OXYCODONE AND ACETAMINOPHEN  - oxycodone hydrochloride and acetaminophen tablet 
Lake Erie Medical DBA Quality Care products LLC

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Oxycodone APAP 5mg 325mg






























Absorption and Distribution –

































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 OVERDOSAGE).

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.

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.

Precaution should be taken in patients with liver disease. Hepatotoxicity and severe hepatic failure occurred in chronic alcoholics following therapeutic doses.







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.

Patients receiving 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.

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.

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.

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 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; Cessation of Therapy).

The following information should be provided to patients receiving oxycodone and acetaminophen tablets by their physician, nurse, pharmacist, or caregiver:

  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.

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.

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.



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 (Propanolol) – Propanolol 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

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.

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.

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.

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 tablets can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Oxycodone and acetaminophen tablets 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.

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.

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.

Safety and effectiveness in pediatric patients have not been established.

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.

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.

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.







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 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

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, gastro-intestinal 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 and acetaminophen tablets are a Schedule II controlled substance. Oxycodone is a mu-agonist 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 multi-disciplinary 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 infection.

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 record-keeping of prescribing information, including quantity, frequency, and renewal requests 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.

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.

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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The total daily dose of acetaminophen should not exceed 4 grams.

Strength Usual
Adult Dosage
Maximal
Daily Dose
Oxycodone and acetaminophen tablets
5 mg/325 mg
1 tablet every 6 hours
as needed for pain
12
Tablets
Oxycodone and acetaminophen tablets
7.5 mg/325 mg
1 tablet every 6 hours
as needed for pain
8
Tablets
Oxycodone and acetaminophen tablets
7.5 mg/500 mg
1 tablet every 6 hours
as needed for pain
8
Tablets
Oxycodone and acetaminophen tablets
10 mg/325 mg
1 tablet every 6 hours
as needed for pain
6
Tablets

Cessation of Therapy

In patients treated with oxycodone and acetaminophen tablets 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.

HOW SUPPLIED

Each oxycodone and acetaminophen tablet USP 5 mg/325 mg contains oxycodone hydrochloride 5 mg (equivalent to 4.4815 mg oxycodone) and acetaminophen 325 mg. It is available as a round, white scored tablet debossed with a 512 identification number.

Each oxycodone and acetaminophen tablet USP 7.5 mg/325 mg contains oxycodone hydrochloride 7.5 mg (equivalent to 6.7228 mg oxycodone) and acetaminophen 325 mg. It is available as a white to off-white caplet shaped tablet debossed with “M522” on one side and “7.5/325” on the other side.

Each oxycodone and acetaminophen tablet USP 7.5 mg/500 mg contains oxycodone hydrochloride 7.5 mg (equivalent to 6.7228 mg oxycodone) and acetaminophen 500 mg. It is available as a white to off-white oval shaped tablet debossed with “M582” on one side and the other side is plain.

Each oxycodone and acetaminophen tablet USP 10 mg/325 mg contains oxycodone hydrochloride 10 mg (equivalent to 8.9637 mg oxycodone) and acetaminophen 325 mg. It is available as a white to off-white caplet shaped tablet debossed with “M523” on one side and “10/325” on the other side.


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.

Mallinckrodt Inc.,
Hazelwood, MO 63042 USA.

Printed in U.S.A.

COVIDIEN™
Mallinckrodt

Rev 05/2009

Multiple strengths. Do not dispense unless strength is stated.

NDC 0406-0512-05

500 TABLETS

OXYCODONE AND ACETAMINOPHEN TABLETS USP

CII

5 mg*/325 mg

Each tablet contains:
Oxycodone Hydrochloride USP. . . . . . . 5 mg*
Acetaminophen USP . . . . . . . . . . . . . .325 mg

Rx only

Mallinckrodt


Image of labelImage of label


OXYCODONE AND ACETAMINOPHEN 
oxycodone and acetaminophen   tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 49999-852 (00406-512)
Route of Administration ORAL DEA Schedule CII    
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
OXYCODONE HYDROCHLORIDE (OXYCODONE) OXYCODONE HYDROCHLORIDE 5 mg
ACETAMINOPHEN (ACETAMINOPHEN) ACETAMINOPHEN 325 mg
Inactive Ingredients
Ingredient Name Strength
CROSPOVIDONE  
CELLULOSE, MICROCRYSTALLINE  
POVIDONE  
STARCH, CORN  
SILICON DIOXIDE  
STEARIC ACID  
Product Characteristics
Color white (round) Score 2 pieces
Shape ROUND (round) Size 12mm
Flavor Imprint Code 512
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 49999-852-40 40 TABLET In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA087463 06/10/2010

Labeler - Lake Erie Medical DBA Quality Care products LLC (831276758)
Establishment
Name Address ID/FEI Operations
Mallinckrodt Inc. 047021092 manufacture
Establishment
Name Address ID/FEI Operations
Lake Erie Medical DBA Quality Care Products LLC 831276758 repack
Revised: 06/2010 Lake Erie Medical DBA Quality Care products LLC