Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACTIQ vs GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Guaifenesin is an expectorant that increases respiratory tract fluid secretions, reducing mucus viscosity. Dextromethorphan is a centrally acting cough suppressant that binds to NMDA receptors and sigma-1 receptors, elevating the cough threshold.
Management of breakthrough pain in cancer patients aged 16 and older who are already receiving and tolerant to opioid therapy for their underlying persistent cancer pain
Temporary relief of cough due to minor throat and bronchial irritation (FDA-approved),Off-label: symptomatic treatment of upper respiratory tract infections with cough and congestion
200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.
For adults and children ≥12 years: 10 m L (200 mg guaifenesin, 20 mg dextromethorphan) orally every 4 hours, not to exceed 60 m L (1200 mg guaifenesin, 120 mg dextromethorphan) per 24 hours.
Terminal half-life 0.83–2 hours (mean 1.3 h) in adults; note that context: transmucosal absorption leads to rapid onset but short duration; half-life is not correlated with clinical effect due to oral transmucosal route and rapid redistribution.
Guaifenesin: 1-2 hours; Dextromethorphan: 3-6 hours (extensive metabolizers), 18-24 hours (poor metabolizers due to CYP2D6 polymorphism).
Primarily hepatic via CYP3A4 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Guaifenesin is metabolized by oxidation and demethylation; dextromethorphan is extensively metabolized by CYP2D6 to dextrorphan (active metabolite) and other metabolites.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
Guaifenesin: ~60% renal (metabolites), ~35% fecal; Dextromethorphan: ~70% renal (parent and metabolites, 45% as unchanged dextrorphan), ~20% biliary/fecal.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
Guaifenesin: negligible (<10%); Dextromethorphan: ~60-70% (mainly albumin and alpha-1-acid glycoprotein).
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
Guaifenesin: 1.2 L/kg (distributes into tissues); Dextromethorphan: 5-7 L/kg (large Vd due to high tissue binding).
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
Oral: Guaifenesin ~95%; Dextromethorphan ~11% (extensive first-pass metabolism, variable due to CYP2D6).
No specific GFR-based dose adjustment recommended; use with caution in severe renal impairment (Cr Cl < 30 m L/min) and consider dose reduction due to potential accumulation.
No specific guidelines; use with caution in severe renal impairment (Cr Cl <30 m L/min) due to potential accumulation of dextromethorphan metabolite.
Child-Pugh Class A/B: No adjustment. Child-Pugh Class C: Reduce initial dose to 100 mcg and titrate slowly; monitor closely for prolonged effects.
For dextromethorphan: Child-Pugh class C: consider reducing dose by 50% or avoid use; Child-Pugh A/B: no specific adjustment but monitor for CNS effects.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Children 6-11 years: 5 m L (100 mg guaifenesin, 10 mg dextromethorphan) every 4 hours, max 30 m L/day. Children 2-5 years: 2.5 m L (50 mg guaifenesin, 5 mg dextromethorphan) every 4 hours, max 15 m L/day. Not for children <2 years.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
Use the lowest effective dose; consider starting with 5 m L (100 mg guaifenesin, 10 mg dextromethorphan) every 4-6 hours due to increased risk of sedation and anticholinergic effects.
Risk of respiratory depression, addiction, abuse, and misuse; accidental ingestion can be fatal; concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death; not for use in opioid non-tolerant patients; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; serious, life-threatening, or fatal respiratory depression may occur even at recommended doses.
None.
Risk of respiratory depression; addiction, abuse, and misuse; interactions with CNS depressants; serotonin syndrome; adrenal insufficiency; severe hypotension; seizures; withdrawal; use in patients with head injuries, increased intracranial pressure, biliary tract disease, pancreatitis; risk of choking with lozenge; oral mucosal irritation; dental caries; hypokalemia; hyponatremia; use in elderly, cachectic, or debilitated patients.
Avoid use in patients with chronic cough (e.g., smoking, asthma, emphysema) or cough with excessive phlegm.,Concomitant use with MAOIs or within 2 weeks of MAOI use is contraindicated.,Dextromethorphan abuse potential; use caution with CYP2D6 inhibitors.
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected paralytic ileus; hypersensitivity to fentanyl or any component; opioid non-tolerant patients; management of acute or postoperative pain including headache/migraine, dental pain, or emergency department use.
Hypersensitivity to guaifenesin or dextromethorphan,Concurrent use or recent use (within 2 weeks) of monoamine oxidase inhibitors (MAOIs),Severe hypertension, coronary artery disease, or narrow-angle glaucoma (due to sympathomimetic effects if combined with decongestants; note: this combination alone does not contain decongestants, but caution applies)
No significant food interactions. Grapefruit juice may increase fentanyl levels, but specific studies with ACTIQ are lacking. Avoid alcohol, as it may increase sedation and respiratory depression risk.
No significant food interactions; avoid alcohol as it may increase sedation and dizziness.
FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause neonatal opioid withdrawal syndrome; avoid use during labor due to risk of neonatal respiratory depression.
Guaifenesin: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Dextromethorphan: No increased risk of major malformations in first trimester; animal studies show no teratogenicity. Avoid excessive doses in third trimester due to potential neonatal withdrawal or respiratory depression. Overall, both agents are considered low risk but use only if clearly needed.
Excreted in breast milk; M/P ratio not established. Limited data suggest low levels, but risk of infant sedation and respiratory depression. Avoid use while breastfeeding unless potential benefit outweighs risk.
Guaifenesin: Excreted in breast milk in small amounts; unlikely to cause adverse effects in infants. Dextromethorphan: Excreted in breast milk; limited data suggest low infant exposure (M/P ratio not established). Both are considered compatible with breastfeeding; use lowest effective dose and monitor infant for sedation or respiratory depression.
Due to increased plasma volume and hepatic metabolism in pregnancy, dose requirements may increase; adjust based on clinical response and tolerance. Avoid use during labor and delivery due to risk of neonatal respiratory depression; short-term use preferred.
No pharmacokinetic data to support dose adjustments during pregnancy; use lowest effective dose for shortest duration. Guaifenesin: increased renal clearance in pregnancy may theoretically reduce efficacy, but no dose adjustment recommended. Dextromethorphan: metabolism by CYP2D6 may be affected by pregnancy; avoid exceeding standard doses.
ACTIQ is a transmucosal immediate-release fentanyl formulation indicated for breakthrough cancer pain in opioid-tolerant patients. Initiate with the lowest strength (200 mcg) and titrate upward. Avoid use in opioid-naive patients due to risk of fatal respiratory depression. Place the unit between cheek and lower gum, not sublingually. Instruct patient not to bite or suck the unit. Monitor for sedation and respiratory depression. Multiple units may be used per episode if needed, but wait at least 4 hours before next episode. Dispose of partially used units by flushing down toilet.
Monitor for sedation and dizziness, especially in elderly; avoid use with MAOIs due to serotonin syndrome risk; dextromethorphan has abuse potential at high doses; use caution in patients with chronic cough due to smoking, asthma, or COPD; guaifenesin may cause renal calculi with prolonged high doses.
Only use ACTIQ if you are already taking regular around-the-clock opioid pain medicine and are tolerant to opioids.,Do not use ACTIQ for short-term pain like after surgery, headache, or dental pain.,Place the unit in your cheek pouch, not under your tongue. Do not chew or suck it.,If you need more than 4 units per day, contact your doctor as your dose may need adjustment.,Store ACTIQ in a safe place away from children, as accidental ingestion can be fatal.,Dispose of unused or partially used units by flushing them down the toilet.
Do not exceed recommended doses; high doses can cause serious side effects including hallucinations and addiction.,Avoid driving or operating machinery if you feel dizzy or drowsy.,Do not use with other cough and cold medications to avoid overdose.,Increase fluid intake to help loosen mucus.,Stop use and consult a doctor if cough persists more than 7 days or comes with fever, rash, or headache.,Inform your doctor about all medications you take, especially MAOIs or SSRIs.,Keep out of reach of children; accidental overdose may be fatal in children.
No interactions on record
"The combination of dextromethorphan, a centrally acting antitussive with NMDA receptor antagonist and sigma-1 receptor agonist properties, and aceprometazine, a phenothiazine neuroleptic with strong antihistaminergic and moderate anticholinergic and antidopaminergic effects, can result in additive central nervous system depression. This interaction may lead to excessive sedation, respiratory depression, impaired psychomotor function, and an increased risk of falls or cognitive impairment, particularly in elderly or debilitated patients. Concurrent use may also lower the seizure threshold, especially in patients with predisposing factors."
"Dextromethorphan, a serotonergic agent metabolized by CYP2D6, when combined with cariprazine, a dopamine D3/D2 receptor partial agonist, may increase the risk of serotonin syndrome due to additive serotonergic effects. Cariprazine can inhibit CYP2D6, reducing dextromethorphan clearance and elevating its plasma concentration, leading to enhanced serotonin activity. Clinically, patients may present with altered mental status, autonomic instability, and neuromuscular abnormalities."
"Dextromethorphan inhibits CYP2B6 and CYP2C9, which are involved in valproic acid metabolism. This results in decreased valproic acid clearance, potentially elevating valproic acid serum concentrations and increasing the risk of dose-dependent adverse effects such as hepatotoxicity, thrombocytopenia, and sedation. Concurrent use requires dose adjustment and close monitoring for signs of valproate toxicity."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ACTIQ vs GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE, answered by our medical review team.
ACTIQ is a Opioid Analgesic that works by Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.. GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE is a Expectorant/Antitussive Combination that works by Guaifenesin is an expectorant that increases respiratory tract fluid secretions, reducing mucus viscosity. Dextromethorphan is a centrally acting cough suppressant that binds to NMDA receptors and sigma-1 receptors, elevating the cough threshold.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ACTIQ and GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ACTIQ is: 200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.. The standard adult dose of GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE is: For adults and children ≥12 years: 10 m L (200 mg guaifenesin, 20 mg dextromethorphan) orally every 4 hours, not to exceed 60 m L (1200 mg guaifenesin, 120 mg dextromethorphan) per 24 hours.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ACTIQ and GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ACTIQ is classified as Category C. FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause. GUAIFENESIN AND DEXTROMETHORPHAN HYDROBROMIDE is classified as Category C. Guaifenesin: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Dextromethorphan: No increased risk of major malformations in first trimester; . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.