Following an acute overdosage with TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsules, toxicity may result from the dihydrocodeine or the acetaminophen. Toxicity due to the caffeine component is less likely, due to the relatively small amounts in this formulation. An overdose is a potentially lethal polydrug overdose situation, and consultation with a regional Poison Control Center is recommended. A listing of the poison control centers can be found in standard references such as the Physician's Desk Reference®.  
  
Signs and Symptoms: Toxicity from dihydrocodeine poisoning include the opioid triad of: pinpoint pupils, respiratory depression, and loss of consciousness. Convulsions, cardiovascular collapse, and death may occur. A single case of acute rhabdomyolysis associated with an overdose of dihydrocodeine has been reported. 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. Acute caffeine poisoning may cause insomnia, restlessness, tremor, delirium, tachycardia, and extrasystoles.  
  
Because overdose information on this combination product is limited, it is unclear which of the signs and symptoms of toxicity would manifest in any particular overdose situation.  
  
Treatment   
A single or multiple drug overdose with TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsules 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, and vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered. For respiratory depression due to overdosage or unusual sensitivity to dihydrocodeine, parenteral naloxone is a specific and effective antagonist. 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.