Acetaminophen and Oxycodone

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# Black Box Warning

# Overview
Acetaminophen and Oxycodone is a combination of opioid/acetaminophen that is FDA approved for the {{{indicationType}}} of moderate to severe pain. There is a Black Box Warning for this drug as shown here.  Common adverse reactions include constipation, nausea, vomiting, dizziness, headache, lightheadedness, sedation, and somnolence.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Dosage should be adjusted according to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effect of opioids. If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. ENDOCET tablets are given orally.
- ENDOCET 2.5 mg/325 mg;
- The usual adult dosage is one or 2 tablets every 6 hours as needed for pain. The total daily dose of acetaminophen should not exceed 4 grams.
- ENDOCET 5 mg/325 mg; ENDOCET 7.5 mg/325 mg; ENDOCET 10 mg/325 mg
- The usual adult dosage is one tablet every 6 hours as needed for pain. The total daily dose of acetaminophen should not exceed 4 grams.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Acetaminophen and Oxycodone in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Acetaminophen and Oxycodone in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Acetaminophen and Oxycodone in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Acetaminophen and Oxycodone in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Acetaminophen and Oxycodone in pediatric patients.

# Contraindications
- ENDOCET tablets should not be administered to patients with known hypersensitivity to oxycodone, acetaminophen, or any other component of this product.
- Oxycodone is contraindicated in any situation where opioids are contraindicated including patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone is contraindicated in the setting of suspected or known paralytic ileus.

# Warnings
- Misuse, Abuse and Diversion of Opioids
- Oxycodone is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
- Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing ENDOCET tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Concerns about misuse, addiction, and diversion should not prevent the proper management of pain.
- Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.
- Respiratory Depression
- Respiratory depression is a hazard with the use of oxycodone, one of the active ingredients in ENDOCET tablets, as with all opioid agonists. Elderly and debilitated patients are at particular risk for respiratory depression as are non-tolerant patients given large initial doses of oxycodone or when oxycodone is given in conjunction with other agents that depress respiration. Oxycodone should be used with extreme caution in patients with acute asthma, chronic obstructive pulmonary disease (COPD), cor pulmonale, or preexisting respiratory impairment. In such patients, even usual therapeutic doses of oxycodone may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.
- In case of respiratory depression, a reversal agent such as naloxone hydrochloride may be utilized.
- Head Injury and Increased Intracranial Pressure
- The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Oxycodone produces effects on pupillary response and consciousness which may obscure neurologic signs of worsening in patients with head injuries.
- Hypotensive Effect
- Oxycodone may cause severe hypotension particularly in individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs which compromise vasomotor tone such as phenothiazines. Oxycodone, like all opioid analgesics of the morphine-type, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. Oxycodone may produce orthostatic hypotension in ambulatory patients.
- Hepatotoxicity
- 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.
- Serious skin reactions
- 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.
- Hypersensitivity / anaphylaxis
- There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen.  Clinical signs including 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 ENDOCET immediately and seek medical care if they experience these symptoms.  Do not prescribe ENDOCET for patients with acetaminophen allergy.

### Precautions
- Opioid analgesics should be used with caution when combined with CNS depressant drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of respiratory depression, altered mental state, and postural hypotension.
- Acute Abdominal Conditions
- The administration of ENDOCET (Oxycodone and Acetaminophen Tablets, USP) or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
- ENDOCET tablets should be given with caution to patients with CNS depression, elderly or debilitated patients, patients with severe impairment of hepatic, pulmonary, or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy, urethral stricture, acute alcoholism, delirium tremens, kyphoscoliosis with respiratory depression, myxedema, and toxic psychosis.
- ENDOCET tablets may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Oxycodone may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings.
- Following administration of ENDOCET tablets, anaphylactic reactions have been reported in patients with a known hypersensitivity to codeine, a compound with a structure similar to morphine and oxycodone. The frequency of this possible cross-sensitivity is unknown.
- Interactions with Other CNS Depressants
- Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with ENDOCET tablets may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
- Interactions with Mixed Agonist/Antagonist Opioid Analgesics
- Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as oxycodone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone and/or may precipitate withdrawal symptoms in these patients.
- 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.
- Use in Pancreatic/Biliary Tract Disease
- Oxycodone may cause spasm of the Sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone may cause increases in the serum amylase level.
- Tolerance and Physical Dependence
- 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). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.
- The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
- In general, opioids should not be abruptly discontinued.

# Adverse Reactions

## Clinical Trials Experience
- Serious adverse reactions that may be associated with ENDOCET tablet use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock.
- 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 ENDOCET tablets are listed by organ system and in decreasing order of severity and/or frequency as follows:
Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose
Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias
Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness
Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis
Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastro-intestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus
Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder
Hearing loss, tinnitus
Thrombocytopenia
Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction
Hypoglycemia, hyperglycemia, acidosis, alkalosis
Myalgia, rhabdomyolysis
Miosis, visual disturbances, red eye
Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide
Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema
Erythema, urticaria, rash, flushing
Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Acetaminophen and Oxycodone in the drug label.

# Drug Interactions
- Oxycodone
- Opioid analgesics may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.
- Patients receiving CNS depressants such as other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with ENDOCET tablets may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced. The concurrent use of anticholinergics with opioids may produce paralytic ileus.
- Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, and butorphanol) should be administered with caution to a patient who has received or is receiving a pure opioid agonist such as oxycodone. These agonist/antagonist analgesics may reduce the analgesic effect of oxycodone or may precipitate withdrawal symptoms.
- Acetaminophen
- Alcohol, ethyl: Hepatotoxicity has occurred in chronic alcoholics following various dose levels (moderate to excessive) of acetaminophen.
- Anticholinergics: The onset of acetaminophen effect may be delayed or decreased slightly, but the ultimate pharmacological effect is not significantly affected by anticholinergics.
- Oral Contraceptives: Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of acetaminophen.
- Charcoal (activated): Reduces acetaminophen absorption when administered as soon as possible after overdose.
- Beta Blockers (Propranolol): Propranolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of acetaminophen. Therefore, the pharmacologic effects of acetaminophen may be increased.
- Loop diuretics: The effects of the loop diuretic may be decreased because acetaminophen may decrease renal prostaglandin excretion and decrease plasma renin activity.
- Lamotrigine: Serum lamotrigine concentrations may be reduced, producing a decrease in therapeutic effects.
- Probenecid: Probenecid may increase the therapeutic effectiveness of acetaminophen slightly.
- Zidovudine: The pharmacologic effects of zidovudine may be decreased because of enhanced non-hepatic or renal clearance of zidovudine.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category C
- Animal reproductive studies have not been conducted with ENDOCET. It is also not known whether ENDOCET can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. ENDOCET should not be given to a pregnant woman unless in the judgment of the physician, the potential benefits outweigh the possible hazards.
- Nonteratogenic Effects
- Opioids can cross the placental barrier and have the potential to cause neonatal respiratory depression. Opioid use during pregnancy may result in a physically drug-dependent fetus. After birth, the neonate may suffer severe withdrawal symptoms.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Acetaminophen and Oxycodone in women who are pregnant.

### Labor and Delivery
- ENDOCET tablets are not recommended for use in women during and immediately prior to labor and delivery due to its potential effects on respiratory function in the newborn.

### Nursing Mothers
- Ordinarily, nursing should not be undertaken while a patient is receiving ENDOCET tablets 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.

### Pediatric Use
- Safety and effectiveness in pediatric patients have not been established.

### Geriatic Use
- Special precaution should be given when determining the dosing amount and frequency of ENDOCET tablets for geriatric patients, since clearance of oxycodone may be slightly reduced in this patient population when compared to younger patients.

### Gender
There is no FDA guidance on the use of Acetaminophen and Oxycodone with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Acetaminophen and Oxycodone with respect to specific racial populations.

### Renal Impairment
- 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.

### 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.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Acetaminophen and Oxycodone in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Acetaminophen and Oxycodone in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Oral

### Monitoring
There is limited information regarding Monitoring of Acetaminophen and Oxycodone in the drug label.

# IV Compatibility
There is limited information regarding IV Compatibility of Acetaminophen and Oxycodone in the drug label.

# Overdosage

## Acute Overdose

### Signs and Symptoms
- Following an acute overdosage, toxicity may result from the oxycodone or the acetaminophen.
- Toxicity from oxycodone poisoning includes the opioid triad of: pinpoint pupils, depression of respiration, and loss of consciousness.  Serious overdosage with oxycodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.
- In acetaminophen overdosage: dose-dependent potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur.
- Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

### Management
- A single or multiple drug overdose with oxycodone and acetaminophen is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.  Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated.  Assisted or controlled ventilation should also be considered.
- Oxycodone
- Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids, including oxycodone.  Since the duration of action of oxycodone may exceed that of the antagonist, the patient should be kept under continued surveillance, and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.  An opioid antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
- Acetaminophen
- Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.
- Vigorous supportive therapy is required in severe intoxication.  Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.

## Chronic Overdose
There is limited information regarding Chronic Overdose of Acetaminophen and Oxycodone in the drug label.

# Pharmacology

## Mechanism of Action
- Central Nervous System
- Oxycodone is a semisynthetic pure opioid agonist whose principal therapeutic action is analgesia. Other pharmacological effects of oxycodone include anxiolysis, euphoria and feelings of relaxation. These effects are mediated by receptors (notably  and ) in the central nervous system for endogenous opioid-like compounds such as endorphins and enkephalins. Oxycodone produces respiratory depression through direct activity at respiratory centers in the brain stem and depresses the cough reflex by direct effect on the center of the medulla.
- Acetaminophen is a non-opiate, non-salicylate analgesic and antipyretic. The site and mechanism for the analgesic effect of acetaminophen has not been determined. The antipyretic effect of acetaminophen is accomplished through the inhibition of endogenous pyrogen action on the hypothalamic heat-regulating centers.
- Gastrointestinal Tract and Other Smooth Muscle
- Oxycodone reduces motility by increasing smooth muscle tone in the stomach and duodenum. In the small intestine, digestion of food is delayed by decreases in propulsive contractions. Other opioid effects include contraction of biliary tract smooth muscle, spasm of the Sphincter of Oddi, increased ureteral and bladder sphincter tone, and a reduction in uterine tone.
- Cardiovascular System
- Oxycodone may produce a release of histamine and may be associated with orthostatic hypotension, and other symptoms, such as pruritus, flushing, red eyes, and sweating.

## Structure
- Each tablet, for oral administration, contains oxycodone hydrochloride and acetaminophen in the following strengths:
- Oxycodone Hydrochloride, USP                      2.5 mg*
- Acetaminophen, USP                                      325 mg
- 2.5 mg oxycodone HCl is equivalent to 2.2409 mg of oxycodone.
- Oxycodone Hydrochloride, USP                         5 mg*
- Acetaminophen, USP                                      325 mg
- 5 mg oxycodone HCl is equivalent to 4.4815 mg of oxycodone.
- Oxycodone Hydrochloride, USP                      7.5 mg*
- Acetaminophen, USP                                      325 mg
- 7.5 mg oxycodone HCl is equivalent to 6.7228 mg of oxycodone.
- Oxycodone Hydrochloride, USP                      10 mg*
- Acetaminophen, USP                                      325 mg
- 10 mg oxycodone HCl is equivalent to 8.9637 mg of oxycodone.
- All strengths of ENDOCET also contain the following inactive ingredients: Colloidal silicon dioxide, croscarmellose sodium, crospovidone, microcrystalline cellulose, povidone, pregelatinized cornstarch, and stearic acid. In addition, the 2.5 mg/325 mg strength contains FD&C Red No. 40 Aluminum Lake. The 7.5 mg/325 mg strength contains FD&C Yellow No. 6 Aluminum Lake. The 10 mg/325 mg strength contains D&C Yellow No. 10 Aluminum Lake. The 7.5 mg/325 mg strength and 10 mg/325 mg strength may also contain corn starch.
- Oxycodone, 14-hydroxydihydrocodeinone, is a semisynthetic opioid analgesic which occurs as a white, odorless, crystalline powder having a saline, bitter taste. The molecular formula for oxycodone hydrochloride is C18H21NO4HCl and the molecular weight 351.82. It is derived from the opium alkaloid thebaine, and may be represented by the following structural formula:
- Acetaminophen, 4-hydroxyacetanilide, is a non-opiate, non-salicylate analgesic and antipyretic which occurs as a white, odorless, crystalline powder, possessing a slightly bitter taste. The molecular formula for acetaminophen is C8H9NO2 and the molecular weight is 151.17. It may be represented by the following structural formula:

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Acetaminophen and Oxycodone in the drug label.

## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Acetaminophen and Oxycodone in the drug label.

## Nonclinical Toxicology
- Carcinogenesis
- Animal studies to evaluate the carcinogenic potential of oxycodone and acetaminophen have not been performed.
- Mutagenesis
- The combination of oxycodone and acetaminophen has not been evaluated for mutagenicity. Oxycodone alone was negative in a bacterial reverse mutation assay (Ames), an in vitro chromosome aberration assay with human lymphocytes without metabolic activation and an in vivo mouse micronucleus assay. Oxycodone was clastogenic in the human lymphocyte chromosomal assay in the presence of metabolic activation and in the mouse lymphoma assay with or without metabolic activation.
- Fertility
- Animal studies to evaluate the effects of oxycodone on fertility have not been performed.

# Clinical Studies
There is limited information regarding Clinical Studies of Acetaminophen and Oxycodone in the drug label.

# How Supplied
- ENDOCET (Oxycodone and Acetaminophen Tablets, USP) is supplied as follows:
- 2.5 mg/325 mg
- Pink, oval, tablet, debossed with "E701" on one side and "2.5" on the other.
- Bottles of 100                                     NDC 60951-701-70
- 5 mg/325 mg
- White, round, tablet, with one face scored and the other inscribed "Endo" and "602".
- Bottles of 100                                     NDC 60951-602-70
- Bottles of 500                                     NDC 60951-602-85
- 7.5 mg/325 mg
- Peach, oval-shaped, tablet, debossed with "E700" on one side and "7.5/325" on the other.
- Bottles of 100                                     NDC 60951-700-70
- 10 mg/325 mg
- Yellow, capsule-shaped, tablet, debossed with "E712" on one side and "10/325" on the other.
- Bottles of 100                                     NDC 60951-712-70
- Store at 20 to 25C (68 to 77F).
- Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

## Storage
There is limited information regarding Acetaminophen and Oxycodone Storage in the drug label.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
- The following information should be provided to patients receiving ENDOCET tablets by their physician, nurse, pharmacist, or caregiver:
- Do not take ENDOCET if you are allergic to any of its ingredients.
- If you develop signs of allergy such as a rash or difficulty breathing stop taking ENDOCET and contact your healthcare provider immediately.
- Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more than the recommended dose.
- Patients should be aware that ENDOCET tablets contain oxycodone, which is a morphine-like substance.
- Patients should be instructed to keep ENDOCET tablets in a secure place out of the reach of children. In the case of accidental ingestions, emergency medical care should be sought immediately.
- When ENDOCET tablets are no longer needed, the unused tablets should be destroyed by flushing down the toilet.
- Patients should be advised not to adjust the medication dose themselves. Instead, they must consult with their prescribing physician.
- Patients should be advised that ENDOCET tablets may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).
- Patients should not combine ENDOCET tablets with alcohol, opioid analgesics, tranquilizers, sedatives, or other CNS depressants unless under the recommendation and guidance of a physician. When co-administered with another CNS depressant, ENDOCET tablets can cause dangerous additive central nervous system or respiratory depression, which can result in serious injury or death.
- The safe use of ENDOCET tablets during pregnancy has not been established; thus, women who are planning to become pregnant or are pregnant should consult with their physician before taking ENDOCET tablets.
- Nursing mothers should consult with their physicians about whether to discontinue nursing or discontinue ENDOCET tablets because of the potential for serious adverse reactions to nursing infants.
- Patients who are treated with ENDOCET tablets for more than a few weeks should be advised not to abruptly discontinue the medication.  Patients should consult with their physician for a gradual discontinuation dose schedule to taper off the medication.
- Patients should be advised that ENDOCET tablets are a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.

# Precautions with Alcohol
- Alcohol-Acetaminophen and Oxycodone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- ENDOCET

# Look-Alike Drug Names
- Percocet  Darvocet
- Endocet  Indocid
- Percocet  Procet
- Roxicet  Roxanol

# Drug Shortage Status

# Price