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Hydromorphone Hydrochloride

Class: Opiate Agonists
VA Class: CN101
CAS Number: 71-68-1
Brands: Dilaudid, Dilaudid-HP, Exalgo

Medically reviewed on November 13, 2017

Warning

    Abuse Potential
  • Abuse potential similar to that of other opiate agonists.238 239 246

  • Consider abuse potential when prescribing or dispensing hydromorphone in situations where the clinician or pharmacist is concerned about increased risk of misuse, abuse, or diversion.238 239 246

    Respiratory Depression
  • Risk of respiratory depression.238 239 246

    Overdose Risk with Improper Administration of Extended-release Tablets or 10-mg/mL Injection
  • Use highly concentrated injection (10 mg/mL) only in patients who are tolerant to opiate agonists; overdosage and/or death may result if confused with less concentrated formulations and used in patients who are not opiate tolerant.239 a

  • Use extended-release tablets only in patients who are tolerant to opiate agonists; fatal respiratory depression may result if used in patients who are not opiate tolerant.238 Extended-release tablets are not indicated for management of acute or postoperative pain or for as-needed (“prn”) use.246

  • Patients are considered opiate tolerant if they have been receiving at least 60 mg of oral morphine sulfate daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone hydrochloride daily, 8 mg of oral hydromorphone hydrochloride daily, 25 mg of oral oxymorphone hydrochloride daily, or an equianalgesic dosage of another opiate daily for ≥1 week.239 246

  • Breaking, chewing, crushing, or dissolving the extended-release tablets can result in rapid release of hydromorphone and absorption of a potentially fatal dose.246

  • Accidental ingestion of extended-release tablets can result in fatal overdosage, particularly in children.246

    Concomitant Use with Benzodiazepines or Other CNS Depressants
  • Concomitant use of opiate agonists with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.416 417 418 700 701 702 703

  • Reserve concomitant use of opiate analgesics and benzodiazepines or other CNS depressants for patients in whom alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy and monitor closely for respiratory depression and sedation.700 703 (See Specific Drugs under Interactions.)

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for hydromorphone to ensure that the benefits outweigh the risks. (See REMS Program under Dosage and Administration.) The REMS may apply to one or more preparations of hydromorphone and consists of the following: medication guide and elements to assure safe use. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Introduction

Opiate agonist; semisynthetic phenanthrene derivative.a

Uses for Hydromorphone Hydrochloride

Acute Pain

A strong analgesic used in the relief of moderate to severe pain.a f

Usually, temporary relief of moderate to severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.f

Used to provide analgesia during diagnostic and orthopedic procedures.f

Highly concentrated (10-mg/mL) injection is used for relief of moderate to severe pain in opiate-tolerant patients requiring large doses for adequate pain relief (see Boxed Warning); smaller volume may be injected IM or sub-Q, and discomfort of larger volumes avoided.239

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.431 432 433 435 Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.411 431 434 435 Optimize concomitant use of other appropriate therapies.432 434 435 (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

Chronic Pain

For relief of malignant (cancer) pain and chronic nonmalignant pain.f

Extended-release tablets are used orally for management of moderate to severe pain in opiate-tolerant patients who require a continuous, around-the-clock analgesic for an extended period of time; do not use on an as-needed (“prn”) basis.246 (See Boxed Warning.)

In the management of severe, chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.f

Although consideration of the dependence potential of opiate agonists has often limited their effective use by many clinicians in terminally ill patients with severe, chronic pain, such consideration is irrelevant in the context of terminal illness.f

Generally use opiates for management of chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing410 411 412 413 ) that is not associated with active cancer treatment, palliative care, or end-of-life care only if other appropriate nonpharmacologic and nonopiate pharmacologic strategies have been ineffective and expected benefits for both pain relief and functional improvement are anticipated to outweigh risks.411 412 413 414 422 429

If used for chronic pain, opiate analgesics should be part of an integrated approach that also includes appropriate nonpharmacologic modalities (e.g., cognitive-behavioral therapy, relaxation techniques, biofeedback, functional restoration, exercise therapy, certain interventional procedures) and other appropriate pharmacologic therapies (e.g., nonopiate analgesics, analgesic adjuncts such as selected anticonvulsants and antidepressants for certain neuropathic pain conditions).411 412 413 422 429

Available evidence insufficient to determine whether long-term opiate therapy for chronic pain results in sustained pain relief or improvements in function and quality of life411 423 431 432 436 or is superior to other pharmacologic or nonpharmacologic treatments.432 Use is associated with serious risks (e.g., opiate use disorder, overdose).411 431 436 (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

Hydromorphone Hydrochloride Dosage and Administration

General

REMS Program

  • FDA required and approved a REMS for hydromorphone hydrochloride extended-release tablets.247

  • Goals are to minimize potential for abuse, misuse, overdose, and addiction and to ensure safe use.247

  • Medication guide must be distributed to all patients with every prescription; clinicians who prescribe the extended-release tablets must complete special training on appropriate and safe use of the drug.247

Managing Opiate Therapy for Acute Pain

  • Optimize concomitant use of other appropriate therapies.432 434 435

  • When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.411 431 434 435

  • When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.432

  • For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).411 433 434 435 Do not prescribe larger quantities for use in case pain continues longer than expected;411 432 instead, reevaluate patient if severe acute pain does not remit.411 431 435

  • For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.430 431 432

  • Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.430 431

  • Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.430 432 When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.430 431

Managing Opiate Therapy for Chronic Noncancer Pain

  • Although specific recommendations may vary, common elements in clinical guideline recommendations include risk mitigation strategies, upper dosage thresholds, careful dosage titration, and consideration of risks associated with particular opiates and formulations, coexisting diseases, and concomitant drug therapy.410 411 414 415 423

  • Prior to initiating therapy, thoroughly evaluate patient; assess risk factors for misuse, abuse, and addiction;411 412 413 415 422 429 establish treatment goals (including realistic goals for pain and function); and consider how therapy will be discontinued if benefits do not outweigh risks.411 415

  • Regard initial opiate therapy for chronic noncancer pain as a therapeutic trial that will be continued only if there are clinically meaningful improvements in pain and function that outweigh treatment risks.411 412 413

  • Prior to and periodically during therapy, discuss with patients known risks and realistic benefits and patient and clinician responsibilities for managing therapy.411 412 413 414 415

  • Some experts recommend initiating opiate therapy for chronic noncancer pain with conventional (immediate-release) opiate analgesics prescribed at lowest effective dosage.411 415 Individualize opiate selection, initial dosage, and dosage titration based on patient’s health status, prior opiate use, attainment of therapeutic goals, and predicted or observed harms.412 413

  • Evaluate benefits and harms within 1–4 weeks following initiation of therapy or dosage increase411 413 and reevaluate on ongoing basis (e.g., at least every 3 months411 ) throughout therapy.411 412 413 Document pain intensity and level of functioning and assess progress toward therapeutic goals, presence of adverse effects, and adherence to prescribed therapies.412 413 422 423 Anticipate and manage common adverse effects (e.g., constipation, nausea and vomiting, cognitive and psychomotor impairment).412 413 415 If benefits do not outweigh harms, optimize other therapies and taper opiate to lower dosage or taper and discontinue opiate.411 412 413 415

  • When repeated dosage increases required, evaluate potential causes and reassess relative benefits and risks.412 413 Although evidence is limited, some experts state that opiate rotation may be considered in patients with intolerable adverse effects or inadequate benefit despite dosage increases.412 413 415

  • Higher dosages require particular caution,410 412 415 including more frequent and intensive monitoring or referral to specialist.411 412 413 Greater benefits of high-dose opiates for chronic pain not established in controlled clinical studies; higher dosages associated with increased risks (motor vehicle accidents, overdosage, opiate use disorder).411 415 423 424 425 426

  • CDC states that primary care clinicians should carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately ≥12.5 mg of hydromorphone hydrochloride daily) for chronic pain and should avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately ≥22.5 mg of hydromorphone hydrochloride daily) or carefully justify decision to prescribe such dosages.411 Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.423 431 Some states have established opiate dosage thresholds (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with specialist is mandated or recommended)411 420 421 423 or have mandated risk-management strategies (e.g., review of state prescription drug monitoring program [PDMP] data prior to prescribing).411 419 423

  • Recommended strategies for managing risks include written treatment agreements or plans (e.g., “contracts”), urine drug testing, review of state PDMP data, and risk assessment and monitoring tools.410 411 412 413 414 415 422 423 429

  • Taper and discontinue opiate therapy if patient engages in serious or repeated aberrant drug-related behaviors or drug abuse or diversion.412 413 415 Offer or arrange treatment for patients with opiate use disorder.411 412 413

  • Consider providing concomitant naloxone for patients at increased risk of opiate overdosage (e.g., those with history of overdose or substance use disorder, those receiving ≥50 mg of morphine sulfate [or equivalent] daily, those receiving benzodiazepines concomitantly, those with medical conditions that could increase sensitivity to opiate effects).411 431

Administration

Administer orally or by sub-Q, IM, or slow IV injection or infusion.238 239 246 a Has been administered epidurally.240 241 244

Oral Administration

Administer orally as conventional (immediate-release) or extended-release tablets or as an oral solution.238 246

Use caution when prescribing or dispensing hydromorphone to avoid inadvertent interchange of 8-mg extended-release tablets and 8-mg conventional tablets.246

Conventional Tablets and Oral Solution

Conventional tablets and oral solution are bioequivalent.238

Food may decrease rate and extent of absorption of conventional tablets (see Food under Pharmacokinetics), but effects may not be clinically important.238

Extended-release Tablets

Discontinue all other extended-release opiates when initiating therapy with extended-release hydromorphone.246

Do not administer more frequently than once every 24 hours.246

Swallow tablets intact; do not break, crush, dissolve, or chew.246 Ingestion of broken, crushed, chewed, or dissolved tablets may result in rapid drug release and absorption of a potentially fatal dose.246

Administer without regard to food.246

Do not administer with alcohol.246 248 (See Specific Drugs under Interactions.)

Parenteral Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by sub-Q, IM, or slow (over at least 2–3 minutes) IV injection.239

Has been administered by continuous IV or sub-Q infusion in selected opiate-tolerant patients with chronic pain; use extreme caution when administering continuous infusions of opiates to patients with no prior exposure to opiate analgesics.240 241 242 243 244

Also administered IV via controlled-delivery device for patient-controlled analgesia (PCA).241

IM administration of opiate analgesics is discouraged; IM injections can cause pain and are associated with unreliable absorption, resulting in inconsistent analgesia.241 430

Highly Concentrated (10-mg/mL) Injection

Injection is commercially available in various concentrations (1, 2, 4, and 10 mg/mL).239 Use the 10-mg/mL injection only in patients who are tolerant to and already receiving high dosages of opiate agonists.239 (See Boxed Warning.)

Confusion between the different concentrations or between mg and mL can result in accidental overdosage and death.239

Take care to ensure that correct dosages are prescribed and dispensed.239 When writing prescriptions, specify the intended total dose (in mg) along with the corresponding total volume (in mL).239

Use the 10-mg/mL injection only when required volume can be accurately measured.239 a Reserve for patients who require the reduced total volume and higher concentration of this formulation.239

Reconstitution

Reconstitute lyophilized powder immediately prior to use by adding 25 mL of sterile water for injection to a vial containing 250 mg of the drug to provide 10-mg/mL solution.239

Dilution

If the 500-mg single-use (10-mg/mL) vial is used for preparation of an IV infusion solution, remove container seal and rubber stopper in a laminar flow hood or equivalent clean air compounding area; do not penetrate with a syringe.239

Withdraw appropriate amount and then discard any unused portion in an appropriate manner.239

Has been diluted to a concentration of 1 mg/mL in 5% dextrose or 0.9% sodium chloride injection for continuous IV infusion in critically ill adult patients.242

Rate of IV Administration

If rapid onset and shorter duration of analgesia are required, may give IV at slow rate (over at least 2–3 minutes), with special attention to the possibility of respiratory depression and hypotension.239 a

IV injection for PCA: Self-administered intermittently as needed (“prn”) via controlled-delivery device, with usual lockout intervals (minimum time between self-administered doses programmed into device) of 5–10 minutes.241

Dosage

Available as hydromorphone hydrochloride; dosage expressed in terms of the salt.238 239

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.411 413 431 432 435

Reduce dosage in geriatric or debilitated patients and in patients with renal or hepatic impairment.238 239 246 a

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.700 703 (See Specific Drugs under Interactions.)

Individualize dosage to provide adequate analgesia and minimize adverse effects.238 239 241 246

When selecting initial dosage, consider type, severity, and frequency of pain; age, general condition, and medical status of patient; concurrent drug therapy; patient’s risk for abuse or addiction; prior use of opiates; and the acceptable balance between pain relief and adverse effects.238 239 246 In patients being transferred from other opiate therapy, also consider daily dosage, potency, and specific characteristics (e.g., elimination half-life) of the previously administered opiate and reliability of the relative potency estimate used to calculate equivalent hydromorphone dosage.238 239 246

Avoid abrupt discontinuance to avoid precipitation of withdrawal symptoms.238 239 246 a

Pediatric Patients

Pain (Treatment with Conventional [Immediate-release] Preparations)
Oral

Children 6–12 years of age: 0.03–0.08 mg/kg every 4–6 hours as needed.245

Children >12 years of age: 1–4 mg every 4–6 hours as needed.245

IV, IM, or Sub-Q

Children 6–12 years of age: 0.015 mg/kg every 4–6 hours as needed.245

Children >12 years of age: 1–4 mg every 4–6 hours as needed.245

Adults

Pain (Oral Treatment with Conventional [Immediate-release] Preparations)
Oral

Usual initial dosage in non-opiate-tolerant adults is 2–4 mg every 4–6 hours.238 240 For severe pain, initial doses of 4–8 mg have been used.241 Adjust dose and/or frequency of administration gradually based on response.238

Manufacturer states that usual dosage is 2.5–10 mg every 3–6 hours, although some patients may require higher dosages.238

For chronic pain, administer at regularly scheduled intervals (“around the clock”); may give supplemental doses of 5–15% of the total daily dosage every 2 hours as needed for breakthrough pain.238

Switching from Other Opiates to Conventional Hydromorphone Preparations
Oral

Convert total daily dosage of current opiate to equivalent daily dosage of hydromorphone hydrochloride and then administer in divided doses.238

Calculate an equianalgesic dosage of oral hydromorphone hydrochloride using manufacturer’s suggested dosage conversions (see Table 1).238 239 For opiates not in Table 1, convert total daily dosage of current opiate to equivalent morphine sulfate dosage; then use estimated daily morphine sulfate dosage to determine equianalgesic dosage of hydromorphone hydrochloride.238 239

To account for individual variation in response to different opiate agonists, reduce first few doses of hydromorphone hydrochloride to one-half to two-thirds of the estimated equianalgesic dose.238 Adjust dose and/or frequency of administration based on response.238

Table 1. Equianalgesic Potency Conversion

 

Equianalgesic Dose (in mg)

Opiate Agonist or Partial Agonist

Oral

Parenteral

Morphine sulfate

40–60

10

Hydromorphone hydrochloride

6.5–7.5

1.3–2

Oxymorphone hydrochloride

6.6

1–1.1

Levorphanol tartrate

4

2–2.3

Meperidine hydrochloride

300–400

75–100

Methadone hydrochloride

10–20

10

Nalbuphine hydrochloride

10–12

Butorphanol tartrate

1.5–2.5

Pain (Oral Treatment with Extended-release Tablets)
Oral

Carefully individualize dosage; overestimation of initial dose may result in fatal overdosage.246

Manufacturer considers the following dosage recommendations to be suggested approaches to the individual management of each patient.246

Switching from Conventional Hydromorphone to Extended-release Hydromorphone
Oral

Administer same total daily dosage once every 24 hours.246 May titrate dose every 3–4 days based on response.246

In clinical trials, dosage range was 8–64 mg daily.246

Switching from Other Oral Opiates to Extended-release Hydromorphone
Oral

Consult published dosage conversion tables (see Table 2), keeping in mind that such conversion ratios are only approximate.246

For transdermal fentanyl, estimated equianalgesic dosage of extended-release hydromorphone hydrochloride is 12 mg every 24 hours for each 25-mcg/hour increment in fentanyl transdermal dosage.246

Generally initiate at 50% of the calculated total daily dosage, then titrate upward (by suggested increments of 25–50% of the current daily dosage) based on response.246 Do not increase more frequently than once every 3–4 days.246

Table 2. Approximate Equianalgesic Doses for Conversion from Oral Opiate Agonists to Extended-release Hydromorphone

Opiate Agonist

Equianalgesic Oral Dose (in mg)

Hydromorphone hydrochloride

12

Codeine phosphate

200

Hydrocodone bitartrate

30

Methadone hydrochloride

20

Morphine sulfate

60

Oxycodone hydrochloride

30

Oxymorphone hydrochloride

20

Conversion from transdermal fentanyl: Initiate extended-release tablets ≥18 hours following removal of fentanyl transdermal system.246

Conversion from methadone: Particularly close monitoring required; equianalgesic conversion ratios between methadone and other opiates vary widely depending on extent of prior methadone exposure.246

Consider increasing dosage if >2 doses of supplemental (rescue) analgesic are required for breakthrough pain within a 24-hour period on 2 consecutive days.246 Administer extended-release tablets no more frequently than every 24 hours.246

In clinical trials, dosage range was 8–64 mg daily.246

Discontinuance of Therapy with Extended-release Hydromorphone
Oral

Discontinue therapy by reducing dose by 25–50% every 2–3 days until 8 mg is reached.246

Pain (Parenteral Treatment)
Treatment of Opiate-naive Adults
IM or Sub-Q

Initially 1–2 mg every 2–3 hours as needed.239 Some patients may require lower initial dosages.239 Adjust dose and/or frequency of administration based on response.239

IV

Initially 0.2–1 mg by slow injection every 2–3 hours.239 Some patients may require lower initial dosages.239 Adjust dose and/or frequency of administration gradually based on response.239

Treatment of Critically Ill Adults
IV

In ICU setting, loading dose of 0.2–0.6 mg followed by continuous infusion of 0.5–3 mg/hour has been used.242

Has been administered in intermittent IV doses of 10–30 mcg/kg every 1–2 hours or as continuous IV infusion of 7–15 mcg/kg per hour.243

Switching from Other Opiates to Parenteral Hydromorphone
IV, IM, or Sub-Q

Convert total daily dosage of current opiate to equivalent daily dosage of hydromorphone hydrochloride and then administer in divided doses.239

Calculate an equianalgesic dosage of parenteral hydromorphone hydrochloride using manufacturer’s suggested dosage conversions (see Table 1).238 239 For opiates not in Table 1, convert total daily dosage of current opiate to equivalent morphine sulfate dosage; then use estimated daily morphine sulfate dosage to determine equianalgesic dosage of hydromorphone hydrochloride.238 239

Reduce estimated parenteral hydromorphone hydrochloride dosage by one-half because of possible incomplete cross-tolerance.239 Adjust dosage based on response.239

Prescribing Limits

Adults

Pain

For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for the expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).411 433 434 435

CDC recommends that primary care clinicians carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately ≥12.5 mg of hydromorphone hydrochloride daily) for chronic pain and avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately ≥22.5 mg of hydromorphone hydrochloride daily) or carefully justify their decision to prescribe such dosages.411 Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.423 431

Some states have set prescribing limits (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with a specialist is mandated or recommended).411 420 421 423

Special Populations

Hepatic Impairment

Pain
Oral

Reduce initial dosage in patients with moderate hepatic impairment (Child-Pugh class B); use even more conservative dosages in patients with severe hepatic impairment (Child-Pugh class C).238 246

Closely monitor during dosage titrations.238 246

Use oral solution rather than conventional tablets to facilitate dosage titration.238

IV, IM, or Sub-Q

Reduce initial dosage to one-fourth to one-half the usual recommended dosage in patients with moderate hepatic impairment; consider possibility that systemic exposure may be further increased when selecting initial dosage in patients with severe hepatic impairment.239

Closely monitor during dosage titrations.239

Renal Impairment

Pain
Oral

Reduce initial dosage in patients with moderate renal impairment (Clcr 40–60 mL/minute); further reduce dosage in those with severe renal impairment (Clcr <30 mL/minute).238 246

Closely monitor during dosage titrations.238 246

Because extended-release tablets are intended for once-daily administration, consider an alternative analgesic regimen with flexible dosing interval in patients with severe renal impairment.246

Use oral solution rather than conventional tablets to facilitate dosage titration.238

IV, IM, or Sub-Q

Depending on degree of impairment, reduce initial dosage to one-fourth to one-half the usual recommended dosage.239

Closely monitor during dosage titrations.239

Geriatric and Debilitated Patients

Select dosage with caution, and use lower than usual initial dosages.238 239 246 a

Cautions for Hydromorphone Hydrochloride

Contraindications

  • Known hypersensitivity to hydromorphone or any ingredient in the formulation.238 239 246

  • Respiratory depression in unmonitored settings or in the absence of resuscitative equipment.238 239 246

  • Acute or severe asthma or hypercarbia.238 239 246

  • GI obstruction, especially paralytic ileus (see Acute Abdominal Conditions under Cautions).239 246 Because extended-release tablets are nondeformable, contraindications for this formulation also include blind loops in GI tract and prior surgery or underlying disease that would cause narrowing of GI tract.246

  • Conventional (immediate-release) oral preparations contraindicated for use in obstetrical analgesia.238 (See Pregnancy under Cautions.)

  • Extended-release tablets and 10-mg/mL injection are contraindicated in patients not already tolerant to opiate agonists.239 246

Warnings/Precautions

Warnings

Shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.a

Dependence and Abuse

Physical and psychological dependence and tolerance may develop with repeated administration, and abuse potential exists; use with caution.238 239 246 a

Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms.238 239 246 After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.238 239 246

Sudden, marked shortening of GI transit time in patients receiving hydromorphone extended-release tablets may result in decreased absorption of the drug and precipitation of withdrawal symptoms.246

Increased risk of tolerance, dependence, or addiction in patients with alcoholism or other drug dependency.238 239 Use with caution.238 239

Hydromorphone abuse in combination with other CNS depressants may result in serious risk.238 239 246 (See Specific Drugs under Interactions.)

Use of Highly Concentrated Injection

Use 10-mg/mL injection only in patients who are tolerant to opiate agonists; overdosage and/or death may result if confused with less concentrated formulations and used in patients who are not tolerant to opiate agonists.239 (See Boxed Warning.)

Use extreme caution to avoid confusing the highly concentrated injection with the less concentrated injections.239

Opiate Conversions

To avoid errors that may result in overdosage or death when switching patients from other opiate therapy to hydromorphone therapy, use opiate conversion tables to calculate an equianalgesic dosage.239 (See Dosage under Dosage and Administration.) Morphine sulfate and hydromorphone hydrochloride are not equianalgesic on a mg per mg basis.239

Use of Extended-release Tablets

Use the extended-release tablets only in patients who are tolerant to opiate agonists; fatal respiratory depression may result if used in patients who are not tolerant to opiate agonists.246 (See Boxed Warning.)

Do not break, chew, crush, inject, or dissolve extended-release tablets as rapid release of drug and absorption of a potentially fatal dose may occur.246

Respiratory Depression

The major toxicity associated with hydromorphone.238 239 246 d

Occurs most frequently in geriatric or debilitated patients, in those with conditions accompanied by hypoxia or hypercapnia, following large initial doses in patients who are not opiate tolerant, or in patients receiving other agents with respiratory depressant effects.238 239 246

Use with extreme caution in patients with COPD or cor pulmonale, and in patients with substantially decreased respiratory reserve (e.g., asthma, severe obesity, sleep apnea), hypoxia, hypercapnia, or preexisting respiratory depression.238 239 In such patients, even therapeutic hydromorphone doses may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.238 239 246 Consider use of nonopiate analgesics and use hydromorphone under close medical supervision at lowest effective dosage.239 246

Consider offering naloxone when opiate agonists are prescribed for patients at increased risk of opiate overdosage (e.g., those with history of overdose or substance use disorder, those receiving ≥50 mg of morphine sulfate [or equivalent] daily, those receiving benzodiazepines concomitantly, those with medical conditions that could increase sensitivity to opiates).411 431

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiates, including hydromorphone, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiate agonists, alcohol) may result in profound sedation, respiratory depression, coma, and death.416 417 418 700 701 702 703 Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.416 417 418 435 700 701

Reserve concomitant use of hydromorphone and other CNS depressants for patients in whom alternative treatment options are inadequate.700 703 (See Specific Drugs under Interactions.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.400 Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.400

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.400 If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.400 In some patients, switching to a different opiate improved symptoms.400

Head Injury and Increased Intracranial Pressure

Respiratory depressant effects and ability of opiates to increase CSF pressure may be markedly exaggerated in patients with head injury, other intracranial lesions, or preexisting elevation in intracranial pressure.238 239 246

Hydromorphone produces effects (e.g., pupillary changes, altered consciousness) that may obscure clinical course and neurologic signs of further increase in CSF pressure in patients with head injuries.238 239 246

Use with extreme caution, if at all, in comatose patients and those with head injury, brain tumor, or elevated CSF pressure.f

Hypotension

Possible severe hypotension in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant drugs that compromise vascular tone (e.g., phenothiazines, general anesthetics).238 239 246 (See Specific Drugs under Interactions.)

May produce orthostatic hypotension in ambulatory patients.238 239

Use with caution in patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and BP.238 239 246

Acute Abdominal Conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.238 239 246

Use with caution, if at all, in patients at risk for ileus.239

Extended-release tablets are nondeformable and may cause obstructive symptoms in patients with or at risk for GI strictures.246 Do not administer to patients with conditions that can cause narrowing of GI tract (e.g., prior GI surgery, GI obstruction, blind loop syndrome, esophageal motility disorders, small bowel inflammatory disease, short-gut syndrome due to adhesions or decreased transit time, history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, Meckel’s diverticulum).246

Sensitivity Reactions

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.238 239 246 a

Latex Sensitivity

Packaging components for some formulations (e.g., 250- and 500-mg vials) contain natural latex proteins in the form of dry natural rubber and/or natural rubber latex; take appropriate precautions for patients with a history of natural latex sensitivity.239 a

General Precautions

CNS Effects

May impair mental alertness or physical coordination; warn patient to use caution when driving or operating machinery.238 239 246

Concurrent use with other CNS depressants may result in profound sedation, respiratory depression, coma, or death.700 703 (See Specific Drugs under Interactions.)

Seizures

May aggravate preexisting seizures in patients with seizure disorders.238 239 246

May induce seizures in some clinical settings.239 246 Mild to severe seizures and myoclonus reported in critically ill patients receiving high parenteral doses of hydromorphone.238 239 a

Debilitated and Special-risk Patients

Use with caution in debilitated patients, patients with myxedema or hypothyroidism, Addison’s disease, prostatic hypertrophy, urethral stricture, gall bladder disease, CNS depression or coma, toxic psychosis, acute alcoholism, delirium tremens, kyphoscoliosis, or following GI surgery.238 239 246

Biliary Disease

Use with caution in patients with biliary disease, including acute pancreatitis, and immediately before biliary tract surgery; may cause sphincter of Oddi spasm and decrease biliary and pancreatic secretions.238 239 246

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;400 401 402 403 404 causality not established.400 Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.400 Perform appropriate laboratory testing in patients with manifestations of hypogonadism.400

Local Effects of Concentrated Injection

Consider possibility of local irritation and induration with IM or sub-Q use of 10-mg/mL injection.a

Specific Populations

Pregnancy

Category C.238 239 246

Administration during labor may cause neonatal respiratory depression and sinusoidal fetal heart rate patterns.238 239 246 a Use hydromorphone injection with caution; an opiate antagonist for reversal of respiratory depression should be readily available.239 Manufacturers of oral formulations recommend against use during labor.238 246

Infants born to women regularly taking opiates during pregnancy will be physically dependent; intensity of withdrawal syndrome does not always correlate with maternal opiate dosage or duration of use.238 239 246

Lactation

Distributed into milk in low concentrations.238 239 246 Women receiving hydromorphone generally should not nurse.238 239 246

Pediatric Use

Safety and efficacy not established in children;238 239 246 however, conventional preparations of hydromorphone have been used in children.245 b (See Pediatric Patients under Dosage and Administration.)

Geriatric Use

Use with caution.238 239 246

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults;238 239 experience with extended-release tablets suggests geriatric patients may be more susceptible to adverse effects.246 Select dosage with caution, and use lower than usual initial dosages.238 239 246 a

Hepatic Impairment

Exposure to drug may be increased.238 239 246 (See Absorption: Special Populations, under Pharmacokinetics.) Use with caution and in reduced dosages.238 239 246

Renal Impairment

Exposure to drug may be increased.238 239 246 (See Absorption: Special Populations, under Pharmacokinetics.) Use with caution and in reduced dosages.238 239 246

Common Adverse Effects

Light-headedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, pruritus.238 239

With extended-release tablets for chronic pain: Constipation, nausea, vomiting, somnolence, headache, dizziness.246

Interactions for Hydromorphone Hydrochloride

Not known whether hydromorphone is metabolized by CYP isoenzymes.j

Minimal potential to inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 3A4, and 4A11.246

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.400 May occur at usual dosages.400 Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.400 (See Advice to Patients.)

If concomitant use of other serotonergic drugs is warranted, monitor patients for serotonin syndrome, particularly during initiation of therapy and dosage increases.400

If serotonin syndrome is suspected, discontinue hydromorphone, other opiate therapy, and/or any concurrently administered serotonergic agents.400

Specific Drugs

Drug

Interaction

Comments

Amphetamine

Dextroamphetamine may enhance opiate agonist analgesiaf

Anticholinergics

Possible increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus239 246

Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), SNRIs (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine), tricyclic antidepressants (TCAs), mirtazapine, nefazodone, trazodone, vilazodone

Risk of serotonin syndrome400

TCAs: Opiates may potentiate the effects of TCAsf

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, the antidepressant, and/or any concurrently administered opiates or serotonergic agents400

TCAs: Use concomitantly with caution; dosage adjustment may be necessaryf

Antiemetics, 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, the 5-HT3 receptor antagonist, and/or any concurrently administered opiates or serotonergic agents400

Antipsychotics (e.g., aripiprazole, asenapine, cariprazine, chlorpromazine, clozapine, fluphenazine, haloperidol, iloperidone, loxapine, lurasidone, molindone, olanzapine, paliperidone, perphenazine, pimavanserin, quetiapine, risperidone, thioridazine, thiothixene, trifluoperazine, ziprasidone)

Risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving hydromorphone, initiate antipsychotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving an antipsychotic, initiate hydromorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Benzodiazepines (e.g., alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, triazolam)

Risk of profound sedation, respiratory depression, hypotension, coma, or death416 417 418 700 701 703 704

Whenever possible, avoid concomitant use410 411 415 435

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving hydromorphone, initiate benzodiazepine, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a benzodiazepine, initiate hydromorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Consider offering naloxone to patients receiving opiates and benzodiazepines concomitantly411 431

Buspirone

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, buspirone, and/or any concurrently administered opiates or serotonergic agents400

CNS depressants (e.g., alcohol, anxiolytics, other opiate agonists, general anesthetics, tranquilizers, phenothiazines)

Additive CNS and respiratory depressant effects; increased risk of respiratory depression, profound sedation, hypotension, coma, or death238 239 246 f 700 703 704

Alcohol: Increased peak plasma hydromorphone concentrations with extended-release tablets, possible ingestion of toxic dose246 248

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving hydromorphone, initiate CNS depressant, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a CNS depressant, initiate hydromorphone, if required, at reduced dosage and titrate based on clinical response700 703

Avoid alcohol use238 246 248 700

Monitor closely for respiratory depression and sedation700 703

Dextromethorphan

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, dextromethorphan, and/or any concurrently administered opiates or serotonergic agents400

Diuretics

Opiate agonists may decrease effects of diuretics used in CHFf

5-HT1 receptor agonists (triptans; e.g., almotriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, the triptan, and/or any concurrently administered opiates or serotonergic agents400

Lithium

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, lithium, and/or any concurrently administered opiates or serotonergic agents400

MAO inhibitors (e.g., isocarboxazid, linezolid, methylene blue, phenelzine, selegiline, tranylcypromine)

Severe, unpredictable potentiation of opiates reported; possible CNS excitation or depression, hypotension or hypertension239 246

Risk of serotonin syndrome400

Some manufacturers recommend allowing 14 days to elapse following discontinuance of MAO inhibitor and initiation of hydromorphone239 246

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, the MAO inhibitor, and/or any concurrently administered opiates or serotonergic agents400

Neuromuscular blocking agents

May enhance the neuromuscular blocking action of skeletal muscle relaxants and increase respiratory depressant effects238 239 246 f

Opiate partial agonists (butorphanol, buprenorphine, nalbuphine, pentazocine)

Possible reduced analgesic effect and/or withdrawal symptoms238 239 246 f

Caution advised;238 239 f some manufacturers state that combined use is not recommended246

Sedative/hypnotic agents (e.g., butabarbital, eszopiclone, pentobarbital, ramelteon, secobarbital, suvorexant, zaleplon, zolpidem)

Risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving hydromorphone, initiate sedative/hypnotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a sedative/hypnotic, initiate hydromorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Skeletal muscle relaxants (e.g., baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, tizanidine)

Risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Cyclobenzaprine: Risk of serotonin syndrome400

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving hydromorphone, initiate skeletal muscle relaxant, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a skeletal muscle relaxant, initiate hydromorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Cyclobenzaprine: If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, cyclobenzaprine, and/or any concurrently administered opiates or serotonergic agents400

St. John’s wort (Hypericum perforatum)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, St. John’s wort, and/or any concurrently administered opiates or serotonergic agents400

Tryptophan

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue hydromorphone, tryptophan, and/or any concurrently administered opiates or serotonergic agents400

Hydromorphone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral, rectal, or parenteral administration.a

Peak plasma concentrations attained within 0.5–1 hour or 12–16 hours after oral administration of conventional (immediate-release) preparations or extended-release tablets, respectively.238 246

Conventional tablets and oral solution are bioequivalent.238

Following oral administration as conventional tablets given 4 times daily or as extended-release tablets given once daily at same total daily dosage, steady-state plasma concentrations are maintained within same concentration range; extended-release tablets produce less fluctuation in concentrations.246

Onset

Usually 15–30 minutes; more rapid than morphine.a d

Duration

Maintained for 4–5 hours following administration as conventional preparation, depending on the route; may have shorter duration of action than morphine.a

Food

Conventional tablets: Food decreases peak plasma concentrations and increases systemic exposure by 25 and 35%, respectively, and delays peak plasma concentrations by 0.8 hour.238

Extended-release tablets: Food does not alter pharmacokinetics.246

Special Populations

Hepatic impairment: Systemic exposure after single oral dose is increased fourfold in individuals with moderate impairment (Child-Pugh class B).238 239 Further increase expected in severe hepatic impairment.238 239

Renal impairment: Systemic exposure after single oral dose is increased twofold in individuals with moderate impairment (Clcr 40–60 mL/minute) and threefold to fourfold in those with severe impairment (Clcr <30 mL/minute).238 239

Distribution

Extent

Crosses the placenta.238 239 246 Distributes into breast milk.238 239

Plasma Protein Binding

8–27%.238 239 246

Elimination

Metabolism

Principally in the liver via glucuronic acid conjugation to hydromorphone-3-glucuronide (95%); minor amounts of 6-hydroxy reduction metabolites.238 239 246 a

Elimination Route

Excreted principally in the urine as hydromorphone-3-glucuronide.238 239 a

Half-life

Conventional preparations: Approximately 2.3–2.8 hours.238 239

Extended-release tablets: Approximately 11 hours (range: 8–15 hours).246

Special Populations

In severe renal impairment, half-life prolonged to 40 hours.238

Stability

Storage

Oral

Conventional Tablets

Tight, light-resistant container at 25°C (may be exposed to 15–30°C).238

Extended-release Tablets

25°C (may be exposed to 15–30°C).246

Solution

Tight, light-resistant container at 25°C (may be exposed to 15–30°C).238

Parenteral

Affected by light and injection may develop a slight yellowish discoloration; this change apparently does not indicate loss of potency.239 a

Powder for Injection, for IV Infusion

20–25°C (may be exposed to 15–30°C).239 Protect from light.239

Injection

20–25°C (may be exposed to 15–30°C).239 Protect from light.239

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Injection reported physically and chemically stable for at least 24 hours in most common IV infusion solutions when protected from light at 25°C.a

Solution CompatibilityHID

Compatible

Dextrose 5% in Ringer’s injection

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in water

Dextrose 5% in sodium chloride 0.45 or 0.9%

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate 1/6 M

Drug Compatibility
Admixture CompatibilityHID

Compatible

Bupivacaine HCl

Clonidine HCI

Fluorouracil

Heparin sodium

Ketamine HCl

Midazolam HCl

Ondansetron HCl

Potassium chloride

Promethazine HCl

Verapamil HCl

Ziconotide acetate

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Allopurinol sodium

Amifostine

Amikacin sulfate

Atropine sulfate

Aztreonam

Bivalirudin

Caspofungin acetate

Cefotaxime sodium

Cefoxitin sodium

Ceftaroline fosamil

Ceftazidime

Cefuroxime sodium

Chloramphenicol sodium succinate

Cisatracurium besylate

Cladribine

Clindamycin phosphate

Co-trimoxazole

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Docetaxel

Dopamine HCl

Doripenem

Doxorubicin HCl liposome injection

Doxycycline hyclate

Epinephrine HCl

Erythromycin lactobionate

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Filgrastim

Fludarabine phosphate

Foscarnet sodium

Furosemide

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Hydroxyzine HCl

Ketorolac tromethamine

Labetalol HCl

Levofloxacin

Linezolid

Lorazepam

Magnesium sulfate

Melphalan HCl

Metoclopramide HCI

Metronidazole

Micafungin sodium

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nafcillin sodium

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Ondansetron HCl

Oxacillin sodium

Oxaliplatin

Paclitaxel

Palonosetron HCl

Pemetrexed disodium

Penicillin G potassium

Piperacillin sodium–tazobactam sodium

Propofol

Ranitidine HCl

Remifentanil HCl

Scopolamine HBr

Tacrolimus

Teniposide

Thiotepa

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Vinorelbine tartrate

Incompatible

Amphotericin B cholesteryl sulfate complex

Gallium nitrate

Phenytoin sodium

Sargramostim

Variable

Ampicillin sodium

Cefazolin sodium

Diazepam

Phenobarbital sodium

Actions

  • A potent analgesic; shares actions of the opiate agonists.238 239 246 a

  • Opiate agonists alter perception of and emotional response to pain.f

  • Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.238 239 246 f

  • Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).f

  • Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.f

  • Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.f

  • Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.f

  • Agonist activity at the μ-receptor can also result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).f

  • Respiratory depression may be mediated by μ-receptors, possibly μ2-receptors (which may be distinct from μ1-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.f

  • May depress the cough reflex by a direct effect on the cough centers in the medulla; cough-suppressant opiate receptors have also been suggested.f

  • Nausea, vomiting, constipation, and euphoria may be less marked with hydromorphone than with morphine.f

Advice to Patients

  • Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.238 239 246 f

  • Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.700 703 Importance of informing patients that hydromorphone should not be combined with alcohol.238 239 246 700

  • Importance of informing patients that this is a drug of potential abuse and should also be protected from theft.238 239 246 Risk of severe or fatal respiratory depression if misused or if used in individuals for whom drug was not prescribed.238 246

  • Importance of informing patients to keep the drug in a secure location and out of the reach of children.238 246

  • Importance of informing patients that hydromorphone dosage should not be adjusted without consulting with a clinician.238 246 Importance of not abruptly discontinuing hydromorphone following prolonged opiate therapy.238 246

  • Importance of informing clinician of any breakthrough pain or adverse effects (e.g., constipation) that occur during therapy, so that therapy may be adjusted based on individual patient requirements.238 246

  • Potential risk of serotonin syndrome with concurrent use of hydromorphone and other serotonergic agents.400 Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.400

  • Potential risk of adrenal insufficiency.400 Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.400

  • Potential for severe constipation to occur.246 Importance of considering use of appropriate laxative therapy upon initiation of therapy for chronic pain.246

  • Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.400 Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.400

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.238 239 246 f

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.238 239 246 a

  • Importance of informing patients of other important precautionary information. (See Cautions.)

    Hydromorphone Extended-release Tablets
  • Medication guide must be dispensed with every prescription for the extended-release tablets.247 Importance of patients reading the medication guide before initiating therapy and each time the extended-release tablets are dispensed.246

  • Importance of not breaking, crushing, chewing, or dissolving extended-release tablets; potentially fatal overdose can occur.246

  • Importance of using extended-release tablets exactly as prescribed and only if opiate tolerant.246 If hydromorphone therapy has been interrupted for 3 or more days, importance of contacting clinician prior to reinitiating treatment.246

  • Risk of GI obstruction in patients with preexisting severe narrowing of GI tract.246 Importance of informing clinician of prior GI surgeries and GI conditions that may cause narrowing.246 Importance of promptly reporting symptoms of GI obstruction (e.g., abdominal pain or distension, severe constipation, vomiting).246

  • Importance of informing patients that shell of extended-release tablet is nonabsorbable and may be passed in the stool.246

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

HYDROmorphone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

HYDROmorphone Hydrochloride Powder for Prescription Compounding ( C-II)

Oral

Solution

5 mg/5 mL

Dilaudid ( C-II)

Purdue Pharma

HYDROmorphone Hydrochloride Solution ( C-II)

Tablets

2 mg*

Dilaudid ( C-II)

Purdue Pharma

HYDROmorphone Hydrochloride Tablets ( C-II)

4 mg*

Dilaudid ( C-II)

Purdue Pharma

HYDROmorphone Hydrochloride Tablets ( C-II)

8 mg*

Dilaudid ( C-II; scored)

Purdue Pharma

HYDROmorphone Hydrochloride Tablets ( C-II)

Tablets, extended-release

8 mg

Exalgo ( C-II)

Mallinckrodt

12 mg

Exalgo ( C-II)

Mallinckrodt

16 mg

Exalgo ( C-II)

Mallinckrodt

Parenteral

For injection, for preparation of IV infusion

250 mg

Dilaudid-HP Lyophilized ( C-II)

Purdue Pharma

Injection

1 mg/mL*

Dilaudid ( C-II)

Purdue Pharma

HYDROmorphone Hydrochloride Injection ( C-II)

2 mg/mL*

Dilaudid ( C-II)

Purdue Pharma

HYDROmorphone Hydrochloride Injection ( C-II)

4 mg/mL*

Dilaudid ( C-II)

Purdue Pharma

HYDROmorphone Hydrochloride Injection ( C-II)

10 mg/mL (10, 50, or 500 mg)*

Dilaudid-HP ( C-II)

Purdue Pharma

HYDROmorphone Hydrochloride Injection ( C-II)

AHFS DI Essentials. © Copyright 2018, Selected Revisions November 13, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

238. Purdue Pharma. Dilaudid (hydromorphone hydrochloride) oral liquid and tablets prescribing information. Stamford, CT; 2009 Oct 21.

239. Purdue Pharma. Dilaudid and Dilaudid-HP (hydromorphone hydrochloride) injection prescribing information. Stamford, CT; 2011 Jul .

240. Quigley C. Hydromorphone for acute and chronic pain. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD003447. DOI: 10.1002/14651858.CD003447.

241. Principles of analgesic use in the treatment of acute pain and cancer pain. 5th ed. Glenview, IL: American Pain Society; 2004:13-41.

242. Sessler CN, Varney K. Patient-focused sedation and analgesia in the ICU. Chest. 2008; 133:552-65. http://www.ncbi.nlm.nih.gov/pubmed/18252923?dopt=AbstractPlus

243. Jacobi J, Fraser GL, Coursin DB et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002; 30:119-41. http://www.ncbi.nlm.nih.gov/pubmed/11902253?dopt=AbstractPlus

244. Murray A, Hagen NA. Hydromorphone. J Pain Symptom Manage. 2005; 29(5 Suppl):S57-66. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1945048&blobtype=pdf

245. In: Kliegman RM, Behrman RE, Jenson HB et al, eds. Nelson textbook of pediatrics. 18th ed. Philadelphia: Saunders; 2007:2460, 2978.

246. Mallinckrodt. Exalgo (hydromorphone hydrochloride) extended-release tablets prescribing information. Hazelwood, MO; 2010 Nov.

247. Food and Drug Administration. Exalgo (hydromorphone hydrochloride) extended-release tablets. Risk Evaluation and Mitigation Strategy (REMS) document. Rockville, MD; 2010 Mar 24. From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021217s001REMSExalgo.pdf

248. Mallinckrodt. Exalgo (hydromorphone hydrochloride) extended-release tablets medication guide. Hazelwood, MO; 2010 Nov.

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401. Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009; 25:170-5. http://www.ncbi.nlm.nih.gov/pubmed/19333165?dopt=AbstractPlus

402. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL et al. Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer. 2004; 100:851-8. http://www.ncbi.nlm.nih.gov/pubmed/14770444?dopt=AbstractPlus

403. Abs R, Verhelst J, Maeyaert J et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. 2000; 85:2215-22. http://www.ncbi.nlm.nih.gov/pubmed/10852454?dopt=AbstractPlus

404. Fraser LA, Morrison D, Morley-Forster P et al. Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women. Exp Clin Endocrinol Diabetes. 2009; 117:38-43. http://www.ncbi.nlm.nih.gov/pubmed/18523930?dopt=AbstractPlus

410. Nuckols TK, Anderson L, Popescu I et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med. 2014; 160:38-47. http://www.ncbi.nlm.nih.gov/pubmed/24217469?dopt=AbstractPlus

411. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016; 65:1-49. http://www.ncbi.nlm.nih.gov/pubmed/26987082?dopt=AbstractPlus

412. Chou R, Fanciullo GJ, Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10:113-30. http://www.ncbi.nlm.nih.gov/pubmed/19187889?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4043401&blobtype=pdf

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