Version May 2024
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)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(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 (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.
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.
There are no dosage adjustments provided in manufacturer's labeling. See individual agents
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
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.
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 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 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 access: Discuss the availability of naloxone 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 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 (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, 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.
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).
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]
Trymine CG: Guaifenesin 225 mg and codeine phosphate 7.5 mg per 5 mL (473 mL [DSC]) [alcohol free, sugar free; contains polyethylene glycol (macrogol), propylene glycol, saccharin sodium, sodium benzoate; cherry 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; cherry flavor]
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; cherry flavor]
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) [contains alcohol, usp, disodium edta, fd&c red #40 (allura red ac dye), saccharin sodium, sodium benzoate; cherry flavor]
Yes
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.
C-V
Oral: Administer with full glass of water. Administer with an accurate measuring device; do not use a household teaspoon (overdosage may occur).
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.
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.
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]).
Refer to individual components.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification
Amphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: 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. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: 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. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification
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. Risk C: 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. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect 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 enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Disulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination
Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: 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. Risk D: Consider therapy modification
Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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 diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect 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
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, a disulfiram-like reaction may occur and CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Codeine. Risk X: Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nalfurafine: Opioid Agonists may enhance the adverse/toxic effect of Nalfurafine. Opioid Agonists may diminish the therapeutic effect of Nalfurafine. Risk C: Monitor therapy
Nalmefene: May diminish the therapeutic effect 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 diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid combination
Nefazodone: Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the 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 therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: 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. Risk X: Avoid combination
Ornidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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 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. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: 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). Risk C: Monitor therapy
Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Risk C: 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. Risk D: Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: 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. Risk D: Consider therapy modification
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Samidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combination
Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination
Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may diminish the therapeutic effect 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 therapy
Serotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4 and CYP2D6) 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. Risk C: 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. Risk D: Consider therapy modification
Somatostatin Analogs: May decrease serum concentrations of the active metabolite(s) of Codeine. Specifically, the concentrations of the active metabolite morphine may be reduced. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: 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. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect 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
Refer to individual monographs.
Refer to individual monographs.
Some products may contain sodium.
Relief of symptoms; respiratory and mental status; signs of misuse, abuse, and substance use disorder.
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
See individual agents.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
