Usage
- Dextromethorphan Hydrochloride is prescribed for the temporary relief of cough caused by minor throat and bronchial irritation associated with the common cold or inhaled irritants. It is not effective for chronic cough associated with smoking, asthma, or emphysema, or when cough is accompanied by excessive phlegm.
- Pharmacological Classification: Antitussive (Cough Suppressant).
- Mechanism of Action: Dextromethorphan works primarily in the medulla oblongata of the brainstem, where it suppresses the cough reflex by increasing the cough threshold. Although structurally similar to opioids, dextromethorphan has no analgesic or addictive properties at recommended doses.
Alternate Names
- Dextromethorphan Hydrobromide (HBr)
- DXM
- Robitussin DM (and other brand names containing “DM”)
- Delsym
How It Works
- Pharmacodynamics: Dextromethorphan exerts its antitussive effect by acting on sigma-1 receptors and, to a lesser extent, NMDA receptors in the central nervous system. It does not bind to opioid receptors like codeine, explaining its lack of analgesic and addictive potential.
- Pharmacokinetics:
- Absorption: Well-absorbed from the gastrointestinal tract.
- Metabolism: Extensively metabolized in the liver, primarily by the cytochrome P450 2D6 (CYP2D6) enzyme to dextrorphan, an active metabolite that also contributes to the antitussive effect.
- Elimination: Excreted primarily in the urine as metabolites.
- Mode of Action: Dextromethorphan acts centrally to increase the threshold for coughing. This effect is primarily achieved by binding to the sigma-1 receptors. Its sigma-1 receptor agonism may also play a role in treating pseudobulbar affect by an unknown mechanism.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Sigma-1 receptor agonist, NMDA receptor antagonist at high doses. The primary route of metabolism is via CYP2D6 to its active metabolite, dextrorphan. About 10% of individuals are considered “poor metabolizers” and can experience greater side effects.
- Elimination Pathways: Primarily renal excretion of metabolites after hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Immediate-release: 10-20 mg every 4 hours or 30 mg every 6-8 hours, not to exceed 120 mg in 24 hours.
- Extended-release: 60 mg every 12 hours, not to exceed 120 mg in 24 hours.
Children:
- Under 4 years: Not recommended.
- 4-6 years:
- Immediate-release: 2.5-5 mg every 4 hours or 7.5 mg every 6-8 hours, not to exceed 30 mg in 24 hours.
- Extended-release: 15 mg every 12 hours, not to exceed 30 mg in 24 hours.
- 6-12 years:
- Immediate-release: 5-10 mg every 4 hours or 15 mg every 6-8 hours, not to exceed 60 mg in 24 hours.
- Extended-release: 30 mg every 12 hours, not to exceed 60 mg in 24 hours.
- 12 years and older: Same as adult dose.
- Lozenges and strips have specific dose recommendations.
Special Cases:
- Elderly Patients: Use with caution due to potential age-related decline in hepatic and renal function. Start with the lower end of the dosing range.
- Patients with Renal Impairment: No specific dosage adjustment is typically required, but caution is advised.
- Patients with Hepatic Dysfunction: Use with caution due to potential impaired metabolism. Consider a lower starting dose.
- Patients with Comorbid Conditions: Caution should be exercised in patients with respiratory conditions like asthma or COPD.
Clinical Use Cases
Dextromethorphan is generally not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its sole indicated use is the symptomatic relief of cough.
Dosage Adjustments
Dose adjustments may be necessary in elderly patients, those with hepatic impairment, or those who are known poor metabolizers of CYP2D6. A lower starting dose and careful monitoring are recommended in these populations.
Side Effects
Common Side Effects:
- Dizziness
- Drowsiness
- Nausea
- Vomiting
- Constipation
- Nervousness
- Restlessness
- Confusion
- Dry mouth
Rare but Serious Side Effects:
- Allergic reactions (e.g., hives, difficulty breathing, swelling)
- Seizures
- Hallucinations
- Serotonin syndrome
- Respiratory depression (at very high doses)
- Tachycardia
Long-Term Effects:
Limited data on long-term effects, but chronic high-dose abuse can lead to neurological and psychological problems.
Adverse Drug Reactions (ADR):
Any of the rare but serious side effects listed above warrant immediate medical attention.
Contraindications
- Hypersensitivity to dextromethorphan.
- Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping MAOI therapy.
- Patients with respiratory depression or at risk of respiratory failure.
- Severe hepatic impairment.
Drug Interactions
- MAOIs: Co-administration can lead to serotonin syndrome, a potentially life-threatening condition.
- SSRIs, SNRIs, TCAs: Increased risk of serotonin syndrome.
- CYP2D6 inhibitors: May increase dextromethorphan levels and the risk of side effects.
- Alcohol and other CNS depressants: Additive sedative effects.
- Quinidine: Increases the risk of QT interval prolongation.
- Amiodarone, procainamide: Increased risk of QT prolongation, arrhythmias.
- Medications for Parkinson’s disease: Potential interactions exist.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Animal studies have shown adverse effects, but there are no adequate studies in humans). Dextromethorphan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Dextromethorphan is excreted in breast milk in small amounts. While generally considered safe, it’s important to choose alcohol-free formulations and monitor the infant for potential side effects like rash.
Drug Profile Summary
- Mechanism of Action: Centrally acting cough suppressant, primarily via sigma-1 receptor agonism.
- Side Effects: Dizziness, drowsiness, nausea, vomiting, constipation. Rarely: hallucinations, seizures, serotonin syndrome.
- Contraindications: Hypersensitivity, concurrent MAOI use, respiratory depression, severe hepatic impairment.
- Drug Interactions: MAOIs, SSRIs, SNRIs, TCAs, alcohol, CYP2D6 inhibitors, quinidine.
- Pregnancy & Breastfeeding: Use with caution during pregnancy (Category C); generally safe during breastfeeding (choose alcohol-free formulations).
- Dosage: Adults: 10-30 mg every 4-8 hours (IR), 60 mg every 12 hours (ER), max 120 mg/day. Pediatric dosing varies by age.
- Monitoring Parameters: Respiratory rate, mental status (especially in high-dose or combined use with serotonergic drugs).
Popular Combinations
- Dextromethorphan + Guaifenesin: Combines a cough suppressant with an expectorant to relieve both dry and chesty coughs.
- Dextromethorphan + Phenylephrine/Pseudoephedrine: Adds a decongestant to relieve nasal congestion.
Precautions
- General Precautions: Assess for allergies, respiratory function, and concurrent medication use.
- Pregnant Women: Use only if clearly needed and weigh the potential risks and benefits.
- Breastfeeding Mothers: Choose alcohol-free formulations and monitor the infant for adverse effects.
- Children & Elderly: Follow age-specific dosing guidelines and monitor for potential side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dextromethorphan Hydrochloride?
A: The dosage varies depending on age, formulation (immediate-release or extended-release), and individual patient factors. Please refer to the detailed dosage guidelines provided earlier in this document.
Q2: How does Dextromethorphan differ from codeine as a cough suppressant?
A: Unlike codeine, dextromethorphan does not bind to opioid receptors. This means it lacks analgesic and addictive properties at recommended doses, making it a safer option, especially in children.
Q3: Can Dextromethorphan be used in patients with asthma?
A: Dextromethorphan is generally not recommended for patients with asthma or other chronic respiratory conditions, as it can mask underlying breathing problems.
Q4: What are the signs of Dextromethorphan overdose?
A: Overdose can cause respiratory depression, seizures, hallucinations, confusion, and serotonin syndrome. Seek immediate medical attention if overdose is suspected.
Q5: Can Dextromethorphan interact with antidepressants?
A: Yes, dextromethorphan can interact with certain antidepressants, especially MAOIs, SSRIs, SNRIs, and TCAs, increasing the risk of serotonin syndrome. Concurrent use should be avoided or carefully monitored.
Q6: Is Dextromethorphan safe to use during pregnancy?
A: Dextromethorphan is a Pregnancy Category C drug, meaning animal studies have shown adverse effects, but adequate human studies are lacking. It should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
Q7: What should patients be advised regarding the use of Dextromethorphan?
A: Patients should be advised to follow the recommended dosage, avoid alcohol and other CNS depressants, and report any unusual symptoms to their healthcare provider. They should also be informed about potential drug interactions.
Q8: Can patients with liver disease take Dextromethorphan?
A: Patients with hepatic impairment should use dextromethorphan with caution, as it is extensively metabolized by the liver. A lower starting dose and careful monitoring are recommended.
Q9: What is the mechanism of serotonin syndrome associated with dextromethorphan?
A: Dextromethorphan can inhibit serotonin reuptake, particularly at high doses or in combination with other serotonergic drugs like MAOIs and SSRIs. This can lead to excessive serotonin levels in the synapse, causing symptoms like agitation, confusion, tremor, hyperthermia, and potentially life-threatening complications.
