Centrally acting cough suppressant
Brand names: Bisolvon Antitusivo, Romilar, Robitussin Tos, Delsym
Updated · Methodology
Second line
Used in dry non-productive cough disturbing sleep or daily activity. ACCP 2018 and NG120 (2019) do not list central cough suppressants as first-line – modest efficacy data in acute cough (2014 Cochrane meta-analysis showed no significant advantage over placebo in adults). Adult dose 15–30 mg 3–4 times daily. Short course, no more than 7 days.
Sources
ICD-10: R05 · ICD-11: MD12
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Dextromethorphan is a cough suppressant and NMDA-receptor antagonist. It is used for symptomatic treatment of dry cough during respiratory infections (AAFP 2020 and CDC guidelines). In biohacker circles, dextromethorphan is taken at high doses as an antidepressant and for altered states of consciousness with empathogenic effects. The issued a 2010 warning about severe side effects with abuse: serotonin syndrome (especially in combination with SSRI or MAOI antidepressants), psychosis, motor disturbances, and acetaminophen-related hepatotoxicity in combination products. High-dose dextromethorphan is a psychoactive substance with abuse potential. If dextromethorphan is being taken for mood or cognition, consider seeking a second opinion: for depression there are drugs with confirmed efficacy.
The dextro-isomer of levomethorphan (opioid), but without analgesic or narcotic action. At therapeutic doses, selectively suppresses the medullary cough center without respiratory depression. At doses 10–30 times therapeutic, produces dissociative effects via NMDA receptor antagonism and serotonin reuptake inhibition – basis of recreational misuse. CYP2D6-metabolized to dextrorphan (active metabolite with greater NMDA activity).
Avoid in T1 where possible. For dry cough in pregnancy, first-line is non-pharmacological (hydration, humidification); paracetamol if fever is present.
Single doses are acceptable during lactation; regular use is not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
According to the Intertos SmPC, grapefruit and bitter orange juice inhibit CYP2D6 and CYP3A4, the enzymes that break down dextromethorphan, and raise its levels. Excess causes dizziness, drowsiness, nausea and confusion. The SmPC says not to take it with grapefruit or bitter orange juice.
Source: AEMPS: Ficha técnica de Intertos 15 mg comprimidos (dextrometorfano) (2020)
3 pairs found. Sorted from critical to minor.
Mechanism
Linezolid is a reversible MAO inhibitor. Dextromethorphan is a weak serotonin reuptake inhibitor and sigma-1 agonist. The combination produces synaptic serotonin accumulation and serotonin syndrome.
Symptoms
Within hours of co-administration: agitation, confusion, tachycardia, hypertension, hyperthermia, tremor, myoclonus, hyperreflexia. Severe cases – seizures, coma, rhabdomyolysis.
Management
The AEMPS label for dextromethorphan lists linezolid among contraindicated combinations. Avoid dextromethorphan for the linezolid course (typically 7–14 days). Alternative antitussives: guaifenesin or honey for nocturnal cough. If dextromethorphan was already taken, stop linezolid; serotonin syndrome resolves within 24 hours.
Sources
Mechanism
Moclobemide inhibits monoamine oxidase (MAO), mainly type A, and slows the breakdown of noradrenaline, dopamine and serotonin (moclobemide summary of product characteristics, SmPC, section 5.1). Dextromethorphan combined with drugs that affect serotonin metabolism, MAO inhibitors included, has caused life-threatening serotonin syndrome (dextromethorphan SmPC, section 4.4). According to the dextromethorphan SmPC, severe reactions with MAO inhibitors, moclobemide among them, may also result from slower breakdown of dextromethorphan in the liver (section 4.5). Moclobemide inhibits MAO reversibly, and its half-life is about 3 hours (moclobemide SmPC, sections 5.1 and 5.2). Even so, the dextromethorphan SmPCs require a 14-day interval after stopping any MAO inhibitor, moclobemide included (sections 4.3 and 4.5).
Symptoms
When combined with dextromethorphan, monoamine oxidase (MAO) inhibitors, moclobemide included, have caused serotonin syndrome with agitation, sweating, rigidity and hypertension (dextromethorphan summary of product characteristics, SmPC, section 4.5). According to the SmPC of dextromethorphan orodispersible tablets, nausea, coma, hypotension, leg tremor, muscle spasms and hyperpyrexia can also occur, up to myocardial infarction and death (section 4.5). Serotonin syndrome may include changes in mental state, autonomic instability, neuromuscular abnormalities and gastrointestinal symptoms (dextromethorphan and moclobemide SmPCs, section 4.4). Isolated cases of serious central nervous system adverse reactions have occurred after moclobemide and dextromethorphan were taken together (moclobemide SmPC, section 4.5).
Management
The combination is contraindicated. The moclobemide summary of product characteristics (SmPC) lists dextromethorphan (section 4.3). The dextromethorphan SmPCs name moclobemide among the monoamine oxidase inhibitors, or MAOIs (sections 4.3 and 4.5). The over-the-counter dextromethorphan label of the US Food and Drug Administration () also rules out the combination. Do not take dextromethorphan within 14 days after stopping moclobemide (dextromethorphan SmPCs, sections 4.3 and 4.5; FDA dextromethorphan label). Cough and cold medicines may contain dextromethorphan. Patients taking moclobemide are told not to use them without checking first, and cough is treated with products that do not contain dextromethorphan (moclobemide SmPC, sections 4.4 and 4.5). Patients who are not sure whether a prescription drug is an MAOI are advised to check before taking dextromethorphan (FDA dextromethorphan label). If serotonin syndrome is suspected, stop dextromethorphan (dextromethorphan SmPCs, section 4.4) and, depending on the severity of symptoms, reduce the moclobemide dose or stop moclobemide as well (moclobemide SmPC, section 4.4). Benzodiazepines can be used for seizures, and benzodiazepines with external cooling for hyperthermia caused by serotonin syndrome (dextromethorphan SmPCs, section 4.9).
Sources
Mechanism
Tranylcypromine is an irreversible, non-selective monoamine oxidase (MAO) inhibitor; MAO is the enzyme that breaks down serotonin, noradrenaline and dopamine (tranylcypromine SmPC, section 5.1). Dextromethorphan has serotonergic effects, and together with MAO inhibitors it can cause life-threatening serotonin syndrome (dextromethorphan SmPC, section 4.4). Part of the reaction may come from slower breakdown of dextromethorphan in the liver (dextromethorphan SmPC, section 4.5). Because MAO inhibition is irreversible, enzyme activity takes 3–5 days to return after the last dose of tranylcypromine (tranylcypromine SmPC, section 5.1). Inhibition may persist for up to 10 days (US Food and Drug Administration () tranylcypromine label).
Symptoms
Monoamine oxidase inhibitors combined with dextromethorphan have caused serotonin syndrome with agitation, sweating, rigidity and hypertension (dextromethorphan SmPC, section 4.5). The combination has also caused nausea, coma, hypotension, leg tremor, muscle spasms and hyperpyrexia that can lead to myocardial infarction and death (dextromethorphan orodispersible tablets SmPC, section 4.5). Serotonin syndrome may include changes in mental state, autonomic instability, neuromuscular abnormalities and gastrointestinal symptoms (dextromethorphan SmPC, section 4.4). Tranylcypromine and dextromethorphan together can have life-threatening effects on the central nervous system, breathing and circulation (tranylcypromine SmPC, section 4.5). Psychosis and bizarre behaviour are also possible (US Food and Drug Administration () tranylcypromine label).
Management
The combination is contraindicated (dextromethorphan SmPC, sections 4.3 and 4.5, which name tranylcypromine; tranylcypromine SmPC, sections 4.3 and 4.5; US Food and Drug Administration () tranylcypromine label, section 4.1). Avoid dextromethorphan for 14 days after stopping tranylcypromine (dextromethorphan SmPC, sections 4.3 and 4.5; tranylcypromine SmPC, section 4.2; FDA over-the-counter dextromethorphan label). Start tranylcypromine no earlier than 4–5 half-lives of dextromethorphan and its active metabolite after the last dose of dextromethorphan (FDA tranylcypromine label, section 7.1). Dextromethorphan is an ingredient of cough medicines (tranylcypromine SmPC, section 4.3). A patient taking tranylcypromine should therefore not use over-the-counter medicines or supplements without first asking a doctor or pharmacist (FDA tranylcypromine label, section 7.1). Nasal, cough and cold products may also contain indirect sympathomimetics, which are contraindicated with tranylcypromine because of the risk of severe hypertensive crisis (tranylcypromine SmPC, sections 4.3 and 4.5). If serotonin syndrome is suspected, stop dextromethorphan (dextromethorphan SmPC, section 4.4), stop tranylcypromine and other serotonergic drugs at once and start supportive symptomatic treatment (FDA tranylcypromine label, section 5.3).
Sources
Verbatim lines from the interaction sections, in the language of the label
«- Tratamiento, concomitante o en las 2 semanas precedentes, con IMAO (ver sección 4.5.)»AEMPS, section 4.3 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Antidepresivos inhibidores de la monoaminoxidasa (IMAO) como moclobemida y tranilcipromina; antidepresivos inhibidores de la recaptación de la serotonina (ISRS) como fluoxetina y paroxetina…»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«- Antiarrítmicos ( amiodarona o quinidina ). Aumentan las concentraciones plasmáticas de dextrometorfano pudiendo alcanzarse niveles tóxicos. Podría ser necesario un reajuste de dosis.»AEMPS, section 4.5 · Open on CIMA
«- Antiarrítmicos ( amiodarona o quinidina ). Aumentan las concentraciones plasmáticas de dextrometorfano pudiendo alcanzarse niveles tóxicos. Podría ser necesario un reajuste de dosis.»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«- Antiarrítmicos ( amiodarona o quinidina ). Aumentan las concentraciones plasmáticas de dextrometorfano pudiendo alcanzarse niveles tóxicos. Podría ser necesario un reajuste de dosis.»AEMPS, section 4.5 · Open on CIMA
«- Inhibidores de CYP2D6: El dextrometorfano se metaboliza por el CYP2D6 y tiene un elevado metabolismo de primer paso. El uso concomitante de inhibidores potentes de la enzima CYP2D6 puede aumentar…»AEMPS, section 4.5 · Open on CIMA
«- AINE inhibidores de la COX-2 (Coxib). En estudios farmacocinéticos se ha podido observar que las concentraciones plasmáticas de dextrometorfano podrían verse aumentadas al administrar junto con…»AEMPS, section 4.5 · Open on CIMA
«Dextrometorfano,»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics. Excitation, seizures, delirium…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Rasagiline is contraindicated for use with meperidine, tramadol, methadone, propoxyphene and MAO inhibitors (MAOIs), including other selective MAO-B inhibitors, because of risk of…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: • EMSAM (selegiline transdermal system) is contraindicated with selective serotonin reuptake inhibitors (SSRIs, e.g., fluoxetine, sertraline, and paroxetine); serotonin and…»FDA, section 4 · Open on DailyMed
«petidina, tramadol, dextrometorfano (dextrometorfano contenido en antitusivos);»AEMPS, section 4.3 · Open on CIMA
«Combination with Certain Drugs: dextromethorphan milnacipran tryptophan»FDA, section 4 · Open on DailyMed
«Se debe evitar el uso concomitante de memantina y amantadina, por el riesgo de psicosis farmacotóxica. Los dos compuestos están químicamente relacionados con los antagonistas del NMDA. Esto mismo…»AEMPS, section 4.5 · Open on CIMA
«Dextrometorfano: Existen informes de interacciones medicamentosas con el empleo concomitante de dextrometorfano e inhibidores de la MAO no selectivos. Por ello, y teniendo en cuenta la actividad…»AEMPS, section 4.5 · Open on CIMA
«Effects of Abiraterone on Drug Metabolizing Enzymes: Abiraterone acetate is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In a CYP2D6 drug-drug interaction trial, the C max…»FDA, section 7 · Open on DailyMed
«Substratos CYP2D6: Clobazam es un inhibidor débil del CYP2D6. Puede ser necesario un ajuste de la dosis de los medicamentos metabolizados por el CYP2D6 (por ejemplo, dextrometorfano, pimozida…»AEMPS, section 4.5 · Open on CIMA
«Sustratos de CYP2D6: codeína, dextrometorfano, flecainida, mexiletina, ondansetron, tamoxifeno, el tramadol.»AEMPS, section 4.5 · Open on CIMA
«Use with Other N-methyl-D-aspartate (NMDA) Antagonists: The combined use of memantine hydrochloride with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: In vivo studies have shown that terbinafine is an inhibitor of the CYP450 2D6 isozyme. Drugs predominantly metabolized by the CYP450 2D6 isozyme include the following drug…»FDA, section 7 · Open on DailyMed
«Posibilidad de que afecte a la exposición de otros medicamentos: En un estudio realizado para evaluar los efectos del acetato de abiraterona (administrado conjuntamente con prednisona) en una sola…»AEMPS, section 4.5 · Open on CIMA
«Interacción de aripiprazol con otros medicamentos: En ensayos clínicos, dosis de aripiprazol de 10-30 mg/AEMPS, section 4.5 · Open on CIMA
«Drugs Having No Clinically Important Interactions with Aripiprazole: In addition, no dosage adjustment is necessary for substrates of CYP2D6 (e.g., dextromethorphan, fluoxetine, paroxetine, or…»FDA, section 7 · Open on DailyMed
«Inhibición del CYP2D6: concentraciones plasmáticas de dextrometorfano y metoprolol (sustratos del CYP2D6) respectivamente.»AEMPS, section 4.5 · Open on CIMA
«En estudios de interacción clínica, ezetimiba no tuvo efecto sobre la farmacocinética de dapsona, dextrometorfano, digoxina, anticonceptivos orales (etinilestradiol y levonorgestrel), glipizida…»AEMPS, section 4.5 · Open on CIMA
«Interacciones serotoninérgicas potenciales: En voluntarios sanos, se estudió el potencial de interacción farmacológica de linezolid con dextrometorfano. Se administro dextrometorfano (dos dosis de 20…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone.»FDA, section 7 · Open on DailyMed
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Dextromethorphan is evaluated for the following indications with varying evidence strength: Dry cough (evidence tier C), Memory and concentration enhancement (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Dextromethorphan (≥ 1 in 100): Drowsiness, Dizziness, Nausea, Dry mouth, Constipation. See the Safety section for uncommon and serious reactions.
Avoid in T1 where possible. For dry cough in pregnancy, first-line is non-pharmacological (hydration, humidification); paracetamol if fever is present.
Single doses are acceptable during lactation; regular use is not recommended.
Dextromethorphan is contraindicated in: Dextromethorphan hypersensitivity; Concurrent MAO inhibitors or within 14 days of stopping; Age under 6 (most OTC forms); Severe hepatic impairment; Respiratory failure. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Acetylcysteine, Ambroxol, Bromhexine, Carbocisteine, Cloperastine, Guaifenesin, Ivy leaf dry extract (Hedera helix), Paracetamol + Chlorpheniramine + Phenylephrine