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Dextromethorphan
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10 to 20 mg PO every 4 hours as needed; or 30 mg PO every 6 to 8 hours as needed. Follow the directions on the consumer label for the product chosen. Max: 120 mg/day PO.
10 to 20 mg PO every 4 hours as needed; or 30 mg PO every 6 to 8 hours as needed. Follow the directions on the consumer label for the product chosen. Max: 120 mg/day PO.
5 to 10 mg PO every 4 hours as needed; or 15 mg PO every 6 to 8 hours as needed. Follow the directions on the consumer label for the product chosen. Max: 60 mg/day PO.
2.5 to 5 mg PO every 4 hours as needed; or 7.5 mg PO every 6 to 8 hours as needed. Follow the directions on the consumer label for the product chosen. Max: 30 mg/day PO.
60 mg (10 mL) PO every 12 hours as needed. Max: 120 mg/day PO.[57854] [70453]
60 mg (10 mL) PO every 12 hours as needed. Max: 120 mg/day PO.[57854] [70453]
30 mg (5 mL) PO every 12 hours as needed. Max: 60 mg/day PO.[57854] [70453]
15 mg (2.5 mL) PO every 12 hours as needed. Max: 30 mg/day PO.[57854] [70453]
A median dose of 400 mg/day PO, given in 4 divided doses, has been used in clinical trials. Doses are initiated at 30 mg PO 4 times daily, then titrated to effectiveness and maximal tolerance. Limited, small, randomized trials have suggested that high doses of dextromethorphan may produce moderate reductions of painful diabetic neuropathy (PDN); however, significant adverse effects occur. Max: 960 mg/day PO given in 4 divided doses.[61483] [61484] American Academy of Neurology guidelines consider dextromethorphan as probably effective in lessening pain and improving quality of life; moderate pain reductions of 16% to 24% are achieved; however, sedation approaches 58% and other substantial adverse effects (e.g., anorexia, constipation, ataxia, confusion) may occur.[58281] Because of the dosages used, commercially available products are not amenable for dosing; trials used extemporaneously compounded capsules for dosing.[58281]
120 mg/day PO for extended- and immediate-release formulations as a cough suppressant; off-label suggested maximum for diabetic neuropathy: 960 mg/day PO of immediate-release formulations.
120 mg/day PO for extended- and immediate-release formulations as a cough suppressant; off-label suggested maximum for neuropathy: 960 mg/day PO of immediate-release formulations.
120 mg/day PO for extended- and immediate-release formulations.
12 years: 120 mg/day PO for extended and immediate-release formulations.
6 to 11 years: 60 mg/day PO for extended and immediate-release formulations.
4 to 5 years: 30 mg/day PO for extended and immediate-release formulations.
1 to 3 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Dextromethorphan is extensively metabolized by the liver and should be used with caution in patients with severe hepatic disease because of possible increased drug concentrations.[70455] However, no dosage adjustments are recommended in the product labels when used as a nonprescription cough suppressant.[57854] [70453]
No dosage adjustments are needed; renal elimination is not a significant elimination pathway for dextromethorphan.[70456]
† Off-label indication
Dextromethorphan is an oral non-opioid antitussive agent. Although it is related to the opioid agonists (dextromethorphan is the methyl ether of the d-isomer of levorphanol), dextromethorphan does not exhibit typical opioid characteristics. The only opioid-like characteristic dextromethorphan retains is its antitussive property. Dextromethorphan is primarily used to treat nonproductive cough; it has no expectorant activity. When ingested at recommended dosage levels for intended purposes, dextromethorphan is generally regarded as a safe and effective cough suppressant; however, the drug's utility for cough due to upper respiratory infection (URI) is not robust. There is some evidence dextromethorphan is helpful for patients with cough due to chronic bronchitis or COPD. Dextromethorphan has been identified as an antagonist to N-methyl-D-aspartate (NMDA) receptors and has been studied in the treatment of pain including cancer pain, postoperative pain, and neuropathic pain with mixed results and, in some cases, intolerable side effects due to the high doses employed for these uses. Abuse of dextromethorphan has been reported and excessive dosage can cause serious side effects, including ataxia, impaired cognition, psychosis, disassociation, and serotonin syndrome. A variety of oral formulations of dextromethorphan are available without a prescription, and dextromethorphan is also frequently found in nonprescription combination cough and cold products.[57854][61317][61874][70453][70462]
For storage information, see the specific product information within the How Supplied section.
Tablets and Softgel capsules:
Oral solutions or syrup (immediate-release, dextromethorphan hydrobromide):
Extended-release oral suspension (dextromethorphan polistirex suspension):
Adverse reactions to dextromethorphan at usual doses used for cough suppression are generally mild and infrequent. Drowsiness, dizziness, and fatigue are not reported often. Rash, urticaria and anaphylactoid reactions have rarely been reported.[61317]
Excessive dextromethorphan dosage due to higher than recommended doses or substance abuse may result in additional adverse effects consistent with the serotonin syndrome including: confusion, excitement, nervousness, restlessness, irritability, nausea, vomiting, and dysarthria (slurred speech). Psychosis, hallucinations, ataxia, disassociation, and other CNS and neurological effects have been reported with abuse or overdosage. Although dextromethorphan is the dextro-isomer of levorphanol, it has little dependence liability since it lacks the opiate agonist effects.[61053] [61317] [63409] [70462]
Patients with a chronic cough that lasts such as occurs with tobacco smoking, asthma, or emphysema, or a cough that occurs with too much phlegm (mucus), should consult their care team before use. Patients should stop use and consult their care team if a cough lasts more than 7 days, comes back, or occurs with fever, rash, or persistent headache. These could be signs of a serious condition.[57854] [70453]
Dextromethorphan is extensively metabolized by the liver and should be used with caution in patients with severe hepatic disease because of possible increased drug concentrations.[70455] However, no dosage adjustments are recommended in the product labels when used as a nonprescription cough suppressant.[57854] [70453]
Due to the risk for serious adverse reactions, the FDA recommends against administration of over the counter (OTC) cough and cold products to infants and children younger than 2 years of age; most dextromethorphan products are labeled for children 4 years of age and older. When administering OTC medications to older pediatric patients, advise caregivers to read product labels carefully, use caution when administering multiple products to avoid duplication of ingredients, and use only measuring devices specifically designed for use with medications. Thoroughly assess each patient's use of similar products, both prescription and nonprescription, to avoid duplication of therapy and the potential for inadvertent overdose.[66367] [66370] [57854] [70453]
There are no adequate and well-controlled studies of dextromethorphan use during pregnancy. Dextromethorphan is available without a prescription, and because it acts as a low affinity antagonist to the glutamate receptor subtype N-methyl-D-aspartate (NMDA) in the CNS, there has been some concern about its safe use during pregnancy. Dextromethorphan exhibited adverse developmental effects in avian embryos; however, the avian study data have limited applicability to human gestation.[24591] Human surveillance data and retrospective studies have shown dextromethorphan to be relatively safe during the first trimester; a human epidemiologic study and a smaller controlled study have not demonstrated elevated risks of congenital malformations. In one controlled study, there were no cases of neural tube defects, and no differences in number of live births, spontaneous or elective abortions, stillbirths, or major or minor malformations among infants exposed to dextromethorphan during the first trimester and those who were not. The results suggested that use during pregnancy does not pose a risk to the fetus; however, due to the small sample size, an increased risk of rare malformations could not be ruled out.[26485] [61291] In a large, population-based case control study of maternal use of cough medications during early pregnancy, dextromethorphan use was associated with a small number of birth defects, including hydrocephalus, atrioventricular septal defect and transverse limb deficiency.[69304]
Limited data are available regarding the use of dextromethorphan during breast-feeding. Based on dextromethorphan's relatively low molecular weight, some transfer into breast milk is expected. Some experts consider dextromethorphan, at usual adult doses for cough, to be compatible with breast-feeding and unlikely to be harmful to the nursing infant. One study estimated infant exposure via breast milk to be less than 1% of the usual maternal dose.[39683] Some dextromethorphan cough products contain alcohol and these products should be avoided while breast-feeding.
Patients should not use dextromethorphan if they are taking a prescription monoamine oxidase inhibitor (MAOI therapy) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping the MAOI drug. This combination is considered contraindicated due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome.[57854] [70453] [61317]
Dextromethorphan is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors in the brain and spinal cord, and this activity is responsible for its therapeutic and toxic effects. [30175][61317][61483] The NMDA receptor complex is a ligand-gated ion channel capable of allowing intracellular entry of calcium ions, which, in turn, stimulates second and third messenger signaling pathways. The NMDA receptor is found throughout the nervous system and is involved in processes such as development, learning, and memory. The NMDA receptor is also thought to sensitize interneurons following repetitive activation of nociceptors. Sustained activation of the NMDA receptor is believed to be involved in allodynia, hyperalgesia, and reduced efficacy of opioids. Activation of NMDA receptors by glutamate and aspartate may play a role in the "wind-up" phenomenon or secondary pain. Secondary pain occurs due to C-fiber stimulation of nociceptors. As compared to A-fibers, the afferent C-fibers are small and have slow conduction, resulting in delayed sensation of dull, persistent, poorly localized pain. The overactivity of these receptors has been shown to produce neurotoxicity that may lead to nerve death. NMDA antagonists, such as dextromethorphan, can block these actions and, in theory, may be neuroprotective. NMDA antagonists can also potentiate opioids and reduce the development of tolerance to opiates, which may be helpful in treating neuropathic pain.[61483][61317]
As an antitussive, dextromethorphan acts centrally on the cough center in the medulla to raise the threshold for coughing by decreasing the excitability of the cough center. Dextromethorphan is about equal to codeine in depressing the cough reflex. It is the d-isomer of levorphanol but has none of the analgesic, respiratory depressive, or sedative effects associated with opiate agonists when used in usual antitussive dosages. In therapeutic dosage dextromethorphan also does not inhibit ciliary activity. Naloxone, an opiate-antagonist, does not block the antitussive effects of dextromethorphan.[30175][33648][43973][63425]
Revision Date: 09/12/2024, 01:46:00 AMDextromethorphan is administered orally. Dextromethorphan is approximately 60% to 70% protein bound. Dextromethorphan is primarily metabolized in the liver by CYP2D6. When dextromethorphan is administered to extensive CYP2D6 metabolizers (normal metabolizers), the drug undergoes rapid and extensive hepatic metabolism to demethylated metabolites. Excretion of dextromethorphan is primarily by renal elimination of metabolites. In humans, (+)-3-hydroxy-N-methylmorphinan, (+)-3-hydroxy-morphinan, and traces of unmetabolized drug were found in urine after oral administration.
Affected Cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6
Dextromethorphan is primarily metabolized by the CYP2D6 isoenzyme and is a senstive substrate.[56579]
Dextromethorphan is rapidly absorbed from the GI tract, with antitussive activity appearing within 15 to 30 minutes. Food does not affect absorption. Antitussive activity can last for 3 to 6 hours.
Dextromethorphan pharmacokinetics (exposure, maximum concentrations, clearance) are similar in patients with mild to moderate hepatic impairment and healthy subjects. Caution is recommended for patients with severe hepatic disease since drug concentrations may increase.[70455][70456]
Subjects with renal impairment show little difference in dextromethorphan pharmacokinetics compared to healthy subjects. Renal elimination is not a significant elimination pathway for dextromethorphan.[70456]
CYP2D6 Poor Metabolizers
The rate of dextromethorphan metabolism varies between individuals according to CYP2D6 phenotype (extensive or poor metabolizers). In poor metabolizers (PMs) of CYP2D6, dextromethorphan exposure is naturally increased and the action is prolonged, and dextromethorphan-related adverse effects may be possible in some of these patients. Approximately 7% to 10% of Caucasians and 3% to 8% of African Americans are classified as CYP2D6 PMs.
There are no adequate and well-controlled studies of dextromethorphan use during pregnancy. Dextromethorphan is available without a prescription, and because it acts as a low affinity antagonist to the glutamate receptor subtype N-methyl-D-aspartate (NMDA) in the CNS, there has been some concern about its safe use during pregnancy. Dextromethorphan exhibited adverse developmental effects in avian embryos; however, the avian study data have limited applicability to human gestation.[24591] Human surveillance data and retrospective studies have shown dextromethorphan to be relatively safe during the first trimester; a human epidemiologic study and a smaller controlled study have not demonstrated elevated risks of congenital malformations. In one controlled study, there were no cases of neural tube defects, and no differences in number of live births, spontaneous or elective abortions, stillbirths, or major or minor malformations among infants exposed to dextromethorphan during the first trimester and those who were not. The results suggested that use during pregnancy does not pose a risk to the fetus; however, due to the small sample size, an increased risk of rare malformations could not be ruled out.[26485] [61291] In a large, population-based case control study of maternal use of cough medications during early pregnancy, dextromethorphan use was associated with a small number of birth defects, including hydrocephalus, atrioventricular septal defect and transverse limb deficiency.[69304]
Limited data are available regarding the use of dextromethorphan during breast-feeding. Based on dextromethorphan's relatively low molecular weight, some transfer into breast milk is expected. Some experts consider dextromethorphan, at usual adult doses for cough, to be compatible with breast-feeding and unlikely to be harmful to the nursing infant. One study estimated infant exposure via breast milk to be less than 1% of the usual maternal dose.[39683] Some dextromethorphan cough products contain alcohol and these products should be avoided while breast-feeding.
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