codeine/guaifenesin (Rx)

>10%

Codeine

• Drowsiness
• Constipation

1-10%

Codeine

• Bradycardia, hypotension, tachycardia
• Confusion, dizziness, false feeling of well being, headache, lightheadedness, malaise, paradoxical CNS stimulation, restlessness, weakness
• Rash, urticaria
• Anorexia, nausea, vomiting, xerostomia
• LFT's increased
• Ureteral spasm, urination decreased
• Dyspnea
• Burning at injection site, blurred vision, histamine release

Frequency Not Defined

Codeine (serious)

• Hypotension, with IV use
• Seizure, with excessive doses
• Anaphylactoid reaction (rare)
• Respiratory depression

Guaifensesin

• Headache
• Rash
• Nausea
• Vomiting

Contraindications

Codeine

• Absolute: Acute abdominal condition, diarrhea associated with toxins, pseudomembranous colitis, respiratory depression
• Relative: Asthma (acute), inflammatory bowel disease, respiratory impairment

Guaifenesin

• Do not use as self-medication in chronic or persistent coughs
• Hypersensitivity

Cautions

Use caution in cardiac arrhythmias, emotional lability, gallbladder disease, hepatic impairment, renal impairment, surethral stricture, urinary tract surgery

Ibuprofen is more effective than codeine for pain from musculoskeletal injuries in children

Children are particularly sensitive to the respiratory depressant effects of codeine; because of risk of life-threatening respiratory depression and death, the use of codeine products is contraindicated in children less than 12 years of age, and in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy

Use in children also exposes them to risks of addiction, abuse, and misuse, which can lead to overdose and death; because benefits of symptomatic treatment of cough associated with allergies or common cold do not outweigh risks of use of codeine in pediatric patients, use is not indicated in patients younger than 18 years of age

Life-threatening respiratory depression and death have occurred in children who received codeine; codeine is subject to variability in metabolism based upon CYP2D6 genotype; based upon post-marketing reports, children < 12 years appear to be more susceptible to respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression; cases of death have been reported in the post-operative period following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine

Children with obstructive sleep apnea who are treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to its respiratory depressant effect; because of risk of life-threatening respiratory depression and death: codeine is contraindicated in all children younger than 12 years of age; it is also contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy

Avoid the use of codeine in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to respiratory depressant effects of codeine; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

Healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about these risks and signs of opioid overdose

Dosage should not be increased if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease

Therapy in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients

The active ingredients may produce marked drowsiness and impair mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery

Codeine is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; the use of codeine may obscure the diagnosis or clinical course of patients with acute abdominal conditions; the concurrent use of anticholinergics may produce paralytic ileus

Codeine therapy may result in constipation or obstructive bowel disease, especially in patients with underlying intestinal motility disorders; use with caution in patients with underlying intestinal motility disorders

Avoid therapy in patients with head injury, intracranial lesions, or a pre-existing increase in intracranial pressure; in patients who may be susceptible to intracranial effects of CO2 retention may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; opioids also produce adverse reactions that may obscure clinical course of patients with head injuries

The codeine may increase frequency of seizures in patients with seizure disorders, and may increase risk of seizures occurring in other clinical settings associated with seizures; monitor patients with a history of seizure disorders for worsened seizure control during therapy

Use is contraindicated in patients receiving monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping such therapy; MAOIs may potentiate effects of codeine’s active metabolite, including respiratory depression, coma, and confusion

May cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) monitor these patients for signs of hypotension after initiating therapy

Not recommended for use in pregnant women; Prolonged use during pregnancy can result in withdrawal in the neonate; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use; if adrenal insufficiency is suspected, confirm diagnosis with diagnostic testing as soon as possible; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers

Guaifenesin is often included in combos, check brand name/other constituents

Pregnancy category: C; category D if used for prolonged periods or in high doses at term

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.

Mechanism of Action

Codeine

• Narcotic agonist analgesic with antitussive activity, mu receptor agonist

Guaifenesin

• Reduces viscosity of secretions by increasing amount of respiratory tract fluid

Absorption

Codeine

• Onset: 30-60 min
• Duration: 4-6 hr

Guaifenesin

• Onset: 30 min
• Duration: 4-6 hr

Distribution

Codeine

• Peak plasma time: 0.5-1 hr
• Protein bound: 25%

Metabolism

Codeine

• Inactive but metabolized to morphine by CYP2D6 (missing in 5-10% of population)

Guaifenesin

• Metabolism: Liver
• Metabolite: b-(2-methoxyphenoxy) lactic acid

Elimination

Codeine

• Half-life: 3-4 hr
• Excretion: urine, feces

Guaifenesin

• Half-life: 1 hr
• Excretion: Urine

Oral Administration

Give with food or milk if GI upset

Administer with special measuring device for accurate dose