hypotension after
initiating or titrating the dosage of VANTRELA ER. In patients with circulatory
shock, VANTRELA ER may cause vasodilation that can further reduce cardiac
output and blood pressure. Avoid the use of VANTRELA ER in patients with
Risks Of Use In Patients With Increased Intracranial
Pressure, Brain Tumors, Head Injury, Or Impaired Consciousness
In patients who may be susceptible to the intracranial
effects of CO2 retention (e.g., those with evidence of increased intracranial
pressure as can be caused by certain brain tumors), VANTRELA ER may reduce
respiratory drive, and the resultant CO2 retention can further increase
intracranial pressure. Monitor such patients for signs of sedation and
respiratory depression, particularly when initiating therapy with VANTRELA ER.
Opioids may also obscure the clinical course in a patient
with a head injury. Avoid the use of VANTRELA ER in patients with impaired
consciousness or coma.
Risks Of Use In Patients With Gastrointestinal Conditions
VANTRELA ER is contraindicated in patients with known or
suspected gastrointestinal obstruction, including paralytic ileus.
The hydrocodone in VANTRELA ER may cause spasm of the
sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor
patients with biliary tract disease, including acute pancreatitis, for
Increased Risk Of Seizures In Patients With Seizure
The hydrocodone in VANTRELA ER may increase the frequency
of seizures in patients with seizure disorders, and may increase the risk of
seizures occurring in other clinical settings associated with seizures. Monitor
patients with a history of seizure disorders for worsened seizure control
during VANTRELA ER therapy.
Avoid the use of mixed agonist/antagonist (e.g.,
pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine)
analgesics in patients who are receiving a course of therapy with a full opioid
agonist analgesic, including VANTRELA ER. In these patients, mixed agonist/antagonist
and partial agonist analgesics may reduce the analgesic effect and/or may precipitate
withdrawal symptoms [see DRUG INTERACTIONS].
When discontinuing VANTRELA ER, gradually taper the
dosage [see DOSAGE AND ADMINISTRATION]. Do not abruptly discontinue
VANTRELA ER [see Drug Abuse and Dependence].
Risks Of Driving And Operating Machinery
VANTRELA ER may impair the mental and physical abilities
needed to perform potentially hazardous activities such as driving a car or
operating machinery. Warn patients not to drive or operate dangerous machinery
unless they are tolerant to the effects of VANTRELA ER and know how they will
react to the medication.
Risk Of QTc Interval Prolongation
QTc prolongation has been observed with VANTRELA ER [see
CLINICAL PHARMACOLOGY]. Consider this observation when making clinical
decisions regarding monitoring of patients with congestive heart failure,
bradyarrhythmias, or electrolyte abnormalities, or who are taking medications
that are known to prolong the QTc interval. Avoid use of VANTRELA ER in patients
with congenital long QT syndrome. In patients who develop QTc prolongation,
consider changing to an alternate analgesic. Do not exceed a dose of 90 mg
every 12 hours (180 mg per day). Higher doses have not been studied.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (Medication Guide).
Addiction, Abuse, And Misuse
Inform patients that the use of VANTRELA ER, even when
taken as recommended, can result in addiction which can lead to overdose or
death [see WARNINGS AND PRECAUTIONS]. Instruct patients not to share
VANTRELA ER with others and to take steps to protect VANTRELA ER from theft or
Life-threatening Respiratory Depression
Inform patients of the risk of life-threatening
respiratory depression, including information that the risk is greatest when
starting VANTRELA ER or when the dosage is increased, and that it can occur
even at recommended dosages [see WARNINGS AND PRECAUTIONS]. Advise
patients how to recognize respiratory depression and to seek medical attention
if they are experiencing breathing difficulties.
Inform patients that accidental ingestion, especially by
children, may result in respiratory depression or death [see WARNINGS AND
PRECAUTIONS]. Instruct patients to take steps to store VANTRELA ER securely
and to dispose of unused VANTRELA ER by flushing the tablets down the toilet.
Interaction With Benzodiazepines And Other CNS
Inform patients and caregivers that potentially fatal
additive effects may occur if VANTRELA ER is used with benzodiazepines or other
CNS depressants, including alcohol, and not to use these concomitantly unless
supervised by a healthcare provider [see WARNINGS AND PRECAUTIONS, DRUG
Inform patients that opioids could cause a rare but
potentially life-threatening condition resulting from concomitant
administration of serotonergic drugs. Warn patients of the symptoms of serotonin
syndrome and to seek medical attention right away if symptoms develop. Instruct
patients to inform their healthcare providers if they are taking, or plan to
take serotonergic medications [see DRUG INTERACTIONS].
Inform patients to avoid taking VANTRELA ER while using
any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while
taking VANTRELA ER [see DRUG INTERACTIONS].
Inform patients that opioids could cause adrenal
insufficiency, a potentially life-threatening condition. Adrenal insufficiency
may present with non-specific symptoms and signs such as nausea, vomiting,
anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients
to seek medical attention if they experience a constellation of these symptoms [see
WARNINGS AND PRECAUTIONS].
Important Administration Instructions
Instruct patients how to properly take VANTRELA ER,
including the following:
- Swallow VANTRELA ER tablets whole. Do not crush, chew, or
dissolve the tablet or its contents.
- Use VANTRELA ER exactly as prescribed to reduce the risk
of life-threatening adverse reactions (e.g., respiratory depression).
- Do not discontinue VANTRELA ER without first discussing
the need for a tapering regimen with the prescriber [see DOSAGE AND
Inform patients that VANTRELA ER may cause orthostatic
hypotension and syncope. Instruct patients how to recognize symptoms of low
blood pressure and how to reduce the risk of serious consequences should
hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying
position) [see WARNINGS AND PRECAUTIONS].
QT Interval Prolongation
Inform patients that QT prolongation has been observed
with VANTRELA ER [see CLINICAL PHARMACOLOGY]. VANTRELA ER should be
avoided in patients with congenital long QT syndrome. Instruct patients with a
history of congestive heart failure or bradyarrhythmias, and patients at risk
for electrolyte abnormalities, or who are taking other medications known to prolong
the QT interval, that periodic monitoring of electrocardiograms and
electrolytes may be necessary during therapy with VANTRELA ER [see WARNINGS
Inform patients that anaphylaxis has been reported with
ingredients contained in VANTRELA ER. Advise patients how to recognize such a
reaction and when to seek medical attention [see CONTRAINDICATIONS, ADVERSE
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that
prolonged use of VANTRELA ER during pregnancy can result in neonatal opioid
withdrawal syndrome, which may be life-threatening if not recognized and
treated [see WARNINGS AND PRECAUTIONS, Use in Specific Populations].
Inform female patients of reproductive potential that
VANTRELA ER can cause fetal harm and to inform their healthcare provider of a
known or suspected pregnancy [see Use in Specific Populations].
Advise patients that breastfeeding is not recommended
during treatment with VANTRELA ER [see Use in Specific Populations].
Inform patients that chronic use of opioids may cause
reduced fertility. It is not known whether these effects on fertility are
reversible [see ADVERSE REACTIONS, Use in Specific Populations].
Driving Or Operating Heavy Machinery
Inform patients that VANTRELA ER may impair the ability
to perform potentially hazardous activities such as driving a car or operating
heavy machinery. Advise patients not to perform such tasks until they know how
they will react to the medication [see WARNINGS AND PRECAUTIONS].
Advise patients of the potential for severe constipation,
including management instructions and when to seek medical attention [see
Disposal Of Unused VANTRELA ER
Advise patients to flush any unused tablets down the
toilet when VANTRELA ER is no longer needed.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Hydrocodone was evaluated for carcinogenic potential in
rats and mice. In a two-year bioassay in rats, doses up to 30 mg/kg in males
and 100 mg/kg in females were administered orally and no treatment-related
neoplasms were observed (exposure is equivalent to 0.06 times and 0.4 times for
males and females, respectively the human hydrocodone dose of 180 mg/day based
on AUC exposure comparisons). In a two-year bioassay in mice, doses up to 100
mg/kg in males and females were administered orally and no treatment-related
neoplasms were observed (exposure is equivalent to 0.6 times and 1.1 times,
respectively, the human hydrocodone dose of 180 mg/day based on AUC exposure
Clastogenicity was observed with hydrocodone in the
chromosomal aberration assay in human lymphocytes. There was no evidence of
genotoxic potential in an in vitro bacterial reverse mutation assay (Salmonella
typhimurium and Escherichia coli) or in an in vivo assay for chromosomal
aberrations (mouse bone marrow micronucleus assay).
Impairment Of Fertility
In a fertility and general reproductive performance
study, rats were administered doses of 0 (vehicle), 7, 20 and 60 mg/kg/day
(equivalent to approximately 0.4, 1.1 and 3.2 times an adult human dose of 180
mg/day on a mg/m² basis). Male and female rats were dosed prior to cohabitation
(28 and 14 days, respectively), during cohabitation and through gestation day 6
(implantation). Females were treated for at least 20 days while males received
at least 42 daily doses prior to necropsy. Treated males were mated with
untreated females and treated females were mated with untreated males. Overall
mating performance was unaffected by treatment with hydrocodone bitartrate,
although the weights of male and female reproductive organs were decreased in
males and females treated with 20 and 60 mg/kg. Additionally, the latency to
mate was increased in the 20 and 60 mg/kg treated males. In the pregnant
females, early embryonic development was not affected by treatment with
hydrocodone bitartrate at doses up to 60 mg/kg (approximately 3.2 times the
adult human daily dose of 180 mg/day on a mg/m² basis).
Use In Specific Populations
Prolonged use of opioid analgesics during pregnancy may
cause neonatal opioid withdrawal syndrome [see WARNINGS AND PRECAUTIONS].
There are no available data on VANTRELA ER use in pregnant women to inform any
drug associated risks. In animal toxicology studies, hydrocodone administered
to pregnant rats during the period of organogenesis resulted in embryo-fetal
toxicities including increased post-implantation loss and non-viable litters at
doses approximately 2 fold the human hydrocodone dose of 180 mg/day. In another
study, decreases in survival were seen in the offspring of rats administered
hydrocodone during gestation and lactation at doses equivalent to the human
dose of 180 mg/day. Additionally, in these rats increased post-implantation
loss and decreased body weights of the pups from birth through weaning was seen
at doses of hydrocodone 3 fold the human hydrocodone dose of 180 mg/day. No
teratogenicity was observed in the offspring of rats and rabbits administered
oral hydrocodone during the period of organogenesis at doses in both species 5
fold the human dose of 180 mg/day. Advise pregnant women of the potential risks
to a fetus.
The 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 2-4% and 15-20%,
Fetal/Neonatal Adverse Reactions
Prolonged use of opioid analgesics during pregnancy for
medical or nonmedical purposes can result in physical dependence in the neonate
and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid
withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep
pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain
weight. The onset, duration, and severity of neonatal opioid withdrawal
syndrome vary based on the specific opioid used, duration of use, timing and
amount of last maternal use, and rate of elimination of the drug by the
newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and
manage accordingly [see WARNINGS AND PRECAUTIONS].
Labor and Delivery
Opioids cross the placenta and may produce respiratory
depression and psycho-physiologic effects in neonates. An opioid antagonist
such as naloxone must be available for reversal of opioid induced respiratory
depression in the neonate. VANTRELA ER is not recommended for use in women
immediately prior to labor, when use of shorter-acting analgesics or other analgesic
techniques are more appropriate. Opioid analgesics, including VANTRELA ER, can prolong
labor through actions which temporarily reduce the strength, duration, and
frequency of uterine contractions. However, this effect is not consistent and
may be offset by an increased rate of cervical dilatation, which tends to
shorten labor. Monitor neonates exposed to opioid analgesics during labor for
signs of excess sedation and respiratory depression.
Oral doses of hydrocodone were administered to pregnant
rats and rabbits during the period of organogenesis. In rats, embryo-fetal
toxicities including increased post-implantation loss and non-viable litters
were observed at doses of 33 mg/kg and above (approximately 2 fold the human
hydrocodone dose of 180 mg/day based on body surface area comparisons).
Maternal toxicity (body weight loss) was present in the study at all doses. In
rabbits, no adverse effects on embryo-fetal development were observed at doses
up to 48 mg/kg (approximately 5 fold the human hydrocodone dose of 180 mg/day
based on body surface area comparisons). No evidence of teratogenicity was
observed in either study at doses up to 100 mg/kg in rat and 48 mg/kg in rabbit (approximately 5 fold for both rats and rabbits
the human hydrocodone dose of 180 mg/day based on body surface area exposure
Hydrocodone was administered orally to female rats during
gestation and lactation in a pre- and post-natal development study. Decreases
in pup survival at doses of 20 mg/kg and above (equivalent to the human
hydrocodone dose of 180 mg/day, based on body surface area comparisons).
Increased post-implantation loss and decreased body weights of the F1
generation pups from birth through weaning were seen at 60 mg/kg/day (3 fold
the human hydrocodone dose of 180 mg/day, based on body surface area comparisons).
Maternally toxic decreases in body weight were also observed at these doses.
Hydrocodone is present in human milk. Lactation studies
have not been conducted with extended-release hydrocodone, including VANTRELA
ER, and no information is available on the effects of the drug on the breastfed
infant or the effects of the drug on milk production. Because of the potential
for serious adverse reactions, including excess sedation and respiratory depression
in a breastfed infant, advise patients that breastfeeding is not recommended
during treatment with VANTRELA ER.
Monitor infants exposed to VANTRELA ER through breast
milk for excess sedation and respiratory depression. Withdrawal symptoms can
occur in breastfed infants when maternal administration of an opioid analgesic
is stopped, or when breast-feeding is stopped.
Females And Males Of Reproductive Potential
Chronic use of opioids may cause reduced fertility in
females and males of reproductive potential. It is not known whether these
effects on fertility are reversible [see ADVERSE REACTIONS, CLINICAL
In animal studies, male rats treated with hydrocodone
bitartrate at 3.2 times the human daily dose of 180 mg demonstrated decreased
epididymides weights and male rats treated with 1 times the human daily dose
demonstrated decreased latency to mating. Female rats treated with 1 times the human
daily dose of 180 mg demonstrated decreased corpora lutea and at 3.2 times the
human daily dose of 180 mg decreased implantation sites [see Nonclinical
The safety and effectiveness of VANTRELA ER in patients
less than 18 years of age has not been established.
There were no dedicated studies to assess efficacy,
safety or PK for the geriatric population. However, when the safety of VANTRELA
ER was compared in the phase 3 double-blind studies in patients ≤ 65
(n=986) and > 65 (N=190) years old, there was a higher incidence of adverse events
in patients > 65 years of age compared with those ≤ 65 years of age for
both the placebo and VANTRELA ER groups. In general, dosage selection for an
elderly patient should be cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal, or
cardiac function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly
patients treated with opioids, and has occurred after large initial doses were
administered to patients who were not opioid-tolerant or when opioids were
co-administered with other agents that depress respiration. Titrate the dosage
of VANTRELA ER slowly in geriatric patients and monitor closely for signs of
central nervous system and respiratory depression [see WARNINGS AND
Hydrocodone 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, care should be taken in dose selection, and
it may be useful to monitor renal function.
Patients with hepatic impairment may have higher plasma
concentrations of hydrocodone than those with normal hepatic function.
Therefore, a dosage reduction is recommended in patients with mild and moderate
hepatic impairment [see DOSAGE AND ADMINISTRATION]. VANTRELA ER is not
recommended in patients with severe hepatic impairment. Monitor these patients
closely for adverse events such as respiratory depression [see CLINICAL
No adjustment in starting dose with VANTRELA ER is
required for patients with mild renal impairment. Patients with moderate or
severe renal impairment or end stage renal disease may have higher plasma
concentrations than those with normal renal function. Therefore, a dosage reduction
is recommended in patients with moderate or severe renal impairment, or end
stage renal disease [see DOSAGE AND ADMINISTRATION]. Monitor all
patients closely for adverse events such as respiratory depression, sedation,
and hypertension [see CLINICAL PHARMACOLOGY].