codeine

 Indications

Management of mild to moderate pain. Antitussive (in

smaller doses). Unlabeled Use: Management of diarrhea.

Action

Binds to opiate receptors in the CNS. Alters the perception

of and response to painful stimuli while producing

generalized CNS depression. Decreases cough reflex.

Decreases GI motility. Therapeutic Effects: Decreased

severity of pain. Suppression of the cough reflex.

Relief of diarrhea.

Pharmacokinetics

Absorption: 50% absorbed from the GI tract.

Distribution: Widely distributed. Crosses the placenta;

enters breast milk.

Protein Binding: 7%.

Metabolism and Excretion: Mostly metabolized

by the liver (primarily via CYP2D6); 10% converted to

morphine; the CYP2D6 enzyme system exhibits genetic

polymorphism (some patients [1–10% Whites,

3% African Americans, 16–28% North Africans/Ethiopians/

Arabs] may be ultra-rapid metabolizers and may

haveqmorphine concentrations and anqrisk of adverse

effects); 5–15% excreted unchanged in urine.

Half-life: 2.5–4 hr.

TIME/ACTION PROFILE (analgesia)

ROUTE ONSET PEAK DURATION

PO 30–45 min 60–120 min 4 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Ultra-rapid

metabolizers of codeine; Lactation: Avoid use in breast

feeding (qrisk of drowsiness and respiratory difficulty

in infant); Pedi: Children 12 yr and children 18 yr

following tonsillectomy and/or adenoidectomy (qrisk

of respiratory depression and death).

Use Cautiously in: Head trauma;qintracranial

pressure; Severe renal, hepatic, or pulmonary disease;

Hypothyroidism; Adrenal insufficiency; Alcoholism;

Prostatic hyperplasia; Undiagnosed abdominal pain;

Geri: Geriatric or debilitated patients (doseprequired;

more susceptible to CNS depression, constipation); OB:

Has been used during labor; respiratory depression

may occur in the newborn; Pedi: Children 12–18 yr

who are postoperative; have obstructive sleep apnea,

obesity, or severe pulmonary disease, neuromuscular

disease; or are taking other medications that cause respiratory

depression (qrisk of respiratory depression).

Adverse Reactions/Side Effects

CNS: confusion, sedation, dysphoria, euphoria, floating

feeling, hallucinations, headache, unusual dreams.

EENT: blurred vision, diplopia, miosis. Resp: respiratory

depression. CV: hypotension, bradycardia. GI:

constipation, nausea, vomiting. GU: urinary retention.

Derm: flushing, sweating. Misc: physical dependence,

psychological dependence, tolerance.

Interactions

Drug-Drug: Use with extreme caution in patients receiving

MAO inhibitors (pinitial dose to 25% of usual

dose). Additive CNS depression with alcohol, antidepressants,

antihistamines, and sedative/hypnotics.

CYP3A4 inhibitors, inclulding erythromycin,

clarithromycin, ketoconazole, itraconazole, and

protease inhibitors mayqlevels and risk of respiratory

depression. CYP3A4 inducers mayplevels.

CYP2D6 inhibitors, including amiodarone and

quinidine maypanalgesic effects. Administration of

partial antagonists (buprenorphine, butorphanol,

nalbuphine, or pentazocine) may precipitate

opioid withdrawal in physically dependent patients.

Nalbuphine or pentazocine maypanalgesia.

Drug-Natural Products: Concomitant use of

kava-kava, valerian, skullcap, chamomile, or

hops canqCNS depression.

Route/Dosage

PO (Adults): Analgesic—15–60 mg q 3–6 hr as

needed. Antitussive—10–20 mg q 4–6 hr as needed

(not to exceed 120 mg/day). Antidiarrheal —30 mg

up to 4 times daily.

PO (Children 6–12 yr): Analgesic—0.5–1 mg/kg

(up to 60 mg) q 4–6 hr (up to 4 times daily) as

needed. Antitussive—5–10 mg q 4–6 hr as needed

(not to exceed 60 mg/day). Antidiarrheal—0.5 mg/kg

up to 4 times daily.

PO (Children 2–5 yr): Analgesic—0.5–1 mg/kg (up

to 60 mg) q 4–6 hr (up to 4 times daily) as needed. Antitussive—

1–1.5 mg/kg divided q 4–6 hr as needed.

Antidiarrheal—0.5 mg/kg up to 4 times daily.

Renal Impairment

(Adults and Children): CCr 10–50 mL/min—Administer

75% of the dose; CCr 10 mL/min—Administer

50% of the dose.

Availability (generic available)

Tablets: 15 mg, 30 mg, 60 mg. Oral solution: 10

mg/5 mL, 25 mg/5 mL. In combination with: antihistamines,

decongestants, antipyretics, caffeine, butalbital,

and nonopioid analgesics. See Appendix B.