DESCRIPTION: Each tablet contains: codeine phosphate 20 mg & acetaminophen 300 mg. Acetaminophen, is a non-opiate, non-salicylate analgesic and antipyretic. Codeine is an alkaloid, obtained from opium or prepared from morphine by methylation.

CLINICAL PHARMACOLOGY: Acetaminophen and codeine phosphate tablets combine the analgesic effects of a centrally acting analgesic, codeine, with a peripherally acting analgesic, acetaminophen. Both ingredients are well absorbed orally. The plasma elimination half-life ranges from 1 to 4 hours for acetaminophen, and from 2.5 to 3 hours for codeine. Following absorption, codeine is metabolized by the liver and metabolic products are excreted in the urine. Acetaminophen is metabolized primarily in the liver.

WARNINGS: Acetaminophen and codeine phosphate tablets contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms.

PRECAUTIONS:

Head injury and increased intracranial pressure, acute abdominal conditions & special risk patients: such as the elderly or debilitated, and with severe impairment of hepatic or renal function, hypothyroidism, addison's disease, and prostatic hypertrophy or urethral stricture.

Pregnancy: Pregnancy Category C. Acetaminophen and codeine phosphate tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Dependence has been reported in newborns whose mothers took opiates regularly during pregnancy. Withdrawal signs include irritability, excessive crying, tremors, hyperreflexia, fever, vomiting, and diarrhea. In nursing mothers the possibility of clinically important amounts being excreted in breast milk in individuals abusing codeine should be considered.

 DRUG ABUSE AND DEPENDENCE: Codeine can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychic dependence, physical dependence and tolerance may develop upon repeated administration of this drug.

Drug Interactions: Other narcotic analgesics, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantly with this drug may exhibit an additive CNS depression. The concurrent use of anticholinergics with codeine may produce paralytic ileus.

SIDE EFFECTS: The most frequently observed adverse reactions include lightheadedness, dizziness, and sedation, shortness of breath, nausea and vomiting. Other adverse reactions include allergic reactions, euphoria, dysphoria, constipation, abdominal pain and pruritus. At higher doses, codeine has most of the disadvantages of morphine including respiratory depression.

OVERDOSAGE:

Acetaminophen: 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. Treatment:  The stomach should be emptied promptly by lavage or by induction of emesis with syrup of ipecac. Serum acetaminophen assay should be obtained as early as possible, but no sooner than four hours following ingestion. Liver function studies should be obtained initially and repeated at 24-hour intervals. The antidote, N-acetylcysteine, should be administered as early as possible, preferably within 16 hours of the overdose ingestion for optimal results, but in any case, within 24 hours.

Codeine: serious overdose with codeine is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur. 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. The narcotic antagonist naloxone is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including codeine. Therefore, an appropriate dose of naloxone hydrochloride should be administered, and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated. Gastric emptying may be useful in removing unabsorbed drug.

DOSAGE AND ADMINISTRATION:

The usual adult dosage for tablets is: 1 Tablet every 6 hours.

Single Doses (Range): Codeine Phosphate 15mg-60mg, Acetaminophen 300mg-1000mg

Maximum 24 Hour Dose: Codeine Phosphate 360mg, Acetaminophen 4000mg.

How Supplied: Each package of Ruz-Acetaminophen Codeine contains 10 blisters and each blister contains 10 white & round scored tablets. Store below 30°C.

Reference: PDR 2000, page 2216-7

                USPDI for Professional Health Care, 2004, Page 2168-9