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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(hye droe MOR fone)
Generic Available (U.S.)
Yes: Excludes extended release tablet, liquid, powder for injection
Index Terms
Controlled Substance
C-II
Medication Guide
An FDA-approved patient medication guide for Exalgo™, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM204267.pdf, must be dispensed with this medication every time it is dispensed. Medication guides are also available at http://www.exalgorems.com.
REMS Components
Exalgo™: Elements to Assure Safe Use; Medication Guide
Prescribing and Access Restrictions
Exalgo™: As a requirement of the REMS program, healthcare providers who prescribe Exalgo™ need to receive training on the proper use and potential risks of Exalgo™. For training, please refer to http://www.exalgorems.com. Prescribers will need retraining every 2 years or following any significant changes to the Exalgo™ REMS program.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of moderate-to-severe pain
Exalgo™: Management of moderate-to-severe pain in opioid-tolerant patients (requiring around-the-clock analgesia for an extended period of time)
Pregnancy Risk Factor
C
Pregnancy Considerations
Hydromorphone was teratogenic in some, but not all, animal studies; however, maternal toxicity was also reported. Hydromorphone crosses the placenta. Chronic opioid use during pregnancy may lead to a withdrawal syndrome in the neonate. Symptoms include irritability, hyperactivity, loss of sleep pattern, abnormal crying, tremor, vomiting, diarrhea, weight loss, or failure to gain weight.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Low concentrations of hydromorphone can be found in breast milk. Withdrawal symptoms may be observed in breast-feeding infants when opioid analgesics are discontinued. Breast-feeding is not recommended.
Contraindications
Hypersensitivity to hydromorphone, any component of the formulation; acute or severe asthma, severe respiratory depression (in absence of resuscitative equipment or ventilatory support); severe CNS depression
Additional product-specific contraindications:
Dilaudid®, Dilaudid-HP®: Obstetrical analgesia
Exalgo™: Opioid nontolerant patients, paralytic ileus, preexisting GI surgery or diseases resulting in narrowing of GI tract, loops in the GI tract or GI obstruction
Warnings/Precautions
Boxed warnings:
• Abuse/misuse/diversion: See “Other warnings/precautions” below.
• Extended release tablets: See “Dosage form specific issues” below.
• Injection: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).
• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydrocodone, levorphanol, oxycodone, oxymorphone).
• Seizures: Myoclonus and seizures have been reported with high doses.
Disease-related concerns:
• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease.
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction. Hydromorphone may increase biliary tract pressure following spasm in sphincter of Oddi. Use caution in patients with inflammatory or obstructive bowel disorder, acute pancreatitis secondary to biliary tract disease, and patients undergoing biliary surgery.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease.
• CNS depression/coma: Use with caution in patients with CNS depression or coma.
• Delirium tremens: Use with caution in patients with delirium tremens.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
• Gastrointestinal narrowing: Exalgo™ tablets are nondeformable; do not administer to patients with preexisting severe gastrointestinal narrowing (eg, esophageal motility, small bowel inflammatory disease, short gut syndrome, history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, Meckel's diverticulum); obstruction may occur.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Psychoses: Use with caution in patients with toxic psychoses.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
• MAO inhibitors: Exalgo™ is not recommended for use within 14 days of MAO inhibitors; severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues:
• Controlled release capsules: Should only be used when continuous analgesia is required over an extended period of time. Controlled release products are not to be used on an "as needed" (PRN) basis.
• Extended release tablets: Exalgo™: [U.S. Boxed Warning]: For use in opioid tolerant patients only; fatal respiratory depression may occur in patients who are not opioid tolerant. Indicated for the management of moderate-to-severe pain when around the clock pain control is needed for an extended time period. Not for use as an as-needed analgesic or for the management of acute or postoperative pain. Tablets should be swallowed whole; do not crush, break, chew, dissolve or inject; doing so may lead to rapid release and absorption of a potentially fatal dose of hydromorphone. Injection of the tablet excipients may be toxic and cause lethal complications. Accidental consumption may lead to fatal overdose, especially in children. Tablets may be visible on abdominal x-rays, especially when digital enhancing techniques are used.
• Injection: [U.S. Boxed Warning]: Extreme caution should be taken to avoid confusing the highly-concentrated (Dilaudid-HP®) injection with the less-concentrated (Dilaudid®) injectable product. Dilaudid-HP® should only be used in patients who are opioid-tolerant.
• Sodium metabisulfite: Some dosage forms contain trace amounts of sodium metabisulfite which may cause allergic reactions in susceptible individuals.
Other warnings/precautions:
• Abuse/misuse/diversion: [U.S. Boxed Warning]: Hydromorphone has a high potential for abuse; healthcare provider should be alert to problems of abuse, misuse, and diversion.
• I.M. administration: Variable absorption and a lag time to peak effect may result from I.M. use.
• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.
• Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
Adverse Reactions
Frequency not defined.
Cardiovascular: Bradycardia, extrasystoles, flushing of face, hyper-/hypotension, palpitation, peripheral edema, peripheral vasodilation, syncope, tachycardia
Central nervous system: Abnormal dreams, abnormal feelings, agitation, aggression, apprehension, attention disturbances, chills, coordination impaired, CNS depression, confusion, cognitive disorder, crying, dizziness, drowsiness, dysphoria, encephalopathy, euphoria, fatigue, hallucinations, headache, hyper-reflexia, hypo/hyperesthesia, hypothermia, increased intracranial pressure, insomnia, lightheadedness, listlessness, malaise, memory impairment, mental depression, mood alterations, nervousness, panic attacks, paranoia, psychomotor hyperactivity, restlessness, sedation, seizure, somnolence, suicide ideation, vertigo
Dermatologic: Hyperhidrosis, pruritus, rash, urticaria
Endocrine & metabolic: Amylase decreased, dehydration, erectile dysfunction, fluid retention, hyperuricemia, hypogonadism, hypokalemia, libido decreased, sexual dysfunction, testosterone decreased
Gastrointestinal: Abdominal distention, anal fissure, anorexia, appetite increased, bezoar (Exalgo™), biliary tract spasm, constipation, diarrhea, diverticulum, diverticulitis, duodenitis, dysgeusia, dysphagia, eructation, flatulence, gastric emptying impaired, gastrointestinal motility disorder (Exalgo™), gastroenteritis, hematochezia, ileus, intestinal obstruction (Exalgo™), large intestine perforation (Exalgo™), nausea, painful defecation, paralytic ileus, stomach cramps, taste perversion, vomiting, weight loss, xerostomia
Genitourinary: Dysuria, micturition disorder, ureteral spasm, urinary frequency, urinary hesitation, urinary retention, urinary tract spasm, urination decreased
Hepatic: LFTs increased
Local: Pain at injection site (I.M.), wheal/flare over vein (I.V.)
Neuromuscular & skeletal: Arthralgia, dysarthria, dyskinesia, muscle rigidity, muscle spasms, myalgia, myoclonus, paresthesia, trembling, tremor, uncoordinated muscle movements, weakness
Ocular: Blurred vision, diplopia, dry eyes, miosis, nystagmus
Otic: Tinnitus
Respiratory: Apnea, bronchospasm, dyspnea, hyperventilation, hypoxia, laryngospasm, oxygen saturation decreased, respiratory depression/distress, rhinorrhea
Miscellaneous: Antidiuretic effects, balance disorder, diaphoresis, difficulty walking, histamine release, physical and psychological dependence
Metabolism/Transport Effects
None known.
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MAO Inhibitors: May enhance the adverse/toxic effect of HYDROmorphone. Risk X: Avoid combination
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk D: Consider therapy modification
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Ethanol may increase CNS depression. Management: Monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Gotu kola, valerian, and kava kava may increase CNS depression. Management: Avoid gotu kola, valerian, and kava kava.
Storage
Store injection and oral dosage forms at 15°C to 30°C (59°F to 86°F). Protect tablets from light. A slightly yellowish discoloration has not been associated with a loss of potency.
Compatibility
Stable in D5LR, D5W, D51/2NS, D5NS, LR, 1/2NS, NS.
Y-site administration: Compatible: Acetaminophen, acyclovir, allopurinol, amifostine, amikacin, amsacrine, anidulafungin, atropine, aztreonam, bivalirudin, caspofungin, cefepime, cefotaxime, cefoxitin, ceftazidime, cefuroxime, chloramphenicol, cisatracurium, cisplatin, cladribine, clindamycin, cyclophosphamide, cytarabine, dexmedetomidine, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doripenem, doxorubicin, doxorubicin liposome, doxycycline, epinephrine, erythromycin lactobionate, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, fludarabine, foscarnet, furosemide, gemcitabine, gentamicin, granisetron, haloperidol, hetastarch in lactate electrolyte injection (Hextend®), hydroxyzine, kanamycin, ketorolac, labetalol, levofloxacin, linezolid, lorazepam, magnesium sulfate, melphalan, methotrexate, methotrimeprazine, metoclopramide, metronidazole, micafungin, midazolam, milrinone, morphine, nafcillin, nicardipine, nitroglycerin, norepinephrine, ondansetron, oxacillin, oxaliplatin, paclitaxel, palonosetron, pemetrexed, penicillin G potassium, piperacillin, piperacillin/tazobactam, propofol, ranitidine, remifentanil, scopolamine, sulfamethoxazole/trimethoprim, tacrolimus, teniposide, thiotepa, tobramycin, vancomycin, vecuronium, vinorelbine. Incompatible: Amphotericin B cholesteryl sulfate complex, gallium nitrate, hyaluronidase, minocycline, pantoprazole, phenytoin, sargramostim, thiopental. Variable (consult detailed reference): Ampicillin, cefazolin, cloxacillin, dexamethasone sodium phosphate, diazepam, heparin, phenobarbital.
Compatibility in syringe: Compatible: Atropine, bupivacaine, ceftazidime, chlorpromazine, cimetidine, diphenhydramine, fentanyl, glycopyrrolate, hydroxyzine, lorazepam, methotrimeprazine, metoclopramide, midazolam, pentazocine, pentobarbital, potassium chloride, prochlorperazine mesylate, ranitidine, scopolamine, tetracaine, trimethobenzamide, ziconotide. Incompatible: Ampicillin, diazepam, heparin, hyaluronidase, pantoprazole, phenobarbital, phenytoin. Variable (consult detailed reference): Cefazolin, cloxacillin, dexamethasone sodium phosphate, dimenhydrinate, haloperidol, ketorolac, prochlorperazine edisylate, promethazine.
Mechanism of Action
Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression
Pharmacodynamics/Kinetics
Onset of action: Analgesic: Immediate release formulations:
Oral: 15-30 minutes; Peak effect: 30-60 minutes
I.V.: 5 minutes; Peak effect: 10-20 minutes
Duration: Immediate release formulations: Oral, I.V.: 4-5 hours
Absorption: I.M.: Variable and delayed
Distribution: Vd: 4 L/kg
Protein binding: ~8% to 19%
Metabolism: Hepatic via glucuronidation; to inactive metabolites
Bioavailability: 62%
Half-life elimination:
Immediate release formulations: 2-3 hours
Extended release tablets (Exalgo™): ~11 hours
Excretion: Urine (primarily as glucuronide conjugates)
Dosage
Acute pain (moderate-to-severe):
Note: These are guidelines and do not represent the maximum doses that may be required in all patients. Doses should be titrated to provide adequate pain relief. When changing routes of administration, oral doses and parenteral doses are NOT equivalent; parenteral doses are up to 5 times more potent. Therefore, when administered parenterally, one-fifth of the oral dose will provide similar analgesia.
Children ≥6 months and <50 kg:
Oral: 0.03-0.08 mg/kg/dose every 3-4 hours as needed. Note: In children with severe pain, the American Pain Society recommends an initial dose of 0.06 mg/kg.
I.V.: 0.015 mg/kg/dose every 3-6 hours as needed
Patient-controlled analgesia (PCA) (American Pain Society, 2008): Note: Opiate-naive: Consider lower end of dosing range:
Usual concentration: 0.2 mg/mL
Demand dose: Usual: 0.003-0.004 mg/kg/dose; range: 0.003-0.005 mg/kg/dose
Lockout interval: 6-10 minutes
Usual basal rate: 0-0.004 mg/kg/hour
Children >50 kg and Adults:
Oral: Initial: Opiate-naive: 2-4 mg every 3-4 hours as needed; elderly/debilitated patients may require lower doses; patients with prior opiate exposure may require higher initial doses. Note: In adults with severe pain, the American Pain Society recommends an initial dose of 4-8 mg.
I.V.: Initial: Opiate-naive: 0.2-0.6 mg every 2-3 hours as needed; patients with prior opiate exposure may require higher initial doses
Mechanically ventilated/critically ill patients (unlabeled use): 0.7-4 mg (based on 70 kg patient) every 4 hours as needed. Note: More frequent dosing may be needed (eg, every 1-2 hours); dose should be adjusted based on patient response; elderly patients may be more sensitive (Jacobi, 2002).
Continuous infusion: Usual dosage range: 0.5-1 mg/hour (based on 70 kg patient) or 7-15 mcg/kg/hour
Patient-controlled analgesia (PCA): Note: Opiate-naive: Consider lower end of dosing range:
Usual concentration: 0.2 mg/mL
Demand dose: Usual: 0.1-0.2 mg; range: 0.05-0.4 mg
Lockout interval: 5-10 minutes
Epidural PCA (de Leon-Casasola, 1996; Liu, 2010; Smith, 2009):
Bolus dose: 0.4-1 mg
Infusion rate: 0.03-0.3 mg/hour
Demand dose: 0.02-0.05 mg
Lockout interval: 10-15 minutes
I.M., SubQ: Note: I.M. use may result in variable absorption and lag time to peak effect.
Initial: Opiate-naive: 0.8-1 mg every 4-6 hours as needed; patients with prior opiate exposure may require higher initial doses; usual dosage range: 1-2 mg every 4-6 hours as needed
Rectal: 3 mg every 6-8 hours as needed
Chronic pain: Adults: Oral: Note: Patients taking opioids chronically may become tolerant and require doses higher than the usual dosage range to maintain the desired effect. Tolerance can be managed by appropriate dose titration. There is no optimal or maximal dose for hydromorphone in chronic pain. The appropriate dose is one that relieves pain throughout its dosing interval without causing unmanageable side effects.
Controlled release formulation (Hydromorph Contin®, not available in U.S.): 3-30 mg every 12 hours. Note: A patient's hydromorphone requirement should be established using prompt release formulations; conversion to long acting products may be considered when chronic, continuous treatment is required. Higher dosages should be reserved for use only in opioid-tolerant patients.
Extended release formulation (Exalgo™): Dosing range: 8-64 mg every 24 hours. For use in opioid-tolerant patients only; discontinue all other extended release opioids when starting therapy. Suggested recommendations for converting to Exalgo™ from other analgesics are presented, but when selecting the initial dose, other characteristics (eg, patient status, degree of opioid tolerance, concurrent medications, type of pain, risk factors for addiction or diversion, etc) should also be considered.
Individualization of dose: Pain relief and adverse events should be assessed frequently. Dose increases may occur not more often than every 3-4 days; consider titrating with increases of 25% to 50% of the current daily dose. If more than 2 doses of rescue medications are needed within 24 hours for 2 consecutive days, consider increasing the dose of Exalgo™. Do not administer more frequently than every 24 hours.
Discontinuing Exalgo™: Taper by gradually decreasing the dose by 25% to 50% every 2-3 days to a dose of 8 mg every 24 hours before discontinuing therapy.
Conversion from other oral hydromorphone formulations to Exalgo™: Start with the equivalent total daily dose of hydromorphone administered once daily. May titrate every 3-4 days until adequate pain relief with tolerable side effects have been achieved.
Conversion from other opioids to Exalgo™: In general, start Exalgo™ at 50% of the calculated total daily dose every 24 hours. Titrate until adequate pain relief with tolerable side effects has been achieved. The following conversion ratios may be used to convert from oral opioid therapy to Exalgo™.
Conversion ratios to Exalgo™ (see table): Select the opioid, sum the total daily dose, then multiply by the conversion ratio to calculate the approximate oral hydromorphone equivalent; start Exalgo™ at 50% of the calculated total daily dose every 24 hours. (Note: The conversion ratios and approximate equivalent doses in this conversion table are only to be used for the conversion from current opioid therapy to Exalgo™).
Conversion Ratios to Exalgo™1
Previous Opioid
Approximate Equivalent Oral Dose
Oral Conversion Ratio2
Hydromorphone
12 mg
1
Codeine
200 mg
0.06
Hydrocodone
30 mg
0.4
Methadone3
20 mg
0.6
Morphine
60 mg
0.2
Oxycodone
30 mg
0.4
Oxymorphone
20 mg
0.6
1
Approximate equivalent doses for conversion from current opioid therapy to Exalgo™.
2Ratio for converting oral opioid dose to approximate hydromorphone equivalent dose.
3Monitor closely; ratio between methadone and other opioid agonists may vary widely as a function of previous drug exposure. Methadone has a long half-life and may accumulate in the plasma.
Table has been converted to the following text.
Conversion ratios to Exalgo™
To get the approximate equivalent doses for conversion from current opioid therapy to Exalgo™, select the opioid, sum the total daily dose, then multiply by the conversion ratio to calculate the approximate oral hydromorphone equivalent; start Exaglo™ at 50% of the calculated total daily dose every 24 hours. (Note: The conversion ratios and approximate equivalent doses in this conversion table are only to be used for the conversion from current opioid therapy to Exalgo™).
Previous opioid:
Hydromorphone:
Approximate equivalent oral dose: 12 mg
Oral conversion ratio: 1
Codeine:
Approximate equivalent oral dose: 200 mg
Oral conversion ratio: 0.06
Hydrocodone:
Approximate equivalent oral dose: 30 mg
Oral conversion ratio: 0.4
Methadone:
Approximate equivalent oral dose: 20 mg
Oral conversion ratio: 0.6
Monitor closely; ratio between methadone and other opioid agonists may vary widely as a function of previous drug exposure. Methadone has a long half-life and may accumulate in the plasma.
Morphine:
Approximate equivalent oral dose: 60 mg
Oral conversion ratio: 0.2
Oxycodone:
Approximate equivalent oral dose: 30 mg
Oral conversion ratio: 0.4
Oxymorphone:
Approximate equivalent oral dose: 20 mg
Oral conversion ratio: 0.6
Conversion from transdermal fentanyl to Exalgo™: Treatment with Exalgo™ can be started 18 hours after the removal of the transdermal fentanyl patch. For every fentanyl 25 mcg/hour transdermal dose, the equianalgesic dose of Exalgo™ is 12 mg every 24 hours. An appropriate starting dose is 50% of the calculated total daily dose given every 24 hours.
Dosing adjustment in renal impairment: Exalgo™:
Moderate impairment: Start with a reduced dose and monitor closely.
Severe impairment: Consider use of an alternate analgesic with better dosing flexibility.
Dosing adjustment in hepatic impairment: Dose adjustment should be considered. Exalgo™: In patients with moderate and severe hepatic impairment, start with a reduced dose and monitor closely. Consider use of an alternate analgesic with better dosing flexibility.
Administration: Oral
Hydromorphone is available in an 8 mg immediate release tablet and an 8 mg extended release tablet. Extreme caution should be taken to avoid confusing dosage forms.
Exalgo™: Tablets should be swallowed whole; do not crush, break, chew, dissolve or inject. May be taken with or without food.
Hydromorph Contin®: Capsule should be swallowed whole; do not crush or chew; contents may be sprinkled on soft food and swallowed
Administration: I.M.
May be given SubQ or I.M.; vial stopper contains latex
Administration: I.V.
For IVP, must be given slowly over 2-3 minutes (rapid IVP has been associated with an increase in side effects, especially respiratory depression and hypotension)
Administration: Other
May be given SubQ or I.M.
Administration: I.V. Detail
pH: 4.0-5.5
Monitoring Parameters
Pain relief, respiratory and mental status, blood pressure
Test Interactions
Some quinolones may produce a false-positive urine screening result for opiates using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opiate screens by more specific methods should be considered.
Patient Education
Exalgo™ tablets should be swallowed whole; do not crush, break, chew, dissolve, or inject. May cause physical and/or psychological dependence. Do not use alcohol, sedatives, tranquilizers, antihistamines, or pain medications without consulting prescriber. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause dizziness, drowsiness, impaired coordination, or blurred vision; loss of appetite, nausea, or vomiting; or constipation (if unresolved, consult prescriber about use of stool softeners). Report chest pain, slow or rapid heartbeat, dizziness, or persistent headache; confusion or respiratory difficulties; or severe constipation.
Geriatric Considerations
Elderly may be particularly susceptible to the CNS depressant and constipating effects of narcotics.
Additional Information
Equianalgesic doses: Morphine 10 mg I.M. = hydromorphone 1.5 mg I.M.
Exalgo™ is indicated for the management of moderate-to-severe pain in opioid-tolerant patients (requiring around-the-clock analgesia for an extended period of time). Patients are considered to be opioid tolerant if they have been taking oral morphine ≥60 mg/day, fentanyl transdermal ≥25 mcg/hour, oral oxycodone ≥30 mg/day, oral hydromorphone ≥8 mg/day , oral oxymorphone ≥25 mg/day, or an equianalgesic dose of another opioid for ≥1 week.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Hydromorphone does not have any active metabolites, has less protein binding than other opioids, and does not cause histamine release. If the patient has required high-dose analgesia or has used for a prolonged period (~7 days), taper dose to prevent withdrawal.
Evidence-Based Information: The 2002 ACCM/SCCM guidelines for analgesia (critically ill adult) recommend fentanyl or hydromorphone in patients who are hypotensive or have renal dysfunction. Morphine or hydromorphone is recommended for intermittent, scheduled therapy. Both have a longer duration of action requiring less frequent administration.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness and dizziness are common; may cause nervousness or restlessness; may rarely cause hallucinations or depression
Mental Health: Effects on Psychiatric Treatment
Concurrent use with psychotropics may produce additive sedation
Nursing: Physical Assessment/Monitoring
Monitor for effectiveness of pain relief. Assess patient's physical and/or psychological dependence. Monitor blood pressure, CNS and respiratory status, and degree of sedation prior to treatment and periodically throughout. For inpatients, implement safety measures to prevent falls. Discontinue slowly after prolonged use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as hydrochloride:
Dilaudid-HP®: 250 mg [contains natural rubber/natural latex in packaging, sodium metabisulfite]
Injection, solution, as hydrochloride: 1 mg/mL (1 mL); 2 mg/mL (1 mL, 20 mL); 4 mg/mL (1 mL); 10 mg/mL (1 mL, 5 mL, 50 mL)
Dilaudid-HP®: 10 mg/mL (50 mL) [contains natural rubber/natural latex in packaging, sodium metabisulfite]
Dilaudid-HP®: 10 mg/mL (1 mL, 5 mL) [contains sodium metabisulfite]
Dilaudid®: 1 mg/mL (1 mL); 2 mg/mL (1 mL); 4 mg/mL (1 mL) [contains sodium metabisulfite]
Injection, solution, as hydrochloride [preservative free]: 10 mg/mL (1 mL, 5 mL, 50 mL)
Liquid, oral, as hydrochloride:
Dilaudid®: 1 mg/mL (473 mL) [contains sodium metabisulfite (may have trace amounts)]
Powder, for prescription compounding, as hydrochloride: USP: 100% (972 mg)
Suppository, rectal, as hydrochloride: 3 mg (6s)
Tablet, oral, as hydrochloride: 2 mg, 4 mg, 8 mg
Dilaudid®: 2 mg, 4 mg [contains sodium metabisulfite (may have trace amounts)]
Dilaudid®: 8 mg [scored; contains sodium metabisulfite (may have trace amounts)]
Tablet, extended release, oral, as hydrochloride:
Exalgo™: 8 mg, 12 mg, 16 mg [contains sodium metabisulfite]
Pricing: U.S. (www.drugstore.com)
Liquid (Dilaudid-5)
1 mg/mL (473): $192.60
Solution (HYDROmorphone HCl)
4 mg/mL (20): $39.83
Tablets (Dilaudid)
2 mg (20): $23.99
4 mg (20): $36.99
8 mg (20): $57.77
Tablets (HYDROmorphone HCl)
2 mg (20): $15.33
4 mg (20): $16.01
8 mg (20): $29.51
References
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Liu SS, Bieltz M, Wukovits B, et al, "Prospective Survey of Patient-Controlled Epidural Analgesia With Bupivacaine and Hydromorphone in 3736 Postoperative Orthopedic Patients," Reg Anesth Pain Med, 2010, 35(4):351-4.
Lugo RD and Kern SE, “Pharmacokinetics of Opioids,” Management of Pain, Lipman AG ed, Bethesda, MD: ASHP, 2004, 77.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Nasraway SA Jr, “Use of Sedative Medications in the Intensive Care Unit,” Sem Resp Crit Care Med, 2001, 22(2):165-74.
“Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain,” 6th ed, Glenview, IL: American Pain Society, 2008.
Smith HS, Current Therapy in Pain, 1st ed, Philadelphia, PA: Saunders, 2009.
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International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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