Dosage should be adjusted according to severity of pain and response of the patient.
The usual adult dosage is:
Single Doses (range) Maximum 24 Hour Dose
Codeine Phosphate 15 mg to 60 mg 360 mg
Acetaminophen 300 mg to 1000 mg 4000 mg
The usual dose of codeine phosphate in children is 0.5 mg/kg.
Doses may be repeated up to every 4 hours.
The prescriber must determine the number of tablets per dose, and the maximum number of tablets per
24 hours based upon the above dosage guidance. This information should be conveyed in the
prescription.
It should be kept in mind, however, that tolerance to codeine can develop with continued use and that the
incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg fail to give
commensurate relief of pain but merely prolong analgesia and are associated with an appreciably
increased incidence of undesirable side effects. Equivalently high doses in children would have similar
effects.

Following an acute overdosage, toxicity may result from codeine or acetaminophen.
Signs and Symptoms
Toxicity from codeine poisoning includes the opioid triad of: pinpoint pupils, depression of respiration,
and loss of consciousness. Convulsions may occur.
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.
Treatment
A single or multiple drug overdose with acetaminophen and codeine 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, 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 codeine, 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.

ACETAMINOPHEN AND CODEINE PHOSPHATE TABLETS, USP CIII
Rx only

Acetaminophen and codeine are supplied in tablet form for oral administration.
Acetaminophen, USP, 4'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a
non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:
C H NO M.W. 151.16
Codeine phosphate, USP, 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate
(1:1) (salt) hemihydrate, a white crystalline powder, is a narcotic analgesic and antitussive. It has the
following structural formula:
8 9 2
C H NO •H PO •1/2H O M.W. 406.37
Each tablet contains:
acetaminophen, USP...........................300 mg
codeine phosphate, USP.......................15 mg
(Warning: May be habit forming)
OR
acetaminophen, USP...........................300 mg
codeine phosphate, USP....................... 30 mg
(Warning: May be habit forming)
OR
acetaminophen, USP...........................300 mg
codeine phosphate, USP....................... 60 mg
(Warning: May be habit forming)
In addition, each tablet contains the following inactive ingredients: corn starch, colloidal silicon
dioxide, croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 300 mg/60
mg strength tablets also contain crospovidone, povidone, pregelatinized starch, and stearic acid.
CLINICAL PHARMACOLOGY
This product combines the analgesic effects of a centrally acting analgesic, codeine, with a
peripherally acting analgesic, acetaminophen.
Pharmacokinetics
The behavior of the individual components is described below.
Codeine
Codeine is readily absorbed from the gastrointestinal tract. It is rapidly distributed from the
intravascular spaces to the various body tissues, with preferential uptake by parenchymatous organs
such as the liver, spleen and kidney. Codeine crosses the blood-brain barrier, and is found in fetal tissue
and breast milk. The plasma concentration does not correlate with brain concentration or relief of pain;
however, codeine is not bound to plasma proteins and does not accumulate in body tissues.
The plasma half-life is about 2.9 hours. The elimination of codeine is primarily via the kidneys, and
about 90% of an oral dose is excreted by the kidneys within 24 hours of dosing. The urinary secretion
products consist of free and glucuronide conjugated codeine (about 70%), free and conjugated
norcodeine (about 10%), free and conjugated morphine (about 10%), normorphine (4%), and
hydrocodone (1%). The remainder of the dose is excreted in the feces.
18 21 3 3 4 2
At therapeutic doses, the analgesic effect reaches a peak within 2 hours and persists between 4 and 6
hours.
See OVERDOSAGE for toxicity information.
Acetaminophen
Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most
body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and
following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation)
and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine
within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other
conjugates and unchanged drug.
See OVERDOSAGE for toxicity information.
INDICATIONS AND USAGE
Acetaminophen and codeine phosphate tablets are indicated for the relief of mild to moderately severe
pain.

[image: img_2a56fff3-1702-5e2e-e054-00144ff8d46c]

HOW SUPPLIED
Acetaminophen and codeine phosphate tablets USP (white, round, unscored):
Acetaminophen and codeine phosphate tablets USP (white, round, unscored):
List No. 0050, acetaminophen 300 mg and codeine phosphate 15 mg, debossed “2” on one side and
“TV”-“50” on the other side of tablet is available in bottles of 100 (NDC 0093-0050-01) tablets.
List No. 0150, acetaminophen 300 mg and codeine phosphate 30 mg, debossed “3” on one side and
“TV”-“150” on the other side of tablet is available in bottles of 100 (NDC 0093-0150-01) and 1000
(NDC 0093-0150-10) tablets.
List No. 0350, acetaminophen 300 mg and codeine phosphate 60 mg, debossed “4” on one side and
“93”-“350” on the other side of tablet is available in bottles of 100 (NDC 0093-0350-01), 500 (NDC
0093-0350-05), and 1000 (NDC 0093-0350-10) tablets.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from moisture.
PROTECT FROM LIGHT
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as
required).
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
Distributed By:
TEVA PHARMACEUTICALS USA, INC.
North Wales, PA 19454
Rev. AI 8/2015