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 Formulations:

Initial Doses:
Oral Tablets: 2 to 4 mg orally every 4 to 6 hours as needed
Oral Liquid: 2.5 to 10 mg orally every 3 to 6 hours as needed
IM or Subcutaneous: 1 mg to 2 mg IM or subcutaneously every 2 to 3 hours as needed (lower initial doses may be appropriate in opioid naive patients)
IV: Initial dose: 0.2 mg to 1 mg IV every 2 to 3 hours as needed

Dose Titration:

• Titrate to a dose that provides adequate analgesia and minimizes adverse reactions; continually assess pain control and tolerability; monitor for possible signs of addiction, abuse, or misuse

HIGH-POTENCY (HP) Injection: For OPIOID-TOLERANT patients only; for use in patients who require higher doses

CONVERSION FROM PRIOR OPIOIDS:

• Initial daily dose should be 50% of the 24-hour calculated hydromorphone requirement
• Dose should be titrated to achieve acceptable analgesia and tolerable adverse events

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 pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

SUPPOSITORY:

• This formulation has not been found by the US FDA to be safe and effective and therefore labeling has not been approved.
• According to the manufacturer, this formulation may provide longer duration of relief and obviate additional medication needs during the sleeping hours.
• Dose: 3 mg rectally every 6 to 8 hours

Usual Adult Dose for Chronic Pain

For OPIOID-TOLERANT Patients Only: Extended-release hydromorphone tablets are not for use as first opioid

• Discontinue or taper all other extended-release opioids prior to initiating therapy

Extended-release Tablets:

Starting Doses:
Conversion from Other Oral Hydromorphone Formulations: Starting dose is equivalent to total daily hydromorphone dose taken as extended-release tablet orally once a day

Conversion from Other Oral Opioids: Starting dose is equivalent to 50% of the calculated daily hydromorphone requirement taken as extended-release tablet orally once a day

• To determine daily hydromorphone requirement: Sum total daily dose of prior oral opioid and multiply by oral conversion factor (CF), divide by 2 (to get 50%); round down if needed to available tablet strength
• Conversion Factors: Hydromorphone, CF=1; Codeine, CF=0.06; Hydrocodone, CF=0.4; Oxycodone, CF=0.4; Methadone, CF=0.6; Morphine, CF=0.2, Oxymorphone, CF=0.6
• NOTE: Product of dose and CF does not represent an equianalgesic dose and therefore should not be used to convert hydromorphone extended-release tablets to another opioid

Conversion from Transdermal Fentanyl: Remove fentanyl patch 18 hours prior to starting extended-release therapy

• Using the conversion of a single 25 mcg/hr fentanyl transdermal patch to a 12 mg extended-release hydromorphone tablet, calculate conversion dose and reduce by 50% to obtain the starting dose of the extended-release hydromorphone tablet, round down if needed to available tablet strength

Conversion from Methadone: The ratio between methadone and other opioid agonists including hydromorphone varies widely; methadone can accumulate in the plasma due to its long half-life; close monitoring and a conservative approach are of particular importance during conversion.

TITRATION AND MAINTENANCE:

• Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; dose adjustments may be made in 4 to 8 mg increments every 24 hours, every 3 to 4 days
• Breakthrough Pain: If the level of pain increases after dose stabilization, attempt to identify the source before increasing dose; rescue medication with appropriate immediate-release analgesia may be helpful

Comments:

• Therapy should be individualized taking into consideration severity of pain, response to therapy, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.
• Due to substantial inter-patient variability, a conservative approach is advised when converting patients from prior opioid therapies. It is safer to underestimate a patient's 24-hour oral hydromorphone dosage and provide rescue medication (e.g., immediate-release opioid) than to overestimate the dose and manage an adverse reaction due to overdose.
• Close observation and frequent titration are warranted until pain management is stable; monitor for respiratory depression, signs and symptoms of opioid withdrawal, and other signs of toxicity.
• Therapy should be gradually reduced when no longer needed; taper by 25% to 50% every 2 to 3 days while monitoring for signs and symptoms of withdrawal.
• Opioid tolerant patients are those patients taking for 1 week or longer, at least: oral morphine 60 mg/day, fentanyl transdermal 25 mcg/hour, oral oxycodone 30 mg/day, oral hydromorphone 8 mg/day, oral oxymorphone 25 mg/day, oral hydrocodone 60 mg/day or an equianalgesic dose of another opioid.

Use: 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.

Renal Dose Adjustments

Immediate-release formulations:

• Initiate therapy with 25% to 50% of usual starting dose depending on degree of impairment

Extended-release:

• Moderate renal impairment: Starting dose should be 50% of usual starting dose
• Severe renal impairment: Consider alternative agents that may permit more flexibility with dosing interval

Closely monitor patients with renal impairment for respiratory and CNS depression during initiation and during dose titration

Liver Dose Adjustments

Immediate-release formulations:

• Initiate therapy with 25% to 50% of usual starting dose depending on degree of impairment

Extended-release:

• Moderate renal impairment: Starting dose should be 50% of usual starting dose
• Severe renal impairment: Consider alternative agents that may permit more flexibility with dosing interval

Closely monitor patients with renal impairment for respiratory and CNS depression during initiation and during dose titration

Dose Adjustments

Elderly patients: Closely monitor for respiratory and CNS depression during initiation and dose escalation

Therapy Discontinuation:

• Do not abruptly discontinue in the opioid-tolerant patient
• Extended-release: Taper by 25% to 50% every 2 to 3 days; monitor for signs and symptoms of withdrawal; if patient exhibits withdrawal, increase the dose to the previous level and taper more slowly.
• Immediate-release: Taper by 25% to 50% every 2 to 4 days; monitor for signs and symptoms of withdrawal; if patient exhibits withdrawal, 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: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:

• Risk of Medication Errors: Ensure accuracy when prescribing, dispensing, and administering hydromorphone oral solution; dosing errors due to confusion between mg and mL can result in accidental overdose and death.
• 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 with use; monitor for respiratory depression, especially during initiation or following a dose increase. Instruct patients to swallow extended-release tablets whole; crushing, chewing or dissolving can cause rapid release and absorption of a potentially fatal dose.
• Accidental Ingestion: Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose.
• 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, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
• 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 or any products ingredients (some formulations contain metabisulfite)
• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal (GI) obstruction including paralytic ileus
• Extended-release: Narrowing of the GI tract or blind loops

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:

• To avoid medication errors, prescribers and pharmacists must be aware that hydromorphone is available as both immediate-release 8 mg tablet and an extended-release 8 mg tablet

ORAL: May take with or without food
Immediate-release oral liquid: Measure dose with a calibrated measuring cup or oral syringe; confirm dose in mg and mL
Extended-release tablets: For use in opioid tolerant patients only

• Swallow whole; do not cut, break, chew, dissolve, or crush
• The non-dissolvable shell of the extended-release product may appear in the stool

PARENTERAL: May be administered IM, IV, or subcutaneously

• IV: Administer slowly over at least 2 to 3 minutes
• IV: High-Potency (HP) injection should be used in opioid tolerant patients only

Storage requirements: Protect from light

General:

• The extended-release tablets should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of pain.
• Because of the greater risk of overdose and death with opioids, use should be reserved for 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, 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.
• The extended-release tablet should not be used as an as-needed pain medication.

Monitoring:

• Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dose increases.
• Monitor all patients regularly for the development of addiction, abuse, and misuse.
• Monitor patients for signs of hypotension upon initiating therapy and following dose increases, especially 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.
• 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.

Frequently asked questions

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