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HYDROmorphone

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

Medically reviewed by Drugs.com on Mar 29, 2021. Written by ASHP.

Warning

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

  • 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.

    Respiratory Depression
  • Risk of respiratory depression. (See Respiratory Depression under Cautions.)

    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.

  • 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. Extended-release tablets are not indicated for management of acute or postoperative pain or for as-needed (“prn”) use.

  • 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.

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

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

    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.

  • 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. (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. 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.

Uses for HYDROmorphone

Acute Pain

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

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.

Used to provide analgesia during diagnostic and orthopedic procedures.

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.

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. Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain. Optimize concomitant use of other appropriate therapies. (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

Chronic Pain

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

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. (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.

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.

Generally use opiates for management of chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing ) 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.

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).

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 or is superior to other pharmacologic or nonpharmacologic treatments. Use is associated with serious risks (e.g., opiate use disorder [OUD], overdose). (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

HYDROmorphone Dosage and Administration

General

Managing Opiate Therapy for Acute Pain

  • Optimize concomitant use of other appropriate therapies.

  • 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.

  • Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage. (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.

  • 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). Do not prescribe larger quantities for use in case pain continues longer than expected; instead, reevaluate patient if severe acute pain does not remit.

  • 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.

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

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

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.

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

  • 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.

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

  • Some experts recommend initiating opiate therapy for chronic noncancer pain with conventional (immediate-release) opiate analgesics prescribed at lowest effective dosage. 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.

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

  • When repeated dosage increases required, evaluate potential causes and reassess relative benefits and risks. 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.

  • Higher dosages require particular caution, including more frequent and intensive monitoring or referral to specialist. 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).

  • 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. Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily. 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) or have mandated risk-management strategies (e.g., review of state prescription drug monitoring program [PDMP] data prior to prescribing).

  • 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.

  • Taper and discontinue opiate therapy if patient engages in serious or repeated aberrant drug-related behaviors or drug abuse or diversion. Offer or arrange treatment for patients with OUD.

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

Administration

Administer orally or by sub-Q, IM, or slow IV injection or infusion. Has been administered epidurally.

Oral Administration

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

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

Conventional Tablets and Oral Solution

Conventional tablets and oral solution are bioequivalent.

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

Extended-release Tablets

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

Do not administer more frequently than once every 24 hours.

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

Administer without regard to food.

Do not administer with alcohol. (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.

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.

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

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

Highly Concentrated (10-mg/mL) Injection

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

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

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

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

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.

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.

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

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.

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.

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.

Dosage

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

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.

Reduce dosage in geriatric or debilitated patients and in patients with renal or hepatic impairment.

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

Individualize dosage to provide adequate analgesia and minimize adverse effects.

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. 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.

Avoid abrupt discontinuance to avoid precipitation of withdrawal symptoms.

Pediatric Patients

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

Children weighing <50 kg: Initially, 0.03–0.08 mg/kg every 3–4 hours as needed. For severe pain, initial doses of 0.06 mg/kg have been used.

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

IV, IM, or Sub-Q

Children weighing <50 kg: Initially, 0.015 mg/kg every 3–6 hours as needed.

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.

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. For severe pain, initial doses of 4–8 mg have been used. Adjust dose and/or frequency of administration gradually based on response.

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

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.

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.

Calculate an equianalgesic dosage of oral hydromorphone hydrochloride using manufacturer’s suggested dosage conversions (see Table 1). 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.

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. Adjust dose and/or frequency of administration based on response.

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.

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

Switching from Conventional Hydromorphone to Extended-release Hydromorphone
Oral

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

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

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.

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.

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. Do not increase more frequently than once every 3–4 days.

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.

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

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

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

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.

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

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

IV

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

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.

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.

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.

Calculate an equianalgesic dosage of parenteral hydromorphone hydrochloride using manufacturer’s suggested dosage conversions (see Table 1). 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.

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

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).

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. Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.

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).

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).

Closely monitor during dosage titrations.

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

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.

Closely monitor during dosage titrations.

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).

Closely monitor during dosage titrations.

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.

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

IV, IM, or Sub-Q

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

Closely monitor during dosage titrations.

Geriatric and Debilitated Patients

Select dosage with caution, and use lower than usual initial dosages.

Cautions for HYDROmorphone

Contraindications

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

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

  • Acute or severe asthma or hypercarbia.

  • GI obstruction, especially paralytic ileus (see Acute Abdominal Conditions under Cautions). 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.

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

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

Warnings/Precautions

Warnings

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

Dependence and Abuse

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

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

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.

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

Hydromorphone abuse in combination with other CNS depressants may result in serious risk. (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. (See Boxed Warning.)

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

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. (See Dosage under Dosage and Administration.) Morphine sulfate and hydromorphone hydrochloride are not equianalgesic on a mg per mg basis.

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. (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.

Respiratory Depression

The major toxicity associated with hydromorphone.

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.

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. In such patients, even therapeutic hydromorphone doses may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Consider use of nonopiate analgesics and use hydromorphone under close medical supervision at lowest effective dosage.

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

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) or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage. 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).

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. Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.

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

Adrenal Insufficiency

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

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. 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. In some patients, switching to a different opiate improved symptoms.

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.

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.

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

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). (See Specific Drugs under Interactions.)

May produce orthostatic hypotension in ambulatory patients.

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

Acute Abdominal Conditions

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

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

Extended-release tablets are nondeformable and may cause obstructive symptoms in patients with or at risk for GI strictures. 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).

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.

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.

General Precautions

CNS Effects

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

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

Seizures

May aggravate preexisting seizures in patients with seizure disorders.

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

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.

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.

Hypogonadism

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

Local Effects of Concentrated Injection

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

Specific Populations

Pregnancy

Category C.

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

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.

Lactation

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

Pediatric Use

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

Geriatric Use

Use with caution.

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

Hepatic Impairment

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

Renal Impairment

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

Common Adverse Effects

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

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

Interactions for HYDROmorphone

Not known whether hydromorphone is metabolized by CYP isoenzymes.

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

Drugs Associated with Serotonin Syndrome

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

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

Specific Drugs

Drug

Interaction

Comments

Amphetamine

Dextroamphetamine may enhance opiate agonist analgesia

Anticholinergics

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

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 syndrome

TCAs: Opiates may potentiate the effects of TCAs

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

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

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

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

Risk of serotonin syndrome

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

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

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 death

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

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

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

Monitor closely for respiratory depression and sedation

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 death

Whenever possible, avoid concomitant use

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

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 response

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

Monitor closely for respiratory depression and sedation

Consider prescribing naloxone for patients receiving opiates and benzodiazepines concomitantly

Buspirone

Risk of serotonin syndrome

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

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

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 death

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

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

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 response

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

Monitor closely for respiratory depression and sedation

Consider prescribing naloxone for patients receiving opiates and other CNS depressants concomitantly

Avoid alcohol use

Dextromethorphan

Risk of serotonin syndrome

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

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

Diuretics

Opiate agonists may decrease effects of diuretics used in CHF

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

Risk of serotonin syndrome

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

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

Lithium

Risk of serotonin syndrome

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

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

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

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

Risk of serotonin syndrome

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

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

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

Neuromuscular blocking agents

May enhance the neuromuscular blocking action of skeletal muscle relaxants and increase respiratory depressant effects

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

Possible reduced analgesic effect and/or withdrawal symptoms

Caution advised; some manufacturers state that combined use is not recommended

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

Risk of profound sedation, respiratory depression, hypotension, coma, or death

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

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 response

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

Monitor closely for respiratory depression and sedation

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

Risk of profound sedation, respiratory depression, hypotension, coma, or death

Cyclobenzaprine: Risk of serotonin syndrome

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

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 response

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

Monitor closely for respiratory depression and sedation

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

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

St. John’s wort (Hypericum perforatum)

Risk of serotonin syndrome

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

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

Tryptophan

Risk of serotonin syndrome

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

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

HYDROmorphone Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral, rectal, or parenteral administration.

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.

Conventional tablets and oral solution are bioequivalent.

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.

Onset

Usually 15–30 minutes; more rapid than morphine.

Duration

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

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.

Extended-release tablets: Food does not alter pharmacokinetics.

Special Populations

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

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).

Distribution

Extent

Crosses the placenta. Distributes into breast milk.

Plasma Protein Binding

8–27%.

Elimination

Metabolism

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

Elimination Route

Excreted principally in the urine as hydromorphone-3-glucuronide.

Half-life

Conventional preparations: Approximately 2.3–2.8 hours.

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

Special Populations

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

Stability

Storage

Oral

Conventional Tablets

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

Extended-release Tablets

25°C (may be exposed to 15–30°C).

Solution

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

Parenteral

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

Powder for Injection, for IV Infusion

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

Injection

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

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.

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.

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

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

  • 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).

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

  • 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.

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

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

  • 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.

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

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

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.

  • Risk of respiratory depression following overdosage. Advise patients of the benefits of naloxone following opiate overdose and of their options for obtaining the drug.

  • 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. Importance of informing patients that hydromorphone should not be combined with alcohol.

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

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

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

  • 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.

  • Potential risk of serotonin syndrome with concurrent use of hydromorphone and other serotonergic agents. 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.

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

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

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

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

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

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

    Hydromorphone Extended-release Tablets
  • Importance of patients reading the medication guide before initiating therapy and each time the extended-release tablets are dispensed.

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

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

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

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

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 2021, Selected Revisions March 29, 2021. 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.

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