PERCOCET 10/325mg.

BOXED WARNING

As with other opiate agonists, products containing oxycodone should be avoided in patients with severe pulmonary disease. Additionally, avoid coadministration with other CNS depressants unless no other alternatives are available, as this significantly increases the risk for respiratory depression, low blood pressure, and death. Acetaminophen; oxycodone use is contraindicated in patients with significant respiratory depression, and in patients with acute or severe asthma (e.g., status asthmaticus) or hypercarbia in unmonitored care settings or in the absence of resuscitative equipment. Receipt of moderate oxycodone doses in these patients may significantly decrease pulmonary ventilation. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to acetaminophen; oxycodone, as even usual therapeutic doses of oxycodone may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxycodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep apnea syndrome and/or decreased respiratory reserve. Respiratory depression, if left untreated, may cause respiratory arrest and death. Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Due to the risk of serious respiratory depression, the extended-release tablets should be reserved for patients in whom alternative treatment options (e.g., non-opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Do not use extended-release tablets on an as needed basis. Proper dosing and titration are essential; patients should be monitored for respiratory depression, particularly during the first 24—72 hours after therapy initiation or after a dose increase. Patients must be instructed to keep acetaminophen; oxycodone away from pediatric patients and others for whom the drug was not prescribed, as accidental exposure or improper use may lead to fatal respiratory depression. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

Oxycodone is a strong opiate agonist; therefore, acetaminophen; oxycodone is subject to substance abuse and psychologic dependence. Addiction may occur in patients appropriately prescribed oxycodone. Patients with a previous history of substance abuse may be at increased risk of relapse if treated with acetaminophen; oxycodone. Also, patients with mental illness (e.g., major depression) or a family history of substance abuse or alcoholism may be at greater risk. Monitor patients for signs of misuse, abuse, or addiction. Abuse or misuse of the extended-release tablets by crushing, chewing, snorting, or injecting the dissolved product will lead to uncontrolled drug delivery that may be fatal. Health care professionals should not let concerns over psychologic dependence deter them from using adequate amounts of opiate agonists in the management of severe pain.

Acetaminophen; oxycodone is classified as FDA pregnancy risk category C. No well-controlled studies in pregnant women have been performed. Some experts suggest increased risk of oxycodone if used for prolonged periods or at high doses near term. Chronic maternal use of opioids during pregnancy may result in neonatal opioid withdrawal syndrome. This syndrome can be life-threatening and includes symptoms such as poor feeding, irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, rigidity, and seizures. Neonates whose mothers have been taking oxycodone chronically may show some respiratory depression and/or withdrawal symptoms at birth or within a few days. Neonatal opioid withdrawal syndrome may be life-threatening and should be treated according to protocols developed by neonatology experts. Acetaminophen; oxycodone should not be used immediately prior to or during labor or obstetric delivery due to the potential for respiratory depression in the newborn. No overall increase in fetal mortality, as determined by pregnancy outcomes of mothers that overdosed on various amounts of acetaminophen, was apparent amongst 300 women. Treatment with acetylcysteine or methionine did not appear to affect fetal or neonatal toxicity. Of 235 babies exposed to an overdose of only acetaminophen, 168 were normal, 8 had malformations, 16 were spontaneously aborted, and 43 were electively terminated. Of 67 babies exposed to an overdose of a combination acetaminophen product, 51 were normal, 3 had malformations, 2 were spontaneously aborted (late fetal deaths), and 11 were electively terminated. None of the babies with malformations were exposed during the first trimester, but all of the spontaneous abortions and one of the late fetal deaths were subsequent to first trimester exposure.

Acetaminophen has the potential for overdose or poisoning that can cause acute hepatic failure, at times resulting in liver transplantation or death. Most cases of hepatotoxicity are a result of exceeding maximum daily dosage limits and often involve the use of more than one acetaminophen-containing product. Acetaminophen; oxycodone should be used with caution in patients with alcoholism, chronic malnutrition, active hepatitis, or severe hypovolemia, as these patients may be at increased risk for acetaminophen-induced hepatotoxicity. In patients with chronic hepatic disease, acetaminophen can be used safely and is often preferred to nonsteroidal anti-inflammatory drugs (NSAIDs) due to the absence of platelet impairment, gastrointestinal toxicity, and nephrotoxicity. Though the half-life of acetaminophen may be prolonged, repeated dosing does not result in drug or metabolite accumulation. In addition, cytochrome P450 activity is not increased and glutathione stores are not depleted in hepatically impaired patients taking therapeutic doses, therefore toxic metabolite formation and accumulation is not altered. Although it is always prudent to use the smallest dose of acetaminophen for the shortest duration necessary, courses less than 2 weeks in length have been administered safely to adult patients with stable chronic liver disease. In patients without pre-existing hepatic impairment, hepatotoxicity may occur if the total daily dose exceeds 4,000 mg/day or more than 3 alcoholic beverages per day are consumed while taking acetaminophen. Patients and caregivers should be appropriately counseled on acetaminophen intake and reminded that all acetaminophen-containing prescription and over-the-counter products, both single-entity and combination, must be considered in the total daily dosage. Oxycodone may accumulate leading to a prolonged duration of action in patients with decreased liver function. Close monitoring is warranted to avoid respiratory depression. Guidelines for use of the extended-release tablets in patients with hepatic impairment recommend initiating treatment at 50% of the normal starting dosage.

DEA CLASS

Rx, schedule II

DESCRIPTION

Combination product to treat moderate to severe pain. Acetaminophen is a non-salicylate analgesic; oxycodone is an oral semisynthetic opiate agonist. The combination produces additive analgesia as compared to either agent alone.

COMMON BRAND NAMES

Endocet, Nalocet, Percocet, Primlev, Roxicet, XARTEMIS XR

HOW SUPPLIED

Endocet/Nalocet/Oxycodone Hydrochloride, Acetaminophen/Oxycodone, Acetaminophen/Percocet/Primlev/Roxicet Oral Tab: 10-300mg, 10-325mg, 2.5-300mg, 2.5-325mg, 5-300mg, 5-325mg, 7.5-300mg, 7.5-325mg
Oxycodone Hydrochloride, Acetaminophen/Oxycodone, Acetaminophen/Roxicet Oral Sol: 5mL, 5-325mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

Immediate-release formulations: Acetaminophen 4 g/day PO; the maximum dose of the acetaminophen; oxycodone combination is limited by the total daily limit of acetaminophen.
Extended-release tablets: 4 tablets/day PO. Total daily dose of acetaminophen from all products should not exceed 4 g/day PO.

Immediate-release formulations: Acetaminophen 4 g/day PO; the maximum dose of the acetaminophen; oxycodone combination is limited by the total daily limit of acetaminophen.
Extended-release tablets: 4 tablets/day PO. Total daily dose of acetaminophen from all products should not exceed 4 g/day PO.

Immediate-release formulations: Safety and efficacy have not been established. Doses containing up to acetaminophen 4 g/day PO have been used. The maximum dose of the acetaminophen; oxycodone combination is limited by the total daily limit of acetaminophen.
Extended-release tablets: Safety and efficacy have not been established.

Immediate-release formulations: Safety and efficacy have not been established. Doses up to acetaminophen 75 mg/kg/day PO or 4 g/day PO, whichever is less, have been used. The maximum dose of the acetaminophen; oxycodone combination is limited by the total daily limit of acetaminophen.
Extended-release tablets: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Dosage should be modified depending upon the clinical response and degree of hepatic impairment. For initiation of the extended-release tablets, give 1 tablet and adjust dosage as needed.

Dosage should be modified depending upon the clinical response and degree of renal impairment. For initiation of the extended-release tablets, give 1 tablet and adjust dosage as needed.

ADMINISTRATION

Immediate-release formulations:
Administer with a full glass of water. May be taken food or milk to minimize GI irritation.
Extended-release tablets:
Swallow whole, 1 tablet at a time, with enough water to ensure complete swallowing immediately after placing in mouth.
May be given with or without food.
Do not break, chew, crush, cut, dissolve, or split the tablets due to the risk of uncontrolled drug delivery.

STORAGE

Endocet:
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Magnacet:
– Store at controlled room temperature (between 68 and 77 degrees F)
Nalocet:
– Protect from moisture
– Store between 68 to 77 degrees F
Narvox:
– Store at controlled room temperature (between 68 and 77 degrees F)
Percocet:
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Perloxx:
– Protect from light
– Store at controlled room temperature (between 68 and 77 degrees F)
Primalev:
– Store at controlled room temperature (between 68 and 77 degrees F)
Primlev:
– Store at controlled room temperature (between 68 and 77 degrees F)
Roxicet:
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Tylox:
– Protect from moisture
– Store at room temperature (between 59 to 86 degrees F)
XARTEMIS XR:
– Store at 77 degrees F; excursions permitted to 59-86 degrees F
Xolox:
– Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

NOTE: This monograph discusses the contraindications/precautions of acetaminophen; oxycodone combination products. Clinicians may wish to consult the individual monographs for more information about each agent.

Acetaminophen; oxycodone combinations are contraindicated in patients with known acetaminophen hypersensitivity, oxycodone hypersensitivity, or opiate agonist hypersensitivity.   Acetaminophen hypersensitivity reactions are rare, but severe sensitivity reactions are possible. Although true opiate agonist hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to oxycodone should not receive other opioid agonists of the phenanthrene subclass including morphine, codeine, and hydromorphone. Use with caution in patients with sulfite hypersensitivity, as some acetaminophen; oxycodone capsules contain sodium metabisulfite and some tablet dosage formulations may as well. Sulfite may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Oxycodone is contraindicated in patients who have or are suspected of having paralytic ileus. Due to the effects of opiate agonists on the gastrointestinal tract, all forms of acetaminophen; oxycodone should be used cautiously in patients with GI disease including GI obstruction, ulcerative colitis, or pre-existing constipation. Patients with ulcerative colitis or other inflammatory bowel disease may be more sensitive to constipation caused by opiate agonists. Opiate agonists may obscure the diagnosis or clinical course in patients with an acute abdomen. The extended-release tablets may swell and become sticky when exposed to liquids such as saliva; consider the use of an alternative analgesic in patients with pre-existing esophageal stricture or dysphagia. Do not pre-soak, lick, or wet the extended-release tablet prior to ingestion, or give via feeding tubes as it may cause obstruction.

As with other opiate agonists, products containing oxycodone should be avoided in patients with severe pulmonary disease. Additionally, avoid coadministration with other CNS depressants unless no other alternatives are available, as this significantly increases the risk for respiratory depression, low blood pressure, and death. Acetaminophen; oxycodone use is contraindicated in patients with significant respiratory depression, and in patients with acute or severe asthma (e.g., status asthmaticus) or hypercarbia in unmonitored care settings or in the absence of resuscitative equipment. Receipt of moderate oxycodone doses in these patients may significantly decrease pulmonary ventilation. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to acetaminophen; oxycodone, as even usual therapeutic doses of oxycodone may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with oxycodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep apnea syndrome and/or decreased respiratory reserve. Respiratory depression, if left untreated, may cause respiratory arrest and death. Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Due to the risk of serious respiratory depression, the extended-release tablets should be reserved for patients in whom alternative treatment options (e.g., non-opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Do not use extended-release tablets on an as needed basis. Proper dosing and titration are essential; patients should be monitored for respiratory depression, particularly during the first 24—72 hours after therapy initiation or after a dose increase. Patients must be instructed to keep acetaminophen; oxycodone away from pediatric patients and others for whom the drug was not prescribed, as accidental exposure or improper use may lead to fatal respiratory depression. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

Abrupt discontinuation of prolonged oxycodone therapy can result in withdrawal symptoms. Patients who have been taking acetaminophen; oxycodone regularly and may be physically dependent should be gradually tapered off the medication to avoid a withdrawal reaction. A downward titration of 50% of the dose every 2—4 days may be used in patients taking the extended-release tablets.

Oxycodone is a strong opiate agonist; therefore, acetaminophen; oxycodone is subject to substance abuse and psychologic dependence. Addiction may occur in patients appropriately prescribed oxycodone. Patients with a previous history of substance abuse may be at increased risk of relapse if treated with acetaminophen; oxycodone. Also, patients with mental illness (e.g., major depression) or a family history of substance abuse or alcoholism may be at greater risk. Monitor patients for signs of misuse, abuse, or addiction. Abuse or misuse of the extended-release tablets by crushing, chewing, snorting, or injecting the dissolved product will lead to uncontrolled drug delivery that may be fatal. Health care professionals should not let concerns over psychologic dependence deter them from using adequate amounts of opiate agonists in the management of severe pain.

Use acetaminophen; oxycodone with caution in patients with CNS depression, toxic psychosis, head trauma, intracranial mass, or increased intracranial pressure. Opioids may aggravate these conditions and alter neurologic parameters (e.g., level of consciousness, pupillary responses). Oxycodone-induced hypoventilation can produce cerebral hypoxia, carbon dioxide retention, and raise cerebrospinal fluid pressure. Monitor for signs of drowsiness or depressed respirations.

Use acetaminophen; oxycodone with caution in patients with cardiac disease, cardiac arrhythmias, hypotension, orthostatic hypotension, or hypovolemia. Opiate agonists, such as oxycodone, induce histamine release and produce cholinergic side effects like bradycardia, peripheral vasodilation, and hypotension. These effects may produce severe hypotension in patients whose ability to maintain blood pressure has been compromised by a depleted blood volume. Orthostatic hypotension may occur.

Acetaminophen; oxycodone is classified as FDA pregnancy risk category C. No well-controlled studies in pregnant women have been performed. Some experts suggest increased risk of oxycodone if used for prolonged periods or at high doses near term. Chronic maternal use of opioids during pregnancy may result in neonatal opioid withdrawal syndrome. This syndrome can be life-threatening and includes symptoms such as poor feeding, irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, rigidity, and seizures. Neonates whose mothers have been taking oxycodone chronically may show some respiratory depression and/or withdrawal symptoms at birth or within a few days. Neonatal opioid withdrawal syndrome may be life-threatening and should be treated according to protocols developed by neonatology experts. Acetaminophen; oxycodone should not be used immediately prior to or during labor or obstetric delivery due to the potential for respiratory depression in the newborn. No overall increase in fetal mortality, as determined by pregnancy outcomes of mothers that overdosed on various amounts of acetaminophen, was apparent amongst 300 women. Treatment with acetylcysteine or methionine did not appear to affect fetal or neonatal toxicity. Of 235 babies exposed to an overdose of only acetaminophen, 168 were normal, 8 had malformations, 16 were spontaneously aborted, and 43 were electively terminated. Of 67 babies exposed to an overdose of a combination acetaminophen product, 51 were normal, 3 had malformations, 2 were spontaneously aborted (late fetal deaths), and 11 were electively terminated. None of the babies with malformations were exposed during the first trimester, but all of the spontaneous abortions and one of the late fetal deaths were subsequent to first trimester exposure.

Use caution when prescribing acetaminophen; oxycodone for mothers of breast-feeding infants. According to the manufacturer, oxycodone and acetaminophen are both distributed into breast milk, and acetaminophen; oxycodone generally should not be used by breast-feeding mothers because of the possibility of sedation and/or respiratory depression in the baby. A retrospective study compared central nervous system (CNS) depression in breast-feeing infants of mothers receiving oxycodone (n = 139), codeine (n = 210), or acetaminophen (n = 184). Symptoms of CNS depression were determined through questionnaires to the mothers. CNS depression was significantly higher in breast-fed infants exposed to oxycodone compared to acetaminophen (20.1% vs 0.5%, p < 0.0001) and was not significantly different compared to infants exposed to codeine (16.7%, p > 0.05). The doses of both oxycodone and codeine in the mothers with infants that experienced symptoms were significantly higher compared to those that did not (oxycodone median 0.4 mg/kg/day vs 0.15 mg/kg/day, p = 0.0005; codeine median 1.4 mg/kg/day vs 0.9 mg/kg/day, p < 0.001). As with all opioid-containing products, if acetaminophen; oxycodone is used by a breast-feeding mother, the infant should be monitored for sedation, respiratory depression, and changes in feeding patterns. According to the American Academy of Pediatrics (AAP), acetaminophen as maternal monotherapy has not been associated with any observable changes in nursing infants. The AAP regards acetaminophen as a maternal medicine that is usually compatible with breast feeding. Other alternative analgesics considered to be usually compatible with breast-feeding by the AAP include ibuprofen and morphine; the AAP has not evaluated the use of oxycodone in breast-feeding women. Acetaminophen; oxycodone should not be used chronically during breast-feeding as withdrawal symptoms may occur in the infant when the mother stops chronic oxycodone therapy.

Acetaminophen; oxycodone should be used cautiously in patients with renal impairment or renal failure; dosage adjustments may be required. Oxycodone can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with prostatic hypertrophy, urethral stricture, bladder obstruction or pelvic tumors. In addition, oxycodone may accumulate in these patients leading to a prolonged duration of action and potential increase in side effects. Chronic acetaminophen administration should be avoided in patients with underlying renal disease; however it may be used for episodic pain.

Acetaminophen has the potential for overdose or poisoning that can cause acute hepatic failure, at times resulting in liver transplantation or death. Most cases of hepatotoxicity are a result of exceeding maximum daily dosage limits and often involve the use of more than one acetaminophen-containing product. Acetaminophen; oxycodone should be used with caution in patients with alcoholism, chronic malnutrition, active hepatitis, or severe hypovolemia, as these patients may be at increased risk for acetaminophen-induced hepatotoxicity. In patients with chronic hepatic disease, acetaminophen can be used safely and is often preferred to nonsteroidal anti-inflammatory drugs (NSAIDs) due to the absence of platelet impairment, gastrointestinal toxicity, and nephrotoxicity. Though the half-life of acetaminophen may be prolonged, repeated dosing does not result in drug or metabolite accumulation. In addition, cytochrome P450 activity is not increased and glutathione stores are not depleted in hepatically impaired patients taking therapeutic doses, therefore toxic metabolite formation and accumulation is not altered. Although it is always prudent to use the smallest dose of acetaminophen for the shortest duration necessary, courses less than 2 weeks in length have been administered safely to adult patients with stable chronic liver disease. In patients without pre-existing hepatic impairment, hepatotoxicity may occur if the total daily dose exceeds 4,000 mg/day or more than 3 alcoholic beverages per day are consumed while taking acetaminophen. Patients and caregivers should be appropriately counseled on acetaminophen intake and reminded that all acetaminophen-containing prescription and over-the-counter products, both single-entity and combination, must be considered in the total daily dosage. Oxycodone may accumulate leading to a prolonged duration of action in patients with decreased liver function. Close monitoring is warranted to avoid respiratory depression. Guidelines for use of the extended-release tablets in patients with hepatic impairment recommend initiating treatment at 50% of the normal starting dosage.

Geriatric and debilitated patients are at particular risk for respiratory depression when given large initial doses of oxycodone or when oxycodone is given in conjunction with other agents that depress respiration. Special precaution should be given when determining the dosing amount and frequency of dosing for geriatric patients, since clearance of oxycodone may be slightly reduced in this patient population when compared to younger adults. Monitor patients taking acetaminophen; oxycodone closely, particularly at treatment initiation, with dose titration, or when the drug is given concurrently with other drugs that depress respiration. According to the Beers Criteria, opiate agonists are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these populations, with the exception of pain management due to recent fractures or joint replacement, since opiates can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opiate must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk.

Acetaminophen; oxycodone is used in pediatric patients with moderate to severe pain in clinical practice; however, safety and efficacy have not been established in neonates, infants, children, or adolescents.   Consider pediatric-specific precautions before use. Neonates and infants < 6 months of age have highly variable clearance of opiate agonists. Therefore, infants younger than 6 months of age may be given opiate agonists but must be closely monitored for apnea until 24 hours after their last dose. Clinical practice guidelines suggest close monitoring of children up to 1 year of age.

Patients with G6PD deficiency who overdose with acetaminophen may be at increased risk for drug-induced hemolysis. Practitioners should be aware of this potential complication and monitor at-risk patients for signs and symptoms of hemolysis while taking acetaminophen; oxycodone. Conflicting data exists on whether therapeutic doses of acetaminophen can cause hemolysis in G6PD deficient patients. However, a direct cause and effect relationship has not been well established, and therefore, therapeutic doses are generally considered safe in this population.

Symptoms of acute infection (e.g., fever, pain) can be masked during treatment with acetaminophen; oxycodone in patients who have bone marrow suppression or immunosuppression.

Any patient receiving acetaminophen; oxycodone should be warned about the possibility of sedation and to use caution when driving or operating machinery.

Oxycodone can increase the tone of the biliary tract causing spasms, especially in the sphincter of Oddi. Acetaminophen; oxycodone should be used cautiously in patients with biliary tract disease or acute pancreatitis. Biliary effects of opioids may result in elevations of plasma amylase concentration.

Use acetaminophen; oxycodone with caution in patients with adrenal insufficiency (i.e., Addison’s disease), hypothyroidism, or myxedema. Such patients may be at increased risk of adverse events. Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH); however, the thyroid stimulating hormone may be either stimulated or inhibited by opioids. Rarely, adrenal insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency. In addition, chronic opioid use may lead to symptoms of hypogonadism, resulting from changes in the hypothalamic-pituitary-gonadal axis. Monitor patients for symptoms of opioid-induced endocrinopathy, particularly those receiving a daily dose equivalent to 100 mg or more of morphine. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.