Acetaminophen may act predominantly by inhibiting prostaglandin synthesis in the central nervous system ( CNS ) and , to a lesser extent through a peripheral action by blocking pain – impulse generation . Acetaminophen probably produces antipyresis by acting centrally on the hypothalamic heat – regulation center to produce peripheral vasodilation resulting in increased blood flow through the skin , sweating , and heat loss . Codeine as an opioid analgesic binds with stereospecific opioid receptors at many sites within CNS to alter processes affecting both the perception of pain and the emotional response to pain . Although the precise sites and mechanisms of action have not been fully determined , alterations in release of various neurotransmitter from afferent nerves sensitive to painful stimuli may be partially responsible for the analgesic effects . Codeine as an antidiarrheal agent acts locally and possibly centrally to alter intestinal motility . Codeine as an antitussive suppresses the cough reflex by a direct central action , probably in the medulla or pons .

Acetaminophen codeine is indicated to relieve mild to severe pain ( depending on the dose of codeine ).

Acetaminophen: Agranulocytosis ; Anemia ; Thrombocytopenia ; Allergic dermatitis ; Hepatitis ; Renal colic ; Renal failure ; sterile pyuria .
Codeine:
a – Medical attention needed: Allergic reaction ( skin rash , hives , and / or itching ; swelling of face ) ; Atelectasis ; Bronchospastic allergic reation ; Allergic laryngeal edema ; Allergic laryngospasm ; Respiratory depression ; Paradoxical CNS stimulation ( unusual excitement or restlessness ) , especially in children ; Confusion ; Fast , slow , or pounding heartbeat ; Histamine release ( decreased blood pressure , fast heartbeat , increased sweating , redness or flushing of face , wheezing or troubled breathing ) ; Convulsions ; Hallucinations ; Mental depression ; Muscle rigidity , especially in muscles of respiration ; Paralytic ileus or toxic megacolon ; Trembling or uncontrolled muscle movements ; Hepatotoxicity ; Increased blood pressure ; Ringing or buzzing in the ears .
b – medical attention needed only if continuing or bothersome: Constipation ; Drowsiness ; Antidiuretic effect ( decreased urination ) ; Blurred or double vision or other changes in vision ; Dizziness , feeling faint , or lightheadedness ; Dry mouth ; False sense of well – being ; General feeling of discomfort or illness ; Headache ; Hypotention ; Loss of appetite ; Nausea or vomiting ; Nervousness or restlessness ; Unusual tiredness or weakness ; Ureteral spasm ; Biliary spasm ; Gastrointestinal irritation ( stomach pain or cramps ) ; Nightmare or unusual dreams ; Trouble in sleeping .
c – Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued: Body aches ; Diarrhea ; Fast heartbeat ; Fever ; Runny nose , or sneezing ; Gooseflesh ; Increased sweating ; Increased yawning ; Loss of appetite ; Nausea or vomiting ; Nervousness , restlessness , or irritability ; Shivering or trembling ; Stomach cramps ; Trouble in sleeping ; Unusually large pupils ; Weakness . Withdrawal symptoms produced by codeine are less severe than those produced by stronger opioid agonist analgesics .

Hypersensitivity to acetaminophen , codeine , or any component of the formulation ; Significant respiratory depression ; Acute or severe bronchial asthma ; Hypercapnia ; Paralytic ileus ; Diarrhea associated with pseudomembranous colitis or caused by poisoning , until toxic material has been eliminated from gastrointestinal tract .

Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists ( morphine , hydrocodone ) . Tolerance or drug dependence may result from extended use . Limit total acetaminophen dose to < 4 g / day . Acetaminophen may cause severe hepatic toxicity on acute overdose ; in addition , chronic daily dosing in adults has resulted in liver damage in some patients . Use with caution in patients with alcoholic liver disease . Use caution in patients with known G6PD deficiency . This combination should be used with caution in elderly or debilitated patients , hypotension , adrenocortical insufficiency , thyroid disorders , prostatic hyperplasia , urethral stricture , seizure disorder , CNS depression , head injury or increased intracranial pressure . Codeine causes sedation ; caution must be used in performing tasks which require alertness ( eg , operation machinery or driving ) .

Barbiturates , primidone , carbamazepine , hydantoins , rifampin and sulfinpyrazone may decrease the analgesic effect of acetaminophen . Cholestyramine may decrease acetaminophen absorption ( separate dosing by at least 1 hour ) . Barbiturates , carbamazepine , hydantoins , isoniazid , rifampin , sulfinpyrazone and chronic ethanol abuse increase the hepatotoxic potential of acetaminophen . Effect of warfarin may be enhanced . Prolonged concurrent use of acetaminophen and a salicylate and NSAIDs may increase the risk of adverse renal effects . Concurrent use of alcohol or other CNS depression – producing medications with codeine may result in increased CNS depressant , respiratory depressant , and hypotensive effects ; caution is recommended and dosage of one or both agents should be reduced . Concurrent use of codeine with other CNS depressants having habituation potential may increase the risk of habituation . Concurrent use of codeine with anticholinergics or other medications with anticholinergic activity may result in increased risk of severe constipation , which may lead to paralytic ileus , and / or urinary retention . Concurrent use of antiperistaltic antidiarrheals , such as diphenoxylate , kaolin , pectin , belladonna alkaloids , loperamide , opium tincture and paregoric with codeine may increase the risk of severe constipation as well as CNS depression . The hypotensive effects of ganglionic blockers such as guanethidine , diuretics or other hypotension – producing medications may be potentiated when used concurrently with codeine , leading to increased risk of orthostatic hypotension . Concurrent use of hydroxyzine with codeine may result in increased analgesia as well as CNS depressant and hypotensive effects . Codeine may antagonize the effects of metoclopramide on gastrointestinal motility . Codeine may be used cautiously and in reduced dosage in patients receiving MAO inhibitors, including furazolidone , pargynile , and procarbazine . Naxolone antagonizes the analgesic , CNS , and respiratory depressant effects of codeine . The administration of naltrexone to a patient physically dependent on codeine will precipitate withdrawal symptoms . Also , naltrexone blocks the therapeutic effects of codeine . The effect of warfarin may be enhanced .

Relief of pain ; Respiratory and mental status ; Blood pressure ; Bowel function .

Acetaminophen codeine may be taken with food .

Usual adult dose:
Analgesic – Oral , 1 to 2 tablets every four hours as needed .

• Tablet : acetaminophen 300 mg and codeine 20 mg.

• USP DI, 2005
• Up To Date, Vol. 13.3 (2005)
• Martindale, The Complete Drug Reference, 34 rd edition 2005