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Guaifenesin and Codeine

Pronunciation

(gwye FEN e sin & KOE deen)

Index Terms

  • Codeine and Guaifenesin
  • Guaifenesin/Codeine
  • Guaifenesin/Codeine Phosphate
  • Robitussin AC

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, oral:

M-Clear: Guaifenesin 200 mg and codeine phosphate 9 mg [contains tartrazine]

Liquid, oral:

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

Dex-Tuss: Guaifenesin 300 mg and codeine phosphate 10 mg per 5 mL (473 mL) [ethanol free, gluten free, sugar free; contains propylene glycol; grape flavor]

Iophen C-NR: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (473 mL) [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:

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, 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 (120 mL, 480 mL) [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)

Tablet, oral:

Allfen CD: Guaifenesin 400 mg and codeine phosphate 10 mg

Allfen CDX: Guaifenesin 400 mg and codeine phosphate 20 mg

Brand Names: U.S.

  • Allfen CD
  • Allfen CDX
  • Cheratussin AC
  • Codar GF
  • Dex-Tuss
  • Guaiatussin AC
  • Guaifenesin AC Liquid
  • Iophen C-NR
  • M-Clear
  • M-Clear WC
  • Mar-Cof CG
  • Ninjacof-XG
  • Robafen AC
  • Virtussin A/C

Pharmacologic Category

  • Antitussive
  • Expectorant

Pharmacology

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 is an antitussive that controls cough by depressing the medullary cough center

Use: Labeled Indications

Temporary control of cough due to minor throat and bronchial irritation

Contraindications

Hypersensitivity to guaifenesin, codeine, or any component of the formulation; asthma

Dosing: Adult

Cough (antitussive/expectorant): Oral:

Capsule: Guaifenesin 200 mg and codeine 9 mg: Two capsules every 4 hours (maximum: 12 capsules/24 hours)

Liquid:

Guaifenesin 100 mg and codeine 6.33 mg per 5 mL: 15 mL every 4-6 hours (maximum: 45 mL/24 hours)

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

Guaifenesin 300 mg and codeine 10 mg per 5 mL: 5 mL every 4-6 hours (maximum: 40 mL/24 hours)

Tablet: Guaifenesin 400 mg and codeine 10-20 mg: One tablet every 4-6 hours (maximum: 6 tablets/24 hours)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Cough (antitussive/expectorant): Oral:

Children 6-11 years:

Capsule: Guaifenesin 200 mg and codeine 9 mg: One capsule every 4 hours (maximum: 6 capsules/24 hours)

Liquid:

Guaifenesin 100 mg and codeine 6.33 mg per 5 mL: 7.5 mL every 4-6 hours (maximum: 45 mL/24 hours)

Guaifenesin 100-200 mg and codeine 8-10 mg per 5 mL: 5 mL every 4 hours (maximum: 30 mL/24 hours)

Guaifenesin 300 mg and codeine 10 mg per 5 mL: 2.5 mL every 4-6 hours (maximum: 20 mL/24 hours)

Tablet: Guaifenesin 400 mg and codeine 10-20 mg: One-half tablet every 4-6 hours (maximum: 3 tablets/24 hours)

Children ≥12 years: Refer to adult dosing.

Dietary Considerations

Some products may contain phenylalanine and/or sodium.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alvimopan: Analgesics (Opioid) 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 Analgesics (Opioid). Monitor therapy

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

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Monitor therapy

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

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

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. 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

Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

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

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

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. 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 (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Eluxadoline: Analgesics (Opioid) may enhance the constipating effect of Eluxadoline. Avoid combination

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

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

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

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

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

MAO Inhibitors: May enhance the adverse/toxic effect of Codeine. 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: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). 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

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

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

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

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

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

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

Pegvisomant: Analgesics (Opioid) 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

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

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

Ramosetron: Analgesics (Opioid) 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

Serotonin Modulators: Analgesics (Opioid) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

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 Analgesics (Opioid). 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: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

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

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

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

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

May cause a colorimetric interference with certain laboratory determinations of 5-hydroxy indoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA)

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).

• 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).

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's disease.

• CNS depression/coma: Avoid use in patients with CNS depression or coma as these patients are susceptible to intracranial effects of CO2 retention.

• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.

• Fever: Use with caution in patients with fever.

• 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.

• Renal impairment: Use with caution in patients with severe renal impairment.

• Respiratory disease: Use with caution in patients with pulmonary disease or decrease ventilatory function; dose-related respiratory depression occurs.

• Seizure disorder: Use with caution in patients with a history of seizure disorder.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

• Ulcerative colitis: Use with caution in patients with ulcerative colitis.

Concurrent drug therapy issues:

• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• 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.

• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.

• Surgery: Use with caution in patients with recent GI or urinary tract surgery.

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.

• Phenylalanine: Some products may contain phenylalanine.

Other warnings/precautions:

• Cough: Appropriate use: Underlying cause of cough should be determined prior to prescribing. Dose should not be increased if cough does not respond; reevaluate within 5 days for possible underlying pathology.

Pregnancy Considerations

See individual agents.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience sweating a lot. Have patient report immediately to prescriber severe dizziness, passing out, angina, tachycardia, shortness of breath, slow breathing, shallow breathing, noisy breathing, severe fatigue, confusion, arrhythmia, hallucinations, mood changes, seizures, severe abdominal pain, severe headache, difficult urination, tremors, vision changes, severe nausea, severe vomiting, severe constipation, or severe loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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