OXYCODONE AND ACETAMINOPHEN 5 mg/5mL; 325 mg/5mL Solution, 500 mL — NDC 10702-238-50 (Billing 10702-0238-50)

WARNINGS Risk of Accidental Overdose and Death due to Medication Errors 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.

Instruct patients and caregivers on how to measure and take or administer the correct dose of oxycodone hydrochloride and acetaminophen oral solution and to use extreme caution when measuring the dose. Strongly advise patients to obtain and always use a graduated device that can measure and deliver the prescribed dose accurately, and to never use household teaspoons or tablespoons to measure a dose because these are not accurate measuring devices. Addiction, Abuse, and Misuse 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.

The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see A dverse Reactions ]. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing oxycodone hydrochloride and acetaminophen oral solution, and reassess 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 frequent reevaluation for signs of addiction, abuse, and misuse.

Consider recommending or prescribing an opioid overdose reversal agent [see Warnings; Life-Threatening Respiratory Depression, Dosage and Administration; Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose] . Opioids are sought for nonmedical use and are subjected to diversion from legitimate prescribed use. 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 careful storage of the drug during the course of treatment and the proper disposal of unused drug . 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 overdose reversal agents (e.g., naloxone,… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS 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 has 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 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). Postmarketing Experience 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… [Excerpted — this section continues on DailyMed.]

PRECAUTIONS Risks of Driving and Operating Machinery 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 ]. 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 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 . Inform patients that leaving oxycodone hydrochloride and acetaminophen oral solution 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 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. Medication Errors Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication.

Inform patients and caregivers that oral dosing devices may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure oxycodone hydrochloride and acetaminophen oral solution [see Warnings ]. Addiction, Abuse, and Misuse 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.

Life-Threatening Respiratory Depression 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. Educate patients and caregivers how to recognize respiratory depression emphasize the importance of calling 911 or getting emergency help right away in the event of a known or suspected overdose [see Warnings; Life Threatening Respiratory Depression ].

Patient Access to an Opioid Overdose Reversal Agent Naloxone for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.

Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, 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… [Excerpted — this section continues on DailyMed.]

DRUG ABUSE AND DEPENDENCE Controlled Substance Oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a Schedule II controlled substance. Abuse Oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings ]. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of Oxycodone hydrochloride and acetaminophen oral solution increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death.

The risk is increased with concurrent abuse of Oxycodone hydrochloride and acetaminophen oral solution with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Oxycodone hydrochloride and acetaminophen oral solution abuse include those with a history of prolonged use of any opioid, including products containing oxycodone, those with a history of drug or alcohol abuse, or those who use Oxycodone hydrochloride and acetaminophen oral solution in combination with other abused drugs. “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 healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Oxycodone hydrochloride and acetaminophen oral solution, like other opioids, can be diverted for nonmedical 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 reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Oxycodone Hydrochloride and Acetaminophen Oral Solution Abuse of Oxycodone hydrochloride and acetaminophen oral solution poses a risk of overdose and death. The risk is increased with concurrent use of Oxycodone hydrochloride and acetaminophen oral solution with alcohol and/or other CNS 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. Dependence Both tolerance and physical dependence can de… [Excerpted — this section continues on DailyMed.]