Skip to Content

Opana

Generic Name: Oxymorphone Hydrochloride
Class: Opiate Agonists
VA Class: CN101
CAS Number: 357-07-3

Warning

    Abuse Potential
  • Schedule II controlled substance with abuse liability similar to morphine.501

  • Potential for abuse in a manner similar to other legal or illicit opiates.501 Consider abuse potential when prescribing or dispensing oxymorphone extended-release tablets in situations where the clinician or pharmacist is concerned about increased risk of misuse, abuse, or diversion.501

    Intended Uses of Extended-release Tablets
  • Oxymorphone hydrochloride extended-release tablets are indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.501

  • Oxymorphone hydrochloride extended-release tablets are not intended for use as a prn analgesic.501

    Overdose Risk with Improper Administration of Extended-release Tablets
  • Oxymorphone hydrochloride extended-release tablets are to be swallowed whole and are not to be broken, chewed, dissolved, or crushed.501

  • Chewing, crushing, or dissolving the extended-release tablets could result in rapid release and absorption of a potentially fatal dose of oxymorphone.501

  • Consuming alcohol while receiving extended-release tablets could result in increased plasma concentrations of oxymorphone and a potentially fatal dose of the drug; patients must not consume alcoholic beverages or alcohol-containing prescription or nonprescription preparations during therapy with extended-release tablets.501

    Concomitant Use with Benzodiazepines or Other CNS Depressants
  • Concomitant use of opiate agonists with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.416 417 418 700 701 702 703

  • Reserve concomitant use of opiate analgesics and benzodiazepines or other CNS depressants for patients in whom alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy and monitor closely for respiratory depression and sedation.700 703 (See Specific Drugs under Interactions.)

REMS:

FDA approved a REMS for oxymorphone to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of oxymorphone and consists of the following: medication guide and elements to assure safe use. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Opiate agonist; phenanthrene derivative.500 501 502 a e

Uses for Opana

Acute and Chronic Pain

Relief of moderate to severe pain.500 501 502

Symptomatic relief of moderate to moderately severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.e

Extended-release tablets are used orally for management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.501 The extended-release tablets are not intended for use on an as-needed (“prn”) basis.501

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.431 432 433 435 Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.411 431 434 435 Optimize concomitant use of other appropriate therapies.432 434 435 (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

In the management of chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.e

Generally use opiates for management of chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing410 411 412 413 ) that is not associated with active cancer treatment, palliative care, or end-of-life care only if other appropriate nonpharmacologic and nonopiate pharmacologic strategies have been ineffective and expected benefits for both pain relief and functional improvement are anticipated to outweigh risks.411 412 413 414 422 429

If used for chronic pain, opiate analgesics should be part of an integrated approach that also includes appropriate nonpharmacologic modalities (e.g., cognitive-behavioral therapy, relaxation techniques, biofeedback, functional restoration, exercise therapy, certain interventional procedures) and other appropriate pharmacologic therapies (e.g., nonopiate analgesics, analgesic adjuncts such as selected anticonvulsants and antidepressants for certain neuropathic pain conditions).411 412 413 422 429

Available evidence insufficient to determine whether long-term opiate therapy for chronic pain results in sustained pain relief or improvements in function and quality of life411 423 431 432 436 or is superior to other pharmacologic or nonpharmacologic treatments.432 Use is associated with serious risks (e.g., opiate use disorder, overdose).411 431 436 (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

Surgery

Used parenterally as a supplement to anesthesia.502 a

Analgesia During Labor

Used parenterally for analgesia during labor.502

Acute Pulmonary Edema

Used in patients with acute pulmonary edema for its cardiovascular effects and to allay anxiety.502 a e Should not be used in the treatment of pulmonary edema resulting from a chemical respiratory irritant.502

Opana Dosage and Administration

General

Managing Opiate Therapy for Acute Pain

  • Optimize concomitant use of other appropriate therapies.432 434 435

  • When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.411 431 434 435

  • When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.432

  • For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).411 433 434 435 Do not prescribe larger quantities for use in case pain continues longer than expected;411 432 instead, reevaluate patient if severe acute pain does not remit.411 431 435

  • For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.430 431 432

  • Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.430 431

  • Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.430 432 When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.430 431

Managing Opiate Therapy for Chronic Noncancer Pain

  • Although specific recommendations may vary, common elements in clinical guideline recommendations include risk mitigation strategies, upper dosage thresholds, careful dosage titration, and consideration of risks associated with particular opiates and formulations, coexisting diseases, and concomitant drug therapy.410 411 414 415 423

  • Prior to initiating therapy, thoroughly evaluate patient; assess risk factors for misuse, abuse, and addiction;411 412 413 415 422 429 establish treatment goals (including realistic goals for pain and function); and consider how therapy will be discontinued if benefits do not outweigh risks.411 415

  • Regard initial opiate therapy for chronic noncancer pain as a therapeutic trial that will be continued only if there are clinically meaningful improvements in pain and function that outweigh treatment risks.411 412 413

  • Prior to and periodically during therapy, discuss with patients known risks and realistic benefits and patient and clinician responsibilities for managing therapy.411 412 413 414 415

  • Some experts recommend initiating opiate therapy for chronic noncancer pain with conventional (immediate-release) opiate analgesics prescribed at lowest effective dosage.411 415 Individualize opiate selection, initial dosage, and dosage titration based on patient’s health status, prior opiate use, attainment of therapeutic goals, and predicted or observed harms.412 413

  • Evaluate benefits and harms within 1–4 weeks following initiation of therapy or dosage increase411 413 and reevaluate on ongoing basis (e.g., at least every 3 months411 ) throughout therapy.411 412 413 Document pain intensity and level of functioning and assess progress toward therapeutic goals, presence of adverse effects, and adherence to prescribed therapies.412 413 422 423 Anticipate and manage common adverse effects (e.g., constipation, nausea and vomiting, cognitive and psychomotor impairment).412 413 415 If benefits do not outweigh harms, optimize other therapies and taper opiate to lower dosage or taper and discontinue opiate.411 412 413 415

  • When repeated dosage increases required, evaluate potential causes and reassess relative benefits and risks.412 413 Although evidence is limited, some experts state that opiate rotation may be considered in patients with intolerable adverse effects or inadequate benefit despite dosage increases.412 413 415

  • Higher dosages require particular caution,410 412 415 including more frequent and intensive monitoring or referral to specialist.411 412 413 Greater benefits of high-dose opiates for chronic pain not established in controlled clinical studies; higher dosages associated with increased risks (motor vehicle accidents, overdosage, opiate use disorder).411 415 423 424 425 426

  • CDC states that primary care clinicians should carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately ≥17 mg of oxymorphone hydrochloride daily) for chronic pain and should avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately ≥30 mg of oxymorphone hydrochloride daily) or carefully justify decision to prescribe such dosages.411 Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.423 431 Some states have established opiate dosage thresholds (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with specialist is mandated or recommended)411 420 421 423 or have mandated risk-management strategies (e.g., review of state prescription drug monitoring program [PDMP] data prior to prescribing).411 419 423

  • Recommended strategies for managing risks include written treatment agreements or plans (e.g., “contracts”), urine drug testing, review of state PDMP data, and risk assessment and monitoring tools.410 411 412 413 414 415 422 423 429

  • Taper and discontinue opiate therapy if patient engages in serious or repeated aberrant drug-related behaviors or drug abuse or diversion.412 413 415 Offer or arrange treatment for patients with opiate use disorder.411 412 413

  • Consider providing concomitant naloxone for patients at increased risk of opiate overdosage (e.g., those with history of overdose or substance use disorder, those receiving ≥50 mg of morphine sulfate [or equivalent] daily, those receiving benzodiazepines concomitantly, those with medical conditions that could increase sensitivity to opiate effects).411 431

Administration

Administer orally,500 501 or by sub-Q, IM, or IV injection.502 a

Oral Administration

Administer orally as conventional tablets or extended-release tablets.500 501

Administer conventional and extended-release tablets on an empty stomach, at least 1 hour before or 2 hours after food.500 501 Food affects oral absorption.500 501 (See Food under Pharmacokinetics.)

Extended-release tablets: Swallow tablets whole; do not divide, crush, or chew.501 Do not administer with alcohol.501 (See Boxed Warning.)

IV Administration

Administer by direct IV injection.e

When administered IV, an opiate antagonist and facilities for administration of oxygen and control of respiration should be available.a e

IM Administration

IM administration of opiate analgesics is discouraged; IM injections can cause pain and are associated with unreliable absorption, resulting in inconsistent analgesia.430

Dosage

Available as oxymorphone hydrochloride; dosage expressed in terms of the salt.500 501

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.411 413 431 432 435

Individualize dosage according to clinical status of the patient, desired therapeutic effect, degree of existing opiate tolerance, and age and weight; assess dosage at periodic intervals.500 501 502

Reduce dosage in poor-risk patients and in geriatric patients.a

When switching patients receiving chronic opiate therapy from one opiate analgesic to another, generally reduce the calculated equianalgesic dosage of the new opiate agonist by about 25–50% to avoid inadvertent overdosage.410 412 This calculation does not apply when switching to methadone; consult specific recommendations for methadone dosage.412

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.700 703 (See Specific Drugs under Interactions.)

Avoid abrupt withdrawal from relatively high dosages (e.g., in chronic pain patients) since precipitation of severe abstinence syndrome is likely.500 501 502

Extended-release tablets usually are administered twice daily in 2 equally divided doses; an asymmetric daily dosing regimen (i.e., different dose in the morning than in the evening) may be appropriate in some patients, depending on the pain pattern.501

Adults

Pain (Oral Treatment)
Conventional Tablets
Oral

Opiate-naive patients: Usually, initiate with 10–20 mg every 4–6 hours as needed.500 Alternatively, use 5 mg every 4–6 hours.500 Do not initiate with doses >20 mg.500 Adjust according to response and tolerance.500

Switching from Parenteral Oxymorphone to Conventional Tablets
Oral

Calculate the total daily dosage of the parenteral preparation, multiply by a factor of 10 and administer as conventional tablets in 4 or 6 equally divided doses.500 For example, 10 mg of oral oxymorphone hydrochloride given every 6 hours as conventional tablets can be substituted for a total daily IM oxymorphone hydrochloride dosage of 4 mg.500

Extended-release Tablets
Oral

Opiate-naive patients: Initiate with 5 mg every 12 hours.501 Adjust according to response and tolerance.501 Titrate in increments of 5–10 mg every 12 hours every 3–7 days to provide adequate analgesia.501

Switching from Conventional Oxymorphone Tablets to Extended-release Tablets
Oral

Calculate the total daily dosage of the conventional preparation and give as extended-release tablets in 2 divided doses at 12-hour intervals.501

Switching from Parenteral Oxymorphone to Extended-release Tablets
Oral

Calculate the total daily dosage of the parenteral preparation, multiply by a factor of 10 and administer as extended-release tablets in 2 equally divided doses.501 For example, 20 mg of oral oxymorphone hydrochloride given every 12 hours as extended-release tablets can be substituted for a total daily IM oxymorphone hydrochloride dosage of 4 mg.501

Monitor closely to ensure adequate analgesia and to minimize side effects.501

Switching from Other Oral Opiates to Extended-release Tablets
Oral

The equivalent total daily dosage of oxymorphone hydrochloride should be calculated based on standard conversion factors suggested by the manufacturer (table below); initiate therapy with oxymorphone hydrochloride extended-release tablets by administering half the calculated dose in 2 divided doses at 12-hour intervals.501 Titrate dosage to provide adequate analgesia.501

If patients are on a regimen of several opiates, calculate the approximate oral oxymorphone dose for each opiate and add the totals to estimate the total daily oxymorphone hydrochloride dosage.501

Converting Daily Opiate Dosages to Oxymorphone Hydrochloride Extended-release Tablets (mg/day prior opiate × factor = approximate mg/day oral oxymorphone hydrochloride)501

Prior Opiate

Approximate Oral Equivalent Dose

Factor Oral

Oxymorphone

10 mg

1

Hydrocodone

20 mg

0.5

Oxycodone

20 mg

0.5

Methadone

20 mg

0.5

Morphine

30 mg

0.333

Table to be used only for conversion to oxymorphone extended-release tablets.501

Refer to published relative potency information, keeping in mind that conversion ratios are only approximate.501

When converting from methadone to oxymorphone, monitor patients closely.501

Pain (Parenteral Routes)
IV

Initially, 0.5 mg.502 Adjust according to response and tolerance.502

Sub-Q or IM

1–1.5 mg every 4 to 6 hours as necessary.502

Analgesia During Labor
IM

0.5–1 mg.502

Prescribing Limits

Adults

Oral

Conventional tablet: Maximum initial dose is 20 mg.500

For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for the expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).411 433 434 435

CDC recommends that primary care clinicians carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately 17 mg of oxymorphone hydrochloride daily) for chronic pain and avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately 30 mg of oxymorphone hydrochloride daily) or carefully justify their decision to prescribe such dosages.411 Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.423 431

Some states have set prescribing limits (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with a specialist is mandated or recommended).411 420 421 423

Special Populations

Hepatic Impairment

In patients with mild hepatic impairment, initiate with lowest dosage and increase dose slowly.500 501 502 (See Contraindications.)

Renal Impairment

In patients with Clcr <50 mL/minute, reduce dosage.500 501 502 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

Select dosage with caution; use lower than usual initial dosages.500 501 502 (See Geriatric Use under Cautions and see Special Populations under Pharmacokinetics.)

Cautions for Opana

Contraindications

  • Known hypersensitivity to oxymorphone, morphine analogs such as codeine, or any ingredient in the formulation.500 501 502

  • Respiratory depression in the absence of resuscitative equipment.500 501 502

  • Acute or severe asthma or hypercarbia.500 501 502

  • Known or suspected paralytic ileus.500 501 502

  • Moderate or severe hepatic impairment.500 501 502

  • Extended-release preparation contraindicated in the management of immediate postoperative pain (first 12–24 hours following surgery), in patients with mild pain, and in those who are expected to require analgesia for a short period of time.501

  • Parenteral use contraindicated in the treatment of pulmonary edema resulting from a chemical respiratory irritant.502

Warnings/Precautions

Warnings

Dependence and Abuse

Possible tolerance, psychologic dependence, and physical dependence following prolonged administration.500 501 Use only with careful surveillance in patients with a history of drug or alcohol dependence or abuse.500 501 Clinicians should consider abuse potential when prescribing or dispensing oxymorphone in situations where they are concerned about an increased risk of misuse, abuse, or diversion.502 However, concerns about abuse, addiction, and diversion should not prevent the proper management of pain.501 502

Oxymorphone tablets can be abused by crushing, chewing, “snorting” the powder, or dissolving the contents in water and injecting.501 502

Breaking, chewing, or crushing of extended-release tablets results in immediate release of the opiate and the risk of a potentially fatal overdose.501 (See Boxed Warning.)

Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms.500 501 502 After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.500 501 502

Health-care professionals should contact the professional licensing board or controlled substance authority in their states for information about prevention and detection of abuse or diversion.501 502

Respiratory Depression

The major toxicity associated with oxymorphone.501 502 e

Occurs most frequently in geriatric or debilitated patients and in those with conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic opiate dosages may dangerously decrease pulmonary ventilation.501 502 e

Use with extreme caution in patients with hypoxia, hypercapnia, or substantially decreased respiratory reserve (e.g., asthma, COPD, cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression, coma).501 502 e In such patients, even therapeutic oxymorphone doses may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.501 502 e Consider use of non-opiate analgesics.501 502 e Use oxymorphone only with careful medical supervision and at lowest effective dosage.501 502 e

Consider offering naloxone when opiate agonists are prescribed for patients at increased risk of opiate overdosage (e.g., those with history of overdose or substance use disorder, those receiving ≥50 mg of morphine sulfate [or equivalent] daily, those receiving benzodiazepines concomitantly, those with medical conditions that could increase sensitivity to opiates).411 431

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiates, including oxymorphone, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiate agonists, alcohol) may result in profound sedation, respiratory depression, coma, and death.416 417 418 700 701 702 703 Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.416 417 418 435 700 701

Reserve concomitant use of oxymorphone and other CNS depressants for patients in whom alternative treatment options are inadequate.700 703 (See Specific Drugs under Interactions.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.400 Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.400

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.400 If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.400 In some patients, switching to a different opiate improved symptoms.400

Head Injury and Increased Intracranial Pressure

Respiratory depressant effects of oxymorphone (with CO2 retention and secondary elevation of CSF pressure) may be markedly exaggerated in the presence of head injury, other intracranial lesions, or preexisting increase in intracranial pressure.501 502 e

Opiates produce effects (e.g., pupillary changes) that may obscure neurologic signs of further increase in pressure in patients with head injuries.501 502 e

Hypotensive Effects

Possible severe hypotension in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant drugs that compromise vasculature tone (e.g., phenothiazines, general anesthetics).500 501 502 e

Use with caution in patients in circulatory shock, because vasodilation produced by the drug may further reduce cardiac output and BP.500 501 502

General Precautions

Acute Abdominal Conditions

Administration may complicate assessment of patients with acute abdominal conditions.500 501 502 (See GI Effects under Cautions.)

Seizures

May aggravate preexisting seizures in patients with seizure disorders.501 502 e May induce seizures.500 501 502

Debilitated and Special-Risk Patients.

Use with caution in debilitated patients, those sensitive to CNS depressants, patients with Addison's disease, CNS depression or coma, kyphoscoliosis, myxedema or hypothyroidism, prostatic hypertrophy, urethral stricture, severe impairment of pulmonary function, toxic psychosis, acute alcoholism, delirium tremens, or following GI surgery.500 501 502

Pancreatic and Biliary Disease

May cause spasm of the sphincter of Oddi.500 501 502 Use with caution in patients with biliary tract disease, including acute pancreatitis, and patients undergoing biliary tract surgery.500 501 502

GI Effects

Monitor for decreased bowel motility in post-operative patients.500 501 502 (See Acute Abdominal Conditions under Cautions.)

Contraindicated in patients with known or suspected paralytic ileus.500 501 502

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;400 401 402 403 404 causality not established.400 Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.400 Perform appropriate laboratory testing in patients with manifestations of hypogonadism.400

Specific Populations

Pregnancy

Category C.500 501 502

Use parenteral preparation with caution during labor.502 Administration during labor may cause neonatal respiratory depression.502 An opiate antagonist and resuscitative equipment for reversal of opiate-induced respiratory depression should be readily available when opiates are administered during labor and delivery.502

Use of oxymorphone tablets and extended-release tablets not recommended during or immediately prior to labor.501

Infants born to women regularly taking opiates during pregnancy may be physically dependent.500 501 502

Lactation

Not known whether oxymorphone is distributed into human milk.500 501 502 Women receiving oxymorphone generally should not nurse.500 501 502

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.500 501 502

Geriatric Use

No substantial difference in efficacy of oral preparations in geriatric patients relative to younger adults.500 501 Dizziness, somnolence, confusion, nausea reported more frequently in geriatric adults than in younger adults.500 501

Following oral administration, plasma concentrations of oxymorphone are higher in geriatric patients ≥65 years of age than in younger patients.500 501 502 (See Special Populations under Pharmacokinetics.)

Parenteral preparation not systematically evaluated in geriatric adults.502

Select dose with caution, starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.500 501 502

Hepatic Impairment

Use with caution in patients with mild hepatic impairment.500 501 502 (See Hepatic Impairment under Dosage and Administration.)

Contraindicated in patients with moderate or severe hepatic impairment.500 501 502

Renal Impairment

Use with caution in patients with moderate or severe renal impairment.500 501 502 Dosage adjustment needed in these patients.500 501 502 (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Nausea, constipation, pyrexia, somnolence, vomiting, pruritus, headache, dizziness, confusion.500 501 502

Interactions for Opana

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.400 May occur at usual dosages.400 Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.400 (See Advice to Patients.)

If concomitant use of other serotonergic drugs is warranted, monitor patients for serotonin syndrome, particularly during initiation of therapy and dosage increases.400

If serotonin syndrome is suspected, discontinue oxymorphone, other opiate therapy, and/or any concurrently administered serotonergic agents.400

Specific Drugs

Drug

Interaction

Comments

Anticholinergic agents

Increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus500 501 502

Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), SNRIs (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine), tricyclic antidepressants (TCAs), mirtazapine, nefazodone, trazodone, vilazodone

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, the antidepressant, and/or any concurrently administered opiates or serotonergic agents400

Antiemetics, 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, the 5-HT3 receptor antagonist, and/or any concurrently administered opiates or serotonergic agents400

Antipsychotics (e.g., aripiprazole, asenapine, cariprazine, chlorpromazine, clozapine, fluphenazine, haloperidol, iloperidone, loxapine, lurasidone, molindone, olanzapine, paliperidone, perphenazine, pimavanserin, quetiapine, risperidone, thioridazine, thiothixene, trifluoperazine, ziprasidone)

Risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving oxymorphone, initiate antipsychotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving an antipsychotic, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Benzodiazepines (e.g., alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, triazolam)

Risk of profound sedation, respiratory depression, hypotension, coma, or death416 417 418 700 701 703 704

Whenever possible, avoid concomitant use410 411 415 435

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving oxymorphone, initiate benzodiazepine, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a benzodiazepine, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Consider offering naloxone to patients receiving opiates and benzodiazepines concomitantly411 431

Buspirone

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, buspirone, and/or any concurrently administered opiates or serotonergic agents400

Cimetidine

Adverse CNS effects (confusion, disorientation, respiratory depression, apnea, seizures) reported with opiates500 501 502

Caution500 501 502

CNS depressants (e.g., other opiate agonists, anxiolytics, general anesthetics, tranquilizers, phenothiazines, alcohol)

Additive CNS effects;500 502 increased risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Alcohol: Increased or decreased plasma oxymorphone concentrations reported in patients receiving oxymorphone extended-release tablets501

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving oxymorphone, initiate CNS depressant, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a CNS depressant, initiate oxymorphone, if required, using 1/3 to ½ the usual dosage and titrate based on clinical response500 502 700 703

Avoid alcohol use500 501 700

Monitor closely for respiratory depression and sedation700 703

Dextromethorphan

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, dextromethorphan, and/or any concurrently administered opiates or serotonergic agents400

5-HT1 receptor agonists (triptans; e.g., almotriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, the triptan, and/or any concurrently administered opiates or serotonergic agents400

Lithium

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, lithium, and/or any concurrently administered opiates or serotonergic agents400

MAO inhibitors (e.g., isocarboxazid, linezolid, methylene blue, phenelzine, selegiline, tranylcypromine)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, the MAO inhibitor, and/or any concurrently administered opiates or serotonergic agents400

Opiate partial agonists (butorphanol, buprenorphine, nalbuphine, pentazocine)

Possible reduced analgesic effect and/or withdrawal symptoms500 501 502

Avoid concomitant use500 501 502

Sedative/hypnotic agents (e.g., butabarbital, eszopiclone, pentobarbital, ramelteon, secobarbital, suvorexant, zaleplon, zolpidem)

Risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving oxymorphone, initiate sedative/hypnotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a sedative/hypnotic, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Skeletal muscle relaxants (e.g., baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, tizanidine)

Risk of profound sedation, respiratory depression, hypotension, coma, or death700 703 704

Cyclobenzaprine: Risk of serotonin syndrome400

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy700 703

In patients receiving oxymorphone, initiate skeletal muscle relaxant, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response700 703

In patients receiving a skeletal muscle relaxant, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response700 703

Monitor closely for respiratory depression and sedation700 703

Cyclobenzaprine: If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, cyclobenzaprine, and/or any concurrently administered opiates or serotonergic agents400

St. John’s wort (Hypericum perforatum)

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, St. John’s wort, and/or any concurrently administered opiates or serotonergic agents400

Tryptophan

Risk of serotonin syndrome400

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases400

If serotonin syndrome suspected, discontinue oxymorphone, tryptophan, and/or any concurrently administered opiates or serotonergic agents400

Opana Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is 10%.500 501

Onset

5–10 minutes following IV administration.502 a

10–15 minutes following sub-Q or IM administration.a

Duration

3–6 hours following parenteral administration.502 a

Food

Conventional tablets with high-fat meal: Peak plasma concentration and AUC increase 38%.500

Extended-release tablets with food: Peak plasma concentrations increase 50%; time to peak plasma concentrations delayed; no change in AUC or small increase.501

Special Populations

Oxymorphone extended-release tablets: Bioavailability increased 26, 57, or 65% in patients with mild (Clcr 51–80 mL/minute), moderate (Clcr 30–50 mL/minute), or severe renal impairment (Clcr <30 mL/minute), respectively.501

Oxymorphone extended-release tablets: Based on information from a few individuals with hepatic impairment, bioavailability increased 1.6-, 3.7-, or 12.2-fold in patients with mild, moderate, or severe hepatic impairment, respectively.501

Oxymorphone extended-release tablets: Plasma concentrations increased 40% in geriatric individuals.501

Distribution

Plasma Protein Binding

10–12%.500 501

Elimination

Metabolism

Extensively metabolized in the liver; undergoes reduction or conjugation with glucuronic acid to form oxymorphone-3-glucuronide and 6-OH-oxymorphone.500 501 502

Elimination Route

33–38% excreted in the urine as oxymorphone-3-glucuronide, <1% excreted in urine as 6-OH-oxymorphone, <1% excreted unchanged in the urine.500 501 502

Half-life

Extended-release tablets: 9.4–11.3 hours.501

Stability

Storage

Oral

Conventional Tablets

Tight container at 25°C (may be exposed to 15–30°C).500

Extended-release Tablets

Tight container at 25°C (may be exposed to 15–30°C).501

Parenteral

Injection

25°C (may be exposed to 15°–30°C).502 Protect from light.502

Actions

  • A potent analgesic; shares the actions of the opiate agonists.500 501 502

  • Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.e

  • Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).e

  • Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.e

  • Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.e

  • Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.e

  • Agonist activity at the μ-receptor can also result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).e

  • Respiratory depression may be mediated by μ-receptors, possibly μ2-receptors (which may be distinct from μ1-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.e

Advice to Patients

  • Importance of not breaking, crushing, or chewing extended-release tablets; potentially fatal overdose can occur.501

  • Conventional and extended-release tablets: Advise patients to take tablets on an empty stomach, at least 1 hour before or 2 hours after food.500 501

  • Importance of taking only as prescribed; do not increase dosage or abruptly discontinue without consulting a clinician.500 501 502

  • Advise patients to report any episodes of breakthrough pain or adverse experiences to their clinician.500 501 502

  • Importance of informing patients that this is a drug of potential abuse and should be protected from theft.500 501 502

  • Importance of informing patients that oxymorphone should never be given to anyone other than the individual for whom it was prescribed.500 501 502

  • Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.700 703 Advise patients that oxymorphone should not be combined with alcohol.500 501 502 700

  • Importance of informing patients that oxymorphone may impair mental and/or physical ability required for performance of potentially hazardous tasks; avoid driving or operating heavy machinery until effects on individual are known.500 501 502

  • Potential risk of serotonin syndrome with concurrent use of oxymorphone and other serotonergic agents.400 Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.400

  • Potential risk of adrenal insufficiency.400 Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.400

  • Potential for severe constipation.500 501 502 Counsel patients on appropriate laxatives and/or stool softeners and other therapeutic approaches.500 501 502

  • Risk of dizziness and other adverse events.500 501 502

  • Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.400 Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.400

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.500 501 502

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.500 501 502

  • Importance of informing patients of other important precautionary information.500 501 502 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Oxymorphone hydrochloride is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.

In July 2017, Endo voluntarily agreed to comply with FDA request to remove Opana ER extended-release tablets from US market.503 504 FDA's request was based on data indicating that route of Opana ER abuse shifted from nasal to injection abuse following reformulation with properties intended to deter nasal and injection abuse in 2012.503 FDA stated that abuse by injection of the reformulated preparation had been associated with a serious outbreak of HIV and HCV infection, as well as cases of thrombotic microangiopathy.503 FDA concluded that the benefits associated with the reformulated preparation may no longer outweigh its risks.503

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

oxyMORphone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

5 mg*

Opana ( C-II)

Endo

oxyMORphone Hydrochloride Tablets (C-II)

10 mg*

Opana ( C-II)

Endo

oxyMORphone Hydrochloride Tablets (C-II)

Tablet, extended-release

5 mg*

oxyMORphone Hydrochloride Extended-release Tablets (C-II)

7.5 mg*

oxyMORphone Hydrochloride Extended-release Tablets (C-II)

10 mg*

oxyMORphone Hydrochloride Extended-release Tablets (C-II)

15 mg*

oxyMORphone Hydrochloride Extended-release Tablets (C-II)

20 mg*

oxyMORphone Hydrochloride Extended-release Tablets (C-II)

30 mg*

oxyMORphone Hydrochloride Extended-release Tablets (C-II)

40 mg*

oxyMORphone Hydrochloride Extended-release Tablets (C-II)

Parenteral

Injection

1 mg/mL

Opana ( C-II)

Endo

AHFS DI Essentials. © Copyright 2017, Selected Revisions November 13, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

400. US Food and Drug Administration. Drug safety communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. Silver Spring, MD; 2016 Mar 22. From FDA website.

401. Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009; 25:170-5. [PubMed 19333165]

402. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL et al. Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer. 2004; 100:851-8. [PubMed 14770444]

403. Abs R, Verhelst J, Maeyaert J et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. 2000; 85:2215-22. [PubMed 10852454]

404. Fraser LA, Morrison D, Morley-Forster P et al. Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women. Exp Clin Endocrinol Diabetes. 2009; 117:38-43. [PubMed 18523930]

410. Nuckols TK, Anderson L, Popescu I et al. Opioid prescribing: a systematic review and critical appraisal of guidelines for chronic pain. Ann Intern Med. 2014; 160:38-47. [PubMed 24217469]

411. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016; 65:1-49. [PubMed 26987082]

412. Chou R, Fanciullo GJ, Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10:113-30. [PubMed 19187889]

413. Management of Opioid Therapy for Chronic Pain Working Group, US Department of Veterans Affairs and Department of Defense. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. 2010 May.

414. Chou R, Cruciani RA, Fiellin DA et al. Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. J Pain. 2014; 15:321-37. [PubMed 24685458]

415. Manchikanti L, Abdi S, Atluri S et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician. 2012; 15(3 Suppl):S67-116.

416. Park TW, Saitz R, Ganoczy D et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015; 350:h2698. [PubMed 26063215]

417. Jones CM, McAninch JK. Emergency Department Visits and Overdose Deaths From Combined Use of Opioids and Benzodiazepines. Am J Prev Med. 2015; 49:493-501. [PubMed 26143953]

418. Dasgupta N, Funk MJ, Proescholdbell S et al. Cohort Study of the Impact of High-Dose Opioid Analgesics on Overdose Mortality. Pain Med. 2016; 17:85-98. [PubMed 26333030]

419. Prescription Drug Monitoring Program Training and Technical Assistance Center (PDMP TTAC). Criteria for mandatory enrollment or query of PDMP. From PDMP TTAC website. Accessed 2016 Sep 14.

420. National Alliance for Model State Drug Laws (NAMSLD). Overview of state pain management and prescribing policies. From NAMSLD webiste. Accessed 2016 Sep 14.

421. Bennett A (Maine Office of Governor). Augusta, ME: 2016 Apr 19. Governor signs major opioid prescribing reform bill. Press release.

422. American Academy of Pain Medicine (AAPM). Use of opioids for the treatment of chronic pain. A statement from the American Academy of Pain Medicine. From AAPM website. 2013 Feb.

423. Franklin GM, American Academy of Neurology. Opioids for chronic noncancer pain: a position paper of the American Academy of Neurology. Neurology. 2014; 83:1277-84. [PubMed 25267983]

424. Dunn KM, Saunders KW, Rutter CM et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010; 152:85-92. [PubMed 20083827]

425. Gomes T, Mamdani MM, Dhalla IA et al. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011; 171:686-91. [PubMed 21482846]

426. Bohnert AS, Valenstein M, Bair MJ et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-21. [PubMed 21467284]

429. Paice JA, Portenoy R, Lacchetti C et al. Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016; 34:3325-45. [PubMed 27458286]

430. Chou R, Gordon DB, de Leon-Casasola OA et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016; 17:131-57. [PubMed 26827847]

431. Washington State Agency Medical Directors' Group (AMDG). Interagency guideline on prescribing opioids for pain, 3rd ed. From Washington State AMDG website. 2015 Jun.

432. Hegmann KT, Weiss MS, Bowden K et al. ACOEM practice guidelines: opioids for treatment of acute, subacute, chronic, and postoperative pain. J Occup Environ Med. 2014; 56:e143-59.

433. Cantrill SV, Brown MD, Carlisle RJ et al. Clinical policy: critical issues in the prescribing of opioids for adult patients in the emergency department. Ann Emerg Med. 2012; 60:499-525. [PubMed 23010181]

434. Thorson D, Biewen P, Bonte B et al, for Institute for Clinical Systems Improvement (ICSI). Acute pain assessment and opioid prescribing protocol. From ICSI website. 2014 Jan.

435. New York City Department of Health and Mental Hygiene. New York City emergency department discharge opioid prescribing guidelines. From NYC Health website. 2013 Jan.

436. Chou R, Deyo R, Devine B et al. The effectiveness and risks of long-term opioid treatment of chronic pain. Evidence report/technology assessment No. 218. Rockville, MD: Agency for Healthcare Research and Quality (AHRQ); 2014 Sep.

500. Endo Pharmaceuticals Inc. Opana (oxymorphone hydrochloride) tablets prescribing information. Chadds Ford, PA; 2006 Jul.

501. Endo Pharmaceuticals Inc. Opana ER (oxymorphone hydrochloride) extended-release tablets prescribing information. Chadds Ford, PA; 2007 June.

502. Endo Pharmaceuticals Inc. Opana (oxymorphone hydrochloride) injection prescribing information. Chadds Ford, PA; 2006 Sept.

503. US Food and Drug Administration. FDA requests removal of Opana ER for risks related to abuse. Rockville, MD; 2017 Jun 8. News release from FDA website.

504. Endo Pharmaceuticals. Endo provides update on Opana ER. Malvern, PA; 2017 Jul 6. News release from Endo website.

700. US Food and Drug Administration. Drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Silver Spring, MD; 2016 Aug 31. From FDA website.

701. Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. JAMA. 2013; 309:657-9. [PubMed 23423407]

702. Jones CM, Paulozzi LJ, Mack KA et al. Alcohol involvement in opioid pain reliever and benzodiazepine drug abuse-related emergency department visits and drug-related deaths - United States, 2010. MMWR Morb Mortal Wkly Rep. 2014; 63:881-5. [PubMed 25299603]

703. Hertz S. Letter to manufacturers of opioid analgesics: safety labeling change notification. Silver Spring, MD: US Food and Drug Administration. Accessed 2017 Mar 20.

704. Endo Pharmaceuticals, Inc. Opana (oxymorphone hydrochloride) tablets prescribing information. Malvern, PA; 2016 Dec.

a. AHFS drug information 2007. McEvoy GK, ed. Oxymorphone. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2154-5.

e. AHFS drug information 2007. McEvoy GK, ed. Opioid Agonists General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2123-8.

Hide