Brand name: Dilaudid
Drug class: Opoid Agonists

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Opiate agonist; semisynthetic phenanthrene derivative.^a

Uses for Hydromorphone Hydrochloride

Acute Pain

Used parenterally or orally as conventional preparations (immediate-release tablets, oral solution) for relief of pain that is severe enough to require an opiate analgesic and for which alternative treatments (e.g., nonopiate analgesics, opiate-containing fixed combinations) have not been, or are not expected to be, adequate or tolerated.^{238 239}

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

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.)

Use highly concentrated (10-mg/mL) injection only in opiate-tolerant patients who require higher dosages of opiate analgesics (see Highly Concentrated [10-mg/mL] Injection under Dosage and Administration); during treatment with this formulation, patient must remain on around-the-clock opiate therapy.²³⁹

Reserve extended-release tablets for use in opiate-tolerant patients with pain severe enough to require long-term, daily, around-the-clock use of an opiate analgesic when alternative treatment options (e.g., nonopiate analgesics, immediate-release opiates) are inadequate or not tolerated; not indicated for as-needed (“prn”) use.²⁴⁶

Chronic Pain

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

Extended-release tablets are used orally in opiate-tolerant patients for management of pain that is severe enough to require long-term, daily, around-the-clock use of an opiate analgesic; reserve for use in patients for whom alternative treatment options (e.g., nonopiate analgesics, immediate-release opiates) are inadequate or not tolerated.²⁴⁶ Do not use on an as-needed (“prn”) basis.²⁴⁶ (See Pain [Oral Treatment with Extended-release Tablets] under Dosage and Administration.)

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 healing^{410 411 412 413} ) 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 life^{411 423 431 432 436} or is superior to other pharmacologic or nonpharmacologic treatments.⁴³² Use is associated with serious risks (e.g., opiate use disorder [OUD], overdose).^{411 431 436} (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

Related/similar drugs

gabapentin, acetaminophen, tramadol, cyclobenzaprine, naproxen, oxycodone, Tylenol

Hydromorphone Hydrochloride Dosage and Administration

General

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}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Depression under Cautions.)

• 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 increase^{411 413} 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, OUD).^{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 OUD.^{411 412 413}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Depression under Cautions.)

Administration

Administer orally or by sub-Q, IM, or slow IV injection or infusion.^{238 239 246 a} Has been administered IV via a controlled-delivery device for patient-controlled analgesia (PCA). Has been administered epidurally^{† [off-label]}.^{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 to avoid inadvertent interchange of 8-mg extended-release tablets and 8-mg conventional tablets.²⁴⁶

Conventional Tablets

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

Oral Solution

Use caution when prescribing or dispensing to avoid confusion between mg and mL.²³⁸ When writing prescriptions, specify the intended total dose (in mg) along with the corresponding total volume (in mL).²³⁸

Always use a calibrated measuring device to ensure that the oral solution dose is measured and administered accurately; do not use a household teaspoon or tablespoon.²³⁸

Oral solution and conventional tablets are bioequivalent.²³⁸

Extended-release Tablets

Only clinicians who are knowledgeable in the use of potent opiates for the management of chronic pain should prescribe the extended-release tablets.²⁴⁶

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

Administer 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 (See Specific Drugs under Interactions.)

Parenteral Administration

Administer by sub-Q, IM, or slow (over at least 2–3 minutes depending on dose) 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 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 (0.2, 1, 2, 4, and 10 mg/mL).^{239 251} 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.)

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, 60 mg of oral hydrocodone bitartrate 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}

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

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

Dilution

If using the 500-mg single-use (10-mg/mL) vial to prepare an IV infusion solution, withdraw appropriate amount and then discard any unused portion in an appropriate manner.²³⁹

Has been diluted (e.g., 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 depending on dose), 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

Standardize 4 Safety

Standardized concentrations for hydromorphone have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label.^{249 250} For additional information on S4S (including updates that may be available), see [Web].

Concentration standard for adults is for continuous infusions not delivered by a PCA device. Concentration standard for pediatric patients also is for continuous infusions and not for delivery via PCA device.

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}

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.^{238 239} When selecting initial dosage, consider severity of patient’s pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.^{238 239 246}

Because of substantial interpatient variability in relative potency of opiate analgesics and analgesic formulations, it is preferable to underestimate the patient's 24-hour opiate requirements when converting from other opiates to hydromorphone than to overestimate the requirements and manage an adverse reaction.^{238 239 246}

Monitor closely for respiratory depression, especially during the first 24–72 hours of therapy and following any increase in dosage.^{238 239 246}

Continually reevaluate for adequacy of pain control and for adverse effects, as well for development of addiction, abuse, or misuse.^{238 239 246} During long-term therapy, periodically reevaluate need for continued opiate therapy.²⁴⁶

Frequent communication among the prescriber, other members of the healthcare team, the patient, and the patient's caregiver or family is important during periods of changing analgesic requirements, including the initial dosage titration period.^{238 239 246}

If level of pain increases after dosage stabilization, attempt to identify cause of increased pain before increasing dosage.^{238 239 246}

Avoid abrupt discontinuance to avoid precipitation of withdrawal symptoms.^{238 239 246 a} (See Dependence and Tolerance under Cautions.)

Pediatric Patients

Pain† [off-label] (Treatment with Conventional [Immediate-release] Preparations)

Oral

Children weighing <50 kg: Initially, 0.03–0.08 mg/kg every 3–4 hours as needed.^{245 437 438 439 440} For severe pain, initial doses of 0.06 mg/kg have been used.²⁴¹

Children and adolescents weighing ≥50 kg: Initially, 1–2 mg every 3–4 hours as needed.^{437 439}

IV, IM, or Sub-Q

Children weighing <50 kg: Initially, 0.015 mg/kg every 3–6 hours as needed.^{437 438 439}

Children and adolescents weighing ≥50 kg: Initially, 0.2–0.6 mg IV every 2–4 hours or 0.8–1 mg by IM or sub-Q injection every 4–6 hours as needed.⁴³⁷

Adults

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

Oral

Immediate-release tablets: Usual initial dosage in non-opiate-tolerant adults is 2–4 mg every 4–6 hours.^{238 240}

Oral solution: Usual initial dosage in non-opiate-tolerant adults is 2.5–10 mg every 3–6 hours as needed.²³⁸

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

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

Conventional tablets: Manufacturer states that safest approach is to initiate hydromorphone hydrochloride at one-half the usual initial dose administered every 4–6 hours.²³⁸ Adjust dose and/or frequency of administration based on response.²³⁸

Oral solution: Manufacturer states that safest approach is to initiate hydromorphone hydrochloride at one-half the usual initial dose administered every 3–6 hours.²³⁸ Adjust dose and/or frequency of administration based on response.²³⁸

Pain (Oral Treatment with Extended-release Tablets)

Oral

Use only in opiate-tolerant patients.²⁴⁶ Discontinue all other around-the-clock opiate analgesics when therapy with the extended-release tablets is initiated.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, 60 mg of oral hydrocodone bitartrate 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}

Switching from Conventional Hydromorphone to Extended-release Hydromorphone

Oral

Administer same total daily dosage once every 24 hours.²⁴⁶

Switching from Other Oral Opiates to Extended-release Hydromorphone

Oral

Use approximate oral conversion factors in Table 6 to calculate estimated daily hydromorphone hydrochloride requirement.²⁴⁶ Recommended initial dosage is 50% of the calculated estimated daily requirement administered once daily (e.g., if total daily oral oxycodone hydrochloride dosage is 60 mg, estimated daily oral hydromorphone hydrochloride requirement would be 24 mg and approximate initial dosage of hydromorphone hydrochloride extended-release tablets would be 12 mg once daily).²⁴⁶

For patients receiving >1 opiate, calculate approximate oral hydromorphone hydrochloride dosage for each opiate separately and then sum the totals; for patients receiving fixed-combination analgesics, consider only the opiate component.²⁴⁶

Always round the calculated dosage down, when necessary, to an appropriate available tablet strength.²⁴⁶

Table 6 is not a table of equianalgesic doses.²⁴⁶ Use the conversion factors in Table 6 only to switch patients from the listed oral opiate analgesics to hydromorphone hydrochloride extended-release tablets; use of the conversion factors to switch patients from hydromorphone hydrochloride extended-release tablets to another opiate will result in overestimation of the dosage of the new opiate and possible fatal overdosage.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

Switching from Transdermal Fentanyl to Extended-release Hydromorphone

Oral

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

Initiate extended-release hydromorphone hydrochloride at 50% of the calculated total daily dosage.²⁴⁶ Always round the calculated dosage down, when necessary, to an appropriate available tablet strength.²⁴⁶

Can initiate extended-release tablets 18 hours following removal of fentanyl transdermal system.²⁴⁶

Dosage Adjustment to Achieve Adequate Analgesia

Oral

Patients who experience breakthrough pain may require dosage adjustment or supplemental analgesia (i.e., “rescue” therapy with an immediate-release analgesic).²⁴⁶

Titrate dosage of extended-release tablets in increments of 4–8 mg every 3–4 days based on response.²⁴⁶

In clinical trials, dosage range was 12–64 mg daily.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, then reduce estimated parenteral hydromorphone hydrochloride dosage by one-half because of possible incomplete cross-tolerance; administer in divided doses.²³⁹ Adjust dosage based on response.²³⁹

Discontinuance of Analgesic Therapy with Hydromorphone

Oral

In patient who may be physically dependent on opiates, generally reduce dosage by no more than 10–25% every 2–4 weeks.^{238 246} Patients taking opiates for briefer periods of time may tolerate more rapid taper.^{238 246}

Monitor for manifestations of opiate withdrawal, adequacy of pain control, changes in mood, and emergence of suicidal thoughts during dosage taper.^{238 246} (See Dependence and Tolerance under Cautions.) If manifestations of withdrawal occur, may need to pause the taper or increase dosage to prior level before tapering dosage more slowly.^{238 246}

IV, IM, or Sub-Q

In patient who may be physically dependent on opiates, manufacturer recommends reducing dosage by 25–50% every 2–4 days.²³⁹

If manifestations of withdrawal occur, increase dosage to prior level and taper more slowly (i.e., increase interval between dosage reductions and/or reduce amount of each incremental change in dose).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 (Conventional [Immediate-release] Preparations)

Depending on degree of impairment, reduce initial dosage to one-fourth to one-half the usual recommended dosage.²³⁸

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

Oral (Extended-release Tablets)

Reduce initial dosage in patients with moderate hepatic impairment to one-fourth the usual recommended dosage.²⁴⁶

Closely monitor during initiation of therapy and dosage titrations.²⁴⁶

Use of alternative analgesic preparations recommended in those with severe hepatic impairment.²⁴⁶

IV, IM, or Sub-Q

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

Closely monitor during dosage titrations.²³⁹

Renal Impairment

Pain

Oral (Conventional [Immediate-release] Preparations)

Depending on degree of impairment, reduce initial dosage to one-fourth to one-half the usual recommended dosage.²³⁸

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

Closely monitor during dosage titrations.²³⁸

Oral (Extended-release Tablets)

Reduce initial dosage in patients with moderate renal impairment to one-half the usual recommended dosage.²⁴⁶

Closely monitor during initiation of therapy and dosage titrations.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

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}

May reduce IV dose to 0.2 mg.²³⁹

Cautions for Hydromorphone Hydrochloride

Contraindications

• Known hypersensitivity (e.g., anaphylaxis) to hydromorphone or any ingredient in the formulation.^{238 239 246}

• Substantial respiratory depression.^{238 239 246}

• Acute or severe bronchial asthma in unmonitored settings or in the absence of resuscitative equipment.^{238 239 246}

• Known or suspected GI obstruction, including paralytic ileus.^{238 239 246} 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 (See GI Complications with Extended-release Tablets 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

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

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

Dosing Errors with Oral Solution

Dosing errors can result in accidental overdosage and death.²³⁸ Ensure that the dose is clearly communicated and accurately dispensed.²³⁸ (See Oral Solution under Dosage and Administration.) Always use a calibrated measuring device to accurately measure and administer the oral solution.²³⁸

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

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

Addiction, Abuse, and Misuse

Risk of addiction, abuse, and misuse, which can lead to overdosage and death.^{238 239 246} Addiction can occur at recommended dosages or with misuse or abuse.^{238 239 246} Concurrent abuse of alcohol and other CNS depressants increases risk of toxicity.^{238 239 246} Abuse potential similar to that of other potent opiate agonists.^{238 239 246}

Modified-release (e.g., extended-release) opiates are associated with a greater risk of overdose and death because of the larger amount of drug contained in each dosage unit.²⁴⁶

Abuse or misuse of hydromorphone extended-release tablets by crushing or chewing the tablets, snorting the contents, or injecting the dissolved contents will result in uncontrolled delivery of hydromorphone and can result in a fatal overdose.²⁴⁶ IV injection of tablet excipients can result in local tissue necrosis, infection, pulmonary granulomas, embolism, and death and can increase the risk of endocarditis and valvular heart injury.²⁴⁶

Assess each patient’s risk for addiction, abuse, and misuse prior to prescribing; monitor all patients for development of these behaviors or conditions.^{238 239 246} Personal or family history of substance abuse (drug or alcohol addiction or abuse) or mental illness (e.g., major depression) increases risk.^{238 239 246}

The potential for addiction, abuse, and misuse should not prevent opiate prescribing for appropriate pain management, but does necessitate intensive counseling about risks and proper use and intensive monitoring for signs of addiction, abuse, and misuse.^{238 239 246}

Prescribe only in the smallest appropriate quantity and instruct patients on secure storage and proper disposal to prevent theft.^{238 239 246}

When opiate analgesics are being discontinued because of a suspected substance use disorder (SUD), evaluate and treat the patient or refer for evaluation and treatment of SUD.^{238 246}

Respiratory Depression

Serious, life-threatening, or fatal respiratory depression can occur with use of opiates, even when used as recommended; can occur at any time during therapy, but risk is greatest during initiation of therapy and following dosage increases.^{238 239 246} Monitor for respiratory depression, especially during first 24–72 hours of therapy and following any dosage increase.^{238 239 246}

Carbon dioxide retention from opiate-induced respiratory depression can exacerbate the drug's sedative effects and, in certain patients, can lead to elevated intracranial pressure.^{238 239 246} (See Head Injury and Increased Intracranial Pressure under Cautions.)

Opiates can cause sleep-related breathing disorders, including central sleep apnea and sleep-related hypoxemia.^{238 239 246} Risk of central sleep apnea is dose dependent; consider tapering opiate dosage if central sleep apnea occurs.^{238 239 246}

Geriatric, cachectic, or debilitated patients are at increased risk for life-threatening respiratory depression.^{238 239 246} Closely monitor such patients, particularly following initiation of therapy, during dosage titration, and during concomitant therapy with other respiratory depressants.^{238 239 246} Consider use of nonopiate analgesics.^{238 239 246}

Even recommended doses of hydromorphone may decrease respiratory drive to the point of apnea in patients with COPD, cor pulmonale, substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression.^{238 239 246} Closely monitor such patients, particularly following initiation of therapy, during dosage titration, and during concomitant therapy with other respiratory depressants.^{238 239 246} Consider use of nonopiate analgesics.^{238 239 246} (See Contraindications under Cautions.)

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.^{238 239 246} Overestimation of the dosage when transferring patients from another opiate analgesic can result in fatal overdosage with the first dose.^{238 239 246}

Accidental ingestion of even 1 dose, especially by a child, can result in respiratory depression and fatal overdosage.^{238 246}

If respiratory depression occurs, follow usual guidelines for management of opiate agonist-induced respiratory depression.^{238 239 246}

Routinely discuss availability of the opiate antagonist naloxone with all patients receiving new or reauthorized prescriptions for opiate analgesics, including hydromorphone.⁷⁵⁰

Consider prescribing naloxone for patients receiving opiate analgesics who are at increased risk of opiate overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with history of opiate or substance use disorder, those with medical conditions that could increase sensitivity to opiate effects, those who have experienced a prior opiate overdose)^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ Even if patients are not receiving an opiate analgesic, consider prescribing naloxone if the patient is at increased risk of opiate overdosage (e.g., those with current or past diagnosis of OUD, those who have experienced a prior opiate overdose).⁷⁵⁰

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.)

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 may 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.^a

Other Warnings and Precautions

General Opiate Agonist Precautions

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

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

Hypotension

May cause severe hypotension, including orthostatic hypotension and syncope, in ambulatory patients, especially in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant use of certain CNS depressants (e.g., phenothiazines, general anesthetics).^{238 239 246} Monitor BP following initiation of therapy and dosage increases in such patients.^{238 239 246} (See Specific Drugs under Interactions.)

Vasodilation produced by the drug may further reduce cardiac output and BP in patients with circulatory shock.^{238 239 246} Avoid use in such patients.^{238 239 246}

Head Injury and Increased Intracranial Pressure

Potential for increased carbon dioxide retention and secondary elevation of intracranial pressure; in patients particularly susceptible to these effects (e.g., those with evidence of elevated intracranial pressure or brain tumors), monitor closely for sedation and respiratory depression, particularly during initiation of therapy.^{238 239 246}

Opiates may obscure the clinical course in patients with head injuries.^{238 239 246}

Avoid use in patients with impaired consciousness or coma.^{238 239 246}

Acute Abdominal Conditions

Contraindicated in patients with known or suspected GI obstruction, including paralytic ileus.^{238 239 246}

GI Complications with Extended-release Tablets

Extended-release tablets are nondeformable and do not appreciably change shape in the GI tract; obstructive symptoms reported in patients with or at risk for GI strictures (e.g., because of prior GI surgery) who ingested nondeformable extended-release drug formulations.²⁴⁶

Hydromorphone extended-release tablets contraindicated in patients with GI obstruction or with severe narrowing of the GI tract due to any pathologic or iatrogenic condition (e.g., 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

Extended-release tablets may be visible on abdominal radiographs under certain circumstances, especially when digital enhancing techniques are utilized.²⁴⁶

Pancreatic and Biliary Disease

May cause spasm of the sphincter of Oddi and increase serum amylase concentrations; monitor patients with biliary disease, including acute pancreatitis, for worsening symptoms.^{238 239 246}

Seizures

May aggravate preexisting seizures in patients with seizure disorders.^{238 239 246} Monitor for worsened seizure control.^{238 239 246}

May increase risk of seizures in other settings associated with seizures.^{238 239 246}

Dependence and Tolerance

Physical dependence and tolerance can develop during prolonged opiate therapy.^{238 239 246}

Rapid or abrupt discontinuance of opiates in physically dependent patients has resulted in serious withdrawal symptoms (e.g., restlessness, lacrimation, rhinorrhea, yawning, sweating, chills, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased BP, respiratory rate, or heart rate), uncontrolled pain, suicide, attempts to find other sources of opiate analgesics, and attempts to treat pain or withdrawal symptoms with illicit substances.^{238 239 246}

Gradually taper dosage when discontinuing opiates in patients who may be physically dependent; consider dosage and treatment duration, type of pain, and physical and psychologic attributes of patient.^{238 246} (See Discontinuance of Analgesic Therapy with Hydromorphone under Dosage and Administration.) Ensure ongoing care of patient and agree on tapering schedule and follow-up plan with clear and realistic goals and expectations.^{238 246}

Ensure that a multimodal approach to pain management is in place prior to initiating an opiate taper, particularly for patients receiving high dosages and/or long-term opiate therapy for chronic pain.^{238 246}

Avoid concomitant use of opiate partial agonists.^{238 239 246} (See Specific Drugs under Interactions.)

Infants born to women who are physically dependent on opiates also will be physically dependent and may exhibit respiratory difficulties and manifestations of opiate withdrawal.^{238 239 246} (See Pregnancy under Cautions.)

CNS Depression

May impair mental alertness or physical coordination; warn patient to avoid driving or operating machinery until effects on individual are known.^{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.)

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

No available data in pregnant women to inform a drug-associated risk for major birth defects and spontaneous abortion.^{238 239 246} Neural tube defects, soft tissue and skeletal abnormalities, reduced postnatal pup survival, developmental delays, and altered behavioral responses observed in animal studies with hydromorphone.^{238 239 246}

Analysis of data from the National Birth Defects Prevention Study (large population-based, case-control study) suggests therapeutic use of opiates in pregnant women during organogenesis is associated with a low absolute risk of birth defects, including heart defects, spina bifida, and gastroschisis.^{253 254}

Use of opiates in pregnant women during labor can result in neonatal respiratory depression and psychophysiologic effects.^{238 239 246} Monitor neonates whose mothers received opiates for respiratory depression; opiate antagonist must be readily available for reversal of respiratory depression.^{238 239 246} Hydromorphone is not recommended for use in pregnant women during and immediately before labor.^{238 239 246}

Prolonged maternal use of opiates during pregnancy can result in neonatal opiate withdrawal syndrome; in contrast to adults, withdrawal syndrome in neonates may be life-threatening and requires management according to protocols developed by neonatology experts.^{238 239 246 a} Syndrome presents with irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.^{238 239 246 a} Onset, duration, and severity vary depending on the specific opiate used, duration of use, timing and amount of last maternal use, and rate of drug elimination by the neonate.^{238 239 246 a}

Lactation

Distributed into milk in low concentrations.^{238 239 246}

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for hydromorphone and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.^{238 239} Manufacturer states that women receiving hydromorphone extended-release tablets should not breast-feed infants.²⁴⁶

Monitor infants exposed to hydromorphone for excessive sedation and respiratory depression.^{238 239 246}

Symptoms of withdrawal can occur in opiate-dependent breast-fed infants upon cessation of maternal opiate use or cessation of breast-feeding by women receiving hydromorphone.^{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.^{245 437 438 439 440} (See Pediatric Patients under Dosage and Administration.)

Geriatric Use

Possible increased sensitivity to the drug's effects.^{238 239 246} Increased risk of respiratory depression.^{238 239 246}

Select dosage with caution; usually initiate therapy at low end of dosage range and titrate slowly with close monitoring for CNS or respiratory depression.^{238 239 246}

Consider greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or drug therapy in geriatric patients.^{238 239 246} Possible increased risk of adverse reactions in patients with renal impairment.^{238 239 246} May be useful to monitor renal function.^{238 239 246}

Hepatic Impairment

Exposure to drug may be increased.^{238 239 246} (See Absorption: Special Populations, under Pharmacokinetics.) Use conservative initial dosage and monitor closely for CNS or respiratory depression.^{238 239 246} (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Exposure to drug may be increased.^{238 239 246} (See Absorption: Special Populations, under Pharmacokinetics.) Use conservative initial dosage and monitor closely for CNS or respiratory depression.^{238 239 246} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Lightheadedness, 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

Drug Interactions

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 Examples include serotonin type 1 (5-HT₁) receptor agonists (“triptans”), SSRIs, SNRIs, tricyclic antidepressants, antiemetics that are 5-HT₃ receptor antagonists, buspirone, cyclobenzaprine, dextromethorphan, lithium, metaxalone, St. John’s wort (Hypericum perforatum), tryptophan, other serotonin modulators (e.g., mirtazapine, nefazodone, trazodone, vilazodone), and MAO inhibitors (those used to treat psychiatric disorders and others [e.g., linezolid, methylene blue, selegiline]).^{238 239 400}

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

Hydromorphone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

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

Undergoes extensive first-pass metabolism following oral administration.²³⁸ Bioavailability following oral administration of a single 8-mg conventional tablet is approximately 24%.²³⁸

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}

Systemic exposure is dose proportional over a dose range of 2–8 mg as conventional tablets.²³⁸

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 with conventional preparations; more rapid than morphine.^a

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 (Cl_cr 40–60 mL/minute) and threefold to fourfold in those with severe impairment (Cl_cr <30 mL/minute).^{238 239}

Distribution

Extent

Crosses the placenta.^{238 239 246} Distributes into breast milk.^{238 239}

Plasma Protein Binding

Approximately 8–19% at therapeutic plasma concentrations.²³⁸

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

Age and sex do not substantially alter pharmacokinetics.²³⁸

Stability

Storage

Oral

Conventional Tablets

20–25°C.²³⁸ Protect from light.²³⁸

Extended-release Tablets

20–25°C.²⁴⁶

Solution

20–25°C.²³⁸ Protect from light.²³⁸

Parenteral

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

Injection

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

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

• Importance of reading the manufacturer’s patient information (e.g., medication guide) each time the drug is dispensed.^{238 246}

• Potential for addiction, abuse, and misuse, which can lead to overdosage or death, even when used as recommended.^{238 246} Protect from theft or misuse; properly dispose of any unused drug.^{238 246} Do not share hydromorphone with others.^{238 246}

• Instruct patients on proper measurement of hydromorphone oral solution to ensure appropriate dose is accurately measured and administered.²³⁸ Advise patients to always use a calibrated measuring device.²³⁸ If the prescribed concentration is changed, instruct patients on how to correctly measure the new dose.²³⁸

• Risk of life-threatening respiratory depression; most likely to occur following initiation of therapy or increase in dosage; may occur at recommended dosages.^{238 246 750} Importance of seeking immediate medical attention if signs or symptoms of respiratory depression occur.^{238 246} Advise patients of the benefits of naloxone following opiate overdose and of their options for obtaining the drug.^{238 750}

• Accidental ingestion, especially by a child, may result in respiratory depression or death.^{238 246} Instruct patients to keep the drug in a secure location and out of the reach of children.^{238 246}

• 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.^{238 246 700 703}

• 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

• Importance of avoiding concomitant use of MAO inhibitors.^{238 246}

• 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

• Importance of using extended-release tablets exactly as prescribed and only if opiate tolerant.²⁴⁶ Importance of not breaking, cutting, crushing, chewing, or dissolving extended-release tablets; potentially fatal overdose can occur.²⁴⁶

• To avoid withdrawal symptoms following prolonged therapy, importance of not discontinuing hydromorphone without first discussing a tapering plan with clinician.^{238 246}

• Risk of GI obstruction with use of hydromorphone extended-release tablets 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

• Potential for orthostatic hypotension and syncope to occur.^{238 246} Inform patients of symptoms of low BP and steps to take if hypotension occurs (e.g., sit or lie down, carefully rise from a seated or supine position).^{238 246}

• Possibility of anaphylaxis and importance of seeking appropriate medical attention.^{238 246}

• Potential for fetal harm; importance of women informing their clinician of known or suspected pregnancy.^{238 246} Importance of clinician informing women that chronic use during pregnancy may result in neonatal opiate withdrawal syndrome, which can be life-threatening if not recognized and treated.^{238 246}

• Advise nursing women to monitor infants exposed to opiates for increased sleepiness, breathing difficulties, or limpness and to seek immediate medical care if such manifestations occur.²³⁸ Advise women that use of extended-release hydromorphone in nursing women is not recommended.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

• Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.^{238 246 f}

• Potential for severe constipation to occur.²⁴⁶ Advise patients on appropriate management of constipation.^{238 246}

• Importance of informing clinician of any breakthrough pain so that therapy may be adjusted based on individual patient requirements.^{238 246}

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

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

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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

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