WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Addiction, Abuse, And Misuse
TROXYCA ER contains oxycodone,
a Schedule II controlled substance. As an opioid, TROXYCA ER exposes users to
the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence].
As extended-release products such as TROXYCA 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 oxycodone present [see Drug Abuse and Dependence].
Although the risk of addiction
in any individual is unknown, it can occur in patients appropriately prescribed
TROXYCA ER and in those who obtain the drug illicitly. 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 TROXYCA ER, and monitor
all patients receiving TROXYCA 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 TROXYCA ER, but use in such
patients necessitates intensive counseling about the risks and proper use of
TROXYCA ER along with intensive monitoring for signs of addiction, abuse, and
misuse.
Abuse or misuse of TROXYCA ER
by cutting, breaking, chewing, crushing, or dissolving the pellets in TROXYCA
ER and then swallowing, snorting or injecting will result in the uncontrolled
delivery of the oxycodone and can result in overdose and death [see
OVERDOSAGE]. Misuse or abuse of TROXYCA ER by these methods may also
release sufficient naltrexone to precipitate withdrawal in opioid-dependent
individuals [see Withdrawal].
Opioids are sought by drug
abusers and people with addiction disorders and are subject to criminal
diversion. Consider these risks when prescribing or dispensing TROXYCA 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 the 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 TROXYCA ER, the risk is greatest during the initiation of therapy or
following a dosage increase. Monitor patients closely for respiratory
depression, especially within the first 24-72 hours of initiating therapy with
and following dosage increases of TROXYCA ER.
To reduce the risk of
respiratory depression, proper dosing and titration of TROXYCA ER are essential
[see DOSAGE AND ADMINISTRATION]. Overestimating the TROXYCA ER dosage
when converting patients from another opioid product can result in fatal
overdose with the first dose.
Accidental ingestion of even
one dose of TROXYCA ER, especially by children, can result in respiratory
depression and death due to an overdose of oxycodone.
Neonatal Opioid Withdrawal
Syndrome
Prolonged use of TROXYCA ER
during pregnancy can result in withdrawal 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, PATIENT INFORMATION].
Risks Of Concomitant Use Or Discontinuation
Of Cytochrome P450 3A4 Inhibitors And Inducers
Concomitant use of TROXYCA ER
with a CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin),
azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g.,
ritonavir), may increase plasma concentrations of oxycodone 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 TROXYCA ER is achieved. Similarly, discontinuation of a CYP3A4 inducer,
such as rifampin, carbamazepine, and phenytoin, in TROXYCA ER-treated patients
may increase oxycodone plasma concentrations and prolong opioid adverse
reactions. When using TROXYCA ER with CYP3A4 inhibitors or discontinuing CYP3A4
inducers in TROXYCA ER-treated patients, monitor patients closely at frequent
intervals and consider dosage reduction of TROXYCA ER until stable drug effects
are achieved [see DRUG INTERACTIONS].
Concomitant use of TROXYCA ER
with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease
oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to
a withdrawal syndrome in a patient who had developed physical dependence to
oxycodone. When using TROXYCA 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 CNS Depressants
Profound sedation, respiratory
depression, coma, and death may result from the concomitant use of TROXYCA 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 DRUG INTERACTIONS].
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 TROXYCA 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 and PATIENT INFORMATION].
Life-Threatening Respiratory Depression In Patients With Chronic
Pulmonary Disease Or In Elderly, Cachectic, Or Debilitated Patients
The use of TROXYCA 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
TROXYCA 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 TROXYCA 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 TROXYCA ER and when TROXYCA 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 patients.
Adrenal Insufficiency
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.
Severe Hypotension
TROXYCA ER may cause severe hypotension including
orthostatic hypotension and syncope in ambulatory patients. There is an
increased risk in patients whose ability to maintain blood pressure has already
been compromised by a reduced blood volume or concurrent administration of
certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see
DRUG INTERACTIONS]. Monitor these patients for signs of hypotension
after initiating or titrating the dosage of TROXYCA ER. In patients with
circulatory shock, TROXYCA ER may cause vasodilation that can further reduce
cardiac output and blood pressure. Avoid the use of TROXYCA ER in patients with
circulatory shock.
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 or brain tumors), TROXYCA 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 TROXYCA ER.
Opioids may also obscure the clinical course in a patient
with a head injury. Avoid the use of TROXYCA ER in patients with impaired
consciousness or coma.
Risks Of Use In Patients With Gastrointestinal Conditions
TROXYCA ER is contraindicated in patients with
gastrointestinal obstruction, including paralytic ileus.
The oxycodone in TROXYCA 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
worsening symptoms.
Increased Risk Of Seizures In Patients With Seizure
Disorders
The oxycodone in TROXYCA ER may increase the frequency of
seizures in patients with seizure disorders and may increase the risk of
seizures in other clinical settings associated with seizures. Monitor patients
with a history of seizure disorders for worsened seizure control during TROXYCA
ER therapy.
Withdrawal
Avoid the use of mixed agonist/antagonist (e.g.,
pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g.,
buprenorphine) analgesics in patients who have received or are receiving a
course of therapy with a full opioid agonist analgesic, including TROXYCA ER.
In these patients, mixed agonists/antagonist and partial agonist analgesics may
reduce the analgesic effect and/or may precipitate withdrawal symptoms.
Consuming TROXYCA ER that has been altered by crushing,
chewing, or dissolving the pellets can release sufficient naltrexone to
precipitate withdrawal in opioid-dependent individuals. Symptoms of withdrawal
usually appear within five minutes of ingestion of naltrexone, can last for up
to 48 hours, and can include mental status changes, restlessness, lacrimation,
rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Significant
fluid losses from vomiting and diarrhea can require intravenous fluid
administration.
When discontinuing TROXYCA ER, gradually taper the dosage
[see DOSAGE AND ADMINISTRATION]. Do not abruptly discontinue TROXYCA ER [see
Drug Abuse and Dependence].
Risks Of Driving And Operating Machinery
TROXYCA ER may impair the mental or 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 TROXYCA ER and know how they will
react to the medication [see PATIENT INFORMATION].
Laboratory Tests And Monitoring
Naltrexone does not interfere with thin-layer,
gas-liquid, or high pressure liquid chromatographic methods which may be used
for the separation and detection of morphine, methadone, oxycodone, or quinine
in the urine. Naltrexone may or may not interfere with enzymatic methods for
the detection of opioids depending on the sensitivity and specificity of the
test. Consult the test manufacturer for details.
Not every urine drug test for “opioids” or “opiates”
detects oxycodone reliably, especially those designed for in-office use.
Further, many laboratories will report urine drug concentrations below a
specified “cut-off” value as “negative”. Therefore, if urine testing for
oxycodone is considered in the clinical management of an individual patient,
ensure that the sensitivity and specificity of the assay is appropriate, and
consider the limitations of the testing used when interpreting results.
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Medication Guide and Instructions for Use).
Addiction, Abuse, And Misuse
Inform patients that the use of TROXYCA ER, even when
taken as recommended, can result in addiction, abuse, and misuse, which can
lead to overdose or death [see WARNINGS AND PRECAUTIONS]. Instruct
patients not to share TROXYCA ER with others and to take steps to protect
TROXYCA ER from theft or misuse.
Life-threatening Respiratory Depression
Inform patients of the risk of life-threatening
respiratory depression, including information that the risk is greatest when
starting TROXYCA 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
breathing difficulties develop.
Accidental Ingestion
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 TROXYCA ER securely
and to dispose of unused TROXYCA ER by flushing the capsules down the toilet.
Interactions With Benzodiazepines And Other CNS
Depressants
Inform patients and caregivers that potentially fatal
additive effects may occur if TROXYCA 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
INTERACTIONS].
Serotonin Syndrome
Inform patients that TROXYCA ER 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 physicians if they are taking, or
plan to take serotonergic medications [see DRUG INTERACTIONS].
MAOI Interaction
Inform patients to avoid taking TROXYCA ER while using
any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while
taking TROXYCA ER [see DRUG INTERACTIONS].
Adrenal Insufficiency
Inform patients that TROXYCA ER 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 TROXYCA ER,
including the following:
- Swallow TROXYCA ER capsules whole or sprinkle the capsule
contents on applesauce and then swallow immediately without chewing [see DOSAGE
AND ADMINISTRATION].
- Do not crush, chew, or dissolve the pellets contained in
the capsules due to a risk of fatal oxycodone overdose or naltrexone
precipitated withdrawal symptoms in opioid-dependent individuals [see DOSAGE
AND ADMINISTRATION].
- Use TROXYCA ER exactly as prescribed to reduce the risk
of life-threatening adverse reactions (e.g., respiratory depression) [see WARNINGS
AND PRECAUTIONS].
- Do not discontinue TROXYCA ER without first discussing
the need for a tapering regimen with the prescriber [see WARNINGS AND
PRECAUTIONS].
Hypotension
Inform patients that TROXYCA ER may cause 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].
Anaphylaxis
Inform patients that anaphylaxis has been reported with
ingredients contained in TROXYCA ER. Advise patients how to recognize such a
reaction and when to seek medical attention [see CONTRAINDICATIONS, ADVERSE
REACTIONS].
Pregnancy
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that
prolonged use of TROXYCA 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].
Embryofetal Toxicity
Inform female patients of reproductive potential that
TROXYCA ER can cause fetal harm and to inform their healthcare provider of a
known or suspected pregnancy [see Use in Specific Populations].
Lactation
Advise patients that breastfeeding is not recommended
during treatment with TROXYCA ER [see Use in Specific Populations].
Infertility
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].
Driving Or Operating Heavy Machinery
Inform patients that TROXYCA 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].
Constipation
Advise patients of the potential for severe constipation,
including management instructions and when to seek medical attention [see ADVERSE
REACTIONS].
Disposal Of Unused TROXYCA ER
Advise patients to flush the unused capsules down the
toilet when TROXYCA ER is no longer needed.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenesis
Long-term studies in animals to evaluate the carcinogenic
potential of TROXYCA ER or oxycodone have not been conducted.
Mutagenesis
Oxycodone HCl was genotoxic in an in vitro mouse lymphoma
assay in the presence of metabolic activation. There was no evidence of
genotoxic potential in an in vitro bacterial reverse mutation assay (Salmonella
typhimurium and Escherichia coli) or in an assay for chromosomal aberrations (in
vivo mouse bone marrow micronucleus assay).
Impairment Of Fertility
Fertility studies have not been performed in animals to
evaluate the potential impact on fertility of TROXYCA ER or oxycodone.
Use In Specific Populations
Pregnancy
Risk Summary
Prolonged use of opioid
analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see WARNINGS
AND PRECAUTIONS].
There are no available data with TROXYCA ER in pregnant women to inform a
drug-associated risk for major birth defects and miscarriage. Because plasma
naltrexone levels were detectable in some patients administered TROXYCA ER in
the clinical trials [see CLINICAL PHARMACOLOGY], the naltrexone
component of TROXYCA ER may precipitate withdrawal in a fetus due to the
immaturity of the fetal blood-brain barrier.
Animal reproduction studies
with oral administrations of oxycodone HCl in rats and rabbits during the
period of organogenesis at doses 2.6 and 8.1 times, respectively, the human
dose of 60 mg/day did not reveal evidence of teratogenicity or embryo-fetal toxicity.
In several published studies, treatment of pregnant rats with oxycodone at
clinically relevant doses and below, resulted in neurobehavioral effects in
offspring [see Data]. Based on animal data, advise pregnant women of the
potential risk to a fetus.
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
2-4% and 15-20%, respectively.
Clinical Considerations
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 or 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. TROXYCA ER is not
recommended for use in pregnant women during and immediately prior to labor,
when use of shorter acting analgesics or other analgesic techniques are more
appropriate. Opioid analgesics, including TROXYCA ER, can prolong labor through
actions that 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. Â
Data
Animal Data
In embryo-fetal development studies in rats and rabbits,
pregnant animals received oral doses of oxycodone HCl administered during the
period of organogenesis up to 16 mg/kg/day and up 25 mg/kg/day, respectively.
These studies revealed no evidence of teratogenicity or embryo-fetal toxicity
due to oxycodone. The highest doses tested in rats and rabbits were equivalent
to approximately 2.6 and 8.1 times an adult human dose of 60 mg/day,
respectively, on a mg/m² basis. In published studies, offspring of pregnant
rats administered oxycodone during gestation have been reported to exhibit
neurobehavioral effects including altered stress responses, increased
anxiety-like behavior (2 mg/kg/day IV from Gestation Day 8 to 21 and Postnatal
Day 1, 3, and 5; 0.3-times an adult human dose of 60 mg/day, on a mg/m² basis)
and altered learning and memory (15 mg/kg/day orally from breeding through
parturition; 2.4 times an adult human dose of 60 mg/day, on a mg/m² basis).
Lactation
Risk Summary
Oxycodone is present in breast
milk. Published lactation studies report variable concentrations of oxycodone
in breast milk with administration of immediate-release oxycodone to nursing
mothers in the early postpartum period. The lactation studies did not assess
breastfed infants for potential adverse reactions. Lactation studies have not
been conducted with extended-release oxycodone, including TROXYCA 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 TROXYCA ER.
Clinical Considerations
Monitor infants exposed to
TROXYCA 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 breastfeeding is stopped. Because
plasma naltrexone levels were detectable in some patients administered TROXYCA
ER in the clinical trials [see CLINICAL PHARMACOLOGY], the naltrexone
component of TROXYCA ER may precipitate opioid withdrawal in a breastfed infant.
Females And Males Of Reproductive
Potential
Infertility
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 PHARMACOLOGY].
Pediatric Use
The safety and efficacy of
TROXYCA ER in patients less than 18 years of age have not been established.
Geriatric Use
The pharmacokinetics of TROXYCA
ER have not been investigated in elderly patients ( ≥ 65 years) although
such patients were included in clinical studies. Clinical studies with TROXYCA
ER did not include sufficient numbers of subjects aged 65 and older to
determine if they respond differently than younger subjects. Other reported clinical
experience has not identified differences in responses between the elderly and
younger patients.
Elderly patients (aged 65 years
or older) may have increased sensitivity to oxycodone. In general, use caution
when selecting a dosage for an elderly patient, usually starting at the low end
of the dosing range, reflecting the greater frequency of decreased hepatic,
renal, or cardiac function, concomitant disease, and use of 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 TROXYCA ER slowly in geriatric patients and
monitor closely for signs of central nervous system and respiratory depression [see
WARNINGS AND PRECAUTIONS].
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, care should be taken
in dose selection, and it may be useful to monitor renal function.
Hepatic Impairment
Since oxycodone is extensively
metabolized in the liver, its clearance may decrease in patients with hepatic
impairment. Naltrexone is sequestered in the TROXYCA ER capsules and is not
intended to be released when TROXYCA ER is used as directed. However,
measurable naltrexone plasma concentrations have been observed in some patients
in clinical trials with TROXYCA ER [see CLINICAL PHARMACOLOGY]. An
increase in naltrexone AUC in patients with compensated and decompensated liver
cirrhosis, compared with subjects with normal liver function, has been reported
[see CLINICAL PHARMACOLOGY]. These data also suggest that alterations in
naltrexone bioavailability are related to liver disease severity.
Dose initiation of TROXYCA ER
should follow a conservative approach in patients with hepatic impairment. In
patients with hepatic impairment, there is a potential for differential
increase in naltrexone exposure compared to oxycodone exposure. Hence, when
administering TROXYCA ER to patients with hepatic impairment, monitor patients
closely for signs of central nervous system or respiratory depression due to
elevated levels of oxycodone and for signs of withdrawal due to elevated levels
of naltrexone and adjust the dose based on the clinical response.
Renal Impairment
Elimination of oxycodone is
reported to be impaired in patients with renal impairment.
Although naltrexone is
sequestered in the TROXYCA ER formulations, measurable naltrexone plasma
concentrations have been observed in some patients in clinical trials with
TROXYCA ER [see CLINICAL PHARMACOLOGY]. Since naltrexone and its primary
metabolite are excreted primarily in urine, their plasma concentrations may be
increased in patients with renal impairment.
Dose initiation of TROXYCA ER
should follow a conservative approach in patients with renal impairment. In
patients with renal impairment, there is a potential for differential increase
in naltrexone exposure compared to oxycodone exposure. Hence, when
administering TROXYCA ER to patients with renal impairment, monitor patients
closely for signs of central nervous system or respiratory depression due to
elevated levels of oxycodone and for signs of withdrawal due to elevated levels
of naltrexone and adjust the dose based on the clinical response.
Sex Differences
There are no clinically
significant differences in oxycodone pharmacokinetics following oral
administration of TROXYCA ER to males or females; therefore, no specific dosage
adjustment is recommended for the initiation or maintenance of TROXYCA ER doses
based on the sex of the patient [see CLINICAL PHARMACOLOGY].