tory 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). 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. hepatoxicity 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. 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 oxycodone and acetaminophen tablets immediately and seek medical care if they experience these symptoms. do not prescribe oxycodone and acetaminophen tablets for patients with acetaminophen allergy.

longer require therapy, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

osis. 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

th 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. 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. metabolism 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 80-85% 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 with in 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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