Hydromorphone hydrochloride, Dilaudid®

• Dilaudid®
• Hydromorph contine®
• Hydromporphone®

• Narcotic analgesic
• Mu-opioid agonist
• Pain killer

• Dilaudid: tabs 1 mg, 2 mg, 4 mg, 8 mg
• Hydromorph contine: Caps 3 mg, 4.5 mg, 6 mg, 9 mg, 12 mg, 18 mg, 24 mg, 30 mg
• Hydromporphone: Tabs 1 mg, 2 mg, 4 mg, 8 mg

• Pain management

• Mu-opioid receptor agonist

Absorption:

• Hydromorphone is rapidly absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism.
• Exposure of hydromorphone is dose-dependent at a dose range of 2 and 8 mg. Bioavailability following single-dose administration of the 8 mg DILAUDID tablet is approximately 24%.

Metabolism:

• Hydromorphone is extensively metabolized via glucuronidation in the liver, with greater than 95% of the dose metabolized to hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.

Elimination:

• Only a small amount of the hydromorphone dose is excreted unchanged in the urine. Most of the dose is excreted as hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.
• The systemic clearance is approximately 1.96 (20%) liters/minute.  The terminal elimination half-life of hydromorphone after an intravenous dose is about 2.3 hours.

• Initial dosing should be patient specific taking into account pain severity, age, and kidney and liver function
• For PRN uses can be started at doses 2-4 mg every 4 hours conditioned that patient is not drowsy, has no shortness of breath or respiratory depression

• The depressant effects of morphine may be enhanced by other CNS depressants such as alcohol, anaesthetics, hypnotics and sedatives, tricyclic antidepressants, phenothiazines and antipsychotics.
• Concurrent use may result in potentiation of respiratory depression, hypotension, profound sedation or coma and death may occur. If used concurrently with CNS depressants, dosage adjustment may be required.
• Antihistamines, beta-blockers and skeletal muscle relaxants may also enhance the depressant effects of morphine.
• Agonist/antagonist analgesics e.g. buprenorphine should not be administered to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic. The analgesic effect may be reduced or withdrawal symptoms may occur.
• Alcohol
• MAOi: intensify the effect of opioids which may result in anxiety, confusion, and decreased respiration. Hydromorphone should not be given to patients receiving MAOIs or within 14 days of their discontinuation. Non-selective MAOIs intensify the effects of morphine and other opioids which can cause anxiety, confusion and significant depression of respiration sometimes leading to coma.

Gastrointestinal:

• Dry mouth
• Nausea, vomiting
• Decreased gastric, biliary and pancreatic secretions
• Rreduction in motility associated with an increase in tone in the gastric antrum and duodenum.
• Decreased digestion of food in the small intestine is delayed and propulsive contractions are decreased which results in constipation
• Taste alteration

CNS:

• Hydromorphone depresses the cough reflex and respiratory reflex by direct effect on the cough center in the medulla and respiratory centre in the brain stem. It also reduces the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension.
• Confusion, headache, insomnia, involuntary muscle contractions, somnolence, thought abnormalities.
• Agitation, dysphoria, euphoria, hallucinations, malaise, mood changes, respiratory depression, seizure, paresthesia, vertigo, vision abnormalities, withdrawal syndrome.

Genitourinary:

• Amenorrhea, decreased libido, impotence, urinary retention.

Cardiovascular:

• Hypotension as a results of peripheral vascular dilatation
• Bradycardia
• Syncope

Metabolic:

• Peripheral edema, pulmonary edema

Respiratory:

• Bronchospasm, cough decreased, respiratory depression.

Dermatological:

• Rash
• Pruritus, flushing, and red eyes as a result of histamine release

General:

• Chills, sweating.
• Allergic reaction, anaphylactic/anaphylactoid reactions, drug dependence, facial flushing, hypertonia, miosis, tolerance.

• Known morphine sensitivity
• Acute hepatic disease or severe cirrhosis
• Acute alcoholism, Delirium tremens
• Co-ingestion with alcohol (in the presence of alcohol, dose-dumping of opioid to potentially fatal plasma levels may occur, even in opioid-tolerant patients)
• Respiratory depression especially in the presence of cyanosis and excessive bronchial secretion
• Obstructive airways disease, acute attacks of bronchial asthma
• Severe CNS depression
• Convulsive disorders (may lower the seizure threshold)
• Head injuries, brain tumours and other conditions in which cerebrospinal or intracranial pressure is raised (may cause marked exaggeration of cerebrospinal fluid pressure and mask the clinical course).
• Heart failure secondary to chronic lung disease, cor pulmonale.
• Cardiac arrhythmias.
• Surgical anastomosis (narcotics may cause increase in intraluminal pressure).
• Concurrent administration with or within 2 weeks of discontinuation of monoamine oxidase inhibitors (MAOIs).
• Patients with paralytic ileus, acute abdomen, or delayed gastric emptying.
• Patients with phaeochromocytoma as morphine appears to increase catecholamine levels
• m-Eslon is not to be used as a pre-operative medication.
• Patients with chronic pain of non-malignant origin who have a prior history of substance abuse.
• Children under the age of 6 months.
• Should be given with caution to elderly

• Opioids can cross the placenta, resulting fetal exposure. Such infants may experience opioid withdrawal symptoms at birth. Opioids should be given to pregnant women only if potential benefits overweight the risks.
• Low levels of opioid analgesics have been detected in human milk.

Hepatic Impairment:

• After single dose of oral administration of hydromorphone 4 mg, mean exposure (C max) is increased 4 folds. For this reasons the initial dose of hydromorphone in clients with hepatic impairment should be as low as possible and titrated up slowly.

Renal Impairment:

• After oral administration of hydromorphone at a single 4 mg dose (equal to 2 mg Dilaudid IR Tablets), exposure to hydromorphone (C max and AUC_0-48) is increased in patients with impaired renal function by 2-fold in moderate (CLcr = 40 – 60 mL/min) and 3-fold in severe (CLcr < 30 mL/min) renal impairment compared with normal subjects (CLcr > 80 mL/min).
• In addition, in patients with severe renal impairment hydromorphone appeared to be more slowly eliminated with longer terminal elimination half-life (40 hr) compared to patients with normal renal function (15 hr).
• Starting dose of hydromorphone for patients with moderate to severe renal impairment should be as low as possible
• Close monitoring of patients with renal impairment is recommended

• The respiratory depressant effects of morphine with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure may be exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure.
• Also, morphine may produce confusion, miosis, vomiting and other side effects which obscure the clinical course of patients with head injury. In such patients, morphine must be used with extreme caution and only if it is judged to be essential.
• Morphine should be administered with caution to patients in circulatory shock as its vasodilatory effects may further reduce cardiac output and blood pressure.
• Morphine may also lead to acute retention of urine by causing spasm of the sphincter of the bladder especially in men with prostatism. Monitoring of patients at risk is recommended.
• OVERDOSAGE:
  • Serious overdosage is characterized by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes bradycardia and hypotension.

This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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