codeine

Contraindicated in:

Hypersensitivity;
Significant respiratory depression;
Acute or severe bronchial asthma (in unmonitored setting or in absence of resuscitative equipment);
Known or suspected GI obstruction (including paralytic ileus);
Concurrent use of MAO inhibitors (or use within the past 14 days);
Ultra-rapid CYP2D6 metabolizers of codeine;
Lactation: Lactation;
Pedi: Children <12 yr, children <18 yr following tonsillectomy and/or adenoidectomy, and children 12–18 yr who are postoperative; have obstructive sleep apnea, obesity, severe pulmonary disease, or neuromuscular disease; or are taking other medications that cause respiratory depression (↑ risk of respiratory depression and death).

Use Cautiously in:

Personal or family history of substance use disorder or mental illness;
Head trauma;
↑intracranial pressure;
Severe renal impairment;
Severe hepatic impairment;
Severe pulmonary disease;
Hypothyroidism;
Adrenal insufficiency;
Prostatic hyperplasia;
Undiagnosed abdominal pain;
OB: Avoid chronic use; prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome;
Geri: Older adults may be more susceptible to CNS depression and constipation (dose ↓ required).

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, bradycardia

Derm: flushing, sweating

EENT: blurred vision, diplopia, miosis

GI: constipation, nausea, vomiting

GU: urinary retention

Neuro: confusion, sedation, dysphoria, euphoria, floating feeling, hallucinations, headache, unusual dreams

Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA)

Misc: allodynia, opioid-induced hyperalgesia, physical dependence, psychological dependence, tolerance

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors↑ risk of adverse reactions; concurrent use or use within previous 14 days contraindicated.
Use with benzodiazepines or other CNS depressants, including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
CYP3A4 inhibitors, including erythromycin, clarithromycin, ketoconazole, itraconazole, and protease inhibitors, may ↑ levels and risk of respiratory depression.
CYP3A4 inducers may ↓ levels and effectiveness.
CYP2D6 inhibitors, including amiodarone and quinidine, may ↓ analgesic effects.
Mixed agonist/antagonist analgesics, including nalbuphine or butorphanol, and partial agonist analgesics, including buprenorphine, may ↓ meperidine's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5HT3 receptor antagonists, linezolid, methylene blue, and triptans, may ↑ risk of serotonin syndrome.

Drug-Natural Products:

Kava-kava, valerian, skullcap, chamomile, or hops can ↑ risk of CNS depression.

Availability ⬆ ⬇

(Generic available)

Tablets: 15 mg; 30 mg; 60 mg

Route/Dosage ⬆ ⬇

PO (Adults ): Analgesic: 15–60 mg every 4 hr as needed (not to exceed 360 mg/day). Antitussive: 10–20 mg every 4–6 hr as needed (not to exceed 120 mg/day).

Renal Impairment

(Adults ): CCr 10–50 mL/min: Administer 75% of the dose; CCr <10 mL/min: Administer 50% of the dose.

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.

Classifications ⬆ ⬇

Therapeutic Classification: allergy, cold and cough remedies, antitussives, opioid analgesics

Pharmacologic Classification: opioid agonists

Pharmacokinetics ⬆ ⬇

Absorption: 50% absorbed from the GI tract.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP2D6 isoenzyme; 10% converted to morphine; the CYP2D6 isoenzyme exhibits genetic polymorphism (some patients [1–10% White patients, 3% Black patients, 16–28% North African/Ethiopian/Arabic patients] may be ultra-rapid metabolizers and may have ↑ morphine concentrations and an ↑ risk of adverse effects); 5–15% excreted unchanged in urine.

Half-Life: 2.5–4 hr.

Contr. Subst. Schedule ⬆ ⬇

Schedule II (C-II)
Schedule III (C-III)
Schedule IV (C-IV)
Schedule V (C-V)depends on content

Time/Action Profile ⬆ ⬇

(analgesia)

ROUTE	ONSET	PEAK	DURATION
PO	30–45 min	60–120 min	4 hr

Patient/Family Teaching ⬆ ⬇

Instruct patient on how and when to ask for and take pain medication. Do not stop abruptly without consulting health care provider.
REMS: Instruct patient on risk of addiction, abuse, and misuse, which could lead to death. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide is available at www.fda.gov/OpioidAnalgesicREMSPCG. Advise patient not to share codeine with others and to protect from theft or misuse.
Advise patient that codeine is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (by prescription, directly from a pharmacist, or as part of a community-based program).
May cause drowsiness or dizziness. Advise patient to call for assistance when ambulating or smoking. Caution ambulatory patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to change positions slowly to minimize orthostatic hypotension.
Caution patient to avoid concurrent use of alcohol or other CNS depressants with this medication.
Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
Advise patient that good oral hygiene, frequent mouth rinses, and sugarless gum or candy may decrease dry mouth.
Rep: Advise patient to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, failure to gain weight); usually occur the first days after birth. Monitor infants exposed to codeine through breast milk for excess sedation and respiratory depression.

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Indications ⬇

Contraind./Precautions ⬆ ⬇