Included as part of the "PRECAUTIONS" Section
Addiction, Abuse, And Misuse
OXYCONTIN contains oxycodone, a Schedule II controlled substance. As an opioid,
OXYCONTIN exposes users to the risks of addiction, abuse, and misuse. Because extendedrelease
products such as OXYCONTIN 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 OXYCONTIN. Addiction can occur at recommended doses and if the
drug is misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing
OXYCONTIN, and monitor all patients receiving OXYCONTIN for the development of these
behaviors and 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
OXYCONTIN, but use in such patients necessitates intensive counseling about the risks and
proper use of OXYCONTIN along with intensive monitoring for signs of addiction, abuse, and
Abuse or misuse of OXYCONTIN by crushing, chewing, snorting, or injecting the dissolved
product will result in the uncontrolled delivery of oxycodone and 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 OXYCONTIN.
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:
- 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
patient-prescriber 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 www.fda.gov/OpioidAnalgesicREMSBlueprint .
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 of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the
use of OXYCONTIN, 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 OXYCONTIN.
To reduce the risk of respiratory depression, proper dosing and titration of OXYCONTIN are
essential [see DOSAGE AND ADMINISTRATION]. Overestimating the OXYCONTIN dosage when
converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of OXYCONTIN, especially by children, can result in
respiratory depression and death due to an overdose of oxycodone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of OXYCONTIN 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
Concomitant use of OXYCONTIN 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 OXYCONTIN is
achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine,
and phenytoin, in OXYCONTIN-treated patients may increase oxycodone plasma concentrations
and prolong opioid adverse reactions. When using OXYCONTIN with CYP3A4 inhibitors or
discontinuing CYP3A4 inducers in OXYCONTIN-treated patients, monitor patients closely at
frequent intervals and consider dosage reduction of OXYCONTIN until stable drug effects are
achieved [see DRUG INTERACTIONS].
Concomitant use of OXYCONTIN with CYP3A4 inducers or discontinuation of a 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 OXYCONTIN 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 if OXYCONTIN is used
concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., nonbenzodiazepines
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
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
OXYCONTIN 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
Or In Elderly, Cachectic, Or Debilitated Patients
The use of OXYCONTIN 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
OXYCONTIN-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
OXYCONTIN [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 OXYCONTIN and when
OXYCONTIN is given concomitantly with other drugs that depress respiration [see Life-Threatening Respiratory Depression, 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.
OXYCONTIN 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 OXYCONTIN. In patients with circulatory shock, OXYCONTIN may cause
vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of
OXYCONTIN 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), OXYCONTIN 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 OXYCONTIN.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of
OXYCONTIN in patients with impaired consciousness or coma.
Difficulty In Swallowing And Risk For Obstruction In Patients At Risk For A Small
There have been post-marketing reports of difficulty in swallowing OXYCONTIN tablets. These
reports included choking, gagging, regurgitation and tablets stuck in the throat. Instruct patients
not to pre-soak, lick, or otherwise wet OXYCONTIN tablets prior to placing in the mouth, and to
take one tablet at a time with enough water to ensure complete swallowing immediately after
placing in the mouth.
There have been rare post-marketing reports of cases of intestinal obstruction, and exacerbation
of diverticulitis, some of which have required medical intervention to remove the tablet. Patients
with underlying GI disorders such as esophageal cancer or colon cancer with a small
gastrointestinal lumen are at greater risk of developing these complications. Consider use of an
alternative analgesic in patients who have difficulty swallowing and patients at risk for
underlying GI disorders resulting in a small gastrointestinal lumen.
Risks Of Use In Patients With Gastrointestinal Conditions
OXYCONTIN is contraindicated in patients with known or suspected gastrointestinal
obstruction, including paralytic ileus.
The oxycodone in OXYCONTIN 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 symptoms.
Increased Risk Of Seizures In Patients With Seizure Disorders
The oxycodone in OXYCONTIN 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 OXYCONTIN 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 full opioid agonist
analgesic, including OXYCONTIN. In these patients, mixed agonist/antagonist and partial
agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.
When discontinuing OXYCONTIN, gradually taper the dosage [see DOSAGE AND ADMINISTRATION]. Do not abruptly discontinue OXYCONTIN [see Drug Abuse And Dependence].
Risks Of Driving And Operating Machinery
OXYCONTIN 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 OXYCONTIN and know
how they will react to the medication [see PATIENT INFORMATION].
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).
Addiction, Abuse And Misuse
Inform patients that the use of OXYCONTIN, 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 OXYCONTIN with others and to take steps to
protect OXYCONTIN 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 OXYCONTIN 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
To guard against excessive exposure to OXYCONTIN by young children, advise caregivers to
strictly adhere to recommended OXYCONTIN dosing.
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
OXYCONTIN securely and to dispose of unused OXYCONTIN by flushing the tablets down the
Interactions With Benzodiazepines Or Other CNS Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if OXYCONTIN
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 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 provider if they are taking, or plan to take serotonergic
medications [see DRUG INTERACTIONS].
Inform patients to avoid taking OXYCONTIN while using any drugs that inhibit monoamine
oxidase. Patients should not start MAOIs while taking OXYCONTIN [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 OXYCONTIN, including the following:
- OXYCONTIN is designed to work properly only if swallowed intact. Taking cut,
broken, chewed, crushed, or dissolved OXYCONTIN tablets can result in a fatal overdose
[see DOSAGE AND ADMINISTRATION].
- OXYCONTIN tablets should be taken one tablet at a time [see DOSAGE AND ADMINISTRATION].
- Do not pre-soak, lick, or otherwise wet the tablet prior to placing in the mouth [see DOSAGE AND ADMINISTRATION].
- Take each tablet with enough water to ensure complete swallowing immediately after
placing in the mouth [see DOSAGE AND ADMINISTRATION].
- Do not discontinue OXYCONTIN without first discussing the need for a tapering
regimen with the prescriber [see DOSAGE AND ADMINISTRATION].
Inform patients that OXYCONTIN 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 OXYCONTIN.
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 OXYCONTIN
during pregnancy can result in neonatal opioid withdrawal syndrome, which may be lifethreatening
if not recognized and treated [see WARNINGS AND PRECAUTIONS , Use In Specific Populations].
Inform female patients of reproductive potential that OXYCONTIN 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 OXYCONTIN [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 Use In Specific Populations].
Driving Or Operating Heavy Machinery
Inform patients that OXYCONTIN 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 ADVERSE REACTIONS].
Disposal Of Unused OXYCONTIN
Advise patients to flush the unused tablets down the toilet when OXYCONTIN is no longer
Healthcare professionals can telephone Purdue Pharma’s Medical Services Department (1-888-
726-7535) 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
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/day). Male rats were dosed for 28 days
before cohabitation with females, during the cohabitation and until necropsy (2-3 weeks postcohabitation).
Females were dosed for 14 days before cohabitation with males, during
cohabitation and up to Gestation Day 6. Oxycodone hydrochloride did not affect reproductive
function in male or female rats at any dose tested (up to 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
OXYCONTIN 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 60 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%,
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
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. OXYCONTIN 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 OXYCONTIN, 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.
Pregnant rats were treated with 0.5, 2, 4, and 8 mg/kg oxycodone hydrochloride (0.08, 0.3, 0.7,
and 1.3 times the human daily dose of 60 mg/day, respectively based on a mg/m2 basis) during
the period of organogenesis. Oxycodone did not cause adverse effects to the fetus at exposures
up to 1.3 times the human dose of 60 mg/day. The high dose produced maternal toxicity
characterized by excessive gnawing on forelimbs and decreased body weight gain.
Pregnant rabbits were treated with 1, 5, 25, and 125 mg/kg oxycodone hydrochloride (0.3, 2, 8,
and 40 times the human daily dose of 60 mg/day, respectively, based on a mg/m2 basis) during
the period of organogenesis. Oxycodone did not cause adverse effects to the fetus at exposures
up to 40 times the human dose of 60 mg/day. The 25 mg/kg and 125 mg/kg doses high doses
produced maternal toxicity characterized by decreased food consumption and body weight gain.
Pregnant rats were treated with 0.5, 2, and 6 mg/kg oxycodone hydrochloride (0.08, 0.32, and 1
times the human daily dose of 60 mg/kg, respective, based on a mg/m2 basis, during the period of
organogenesis through lactation. Decreased body weight was found during lactation and the
early post-weaning phase in pups nursed by mothers given the highest dose used (6 mg/kg/day,
equivalent to an adult human dose of 60 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 OXYCONTIN, 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
Infants exposed to OXYCONTIN through breast milk should be monitored for excess sedation
and respiratory depression. Withdrawal symptoms can occur in breast-fed 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].
The safety and efficacy of OXYCONTIN have been established in pediatric patients ages 11 to
16 years. Use of OXYCONTIN is supported by evidence from adequate and well-controlled
trials with OXYCONTIN in adults as well as an open-label study in pediatric patients ages 6 to
16 years. However, there were insufficient numbers of patients less than 11 years of age enrolled
in this study to establish the safety of the product in this age group.
The safety of OXYCONTIN in pediatric patients was evaluated in 155 patients previously
receiving and tolerating opioids for at least 5 consecutive days with a minimum of 20 mg per day
of oxycodone or its equivalent on the two days immediately preceding dosing with
OXYCONTIN. Patients were started on a total daily dose ranging between 20 mg and 100 mg
depending on prior opioid dose.
The most frequent adverse events observed in pediatric patients were vomiting, nausea,
headache, pyrexia, and constipation [see DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS , CLINICAL PHARMACOLOGY and Clinical Trials].
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 (445) in clinical studies of oxycodone hydrochloride controlled-release
tablets, 148 (33.3%) were age 65 and older (including those age 75 and older) while 40 (9.0%)
were age 75 and older. In clinical trials with appropriate initiation of therapy and dose titration,
no untoward or unexpected adverse reactions were seen in the elderly patients who received
oxycodone hydrochloride controlled-release tablets. Thus, the usual doses and dosing intervals
may be appropriate for elderly patients. However, a dosage reduction in debilitated, non-opioidtolerant
patients is recommended [see DOSAGE AND ADMINISTRATION].
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred
after large initial doses were administered to patients who are not opioid-tolerant or when opioids
were co-administered with other agents that depress respiration. Titrate the dosage of
OXYCONTIN slowly in these patients and monitor closely for signs of central nervous system
and respiratory depression. [see WARNINGS AND PRECAUTIONS].
Oxycodone 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.
A study of OXYCONTIN in patients with hepatic impairment demonstrated greater plasma
concentrations than those seen at equivalent doses in persons with normal hepatic function [see CLINICAL PHARMACOLOGY]. Therefore, a dosage reduction is recommended for these
patients [see DOSAGE AND ADMINISTRATION]. Monitor closely for signs of respiratory
depression, sedation, and hypotension.
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 [see CLINICAL PHARMACOLOGY]. Follow a conservative approach
to dose initiation and adjust according to the clinical situation.
In pharmacokinetic studies with OXYCONTIN, opioid-naïve females demonstrate up to 25%
higher average plasma concentrations and greater frequency of typical opioid adverse events than
males, even after adjustment for body weight. The clinical relevance of a difference of this
magnitude is low for a drug intended for chronic usage at individualized dosages, and there was
no male/female difference detected for efficacy or adverse events in clinical trials.