Usual Adult Dose for Pain

Immediate-release:
Oxycodone 2.5 mg/acetaminophen 300 or 325 mg: 1 to 2 tablets every 6 hours
Maximum dose: 12 tablets in 24 hours

Oxycodone 5 mg/acetaminophen 300 or 325 mg: 1 tablet orally every 6 hours as needed for pain
Maximum dose: 12 tablets in 24 hours

Oxycodone 7.5 mg/acetaminophen 300 or 325 mg: 1 tablet orally every 6 hours as needed for pain
Maximum dose: 8 tablets in 24 hours

Oxycodone 10 mg/acetaminophen 300 or 325 mg: 1 tablet orally every 6 hours as needed for pain
Maximum dose: 6 tablets in 24 hours

Oral Solution: Oxycodone 5 mg/acetaminophen 325 mg per 5 mL:
Usual dose: Oxycodone 5 mg/acetaminophen 325 mg (5 mL) orally every 6 hours as needed for pain
Maximum dose: Oxycodone 60 mg/acetaminophen 3900 mg (60 mL) in 24 hours

• Verify dose in mg and mL prior to administration

EXTENDED-RELEASE (ER) DOSING:
As First Opioid Analgesic: 2 tablets orally every 12 hours (each ER tablet contains oxycodone 7.5 mg/acetaminophen 325 mg)

• The second dose may be administered as early as 8 hours after initial dose if needed; however, subsequent doses should be administered every 12 hours

Comments:

• Doses should be individually titrated to provide adequate analgesia while minimizing adverse reactions.
• Because of the risks of addiction, abuse and misuse, the lowest effective dose for the shortest duration consistent with individual patient treatment goals should be used.
• Monitor patients closely for respiratory depression within the first 24 to 72 hours of initiating therapy and following any increase in dose.
• Oxycodone/acetaminophen ER Tablets are not interchangeable with other oxycodone/acetaminophen products.

Use: For the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Renal Dose Adjustments

Immediate-release:

• Use with caution; therapy should be initiated with a lower than usual dose; titrate carefully

Extended-release (ER):
Initial dose: Oxycodone 7.5 mg/Acetaminophen 325 mg ER: 1 tablet orally every 12 hours; adjust does as needed

Liver Dose Adjustments

Immediate-release:

• Use with caution; therapy should be initiated with a lower than usual dose; titrate carefully

Extended-release (ER):
Initial dose: Oxycodone 7.5 mg/Acetaminophen 325 mg ER: 1 tablet orally every 12 hours; adjust dose as needed

Dose Adjustments

Elderly, Cachectic, or Debilitated Patients: Use with caution generally starting at the low end of the dosing range, titrate dose slowly while monitoring closely for signs of CNS or respiratory depression.

Maximum Acetaminophen Dose is 4 g in 24 hours

• Take into account all acetaminophen products when calculating daily dose.
• To avoid overdose of acetaminophen, it is best to use just 1 acetaminophen product at a time.

Concomitant Use of CNS depressants:

• Initial dose: Oxycodone 7.5 mg/Acetaminophen 325 mg ER: 1 tablet orally every 12 hours; adjust dose as needed
• Consider decreasing dose of concomitant CNS depressant drug; monitor for signs of respiratory depression, sedation, and hypotension.

• Concomitant use of CYP450 3A4 inducers or inhibitors may require dose adjustment: Consult drug interactions

Discontinuation of Therapy in the Physically Dependent Patient:

• Taper dose gradually, by 25% to 50% every 2 to 4 days
• Monitor for signs and symptoms of withdrawal; if they occur, raise the dose to the previous level and taper more slowly
• Do not abruptly discontinue in the physically dependent patient

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS: ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYP450 3A4 INTERACTION; HEPATOTOXICITY; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS and RISKS OF MEDICATION ERRORS:

• Addiction, Abuse, and Misuse: This drug exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
• Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required 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, especially during initiation or following a dose increase.
• Accidental Ingestion: Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose of oxycodone.
• Neonatal Opioid Withdrawal Syndrome: Prolonged use 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, the patient should be advised of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment will be available.
• CYP450 3A4 Interaction: Concomitant use of CYP450 3A4 inhibitors may result in increased 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 CYP450 3A4 inducer may result in increased oxycodone plasma concentrations. Monitor patients concomitantly receiving any CYP450 3A4 inhibitor or inducer.
• Hepatotoxicity: Acetaminophen has been associated with case of acute liver failure, at times resulting in liver transplant and death; most cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 mg per day, and often involve more than one acetaminophen-containing product.
• Concomitant Use with Benzodiazepines or Other CNS Depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Concomitant use should be reserved for use in patients for whom alternative treatment options are inadequate. If needed, limit dose and duration to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.
• Risks of Medication Errors: Ensure accuracy when prescribing, dispensing, and administering oxycodone/acetaminophen oral solution; dosing errors due to confusion between mg and mL, and other oxycodone/acetaminophen oral solutions of different concentrations can result in accidental overdose and death.

CONTRAINDICATIONS:

• Significant respiratory depression
• Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Hypersensitivity to the active components or any of the product ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available

Other Comments

Administration advice:

• Take orally with or without food

Oral Solution:

• Verify dose in mg and mL prior to administration
• Measure dose with a calibrated measuring device

Extended-release tablets

• Swallow whole, 1 tablet at a time with sufficient water to ensure complete swallowing
• Do not break, chew, crush, cut, dissolve, or split tablets

Storage requirements:

• Protect from light and moisture

General:

• The total acetaminophen dose should not exceed 4 g in 24 hours; be sure to account for all acetaminophen use when calculating total daily dose.
• Because of the risks of addiction, abuse and misuse, the lowest dose for the shortest duration consistent with individual patient treatment goals should be used.
• Frequent communication between members of the healthcare team, patients, and their caregiver/family is important during periods of changing analgesic requirements; if the level of pain increases after dose stabilization, an attempt should be made to identify the source of increased pain before increasing the dose of pain medication.
• Oxycodone/acetaminophen formulations are not interchangeable because of differing pharmacokinetics; if patients switch from the immediate-release formulation to the extended-release tablet, monitor closely for signs of excessive sedation and respiratory depression.

Monitoring:

• Monitor for respiratory depression, especially during initiation and following any increase in dose; close monitoring will be necessary in patients at increased risk and/or those receiving concomitant medications that increase the risk of respiratory depression
• Monitor for signs of hypotension
• Monitor for signs of constipation
• Monitor for the development of behaviors indicative of addiction, abuse, or misuse

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• Advise patients to store this drug safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
• Patients should understand that this drug, even when taken as recommended can result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect their drug from theft or misuse.
• Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest; patients and caregivers should be instructed to get emergency help right away if too much drug is taken or if breathing problems occur.
• Patients should be instructed to check with their healthcare provider before taking any new medications, herbal supplements, and over the counter products; patients should not drink alcohol while taking this drug.
• Patients should seek medical advice for signs and symptoms of gastrointestinal events, allergic reactions, and bleeding events; this drug effects platelets and may cause them to bruise or bleed more easily; however, any prolonged, unusual or excessive bleed should be reported promptly.
• This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary; this drug should not be used at 30 weeks gestation or later.