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Drug Criteria & Outcomes
Oxymorphone (Opana®) Formulary Evaluation
Part 1: Indications, Mechanism of Action, Pharmacokinetics, Contraindications, and Adverse Effects
By Erica Oelfke, PharmD Candidate, Auburn (AL) University
Oxymorphone hydrochloride (Opana® and Opana ER®) is a semi-synthetic opioid analgesic tablet for oral administration. It is a morphine-like agonist and a CII drug with an abuse liability similar to other opioids. Oxymorphone is available as 5 mg and 10 mg tablets for oral administration. The extended release (ER) formulation is available as 5 mg, 10 mg, 20 mg, and 40 mg tablets, also for oral administration. (See Table) Oxymorphone injection (Opana injection®) is available in 1 mg/mL in 1 mL ampules and 1.5 mg/mL in 10 mL multiple - dose vials.
Morphine immediate release (IR) and controlled release (CR)/extended release (ER) is the standard opium alkaloid for comparative purposes.
Oxymorphone is indicated for relief of moderate-to-severe acute pain where the use of an opioid is appropriate. Oxymorphone ER is indicated when continuous opioid therapy is necessary for an extended period of time. Oxymorphone injection may be useful in patients in whom IM or SC administration of large volumes of other opiate agonists is associated with discomfort or is precluded because of small muscle mass.
Morphine IR tablets/solution is indicated for relief of moderate-to-severe pain, while morphine SR tablets/capsules may be preferable in those requiring continuous opioid therapy for an extended period of time. Morphine SR is not intended for use as an as-needed analgesic. Morphine injection is indicated for relief of moderate-to-severe pain, preoperative apprehension, preoperative sedation, control of postoperative pain, supplement to anesthesia, analgesia during labor, and acute pulmonary edema.
Mechanism of Action
Oxymorphone is a semi-synthetic phenanthrene-derivative opiate agonist. The precise mechanism of action of oxymorphone is unknown, but its effects are believed to result in analgesia.
Morphine is a phenanthrene - derivative opiate agonist; morphine is the principal alkaloid of opium and considered to be the prototype of the opiate agonists.
Oxymorphone modulates pain and exhibits significant specificity at the opioid µ receptor, with less binding to the κ receptor. Oxymorphone differs from morphine in a ketone-group, which makes the molecule more lipid-soluble, conferring greater potency and a more rapid onset of action than morphine. The moderate lipid solubility of oxymorphone facilitates rapid penetration into neurovascular membranes of the brain and spinal cord.
Opioids selective for the µ receptors should display analgesia, decrease respiratory function, slow gastrointestinal function, increase sedation, and inhibit the release of acetylcholine and dopamine. Opioids selective for the κ receptors should display more analgesia, reduce GI motility, increase psychotomimesis, increase sedation, and increase diuresis. It is important to note that drugs that are relatively selective at standard doses may interact with other receptor subtypes when given at higher doses, leading to changes in their pharmacological profile. Morphine, oxycodone, and other related opiates are principally strong µ agonists. Buprenorphine (Buprenex®), butorphanol (Talwin®), and nalbuphine (Nubain®) are examples of κ agonists.
Food may lead to excessive peaks in absorption of oxymorphone; doses should be given at least one hour prior to eating or two hours after. Oral bioavailability is ~10%; the onset of action with oral immediate release is 15-30 minutes and analgesia is maintained for 4-5 hours, depending on the route of administration. Opana injection has an onset of action of 5-10 minutes and analgesia is maintained for 3-6 hours.
Morphine administration with food may decrease the rate of absorption of ER capsules. Oral bioavailability is 20-40%. Peak analgesia occurs within 60 minutes following oral administration and 20-60 minutes after rectal administration. Peak analgesia occurs within 50-90 minutes following subcutaneous injection, 30-60 minutes after IM injection, and 20 minutes after IV injection. Analgesia is maintained for 3-6 hours with morphine.
Oxymorphone protein binding ranges from 10-12%; it is highly metabolized by the liver. Mean half-life is 3-4 hours and less than 1% of oxymorphone is excreted in the urine as the parent drug.
Morphine protein binding is 36%; it is highly metabolized by the liver. Mean half-life is 2-3 hours and up to 2-12% of morphine is eliminated unchanged in the urine.
The Table above summarizes information regarding dosage, availability, and administration.
Both oxymorphone and morphine display similar adverse effects. Due to morphine's high usage, more adverse effects are reported compared to oxymorphone.
Oxymorphone should not be administered to patients with respiratory depression, acute or severe bronchial asthma; hypercarbia; paralytic ileus; moderate-to-severe hepatic impairment; or known hypersensitivity to oxymorphone or morphine analogs such as codeine.
Morphine should not be administered to patients with respiratory depression; known or suspected paralytic ileus; pruritus; or urinary retention, which may persist for 10-20 hours after administration.
Epidural and intrathecal injection of morphine is contraindicated in patients whose concomitant drug therapy or medical condition would contraindicate administration of the drug by these routes, such as when infection is present at the injection site or the patient has uncontrolled bleeding diathesis or is receiving anticoagulants.
In patients with myocardial infarction, morphine causes a decrease in systemic vascular resistance, which may result in a transient fall in systemic arterial pressure and lead to severe hypotension; however, this usually is not a particular threat to supine patients. Morphine should be used with caution in patients with toxic psychoses. Some commercially available formulations of morphine sulfate injection contain sulfites that may cause allergic-type reactions. Morphine sulfate ER (Avinza®) contains fumaric acid. Safety of dosages exceeding 1.6 g daily has not been established; dosages contain a quantity of fumaric acid that may be associated with serious renal toxicity.
Warnings and Precautions
Oxymorphone use with alcohol and drugs of abuse is associated with additive effects; oxymorphone has an abuse liability similar to morphine and other opioid agonists.
Respiratory depression is the chief hazard. Respiratory depression is a particular potential problem in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.
Serious adverse events and deaths have occurred as a result of inadvertent overdosage of concentrated morphine sulfate oral solutions. Milligrams (mg) were mistakenly interchanged for milliliters (mL) of the concentrated preparation, resulting in 20-fold overdoses. It is important that prescriptions for morphine sulfate oral solution be written clearly and filled with the proper concentration of morphine sulfate oral solution to prevent potential medication errors.
Commercially available strengths of morphine sulfate ER capsules are not appropriate for children; the contents of the capsules should not be sprinkled onto applesauce for administration to children.
Adverse effects for oxymorphone and morphine are similar. With oxymorphone, the most common (> 10%) include: hypotension, fatigue, drowsiness, dizziness, nausea, vomiting, constipation, weakness, and histamine release.
With morphine, the most common (> 10%) include: palpitations, hypotension, bradycardia, drowsiness (48%, tolerance usually develops to drowsiness with regular dosing for one to two weeks), dizziness (20%), confusion, headache, pruritus (may be secondary to histamine release), nausea (28%, tolerance usually develops to nausea and vomiting with chronic use), constipation (40%, tolerance develops very slowly if at all), xerostomia (78%), urinary retention (16%; may be prolonged, up to 20 hours, following epidural or intrathecal use), and pain at the injection site.
Neither drug should be administered during pregnancy or lactation unless the benefits outweigh the risks. It is unknown whether either drug is excreted in breast milk.
Potential for Medication Error
Look-alike/Sound-alike errors: oxycodone/oxymorphone, hydrocodone/hydromorphone, morphine/meperidine, opa/opcon-A solution.
Other potential medication errors include: confusing oxymorphone with oxymorphone ER, confusing hydromorphone injection with oxymorphone injection, and confusing oral and parenteral drug ratios to morphine.
Combining oxymorphone with alcohol and drugs of abuse may result in additive effects. The effect of co-ingestion of alcohol with oxymorphone has not been evaluated. Patients must not consume alcoholic beverages or prescription or nonprescription medication containing alcohol while taking oxymorphoen ER. The co-ingestion of alcohol with oxymorphone ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone.
Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased urinary retention and/or severe constipation, which may lead to paralytic ileus.
Respiratory depression is an adverse drug event. Respiratory depression is a particular problem in the elderly and in debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Interactions with other central nervous system depressants may occur.
Oxymorphone has an abuse liability similar to morphine and other opioid agonists. Oxymorphone tablets may be abused by crushing, chewing, snorting, or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death.