Usual Adult Dose for Pain

Individualize therapy taking into consideration severity of pain, response to therapy, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse:

Immediate-Release:
Initial dose: 50 to 100 mg orally every 4 to 6 hours as needed for pain

• Day 1: A second dose may be administered as soon as 1 hour after the first dose if needed
• Subsequent dosing: 50, 75, or 100 mg orally every 4 to 6 hours; adjust dosing to maintain adequate analgesia with acceptable tolerability

Maximum dose: 700 mg on day 1, then 600 mg/day on subsequent days

Comments:

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
• Monitor closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and with each dose increase.
• Due to risks of addiction, abuse, and misuse, even at recommended doses, reserve use for patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products) have not been tolerated, or are not expected to be tolerated, or have not provided adequate analgesia, or are not expected to provide adequate analgesia.

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

Usual Adult Dose for Chronic Pain

Individualize therapy taking into consideration severity of pain, response to therapy, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse:

• Discontinue all other tapentadol and tramadol products prior to starting tapentadol extended-release tablets

EXTENDED RELEASE TABLETS:
Initial dose: 50 mg orally twice a day

• Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; dose increases should not exceed 50 mg twice a day every 3 days

Maintenance dose: 100 mg to 250 mg orally twice a day
Maximum dose: 500 mg/day

CONVERSION from IMMEDIATE-RELEASE to EXTENDED-RELEASE:

• Provide same total daily dose of tapentadol divided into 2 equal doses and administered orally twice a day approximately 12 hours apart

CONVERSION from Other Opioids:

• As there are no established conversion ratios from other opioids, initiate at 50 mg orally every 12 hours
• Close observation and frequent titration are warranted until pain is controlled; monitor for signs and symptom of opioid withdrawal
• Provide rescue medication with an appropriate dose of an immediate-release analgesic as appropriate

Comments:

• For patients with breakthrough pain a rescue medication with an appropriate dose of an immediate-release analgesic may be needed.
• If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing dose.
• Because of the risks of addiction, abuse, and misuse even at recommended doses, use should be limited to 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 pain management.
• This drug is not for use as an as-needed analgesic.

Uses:

• For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
• For the management of neuropathic pain associated with diabetic peripheral neuropathy severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Renal Dose Adjustments

Mild to moderate renal dysfunction: No adjustment recommended
Severe renal dysfunction (CrCl less than 30 mL/min): Not recommended

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh 5-6): No adjustment recommended

Moderate liver dysfunction (Child-Pugh 7 to 9):

• Immediate release: Initial dose 50 mg orally no more frequently than every 8 hours; if additional analgesia is needed, titrate slowly with close monitoring
• Extended release tablets: Initial dose 50 mg orally once a day; Maximum dose: 100 mg/day

Severe liver dysfunction (Child-Pugh 10-15): Not recommended

Dose Adjustments

Elderly: Dose selection should be conservative; consider monitoring renal function

Drug Discontinuation:

• Do not abruptly discontinue in physically dependent individual
• Taper by 25% to 50% every 2 to 4 days; monitor for signs and symptoms of withdrawal
• If signs and symptoms of withdrawal occur, increase the dose to the previous level and taper more slowly

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; INTERACTION WITH ALCOHOL and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:

• Addiction, Abuse, and Misuse: Addiction to, abuse, or misuse of this drug can lead to overdose and death. Assess each patient's risk before prescribing and monitor regularly for 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: Respiratory depression with fatal outcome can occur. Monitor closely upon initiation or following a dose increase. Instruct patients to swallow the tablets whole; crushing, chewing, or dissolving the tablets can cause rapid release and absorption of a potentially fatal dose.
• Accidental Ingestion: Accidental ingestion, especially in children, can be fatal.
• Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in this life-threatening syndrome 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 and ensure appropriate treatment will be available.
• Interaction with Alcohol: Instruct patients not to consume alcoholic beverages or use products that contain alcohol while taking this drug. Ingestion with alcohol can result in fatal plasma tapentadol levels.
• 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 use to cases when alternative treatment options are inadequate; limit dose and duration to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

CONTRAINDICATIONS:

• Hypersensitivity to the active substance (e.g., anaphylaxis or angioedema) or any product ingredients
• 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 suspected paralytic ileus
• Concurrent use of monoamine oxidase (MAO) inhibitors or use within the last 14 days

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

Extended-Release Tablets:

• Swallow whole; do not cut, break, chew, dissolve, or crush
• Take 1 tablet at a time with enough water to ensure complete swallowing; do not pre-soak, lick, or otherwise wet the tablet before placing in the mouth
• Take twice a day approximately 12 hours apart

General:

• This drug should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
• Because of the greater risk of overdose and death opioids should only be used in patients for whom alternative treatment options are ineffective, not tolerated, or would otherwise be inadequate to provide sufficient pain management.
• For patients receiving other opioid analgesics and switching to this drug or the extended-release tablet formulation, it is safer to underestimate a patient's 24-hour oral requirement and provide rescue medication than overestimate and manage an adverse reaction; there is substantial inter-patient variation in the relative potency of different opioid drugs that conversion tables are not able to capture.
• During chronic therapy, periodically reassess the continued need for opioid analgesics.

Monitoring:

• Monitor closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dose increases.
• Monitor regularly for the development of addiction, abuse, and misuse.
• Monitor for signs of hypotension upon initiating therapy and following dose increases, especially in those whose blood pressure is compromised.
• Monitor for constipation and decreased bowel motility in post-operative patients.

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.
• Advise patients 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.
• Instruct patients not to consume alcoholic beverages, or prescription and non-prescription products that contain alcohol as this may result in increased oxymorphone levels.
• 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.