Animal studies to evaluate the carcinogenic potential of oxycodone and acetaminophen have not been performed.
Updated February 25, 2010.
Free and conjugated noroxycodone, free and conjugated oxycodone, and oxymorphone are excreted in human urine following a single oral dose of oxycodone. A high portion of oxycodone is N-dealkylated to noroxycodone during first-pass metabolism. Approximay 8% to 14% of the dose is excreted as free oxycodone over 24 hours after administration. The metabolism of oxycodone to oxymorphone is catalyzed by CYP2D6. Following a single, oral dose of oxycodone, the mean ± SD elimination half-life is 3.51 ± 1.43 hours. Oxymorphone, is formed by the O-demethylation of oxycodone.
1 Aluminum Lake. All strengths of PERCOCET 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 and the 5 mg/325 mg strength contains FD&C Blue No. The 7.5 mg/325 mg and the 7.5 mg/500 mg strengths contain FD&C Yellow No. 6 Aluminum Lake. The 10 mg/325 mg and the 10 mg/650 mg strengths contain D&C Yellow No. 10 Aluminum Lake.
Therefore, the pharmacologic effects of acetaminophen may be increased. Beta Blockers (Propanolol): Propanolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of acetaminophen.
After hepatic conjugation, 90 to 100% of the drug is recovered in the urine with in the first day. About 80-85% of the acetaminophen in the body is conjugated principally with glucuronic acid and to a lesser extent with sulfuric acid and cysteine. Acetaminophen is metabolized in the liver via cytochrome P450 microsomal enzyme.
PERCOCET tablets are not recommended for use in women during and immediay prior to labor and delivery due to its potential effects on respiratory function in the newborn.
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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. 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.
Loop diuretics: The effects of the loop diuretic may be decreased because acetaminophen may decrease renal prostaglandin excretion and decrease plasma renin activity.
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.
Charcoal (activated): Reduces acetaminophen absorption when administered as soon as possible after overdose.
Lamotrigine: Serum lamotrigine concentrations may be reduced, producing a decrease in therapeutic effects.
Animal reproductive studies have not been conducted with PERCOCET. PERCOCET should not be given to a pregnant woman unless in the judgment of the physician, the potential benefits outweigh the possible hazards. It is also not known whether PERCOCET can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.
Acetaminophen is relatively uniformly distributed throughout most body fluids. Absorption of acetaminophen is rapid and almost complete from the GI tract after oral administration. Binding of the drug to plasma proteins is variable; only 20% to 50% may be bound at the concentrations encountered during acute intoxication. With overdosage, absorption is complete in 4 hours.
PERCOCET 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.
Each tablet, for oral administration, contains oxycodone hydrochloride and acetaminophen in the following strengths:
The frequency of this possible cross-sensitivity is unknown. Following administration of PERCOCET tablets, anaphylactic reactions have been reported in patients with a known hypersensitivity to codeine, a compound with a structure similar to morphine and oxycodone.
PERCOCET is indicated for the relief of moderate to moderay severe pain.
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.
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.
The molecular formula for acetaminophen is C 8 H 9 NO 2 and the molecular weight is 151.17. It 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.
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.
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.
PERCOCET 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.
Standard supportive therapy should be implemented. Caution should be taken to monitor for decreased bowel motility in postoperative patients receiving opioids. Ileus is a common postoperative complication, especially after intra-abdominal surgery with use of opioid analgesia. Oxycodone and other morphine-like opioids have been shown to decrease bowel motility.
Safety and effectiveness in pediatric patients have not been established.
The antipyretic effect of acetaminophen is accomplished through the inhibition of endogenous pyrogen action on the hypothalamic heat-regulating centers. Acetaminophen is a non-opiate, non-salicylate analgesic and antipyretic. The site and mechanism for the analgesic effect of acetaminophen has not been determined.
A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Depending on the sensitivity/specificity and the test methodology, the individual components of PERCOCET (Oxycodone and Acetaminophen Tablets, USP) may cross-react with assays used in the preliminary detection of cocaine (primary urinary metabolite, benzoylecgonine) or marijuana (cannabinoids) in human urine. 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.
It is derived from the opium alkaloid thebaine, and may be represented by the following structural formula:. The molecular formula for oxycodone hydrochloride is C 18 H 21 NO 4 •HCl and the molecular weight 351.83. Oxycodone, 14-hydroxydihydrocodeinone, is a semisynthetic opioid analgesic which occurs as a white, odorless, crystalline powder having a saline, bitter taste.
Zidovudine: The pharmacologic effects of zidovudine may be decreased because of enhanced non-hepatic or renal clearance of zidovudine.
Oxycodone has been shown to be 45% bound to human plasma proteins in vitro. The mean absolute oral bioavailability of oxycodone in cancer patients was reported to be about 87%. The volume of distribution after intravenous administration is 211.9 ±186.6 L.
Acetaminophen may interfere with home blood glucose measurement systems; decreases of >20% in mean glucose values may be noted. This effect appears to be drug, concentration and system dependent.
Oxycodone 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. These effects are mediated by receptors (notably µ and κ) in the central nervous system for endogenous opioid-like compounds such as endorphins and enkephalins. 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.
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. 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. High doses of acetaminophen may deplete the glutathione stores so that inactivation of the toxic metabolite is decreased. It is believed that the toxic metabolite NAPQI (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone) is responsible for liver necrosis.
Oxycodone produces effects on pupillary response and consciousness which may obscure neurologic signs of worsening in patients with head injuries. 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.
Oral Contraceptives: Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of acetaminophen.
Alcohol, ethyl: Hepatotoxicity has occurred in chronic alcoholics following various dose levels (moderate to excessive) of acetaminophen.
Opioid analgesics may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.
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.
In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION: Cessation of Therapy ).
Animal studies to evaluate the effects of oxycodone on fertility have not been performed.
Special precaution should be given when determining the dosing amount and frequency of PERCOCET tablets for geriatric patients, since clearance of oxycodone may be slightly reduced in this patient population when compared to younger patients.
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 and tolerance are not unusual during chronic opioid therapy. Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist.
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. 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.
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.
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.
Acetaminophen is also excreted in breast milk in low concentrations. Ordinarily, nursing should not be undertaken while a patient is receiving PERCOCET 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.
Administration of PERCOCET (Oxycodone and Acetaminophen Tablets, USP) tablets should be closely monitored for the following potentially serious adverse reactions and complications:
The following information should be provided to patients receiving PERCOCET tablets by their physician, nurse, pharmacist, or caregiver:
Oxycodone Hydrochloride, USP 10 mg* Acetaminophen, USP 325 mg *10 mg oxycodone HCl is equivalent to 8.9637 mg of oxycodone.
Anticholinergics: The onset of acetaminophen effect may be delayed or decreased slightly, but the ultimate pharmacological effect is not significantly affected by anticholinergics.
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.
The administration of PERCOCET (Oxycodone and Acetaminophen Tablets, USP) or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
PERCOCET tablets should not be administered to patients with known hypersensitivity to oxycodone, acetaminophen, or any other component of this product.
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. 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). The identities of 6-keto opiates (e.g., oxycodone) can further be differentiated by the analysis of their methoxime-trimethylsilyl (MO-TMS) derivative.
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.
Concerns about misuse, addiction, and diversion should not prevent the proper management of pain. Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing PERCOCET tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with PERCOCET tablets may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Oxycodone is an opioid agonist of the morphine-type.
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. 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 PERCOCET tablets may exhibit an additive CNS depression.
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. 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. The combination of oxycodone and acetaminophen has not been evaluated for mutagenicity.
Oxycodone Hydrochloride, USP 10 mg* Acetaminophen, USP 650 mg *10 mg oxycodone HCl is equivalent to 8.9637 mg of oxycodone.
Oxycodone Hydrochloride, USP 7.5 mg* Acetaminophen, USP 500 mg *7.5 mg oxycodone HCl is equivalent to 6.7228 mg of oxycodone.
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. 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. Respiratory depression is a hazard with the use of oxycodone, one of the active ingredients in PERCOCET tablets, as with all opioid agonists. 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 case of respiratory depression, a reversal agent such as naloxone hydrochloride may be utilized (see OVERDOSAGE ).
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.
Probenecid: Probenecid may increase the therapeutic effectiveness of acetaminophen slightly.
Oxycodone is contraindicated in the setting of suspected or known paralytic ileus. 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.
Precaution should be taken in patients with liver disease. Hepatotoxicity and severe hepatic failure occurred in chronic alcoholics following therapeutic doses.Oxycodone hydrochloride