PERCODAN 10/325mg.

BOXED WARNING

Aspirin; oxycodone use is contraindicated in patients with significant respiratory depression, acute or severe asthma (e.g., status asthmaticus), or hypercapnia in unmonitored care settings or in the absence of resuscitative equipment.[29670] Additionally, avoid coadministration with other CNS depressants when possible as this significantly increases the risk for respiratory depression, low blood pressure, and death.[61143] As with other opioid agonists, oxycodone should be avoided in patients with severe pulmonary disease. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxycodone, as even usual therapeutic doses 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. Oxycodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention. 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. Use of aspirin; oxycodone is also contraindicated in patients with the syndrome of asthma, rhinitis, and nasal polyps; such patients have an increased risk of severe urticaria, angioedema, and bronchospasm. Avoid aspirin in patients with asthma who have a history of aspirin-induced acute bronchospasm.[29670]

Aspirin; oxycodone exposes patients and other users to the risks of opioid addiction and substance abuse/misuse, which has the potential for overdose or poisoning. Oxycodone is subject to psychologic dependence (i.e., drug addiction) or criminal diversion. Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk for harm. Patients with a previous history of substance abuse may be at increased risk of relapse if treated with oxycodone. Abuse and addiction are separate and distinct from physiologic dependence and tolerance. Physicians should be aware that psychologic dependence may not be accompanied by concurrent tolerance and symptoms of physiologic dependence. In addition, abuse of opiate agonists can occur in the absence of true psychologic dependence and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. 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. Patients should also be counseled regarding misconceptions regarding the use of opiate agonists for pain management. Oxycodone is not approved for the management of substance abuse (alcohol or drug dependence). The use of oxycodone in patients with alcohol or drug dependence, either active or in remission, is for the treatment of pain requiring opiate agonist analgesia. Patients receiving opiate substitution therapy for opiate substance abuse will have increased tolerance to the analgesic effects of opiate agonists used for acute pain, and will require higher and more frequent dosing to control their pain. Opiate substitution therapy does not adequately treat pain.

Accidental exposure to even one dose of aspirin; oxycodone, especially by children, can result in fatal overdose.

Avoid aspirin, ASA; oxycodone use during pregnancy, especially in the third trimester.[57732] Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxycodone. In animal studies with rats and rabbits, no embryo-fetal toxicity was detected when oxycodone was given during organogenesis at doses 0.5- to 15-times the adult human dose of 160 mg/day. In a pre- and postnatal study in rats, oxycodone given during gestation and lactation at a dose approximately 0.4 times an adult human dose of 160 mg/day was not associated with any long-term developmental or reproductive adverse effects in pups; however, pup weight was transiently decreased during lactation and the early post-weaning period. No drug-related effects on reproductive performance in female rats were observed. Published data with rats indicate that oxycodone may result in neurobehavioral effects, including altered stress response, increased anxiety-like behavior, and altered learning and memory, in offspring when given at clinically relevant doses and below.[60745] Salicylates readily cross the placenta and by inhibiting prostaglandin synthesis, may cause constriction of ductus arteriosus, resulting in pulmonary hypertension and increased fetal mortality, and possibly other untoward fetal effects. Aspirin use in pregnancy can also result in an alteration in maternal and neonatal hemostasis mechanisms. Maternal aspirin use during later stages of pregnancy may cause low birth weight, increased incidence of intracranial hemorrhage in premature infants, stillbirths, and neonatal death. Aspirin, ASA; oxycodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because opioids can prolong labor through actions which temporarily decrease the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which may shorten labor. Opioid agonists may also cause respiratory depression in the newborn. Monitor neonates exposed to opioids during labor for signs of excess sedation and respiratory depression.[57732] Full doses of aspirin administered to pregnant women near obstetric delivery may cause prolonged labor or bleeding. Further, prolonged maternal use of opioids, such as oxycodone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.[57732]

DEA CLASS

Rx, schedule II

DESCRIPTION

Combination product used to treat moderate to severe pain. Aspirin is an acetylated salicylate analgesic; oxycodone is an opiate analgesic. The combination produces a greater analgesic effect than either drug alone.

COMMON BRAND NAMES

Endodan, Percodan

HOW SUPPLIED

Endodan/Oxycodone Hydrochloride, Aspirin/Oxycodone Hydrochloride, Oxycodone Terephthalate, Aspirin/Oxycodone, Aspirin/Percodan Oral Tab: 4.5-0.38-325mg, 4.8355-325mg

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

Aspirin 4 grams (12 tablets)/day PO. There is no maximum dose of oxycodone; however, careful titration of oxycodone, especially in opiate-naive patients, is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.

Aspirin 4 grams (12 tablets)/day PO. There is no maximum dose of oxycodone; however, careful titration of oxycodone, especially in opiate-naive patients, is required until tolerance develops to some of the side effects (i.e., drowsiness and respiratory depression). Individualize dosage carefully.

Not recommended.

Not recommended.

Not recommended.

DOSING CONSIDERATIONS

Do not use in patients with severe hepatic impairment. Dosage should be modified for patients with mild or moderate hepatic impairment depending upon the clinical response and degree of hepatic impairment. No quantitative recommendations are available.

CrCl >= 10 mL/min: Dosage should be modified for patients with mild or moderate renal impairment depending upon the clinical response and degree of renal impairment. No quantitative recommendations are available.
CrCl < 10 mL/min: Do not use.

ADMINISTRATION

Administer with a full glass of water and food or milk to minimize GI irritation.

STORAGE

Endodan:
– Store at controlled room temperature (between 68 and 77 degrees F)
Percodan:
– Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

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

Aspirin; ASA; oxycodone is contraindicated in patients with salicylate hypersensitivity, opioid hypersensitivity, NSAID hypersensitivity, or hypersensitivity to any other product components. The risk of cross-sensitivity with other nonsteroidal anti-inflammatory drugs is significantly greater with aspirin than with other salicylates. Although true opiate agonist hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to oxycodone should not receive aspirin; oxycodone or other opioid agonists of the phenanthrene subclass, including codeine, hydromorphone, and morphine.

Aspirin; oxycodone use is contraindicated in patients with significant respiratory depression, acute or severe asthma (e.g., status asthmaticus), or hypercapnia in unmonitored care settings or in the absence of resuscitative equipment.[29670] Additionally, avoid coadministration with other CNS depressants when possible as this significantly increases the risk for respiratory depression, low blood pressure, and death.[61143] As with other opioid agonists, oxycodone should be avoided in patients with severe pulmonary disease. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to oxycodone, as even usual therapeutic doses 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. Oxycodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention. 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. Use of aspirin; oxycodone is also contraindicated in patients with the syndrome of asthma, rhinitis, and nasal polyps; such patients have an increased risk of severe urticaria, angioedema, and bronchospasm. Avoid aspirin in patients with asthma who have a history of aspirin-induced acute bronchospasm.[29670]

As opioid agonist are contraindicated in such patients, aspirin; oxycodone use is contraindicated in patients with known or suspected paralytic ileus. Further, aspirin; oxycodone should be used cautiously in patients with GI disease, including GI obstruction, peptic ulcer disease, ulcerative colitis, or pre-existing constipation. Opiate agonists may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Patients with acute ulcerative colitis or other inflammatory bowel disease may be more sensitive to the constipating effects of opiate agonists. Although opiate agonists may exacerbate cases of diarrhea secondary to poisoning or infectious diarrhea, antimotility agents have been used successfully in these patients. If possible, opiate agonists should not be given until the toxic substance has been eliminated. Aspirin can induce gastric or intestinal ulceration that can occasionally be accompanied by anemia from the resultant blood loss. Gastric damage by aspirin is due to local irritation of the drug in addition to inhibition of the biosynthesis of gastric prostaglandins. Patients should not be treated with aspirin-oxycodone if they consume 3 or more alcoholic beverages per day because of the potential increased risk for gastrointestinal bleeding.

Aspirin inhibits platelet aggregation by irreversibly suppressing the synthesis of platelet thromboxane A2. The use of aspirin; oxycodone is contraindicated in patients with hemophilia. Aspirin; oxycodone should be avoided or used cautiously in patients with underlying anemia. As aspirin inhibits platelet aggregation and increases bleeding time, aspirin should be administered cautiously to patients with preexisting thrombocytopenia or coagulopathy. It should also be avoided in patients with aplastic anemia or pancytopenia or other forms of bone marrow suppression. Aspirin; oxycodone should be discontinued at least 1 week before surgery to minimize postoperative bleeding. Finally, intramuscular injections should be administered cautiously to patients receiving aspirin; oxycodone. Intramuscular injections may cause bleeding, bruising, or hematomas due to aspirin-induced inhibition of platelet aggregation.

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

Aspirin; oxycodone is contraindicated in children or teenagers with viral infection with or without fever due to the risk of Reye’s syndrome. Aspirin has been associated with the occurrence of Reye’s syndrome when given to children with varicella (chickenpox) or influenza (flu). Although a causal relationship has not been confirmed, most authorities advise against the use of aspirin in children with chickenpox, flu, or other viral infection. Opiate agonists are may be used in children for moderate to severe pain. Paradoxical excitement can occur in children taking opiate agonists.

Because salicylates may cause or aggravate hemolysis in patients with G6PD deficiency, some reference texts state that aspirin-containing products, such as aspirin; oxycodone, should be used cautiously in these patients. If hemolytic anemia occurs in patients receiving aspirin, it almost always occurs in G6PD-deficient individuals. It appears that aspirin can induce hemolysis at therapeutic concentrations if other oxidative stressors are present. Otherwise, hemolysis only occurs at much higher concentrations.

Abrupt discontinuation of prolonged aspirin; oxycodone therapy can result in withdrawal symptoms. Patients should be gradually tapered off aspirin; oxycodone to avoid a withdrawal reaction. Generally, a 50% decrease every 1—2 days of the daily aspirin; oxycodone dose will prevent withdrawal symptoms in patients who have been receiving > 60 mg/day of oxycodone.

Aspirin; oxycodone exposes patients and other users to the risks of opioid addiction and substance abuse/misuse, which has the potential for overdose or poisoning. Oxycodone is subject to psychologic dependence (i.e., drug addiction) or criminal diversion. Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk for harm. Patients with a previous history of substance abuse may be at increased risk of relapse if treated with oxycodone. Abuse and addiction are separate and distinct from physiologic dependence and tolerance. Physicians should be aware that psychologic dependence may not be accompanied by concurrent tolerance and symptoms of physiologic dependence. In addition, abuse of opiate agonists can occur in the absence of true psychologic dependence and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. 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. Patients should also be counseled regarding misconceptions regarding the use of opiate agonists for pain management. Oxycodone is not approved for the management of substance abuse (alcohol or drug dependence). The use of oxycodone in patients with alcohol or drug dependence, either active or in remission, is for the treatment of pain requiring opiate agonist analgesia. Patients receiving opiate substitution therapy for opiate substance abuse will have increased tolerance to the analgesic effects of opiate agonists used for acute pain, and will require higher and more frequent dosing to control their pain. Opiate substitution therapy does not adequately treat pain.

Patients with head trauma or with increased intracranial pressure should be given aspirin; oxycodone with extreme caution, because, in addition to potential bleeding complications, this combination can make it difficult to evaluate neurologic parameters. Hypoventilation due to the oxycodone component can produce cerebral hypoxia and raise CSF pressure, exaggerating the injury.

Geriatric patients are more sensitive to the analgesic effects of opiate agonists, such as aspirin; oxycodone, as they may be more susceptible to adverse reactions from opiate agonists; especially sedation and respiratory depression probably as a result of altered distribution of the drug and decreased elimination. Initial doses of opiate agonists may need to be reduced and doses should be carefully titrated taking into account analgesic effects and adverse reactions. The older adult receiving high doses of aspirin daily is also more likely to experience GI side effects, including ulceration or bleeding. According to the Beers Criteria, aspirin is a potentially inappropriate medication (PIM) in geriatric patients. Aspirin may cause new or worsening gastric or duodenal ulcers and there is an increased risk of GI bleeding and peptic ulcer disease in high risk groups including those above 75 years of age, or those taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet medications. Therefore, the Beers expert panel recommends avoiding chronic use of aspirin doses above 325 mg/day in high risk patients, unless other alternatives are not effective and a gastro-protective agent can be used. In addition, aspirin doses above 325 mg/day should be avoided in patients with a history of gastric or duodenal ulcers, unless other alternatives are not effective and a gastro-protective agent can be used. The risk of ulcers, gross bleeding, or perforation is cumulative with continued use. The use of a gastro-protective agent, like a proton-pump inhibitor or misoprostol reduces, but does not eliminate, GI risks. The Panel also recommends avoiding NSAIDs in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: heart failure (potential to promote fluid retention and exacerbate the condition) or chronic kidney disease Stage IV or less (CrCl less than 30 mL/min) (may increase the risk of acute kidney injury and cause a further decline of renal function). The Panel states that opiate agonists are 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.

Opiate agonists, such as oxycodone, produce cholinergic side effects (by stimulating medullary vagal nuclei) causing bradycardia and vasovagal syncope, and induce the release of histamine, causing peripheral vasodilatation and orthostatic hypotension. These effects can cause problems in patients with cardiac disease. Aspirin-oxycodone should be used with caution in patients with cardiac arrhythmias, hypotension, or hypovolemia.

Liver function should be monitored in patients with preexisting hepatic disease in order to prevent reversible, dose-dependent aspirin-induced hepatotoxicity and hypoprothrombinemia. Patients with vitamin K deficiency require close monitoring during aspirin therapy. Oxycodone may accumulate leading to a prolonged duration of action in patients with decreased liver function. Avoid aspirin; oxycodone in patients with severe hepatic insufficiency, and use care when aspirin; oxycodone is used in patients with milder hepatic impairment. In acute situations, patients require close monitoring to avoid excessive toxicity. Patients with chronic liver disease may require less frequent dosing intervals.

Avoid aspirin; oxycodone in patients with severe renal failure, which is defined as a glomerular filtration rate less than 10 mL/minute. Aspirin; oxycodone should be used cautiously in patients with milder renal impairment; dosage adjustments may be required. Aspirin may cause reversible decreases in renal blood flow and glomerular filtration rate in patients with renal disease or systemic lupus erythematosus (SLE). 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.

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

Use 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.

Accidental exposure to even one dose of aspirin; oxycodone, especially by children, can result in fatal overdose.

Avoid aspirin, ASA; oxycodone use during pregnancy, especially in the third trimester.[57732] Pregnancy exposure data are insufficient to inform a drug-associated risk of birth defects or miscarriage with oxycodone. In animal studies with rats and rabbits, no embryo-fetal toxicity was detected when oxycodone was given during organogenesis at doses 0.5- to 15-times the adult human dose of 160 mg/day. In a pre- and postnatal study in rats, oxycodone given during gestation and lactation at a dose approximately 0.4 times an adult human dose of 160 mg/day was not associated with any long-term developmental or reproductive adverse effects in pups; however, pup weight was transiently decreased during lactation and the early post-weaning period. No drug-related effects on reproductive performance in female rats were observed. Published data with rats indicate that oxycodone may result in neurobehavioral effects, including altered stress response, increased anxiety-like behavior, and altered learning and memory, in offspring when given at clinically relevant doses and below.[60745] Salicylates readily cross the placenta and by inhibiting prostaglandin synthesis, may cause constriction of ductus arteriosus, resulting in pulmonary hypertension and increased fetal mortality, and possibly other untoward fetal effects. Aspirin use in pregnancy can also result in an alteration in maternal and neonatal hemostasis mechanisms. Maternal aspirin use during later stages of pregnancy may cause low birth weight, increased incidence of intracranial hemorrhage in premature infants, stillbirths, and neonatal death. Aspirin, ASA; oxycodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because opioids can prolong labor through actions which temporarily decrease the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which may shorten labor. Opioid agonists may also cause respiratory depression in the newborn. Monitor neonates exposed to opioids during labor for signs of excess sedation and respiratory depression.[57732] Full doses of aspirin administered to pregnant women near obstetric delivery may cause prolonged labor or bleeding. Further, prolonged maternal use of opioids, such as oxycodone, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.[57732]

Breast-feeding is not recommended during aspirin, ASA; oxycodone therapy. Oxycodone is distributed into breast milk at varying degrees depending upon the dose. There is no information available on the effects of oxycodone on milk production. Monitor infants who are exposed to oxycodone through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants if oxycodone or breast-feeding is discontinued by the mother.[57732] A retrospective study compared central nervous system (CNS) depression in breast-feeding infants of mothers receiving oxycodone (n = 139) or acetaminophen (n = 184). Symptoms of CNS depression were determined through questionnaires completed by the mothers. CNS depression was significantly higher in breast-fed infants exposed to oxycodone compared to acetaminophen (20.1% vs. 0.5%, p less than 0.0001). The median dose of oxycodone in the mothers with infants that experienced symptoms was significantly higher compared to those that did not (0.4 mg/kg/day vs. 0.15 mg/kg/day, p = 0.0005).[45800] Salicylic acid is excreted in breast milk. Adverse effects on platelet function may occur in the infant. The risk of Reye Syndrome caused by salicylate in breast milk is unknown. Consider the developmental and health benefits of breast-feeding along with the mother’s clinical need for aspirin, ASA; oxycodone and any potential adverse effects on the breast-fed infant from aspirin, ASA; oxycodone or the underlying maternal condition.[57732] Alternative analgesics considered to be usually compatible with breast-feeding by previous American Academy of Pediatrics (AAP) recommendations include acetaminophen, ibuprofen, and morphine.[27500]

Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible. Monitor patients for symptoms of opioid-induced endocrinopathy. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.