Hydromorphone

Hydromorphone is an Opioid receptor agonist belonging to the analgesic class.

Hydromorphone is an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.

The immediate-release version of hydromorphone reaches its peak concentration after 30-60 minutes while the extended-release version reaches the peak concentration after 9 hours. When administered orally, hydromorphone is absorbed mainly in the upper small intestine with a bioavailability of 60% due to intensive first-pass metabolism. The volume of distribution of hydromorphone is reported to be 4 L/kg. The protein-bound form of hydromorphone corresponds to about 8-19% of the administered dose. The metabolism of hydromorphone is mainly hepatic and it is represented by the generation of hydromorphone-3-glucuronide through glucuronidation reactions. The main elimination route of hydromorphone is through the urine in the form of the main metabolite hydromorphone-3-glucuronide. The elimination of the parent compound represents 7% of the urine elimination and 1% of the fecal elimination.

Hydromorphone shows side effects like Headache, difficulty falling asleep or staying asleep, dry mouth, light-headedness, drowsiness, heavy sweating, muscle, back or joint pain, stomach pain, anxiety, flushing, itching, depression.

Hydromorphone is available in the form of Injectable solution, oral tablet, rectal suppository, Oral liquid, oral capsule.

Hydromorphone is available in India, Singapore, Germany, Australia, South Africa, Malaysia, Japan and China.

Hydromorphone is an Analgesic belonging to the class Opioid receptor agonist.

Hydromorphone, a phenanthrene derivative, is an opiate agonist w/ greater analgesic potency than morphine. It binds to mc-opioid receptors in the CNS and smooth muscles, causing inhibition of ascending pain pathways, altering perception of and response to pain, and producing generalized CNS depression. Additionally, it may directly supress the resp reflex, thereby causing resp depression.

Time taken to reach peak plasma concentration is ≤1 hours (conventional); 12-16 hours (extended release).

The onset of action of Hydromorphone is approximately 15-30 min (conventional preparations); 6 hr (extended-release preparations); 5 min (IV).

The duration of action of Hydromorphone is 3-4 hours (conventional preparations, IV); approx 13 hours (extended-release preparations).

Hydromorphone is available in the form of Injectable solution, oral tablet, rectal suppository, Oral liquid, oral capsule.

Hydromorphone is an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.

Hydromorphone is an Opioid receptor agonist belonging to the analgesic class.

Hydromorphone binds to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough suppression by direct central action in the medulla; produces generalized CNS depression.

Hydromorphone is approved for use in the following clinical indications

• Acute pain in opioid-naive patients
• Acute pain in opioid-tolerant patients
• Acute postoperative pain, postoperative recovery/postanesthesia care unit
• Acute vaso-occlusive pain in sickle cell disease
• Chronic pain, noncancer, and cancer pain
• Neuraxial analgesia
• Pain and sedation; critically ill patients in the ICU

• Acute pain in opioid-naive patients

Immediate release Oral Dose: Initial: 1 to 2 mg every 4 to 6 hours as needed; adjust dose according to patient response. Usual dosage range: 1 to 4 mg every 4 to 6 hours as needed. If the usual dose and frequency is insufficient, reassess the patient and reconsider pain management strategies. For outpatient use, usually up to 8 mg/day for moderate pain or up to 12 mg/day for severe pain will suffice.

Intermittent dosing IV Dose: Initial: 0.2 to 0.5 mg every 2 to 4 hours as needed; adjust dose according to patient response under close monitoring. Usual dosage range: 0.2 to 1 mg every 2 to 4 hours as needed. If the usual dose and frequency is insufficient, reassess the patient and reconsider pain management strategies.

IM, SUBQ Dose: Initial: 0.2 to 0.5 mg every 2 to 3 hours as needed; adjust dose according to patient response under close monitoring. If the usual dose and frequency is insufficient, reassess the patient and reconsider pain management strategies.

• Acute pain in opioid-tolerant patients

Oral, IV, SUBQ: Usual dose: In conjunction with the scheduled long-acting opioid, administer 5% to 15% (rarely up to 20%) of the 24-hour hydromorphone requirement (or MME) as needed using an IR or parenteral formulation every 3 to 6 hours with subsequent dosage adjustments based on response.

• Acute postoperative pain, postoperative recovery/postanesthesia care unit

IV, SUBQ Dose: 0.2 to 0.5 mg every 3 to 4 hours as needed. If the usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies.

• Acute vaso-occlusive pain in sickle cell disease

Patient weight ≥50 kg:

IV Dose: Initial: 1.5 mg, given once within 30 to 60 minutes of presentation; if severe pain continues, repeat with ~20% to 50% of the original dose every ~30 minutes; monitor for sedation/respiratory depression.

Patient weight <50 kg:

IV Dose: Initial: 0.02 to 0.05 mg/kg (maximum initial dose: 1.5 mg), given once within 30 to 60 minutes of presentation; if severe pain continues, repeat with ~20% to 50% of the original dose every ~30 minutes; monitor for sedation/respiratory depression.

• Chronic pain, noncancer and cancer pain

Immediate release: Oral: Initial: 1 to 2 mg every 3 to 4 hours as needed or scheduled around the clock (eg, cancer pain); adjust dose according to patient response. Usual dosage range: 1 to 4 mg every 3 to 4 hours as needed or scheduled around the clock. If the usual dose and frequency is insufficient, reassess the patient and reconsider pain management strategies.

Extended release: Oral Capsules: Initial: 3 mg every 12 hours; increase dose every 48 hours as needed; maximum total daily dose: 18 mg/day for noncancer, nonpalliative pain.

IV, SUBQ: Initial: 0.2 to 0.4 mg every 2 to 4 hours as needed; adjust dose according to patient response. Usual maintenance dosage range: 0.2 to 1 mg every 2 to 4 hours as needed. If the usual dose and frequency is insufficient, reassess the patient and reconsider pain management strategies.

• Neuraxial analgesia

Epidural:

Single dose: Opioid-naive patients: Epidural: Usual dosage range: 0.4 to 1.5 mg.

Continuous infusion: Opioid-naive patients: Epidural: Usual dosage range: 20 to 300 mcg/hour. May be given alone or usually in combination with local anesthetics (eg, bupivacaine, ropivacaine); when combined with local anesthetic, analgesic effect is increased due to synergy.

Intrathecal:

Single dose: Intrathecal: Dosage range: 50 to 200 mcg.

• Pain and sedation; critically ill patients in the ICU

Intermittent dosing:

IV: Initial: 0.2 to 1 mg every 1 to 3 hours as needed; titrate to clinical effect (ie, pain control or sedation).

Continuous IV infusion (alternative therapy): Note: May be used for breakthrough pain/sedation in patients receiving opioids or to transition from another opioid (eg, tolerance).

IV: After initial intermittent dose, begin continuous infusion with an initial dose of 0.5 to 2 mg/hour; titrate to clinical effect (ie, pain control and/or sedation); usual dosage range: 0.25 to 4 mg/hour.

Hydromorphone is available in various strengths as 2 mg/mL; 4 mg/mL; 1 mg/mL; 3 mg/mL; 10 mg/mL; 2 mg; 4 mg; 8 mg; 3 mg; 250 mg; 12 mg; 16 mg; 32 mg; 0.5 mg/0.5 mL.

Hydromorphone is available in the form of Injectable solution, oral tablet, rectal suppository, Oral liquid, oral capsule.

• Dosage Adjustment in Kidney Patient

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 30 to <60 mL/minute: Administer 50% of usual initial dose.

CrCl <30 mL/minute:

Immediate release: Administer 25% of usual initial dose and extend dosing interval by 25% to 50%.

Extended release: ER opioids are preferably avoided due to increased risk of adverse effects and toxicity. If necessary, administer 25% of usual initial dose. Alternatively, as hydromorphone ER tablets are only intended for once daily administration, consider switching to IR tablets or another analgesic that will permit more flexibility with the dosing interval.

• Dosage Adjustment in Hepatic impairment Patient

Mild to severe impairment: Initiate with 25% to 50% of the usual starting dose depending on the degree of impairment. Use with caution and monitor closely for respiratory and CNS depression.

Hydromorphone is contraindicated in patients with

• Significant respiratory depression.
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.
• Known or suspected gastrointestinal obstruction, including paralytic ileus.
• Hypersensitivity to hydromorphone, hydromorphone salts, any other components of the product, or sulfite-containing medications (e.g., anaphylaxis).

• CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Constipation

May cause constipation, which may be problematic in patients with unstable angina and patients’ post-myocardial infarction (MI). Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.

• Hypotension

May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

• Phenanthrene hypersensitivity

Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).

• Respiratory depression

Fatal respiratory depression may occur. Swallow ER tablets whole; crushing, chewing, or dissolving can cause rapid release and a potentially fatal dose. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately in the event of known or suspected overdose.

• Abdominal conditions

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

• Adrenocortical insufficiency

Use with caution in patients with adrenocortical insufficiency, including Addison disease; dose adjustment may be required. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis.

• Biliary tract impairment

Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.

• CNS depression/coma

Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO₂ retention.

• Delirium tremens

Use with caution in patients with delirium tremens.

• Head trauma

Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment

Use with caution in patients with hepatic impairment; oxycodone clearance may decrease.

• Mental health conditions

Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to potential increased risk for opioid use disorder and overdose; more frequent monitoring is recommended.

• 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; dose adjustment may be required.

• Psychosis

Use with caution in patients with toxic psychosis.

• Renal impairment

Use with caution in patients with renal impairment; oxycodone clearance may decrease.

• Respiratory disease

Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Seizures

Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.

• Sleep-related disorders

Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and CNS depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing.

• Thyroid dysfunction

Use with caution in patients with thyroid dysfunction.

• Benzodiazepines or other CNS depressants

Concomitant use may result in respiratory depression and sedation, which may be fatal. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.

• CYP 3A4 interactions

Use with all CYP3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitant CYP 3A4 inducer may result in increased oxycodone concentrations. Monitor patients receiving oxycodone and any CYP 3A4 inhibitor or inducer.

Low levels of opioid analgesics have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Hydromorphone Oral Solution or Hydromorphone Tablets and any potential adverse effects on the breastfed infant from Hydromorphone Oral Solution or Hydromorphone Tablets or from the underlying maternal condition.

There are no available data to inform a drug-associated risk for major birth defects and miscarriage with this drug; prolonged use of opioids during pregnancy can result in physical dependence in the neonate.

Common

Apnoea, biliary spasm, bradycardia, confusion, constipation, dependence, difficulty in micturition, dizziness, drowsiness, dry mouth, dysphoria, euphoria, flushing, hallucinations, headache, hypotension, lightheadedness, miosis, mood changes, muscle rigidity, nausea, oedema, palpitation, postural hypotension, pruritus, rash, sedation, sexual dysfunction, shock, sleep disturbances, sweating, tachycardia, ureteric spasm, urinary retention, urticaria, vertigo, visual disturbances, vomiting.

• Alizapride

May enhance the CNS depressant effect of CNS Depressants.

Alvimopan

Opioid Agonists 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.

Amphetamines

May enhance the analgesic effect of Opioid Agonists.

Anticholinergic Agents

May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination.

Azelastine (Nasal)

May enhance the CNS depressant effect of CNS Depressants.

Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if co-administering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.

Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

Bromopride

May enhance the CNS depressant effect of CNS Depressants

Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

Cannabinoid-Containing Products

CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products.

Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

CNS Depressants

May enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

Daridorexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended.

Desmopressin

Opioid Agonists may enhance the hyponatremic effect of Desmopressin.

Dexmedetomidine

CNS Depressants may enhance the CNS depressant effect of Dexmedetomidine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants and consider dose reductions of either agent to avoid excessive CNS depression.

Difelikefalin

May enhance the CNS depressant effect of CNS Depressants.

Dimethindene (Topical):

May enhance the CNS depressant effect of CNS Depressants.

Diuretics

Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.

Droperidol

May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use.

Fluradoline

Opioid Agonists may enhance the constipating effect of Eluxadoline.

Flunarizine

CNS Depressants may enhance the CNS depressant effect of Flunarizine.

Flunitrazepam

CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available

Gastrointestinal Agents (Prokinetic)

Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

Hydroxyzine

May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant.

Ixabepilone

May enhance the CNS depressant effect of CNS Depressants.

Kava Kava

May enhance the CNS depressant effect of CNS Depressants.

Kratom

May enhance the CNS depressant effect of CNS Depressants.

Lemborexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary.

Methotrimeprazine

May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression.

Metoclopramide

May enhance the CNS depressant effect of CNS Depressants.

Metyrosine

CNS Depressants may enhance the sedative effect of Metyrosine.

Nalfurafine

Opioid Agonists may enhance the adverse/toxic effect of Nalfurafine. Opioid Agonists may diminish the therapeutic effect of Nalfurafine.

Nalmefene

May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required.

Naltrexone

May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations.

Orphenadrine

CNS Depressants may enhance the CNS depressant effect of Orphenadrine.

Oxomemazine

May enhance the CNS depressant effect of CNS Depressants.

Oxybate Salt Products

CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use.

Oxycodone

CNS Depressants may enhance the CNS depressant effect of Oxycodone. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

Paraldehyde

CNS Depressants may enhance the CNS depressant effect of Paraldehyde.

Ramosetron

Opioid Agonists may enhance the constipating effect of Ramosetron.

Ropeginterferon Alfa-2b

CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania).

Serotonergic Agents (High Risk)

Opioid Agonists may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

Sincalide

Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.

Somatostatin Analogs

Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs.

Suvorexant

CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.

Thalidomide

CNS Depressants may enhance the CNS depressant effect of Thalidomide.

Valerian

May enhance the CNS depressant effect of CNS Depressants.

Zolpidem

CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.

The common side effects of Hydromorphone include the following

• Common side effects

Headache, difficulty falling asleep or staying asleep, dry mouth, lightheadedness, drowsiness, heavy sweating, muscle, back or joint pain, stomach pain, anxiety, flushing, itching, depression.

• Rare side effects

Rash, hives, swelling of the eyes, face, lips, tongue, mouth, throat, arms, hands, feet, ankles, or lower legs, difficulty breathing or swallowing, hoarseness, agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea, nausea, vomiting, loss of appetite, weakness, or dizziness, inability to get or keep an erection, irregular menstruation, decreased sexual desire, seizures, chest pain, extreme drowsiness, fainting, lightheadedness when changing positions.

• Pregnancy

Pregnancy Category C

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. There are no available data with Hydromorphone in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

• Nursing Mothers

Low levels of opioid analgesics have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Hydromorphone Oral Solution or Hydromorphone Tablets and any potential adverse effects on the breastfed infant from Hydromorphone Oral Solution or Hydromorphone Tablets or from the underlying maternal condition.

• Pediatric Use

The safety and effectiveness of Hydromorphone in pediatric patients have not been established.

• Geriatric Use

Elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Hydromorphone slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression. Hydromorphone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Symptoms: Pin-point pupils, resp depression, somnolence progressing to stupor and coma, skeletal muscle flaccidity, and bradycardia; cold and clammy skin, hypotension, apnoea, pulmonary oedema, circulatory collapse.

Management: Supportive treatment w/ primary attention to establishment of patent airway and institution of assisted ventilation. Administer IV naloxone 0.4-2 mg may be repeated at 2 min interval if no response, for severe overdosage; and 0.2 mg, followed by increments of 0.1 mg every 2 min, for less severe cases. Employ activated charcoal if significant amount has been ingested w/in 1-2 hr provided that the patient has intact gag reflex or secured airway.

• Pharmacodynamics

Hydromorphone, a phenanthrene derivative, is an opiate agonist w/ greater analgesic potency than morphine. It binds to mc-opioid receptors in the CNS and smooth muscles, causing inhibition of ascending pain pathways, altering perception of and response to pain, and producing generalised CNS depression. Additionally, it may directly supress the resp reflex, thereby causing resp depression.

• Pharmacokinetics

Absorption

The immediate-release version of hydromorphone reaches its peak concentration after 30-60 minutes while the extended-release version reaches the peak concentration after 9 hours.¹ When administered orally, hydromorphone is absorbed mainly in the upper small intestine with a bioavailability of 60% due to intensive first-pass metabolism.

Distribution

The volume of distribution of hydromorphone is reported to be of 4 L/kg. The protein-bound form of hydromorphone corresponds to about 8-19% of the administered dose.

Metabolism and Excretion

The metabolism of hydromorphone is mainly hepatic and it is represented by the generation of hydromorphone-3-glucuronide through glucuronidation reactions. The main elimination route of hydromorphone is through the urine in the form of the main metabolite hydromorphone-3-glucuronide. The elimination of the parent compound represents 7% of the urine elimination and 1% of the fecal elimination.

• https://www.uptodate.com/contents/hydromorphone-drug-information#F180565
• https://medlineplus.gov/druginfo/meds/a682013.html
• https://www.drugs.com/pregnancy/hydromorphone.html
• https://go.drugbank.com/drugs/DB00327