ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 1 مورد

Guaifenesin and codeine: Drug information

Guaifenesin and codeine: Drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Guaifenesin and codeine: Patient drug information" and "Guaifenesin and codeine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Coditussin AC [OTC];
  • G Tussin AC [OTC];
  • Guaiatussin AC [OTC] [DSC];
  • guaiFENesin AC [OTC] [DSC];
  • M-Clear WC [OTC] [DSC];
  • Mar-Cof CG Expectorant [OTC];
  • Maxi-Tuss AC [OTC];
  • Ninjacof-XG [OTC];
  • Virtussin A/C [OTC] [DSC];
  • Virtussin AC w/ALC [OTC] [DSC]
Pharmacologic Category
  • Antitussive;
  • Expectorant
Dosing: Adult

Dosing may vary by product. Consult specific product labeling.

Cough

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)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Codeine and its metabolites (including morphine-3-glucuronide and morphine-6-glucuronide) are eliminated by the kidneys. Patients with chronic kidney disease who are ultra-rapid metabolizers of codeine are at greatest risk of neurotoxic effects (Ref). Codeine dose adjustment or avoidance may be required based on degree of kidney impairment. See individual agents for more details.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Also see individual agents.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Guaifenesin and codeine: Pediatric drug information")

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

Cough (antitussive/expectorant): Note: Due to risk of adverse effects (slowed or difficult breathing, misuse, abuse, substance use disorder, 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 (Ref).

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

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling. However, clearance of codeine may be reduced; active metabolites may accumulate. Use with caution, consider alternative agent. See individual agents.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling. See individual agents

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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

Contraindications

OTC labeling: When used for self-medication, do not use in children <2 years of age (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.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

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 that require mental alertness (eg, operating machinery, driving).

• Constipation: May cause or aggravate constipation. Consider preventative measures (eg, stool softener, increased fiber) to reduce potential for constipation.

• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute myocardial infarction), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).

• Respiratory depression: Serious, life-threatening, or fatal respiratory depression may occur with opioid use; monitor for respiratory depression, especially during initiation or dose escalation. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of known or suspected overdose.

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. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis (Brennan 2013).

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction or acute pancreatitis.

• 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.

• Obesity: Use with caution in patients who are morbidly obese.

• 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.

• Sleep-related disorders: Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and central nervous system depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing (CDC [Dowell 2022]).

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

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: Concomitant use may result in respiratory depression and sedation, which may be fatal. Consider prescribing naloxone or nalmefene for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.

• CYP3A4 interactions: The effects of concomitant use or discontinuation of CYP3A4 inducers or inhibitors or CYP2D6 inhibitors with codeine are complex. Use of CYP3A4 inducers or inhibitors or CYP2D6 inhibitors with guaifenesin/codeine requires careful consideration of the effects on the parent drug, codeine, and the active metabolite morphine. Avoid use in patients taking a CYP3A4 inhibitor or inducer or a CYP2D6 inhibitor. If concomitant use is necessary, monitor for signs and symptoms of toxicity or withdrawal.

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 "poor metabolizers": Poor metabolizers have decreased metabolism of codeine to its active metabolite, which may diminish analgesia; avoid the use of codeine and consider alternatives that are not metabolized by CYP2D6 (CPIC [Crews 2021]).

• CYP2D6 "ultrarapid metabolizers": Ultrarapid metabolizers have increased metabolism of codeine to its active metabolite, which may increase the risk of serious adverse effects; avoid the use of codeine and consider alternatives that are not metabolized by CYP2D6 (CPIC [Crews 2021]). The prevalence of this phenotype is estimated to be 1% to 10% for White (European and North American) patients; 3% to 4% for Black patients; 1% to 2% for Chinese, Japanese, and Korean patients; and >10% in certain ethnic groups such as Oceanian, Northern African, Middle Eastern, Ashkenazi Jew, and Puerto Rican patients.

• Older adult: Use opioids with caution in older adults; may be more sensitive to adverse effects. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increased adverse effects. Monitor closely for adverse effects associated with opioid therapy (eg, respiratory and central nervous system depression, falls, cognitive impairment, constipation) (CDC [Dowell 2022]).

• Neonates: Neonatal withdrawal syndrome: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant patient, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

• 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 substance abuse disorder; potential for drug dependency exists. Other factors associated with increased risk for misuse include concomitant depression or other mental health conditions, higher opioid dosages, or taking other central nervous system depressants. Consider offering naloxone or nalmefene prescriptions in patients with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally), concomitant benzodiazepine use, and patients at risk for returning to a high dose after losing tolerance (CDC [Dowell 2022]).

• 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.

• Naloxone/nalmefene access: Discuss the availability of naloxone or nalmefene with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced opioid-induced respiratory depression/opioid overdose. Additionally, health care providers should consider prescribing naloxone or nalmefene to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone or nalmefene (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone or nalmefene, and getting emergency help (FDA 2020).

• Self-medication (OTC use): Prior to self-medication (OTC), notify health care provider if you have a persistent cough, a cough that occurs with excessive phlegm, and/or a chronic cough such as occurs with smoking, asthma, chronic bronchitis, emphysema, chronic pulmonary disease, or shortness of breath. 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.

Warnings: Additional Pediatric Considerations

Use of codeine has been associated with a risk of life-threatening or fatal respiratory depression in children and adolescents (AAP [Tobias 2016]). In 2012, the FDA first issued a safety alert regarding the risk of respiratory depression associated with the use of codeine in children after tonsillectomy, adenoidectomy, or adenotonsillectomy (FDA 2012). The agency then followed up by adding a black box warning and contraindication for use in these patients to all codeine and codeine-containing products (FDA 2013). In April 2015, the European Medicines Agency (EMA) stated that codeine-containing medicines should not be used in children <12 years, and use is not recommended in pediatric patients 12 to 18 years who have breathing problems including asthma or other chronic breathing problems (FDA 2015). In January 2018, the FDA expanded the earlier warnings about codeine-containing cough/cold products to include hydrocodone-containing products. The FDA is recommending that labeling for hydrocodone-containing cough and cold products include a contraindication for use in pediatric patients <18 years of age due to risk of adverse events, including slowed or difficult breathing, misuse, abuse, substance use disorder, overdose, and death. Additionally, the FDA will be requiring a black box warning on all prescription cough/cold products that contain codeine or hydrocodone to include the warnings (AAP 2018; FDA 2018a; FDA 2018b).

Safety and efficacy for the use of cough and cold products in pediatric patients <4 years of age is limited; guaifenesin/codeine is contraindicated in children <2 years of age. The AAP warns against the use of these products for respiratory illnesses in young children. Serious adverse effects including death have been reported. Many of these products contain multiple active ingredients, increasing the risk of accidental overdose when used with other products. Health care providers are reminded to ask caregivers about the use of OTC cough and cold products in order to avoid exposure to multiple medications containing the same ingredient (AAP 2018b; CDC 2007; FDA 2017; FDA 2018c).

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).

Dosage Forms: US

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

Liquid, Oral:

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]

Mar-Cof CG Expectorant: Guaifenesin 225 mg and codeine phosphate 7.5 mg per 5 mL (473 mL) [alcohol free, sugar free; contains polyethylene glycol (macrogol), propylene glycol, saccharin sodium, sodium benzoate]

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

Virtussin AC w/ALC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (473 mL [DSC]) [sugar free; contains alcohol, usp, fd&c red #40 (allura red ac dye), menthol, saccharin sodium, sodium benzoate]

Solution, Oral:

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

M-Clear WC: Guaifenesin 100 mg and codeine phosphate 6.33 mg/5 mL (473 mL [DSC]) [alcohol free, dye free, sugar free; contains propylene glycol, saccharin sodium]

Maxi-Tuss AC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (473 mL) [alcohol free, dye free, gluten free, sugar free; contains methylparaben, propylene glycol, propylparaben]

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

Generic: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (5 mL, 10 mL, 118 mL, 120 mL, 237 mL [DSC], 473 mL)

Syrup, Oral:

Guaiatussin AC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (5 mL [DSC], 10 mL [DSC], 118 mL [DSC], 473 mL [DSC]) [sugar free; contains alcohol, usp, fd&c red #40 (allura red ac dye), polyethylene glycol (macrogol), saccharin sodium, sodium benzoate; cherry flavor]

guaiFENesin AC: Guaifenesin 100 mg and codeine phosphate 10 mg per 5 mL (473 mL [DSC]) [contains alcohol, usp, disodium edta, fd&c red #40 (allura red ac dye), saccharin sodium, sodium benzoate; cherry flavor]

Generic Equivalent Available: US

Yes

Pricing: US

Liquid (Mar-Cof CG Expectorant Oral)

225-7.5 mg/5 mL (per mL): $0.18

Liquid (Ninjacof-XG Oral)

200-8 mg/5 mL (per mL): $0.08

Solution (guaiFENesin-Codeine Oral)

100-10 mg/5 mL (per mL): $0.09 - $0.10

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Controlled Substance

C-V

Administration: Adult

Oral: Administer with full glass of water. Administer with an accurate measuring device; do not use a household teaspoon (overdosage may occur).

Administration: Pediatric

Oral: Administer with a large quantity of fluid to ensure proper action; may administer with food to decrease nausea and GI upset from codeine. Administer using a calibrated measuring device (not household teaspoon or tablespoon) to measure doses.

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.

Medication Safety Issues
High alert medication

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (opioids, all formulations and routes of administration; pediatric liquid medications requiring measurement) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Pediatric patients: High-risk medication:

KIDs List: Codeine, when used in pediatric patients <18 years of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of respiratory depression and death unless pharmacogenetic testing completed (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents with Clinically Relevant Anticholinergic Effects: May increase adverse/toxic effects of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor

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

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Alvimopan: Opioid Agonists may increase adverse/toxic effects 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. Risk D: Consider Therapy Modification

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amphetamines: May increase analgesic effects of Opioid Agonists. Risk C: Monitor

Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification

Buprenorphine: May decrease therapeutic effects of Opioid Agonists. Management: Seek alternatives to buprenorphine in patients receiving pure opioid agonists. If combined in certain pain management situations (eg, surgery), monitor for symptoms of therapeutic failure/high dose requirements or opioid withdrawal symptoms. Risk D: Consider Therapy Modification

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

CNS Depressants: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification

CYP2D6 Inhibitors (Moderate): May decrease therapeutic effects of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor

CYP2D6 Inhibitors (Strong): May decrease therapeutic effects of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor

CYP3A4 Inducers (Moderate): May decrease active metabolite exposure of Codeine. Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease active metabolite exposure of Codeine. Risk C: Monitor

CYP3A4 Inhibitors (Moderate): May increase active metabolite exposure of Codeine. Risk C: Monitor

CYP3A4 Inhibitors (Strong): May increase active metabolite exposure of Codeine. Risk C: Monitor

Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Desmopressin: Opioid Agonists may increase hyponatremic effects of Desmopressin. Risk C: Monitor

DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Disulfiram: May increase adverse/toxic effects of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid

Diuretics: Opioid Agonists may increase adverse/toxic effects of Diuretics. Opioid Agonists may decrease therapeutic effects of Diuretics. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

Eluxadoline: Opioid Agonists may increase constipating effects of Eluxadoline. Risk X: Avoid

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification

Gastrointestinal Agents (Prokinetic): Opioid Agonists may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor

Grapefruit Juice: May increase serum concentration of Codeine. Risk C: Monitor

HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): May decrease therapeutic effects of Opioid Agonists. Opioid Agonists may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor

Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lemborexant: May increase CNS depressant effects 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. Risk D: Consider Therapy Modification

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methotrimeprazine: May increase CNS depressant effects of Products Containing Ethanol. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MetroNIDAZOLE (Systemic): May increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk X: Avoid

MetroNIDAZOLE (Topical): May increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk C: Monitor

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Monoamine Oxidase Inhibitors: May increase adverse/toxic effects of Codeine. Risk X: Avoid

Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nalfurafine: Opioid Agonists may increase adverse/toxic effects of Nalfurafine. Opioid Agonists may decrease therapeutic effects of Nalfurafine. Risk C: Monitor

Nalmefene: May decrease therapeutic effects of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider Therapy Modification

Naltrexone: May decrease therapeutic effects of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid

Nefazodone: Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase serum concentration of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for increased opioid effects, including fatal respiratory depression, when these agents are combined and consider opioid dose reductions until stable drug effects are achieved. Additionally, monitor for serotonin syndrome/serotonin toxicity. Risk C: Monitor

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification

Opioids (Mixed Agonist / Antagonist): May decrease analgesic effects 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. Risk X: Avoid

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification

OxyCODONE: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

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

Pegvisomant: Opioid Agonists may decrease therapeutic effects of Pegvisomant. Risk C: Monitor

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

PHENobarbital: May increase CNS depressant effects of Codeine. PHENobarbital may decrease serum concentration of Codeine. Management: Avoid use of codeine and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a moderate CYP3A4 inducer, monitor for decreased codeine efficacy and withdrawal if combined. Risk D: Consider Therapy Modification

Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Primidone: May increase CNS depressant effects of Codeine. Primidone may decrease 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. Risk D: Consider Therapy Modification

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ramosetron: Opioid Agonists may increase constipating effects of Ramosetron. Risk C: Monitor

Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification

ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Samidorphan: May decrease therapeutic effects of Opioid Agonists. Risk X: Avoid

Secnidazole: Products Containing Ethanol may increase adverse/toxic effects of Secnidazole. Risk X: Avoid

Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease therapeutic effects of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for decreased therapeutic response (eg, analgesia) and opioid withdrawal when coadministered with SSRIs that strongly inhibit CYP2D6. Additionally, monitor for serotonin syndrome/serotonin toxicity if these drugs are combined. Risk C: Monitor

Serotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may increase serotonergic effects 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. Risk C: Monitor

Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification

Somatostatin Analogs: May decrease active metabolite exposure of Codeine. Specifically, the concentrations of the active metabolite morphine may be reduced. Risk C: Monitor

Succinylcholine: May increase bradycardic effects of Opioid Agonists. Risk C: Monitor

Suvorexant: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Tilidine: May increase therapeutic effects of Opioid Agonists. Risk X: Avoid

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Zolpidem: CNS Depressants may increase CNS depressant effects 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. Risk D: Consider Therapy Modification

Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification

Pregnancy Considerations

Refer to individual monographs.

Breastfeeding Considerations

Refer to individual monographs.

Dietary Considerations

Some products may contain sodium.

Monitoring Parameters

Relief of symptoms; respiratory and mental status; signs of misuse, abuse, and substance use disorder.

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

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Codelasa;
  • (BE) Belgium: Inalpin;
  • (CH) Switzerland: Resyl Plus | Sano tuss;
  • (CN) China: Codeine and Guaifenesin | Codeine phosphate and guaifenesin;
  • (EE) Estonia: Recipect | Robafen;
  • (LU) Luxembourg: Inalpin;
  • (PE) Peru: Broncotos nf;
  • (PR) Puerto Rico: Brontex | Cheratussin ac | Codeine guaifenesin | Codeine phosphate and guaifenesin | Coditussin ac | Dex Tuss | Execlear c | Ganituss nr | Guaifen-c | Guaifenesin & codeine | Guaifenesin and codeine phosphate | Halotussin ac | M clear wc | Maxi tuss ac | Myci GC | Ninjacof XG | Robafen ac | Trymine cg | Tussiden C | Virtussin ac;
  • (TH) Thailand: Codesia;
  • (TW) Taiwan: Codepin | Cotonpin | Resyl Plus
  1. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
  2. American Academy of Pediatrics (AAP). Cough and cold medicines should not be prescribed, recommended or used for respiratory illnesses in young children. Updated June 12, 2018b. Available at http://www.choosingwisely.org/clinician-lists/american-academy-pediatrics-cough-and-cold-medicines-for-children-under-four/
  3. American Academy of Pediatrics (AAP). FDA: Children should not take cough medicine with codeine. AAP News & Journals Gateway website. http://www.aappublications.org/news/2018/01/11/Codeine011118. Published January 11, 2018. Accessed February 13, 2018.
  4. American Academy of Pediatrics (AAP). Five things physicians and patients should question. March, 2014. Available at http://aapdc.org/wp-content/uploads/2014/03/AAP-Choose-Wisely-Top-10-Updated-Mar-2014.pdf
  5. Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3 suppl 1):S12-S18. doi:10.1016/j.amjmed.2012.12.001 [PubMed 23414717]
  6. Centers for Disease Control (CDC). Neonatal deaths associated with use of benzyl alcohol—United States. MMWR Morb Mortal Wkly Rep. 1982;31(22):290-291. http://www.cdc.gov/mmwr/preview/mmwrhtml/00001109.htm [PubMed 6810084]
  7. Centers for Disease Control and Prevention (CDC). Infant deaths associated with cough and cold medications--two states, 2005. MMWR Morb Mortal Wkly Rep. 2007;56(1):1-4. [PubMed 17218934]
  8. Codeine [prescribing information]. Eatontown, NJ: West-Ward Pharmaceuticals Corp; March 2021.
  9. Coditussin AC (codeine phosphate, guaifenesin) [prescribing information]. Villa Park, IL: Glendale Inc; April 2016.
  10. Coluzzi F, Caputi FF, Billeci D, et al. Safe use of opioids in chronic kidney disease and hemodialysis patients: tips and tricks for non-pain specialists. Ther Clin Risk Manag. 2020;16:821-837. doi:10.2147/TCRM.S262843 [PubMed 32982255]
  11. Crews KR, Monte AA, Huddart R, et al. Clinical pharmacogenetics implementation consortium guideline for CYP2D6, OPRM1, and COMT genotypes and select opioid therapy. Clin Pharmacol Ther. 2021;110(4):888-896. doi:10.1002/cpt.2149 [PubMed 33387367]
  12. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice guideline for prescribing opioids for pain - United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95. doi:10.15585/mmwr.rr7103a1 [PubMed 36327391]
  13. G Tussin AC (codeine phosphate, guaifenesin) [prescribing information]. Leeds, AL: The Generic Pharmaceuticals Company Inc; November 2016.
  14. Kliegman RM, Behrman RE, Jenson HB, et al, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007.
  15. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  16. M-Clear WC (codeine phosphate, guaifenesin) [prescribing information]. Chattanooga, TN: R.A. McNeil Company; February 2017.
  17. Mar-Cof CG (codeine phosphate, guaifenesin) [prescribing information]. Lafayette, LA: Marnel Pharmaceutical Inc; January 2015.
  18. Maxi-Tuss AC (codeine phosphate, guaifenesin) [prescribing information]. Brooksville, FL: MCR American Pharmaceuticals, Inc; May 2020.
  19. Meyers RS, Thackray J, Matson KL, et al. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. J Pediatr Pharmacol Ther. 2020;25(3):175-191. [PubMed 32265601]
  20. Molanaei H, Carrero JJ, Heimbürger O, et al. Influence of the CYP2D6 polymorphism and hemodialysis on codeine disposition in patients with end-stage renal disease. Eur J Clin Pharmacol. 2010;66(3):269-273. doi:10.1007/s00228-009-0759-8 [PubMed 19940985]
  21. Ninjacof-XG (codeine phosphate, guaifenesin) [prescribing information]. Birmingham, AL: Centurion Labs; November 2014.
  22. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  23. Tobias JD, Green TP, Coté CJ, Section of Anesthesiology and Pain Medicine, Committee on Drugs. Codeine: Time To Say "No". Pediatrics. 2016 Sep 19 [Epub ahead of print]. [PubMed 10937472]
  24. US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. Available at https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm.
  25. US Food and Drug Administration (FDA). FDA Drug Safety Communication: codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death. Available at http://www.fda.gov/Drugs/DrugSafety/ucm313631.htm. Published August 15, 2012. Accessed February 16, 2018.
  26. US Food and Drug Administration (FDA). FDA Drug Safety Communication: Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. Available at https://www.fda.gov/downloads/Drugs/DrugSafety/UCM339116.pdf. Published February 20, 2013. Accessed February 16, 2018.
  27. US Food and Drug Administration (FDA). Joint Meeting of the Pulmonary-Allergy 7 Drugs Advisory Committee (PADAC) 8 and the Drug Safety and Risk Management 9 Advisory Committee (DSaRM). December 10, 2015. Available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM487401.pdf
  28. US Food and Drug Administration (FDA). Most young children with a cough or cold don't need medicines. July 18, 2017. Available at https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm422465.htm. Last accessed November 2, 2018.
  29. US Food and Drug Administration (FDA). Postmarket drug safety information for patients and providers: information about naloxone and nalmefene. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-about-naloxone-and-nalmefene. Published April 22, 2024. Accessed August 7, 2024.
  30. US Food and Drug Administration (FDA) Drug Safety Communication. FDA requires labeling changes for prescription opioid cough and cold medicines to limit their use to adults 18 years and older. US Food and Drug Administration website. https://www.fda.gov/Drugs/DrugSafety/ucm590435.htm. Published January 22, 2018a. Accessed February 13, 2018.
  31. US Food and Drug Administration (FDA) News Release. FDA acts to protect kids from serious risks of opioid ingredients contained in some prescription cough and cold products by revising labeling to limit pediatric use. US Food and Drug Administration website. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm592109.htm. Published January 11, 2018b. Accessed February 13, 2018.
  32. US Food and Drug Administration (FDA). Use caution when giving cough and cold products to kids. Available at https://www.fda.gov/drugs/resourcesforyou/specialfeatures/ucm263948.htm. Updated February 8, 2018c. Last accessed November 2, 2018.
  33. US Food and Drug Administration (FDA). FDA Drug Safety Communication. MedWatch. FDA recommends health care professionals discuss naloxone with all patients when prescribing opioid pain relievers or medicines to treat opioid use disorder. https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-health-care-professionals-discuss-naloxone-all-patients-when-prescribing-opioid-pain. Published July 23, 2020. Accessed September 18, 2020.
  34. Virtussin AC (guaifenesin and codeine) [prescribing information]. Langhorne, PA: Virtus Pharmaceuticals; July 2019.
  35. Virtussin in AC W/ALC (guaifenesin and codeine) [prescribing information]. Langhorne, PA: Virtus Pharmaceuticals; July 2019.
  36. World Health Organization (WHO). Report of the WHO Expert Committee, 2011. The selection and use of essential medicines. 2015.
  37. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217-219. [PubMed 17555487]
Topic 8504 Version 363.0