1. Clinical Overview
A fixed-dose combination antitussive medication containing Dextromethorphan, a centrally-acting non-opioid cough suppressant, and Diphenhydramine, a first-generation sedating antihistamine with anticholinergic and antitussive properties. This combination provides synergistic cough suppression by acting on different pathways in the cough reflex arc, offering relief from both dry, non-productive cough and associated symptoms like rhinorrhea and sneezing.
| Onset | Duration | Bioavailability |
|---|---|---|
| Dextromethorphan: 15-30 minutes; Diphenhydramine: 15-60 minutes. | Dextromethorphan: 5-6 hours; Diphenhydramine: 4-6 hours. | Dextromethorphan: Approximately 11% (extensive first-pass metabolism). Diphenhydramine: 40-60%. |
2. Mechanism of Action
The combination works synergistically to suppress the cough reflex. Dextromethorphan acts centrally on the sigma-1 receptor and as an NMDA receptor antagonist in the medullary cough center, raising the threshold for coughing. Diphenhydramine acts both centrally and peripherally: it suppresses the cough center via its sedative/anticholinergic action and provides peripheral H1-antagonism, reducing post-nasal drip and irritation that can trigger cough.
3. Indications & Uses
- Symptomatic relief of dry, non-productive cough associated with upper respiratory tract infections (common cold) and allergic conditions.
- Suppression of cough where cough serves no useful purpose or may be harmful.
4. Dosage & Administration
Adult Dosage: One tablet/capsule (Dextromethorphan HBr 10mg + Diphenhydramine 8mg) every 4 to 6 hours. Maximum: 4 doses in 24 hours.
Administration: Administer orally with or without food. May be taken with a full glass of water. Do not crush or chew sustained-release formulations (if available). Avoid taking with alcohol. Best taken at bedtime if sedation is problematic during daytime.
5. Side Effects
Common side effects may include:
- Drowsiness, sedation
- Dizziness
- Dry mouth, nose, and throat
- Gastrointestinal upset (nausea)
- Thickening of bronchial secretions
- Fatigue
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Monoamine Oxidase Inhibitors (MAOIs) - e.g., Phenelzine, Selegiline, Linezolid | Risk of severe serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability). | Contraindicated |
| Other CNS Depressants (Alcohol, Benzodiazepines, Opioids, Barbiturates) | Additive CNS depression, sedation, impaired psychomotor performance. Increased risk of respiratory depression. | Major |
| Anticholinergic drugs (Atropine, TCAs like Amitriptyline, Antipsychotics) | Additive anticholinergic side effects (dry mouth, constipation, urinary retention, blurred vision, confusion). | Major |
| Serotonergic drugs (SSRIs like Fluoxetine, SNRIs, Tramadol) | Increased risk of serotonin syndrome due to dextromethorphan's serotonergic activity. | Moderate to Major |
| CYP2D6 Inhibitors (Quinidine, Fluoxetine, Paroxetine) | Markedly increased dextromethorphan levels, increasing toxicity and side effects. | Moderate |
7. Patient Counselling
- DO take the exact dose as prescribed by your doctor, not exceeding the maximum daily limit.
- DO take with a full glass of water.
- DO inform your doctor about all other medicines, vitamins, and herbal supplements you are taking.
- DON'T consume alcohol in any form while on this medication.
- DON'T drive, operate heavy machinery, or engage in activities requiring mental alertness.
- DON'T use for chronic cough due to smoking, asthma, or emphysema without doctor's advice.
- DON'T give to children under 6 years of age.
8. Toxicology & Storage
Overdose: Symptoms are primarily an extension of side effects, dominated by diphenhydramine's anticholinergic and CNS effects: Severe CNS depression (coma, respiratory depression) or stimulation (hallucinations, seizures, agitation). Anticholinergic toxidrome: Flushed skin, dry mouth, dilated pupils (mydriasis), tachycardia, hyperthermia, urinary retention, ileus. Dextromethorphan overdose can cause nystagmus, ataxia, slurred speech, and serotonin syndrome in combination with other serotonergic drugs.
Storage: Store at room temperature (15-30°C), protected from light and moisture. Keep in the original container, tightly closed. Keep out of reach and sight of children and pets. Do not use after the expiry date printed on the pack. Do not flush medications down the toilet or pour them into a drain.