OxyContin (oxycodone)

OxyContin is a prescription opioid pain medication used to manage pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatment options are inadequate in:

• Adults; and
• Opioid-tolerant pediatric patients 11 years of age and older who are already receiving and tolerate a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent.

Oxycontin may be used alone or with other medications.

It is not known if Oxycontin is safe and effective in children younger than 18 years of age.

WARNING

ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

OxyContin may cause serious side effects including:

• noisy breathing,
• shallow breathing,
• breathing that stops during sleep (sleep apnea),
• slow heart rate or weak pulse,
• light-headed feeling,
• confusion,
• unusual thoughts or behavior,
• seizure,
• nausea,
• vomiting,
• loss of appetite,
• dizziness, and
• worsening tiredness or weakness,

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of OxyContin include:

• drowsiness,
• headache,
• dizziness,
• tiredness,
• constipation,
• stomach pain,
• nausea, and
• vomiting

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Oxycontin. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Addiction, Abuse, and Misuse

OxyContin exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Each person should be assessed for risk prior to prescribing OxyContin and monitored regularly for the development of these behaviors and conditions.

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 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

• complete a REMS-compliant education program,
• counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• consider other tools to improve patient, household, and community safety.

Life-Threatening Respiratory Depression

• Serious, life-threatening, or fatal respiratory depression may occur with use of OxyContin.
• Monitor for respiratory depression, especially during initiation of OxyContin or following a dose increase. Instruct patients to swallow OxyContin tablets whole; crushing, chewing, or dissolving OxyContin tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone.

Accidental Ingestion

• Accidental ingestion of even one dose of OxyContin, especially by children, can result in a fatal overdose of oxycodone.

Neonatal Opioid Withdrawal Syndrome

• Prolonged use of OxyContin during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
• If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Cytochrome P450 3A4 Interaction

• The concomitant use of OxyContin with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.
• In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving OxyContin and any CYP3A4 inhibitor or inducer.

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

• Reserve concomitant prescribing of OxyContin and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.

• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve OxyContin for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
• OxyContin is not indicated as an as-needed (prn) analgesic.
• OxyContin should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
• OxyContin 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Adult patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
• Initiate the dosing regimen for each patient individually; taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.
• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with OxyContin and adjust the dosage accordingly.
• Instruct patients to swallow OxyContin tablets whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth. Instruct patients not to pre-soak, lick, or otherwise wet the tablet prior to placing in the mouth. Cutting, breaking, crushing, chewing, or dissolving OxyContin tablets will result in uncontrolled delivery of oxycodone and can lead to overdose or death.
• OxyContin is administered orally every 12 hours.

Initial Dosage In Adults Who Are Not Opioid-Tolerant

• The starting dosage for patients who are not opioid tolerant is OxyContin 10 mg orally every 12 hours.
• Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion From Opioids To OxyContin In Adults

Conversion From Other Oral Oxycodone Formulations To OxyContin

• If switching from other oral oxycodone formulations to OxyContin, administer one half of the patient's total daily oral oxycodone dose as OxyContin every 12 hours.

Conversion From Other Opioids To OxyContin

• Discontinue all other around-the-clock opioid drugs when OxyContin therapy is initiated.
• There are no established conversion ratios for conversion from other opioids to OxyContin defined by clinical trials. Initiate dosing using OxyContin 10 mg orally every 12 hours.
• It is safer to underestimate a patient’s 24-hour oral oxycodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone dosage and manage an adverse reaction due to an overdose. While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioids.
• Close observation and frequent titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to OxyContin.

Conversion From Methadone To OxyContin

• Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

Conversion From Transdermal Fentanyl To OxyContin

• Treatment with OxyContin can be initiated after the transdermal fentanyl patch has been removed for at least 18 hours.
• Although there has been no systematic assessment of such conversion, start with a conservative conversion: substitute 10 mg of OxyContin every 12 hours for each 25 mcg per hour fentanyl transdermal patch.
• Follow the patient closely during conversion from transdermal fentanyl to OxyContin, as there is limited documented experience with this conversion.

Initial Dosage In Pediatric Patients 11 Years And Older

The following dosing information is for use only in pediatric patients 11 years and older already receiving and tolerating opioids for at least five consecutive days. For the two days immediately preceding dosing with OxyContin, patients must be taking a minimum of 20 mg per day of oxycodone or its equivalent. OxyContin is not appropriate for use in pediatric patients requiring less than a 20 mg total daily dose.

Table 1, based on clinical trial experience, displays the conversion factor when switching pediatric patients 11 years and older (under the conditions described above) from opioids to OxyContin.

Discontinue all other around-the-clock opioid drugs when OxyContin therapy is initiated.

There is substantial inter-patient variability in the relative potency of different opioid drugs and formulations. Therefore, a conservative approach is advised when determining the total daily dosage of OxyContin. It is safer to underestimate a patient’s 24-hour oral oxycodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone requirements and manage an adverse reaction due to an overdose.

Consider the following when using the information in Table 1.

• This is not a table of equianalgesic doses.
• The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to OxyContin.
• The table cannot be used to convert from OxyContin to another opioid. Doing so will result in an over-estimation of the dose of the new opioid and may result in fatal overdose.
• The formula for conversion from prior opioids, including oral oxycodone, to the daily dose of OxyContin is mg per day of prior opioid x factor = mg per day of OxyContin. Divide the calculated total daily dose by 2 to get the every-12-hour OxyContin dose. If rounding is necessary, always round the dose down to the nearest OxyContin tablet strength available.

Table 1: Conversion Factors When Switching Pediatric Patients 11 Years and Older to OxyContin

Step #1

To calculate the estimated total OxyContin daily dosage using Table 1:

• For pediatric patients taking a single opioid, sum the current total daily dosage of the opioid and then multiply the total daily dosage by the approximate conversion factor to calculate the approximate OxyContin daily dosage.
• For pediatric patients on a regimen of more than one opioid, calculate the approximate oxycodone dose for each opioid and sum the totals to obtain the approximate OxyContin daily dosage.
• For pediatric patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion.

Step #2

• If rounding is necessary, always round the dosage down to the nearest OxyContin tablet strength available and initiate OxyContin therapy with that dose. If the calculated OxyContin total daily dosage is less than 20 mg, there is no safe strength for conversion and do not initiate OxyContin.
• Example conversion from a single opioid (e.g., hydrocodone) to OxyContin: Using the conversion factor of 0.9 for oral hydrocodone in Table 1, a total daily hydrocodone dosage of 50 mg is converted to 45 mg of oxycodone per day or 22.5 mg of OxyContin every 12 hours. After rounding down to the nearest strength available, the recommended OxyContin starting dosage is 20 mg every 12 hours.

Step #3

• Close observation and titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal or for signs of oversedation/ toxicity after converting patients to OxyContin. [see Titration And Maintenance Of Therapy In Adults And Pediatric Patients 11 Years And Older] for important instructions on titration and maintenance of therapy.
• There is limited experience with conversion from transdermal fentanyl to OxyContin in pediatric patients 11 years and older. If switching from transdermal fentanyl patch to OxyContin, ensure that the patch has been removed for at least 18 hours prior to starting OxyContin.
• Although there has been no systematic assessment of such conversion, start with a conservative conversion: substitute 10 mg of OxyContin every 12 hours for each 25 mcg per hour fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to OxyContin.
• If using asymmetric dosing, instruct patients to take the higher dose in the morning and the lower dose in the evening.

Titration And Maintenance Of Therapy In Adults And Pediatric Patients 11 Years And Older

• Individually titrate OxyContin to a dosage that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving OxyContin to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and adverse reactions, as well as monitoring for the development of addiction, abuse and misuse.
•  Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.
• Patients who experience breakthrough pain may require a dosage adjustment of OxyContin or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the OxyContin dosage. Because steady-state plasma concentrations are approximated in 1 day, OxyContin dosage may be adjusted every 1 to 2 days.
• If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioidrelated adverse reactions.
• There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. As a guideline for pediatric patients 11 years and older, the total aily oxycodone dosage usually can be increased by 25% of the current total daily dosage. As a guideline for adults, the total daily oxycodone dosage usually can be increased by 25% to 50% of the current total daily dosage, each time an increase is clinically indicated.

Dosage Modifications With Concomitant Use Of Central Nervous System Depressants

• If the patient is currently taking a central nervous system (CNS) depressant and the decision is made to begin OxyContin, start with one-third to one-half the recommended starting dosage of OxyContin, consider using a lower dosage of the concomitant CNS depressant, and monitor patients for signs of respiratory depression, sedation, and hypotension.

Dosage Modifications In Geriatric Patients Who Are Debilitated And Not Opioid- Tolerant

• For geriatric patients who are debilitated and not opioid tolerant, start dosing patients at one-third to one-half the recommended starting dosage and titrate the dosage cautiously.

Dosage Modifications In Patients With Hepatic Impairment

• For patients with hepatic impairment, start dosing patients at one-third to one-half the recommended starting dosage and titrate the dosage carefully. Monitor for signs of respiratory depression, sedation, and hypotension.

Discontinuation Of OxyContin

• When the patient no longer requires therapy with OxyContin, taper the dosage gradually, by 25% to 50% every 2 to 4 days, while monitoring for signs and symptoms of withdrawal.
• If a patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue OxyContin.

Table 4 includes clinically significant drug interactions with OxyContin.

Table 4: Clinically Significant Drug Interactions with OxyContin

• Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. There are no available data with OxyContin in pregnant women to inform a drug-associated risk for major birth defects and miscarriage.
• 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, breastfeeding is not recommended during treatment with OxyContin.