Oxycodone and Aspirin

Oxycodone and aspirin tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse, with opioids, which can occur at any dosage or duration (see WARNINGS ), reserve oxycodone and aspirin tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics)

• Have not been tolerated, or are not expected to be tolerated,
• Have not provided adequate analgesia, or are not expected to provide adequate analgesia Oxycodone and Aspirin tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

Oxycodone and aspirin tablets are contraindicated in patients with:

• Significant respiratory depression (see WARNINGS )
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see WARNINGS )
• Known or suspected gastrointestinal obstruction, including paralytic ileus (see WARNINGS )
• Hypersensitivity to oxycodone or aspirin, (e.g. angioedema) (see WARNINGS )
• Patients with hemophilia.
• Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye syndrome (see WARNINGS )

Addiction, Abuse, and Misuse Oxycodone and aspirin tablets contain Oxycodone, a Schedule II controlled substance. As an opioid, oxycodone and aspirin tablets exposes users to the risks of addiction, abuse, and misuse (see DRUG ABUSE AND DEPENDENCE ). Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxycodone and aspirin tablets. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing oxycodone and aspirin tablets, and reassess all patients receiving oxycodone and aspirin tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as oxycodone and aspirin tablets but use in such patients necessitates intensive counseling about the risks and proper use of oxycodone and aspirin tablets along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS , DOSAGE AND ADMINISTRATION ]. Opioids are sought by nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing oxycodone and aspirin tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and proper disposal of unused drug (see PRECAUTIONS; Information for Patients /Caregivers). Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status (see OVERDOSAGE ). Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of oxycodone and aspirin tablets, the risk is greatest during the initiation of therapy or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of oxycodone and aspirin tablets are essential (see DOSAGE AND ADMINISTRATION ). Overestimating the oxycodone and aspirin tablets when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of even one dose of oxycodone and aspirin tablets, especially by children can result in respiratory depression and death due to an overdose of oxycodone. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see PRECAUTIONS ; Information for Patients/Caregivers ]. Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper (see DOSAGE AND ADMINISTRATION ). Patients Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with oxycodone and aspirin tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see PRECAUTIONS ; Information for Patients/Caregivers ]. Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of other CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone [see WARNINGS , PRECAUTIONS ; Information for Patients/Caregivers , OVERDOSAGE ]. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of oxycodone and aspirin tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see PRECAUTIONS ; Drug Interactions ]. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS , DOSAGE AND ADMINISTRATION ]. Advise both patient and caregivers about the risks of respiratory depression and sedation when oxycodone and aspirin tablets is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse; and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see PRECAUTIONS ; Drug Interactions ]. […]

General Aspirin has been associated with elevated hepatic enzymes, blood urea nitrogen and serum creatinine, hyperkalemia, proteinuria, and prolonged bleeding time. Hemorrhage Aspirin may increase the likelihood of hemorrhage due to its effect on the gastric mucosa and platelet function (prolongation of bleeding time). Salicylates should be used with caution in the presence of peptic ulcer or coagulation abnormalities. Ambulatory Surgery and Postoperative Use Oxycodone and other morphine-like opioids have been shown to decrease bowel motility. Ileus is a common postoperative complication, especially after intra-abdominal surgery with use of opioid analgesia. Caution should be taken to monitor for decreased bowel motility in postoperative patients receiving opioids. Standard supportive therapy should be implemented. Information for Patients/Caregivers Advise the patient to read the FDA-approved patient labeling (Medication Guide). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store oxycodone and aspirin tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving oxycodone and aspirin tablets unsecured can pose a deadly risk to others in the home (see WARNINGS , DRUG ABUSE AND DEPENDENCE ). Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused oxycodone and aspirin tablets should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines. Addiction, Abuse, and Misuse Inform patients that the use of oxycodone and aspirin tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death (see WARNINGS ). Instruct patients not to share oxycodone and aspirin tablets with others and to take steps to protect oxycodone and aspirin tablets from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting oxycodone and aspirin tablets or when the dosage is increased, and that it can occur even at recommended dosages. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see WARNINGS ]. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death (see WARNINGS ). Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if oxycodone and aspirin tablets is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider (see WARNINGS , PRECAUTIONS ; Drug Interactions ). Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with oxycodone and aspirin tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) [see WARNINGS , DOSAGE AND ADMINISTRATION ]. Educate patients and caregivers on how to recognize the signs and symptoms of an overdose. Explain to patients and caregivers that naloxone’s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered [see OVERDOSAGE ]. If naloxone is prescribed, also advise patients and caregivers:

• How to treat with naloxone in the event of an opioid overdose
• To tell family and friends about their naloxone and to keep it in a place where family and friends can access it in an emergency
• To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do. Hyperalgesia and Allodynia Inform patients and caregivers not to increase opioid dosage without first consulting a clinician. Advise patients to seek medical attention if they experience symptoms of hyperalgesia, including sensitivity to pain, or new pain [see WARNINGS ; ADVERSE REACTIONS ]. Serotonin Syndrome Inform patients that oxycodone and aspirin tablets could cause a rare but potentially life-threatening condition called serotonin syndrome resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications. MAOI Interaction Inform patients to avoid taking oxycodone and aspirin tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking oxycodone and aspirin tablets (see PRECAUTIONS ; Drug Interactions ). Important Administration Instructions Instruct patients how to properly take oxycodone and aspirin tablets. The usual dosage is one tablet every 6 hours as needed for pain. The maximum daily dose of aspirin should not exceed 4 grams (see DOSAGE AND ADMINISTRATION , PRECAUTIONS ) Important Discontinuation Instructions In order to avoid developing withdrawal symptoms, instruct patients not to discontinue oxycodone and aspirin tablets without first discussing a tapering plan with the prescriber (see DOSAGE AND ADMINISTRATION ). Driving or Operating Heavy Machinery Inform patients that oxycodone and aspirin tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see WARNINGS ]. Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see ADVERSE REACTIONS , CLINICAL PHARMACOLOGY ]. Adrenal Insufficiency Inform patients that oxycodone and aspirin tablets could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see WARNINGS ]. Hypotension Inform patients that oxycodone and aspirin tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position). Anaphylaxis Inform patients that anaphylaxis have been reported with ingredients contained in oxycodone and aspirin tablets. Advise patients how to recognize such a reaction and when to seek medical attention (see CONTRAINDICATIONS , ADVERSE REACTIONS ). […]

The following serious adverse reactions are described, or described in greater detail, in other sections:

• Addiction, Abuse, and Misuse (see WARNINGS )
• Life-Threatening Respiratory Depression (see WARNINGS )
• Neonatal Opioid Withdrawal Syndrome (see WARNINGS )
• Opioid-Induced Hyperalgesia and Allodynia [see WARNINGS ]
• Interactions with Benzodiazepines and Other CNS Depressants (see WARNINGS )
• Adrenal Insufficiency (see WARNINGS )
• Severe Hypotension (see WARNINGS )
• Gastrointestinal Adverse Reactions (see WARNINGS )
• Seizures (see WARNINGS )
• Withdrawal (see WARNINGS ) Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Serious adverse reactions that may be associated with oxycodone and aspirin tablet use include, apnea, circulatory depression, hypotension, respiratory arrest, respiratory depression, and shock (see OVERDOSAGE ). The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation and pruritus. Aspirin may increase the likelihood of hemorrhage due to its effect on the gastric mucosa and platelet function. Furthermore, aspirin has the potential to cause anaphylaxis in hypersensitive patients as well as angioedema especially in patients with chronic urticaria. Other adverse reactions due to aspirin use include anorexia, reversible hepatotoxicity, leukopenia, thrombocytopenia, purpura, decreased plasma iron concentration, and shortened erythrocyte survival time. Postmarketing Experience The following adverse reactions have been identified during post approval use of oxycodone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The adverse reactions obtained from postmarketing experiences with oxycodone and aspirin tablets are listed by organ system and in decreasing order of severity and/or frequency as follows: Body as a Whole allergic reaction, malaise, asthenia, headache, anaphylaxis, fever, hypothermia, thirst, increased sweating, accident, accidental overdose, non-accidental overdose. Cardiovascular tachycardia, dysrhythmias, hypotension, orthostatic hypotension, bradycardia, palpitations Central and Peripheral Nervous System stupor, paresthesia, agitation, cerebral edema, coma, confusion, dizziness, headache, subdural or intracranial hemorrhage, lethargy, seizures, anxiety, mental impairment Fluid and Electrolyte dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis Gastrointestinal hemorrhagic gastric/duodenal ulcer, gastric/peptic ulcer, dyspepsia, abdominal pain, diarrhea, eructation, dry mouth, gastrointestinal bleeding, intestinal perforation, nausea, vomiting, transient elevations of hepatic enzymes, hepatitis, Reye syndrome, pancreatitis, intestinal obstruction, ileus Hearing and Vestibular hearing loss, tinnitus. Patients with high frequency loss may have difficulty perceiving tinnitus. In these patients, tinnitus cannot be used as a clinical indicator of salicylism. Hematologic unspecified hemorrhage, purpura, reticulocytosis, prolongation of prothrombin time, disseminated intravascular coagulation, ecchymosis, thrombocytopenia Hypersensitivity acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction Metabolic and Nutritional hypoglycemia, hyperglycemia, acidosis, alkalosis Musculoskeletal rhabdomyolysis Ocular miosis, visual disturbances, red eye Psychiatric drug dependence, drug abuse, somnolence, depression, nervousness, hallucination Reproductive prolonged pregnancy and labor, stillbirths, lower birth weight infants, antepartum and postpartum bleeding, closure of patent ductus arteriosis Respiratory System bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema Skin and Appendages urticaria, rash, flushing, exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE). Urogenital interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention Serotonin syndrome Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis Anaphylaxis has been reported with ingredients contained in oxycodone and aspirin tablets. Androgen deficiency Cases of androgen deficiency have occurred with the use of opioids for an extended period of time (see CLINICAL PHARMACOLOGY ). Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ] Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids . Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

Drug -Drug Interactions (see PRECAUTIONS) Inhibitors of CYP3A4 Since the CYP3A4 isoenzyme plays a major role in the metabolism of oxycodone and aspirin tablets, drugs that inhibit CYP3A4 activity, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may cause decreased clearance of oxycodone, which could lead to an increase in oxycodone plasma concentrations. A published study showed that the co-administration of the antifungal drug, voriconazole, increased oxycodone AUC and Cmax by 3.6 and 1.7 fold, respectively. The expected clinical results would be increased or prolonged opioid effects. Inducers of CYP450 CYP450 inducers, such as rifampin, carbamazepine, and phenytoin, may induce the metabolism of oxycodone, may cause increased clearance of the drug which could lead to a decrease in oxycodone plasma concentrations. A published study showed that the co-administration of rifampin, a drug metabolizing enzyme inducer, decreased oxycodone (oral) AUC and Cmax by 86% and 63% respectively. The expected clinical results would be lack of efficacy or, possibly, development of abstinence syndrome in a patient who had developed physical dependence to oxycodone. Induction of CYP3A4 may be of greatest importance given oxycodone’s metabolic pathways.

Drug/Drug Interactions with Aspirin Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to its indirect effect on the renin-angiotensin conversion pathway. Acetazolamide: Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide (and toxicity) due to competition at the renal tubule for secretion. Anticoagulant Therapy (Heparin and Warfarin): Patients on anticoagulation therapy are at increased risk for bleeding because of drug-drug interactions and the effect on platelets. Aspirin can displace warfarin from protein binding sites, leading to prolongation of both the prothrombin time and the bleeding time. Aspirin can increase the anticoagulant activity of heparin, increasing bleeding risk. Anticonvulsants: Salicylate can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels. Beta Blockers: The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow, and salt and fluid retention. Diuretics: The effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. Methotrexate: Aspirin may enhance the serious side and toxicity of methotrexate due to displacement from its plasma protein binding sites and/or reduced renal clearance. Nonsteroidal Anti-inflammatory Drugs (NSAIDs): The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. Aspirin may enhance the serious side effects and toxicity of ketorolac, due to displacement from its plasma protein binding sites and/or reduced renal clearance. Oral Hypoglycemics Agents: Aspirin may increase the serum glucose-lowering action of insulin and sulfonylureas leading to hypoglycemia. Uricosuric Agents: Salicylates antagonize the uricosuric action of probenecid or sulfinpyrazone.

Risk Summary Use of opioid analgesics for extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome (see WARNINGS ). Available data with oxycodone and aspirin tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Reproduction studies in rats and rabbits demonstrated that oral administration of oxycodone was not teratogenic or embryo-fetal toxic. In several published studies, treatment of pregnant rats with oxycodone at clinically relevant doses and below, resulted in neurobehavioral effects in offspring [see Data] . Based on animal data, advise pregnant women of the potential risk to a fetus. Use of NSAIDs, including aspirin, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of oxycodone and aspirin tablets use between about 20 and 30 weeks of gestation, and avoid oxycodone and aspirin tablets use at about 30 weeks of gestation and later in pregnancy [see WARNINGS; Fetal Toxicity ] . Premature Closure of Fetal Ductus Arteriosus: Use of NSAIDs, including aspirin, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as aspirin, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20% respectively. Clinical Considerations Fetal/Neonatal adverse reactions: Use of opioid analgesics for extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome, and manage accordingly (see WARNINGS ). Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including oxycodone and aspirin tablets, can cause premature closure of the fetal ductus arteriosus [see WARNINGS; Fetal Toxicity ] . Oligohydramnios/Neonatal Renal Impairment: If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If oxycodone and aspirin tablets treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue oxycodone and aspirin tablets and follow up according to clinical practice [see WARNINGS; Fetal Toxicity ] .

Oxycodone and aspirin tablets should not be administered to pediatric patients. Reye Syndrome is a rare but serious disease which can follow flu or chicken pox in children and teenagers. While the cause of Reye Syndrome is unknown, some reports claim aspirin (or salicylates) may increase the risk of developing this disease.

Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of oxycodone and aspirin tablets slowly in geriatric patients and frequently reevaluate the patients for signs of central nervous system and respiratory depression. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. Hepatic Impairment In a pharmacokinetic study of oxycodone in patients with end-stage liver disease, oxycodone plasma clearance decreased and the elimination half-life increased. Care should be exercised when oxycodone is used in patients with hepatic impairment. Avoid aspirin in patients with severe hepatic impairment. Renal Impairment In a study of patients with end stage renal impairment, mean elimination half-life of oxycodone was prolonged in uremic patients due to increased volume of distribution and reduced clearance. Oxycodone should be used with caution in patients with renal impairment. Avoid aspirin in patients with severe renal impairment (glomerular filtration rate less than 10 mL/minute).

Oxycodone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with oxycodone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action of oxycodone is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug. Aspirin (acetylsalicylic acid) works by inhibiting the body’s production of prostaglandins, including prostaglandins involved in inflammation. Prostaglandins cause pain sensations by stimulating muscle contractions and dilating blood vessels throughout the body. In the CNS, aspirin works on the hypothalamus heat-regulating center to reduce fever, however, other mechanisms may be involved.