DILAUDID (hydromorphone hydrochloride), a hydrogenated ketone of morphine, is an opioid analgesic.
The chemical name of DILAUDID (hydromorphone hydrochloride) is 4,5(alpha)-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride. The structural formula is:
Each 5 mL (1 teaspoon) of DILAUDID ORAL LIQUID contains 5 mg of hydromorphone hydrochloride. In addition, other ingredients include purified water, methylparaben, propylparaben, sucrose, and glycerin. DILAUDID ORAL LIQUID may contain traces of sodium metabisulfite.
Each DILAUDID 8 mg TABLET contains 8 mg hydromorphone hydrochloride. In addition, the tablets include lactose anhydrous, and magnesium stearate. DILAUDID 8 mg TABLET may contain traces of sodium metabisulfite.
Many of the effects described below are common to this class of mu-opioid agonist analgesics. In some instances, data may not exist to distinguish the effects of DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS from those observed with other opioid analgesics. However, in the absence of data to the contrary, it is assumed that DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS would possess all the actions of mu-agonist opioids.
Central Nervous System: Opioid analgesics exert their primary effects on the central nervous system and organs containing smooth muscle. The principal actions of therapeutic value are analgesia and sedation. A significant feature of the analgesia is that it can occur without loss of consciousness. Opioid analgesics also suppress the cough reflex and may cause respiratory depression, mood changes, mental clouding, euphoria, dysphoria, nausea, vomiting and electroencephalographic changes.
The precise mode of analgesic action of opioid analgesics is unknown. However, specific CNS opiate receptors have been identified. Opioids are believed to express their pharmacological effects by combining with these receptors.
Opioids depress the cough reflex by direct effect on the cough center in the medulla.
Opioids depress the respiratory reflex by a direct effect on brain stem respiratory centers. The mechanism of respiratory depression also involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension.
Opioids cause miosis. Pinpoint pupils are a common sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings) and marked mydriasis occurs with asphyxia.
Gastrointestinal Tract and Other Smooth Muscle: Gastric, biliary and pancreatic secretions are decreased by opioids. Opioids cause a reduction in motility associated with an increase in tone in the gastric antrum and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, and tone may be increased to the point of spasm. The end result is constipation. Opioids can cause a marked increase in biliary tract pressure as a result of spasm of the sphincter of Oddi.
Cardiovascular System: Certain opioids produce peripheral vasodilation which may result in orthostatic hypotension. Release of histamine may occur with opioids and may contribute to drug-induced hypotension. Other manifestations of histamine release may include pruritus, flushing, and red eyes.
The dosage of opioid analgesics like hydromorphone hydrochloride should be individualized for any given patient, since adverse events can occur at doses that may not provide complete freedom from pain (see INDIVIDUALIZATION OF DOSAGE ).
The analgesic activity of DILAUDID (hydromorphone hydrochloride) is due to the parent drug, hydromorphone. Hydromorphone is rapidly absorbed from the gastrointestinal tract after oral administration and undergoes extensive first-pass metabolism. In vivo bioavailability following single-dose administration of the 8 mg tablet is approximately 24% (coefficient of variation 21%). Bioequivalence between the DILAUDID 8 mg TABLET and an equivalent dose of DILAUDID ORAL LIQUID has been demonstrated. Dose proportionality between DILAUDID 8 mg TABLET and other strength DILAUDID tablets (2 and 4 mg) has not been established.
Absorption: After oral administration of DILAUDID 8 mg liquid or tablets, peak plasma hydromorphone concentrations are generally attained within 1/2 to 1-hour.
Food effects: The effect on the rate and extent of absorption of DILAUDID tablet or oral liquid when given with food has not been studied.
Distribution: At therapeutic plasma levels, hydromorphone is approximately 8-19% bound to plasma proteins. After an intravenous bolus dose, the steady state of volume distribution [mean (%cv)] is 302.9 (32%) liters.
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.