Dosage and Administration

Overview

EMBEDA is available in 6 dosage strengths1

 

Capsules shown are not actual size.

  • EMBEDA 100 mg/4 mg capsules are only for patients in whom tolerance to an opioid of comparable potency is established.1
  • Patients considered opioid-tolerant are those taking, for 1 week or longer, at least 60 mg of morphine daily, at least 30 mg of oral oxycodone daily, at least 8 mg of oral hydromorphine daily, or an equianalgesic dose of another opioid.1

EMBEDA is administered orally at a frequency of either once daily (every 24 hours) or twice daily (every 12 hours).1


Initial dosing with EMBEDA

  • Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.1
  • Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse.1
  • Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with EMBEDA.1

EMBEDA capsules must be taken whole.1

  • EMBEDA capsules contain pellets that consist of morphine sulfate and sequestered naltrexone.1
  • The pellets in the capsules are not to be crushed, dissolved, or chewed.1
  • If the pellets in EMBEDA capsules are crushed, dissolved, or chewed1:
    • It will result in uncontrolled delivery of morphine and can lead to overdose or death.
    • It may reduce the analgesic effects of morphine.
    • They can release sufficient naltrexone to precipitate withdrawal in opioid-dependent individuals.
 

For patients who are unable to swallow EMBEDA

The contents of the EMBEDA pellets may be sprinkled over applesauce and then swallowed. This method is appropriate only for patients able to reliably swallow the applesauce without chewing.1

  • Other foods have not been tested and should not be substituted for applesauce.
  • Instruct the patient to:
  • Open the capsule and sprinkle the pellets over approximately 1 tablespoon of applesauce and consume immediately without chewing.
    • Do not save any of the applesauce and pellets for another dose.
  • Rinse the mouth to ensure all pellets have been swallowed. Do not chew the pellets.
  • Flush the empty EMBEDA capsule down the toilet right away after the contents have been sprinkled on applesauce.

See Instructions for Use.

Do not administer EMBEDA pellets through a nasogastric or a gastric tube.1

 
REFERENCE

1. Embeda [prescribing information]. New York, NY: Pfizer Inc; December 2016.

Initial Dosing

Know the recommended starting dose

  • EMBEDA should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.1
  • Initiate the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience and risk factors for addiction, abuse, and misuse.1
  • Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with EMBEDA.1
  • The first dose of EMBEDA may be taken with the last dose of any immediate-release opioid medication due to the extended-release characteristics of the EMBEDA formulation.1
  • Discontinue all other around-the-clock opioid medications when EMBEDA therapy is initiated.1

Patients on other oral morphine formulations should start on a 1:1 dosage conversion to EMBEDA1

Use of EMBEDA in patients on other oral morphine formulations

  • Administer one-half of the patient’s total daily oral morphine dose as EMBEDA twice daily or administer the total daily oral morphine dose as EMBEDA once daily.1
  • There are no data to support the efficacy or safety of prescribing EMBEDA more frequently than every 12 hours.1
  • The first dose of EMBEDA may be taken with the last dose of any immediate-release opioid medication due to the extended-release characteristics of the EMBEDA formulation.1
  • The sequestered naltrexone hydrochloride in EMBEDA is intended to have no clinical effect when EMBEDA is taken as directed.1

Patients on other opioids should start on EMBEDA 30 mg1

  • There are no established conversion ratios from other opioids to EMBEDA defined by clinical trials.1
  • Discontinue all other around-the-clock opioid drugs when EMBEDA therapy is initiated and initiate dosing using EMBEDA 30 mg orally every 24 hours.1
  • While there are useful tables of opioid equivalents readily available, there is substantial interpatient variation in the relative potency of different opioid drugs and products.1
    • As such, it is safer to underestimate a patient's 24-hour oral morphine requirement and provide rescue medication (eg, immediate-release morphine) than to overestimate and manage an adverse reaction.
  • The first dose of EMBEDA may be taken with the last dose of any immediate-release opioid medication due to the extended-release characteristics of the EMBEDA formulation.1

Special Populations

Pediatric use

  • The safety and efficacy of EMBEDA in patients less than 18 years of age have not been established.1

Geriatric use

  • The pharmacokinetics of EMBEDA have not been investigated in elderly patients (≥65 years).1
  • Elderly patients (aged 65 years or older) may have increased sensitivity to EMBEDA.1
  • Use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range.1
    • This reflects greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
  • Respiratory depression is the chief risk for 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.1
  • Titrate the dosage of EMBEDA slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression.1
  • This drug 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.1
    • 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.

Renal and/or hepatic impairment

  • Initiate treatment at a lower than usual dosage of EMBEDA and titrate slowly. Monitor patients for signs of respiratory depression, sedation, and hypotension.1
  • Morphine pharmacokinetics are altered in patients with renal failure, and have been reported to be significantly altered in patients with cirrhosis.1

Opioid naive

  • Initiate treatment with the 20 mg/0.8 mg capsule orally every 24 hours.1

Non-opioid tolerant

  • The starting dose for patients who are not opioid-tolerant is EMBEDA 20 mg/0.8 mg orally every 24 hours. Patients who are opioid-tolerant are those receiving, for 1 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, or an equianalgesic dose of another opioid.1
  • Use of higher starting doses in patients who are not opioid-tolerant may cause fatal respiratory depression.1

Conversion

When converting patients to EMBEDA from other oral morphine formulations1

Patients should start on a 1:1 dosage conversion

  • Administer one-half of the patient’s total daily dose of EMBEDA twice daily or administer the total daily oral morphine dose as EMBEDA once daily.1
  • There are no data to support the efficacy or safety of prescribing EMBEDA more frequently than every 12 hours.1
  • The first dose of EMBEDA may be taken with the last dose of any immediate-release opioid medication due to the extended-release characteristics of the EMBEDA formulation.1
  • The sequestered naltrexone hydrochloride in EMBEDA is intended to have no clinical effect when EMBEDA is taken as directed.1

When converting patients to EMBEDA from other opioids

  • There are no established conversion ratios from other opioids to EMBEDA defined by clinical trials.1
  • Discontinue all other around-the-clock opioid drugs when EMBEDA therapy is initiated and initiate dosing using EMBEDA 30 mg orally every 24 hours.1
  • While there are useful tables of opioid equivalents readily available, there is substantial interpatient variation in the relative potency of different opioid drugs and products.1
    • As such, it is safer to underestimate a patient's 24-hour oral morphine requirement and provide rescue medication (eg, immediate-release morphine) than to overestimate and manage an adverse reaction.
  • The first dose of EMBEDA may be taken with the last dose of any immediate-release opioid medication due to the extended-release characteristics of the EMBEDA formulation.1

When converting patients to EMBEDA from parenteral morphine or other opioids

  • Parenteral to oral morphine ratio: Between 2 mg and 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of oral morphine that is 3 times the daily parenteral morphine requirement is sufficient.1
  • Other oral or parenteral opioids to oral morphine ratios: Specific recommendations are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. In general, begin with half of the estimated daily morphine requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release morphine.1
  • The first dose of EMBEDA may be taken with the last dose of any immediate-release opioid medication due to the extended-release characteristics of the EMBEDA formulation.1

When converting patients to EMBEDA from methadone

  • Close monitoring is of particular importance when converting from methadone to other opioid agonists.1
  • 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.1
REFERENCE

1. Embeda [prescribing information]. New York, NY: Pfizer Inc; December 2016.

Titration

How to titrate your patients on EMBEDA

  • Individually titrate EMBEDA to a dose that provides adequate analgesia and minimizes adverse reactions.1
  • Continually re-evaluate patients receiving EMBEDA to assess the maintenance of pain control and the relative incidence of adverse reactions, and monitor for the development of addiction, abuse, or misuse.1
  • Frequent communication among the prescriber, other members of the healthcare team, the patient, and the caregiver/family is important, especially during periods of changing analgesic requirements, including initial titration.1
  • During chronic therapy, periodically reassess the continued need for opioid analgesics.1

If the level of pain increases

  • In patients who experience an increase in pain, attempt to identify the source while adjusting the EMBEDA dose to decrease the level of pain.1
  • Because steady-state plasma concentrations are approximated within 24 to 36 hours, EMBEDA dosage adjustments may be done every 1 to 2 days.1

If there is breakthrough pain

  • Patients who experience breakthrough pain may require a dose increase of EMBEDA or may need rescue medication with an appropriate dose of an immediate-release analgesic.1
  • If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the EMBEDA dose.1
  • In patients experiencing inadequate analgesia with once-daily dosing of EMBEDA, consider a twice-daily regimen.1

Maintenance

  • Continually re-evaluate patients receiving EMBEDA to assess the maintenance of pain control and the relative incidence of adverse reactions.1
  • During chronic therapy, periodically reassess the continued need for opioid analgesics.1

Discontinuation

  • When a patient no longer requires therapy with EMBEDA, use a gradual downward titration of the dose every 2 to 4 days to prevent signs and symptoms of withdrawal in the physically dependent patient.1
  • Do not abruptly discontinue EMBEDA.1


Adverse reactions

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.1

REFERENCE

1. Embeda [prescribing information]. New York, NY: Pfizer Inc; December 2016.