Antitussive (cough suppressant)
Dextromethorphan is a cough suppressant used to temporarily relieve dry cough in colds and airway irritation. It is available without prescription. It should not be used for cough with lots of phlegm or for more than 7 days.
Also known as: DXM, dextromethorphan, Romilar
DailyMed/FDA (NIH/NLM) — OTC Dextromethorphan label (Drug Facts): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d99237c-0b52-0af6-e063-6394a90aba14
OTC DailyMed label (Drug Facts): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d99237c-0b52-0af6-e063-6394a90aba14 — pharmacokinetics: PubMed PMID 7593709 (Influence of CYP2D6 phenotype and quinidine inhibition, 1995); PMID 8841152 (The influence of CYP2D6 polymorphism and quinidine, 1996)
Fluoxetine may raise dextromethorphan levels and the risk of serotonin syndrome.
Fluoxetine is a "potent inhibitor of the CYP2D6 enzyme pathway" (fluoxetine label, section 7.7) and dextromethorphan is primarily metabolised by CYP2D6 (its main metabolite, dextrorphan, is active). CYP2D6 inhibition by fluoxetine can significantly raise dextromethorphan concentrations, and both drugs have serotonergic activity — dextromethorphan is a weak serotonin reuptake inhibitor and fluoxetine is a potent SSRI. The risk of serotonin syndrome (agitation, confusion, fever, tremor, clonus, hyperreflexia) adds to the risk of raised dextromethorphan levels (sedation, dizziness, nausea, ataxia). The combination is frequent in over-the-counter cough medicines in patients taking fluoxetine. Avoid dextromethorphan in patients taking fluoxetine; if unavoidable, use the lowest dose and shortest duration possible, and advise the patient to watch for serotonergic symptoms (agitation, twitching, fever) and neurological symptoms (dizziness, ataxia). Consider alternative non-serotonergic antitussives.
Fluoxetine + dextromethorphan: fluoxetine inhibits CYP2D6 (raises dextromethorphan levels) and both are serotonergic — risk of serotonin syndrome.
Fluoxetine inhibits CYP2D6, the main metabolic pathway of dextromethorphan, and both are serotonergic.
Monitor agitation, tremor, hyperthermia, myoclonus and mental status changes.
Serotonin syndrome (hyperthermia, rigidity, confusion).
Avoid the combination; if unavoidable, use the lowest dextromethorphan dose and monitor.
DailyMed (FDA) — approved Dextromethorphan label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d99237c-0b52-0af6-e063-6394a90aba14 ; approved Fluoxetine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09fb3100-1e06-4cdc-8016-7e4f5d097490 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining dextromethorphan with tramadol increases the risk of serotonin syndrome and seizures.
Both dextromethorphan and tramadol have serotonergic action (serotonin reuptake inhibition), and the combination adds up the risk of serotonin syndrome, potentially life-threatening, with symptoms such as agitation, hallucinations, tachycardia, hyperthermia, hyperreflexia, myoclonus and rigidity. The tramadol label warns about serotonin syndrome with concomitant use of serotonergic drugs, and the combination of an antitussive with an opioid should be avoided whenever possible. If unavoidable, use the lowest doses, monitor for serotonin symptoms and consider alternatives (e.g., a non-serotonergic antitussive).
Dextromethorphan + tramadol: risk of serotonin syndrome (two serotonergic drugs). Avoid or monitor closely.
Both drugs raise serotonin; tramadol also lowers the seizure threshold.
Monitor serotonergic and neurological symptoms.
Serotonin syndrome, seizures.
Avoid the combination; if unavoidable, monitor closely and use the lowest effective dose.
DailyMed (FDA) — approved Dextromethorphan label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d99237c-0b52-0af6-e063-6394a90aba14 ; approved Tramadol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f0e33bd-65f8-446a-886f-e7e16a142ce5 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sertraline may potentiate the serotonergic effects of dextromethorphan.
Dextromethorphan has serotonergic action (serotonin reuptake inhibition) and is also a CYP2D6 substrate, an enzyme inhibited by sertraline; the combination with SSRIs such as sertraline increases the risk of serotonin syndrome, potentially life-threatening, with symptoms such as agitation, hallucinations, tachycardia, hyperthermia, hyperreflexia, myoclonus and rigidity. The sertraline label lists serotonergic drugs whose concomitant use increases the risk of serotonin syndrome, and the dextromethorphan label warns about interaction with MAO inhibitors. In patients on SSRIs, prefer alternative antitussives or use with caution, monitoring for serotonin symptoms.
Dextromethorphan + sertraline: risk of serotonin syndrome (serotonergic antitussive + SSRI). Avoid or monitor closely.
Additive serotonergic effect; partial CYP2D6 inhibition by sertraline.
Monitor agitation, diarrhoea, tremor, hyperreflexia and confusion.
Serotonin syndrome.
Monitor for symptoms of serotonergic excess with the combination.
DailyMed (FDA) — approved Dextromethorphan label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d99237c-0b52-0af6-e063-6394a90aba14 ; approved Sertraline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=91e24d17-ff0a-449c-9472-b9df74c98456 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol potentiates the central nervous system depression associated with dextromethorphan.
Avoid alcohol during treatment.
EMC-UK (MHRA) — approved Dextromethorphan SmPC: https://www.medicines.org.uk/emc/product/1523/smpc
Dextromethorphan is a central antitussive; in severe respiratory disease with hypersecretion, cough suppression can worsen secretion retention.
Use with caution in severe respiratory disease and assess the real need for the antitussive.
DailyMed/FDA (NIH/NLM) — approved Dextromethorphan label (Drug Facts): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d99237c-0b52-0af6-e063-6394a90aba14
Dextromethorphan can lower the seizure threshold at high doses or in susceptible patients.
Use with caution in patients with epilepsy and avoid high doses.
DailyMed/FDA (NIH/NLM) — approved Dextromethorphan label (Drug Facts): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0d99237c-0b52-0af6-e063-6394a90aba14
Data on dextromethorphan in pregnancy are limited; use only if needed.
Avoid in the 1st trimester; use the lowest dose and shortest duration possible.
Excreted into breast milk in small amounts; occasional use is probably compatible.
No specific additional contraception.
EMC-UK (MHRA) — approved Dextromethorphan SmPC: https://www.medicines.org.uk/emc/product/1523/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Centrally acting antitussive: raises the cough threshold in the brainstem cough centre (nucleus tractus solitarius), suppressing dry cough without significant analgesic or sedative effect at therapeutic doses. A levorphanol derivative without relevant opioid receptor affinity at usual doses.
Dextromethorphan acts on the cough centre in the brainstem; it is also an NMDA receptor antagonist at high doses (dissociative properties explaining the abuse potential). Its active metabolite dextrorphan contributes to the antitussive effect.
Dextromethorphan is well absorbed orally, with plasma peaks 1–2 hours after the dose; it undergoes hepatic first-pass metabolism. Oral bioavailability is variable (~11–70%) depending on the CYP2D6 phenotype; extended-release formulations have later peaks.
Dextromethorphan is metabolised mainly by CYP2D6 to dextrorphan (O-demethylation), the active metabolite, with minor pathways by CYP3A4/5 (N-demethylation). CYP2D6 polymorphism strongly influences exposure: in poor metabolisers, half-life and levels greatly increase; quinidine and SSRIs inhibit CYP2D6.
The elimination half-life is ~2–4 hours in extensive metabolisers, ~5.6 hours when CYP2D6 is inhibited (e.g. quinidine) and ~19 hours in poor metabolisers (CYP2D6).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
