Source: FDA, National Drug Code (US) Revision Year: 2024
Oxycodone hydrochloride and acetaminophen oral solution is contraindicated in patients with:
Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with oxycodone hydrochloride and acetaminophen oral solutions of different concentrations, when prescribing, dispensing, and administering oxycodone hydrochloride and acetaminophen oral solution. Ensure that the dose is communicated clearly and dispensed accurately. Always use a calibrated measuring device when administering oxycodone hydrochloride and acetaminophen oral solution to ensure the dose is measured and administered accurately.
Oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a Schedule II controlled substance. As an opioid, oxycodone hydrochloride and acetaminophen oral solution 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 hydrochloride and acetaminophen oral solution. 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 hydrochloride and acetaminophen oral solution, and monitor all patients receiving oxycodone hydrochloride and acetaminophen oral solution 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 hydrochloride and acetaminophen oral solution, but use in such patients necessitates intensive counseling about the risks and proper use of oxycodone hydrochloride and acetaminophen oral solution along with intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing oxycodone hydrochloride and acetaminophen oral solution. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the 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.
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:
To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.
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 hydrochloride and acetaminophen oral solution, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of oxycodone hydrochloride and acetaminophen oral solution.
To reduce the risk of respiratory depression, proper dosing and titration of oxycodone hydrochloride and acetaminophen oral solution are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the oxycodone hydrochloride and acetaminophen oral solution dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of oxycodone hydrochloride and acetaminophen oral solution, especially by children, can result in respiratory depression and death due to an overdose of oxycodone hydrochloride and acetaminophen oral solution.
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].
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 hydrochloride and acetaminophen oral solution. 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; Addiction, Abuse, and Misuse, Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants; PRECAUTIONS; Information for Patients/Caregivers].
Prolonged use of oxycodone hydrochloride and acetaminophen oral solution during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see PRECAUTIONS; Information for Patients/Caregivers, Pregnancy].
Concomitant use of oxycodone hydrochloride and acetaminophen oral solution with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone hydrochloride and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see WARNINGS], particularly when an inhibitor is added after a stable dose of oxycodone hydrochloride and acetaminophen oral solution is achieved . Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in oxycodone hydrochloride and acetaminophen oral solution-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using oxycodone hydrochloride and acetaminophen oral solution with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in oxycodone hydrochloride and acetaminophen oral solution-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of oxycodone hydrochloride and acetaminophen oral solution until stable drug effects are achieved [see PRECAUTIONS; Drug Interactions].
Concomitant use of oxycodone hydrochloride and acetaminophen oral solution with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone hydrochloride plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone hydrochloride. When using oxycodone hydrochloride and acetaminophen oral solution with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see PRECAUTIONS; Drug Interactions].
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of oxycodone hydrochloride and acetaminophen oral solution with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). 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. Follow patients closely for signs and symptoms of respiratory depression and sedation.
If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS; Life-Threatening Respiratory Depression, DOSAGE AND ADMINISTRATION; Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose].
Advise both patients and caregivers about the risks of respiratory depression and sedation when oxycodone hydrochloride and acetaminophen oral solution 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.
The use of oxycodone hydrochloride and acetaminophen oral solution in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease: Oxycodone hydrochloride and acetaminophen oral solution-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of oxycodone hydrochloride and acetaminophen oral solution [see WARNINGS; Life Threatening Respiratory Depression].
Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see WARNINGS; Life Threatening Respiratory Depression].
Monitor such patients closely, particularly when initiating and titrating oxycodone hydrochloride and acetaminophen oral solution and when oxycodone hydrochloride and acetaminophen oral solution is given concomitantly with other drugs that depress respiration [see WARNINGS; Life Threatening Respiratory Depression]. Alternatively, consider the use of non-opioid analgesics in these patients.
Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
Oxycodone hydrochloride and acetaminophen oral solution may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see PRECAUTIONS; Drug Interactions]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of oxycodone hydrochloride and acetaminophen oral solution. In patients with circulatory shock oxycodone hydrochloride and acetaminophen oral solution may cause vasodilatation that can further reduce cardiac output and blood pressure. Avoid the use of oxycodone hydrochloride and acetaminophen oral solution with circulatory shock.
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.
The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.
Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.
Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue oxycodone hydrochloride and acetaminophen oral solution immediately and seek medical care if they experience these symptoms. Do not prescribe oxycodone hydrochloride and acetaminophen oral solution for patients with acetaminophen allergy [see PRECAUTIONS; Information for Patients/Caregivers].
In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), oxycodone hydrochloride and acetaminophen oral solution may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with oxycodone hydrochloride and acetaminophen oral solution.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of oxycodone hydrochloride and acetaminophen oral solution in patients with impaired consciousness or coma.
Oxycodone hydrochloride and acetaminophen oral solution is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The administration of oxycodone hydrochloride and acetaminophen oral solution, or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
The oxycodone in oxycodone hydrochloride and acetaminophen oral solution may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
The oxycodone in oxycodone hydrochloride and acetaminophen oral solution may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during oxycodone hydrochloride and acetaminophen oral solution therapy.
Do not abruptly discontinue oxycodone hydrochloride and acetaminophen oral solution in a patient physically dependent on opioids. When discontinuing oxycodone hydrochloride and acetaminophen oral solution in a physically dependent patient, gradually taper the dosage. Rapid tapering of oxycodone hydrochloride and acetaminophen oral solution in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see DOSAGE AND ADMINISTRATION, DRUG ABUSE AND DEPENDENCE].
Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including oxycodone hydrochloride and acetaminophen oral solution. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see PRECAUTIONS; Drug Interactions].
The following adverse reactions have been identified during post approval use of oxycodone hydrochloride and acetaminophen oral solution. 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.
Serious adverse reactions that may be associated with oxycodone hydrochloride and acetaminophen oral solution use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, 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.
Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions. Hematologic reactions may include: thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of agranulocytosis have likewise been associated with acetaminophen use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur.
Other adverse reactions obtained from postmarketing experiences with oxycodone and acetaminophen are listed by organ system and in decreasing order of severity and/or frequency as follows:
Body as a Whole: Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose
Cardiovascular: Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias
Central and Peripheral Nervous System: Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness
Fluid and Electrolyte: Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis
Gastrointestinal: Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastrointestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus
Hepatic: Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder
Hearing and Vestibular: Hearing loss, tinnitus
Hematologic: Thrombocytopenia
Hypersensitivity: Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction
Metabolic and Nutritional: Hypoglycemia, hyperglycemia, acidosis, alkalosis
Musculoskeletal: Myalgia, rhabdomyolysis
Ocular: Miosis, visual disturbances, red eye
Psychiatric: Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide
Respiratory System: Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema
Skin and Appendages: Erythema, urticaria, rash, flushing
Urogenital: Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention
Oxycodone hydrochloride and acetaminophen oral solution may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of oxycodone hydrochloride and acetaminophen oral solution and know how they will react to the medication [see PRECAUTIONS; Information for Patients/Caregivers].
In a pharmacokinetic study of oxycodone in patients with end-stage liver disease, oxycodone plasma clearance decreased and the elimination half-life increased.
Because oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepatic impairment. Initiate therapy in these patients with a lower than usual dosage of oxycodone hydrochloride and acetaminophen oral solution and titrate carefully. Monitor closely for adverse events such as respiratory depression, sedation, and hypotension [see CLINICAL PHARMACOLOGY].
In a study of patients with end stage renal impairment, mean elimination half-life 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.
Because oxycodone is known to be substantially excreted by the kidney, its clearance may decrease in patients with renal impairment. Initiate therapy with a lower than usual dosage of oxycodone hydrochloride and acetaminophen solution and titrate carefully. Monitor closely for adverse events such as respiratory depression, sedation, and hypotension [see CLINICAL PHARMACOLOGY].
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store oxycodone hydrochloride and acetaminophen oral solution securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see WARNINGS, DRUG ABUSE AND DEPENDENCE]. Inform patients that leaving oxycodone hydrochloride and acetaminophen oral solution unsecured can pose a deadly risk to others in the home.
Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused oxycodone hydrochloride and acetaminophen oral solution 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.
Instruct patients how to measure and take the correct dose of oxycodone hydrochloride and acetaminophen oral solution and to always use a calibrated measuring device when administering oxycodone hydrochloride and acetaminophen oral solution to ensure the dose is measured and administered accurately [see WARNINGS].
If the prescribed concentration is changed, instruct patients on how to correctly measure the new dose to avoid errors which could result in accidental overdose and death.
Inform patients that the use of oxycodone hydrochloride and acetaminophen oral solution, 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 hydrochloride and acetaminophen oral solution with others and to take steps to protect oxycodone hydrochloride and acetaminophen oral solution from theft or misuse.
Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting oxycodone hydrochloride and acetaminophen oral solution or when the dosage is increased, and that it can occur even at recommended dosages [see WARNINGS]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
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; Life-Threatening
Respiratory Depression].
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 hydrochloride and acetaminophen oral solution. 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; Life-Threatening Respiratory Depression, 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:
Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see WARNINGS]. Instruct patients to take steps to store oxycodone hydrochloride and acetaminophen oral solution securely and to dispose of unused oxycodone hydrochloride and acetaminophen oral solution by flushing oral solution down the toilet. In the case of accidental ingestions, emergency medical care should be sought immediately.
Inform patients and caregivers that potentially fatal additive effects may occur if oxycodone hydrochloride and acetaminophen oral solution is used with benzodiazepines and other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider [see WARNINGS, PRECAUTIONS; Drug Interactions].
Inform patients that opioids could cause a rare but potentially life-threatening condition 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 healthcare providers if they are taking, or plan to take serotonergic medications [see PRECAUTIONS; Drug Interactions].
Inform patients to avoid taking oxycodone hydrochloride and acetaminophen oral solution while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking oxycodone hydrochloride and acetaminophen oral solution [see PRECAUTIONS; Drug Interactions].
Inform patients that opioids 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].
Instruct patients how to properly take oxycodone hydrochloride and acetaminophen oral solution [see DOSAGE AND ADMINISTRATION, WARNINGS].
Advise patients to always use a calibrated oral syringe/dosing cup when administering oxycodone hydrochloride and acetaminophen oral solution to ensure the dose is measured and administered accurately [see WARNINGS].
Advise patients never to use household teaspoons or tablespoons to measure oxycodone hydrochloride and acetaminophen oral solution.
Advise patients not to adjust the dose of oxycodone hydrochloride and acetaminophen oral solution without consulting with a physician or other healthcare professional.
If patients have been receiving treatment with oxycodone hydrochloride and acetaminophen oral solution for more than a few weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose as abrupt discontinuation of the medication could precipitate withdrawal symptoms. Provide a dose schedule to accomplish a gradual discontinuation of the medication [see DOSAGE AND ADMINISTRATION].
In order to avoid developing withdrawal symptoms, instruct patients not to discontinue oxycodone hydrochloride and acetaminophen oral solution without first discussing a tapering plan with the prescriber [see DOSAGE AND ADMINISTRATION].
Inform patients to not take more than 4000 milligrams of acetaminophen per day. Advise patients to call their prescriber if they take more than the recommended dose.
Inform patients that oxycodone hydrochloride and acetaminophen oral solution may cause orthostatic hypotension and syncope. Advise patients how to recognize such a reaction and when to seek medical attention [see CONTRAINDICATIONS, ADVERSE REACTIONS].
Inform patients that anaphylaxis has been reported with ingredients contained in oxycodone hydrochloride and acetaminophen oral solution. Advise patients how to recognize such a reaction and when to seek medical attention [see CONTRAINDICATIONS, ADVERSE REACTIONS].
Inform female patients of reproductive potential that prolonged use of oxycodone hydrochloride and acetaminophen oral solution during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS, PRECAUTIONS; Pregnancy].
Inform female patients of reproductive potential that oxycodone hydrochloride and acetaminophen oral solution can cause fetal harm and to inform the healthcare provider of a known or suspected pregnancy [see PRECAUTIONS; Pregnancy].
Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see PRECAUTIONS; Nursing Mothers].
Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see ADVERSE REACTIONS].
Inform patients that oxycodone hydrochloride and acetaminophen oral solution 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 PRECAUTIONS].
Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see ADVERSE REACTIONS, CLINICAL PHARMACOLOGY].
Although oxycodone may cross-react with some drug urine tests, no available studies were found which determined the duration of detectability of oxycodone in urine drug screens. However, based on pharmacokinetic data, the approximate duration of detectability for a single dose of oxycodone is roughly estimated to be one to two days following drug exposure.
Urine testing for opiates may be performed to determine illicit drug use and for medical reasons such as evaluation of patients with altered states of consciousness or monitoring efficacy of drug rehabilitation efforts. The preliminary identification of opiates in urine involves the use of an immunoassay screening and thin-layer chromatography (TLC). Gas chromatography/mass spectrometry (GC/MS) may be utilized as a third-stage identification step in the medical investigational sequence for opiate testing after immunoassay and TLC. The identities of 6-keto opiates (e.g., oxycodone) can further be differentiated by the analysis of their methoximetrimethylsilyl (MO-TMS) derivative.
The concomitant use of oxycodone hydrochloride and acetaminophen oral solution and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of oxycodone hydrochloride and acetaminophen oral solution and CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of oxycodone hydrochloride and acetaminophen oral solution is achieved [see WARNINGS].
After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will decrease [see CLINICAL PHARMACOLOGY], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oxycodone hydrochloride and acetaminophen oral solution.
If concomitant use is necessary, consider dosage reduction of oxycodone hydrochloride and acetaminophen oral solution until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the oxycodone hydrochloride and acetaminophen oral solution dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
The concomitant use of oxycodone hydrochloride and acetaminophen oral solution and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of oxycodone [see CLINICAL PHARMACOLOGY], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone hydrochloride and acetaminophen oral solution [see WARNINGS].
After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone plasma concentration will increase [see CLINICAL PHARMACOLOGY], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.
If concomitant use is necessary, consider increasing the oxycodone hydrochloride and acetaminophen oral solution dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider oxycodone hydrochloride and acetaminophen oral solution dosage reduction and monitor for signs of respiratory depression.
Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants such as benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS].
The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tryptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome [see PRECAUTIONS;Information for Patients/Caregivers].
If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue oxycodone hydrochloride and acetaminophen oral solution if serotonin syndrome is suspected.
The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, linezolid, may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS].
The use of oxycodone hydrochloride and acetaminophen oral solution is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may reduce the analgesic effect of oxycodone hydrochloride and acetaminophen oral solution and/or precipitate withdrawal symptoms.
Advise patient to avoid concomitant use of these drugs.
Oxycodone hydrochloride and acetaminophen oral solution may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.
If concomitant use is warranted, monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of oxycodone hydrochloride and acetaminophen oral solution and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS].
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
If concomitant use is warranted, monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
If concomitant use is warranted, monitor patients for signs of urinary retention or reduced gastric motility when oxycodone hydrochloride and acetaminophen oral solution is used concomitantly with anticholinergic drugs.
Hepatotoxicity has occurred in chronic alcoholics following various dose levels (moderate to excessive) of acetaminophen.
Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of acetaminophen.
Reduces acetaminophen absorption when administered as soon as possible after overdose.
Propranolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of acetaminophen. Therefore, the pharmacologic effects of acetaminophen may be increased.
The effects of the loop diuretic may be decreased because acetaminophen may decrease renal prostaglandin excretion and decrease plasma renin activity.
Serum lamotrigine concentrations may be reduced, producing a decrease in therapeutic effects.
Probenecid may increase the therapeutic effectiveness of acetaminophen slightly.
The pharmacologic effects of zidovudine may be decreased because of enhanced non-hepatic or renal clearance of zidovudine.
Pregnancy Category C.
Animal reproductive studies have not been conducted with oxycodone hydrochloride and acetaminophen oral solution. It is also not known whether oxycodone hydrochloride and acetaminophen oral solution can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Oxycodone hydrochloride and acetaminophen oral solution should not be given to a pregnant woman unless in the judgment of the physician, the potential benefits outweigh the possible hazards.
Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid 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].
Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Oxycodone hydrochloride and acetaminophen oral solution is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including oxycodone hydrochloride and acetaminophen oral solution, can prolong labor through actions which temporarily reduce 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 tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.
Ordinarily, nursing should not be undertaken while a patient is receiving oxycodone hydrochloride and acetaminophen oral solution because of the possibility of sedation and/or respiratory depression in the infant. Oxycodone is excreted in breast milk in low concentrations, and there have been rare reports of somnolence and lethargy in babies of nursing mothers taking an oxycodone/acetaminophen product. Acetaminophen is also excreted in breast milk in low concentrations.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxycodone hydrochloride and acetaminophen oral solution and any potential adverse effects on the breastfed infant from oxycodone hydrochloride and acetaminophen oral solution or from the underlying maternal condition.
Infants exposed to oxycodone hydrochloride and acetaminophen oral solution through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
Safety and effectiveness of oxycodone hydrochloride and acetaminophen oral solution in pediatric patients have not been established.
Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone hydrochloride and acetaminophen oral solution. 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 hydrochloride and acetaminophen oral solution slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see WARNINGS].
These drugs are 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 monitor renal function.
Depending on the sensitivity/specificity and the test methodology, the individual components of oxycodone hydrochloride and acetaminophen oral solution may cross-react with assays used in the preliminary detection of cocaine (primary urinary metabolite, benzoylecgonine) or marijuana (cannabinoids) in human urine. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. The preferred confirmatory method is gas chromatography/mass spectrometry (GC/MS). Moreover, clinical considerations and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
Acetaminophen may interfere with home blood glucose measurement systems; decreases of >20% in mean glucose values may be noted. This effect appears to be drug, concentration and system dependent.
Oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a Schedule II controlled substance.
Oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol. Oxycodone hydrochloride and acetaminophen oral solution can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS].
All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
Oxycodone hydrochloride and acetaminophen oral solution, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Oxycodone hydrochloride and acetaminophen oral solution is for oral use only. Abuse of oxycodone hydrochloride and acetaminophen oral solution poses a risk of overdose and death. The risk is increased with concurrent abuse of oxycodone hydrochloride and acetaminophen oral solution with alcohol and other central nervous system depressants.
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death.
Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
Do not abruptly discontinue oxycodone hydrochloride and acetaminophen oral solution in a patient physically dependent on opioids. Rapid tapering of oxycodone hydrochloride and acetaminophen oral solution in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.
When discontinuing oxycodone hydrochloride and acetaminophen oral solution, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxycodone hydrochloride and acetaminophen oral solution the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION, WARNINGS].
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS; Pregnancy].
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