codeine/acetaminophen (Rx)

Brand and Other Names:Tylenol with Codeine, Tylenol #3, more...Tylenol #4
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet: Schedule III

  • 15mg/300mg
  • 30mg/300mg
  • 60mg/300mg

oral suspension: Schedule V

  • (12mg/120mg)/5mL
more...

Mild to Moderately Severe Pain

Tablet: 30-60 mg codeine/dose PO q4-6hr; not to exceed 360 mg codeine/day or 4 g acetaminophen/day

Oral solution: 15 mL (36 mg/360 mg) PO q4hr PRN; not to exceed 4 g acetaminophen/day

Dosing considerations

  • Based on the dosage strength selected and pain severity/tolerance, the prescriber must determine the number of tablets for each dose and frequency of administration (typically q4-6hr)

Cough

15-30 mg codeine/dose PO q4-6hr; not to exceed 360 mg codeine/day or 4 g acetaminophen/day

Dosage Modifications

Renal impairment: Use caution

Hepatic impairment: May tolerate low-dose therapy in hepatic cirrhosis; avoid chronic use

Dosage Forms & Strengths

tablet: Schedule III

  • 15mg/300mg
  • 30mg/300mg
  • 60mg/300mg

oral suspension: Schedule V

  • (12mg/120mg)/5mL
more...

Mild to Moderately Severe Pain

Tablet

  • 7-12 years: 0.5-1 mg codeine/kg/dose PO q4-6hr (not to exceed 5 doses q24hr); 10-15 mg acetaminophen/kg/dose PO q4-6hr (not to exceed 2.6 g acetaminophen q24hr) 
  • >12 years: As adults; single dose range is 15-60 mg/dose for codeine (not to exceed 360 mg q24hr) and 300-1000 mg/dose for acetaminophen (not to exceed 4 g q24hr); may repeat dose q4hr

Oral suspension

  • <3 years: Safety and efficacy not established
  • 3-6 years: 5 mL (12 mg/120 mg) PO q6-8hr
  • 7-12 years: 10 mL (24 mg/240 mg) PO q6-8hr
  • >12 years: 15 mL (36 mg/360 mg) PO q4hr prn

Dosing Considerations

Maximum acetaminophen dose in children should not exceed the following

3 years: 800 mg/day

4-6 years: 1200 mg/day

6-8 years: 1600 mg/day

9-10 years: 2000 mg/day

11-12 years: 2400 mg/day

>12 years: 4000 mg/day

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Interactions

Interaction Checker

and codeine/acetaminophen

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            Adverse Effects

            Frequency Not Defined (Codeine)

            Constipation

            Drowsiness

            Hypotension

            Tachycardia or bradycardia

            Confusion

            Dizziness

            False feeling of well being

            Headache

            Lightheadedness

            Malaise

            Paradoxical CNS stimulation

            Restlessness

            Rash

            Urticaria

            Anorexia

            Nausea

            Vomiting

            Xerostomia

            Ureteral spasm

            Decreased urination

            Increased LFTs

            Burning at injection site

            Weakness

            Blurred vision

            Dyspnea

            Histamine release

            Frequency Not Defined (Acetaminophen)

            Pruritic maculopapular rash

            Urticaria

            Laryngeal edema

            Angioedema

            Anaphylactoid reaction

            Thrombocytopenia

            Leukopenia

            Pancytopenia

            Neutropenia

            Thrombocytopenic purpura

            Agranulocytosis

            Hepatotoxicity

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            Warnings

            Black Box Warnings

            Contains acetaminophen

            Hepatotoxicity may occur with acetaminophen doses that exceed 4 g/day; take into account all acetaminophen-containing products that the patient is taking, including PRN doses and OTC products

            Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplantation or death

            New dosage limit allows no more than 325 mg/dosage unit for prescription medications that contain acetaminophen

            Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times a day (12 dosage units) and still not exceed the maximum daily dose of acetaminophen of 4 g/day

            Respiratory depression and death reported following tonsillectomy and/or adenoidectomy in patients that appeared to be rapid metabolizers of codeine due to CYP2D6 polymorphism

            Contraindications

            Hypersensitivity

            Hepatitis or severe hepatic/renal impairment

            Postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy

            Cautions

            Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplantation and death; risk increases in individuals with underlying liver disease, alcohol ingestion, and/or use of more than 1 acetaminophen-containing product (see Black Box Warnings)

            Acetaminophen: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash

            Acetaminophen may cause serious an potentially fatal skin reactions

            Patients with G6PD deficiency

            Use caution in repeated administration in patients with anemia or with cardiovascular, pulmonary, or renal disease

            Use caution in patients with history of porphyria

            May cause hypotension; use with caution in patients with hypovolemia

            Codeine may cause depression; avoid driving car or operating heavy machinery

            Use caution in patients with conditions associated with hypoxia, hypercapnia, upper respiratory obstruction, or debilitated patients

            May increase respiratory depressant effects; caution with head injury, COPD, or other conditions associated with decreased respiratory drive

            Use caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists including oxymorphone, levorphanol, oxycodone, or hydrocodone

            Codeine may cause tolerance/dependency

            May obscure diagnosis or clinical course of patients with acute abdominal conditions and may worsen gastrointestinal ileus due to reduced GI motility

            Use cuation in adrenal insufficiency, billiary tract impairment, patients susceptible to intracranial effects of CO2 retention, G6PD deficiency, head trauma, prostatic hyperplasia, hepatic/renal impairment, thyroid dysfunction, seizure disorder, or respiratory disease (COPD)

            Codeine may cause or exacerbate constipation; chronic use may result in obstructive bowel disease, especially in patients with existing intestinal motility disorders; reduce potential for constipation by taking preventive measures, including the increase of fiber intake and the use of stool softeners

            Long-term use in patients with adrenal insufficiency may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis

            Use with caution in patients with biliary tract dysfunction, including pancreatitis; may increase amylase/lipase levels and may cause constriction of sphincter of Oddi

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            Pregnancy & Lactation

            Pregnancy category: C; may prolong delivery and cause respiratory depression/withdrawal symptoms in newborn

            Lactation: Excreted in breast milk; caution advised

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Codeine: Opioid agonist; analgesia; blocks pain impulse generation and inhibits ascending pain pathways, thus altering the perception and response to pain; inhibits cough by acting centrally in the medulla; causes CNS depression

            Acetaminophen: Nonopioid, nonsalicylate analgesic; may work peripherally to block pain impulse generation; acts on hypothalamus to produce antipyresis

            Absorption

            Bioavailability: Codeine (53%); acetaminophen (100%)

            Onset: 0.5-1 hr

            Duration: 4-6 hr

            Peak effect: 1-1.5 hr

            Distribution

            Protein bound: Codeine (<25%); acetaminophen (10-25%), higher with toxic concentrations

            Vd: Codeine (3-6 L/kg); acetaminophen (1 L/kg)

            Metabolism

            Codeine

            • Via hepatic UGT2B7 and UGT2B4 to codeine-6-glucuronide
            • 10% of codeine is metabolized in liver to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors; also via CYP3A4 to norcodeine
            • CYPD2D6 poor metabolizers may not achieve adequate analgesia
            • Ultrarapid metabolizers (up to 7% of whites and up to 30% of Asian and African populations) may experience increased toxicity due to rapid conversion to morphine

            Acetaminophen

            • Metabolized in liver by microsomal enzyme systems
            • 80-85% conjugated principally with glucuronic acid and to a lesser extent with sulfuric acid and cysteine
            • 4% metabolized by CYP450 to toxic metabolite (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone [NAPQI]), which is further detoxified by conjugation with glutathione; high doses may deplete fixed amount of glutathione in body, causing NAPQI accumulation

            Elimination

            Codeine

            • Half-life: 3 hr
            • Excretion: Urine (90%)

            Acetaminophen

            • Half-life: 2-4 hr
            • Excretion: Urine (90-100%; principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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