Acetaminophen and codeine

Usual Adult Dose for Pain:

Initial dose: Acetaminophen (300 to 600 mg) and codeine (15 to 60 mg) orally every 4 hours as needed for pain
-Titrate to a dose that provides adequate analgesia and minimizes adverse reactions
Maximum doses: Acetaminophen 4000 mg/24 hours; Codeine: 360 mg/24 hours

Comments:
-Initial doses should be individualized taking into account severity of pain, response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.
-Codeine doses higher than 60 mg have not been shown to improve pain relief and are associated with an increased incidence of adverse effects; tolerance to codeine can develop with continued use.
-Because of the risks of addiction, abuse and misuse, the lowest effective dose for the shortest duration consistent with individual patient treatment goals should be used.
-Monitor patients closely for respiratory depression within the first 24 to 72 hours of initiating therapy and following any increase in dose.

Use: For the management of mild to moderate pain where treatment with an opioid is appropriate and from which alternative treatments are inadequate.

Usual Pediatric Dose for Pain:

Less than 12 years: Contraindicated

12 to 18 years (postoperatively following a tonsillectomy and/or adenoidectomy): Contraindicated

12 to 18 years (with risk factors for respiratory depression): Avoid use

12 to 18 years: Use only if benefits outweigh potential risks
-Initial dose: Acetaminophen (300 to 600 mg) and codeine (15 to 60 mg) orally every 4 hours as needed for pain
Maximum doses: Acetaminophen 4000 mg/24 hours; Codeine: 360 mg/24 hours

Comments:
-Risk factors that increase sensitivity to the respiratory depressant effects of codeine include postoperative status, obstructive sleep apnea, obesity, and other conditions associated with hypoventilation syndromes (e.g., neuromuscular disease), concomitant use of other mediations that cause respiratory depression, and severe pulmonary disease.
-Initial doses should be individualized taking into account severity of pain, response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.
-Codeine doses higher than 60 mg have not been shown to improve pain relief and are associated with an increased incidence of adverse effects.
-Because of the risks of addiction, abuse and misuse, the lowest effective dose for the shortest duration consistent with individual patient treatment goals should be used.
-Monitor patients closely for respiratory depression within the first 24 to 72 hours of initiating therapy and following any increase in dose.

Use: For the management of mild to moderate pain where treatment with an opioid is appropriate and from which alternative treatments are inadequate.

Acetaminophen and codeine oral suspension is used to relieve mild to moderate pain. The oral tablets are used to relieve mild to moderately severe pain.

Acetaminophen is used to relieve pain and reduce fever in patients. It does not become habit-forming when taken for a long time. But acetaminophen may cause other unwanted effects when taken in large doses, including serious liver damage. Although rare, use of acetaminophen has been reported to lead to liver transplantation and death, usually at high doses and when multiple acetaminophen-containing products have been used.

Codeine belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain.

When codeine is used for a long time, it may become habit-forming, causing mental or physical dependence when it is used for a long time or in large doses. Physical dependence may lead to withdrawal side effects when you stop taking the medicine. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

acetaminophen and codeine is available only with your doctor's prescription.

Acetaminophen and Codeine phosphate tablets are indicated for the management of mild to moderate pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate.

Limitations of Use

Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses (see WARNINGS), reserve Acetaminophen and Codeine phosphate tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics)

• Have not provided adequate analgesia, or are not expected to provide adequate analgesia,

• Have not been tolerated, or are not expected to be tolerated.

Acetaminophen and Codeine phosphate tablets are contraindicated in:

• Patients with significant respiratory depression (see WARNINGS).

• Patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see WARNINGS).

• Postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy (see WARNINGS).

• Patients with known or suspected gastrointestinal obstruction, including paralytic ileus (see WARNINGS).

• Patients with hypersensitivity to codeine, acetaminophen, or any of the formulation excipients (e.g., anaphylaxis) (see WARNINGS).

• Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days.

Each Acetaminophen and Codeine Phosphate Tablet USP 300 mg/15 mg tablet contains acetaminophen 300 mg and codeine phosphate 15 mg. It is available as a round, white to off-white tablet debossed with “2” on one side and an M on the other side.

Bottles of 100......................................... NDC 0406-0483-01

Each Acetaminophen and Codeine Phosphate Tablet USP 300 mg/30 mg tablet contains acetaminophen 300 mg and codeine phosphate 30 mg. It is available as a round, white to off-white tablet debossed with “3” on one side and an M on the other side.

Bottles of 20........................................... NDC 0406-0484-20
Bottles of 30........................................... NDC 0406-0484-03
Bottles of 50........................................... NDC 0406-0484-50
Bottles of 100......................................... NDC 0406-0484-01
Bottles of 1000....................................... NDC 0406-0484-10
Unit Dose (10 x 10)............................... NDC 0406-0484-62 

Each Acetaminophen and Codeine Phosphate Tablet USP 300 mg/60 mg tablet contains acetaminophen 300 mg and codeine phosphate 60 mg. It is available as a round, white to off-white tablet debossed with “4” on one side and an M on the other side.

Bottles of 100......................................... NDC 0406-0485-01
Bottles of 500......................................... NDC 0406-0485-05 

Store Acetaminophen and Codeine phosphate tablets 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.

Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals logo and M are trademarks of a Mallinckrodt company.

© 2016 Mallinckrodt.

Mallinckrodt Inc.
Hazelwood, MO 63042 USA 

Rev 11/2016

Mallinckrodt™
Pharmaceuticals

An electronic copy of this medication guide can be obtained from www.mallinckrodt.com/Medguide/MG20A08.pdf or by calling 1-800-778-7898 for alternate delivery options.

This Medication Guide has been approved by the U.S. Food and Drug Administration.                        

Issued: November 2016

MG20A08

(a seet a MIN oh fen & KOE deen)

Acetaminophen: Although not fully elucidated, believed to inhibit the synthesis of prostaglandins in the central nervous system and peripherally block pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center.

Codeine: Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough suppression by direct central action in the medulla; produces generalized CNS depression.

Note: Adult doses ≥60 mg codeine fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of side effects.

Pain management: Oral:

Solution or suspension:

Acetaminophen 120 mg/codeine 12 mg per 5 mL: 15 mL every 4 hours as needed; adjust dose according to severity of pain and response of patient (maximum: acetaminophen 4,000 mg per 24 hours).

Acetaminophen 160 mg/codeine 8 mg per 5 mL [Canadian product]: 10 to 20 mL every 4 hours as needed; adjust dose according to severity of pain and response of patient (maximum: 100 mL per 24 hours)

Tablets: Acetaminophen (300 to 1,000 mg/dose)/codeine (15 to 60 mg/dose) every 4 hours as needed; adjust dose according to severity of pain and response of patient (maximum: acetaminophen 4,000 mg/codeine 360 mg per 24 hours).

Discontinuation of therapy: For patients on long term opioid therapy, decrease dose by 25% to 50% every 2 to 4 days; monitor carefully for signs/symptoms of withdrawal. If patient displays withdrawal symptoms, increase dose to the previous level and then reduce dose more slowly by increasing interval between dose reductions, decreasing amount of daily dose reduction, or both.

Note: The FDA has recommended that codeine not be used in pediatric patients <12 years of age and all pediatric patients undergoing tonsillectomy and/or adenoidectomy due to increased risk of breathing problems (sometimes fatal). Slowed or difficult breathing has been reported in pediatric patients <18 years of age; risk may be increased in pediatric patients who are obese or have conditions such as obstructive sleep apnea or severe lung disease, or who are ultrarapid metabolizers of the drug (FDA 2015; FDA 2017).

Pain management: Oral: Solution or suspension:

Acetaminophen 120 mg/codeine 12 mg per 5 mL:

Children 3 to 6 years: 5 mL 3 to 4 times daily as needed

Children 7 to 12 years: 10 mL 3 to 4 times daily as needed

Adolescents: Refer to adult dosing

Acetaminophen 160 mg/codeine 8 mg per 5 mL [Canadian product]: Children ≥12 years and Adolescents: Refer to adult dosing.

Also see individual agents.

Frequency not defined:

Central nervous system: Dizziness, drowsiness, dysphoria, euphoria, sedation, serotonin syndrome

Dermatologic: Pruritus, skin rash

Endocrine & metabolic: Adrenocortical insufficiency

Gastrointestinal: Abdominal pain, constipation, nausea, vomiting

Hematologic & oncologic: Agranulocytosis, thrombocytopenia

Hypersensitivity: Hypersensitivity reaction

Respiratory: Dyspnea

<1% (Limited to important or life-threatening): Hypogonadism (Brennan 2013; Debono 2011), respiratory depression

TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets are indicated for the relief of mild to moderately severe pain.

In the presence of head injury or other intracranial lesions, the respiratory depressant effects of codeine and other narcotics may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure. Narcotics also produce other CNS depressant effects, such as drowsiness, that may further obscure the clinical course of the patients with head injuries.

Codeine or other narcotics may obscure signs on which to judge the diagnosis or clinical course of patients with acute abdominal conditions.

Codeine is habit forming and potentially abusable. Consequently, the extended use of this product is not recommended.

TYLENOL® with Codeine (acetaminophen and codeine phosphate) tablets contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

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 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 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.

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 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.

Acetaminophen/codeine is a prescription medication used to treat mild to moderately severe pain.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take or use:

• alcohol
• tranquilizers such as chlordiazepoxide
• general anesthetics such as phenobarbital (Donnatal), alprazolam (Xanax), and clonazepam (Klonopin)
• central nervous system (CNS) depressants such as zolpidem (Ambien) or eszopiclone (Lunesta)
• other narcotic analgesics such as morphine (MS Contin), oxycodone (Oxycontin), or methadone (Dolophine)
• other medications containing acetaminophen
• antidepressants such as fluoxetine (Prozac, Sarafem), venlafaxine (Effexor), or citalopram (Celexa)

This is not a complete list of acetaminophen/codeine drug interactions. Ask your doctor or pharmacist for more information.

This medication may impair your thinking or reactions. Avoid driving or operating machinery until you know how acetaminophen and codeine will affect you.

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

US BOXED WARNINGS: ADDICTION, ABUSE AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; HEPATOTOXICITY; INTERACTIONS WITH DRUGS AFFECTING CYP450 ISOENZYMES; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:
-Addiction, Abuse, and Misuse: This drug exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
-Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur, especially during initiation or following a dose increase.
-Accidental Ingestion: Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose.
-Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life-threatening respiratory depression and death have occurred in children who received codeine; most cases following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine due to CYP450 2D6 polymorphism; Codeine is contraindicated in pediatric patients younger than 12 years and in patients less than 18 years undergoing tonsillectomy and/or adenoidectomy. Avoid use in patients 12 to 18 years who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.
-Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, the patient should be advised of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment will be available.
-Hepatotoxicity: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most cases have been associated with use at doses that exceed 4 g per day and often involve more than one acetaminophen-containing product.
-Interactions with Drugs Affecting CYP450 Isoenzymes: The effects of concomitant use or discontinuation of CYP450 3A4 inducers/inhibitors or CYP450 2D6 inhibitors with codeine are complex; concomitant use requires careful consideration of the effects on the parent drug (codeine) and the active metabolite (morphine).
-Concomitant Use with Benzodiazepines or Other CNS Depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Concomitant use should be reserved for use in patients for whom alternative treatment options are inadequate. If needed, limit dose and duration to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.

-Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III