Included as part of the "PRECAUTIONS" Section
Addiction, Abuse, And Misuse
XTAMPZA ER contains oxycodone, a Schedule II controlled substance. As an opioid, XTAMPZA ER exposes
users to the risks of addiction, abuse, and misuse [see Drug Abuse And Dependence]. As extended-release
products such as XTAMPZA 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
XTAMPZA 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 XTAMPZA ER, and
monitor all patients receiving XTAMPZA 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 abuse or
addiction) 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 XTAMPZA ER, but use in such patients necessitates intensive counseling about the risks and proper use of
XTAMPZA ER along with intensive monitoring for signs of addiction, abuse, and misuse.
Abuse or misuse of XTAMPZA ER by snorting or by injecting the dissolved product can result in overdose and
death [see OVERDOSE].
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Consider these risks when prescribing or dispensing XTAMPZA 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.
Opioid Analgesic Risk Evaluation And Mitigation Strategy (REMS)
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and
Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products.
Under the requirements of the REMS, drug companies with approved opioid analgesic products must make
REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly
encouraged to do all of the following:
- Complete a REMS-compliant education program offered by an accredited provider of continuing
education (CE) or another education program that includes all the elements of the FDA Education
Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
- Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients
and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG)
can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.
- Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will
receive from their pharmacist every time an opioid analgesic is dispensed to them.
- Consider using other tools to improve patient, household, and community safety, such as patientprescriber
agreements that reinforce patient-prescriber responsibilities.
To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-
800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at
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 OVERDOSE].
Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of
XTAMPZA ER, the risk is greatest during the initiation of therapy or following a dosage increase. Closely
monitor patients for respiratory depression, especially within the first 24-72 hours of initiating therapy with and
following dosage increases of XTAMPZA ER.
To reduce the risk of respiratory depression, proper dosing and titration of XTAMPZA ER are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the XTAMPZA ER dose when converting patients from
another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of XTAMPZA ER, especially by children, can result in respiratory
depression and death due to an overdose of oxycodone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of XTAMPZA 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
Concomitant use of XTAMPZA 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 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 XTAMPZA ER is achieved. Similarly, discontinuation of a CYP3A4 inducer, such
as rifampin, carbamazepine, and phenytoin, in XTAMPZA ER-treated patients may increase oxycodone plasma
concentrations and prolong opioid adverse reactions. When using XTAMPZA ER with CYP3A4 inhibitors or
discontinuing CYP3A4 inducers in XTAMPZA ER-treated patients, monitor patients closely at frequent
intervals and consider dosage reduction of XTAMPZA ER until stable drug effects are achieved [see DRUG INTERACTIONS].
Concomitant use of XTAMPZA 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 XTAMPZA 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 XTAMPZA
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
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 XTAMPZA 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].
Risk Of Life-Threatening Respiratory Depression In Patients With Chronic
Pulmonary Disease Or In Elderly, Cachectic, Or Debilitated Patients
The use of XTAMPZA 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
XTAMPZA 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 XTAMPZA 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 as they may have altered pharmacokinetics or altered clearance
compared to younger, healthier patients.
Monitor such patients closely, particularly when initiating and titrating XTAMPZA ER and when XTAMPZA
ER is given concomitantly with other drugs that depress respiration [see WARNINGS AND PRECAUTIONS].
Alternatively, consider the use of non-opioid analgesics in these patients. Use an alternative analgesic for
patients who require a dose of XTAMPZA ER less than 9 mg.
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
XTAMPZA 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 XTAMPZA ER. In patients with circulatory shock,
XTAMPZA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the
use of XTAMPZA 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), XTAMPZA 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 XTAMPZA ER.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of XTAMPZA ER
in patients with impaired consciousness or coma.
Risks Of Use In Patients With Gastrointestinal Conditions
XTAMPZA ER is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus.
The oxycodone in XTAMPZA ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in
the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening
Risk Of Use In Patients With Seizure Disorders
The oxycodone in XTAMPZA 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 XTAMPZA 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 have received or are receiving a course of therapy with a full
opioid agonist analgesic, including XTAMPZA ER. In these patients, mixed agonist/antagonist and partial
agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.
When discontinuing XTAMPZA ER, gradually taper the dosage [see DOSAGE AND ADMINISTRATION]. Do not
abruptly discontinue XTAMPZA ER.
Risks Of Driving And Operating Machinery
XTAMPZA 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 XTAMPZA ER and know how they will react to the medication.
Not every urine drug test for “opioids” or “opiates” detects oxycodone reliably, especially those designed for inoffice
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).
Addiction, Abuse, And Misuse
Inform patients that the use of XTAMPZA ER, even when taken as recommended, can result in addiction,
abuse, and misuse, which can lead to overdose and death [see WARNINGS AND PRECAUTIONS]. Instruct
patients not to share XTAMPZA ER with others and to take steps to protect XTAMPZA 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 XTAMPZA 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.
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 XTAMPZA ER securely and to
dispose of unused XTAMPZA ER by flushing the tablets down the toilet.
Interactions With Benzodiazepines And Other CNS Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if XTAMPZA 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].
Inform patients that XTAMPZA 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].
Inform patients to avoid taking XTAMPZA ER while using any drugs that inhibit monoamine oxidase. Patients
should not start MAOIs while taking XTAMPZA ER [see DRUG INTERACTIONS].
Inform patients that XTAMPZA 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].
Because food has an effect on absorption of oxycodone from XTAMPZA ER, each dose of XTAMPZA ER
should be taken with food in order to ensure that appropriate plasma levels are consistently achieved. Instruct
patients to take XTAMPZA ER with approximately the same amount of food regardless of whether they
swallow the capsule whole or sprinkle on soft food or into a cup and then administer directly into the mouth.
XTAMPZA ER may be taken as intact capsules or, alternately, may be administered as a sprinkle on soft foods
or sprinkled into a cup and administered directly into the mouth, or through a nasogastric or gastric feeding tube
[see DOSAGE AND ADMINISTRATION].
Important Administration Instructions
[see DOSAGE AND ADMINISTRATION ,WARNINGS AND PRECAUTIONS]
Instruct patients how to properly take XTAMPZA ER, including the following:
- Taking XTAMPZA ER with food
- Swallowing XTAMPZA ER capsules whole or sprinkling the capsule contents on soft food or into a cup and
administering directly into the mouth
- Using XTAMPZA ER exactly as prescribed to reduce the risk of life-threatening adverse reactions (e.g.,
- Not discontinuing XTAMPZA ER without first discussing the need for a tapering regimen with the
Inform patients that XTAMPZA 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].
Inform patients that anaphylaxis has been reported with ingredients contained in XTAMPZA ER. Advise
patients how to recognize such a reaction and when to seek medical attention [see CONTRAINDICATIONS , ADVERSE REACTIONS].
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that prolonged use of XTAMPZA 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].
Advise females of reproductive potential that XTAMPZA 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 XTAMPZA 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].
Driving Or Operating Heavy Machinery
Inform patients that XTAMPZA 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
Disposal Of Unused XTAMPZA ER
Advise patients to flush the unused capsules down the toilet when XTAMPZA ER is no longer needed.
Healthcare professionals can telephone Collegium Pharmaceutical’s Medical Affairs Department (1-855-331-
5615) for information on this product.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long term studies in animals to evaluate the carcinogenic potential of oxycodone have not been conducted.
Oxycodone was genotoxic in the in vitro mouse lymphoma assay. Oxycodone was negative when tested at
appropriate concentrations in the in vitro chromosomal aberration assay, the in vitro bacterial reverse mutation
assay (Ames test), and the in vivo bone marrow micronucleus assay in mice.
Impairment Of Fertility
In a study of reproductive performance, rats were administered a once daily gavage dose of the vehicle or
oxycodone hydrochloride (0.5, 2, and 8 mg/kg). Male rats were dosed for 28 days before cohabitation with
females, during the cohabitation and until necropsy (2-3 weeks post-cohabitation). Females were dosed for 14
days before cohabitation with males, during cohabitation and up to Gestation Day 6. Oxycodone HCl did not
affect reproductive function in male or female rats at any dose tested (≤ 8 mg/kg/day), up to 1.3 times a human
dose of 60 mg/day.
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 with XTAMPZA ER in pregnant women to
inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, there was
no embryo-fetal toxicity when oxycodone hydrochloride was orally administered to rats and rabbits, during the
period of organogenesis, at doses 1.3 to 40 times the adult human dose of 60 mg/day, respectively. In a pre- and
postnatal toxicity study, when oxycodone was orally administered to rats, there was transiently decreased pup
body weight during lactation and the early post-weaning period at the dose equivalent to an adult dose of 160
mg/day. In several published studies, treatment of pregnant rats with oxycodone hydrochloride 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.
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, highpitched
cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration of use, and severity of
neonatal opioid withdrawal syndrome may 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. XTAMPZA ER is not recommended for use in pregnant women during or immediately prior to
labor, when other analgesic techniques are more appropriate. Opioid analgesics, including XTAMPZA 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
Studies with oral doses of oxycodone hydrochloride in rats up to 8 mg/kg/day and rabbits up to 125 mg/kg/day,
equivalent to 1.3 and 40 times an adult human dose of 160 mg/day, respectively on a mg/m2 basis, did not
reveal evidence of harm to the fetus due to oxycodone. In a pre- and postnatal toxicity study, female rats
received oxycodone during gestation and lactation. There were no drug-related effects on reproductive
performance in these females or any long-term developmental or reproductive effects in pups born to these rats.
Decreased body weight was found during lactation and the early post-weaning phase in pups nursed by dams
given the highest dose used (6 mg/kg/day, equivalent to an adult human dose of 160 mg/day, on a mg/m2 basis).
However, body weight of these pups recovered. In published studies, offspring of pregnant rats administered
oxycodone hydrochloride during gestation have been reported to exhibit neurobehavioral effects including
altered stress responses and 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 oral 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 oral
dose of 60 mg/day on a mg/m2 basis).
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 XTAMPZA 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 XTAMPZA ER.
Infants exposed to XTAMPZA ER through breast milk should be monitored 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 PHARMACOLOGY].
Safety and effectiveness of XTAMPZA ER in pediatric patients below the age of 18 years have not been
In controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was
slightly reduced. Compared to young adults, the plasma concentrations of oxycodone were increased
approximately 15% [see CLINICAL PHARMACOLOGY]. Of the total number of subjects entered into the
titration phase of the Phase 3 study for XTAMPZA ER (740), 88 (12%) were age 65 and older. In this clinical
trial with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were
seen in the elderly patients who received XTAMPZA ER. Thus, the usual doses and dosing intervals may be
appropriate for elderly patients. 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 in 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 XTAMPZA ER slowly in geriatric patients and
monitor closely for signs of central nervous system and respiratory depression [see WARNINGS AND PRECAUTIONS].
A study in patients with hepatic impairment demonstrated greater plasma oxycodone concentrations than those
seen at equivalent doses in persons with normal hepatic function. A similar effect on plasma oxycodone
concentrations can be expected for patients with hepatic impairment taking XTAMPZA ER. Therefore, in the
setting of hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose
titration. Use of alternative analgesics is recommended for patients who require a dose of XTAMPZA ER less
than 9 mg. [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].
In patients with renal impairment, as evidenced by decreased creatinine clearance (<60 mL/min), the
concentrations of oxycodone in the plasma are approximately 50% higher than in subjects with normal renal
function. Follow a conservative approach to dose initiation and adjust according to the clinical situation. Use of
alternative analgesics is recommended for patients who require a dose of XTAMPZA ER less than 9 mg. [see CLINICAL PHARMACOLOGY].
In pharmacokinetic studies with XTAMPZA ER, healthy female subjects demonstrate up to 20% higher
oxycodone plasma exposures than males, even after considering differences in body weight or BMI. The
clinical relevance of a difference of this magnitude is low for a drug intended for chronic usage at
individualized dosages. In the Phase 3 clinical trial there was a greater frequency of typical opioid adverse
events for females than males; there was no male/female difference detected for efficacy.