BOXED WARNING
id: 3b65ccb4-dd3a-7495-e054-00144ff88e88
displayName: BOXED WARNING SECTION
FDA Article Code: 34066-1
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.
DESCRIPTION
id: 3b65ccb4-dd3b-7495-e054-00144ff88e88
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Each tablet contains:
Acetaminophen, USP……………………………………………………..300 mg
Codeine Phosphate, USP……………………………………………………30 mg
(Warning: May be habit forming)
Inactive ingredients: croscarmellose sodium, crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch and stearic acid.
Acetaminophen and codeine is supplied in tablet form for oral administration.
Acetaminophen, 4′-hydroxyacetanlllde, IS a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:
Codeine phosphate, 7,8-didehydro-4,5α-epoxy-3-methoxy-l7-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate, a white crystalline powder, is a narcotic analgesic and antitussive. It has the following structural formula:
CLINICAL PHARMACOLOGY
id: 3b65ccb4-dd3c-7495-e054-00144ff88e88
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
Acetaminophen and Codeine Phosphate Tablets combines the analgesic effects of a centrally acting analgesic, codeine, with a peripherally acting analgesic, acetaminophen.
Pharmacokinetics
The behavior on the individual components is described below.
Codeine
Codeine is rapidly 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 (about 70%), free and conjugated morphine (about 10%), normorphine (4%) and hydrocodone (1%). The remainder of the dose is excreted in the feces.
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
id: 3b65ccb4-dd3d-7495-e054-00144ff88e88
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Acetaminophen and Codeine Phosphate Tablets, USP are indicated for the relief of mild to moderately severe pain.
CONTRAINDICATIONS
id: 3b65ccb4-dd3e-7495-e054-00144ff88e88
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Codeine-containing products are contraindicated for post-operative pain management in children who have undergone tonsillectomy and/or adenoidectomy.
Acetaminophen and Codeine Phosphate Tablets should not be administered to patients who have previously exhibited hypersensitivity to codeine or acetaminophen.
ADVERSE REACTIONS
id: 3b65ccb4-dd4f-7495-e054-00144ff88e88
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
The most frequently observed adverse reactions include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea and vomiting. These effects seem to be more prominent in ambulatory than in non-ambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down.
Other adverse reactions include allergic reactions, euphoria, dysphoria, constipation, abdominal pain, pruritus, rash, thrombocytopenia and agranulocytosis.
At higher doses codeine has most of the disadvantages of morphine including respiratory depression.
OVERDOSAGE
id: 3b65ccb4-dd53-7495-e054-00144ff88e88
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
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 phosphate, 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.
DOSAGE AND ADMINISTRATION
id: 3b65ccb4-dd54-7495-e054-00144ff88e88
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Dosage should be adjusted according to severity of pain and response of the patient.
The usual adult dosage is:
Single Doses Maximum
Range
24-Hour Dose
Codeine Phosphate 15mg to 60mg 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.
HOW SUPPLIED
id: 3b65ccb4-ddd8-7495-e054-00144ff88e88
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Acetaminophen and Codeine Phosphate Tablets, USP 300 mg /30 mg are white, round, flat, beveled edged tablets debossed “IP 33” on obverse and “3” on reverse.
They are available as follows:
Bottles of 15: NDC 66267-001-15
Bottles of 20: NDC 66267-001-20
Bottles of 24: NDC 66267-001-24
Bottles of 30: NDC 66267-001-30
Bottles of 60: NDC 66267-001-60
Store Acetaminophen and Codeine Phosphate Tablets, USP 300 mg/30 mg at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in tight, light-resistant container as defined in the USP.
Questions or Comments?
Call 1-877-835-5472
Monday through Friday 9AM-5PM EST.
Repackaged by:
NuCare Pharmaceuticals, Inc.
Orange, CA 92867
Manufactured by:
Amneal Pharmaceuticals
Hauppauge, NY 11788
Rev. 12-2015-00
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL -Bottle of 30
id: 3b65ccb4-ddda-7495-e054-00144ff88e88
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
