Signs and Symptoms

Serious overdose with oxycodone and acetaminophen tablets is characterized by signs and symptoms of opioid and acetaminophen overdose. Oxycodone overdosage can be manifested 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, pupillary constriction (pupils may be dilated in the setting of hypoxia), and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory

collapse, cardiac arrest and death may occur.

In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma and thrombocytopenia may also occur.

In adults, hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams and fatalities with less than 15 grams. Plasma acetaminophen levels > 300 mcg/ml at 4 hours postingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are < 120 mcg/ml or < 30 mcg/ml at 12 hours after ingestion.

Importantly, young children seem to be more resistant than adults to the hepatotoxic effect of an acetaminophen overdose. Despite this, the measures outlined below should be initiated in any adult or child suspected of having ingested an acetaminophen overdose.

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

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. Supportive measures (including oxygen, intravenous fluids, and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose

as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.

The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids including oxycodone. Therefore, an appropriate dose of naloxone hydrochloride should be administered (usual initial adult dose 0.4 mg-2 mg) preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. 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. Opioid antagonists should not be administered in the absence of clinically significant respiratory of circulatory depression secondary to oxycodone overdose. In patients who are physically dependent on any opioid agonist including oxycodone, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered.

Please see the prescribing information for the specific opioid antagonist for details of their proper use.

Gastric emptying and/or lavage may be useful in removing unabsorbed drug. This procedure is recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of activated charcoal, as a slurry, is beneficial, if less than three hours have passed since ingestion. Charcoal adsorption should not be employed prior to lavage and emesis.

If an acetaminophen overdose is suspected, the stomach should be promptly emptied by lavage. A serum acetaminophen assay should be obtained as soon as possible, but no sooner than 4 hours following ingestion. Liver function studies should be obtained initially and repeated at 24-hour intervals. The antidote N-acetylcysteine (NAC) should be administered as early as possible, preferably within 16 hours of the overdose ingestion, but in any case within 24 hours. As a guide to treatment of acute ingestion, the acetaminophen level can be plotted against time since ingestion on a nomogram (Rumack-Matthew). The upper toxic line on the nomogram is equivalent to 200 mcg/ml at 4 hours while the lower line is equivalent to 50 mcg/ml at 12 hours. If serum level is above the lower line, and entire course of N-acetylcysteine treatment should be instituted. NAC therapy should be withheld if the acetaminophen level is below the lower line.

The toxicity of oxycodone and acetaminophen in combination is unknown.