Guaifenesin and Codeine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Liquid, oral:

Codar GF: Guaifenesin 200 mg and codeine phosphate 8 mg per 5 mL (473 mL [DSC]) [contains propylene glycol; cotton candy flavor]

Coditussin AC: Guaifenesin 200 mg and codeine phosphate 10 mg per 5 mL (473 mL) [alcohol free, dye free, sugar free; contains propylene glycol, saccharin sodium, sorbitol; cotton candy flavor]

Iophen C-NR: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (473 mL [DSC]) [contains propylene glycol, sodium benzoate; raspberry flavor]

M-Clear WC: Guaifenesin 100 mg and codeine phosphate 6.33 mg per 5 mL (473 mL) [contains propylene glycol; cotton candy flavor]

Ninjacof-XG: Guaifenesin 200 mg and codeine phosphate 8 mg per 5 mL (473 mL) [dye free, ethanol free, sugar free; contains propylene glycol; cotton candy flavor]

Solution, oral:

G Tussin AC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (118 mL, 473 mL) [ethanol free, dye free, gluten free, sugar free; contains methylparaben, propylene glycol, propylparaben, sorbitol]

Mar-Cof CG: Guaifenesin 225 mg and codeine phosphate 7.5 mg per 5 mL (473 mL) [ethanol free, sugar free; contains propylene glycol, sodium benzoate, sodium 6 mg/5 mL]

Virtussin A/C: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (118 mL, 473 mL) [sugar free; contains propylene glycol; cherry flavor]

Generic: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (5 mL, 10 mL, 118 mL, 237 mL, 473 mL)

Syrup, oral:

Cheratussin AC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (118 mL, 236 mL, 473 mL) [sugar free; contains ethanol 3.8%, sodium benzoate; cherry flavor]

Guaiatussin AC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (5 mL, 10 mL, 118 mL, 473 mL) [sugar free; contains ethanol 3.5%, sodium 1 mg/5 mL, sodium benzoate; cherry flavor]

Robafen AC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (480 mL [DSC]) [contains ethanol 3.5%, sodium 4 mg/5 mL, sodium benzoate; cherry flavor]

Generic: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (473 mL)

Pharmacology

Mechanism of Action

Guaifenesin: May act as an expectorant by irritating the gastric mucosa and stimulating respiratory tract secretions, thereby increasing respiratory fluid volumes and decreasing phlegm viscosity

Codeine: Antitussive that controls cough by depressing the medullary cough center

Use: Labeled Indications

Cough: Temporary control of cough due to minor throat and bronchial irritation associated with a common cold, allergic rhinitis or other respiratory allergies, or inhaled irritants; loosen mucus and thin bronchial secretions making coughs more productive; cough relief to improve sleep.

Contraindications

OTC labeling: When used for self-medication, do not use in patients with chronic pulmonary disease or shortness of breath; in children <2 years prescription (product specific); use with or within 14 days of MAOI therapy (product specific; consult manufacturer’s product labeling); in children following tonsillectomy and/or adenoidectomy

Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Dosing may vary by product. Consult specific product labeling.

Cough: Oral:

Guaifenesin 100 mg/codeine 6.33 mg per 5 mL: 15 mL every 4 to 6 hours (maximum: 90 mL per 24 hours)

Guaifenesin 100 to 200 mg/codeine 8 to 10 mg per 5 mL: 10 mL every 4 hours (maximum: 60 mL per 24 hours)

Guaifenesin 225 mg/codeine 7.5 mg per 5 mL: 7.5 mL every 4 to 6 hours (maximum: 45 mL per 24 hours)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Multiple concentrations of oral liquid formulations exist; close attention must be paid to the concentration when ordering or administering. Dosage units vary based on product (mg/kg, mL); use caution when verifying dose with product formulation.

Note: Refer to product specific labeling for approved pediatric ages.

Cough (antitussive/expectorant): Note: Due to risk of adverse effects (slowed or difficult breathing, misuse, abuse, addiction, overdose, and death), the FDA in January 2018 recommended against routine use of codeine/hydrocodone-containing cough/cold products for patients <18 years and that future manufacturer labeling for these products include a contraindication in this population (AAP 2018; FDA 2018a; FDA 2018b).

Manufacturer's labeling:

Children 6 to 11 years: Oral:

Guaifenesin 100 mg and codeine 6.33 mg per 5 mL: 7.5 mL every 4 to 6 hours as needed; maximum daily dose: 45 mL/day

Guaifenesin 100 to 200 mg and codeine 8 to 10 mg per 5 mL: 5 mL every 4 hours as needed; maximum daily dose: 30 mL/day

Guaifenesin 225 mg and codeine 7.5 mg per 5 mL: 3.75 mL every 4 to 6 hours as needed; maximum total dose: 22.5 mL/24 hours

Guaifenesin 300 mg and codeine 10 mg per 5 mL: 2.5 mL every 4 to 6 hours as needed; maximum daily dose: 20 mL/day

Children ≥12 years and Adolescents: Oral:

Guaifenesin 100 mg and codeine 6.33 mg per 5 mL: 15 mL every 4 to 6 hours as needed; maximum daily dose: 90 mL/day

Guaifenesin 100 to 200 mg and codeine 8 to 10 mg per 5 mL: 10 mL every 4 hours as needed; maximum daily dose: 60 mL/day

Guaifenesin 225 mg and codeine 7.5 mg per 5 mL: 7.5 mL every 4 to 6 hours as needed; maximum total dose: 45 mL/24 hours

Guaifenesin 300 mg and codeine 10 mg per 5 mL: 5 mL every 4 to 6 hours as needed; maximum daily dose: 40 mL/day

Administration

Administer with an accurate measuring device; do not use a household teaspoon (overdosage may occur).

Dietary Considerations

Some products may contain sodium.

Storage

Store at 15°C to 30°C (59°F to 86°F). Do not refrigerate Robafen AC.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Alvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Opioid Agonists. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

CYP2D6 Inhibitors (Moderate): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Monitor therapy

CYP2D6 Inhibitors (Strong): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Consider therapy modification

Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Desmopressin: Opioid Agonists may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Codeine. Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of nalmefene and opioid agonists. Discontinue nalmefene 1 week prior to any anticipated use of opioid agonistss. If combined, larger doses of opioid agonists will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

PHENobarbital: May enhance the CNS depressant effect of Codeine. PHENobarbital may decrease the serum concentration of Codeine. Management: Avoid use of codeine and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased codeine efficacy and withdrawal if combined. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Primidone: May enhance the CNS depressant effect of Codeine. Primidone may decrease the serum concentration of Codeine. Management: Avoid use of codeine and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased codeine efficacy and withdrawal if combined. Consider therapy modification

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonergic Agents (High Risk): Opioid Agonists may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Somatostatin Analogs: May decrease the metabolism of Codeine. The formation of two major codeine metabolites (morphine and norcodeine) may be impaired by somatostatin analogs. Monitor therapy

Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

See individual agents.

Adverse Reactions

Frequency not defined; also see individual agents.

Cardiovascular: Bradycardia, circulatory depression, flushing, orthostatic hypotension, palpitations, syncope, tachycardia

Central nervous system: Central nervous system depression, convulsions, disorientation, dizziness, dysphoria, euphoria, hallucination (transient), headache, sedation

Dermatologic: Diaphoresis, pruritus, urticaria

Gastrointestinal: Biliary tract spasm, constipation, gastrointestinal hypermotility (colonic motility increase with chronic ulcerative colitis), nausea, stomach pain, toxic megacolon (with acute ulcerative colitis), vomiting

Genitourinary: Oliguria, urinary retention

Hypersensitivity: Anaphylaxis, angioedema

Neuromuscular & skeletal: Weakness

Ophthalmic: Visual disturbance

Respiratory: Laryngeal edema, respiratory depression

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Constipation: May cause or aggravate constipation.
• Hypotension: May cause hypotension.
• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
• Respiratory depression: May cause dose-related respiratory depression. The risk is increased in elderly patients, debilitated patients, and patients with conditions associated with hypoxia, hypercapnia, or upper airway obstruction.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease.
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction or acute pancreatitis.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease).
• CNS depression/coma: Avoid use in patients with CNS depression or coma as these patients are susceptible to intracranial effects of CO₂ retention.
• Delirium tremens: Use with caution in patients with delirium tremens.
• Diabetes: Use with caution in patients with diabetes.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with severe hepatic impairment.
• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.
• Psychosis: Use with caution in patients with toxic psychosis.
• Renal impairment: Use with caution in patients with severe renal impairment.
• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or preexisting respiratory depression, particularly when initiating therapy; critical respiratory depression may occur, even at therapeutic dosages.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• CYP2D6 “ultrarapid metabolizers”: Use caution in patients with two or more copies of the variant CYP2D6*2 allele; may have extensive conversion from codeine to morphine and thus increased opioid-mediated effects. Avoid the use of codeine in these patients; consider alternative analgesics such as morphine or a nonopioid agent (Crews 2012). The occurrence of this phenotype is seen in 0.5% to 1% of Chinese and Japanese, 0.5% to 1% of Hispanics, 1% to 10% of Caucasians, 3% of African-Americans, and 16% to 28% of North Africans, Ethiopians, and Arabs.
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.
• Pediatric: Respiratory depression may occur even at therapeutic dosages; FDA and AAP recommend against use in pediatric patients <18 years due to risk of adverse effects (AAP 2018; FDA 2018a; FDA 2018b). Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine due to a CYP-450 2D6 polymorphism. Codeine is contraindicated in pediatric patients <12 years of age and pediatric patients <18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of codeine in pediatric patients 12 to 18 years of age who have other risk factors that may increase their sensitivity to the 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. Deaths have also occurred in breastfeeding infants after being exposed to high concentrations of morphine because the mothers were ultra-rapid metabolizers.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Abuse/misuse/diversion: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists.
• Administration: Use an accurate measuring device; a household teaspoon is not an accurate measuring device and could lead to overdosage, which can result in serious adverse reactions.
• Cough: Appropriate use: Underlying cause of cough should be determined prior to prescribing. Dose should not be increased if cough does not respond.
• Self-medication (OTC use): Prior to self-medication (OTC), notify health care provider if you have a cough that occurs with excessive phlegm, and/or a chronic cough such as occurs with smoking, asthma, chronic bronchitis, or emphysema. Discontinue use and notify healthcare provider if nervousness, dizziness, or sleepiness occurs; new symptoms occur; or if cough lasts >7 days, returns or is accompanied by fever, rash or persistent headache.

Monitoring Parameters

Relief of symptoms; respiratory and mental status; signs of misuse, abuse, and addiction.

Pregnancy

Pregnancy Considerations

See individual agents.

Patient Education

What is this drug used for?

• It is used to thin mucus so it can be taken from the body by coughing.
• It is used to relieve coughing.

Frequently reported side effects of this drug

• Sweating a lot

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe dizziness
• Passing out
• Chest pain
• Fast heartbeat
• Shortness of breath
• Slow breathing
• Shallow breathing
• Noisy breathing
• Severe fatigue
• Confusion
• Arrhythmia
• Sensing things that seem real but are not
• Mood changes
• Seizures
• Severe abdominal pain
• Severe headache
• Difficult urination
• Tremors
• Vision changes
• Severe nausea
• Severe vomiting
• Severe constipation
• Severe loss of strength and energy
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.