Label: OXYCODONE AND ACETAMINOPHEN- oxycodone and acetaminophen tablet

  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: CII
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated January 28, 2016

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  • BOXED WARNING(What is this?)

    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.

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  • DESCRIPTION

    Oxycodone and Acetaminophen Tablets , USP 7.5 mg / 325 mg CII

    Each tablet, for oral administration, contains oxycodone hydrochloride, USP and acetaminophen, USP in
    the following strengths:
    Oxycodone Hydrochloride, USP 7.5 mg*
    Acetaminophen, USP 325 mg
    *7.5 mg oxycodone HCl, USP is equivalent to 6.7228 mg of oxycodone.
    All strengths of oxycodone and acetaminophen, USP also contain the following inactive ingredients:
    colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, povidone,
    pregelatinized corn starch and stearic acid.
    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, USP is C H NO •HCl and the molecular weight 351.83. It is derived
    from the opium alkaloid thebaine, and may be represented by the following structural formula:
    Acetaminophen, USP, 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, USP is C H NO and the molecular weight is 151.17. It may be represented
    by the following structural formula:
    18 21 4
    8 9 2

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  • CLINICAL PHARMACOLOGY

    Central Nervous Sys tem
    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 µ 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.
    Gas trointes tinal Tract and Other Smooth Mus cle
    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.
    Cardiovas cular Sys tem
    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.

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  • PHARMACOKINETICS

    Absorption and Distribution
    The mean absolute oral bioavailability of oxycodone in cancer patients was reported to be about 87%.
    Oxycodone has been shown to be 45% bound to human plasma proteins in vitro. The volume of
    distribution after intravenous administration is 211.9 ±186.6 L.
    Absorption of acetaminophen is rapid and almost complete from the GI tract after oral administration.
    With overdosage, absorption is complete in 4 hours. Acetaminophen is relatively uniformly distributed
    throughout most body fluids. Binding of the drug to plasma proteins is variable; only 20% to 50% may
    be bound at the concentrations encountered during acute intoxication.
    Metabolis m and Elimination
    A high portion of oxycodone is N-dealkylated to noroxycodone during first-pass metabolism.
    Oxymorphone, is formed by the O-demethylation of oxycodone. The metabolism of oxycodone to
    oxymorphone is catalyzed by CYP2D6. Free and conjugated noroxycodone, free and conjugated
    oxycodone, and oxymorphone are excreted in human urine following a single oral dose of oxycodone.
    Approximately 8% to 14% of the dose is excreted as free oxycodone over 24 hours after
    administration. Following a single, oral dose of oxycodone, the mean ± SD elimination half-life is 3.51
    ± 1.43 hours.
    Acetaminophen is metabolized in the liver via cytochrome P450 microsomal enzyme. About 80% to
    85% of the acetaminophen in the body is conjugated principally with glucuronic acid and to a lesser
    extent with sulfuric acid and cysteine. After hepatic conjugation, 90% to 100% of the drug is recovered
    in the urine within the first day.
    About 4% of acetaminophen is metabolized via cytochrome P450 oxidase to a toxic metabolite which is
    further detoxified by conjugation with glutathione, present in a fixed amount. It is believed that the toxic
    metabolite NAPQI (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone) is responsible for liver
    necrosis. High doses of acetaminophen may deplete the glutathione stores so that inactivation of the
    toxic metabolite is decreased. At high doses, the capacity of metabolic pathways for conjugation with
    glucuronic acid and sulfuric acid may be exceeded, resulting in increased metabolism of acetaminophen
    by alternate pathways.

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  • INDICATIONS & USAGE

    Oxycodone and acetaminophen tablets, USP are indicated for the relief of moderate to moderately
    severe pain.

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  • CONTRAINDICATIONS

    Oxycodone and acetaminophen tablets, USP should not be administered to patients with known
    hypersensitivity to oxycodone, acetaminophen, USP, 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.

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  • WARNINGS

    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 s kin 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.
    Hypers ens itivity/ anaphylaxis
    There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of
    acetaminophen. Clinical signs include swelling of the face, mouth, and throat, respiratory distress,
    urticaria, rash, pruritis, and vomiting. There were infrequent reports of life-threatening anaphylaxis
    requiring emergency medical attention. Instruct patients to discontinue Oxycodone and Acetaminophen
    Tablets, USP immediately and seek medical care if they experience these symptoms. Do not prescribe
    Oxycodone and Acetaminophen Tablets, USP for patients with acetaminophen allergy.
    Mis us e, Abus e and Divers ion 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 oxycodone and acetaminophen 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.
    Administration of oxycodone and acetaminophen tablets should be closely monitored for the following
    potentially serious adverse reactions and complications:
    Res piratory Depres s ion
    Respiratory depression is a hazard with the use of oxycodone, one of the active ingredients in
    oxycodone and acetaminophen 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 disorder (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 (see

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  • OVERDOSAGE

    Head Injury and Increas ed Intracranial Pres s ure
    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 preexisting increase in intracranial pressure. Oxycodone produces effects on
    pupillary response and consciousness which may obscure neurologic signs of worsening in patients
    with head injuries.
    Hypotens ive 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
    Precaution should be taken in patients with liver disease. Hepatotoxicity and severe hepatic failure
    occurred in chronic alcoholics following therapeutic doses.

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  • PRECAUTIONS

    General
    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 oxycodone and acetaminophen tablets or other opioids may obscure the diagnosis
    or clinical course in patients with acute abdominal conditions.
    Oxycodone and acetaminophen 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.
    Oxycodone and acetaminophen 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 oxycodone and acetaminophen 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 Depres s ants
    Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers,
    centrally-acting antiemetics, sedative-hypnotics or other CNS depressants (including alcohol)
    concomitantly with oxycodone and acetaminophen 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 Agonis t/Antagonis t Opioid Analges ics
    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 Pos toperative Us e
    Oxycodone and other morphine-like opioids have been shown to decrease bowel motility. Ileus is a
    common postoperative complication, especially after intraabdominal 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.
    Us e in Pancreatic/Biliary Tract Dis eas e
    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 Phys ical 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 (see DOSAGE AND ADMINISTRATION:
    Ces s ation of Therapy).
    Information for Patients /Caregivers
    The following information should be provided to patients receiving oxycodone and acetaminophen tablets by
    their physician, nurse, pharmacist, or caregiver:
    Do not take oxycodone and acetaminophen tablets if you are allergic to any of its ingredients.
    If you develop signs of allergy such as a rash or difficulty breathing, stop taking oxycodone and
    acetaminophen and contact your healthcare provider immediately.
    Do not take more than 4,000 milligrams of acetaminophen per day. Call your doctor if you took
    more than the recommended dose.
    1. Patients should be aware that oxycodone and acetaminophen tablets contain oxycodone, which is a
    morphine-like substance.
    2. Patients should be instructed to keep oxycodone and acetaminophen tablets in a secure place out of
    the reach of children. In the case of accidental ingestions, emergency medical care should be sought
    immediately.
    3. When oxycodone and acetaminophen tablets are no longer needed, the unused tablets should be
    destroyed by flushing down the toilet.
    4. Patients should be advised not to adjust the medication dose themselves. Instead, they must consult
    with their prescribing physician.
    5. Patients should be advised that oxycodone and acetaminophen tablets may impair mental and/or
    physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating
    heavy machinery).
    6. Patients should not combine oxycodone and acetaminophen 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, oxycodone and acetaminophen
    tablets can cause dangerous additive central nervous system or respiratory depression, which can
    result in serious injury or death.
    7. The safe use of oxycodone and acetaminophen 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 oxycodone and acetaminophen tablets.
    8. Nursing mothers should consult with their physicians about whether to discontinue nursing or
    discontinue oxycodone and acetaminophen tablets because of the potential for serious adverse
    reactions to nursing infants.
    9. Patients who are treated with oxycodone and acetaminophen 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.
    10. Patients should be advised that oxycodone and acetaminophen 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.

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  • LABORATORY TESTS

    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 methoxime-trimethylsilyl (MO-TMS) derivative.

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  • DRUG INTERACTIONS

    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 oxycodone and acetaminophen 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.
    Drug/Drug Interactions with 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 nonhepatic
    or renal clearance of zidovudine.
    Drug/Laboratory Tes t Interactions
    Depending on the sensitivity/specificity and the test methodology, the individual components of
    oxycodone and acetaminophen tablets 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.
    Carcinogenes is , Mutagenes is , Impairment of Fertility
    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.
    Pregnancy
    Teratogenic Effects
    Pregnancy Category C
    Animal reproductive studies have not been conducted with oxycodone and acetaminophen. It is also not
    known whether oxycodone and acetaminophen can cause fetal harm when administered to a pregnant
    woman or can affect reproductive capacity. Oxycodone and acetaminophen 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.
    Labor and Delivery
    Oxycodone and acetaminophen 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.
    Nurs ing Mothers
    Ordinarily, nursing should not be undertaken while a patient is receiving oxycodone and acetaminophen
    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.
    Geriatric Use
    Special precaution should be given when determining the dosing amount and frequency of oxycodone
    and acetaminophen tablets for geriatric patients, since clearance of oxycodone may be slightly reduced
    in this patient population when compared to younger patients.
    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.
    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.

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  • ADVERSE REACTIONS

    Serious adverse reactions that may be associated with oxycodone and acetaminophen tablet 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
    tablets 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
    Cardiovas cular
    Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias
    Central and Peripheral Nervous Sys tem
    Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation,
    cerebral edema, confusion, dizziness
    Fluid and Electrolyte
    Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis
    Gas trointes tinal
    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 Ves tibular
    Hearing loss, tinnitus
    Hematologic
    Thrombocytopenia
    Hypers ens itivity
    Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid
    reaction
    Metabolic and Nutritional
    Hypoglycemia, hyperglycemia, acidosis, alkalosis
    Mus culos keletal
    Myalgia, rhabdomyolysis
    Ocular
    Miosis, visual disturbances, red eye
    Ps ychiatric
    Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of
    consciousness, nervousness, hallucination, somnolence, depression, suicide
    Res piratory Sys tem
    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

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  • DRUG ABUSE AND DEPENDENCE

    Oxycodone and acetaminophen tablets are a Schedule II controlled substance. Oxycodone is a muagonist
    opioid with an abuse liability similar to morphine. Oxycodone, like morphine and other opioids
    used in analgesia, can be abused and is subject to criminal diversion.
    Drug addiction is defined as an abnormal, compulsive use, use for non-medical purposes of a substance
    despite physical, psychological, occupational or interpersonal difficulties resulting from such use, and
    continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a
    multidisciplinary approach, but relapse is common. Opioid addiction is relatively rare in patients with
    chronic pain but may be more common in individuals who have a past history of alcohol or substance
    abuse or dependence. Pseudoaddiction refers to pain relief seeking behavior of patients whose pain is
    poorly managed. It is considered an iatrogenic effect of ineffective pain management. The health care
    provider must assess continuously the psychological and clinical condition of a pain patient in order to
    distinguish addiction from pseudoaddiction and thus, be able to treat the pain adequately.
    Physical dependence on a prescribed medication does not signify addiction. Physical dependence
    involves the occurrence of a withdrawal syndrome when there is sudden reduction or cessation in drug
    use or if an opiate antagonist is administered. Physical dependence can be detected after a few days of
    opioid therapy. However, clinically significant physical dependence is only seen after several weeks of
    relatively high dosage therapy. In this case, abrupt discontinuation of the opioid may result in a
    withdrawal syndrome. If the discontinuation of opioids is therapeutically indicated, gradual tapering of
    the drug over a 2-week period will prevent withdrawal symptoms. The severity of the withdrawal
    syndrome depends primarily on the daily dosage of the opioid, the duration of therapy and medical
    status of the individual.
    The withdrawal syndrome of oxycodone is similar to that of morphine. This syndrome is characterized
    by yawning, anxiety, increased heart rate and blood pressure, restlessness, nervousness, muscle aches,
    tremor, irritability, chills alternating with hot flashes, salivation, anorexia, severe sneezing, lacrimation,
    rhinorrhea, dilated pupils, diaphoresis, piloerection, nausea, vomiting, abdominal cramps, diarrhea and
    insomnia, and pronounced weakness and depression.
    “Drug-seeking” behavior is very common in addicts and drug abusers. 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 physician(s). “Doctor Shopping”
    to obtain additional prescriptions is common among drug abusers and people suffering from untreated
    addiction.
    Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians
    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 and is characterized by misuse for non-medical purposes, often in combination with other
    psychoactive substances. Oxycodone, like other opioids, has been diverted for non-medical use.
    Careful recordkeeping of prescribing information, including quantity, frequency and renewal requests 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.
    Like other opioid medications, oxycodone and acetaminophen tablets are subject to the Federal
    Controlled Substances Act. After chronic use, oxycodone and acetaminophen tablets should not be
    discontinued abruptly when it is thought that the patient has become physically dependent on oxycodone.
    Interactions with Alcohol and Drugs of Abus e
    Oxycodone may be expected to have additive effects when used in conjunction with alcohol, other
    opioids, or illicit drugs that cause central nervous system depression.

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  • OVERDOSAGE

    Following an acute overdosage, toxicity may result from the oxycodone or the acetaminophen.
    Signs and Symptoms
    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.

    Treatment
    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 narcotic
    antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may
    result from overdosage or unusual sensitivity to narcotics, 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. A narcotic 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.

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  • DOSAGE & ADMINISTRATION

    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. Oxycodone
    and acetaminophen tablets, USP are given orally.
    Oxycodone and acetaminophentablets , USP 7.5 mg/325 mg
    The usual adult dosage is one tablet every 6 hours as needed for pain. The total daily dose of
    acetaminophen, USP should not exceed 4 grams.
    Strength Maximal Daily Dos e
    Oxycodone and acetaminophen tablets, USP 7.5 mg/325 mg 8 Tablets
    Ces s ation of Therapy
    In patients treated with oxycodone and acetaminophen tablets, USP for more than a few weeks who no
    longer require therapy, doses should be tapered gradually to prevent signs and symptoms of withdrawal
    in the physically dependent patient.

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  • HOW SUPPLIED

    Oxycodone and acetaminophen tablets, USP, 7.5 mg/ 325 mg, are supplied as white to off-white,
    capsule shaped, biconvex tablets, debossed “IP207” on obverse and plain on the reverse.
    They are available as follows:
    Bottles of 30: NDC: 65162-207-03
    Bottles of 100: NDC: 65162-207-10
    Bottles of 500: NDC: 65162-207-50
    Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
    Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as
    required).
    DEA Order Form Required.
    MFG. ADDRESS
    Manufactured by:
    Amneal Pharmaceuticals of NY
    Hauppauge, NY 11788
    Rev. 08-2015-02

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  • INGREDIENTS AND APPEARANCE
    OXYCODONE AND ACETAMINOPHEN 
    oxycodone and acetaminophen tablet
    Product Information
    Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:61502-915(NDC:65162-207)
    Route of Administration ORAL DEA Schedule CII    
    Active Ingredient/Active Moiety
    Ingredient Name Basis of Strength Strength
    OXYCODONE HYDROCHLORIDE (UNII: C1ENJ2TE6C) (OXYCODONE - UNII:CD35PMG570) OXYCODONE HYDROCHLORIDE 7.5 mg
    ACETAMINOPHEN (UNII: 362O9ITL9D) (ACETAMINOPHEN - UNII:362O9ITL9D) ACETAMINOPHEN 325 mg
    Product Characteristics
    Color white (OFF WHITE) Score no score
    Shape CAPSULE Size 7mm
    Flavor Imprint Code IP207
    Contains     
    Packaging
    # Item Code Package Description Marketing Start Date Marketing End Date
    1 NDC:61502-915-97 500 in 1 BOTTLE; Type 0: Not a Combination Product 01/28/2016
    2 NDC:61502-915-96 100 in 1 BOTTLE; Type 0: Not a Combination Product 01/28/2016
    3 NDC:61502-915-30 30 in 1 BOTTLE; Type 0: Not a Combination Product 01/28/2016
    4 NDC:61502-915-20 20 in 1 BOTTLE; Type 0: Not a Combination Product 01/28/2016
    5 NDC:61502-915-15 15 in 1 BOTTLE; Type 0: Not a Combination Product 01/28/2016
    6 NDC:61502-915-10 10 in 1 BOTTLE; Type 0: Not a Combination Product 01/28/2016
    7 NDC:61502-915-06 6 in 1 BOTTLE; Type 0: Not a Combination Product 01/28/2016
    Marketing Information
    Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
    ANDA ANDA040778 01/28/2016
    Labeler - EPM Packaging Inc (079124340)
    Registrant - EPM Packaging Inc (079124340)
    Establishment
    Name Address ID/FEI Business Operations
    EPM Packaging Inc 079124340 repack(61502-915)
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