ANTITUSSIVE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ANTITUSSIVE (ANTITUSSIVE).
Antitussives suppress cough by acting on the cough center in the medulla oblongata (central antitussives) or by anesthetizing stretch receptors in the respiratory tract (peripheral antitussives).
| Metabolism | Metabolism varies by agent: Dextromethorphan is metabolized via CYP2D6; codeine (opioid antitussive) is metabolized via CYP2D6 to morphine; benzonatate is metabolized by plasma esterases. |
| Excretion | Renal excretion of unchanged drug and metabolites (primarily glucuronide conjugates) accounts for approximately 60-80% of elimination, with biliary/fecal excretion contributing 15-25%. |
| Half-life | Terminal elimination half-life is 3-6 hours in adults; prolonged in renal impairment (up to 12-18 hours). |
| Protein binding | Approximately 35-45% bound to plasma albumin. |
| Volume of Distribution | Vd approximately 3-5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: approximately 40-50% due to first-pass metabolism. |
| Onset of Action | Oral: 15-30 minutes; intranasal: 5-10 minutes (not commonly used). |
| Duration of Action | Oral: 4-6 hours; extended-release formulations: up to 12 hours. |
For dextromethorphan: 10-20 mg orally every 4-6 hours, maximum 120 mg/day. For codeine: 10-20 mg orally every 4-6 hours, maximum 120 mg/day.
| Dosage form | SYRUP |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 25%; GFR 10-29 mL/min: reduce dose by 50%; GFR <10 mL/min: use with caution, avoid if possible. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Dextromethorphan: 2-6 years: 2.5-5 mg every 4-6 hours; 6-12 years: 5-10 mg every 4-6 hours; >12 years: adult dose. Codeine: not recommended for children due to safety concerns. |
| Geriatric use | Initiate at lowest effective dose; monitor for sedation, constipation, and falls; avoid codeine if possible; dextromethorphan: 10 mg every 6-8 hours. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ANTITUSSIVE (ANTITUSSIVE).
| Breastfeeding | Dextromethorphan: Low levels in breast milk; M/P not established; generally compatible. Codeine: M/P ratio ~2.5; risk of CNS depression in infant; use caution or avoid. Monitor infant for sedation. |
| Teratogenic Risk | Antitussive agents (e.g., dextromethorphan, codeine) have limited data. Dextromethorphan: Animal studies show no teratogenicity; human data insufficient. Codeine: Risk of neonatal respiratory depression and withdrawal if used near term; possible association with congenital malformations in first trimester, but evidence inconclusive. Avoid use in first trimester and near term. |
■ FDA Black Box Warning
N/A (No black box warning for general antitussives; specific agents like benzonatate have warnings for severe allergic reactions and accidental ingestion in children.)
| Serious Effects |
["Hypersensitivity to the specific antitussive agent.","Concomitant use of MAOIs or within 14 days (risk of serotonin syndrome with dextromethorphan).","Respiratory depression (especially opioid-containing antitussives)."]
| Precautions | ["Do not exceed recommended dosage (risk of toxicity, especially with dextromethorphan abuse).","Caution in patients with respiratory depression, asthma, or chronic cough due to smoking or COPD.","Avoid in children <2 years (risk of serious adverse events)."] |
| Food/Dietary | Grapefruit juice may increase absorption of dextromethorphan, potentially increasing side effects. Avoid alcohol as it enhances CNS depression. No specific food restrictions for codeine, but avoid high-tyramine foods if taking MAOIs concurrently. |
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| Fetal Monitoring | Monitor maternal respiratory status and sedation. For codeine, monitor neonatal respiratory depression and withdrawal symptoms if used near term. Ultrasound for fetal growth if prolonged use. |
| Fertility Effects | No significant effects on fertility reported in animal studies. Human data lacking. |
| Clinical Pearls | Antitussives like dextromethorphan are effective for nonproductive cough but should not be used in patients with chronic productive cough due to potential suppression of necessary mucus clearance. Abuse potential exists with dextromethorphan at high doses; monitor for serotonin syndrome when combined with MAOIs or SSRIs. Codeine-containing antitussives require caution in CYP2D6 ultra-rapid metabolizers due to risk of morphine toxicity. |
| Patient Advice | Take only for dry, hacking cough; do not use for cough with phlegm unless directed by a doctor. · Do not exceed recommended dose; excessive use can lead to serious side effects including confusion, hallucinations, and rapid heart rate. · Avoid alcohol and sedatives as they may increase drowsiness and respiratory depression. · Seek medical attention if cough persists >1 week, or is accompanied by fever, rash, or headache. · Do not combine with other cough/cold products containing the same active ingredients. |