Dosing and uses of Dilaudid, Exalgo (hydromorphone)
Adult dosage forms and strengths
tablet: Schedule II
- 2mg
- 4mg
- 8mg
tablet, extended-release: Schedule II
- 8mg
- 12mg
- 16mg
- 32mg
injection solution
- 1mg/mL
- 2mg/mL
- 4mg/mL
injection solution, preservative free: Schedule II
- 10mg/mL
oral liquid: Schedule II
- 5mg/5mL
suppository: Schedule II
- 3mg
Prefilled syringe: Schedule II
- 0.2 mg/mL
- 0.6 mg/mL
Moderate-to-Severe Pain
Indicated for moderate-to-severe pain
PO
- Immediate-release: 2-4 mg q4-6hr PRN; a gradual increase in dose may be required
- Oral liquid (usual dose): 2.5-10 mg (2.5-10 mL) q3-6hr PRN
SC/Im
- 1-2 mg q2-3hr PRN; adjust dose according to pain and adverse effects
- IM dose not recommended for use as it may result in variable absorption and lag time to peak effect
IV
- Opioid naive: 0.2-1 mg IV q2-3hr PRN; may require higher doses in patients with prior opioid exposure
- Critically ill patients (opiate-naive patients): 0.2-0.6 mg q1-2hr PRN given slowly over 2-3 minutes; patients with previous opiate exposure may tolerate higher doses
- Continuous infusion: 0.5-3 mg/hr, titrated to response
Patient-controlled analgesia
- Usual concentration, 0.2 mg/mL; demand dose, 0.1-0.2 mg; dose range is 0.05-0.4 mg
- Lockout interval: 5-10 minutes
RectaL
- 3 mg PR q6-8hr
Chronic Severe Pain
Long-acting (Exalgo) is indicated for the management of pain in opioid tolerant patients severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
Opioid tolerant patients only (extended-release:) 8-64 mg PO qDay; may administer a starting dose equivalent to patient's total daily oral hydromorphone dose administered once daily with or without food
Should address pain relief and adverse events frequently; increase dose no more frequently than q3-4days; may titrate with increases of 25-50% of current daily dose; consider increasing dose if more than 2 doses of rescue medications are needed within 24hr within 2 consecutive days
Extented-release tablets should be swallowed whole; crushing, dividing, or dissolving will release opioid content all at once and increase risk of respiratory depression and death
Converting to Exalgo
- Conversion from other oral hydromorphone formulations: Start with equivalent total daily dose of immediate release formulation and administer once daily; may titrate q3-4days until adequate pain relief with tolerable adverse effects achieved
- Conversion from other opioids: Start Exalgo dose at 50% of calculated daily dose q24hr; titrate until adequate pain relief with tolerable adverse effects achieved
- Conversion from transdermal fentanyl to Exalgo: Start Exalgo 18 hr after removal of transdermal fentanyl patch at 50% of calculated total daily dose given over 24hr; for a 25 mcg/hr fentanyl patch the equianalgesic dose is 12 mg PO q24hr
- Discontinuation of Exalgo therapy: Taper gradually by decreasing dose by 25-50% q2-3days to a dose of 8 mg PO q24hr before discontinuing
Opioid-tolerant definition
- Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
- Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid
Limitations of use
- Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
- Not indicated for acute pain or as a PRN analgesic
Cough (Off-label)
1 mg PO q3-4hr PRn
Pediatric dosage forms and strengths
tablet: Schedule II
- 2mg
- 4mg
- 8mg
oral liquid: Schedule II
- 5mg/5mL
injection solution
- 1mg/mL
- 2mg/mL
- 4mg/mL
suppository: Schedule II
- 3mg
Pain (Off-label)
Moderate-to-severe pain
Children: 0.03-0.08 mg/kg PO q4-6hr PRN; not to exceed 5 mg/dose
Adolescents: 1-4 mg/dose PO q4-6hr PRn
Children: 0.015 mg/kg IV q4-6hr PRn
Adolescents: 1-2 mg/dose IV/IM.SC q4-6hr
Patient Controlled Anesthesia (Off-label)
Loading dose: 8 mcg/kg IV bolus
Demand dose (initial): 2 mcg/kg IV with a lockout time of 10 min
Geriatric dosage forms and strengths
Pain
Indicated for moderate-to-severe pain
2-4 mg PO q4-6hr PRN; a gradual increase in dose may be required
Dosing Considerations
Titrate dose to effect; oral and parenteral doses are not equivalent; because parenteral dose 5 times more potent than oral dose, administer one fifth of oral dose when changing to parenteral route
Oral dose: Initiate at low end of dosage range; consider lowering dose by 25-50% in patients >70 years
IV: Reduce initial dose to 0.2 mg q2-3hr
Dilaudid, Exalgo (hydromorphone) adverse (side) effects
Frequency not defined
Anticholinergic: Dry mouth, palpitation, tachycardia, urinary retention
Cardiovascular: Angina pectoris, bradycardia, cardiac arrest, circulatory depression, myocardial infarction, QT-interval prolongation, severe cardiac arrhythmias, shock, ST-segment elevation, syncope, ventricular tachycardia
Central nervous system (CNS): Agitation, coma, dizziness, dysphoria, mental clouding or depression, euphoria, faintness, nervousness, restlessness, sedation, seizures, visual disturbances, weakness
Gastrointestinal (GI): Constipation, nausea, vomiting, anorexia, abdominal distention, bilieary tract spasm, decreased appetite, decreased intestinal motility, gastroesophageal reflux disease, paralytic ileus,
Respiratory: Respiratory depression, respiratory arrest, hypoxia, bronchospasm, dyspnea, rhinorrhea, flu-like symptoms (Exalgo)
Other: Flushing, pruritus, sweating, urticaria, skin rash, hyperhidrosis, warmness of face/neck/upper thorax
Warnings
Black box warnings
Hydromorphone high-potency formulation
- Hydromorphone high-potency injection is highly concentrated solution of hydromorphone, a potent Schedule II controlled opioid agonist intended for use in opioid-tolerant patients; it is not to be confused with standard parenteral formulations of hydromorphone or other opioids; overdose and death could result
- Use caution to avoid confusing the highly concentrated (Dilaudid-HP) injection with the less concentrated (Dilaudid) injectable product
- Schedule II opioid agonists (eg, morphine, oxymorphone, oxycodone, fentanyl, methadone) have highest potential for abuse and risk of producing respiratory depression
- Alcohol, other opioids, and CNS depressants (eg, sedative-hypnotics) potentiate respiratory depressant effects of hydromorphone, increasing risk of respiratory depression that might result in death
- Accidental intake may lead to fatal overdose, especially in children High potential for abuse
Addiction, abuse, and misuse
- Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
- Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions
Life-threatening respiratory depression
- Serious, life-threatening, or fatal respiratory depression may occur
- Monitor for respiratory depression, especially during initiation or following a dose increase
- Instruct patients to swallow tablet/capsule whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal dose
Accidental exposure
- Accidental of even 1 dose, especially by children, can result in a fatal overdose
Neonatal opioid withdrawal syndrome
- Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
- Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
- Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
- If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Contraindications
Hypersensitivity
Dilaudid Liquid and Tablets
- Obstetrical analgesia
Suppository
- Increased intracranial pressure resulting from intracranial lesion; conditions resulting in depressed ventilatory function including COPD, emphysema, status asthmaticus, kyphoscoliosis, cor pulmonale
Dilaudid injection
- Dilaudid HP: Paralytic ileus, opioid nontolerant patients, known ro suspected pre-existing GI surgery or diseases resulting in narrowing of GI tract loops in the GI tract or GI obstruction
- Dilaudid HP is contraindicated in non-opioid tolerant patients
Extended-release (Exalgo)
- Opioid nontolerant patients
- Paralytic ileus, opioid nontolerant patients, known ro suspected pre-existing GI surgery or diseases resulting in narrowing of GI tract loops in the GI tract or GI obstruction
- Significant respiratory depression
- Acute or severe bronchial asthma
Cautions
May impair physical or mental abilities; use caution when performing work that require mental alertness such as operating machinery or driving
Myoclonus and seizures reported with high doses; use caution in patients with history of seizure disorders
Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists, including codeine, hydrocodone, levorphanol, oxycodone, oxymorphone
May cause hyptension especially in patients with cardiovascular disease or hypovolemia; may cause severe hyptension, including orthostatic hypotension and syncope; use caution in patients taking drugs that may exagerate hypotensive effects, including phenothiazines or general anesthetics; avoid use in patients with circultory shock; may reduce cardiac output and blood pressure
May prevent diagnosis of patients with acute abdominal conditions
Use caution in patients with biliary tract dysfunction
Use cautioin in patients with inflammatory or obstructive bowel disorder, acute pancreatitis secondary to biliary tract disease, and patients undergoing biliary surgery
Use with caution in patients with adrenal insufficiency including Addison's disease
Avoid use in patients susceptible to intracranial effects of CO2 retention including CNS depression or coma
Carbon dioxide retention from opioid-induced respiratory depression can exacerbate sedating effects of opioids
Use cuation in delirium tremens
Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis
High potential for abuse; use caution in patients with history of drug abuse or alcoholism
Caution when coadministered with other CNS depressents (eg, barbiturates, benzodiazepines, alcohol)
Use caution in renal/hepatic impairment, obesity, prostatic hyperplasia/urinary stricture, psychoses, respiratory disease or thyroid dysfunction
Use within 14 days of MAO intake not recommended
Controlled-release formulation should only be used when continuous analgesia is required over an extended period of time; not for use PRn
IM formulation may result in variable absorption and a lag time to peak effect
Tailor opioid-containing analgesic regimen to each patient's needs
May cause constipation; consider preventive measures to reduce potential of constipation; use with caution in patients with chronic constipation
Use caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exagerated intracranial pressure may occur with treatment
Use caution in patients who are morbidly obese
Some formulations may contain lactose; consider lactose content prior to initiating therapy in patients with hereditary disease of galatose intolerance
Vial stoppers of single-dose injectable vials may contain latex
Some dosage forms may contain trace amounts of sodium metabisulfite, which may cause allergic reactions
Use of opioid agonists/antagonists my cause withdrawal symptoms
Long-acting opioids
- Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present (see Black box warnings)
- Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary (see Black box warnings)
- Serious, life-threatening, or fatal respiratory depression reported (see Black box warnings)
- Accidental exposure reported, including fatalities (see Black box warnings)
- Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black box warnings)
- Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension
- Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug excreted in breast milk; use not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dilaudid, Exalgo (hydromorphone)
Mechanism of action
Mu-opioid receptor agonist; inhibits ascending pain pathways, thus altering response to pain; main therapeutic action is analgesia
Other pharmacologic effects include respiratory depression and sedation; suppresses cough by acting centrally in medulla
Absorption
Bioavailability: 62%
Onset: 15-30 min (PO); 15 min (SC); 15 min (IM); 5 min (IV); 15-30 min (PR); 6 hr (ER)
Duration: 3-4 hr (PO/IV); extended-release (13 hr)
Peak plasma time: 30-60 min (PO); SC, 30-90 min; IM, 30-60 min; IV, 15-30 min; PR, 30-90 min
Distribution
Protein bound: 8-19%
Vd: 4 L/kg
Metabolism
Metabolized in liver to CYP2D6 via conjugation with glucuronic acid to active metabolite only
Elimination
Half-life: 2-3 hr (immediate-release); 11 hr (extended-release)
Excretion: Urine (primarily)
Administration
IV Incompatibilities
Additive: Sodium bicarbonate, thiopentaL
Syringe: Ampicillin, diazepam, hyaluronidase, phenobarbital, phenytoin
Y-site: Amphotericin B cholesteryl sulfate complex, diazepam, minocycline, phenobarbital, phenytoin, sargramostim, tetracycline, thiopentaL
IV/IM Administration
May be given IV, SC, or Im
Direct injection: Dilute to 4-5 mL with NS or SWI, and administer over at least 2-3 minutes or give 2 mg over 3-5 minutes
Intermittent administration: Dilute in 50-100 mL D5W or NS, and infuse over 15-30 minutes
IV administration (eg, rapid IV push) has been associated with increased systemic effects, especially respiratory depression and hypotension
Monitor patient constantly; keep resuscitation equipment and narcotic antagonist (eg, naloxone) readily available
IV Preparation
Direct injection: Dilute to 4-5 mL with NS or SWI
Continuous infusion: Dilute in 100-1000 mL of D5W, NS, D5/NS, D5½NS, Ringer solution, or Lr
Solution may appear slightly yellow; this does not alter potency
Vial stopper contains latex
Storage
Store at 25°C (77°F)
