Brand Names

ACETAMINOPHEN, CAFFEINE AND DIHYDROCODEINE BITARTRATE
ACETAMINOPHEN, CAFFEINE, AND DIHYDROCODEINE BITARTRATE
DHC PLUS
SYNALGOS-DC
SYNALGOS-DC-A
TREZIX

Boxed Warning

WARNING: Death Related to Ultra-Rapid Metabolism of Codeine to Morphine Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism. Hepatotoxicity 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.

Indications and Usage

TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsulesare indicated for the relief of moderate to moderately severe pain.

Dosage and Administration

The usual adult dosage is two (2) TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsules orally every four (4) hours, as needed. Dosage should be adjusted according to the severity of the pain and the response of the patient. No more than two (2) capsules should be taken in a 4-hour period. No more than five (5) doses, or ten (10) capsules should be taken in a 24-hour period.

Contraindications

Dihydrocodeine-containing products are contraindicated for postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy. This combination product is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, acetaminophen, caffeine, or any of the inactive components listed above, or any situation where opioids are contraindicated including significant respiratory depression (in unmonitored settings or in the absence of resuscitative equipment), acute or severe bronchial asthma or hypercapnia, and paralytic ileus.

Adverse Reactions

Dihydrocodeine: The most frequently observed adverse reactions include light-headedness, dizziness, drowsiness, headache, fatigue, sedation, sweating, nausea, vomiting, constipation, pruritus, and skin reactions. With the exception of constipation, tolerance develops to most of these effects. Other reactions that have been observed with dihydrocodeine or other opioids include respiratory depression, orthostatic hypotension, cough suppression, confusion, diarrhea, miosis, abdominal pain, dry mouth, indigestion, anorexia, spasm of biliary tract, and urinary retention. Physical and psychological dependence are possibilities. Hypersensitivity reactions (including anaphylactoid reactions), hallucinations, vivid dreams, granulomatous interstitial nephritis, severe narcosis and acute renal failure have been reported rarely during dihydrocodeine administration. Acetaminophen: Acetaminophen in therapeutic doses rarely causes adverse reactions. The most serious adverse reaction is hepatoxicity from overdosage (see OVERDOSAGE). Thrombocytopenia, leukopenia, pancytopenia, neutropenia, thrombocytopenic purpura, and agranulocytosis have been reported in patients receiving acetaminophen or p-aminophenol derivatives. Hypersensitivity reactions including urticarial or erythematous skin reactions, laryngeal edema, angioedema, or anaphylactoid reactions are rare. Caffeine: Adverse reactions associated with caffeine use include anxiety, anxiety neurosis, excitement, headaches, insomnia, irritability, lightheadedness, restlessness, tenseness, tremor, extrasystoles, palpitations, tachycardia, diarrhea, nausea, stomach pain, vomiting, diuresis, urticaria, scintillating scotoma, and tinnitus.

Drug Interactions

Dihydrocodeine with Other Central Nervous System Depressants: Patients receiving other opioid analgesics, sedatives or hypnotics, muscle relaxants, general anesthetics, centrally acting anti-emetics, phenothiazines or other tranquilizers, or alcohol concomitantly with this combination product may exhibit additive depressant effects on the central nervous system. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Dihydrocodeine with Monoamine Oxidase Inhibitors: Dihydrocodeine, like all opioid analgesics, interacts with monoamine oxidase inhibitors causing central nervous system excitation and hypertension. Dihydrocodeine with Mixed Agonist/Antagonist Opioid Analgesics: Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) may reduce the analgesic effect of this combination product. Acetaminophen Drug Interactions: Chronic and excessive consumption of alcohol may increase the hepatotoxic risk of acetaminophen. The potential for hepatotoxicity with acetaminophen also may be increased in patients receiving anticonvulsants that induce hepatic microsomal enzymes (including phenytoin, barbiturates, and carbamazepine) or isoniazide. Chronic ingestion of large doses of acetaminophen may slightly potentiate the effects of warfarin- and indandione- derivative anticoagulants. Severe hypothermia is possible in patients receiving acetaminophen concomitantly with phenothiazines. Caffeine Drug Interactions: Caffeine may enhance the cardiac inotropic effects of beta-adrenergic stimulating agents. Co-administration of caffeine and disulfiram may lead to a substantial decrease in caffeine clearance. Caffeine may increase the metabolism of other drugs such as phenobarbital and aspirin. Caffeine accumulation may occur when products or foods containing caffeine are consumed concomitantly with quinolones such as ciprofloxacin.

Overdosage

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 measure

⚠ Caution

Medical Disclaimer: This information is for educational purposes only. Always consult a healthcare professional before taking any medication.