Hydromorphone Hydrochloride

Pronunciation

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

Warning(s)

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

  • 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.n o v

  • Respiratory Depression
  • Risk of respiratory depression.n o v Concomitant use of CNS depressants, including alcohol, increases risk of fatal respiratory depression.n o

  • 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.a o

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

  • 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.o v

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

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

REMS:

FDA approved a REMS for hydromorphone to ensure that the benefits outweigh the risks. (See REMS Program under Dosage and Administration.) The REMS may apply to one or more preparations of hydromorphone and consists of the following: medication guide and elements to assure safe use. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Opiate agonist; semisynthetic phenanthrene derivative.a

Uses for Hydromorphone Hydrochloride

Acute Pain

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

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

Used to provide analgesia during diagnostic and orthopedic procedures.f

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

Slideshow: Fact or Fiction? The Top 15 Osteoarthritis Myths

IV route (including patient-controlled administration) is preferred for administration of opiate agonists after major surgery since repeated IM injections may cause pain and trauma.f

Consider around-the-clock dosing of analgesics in the initial stages of acute pain to avoid wide swings in pain and sedation often associated with as-needed dosing regimens.f

Chronic Pain

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

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

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

Analgesic therapy must be individualized and titrated according to patient response and tolerance.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

As tolerance to initial dosage develops, larger doses may be given as necessary.f

Alternative analgesic adjuncts such as tricyclic antidepressants or anticonvulsants also should be considered in the treatment of chronic nonmalignant pain (e.g., neurogenic pain).f

During prolonged use, especially when opiate agonists are self-administered, precautions should be taken to prevent unnecessary increases in dosage.f

Hydromorphone Hydrochloride Dosage and Administration

General

REMS Program

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

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

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

Administration

Administer orally or by sub-Q, IM, or slow IV injection or infusion.a o n v Has been administered epidurally.i p t

Oral Administration

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

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

Conventional Tablets and Oral Solution

Conventional tablets and oral solution are bioequivalent.n

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

Extended-release Tablets

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

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

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

Administer without regard to food.v

Do not administer with alcohol.v x (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.o

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.i p r s t

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

IM injection is discouraged for any analgesic (e.g., the injection itself is painful, delayed onset).i

Highly Concentrated (10-mg/mL) Injection

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

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

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

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

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.o

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.o

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

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.r

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.a o

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.i

Dosage

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

Give the smallest effective dose as infrequently as possible to minimize the development of tolerance and physical dependence.a

Reduce dosage in geriatric or debilitated patients and in patients with renal or hepatic impairment.a n o v

When administered concomitantly with another CNS depressant (e.g., sedatives, tranquilizers, general anesthetics, phenothiazines), reduce dosage of one or both agents.n o v (See Specific Drugs under Interactions.)

Individualize dosage to provide adequate analgesia and minimize adverse effects.n o i v

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.n o v 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.n o v

Avoid abrupt discontinuance to avoid precipitation of withdrawal symptoms.a n o v

Pediatric Patients

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

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

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

IV, IM, or Sub-Q

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

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

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

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

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.n

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.n

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

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

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)

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

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

Switching from Conventional Hydromorphone to Extended-release Hydromorphone
Oral

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

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

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.v

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.v

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

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.v

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

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

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

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.v

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

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

IV

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

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.r

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.s

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.o

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

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

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).n v

Closely monitor during dosage titrations.n v

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

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.o

Closely monitor during dosage titrations.o

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).n v

Closely monitor during dosage titrations.n v

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.v

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

IV, IM, or Sub-Q

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

Closely monitor during dosage titrations.o

Geriatric and Debilitated Patients

Select dosage with caution, and use lower than usual initial dosages.a n o v

Cautions for Hydromorphone Hydrochloride

Contraindications

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

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

  • Acute or severe asthma or hypercarbia.n o v

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

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

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

Warnings/Precautions

Warnings

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

Dependence and Abuse

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

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

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.v

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

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

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

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

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.v (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.v

Respiratory Depression

The major toxicity associated with hydromorphone.d n o v

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.n o v

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

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.n o v

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.n o v

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

Hypotension

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

May produce orthostatic hypotension in ambulatory patients.n o

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

Acute Abdominal Conditions

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

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

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

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.a n o v

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.a o

General Precautions

CNS Effects

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

Concomitant use of another CNS depressant may have additive effects; decrease dosage of one or both drugs.n o v (See Specific Drugs under Interactions.)

Seizures

May aggravate preexisting seizures in patients with seizure disorders.n o v

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

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.n o v

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.n o v

Local Effects of Concentrated Injection

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

Specific Populations

Pregnancy

Category C.n o v

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

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.n o v

Lactation

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

Pediatric Use

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

Geriatric Use

Use with caution.n o v

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

Hepatic Impairment

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

Renal Impairment

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

Common Adverse Effects

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

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

Interactions for Hydromorphone Hydrochloride

Not known whether hydromorphone is metabolized by CYP isoenzymes.j

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

Specific Drugs

Drug

Interaction

Comments

Amphetamine

Dextroamphetamine may enhance opiate agonist analgesiaf

Anticholinergics

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

Antidepressants, tricyclics

Potentiation of the effects of the antidepressantf

Use concomitantly with caution; dosage adjustment may be necessaryf

CNS depressants (e.g., other opiate agonists, general anesthetics, tranquilizers, sedatives and hypnotics, alcohol)

Additive CNS and respiratory depressant effects; possible hypotension and profound sedation or comaf n o v

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

Reduce dosage of one or both agentsf n o v

Avoid use of alcoholn v x

Diuretics

Opiate agonists may decrease effects of diuretics used in CHFf

MAO inhibitors

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

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

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

Possible reduced analgesic effect and/or withdrawal symptomsf n o v

Caution advised;f n o some manufacturers state that combined use is not recommendedv

Phenothiazines

Some tranquilizers, especially phenothiazines, may antagonize opiate agonist analgesiaf

Possible severe hypotensionn o v

Skeletal muscle relaxants

May enhance the neuromuscular blocking action of skeletal muscle relaxants and increase respiratory depressant effectsf n o v

Hydromorphone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

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

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

Conventional tablets and oral solution are bioequivalent.n

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.v

Onset

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

Duration

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

Food

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

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

Special Populations

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

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).n o

Distribution

Extent

Crosses the placenta.n o v Distributes into breast milk.n o

Plasma Protein Binding

8–27%.n o v

Elimination

Metabolism

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

Elimination Route

Excreted principally in the urine as hydromorphone-3-glucuronide.a n o

Half-life

Conventional preparations: Approximately 2.3–2.8 hours.n o

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

Special Populations

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

Stability

Storage

Oral

Conventional Tablets

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

Extended-release Tablets

25°C (may be exposed to 15–30°C).v

Solution

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

Parenteral

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

Powder for Injection, for IV Infusion

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

Injection

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

Compatibility

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

Parenteral

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

Solution CompatibilityHID

Compatible

Dextrose 5% in Ringer’s injection

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in water

Dextrose 5% in sodium chloride 0.45 or 0.9%

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Drug Compatibility
Admixture CompatibilityHID

Compatible

Bupivacaine HCl

Clonidine HCI

Fluorouracil

Heparin sodium

Ketamine HCl

Midazolam HCl

Ondansetron HCl

Potassium chloride

Promethazine HCl

Verapamil HCl

Ziconotide acetate

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Allopurinol sodium

Amifostine

Amikacin sulfate

Atropine sulfate

Aztreonam

Bivalirudin

Caspofungin acetate

Cefotaxime sodium

Cefoxitin sodium

Ceftaroline fosamil

Ceftazidime

Cefuroxime sodium

Chloramphenicol sodium succinate

Cisatracurium besylate

Cladribine

Clindamycin phosphate

Co-trimoxazole

Dexamethasone sodium phosphate

Dexmedetomidine HCl

Diltiazem HCl

Diphenhydramine HCl

Dobutamine HCl

Docetaxel

Dopamine HCl

Doripenem

Doxorubicin HCl liposome injection

Doxycycline hyclate

Epinephrine HCl

Erythromycin lactobionate

Etoposide phosphate

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Filgrastim

Fludarabine phosphate

Foscarnet sodium

Furosemide

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Hydroxyzine HCl

Ketorolac tromethamine

Labetalol HCl

Levofloxacin

Linezolid

Lorazepam

Magnesium sulfate

Melphalan HCl

Metoclopramide HCI

Metronidazole

Micafungin sodium

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nafcillin sodium

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Ondansetron HCl

Oxacillin sodium

Oxaliplatin

Paclitaxel

Palonosetron HCl

Pemetrexed disodium

Penicillin G potassium

Piperacillin sodium–tazobactam sodium

Propofol

Ranitidine HCl

Remifentanil HCl

Scopolamine HBr

Tacrolimus

Teniposide

Thiotepa

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Vinorelbine tartrate

Incompatible

Amphotericin B cholesteryl sulfate complex

Gallium nitrate

Phenytoin sodium

Sargramostim

Variable

Ampicillin sodium

Cefazolin sodium

Diazepam

Phenobarbital sodium

Actions

  • A potent analgesic; shares actions of the opiate agonists.a n o v

  • 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.f n o v

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

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

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

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

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

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

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

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

Advice to Patients

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

  • Importance of informing patients that hydromorphone should not be combined with alcohol or other CNS depressants (e.g., sleep medications, tranquilizers).n o v

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

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

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

  • 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.n v

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

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

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

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

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

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

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

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

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

Preparations

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

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)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Dilaudid 2MG Tablets (PURDUE PHARMA L.P.): 20/$23.99 or 30/$35.99

Dilaudid 4MG Tablets (PURDUE PHARMA L.P.): 20/$36.99 or 30/$49.97

Dilaudid 8MG Tablets (PURDUE PHARMA L.P.): 20/$57.77 or 30/$86.66

Dilaudid-5 1MG/ML Liquid (PURDUE PHARMA L.P.): 473/$192.60 or 1419/$577.81

HYDROmorphone HCl 2MG Tablets (MALLINCKRODT PHARM): 20/$15.33 or 30/$22.99

HYDROmorphone HCl 4MG/ML Solution (HOSPIRA): 20/$39.83 or 30/$60.19

HYDROmorphone HCl 4MG Tablets (ROXANE): 20/$16.01 or 30/$24.01

HYDROmorphone HCl 8MG Tablets (MALLINCKRODT PHARM): 20/$29.51 or 30/$44.27

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 9, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

a. AHFS Drug Information 2006. McEvoy GK, ed. Hydromorphone. Bethesda, MD: American Society of Health-System Pharmacists; 2006:2108-10.

b. Endo Pharmaceuticals Inc. Hydromorphone hydrochloride tablets prescribing information. Chadds Ford, PA; 2003 May.

d. Abbott Laboratories. Dilaudid (hydromorphone hydrochloride) injection, tablets, and suppositories prescribing information. North Chicago, IL; 2005 Mar.

f. AHFS Drug Information 2006. McEvoy GK, ed. Opiate agonists general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2006:2096-101.

g. Bailey PL. Clinical Pharmacology and Applications of Opioid Agonists. In: Bowdle TA, Horita A, Kharasch ED. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone; 1994:105-7.

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

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

j. Purdue Pharma. Palladone (hydromorphone hydrochloride) extended-release capsules prescribing information. Stamford, CT; 2004 Nov 16.

k. Srinivasan A, Budnitz D, Shehab N et al. Infant deaths associated with cough and cold medications—two states, 2005. MMWR Morb Mortal Wkly Rep. 2007; 56:1-4. [PubMed 17218934]

l. Food and Drug Administration. Cough and cold medications in children less than two years of age. Rockville, MD; 2007 Jan 12. From FDA website.

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

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

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

r. Sessler CN, Varney K. Patient-focused sedation and analgesia in the ICU. Chest. 2008; 133:552-65. [PubMed 18252923]

s. Jacobi J, Fraser GL, Coursin DB et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002; 30:119-41. [PubMed 11902253]

t. Murray A, Hagen NA. Hydromorphone. J Pain Symptom Manage. 2005; 29(5 Suppl):S57-66.

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

w. Food and Drug Administration. Exalgo (hydromorphone hydrochloride) extended-release tablets. Risk Evaluation and Mitigation Strategy (REMS) document. Rockville, MD; 2010 Mar 24. From FDA website.

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

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:630-9.

Hide
(web1)