簡單來說就是使用MAOI（Monoamine oxidase inhibitors）與SSRI（Selective serotonin reuptake inhibitors）這類藥物的患者
非選擇性的有（Nonselective MAO-A/MAO-B inhibitors）
- Isocarboxazid (Marplan)
- Nialamide (Niamid)
- Phenelzine (Nardil, Nardelzine)
- Tranylcypromine (Parnate, Jatrosom)
選擇性MAO A 抑制劑有（Selective MAO-A inhibitors）
- Bifemelane (Alnert, Celeport)
- Moclobemide (Aurorix, Manerix)
- Pirlindole (Pirazidol)
- Toloxatone (Humoryl)
選擇性MAO B 抑制劑（Selective MAO-B inhibitors）
- Rasagiline (Azilect)
- Selegiline (Deprenyl, Eldepryl, Emsam, Zelapar)
- Safinamide (Xadago)
同時，另一類SNRI（Serotonin and norepinephrine reuptake inhibitors）的藥物雖然仿單上沒有提到，但是我覺得也是需要注意，大致上有
於是兩個種類的藥物的血中濃度會同時增加，進而強化了副作用的反應，例如Serotonin syndrome 血清素症候群
Concurrent use of DEXTROMETHORPHAN and SELEGILINE may result in serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes).
The concurrent use of dextromethorphan and selegiline is contraindicated. Allow 14 days to elapse between the discontinuation of selegiline and the initiation of therapy with dextromethorphan or allow a minimum of 7 days to elapse between the discontinuation of the dextromethorphan and the initiation of therapy with selegiline.
The concurrent use of dextromethorphan and selegiline is contraindicated. Allow 14 days to elapse between the discontinuation of selegiline and the initiation of therapy with dextromethorphan or a minimum of 7 days should elapse after discontinuing dextromethorphan before initiating therapy with selegiline (Prod Info EMSAM® transdermal patch, 2006; Prod Info Humibid®DM, 1995). Concomitant use of dextromethorphan and other monoamine oxidase inhibitors has resulted in serotonin syndrome, with symptoms including nausea, hypotension, leg tremors, muscle spasms, hyperpyrexia, and coma, sometimes leading to cardiac arrest and death. Allow 14 days to elapse between withdrawal of selegiline and administration of buspirone (Rivers & Horner, 1970; Sovner & Wolfe, 1988).
Combined therapy with oral dextromethorphan and oral isocarboxazid resulted in neurologic toxicity (Sovner & Wolfe, 1988). A 32-year-old woman with depression took 10 mL of Robitussin DM® (dextromethorphan 15 mg and guaifenesin 100 mg per 5 mL with 1.4% alcohol) after having received isocarboxazid 30 mg daily for eight weeks. The patient developed dizziness and nausea within 20 minutes; leg tremors and muscle spasms in the lower back and abdomen occurred within 45 minutes. Persistent bilateral myoclonic jerks also developed in the legs, with occasional choreoathetoid movements of the feet and marked urinary retention. Diazepam 2 mg produced partial improvement in the symptoms; however, occasional myoclonic jerking prior to sleep was still present two months later.
A 26-year-old female who ingested phenelzine and two ounces of dextromethorphan-containing cough syrup orally as a single dose developed nausea, dizziness, and collapsed thirty minutes after ingesting the cough mixture. It was noted that the last dose of phenelzine was two tablets six hours earlier. The patient became unconscious with rigid extremities and fixed and dilated pupils. The patient was severely hypotensive with a systolic blood pressure which did not rise above 70 mmHg in association with a temperature of 42 to 42.2 degrees Centigrade. Despite vasopressors, anti-arrhythmics, and epinephrine, the patient had a cardiac arrest and subsequently died. Although a definite cause-effect relationship was not established, concomitant use should be avoided (Rivers & Horner, 1970).
Product Information: EMSAM(R) transdermal patch, selegiline transdermal patch. Bristol-Myers Squibb Company, Princeton, NJ, 02/00/2006.
Product Information: Humibid(R)DM, guaifenesin/dextromethorphan bromide. Adams Laboratories, Inc., Fort Worth, TX, 1995.
Rivers N & Horner B: Possible lethal reaction between Nardil and dextromethorphan (letter). Can Med Assoc J 1970; 103:85.
Sovner R & Wolfe J: Interaction between dextromethorphan and monoamine oxidase inhibitor therapy with isocarboxazid (letter). N Engl J Med 1988; 319:1671.
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Concurrent use of DEXTROMETHORPHAN and FLUOXETINE may result in possible dextromethorphan toxicity (nausea, vomiting, blurred vision, hallucinations) or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes).
Caution patients taking fluoxetine that an interaction could occur with dextromethorphan. A reduction in the dextromethorphan dose may be necessary.
competitively inhibited metabolism of both agents
Fluoxetine strongly inhibits hepatic cytochrome P450IID6 (CYP2D6), the isoenzyme known to catalyze dextromethorphan metabolism (Stevens & Wrighton, 1993). Fluoxetine inhibits dextromethorphan metabolism (Otton et al, 1993). With concomitant administration, it is possible that both agents may competitively inhibit each others metabolism, increasing serum levels of both drugs. Serotonin syndrome, characterized by restlessness, myoclonus, and changes in mental status (Sternbach, 1991), is a possibility with the combined use of dextromethorphan and serotonergic agents. There have been two case reports of serotonin syndrome associated with concurrent paroxetine and dextromethorphan therapy (Skop et al, 1994; Skop et al, 1995).
Therapeutic doses of fluoxetine were found to potently inhibit the metabolism of dextromethorphan, a marker of cytochrome P450 2D6 (CYP2D6) function (Otton et al, 1993). A 30 mg dose of dextromethorphan hydrobromide was given to 19 patients taking fluoxetine for clinical depression. In addition, dextromethorphan was given to 208 known extensive metabolizers and to 15 known poor metabolizers (those lacking CYP2D6 function). While dextromethorphan metabolism was reduced in the fluoxetine-treated patients, it was more significantly affected in the poor metabolizer controls. This indicates that patients who are slow metabolizers may be at greater risk for experiencing dextromethorphan toxicity when used in combination with fluoxetine.
A 32-year-old woman experienced visual hallucinations after concomitant use of fluoxetine and dextromethorphan (Achamallah, 1992). She had taken fluoxetine 20 mg daily for 18 days prior to taking two doses of dextromethorphan. After each dose of dextromethorphan she experienced distorted vision and saw bright colors. These effects continued for six to eight hours. Fluoxetine was withdrawn and she had no more hallucinations.
A 51-year old male patient with vascular disease following concurrent use of dextromethorphan and paroxetine developed serotonin syndrome. Two days after self-medication with a dextromethorphan-containing cold product, the patient experienced shortness of breath, nausea, headache, and confusion. Upon arrival to the hospital, the patient presented with diaphoresis, tremor, confusion, abdominal pain, and severe shortness of breath. After administration of benzodiazepines and discontinuation of paroxetine, the patient's condition improved and no further complications were seen (Skop et al, 1994).
Achamallah NS: Visual hallucinations after combining fluoxetine and dextromethorphan. Am J Psychiatry 1992; 149:1406.
Otton SV, Wu D, Joffe RT et al: Inhibition by fluoxetine of cytochrome P450 2D6 activity. Clin Pharmacol Ther 1993; 53:401-409.
Skop BP, Brown TM & Mareth TR: The serotonin syndrome associated with paroxetine. Am J Emerg Med 1995; 13:606-607.
Skop BP, Finkelstein JA, Mareth TR et al: The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease. Am J Emerg Med 1994; 12:642-644.
Sternbach H: The serotonin syndrome. Am J Psychiatry 1991; 148:705-713.
Stevens JC & Wrighton SA: Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochrome P450. J Pharmacol Exp Ther 1993; 266:964-971.
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Concurrent use of DEXTROMETHORPHAN and VENLAFAXINE may result in increased dextromethorphan plasma concentrations and increased risk of serotonin syndrome.
Use caution when prescribing dextromethorphan to patients who are taking an SSRI (such as venlafaxine), as concomitant use may result in an increased risk of serotonin syndrome. Initial dose reductions of dextromethorphan may be warranted when administered with CYP2D6 inhibitors, such as venlafaxine (Prod Info NUEDEXTA(TM) oral capsules, 2010).
inhibition of CYP2D6-mediated dextromethorphan metabolism by venlafaxine
Venlafaxine is a relatively weak CYP2D6 inhibitor (Prod Info Effexor® oral tablets, 2010) and dextromethorphan is a CYP2D6 substrate. While not specifically studied with venlafaxine, the concomitant use of paroxetine (another SSRI) with the combination of dextromethorphan/quinidine in one study resulted in increased AUC and Cmax of paroxetine, dextromethorphan, and quinidine. As the concomitant use of dextromethorphan with venlafaxine may increase the risk of serotonin syndrome, initial dose reductions of dextromethorphan may be warranted (Prod Info NUEDEXTA(TM) oral capsules, 2010) along with monitoring for signs/symptoms of serotonin syndrome (eg, altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor).
In a group of 14 healthy subjects, the administration of paroxetine (20 mg once daily for 12 days) followed by a combination of dextromethorphan 30 mg/quinidine 30 mg (twice daily for 8 days) resulted in an increase in paroxetine AUC and Cmax (1.7- and 1.5-fold, respectively) and a decrease in dextrorphan AUC and Cmax (34% and 33%, respectively). The dextromethorphan/quinidine exposure did not change significantly. In a second group of 13 healthy subjects, the administration of dextromethorphan 30 mg/quinidine 30 mg (twice daily for 8 days) followed by paroxetine (20 mg once daily for 12 days) resulted in an increase in dextromethorphan AUC and Cmax (1.5- and 1.4-fold, respectively), a decrease in dextrorphan AUC and Cmax (14% and 18%, respectively), an increase in quinidine AUC and Cmax (1.4- and 1.3-fold, respectively), and an increase in paroxetine AUC and Cmax (2.3- and 2-fold, respectively) (Prod Info NUEDEXTA(TM) oral capsules, 2010).
Product Information: Effexor(R) oral tablets, venlafaxine hydrochloride oral tablets. Wyeth Pharmaceuticals Inc, Philadelphia, PA, Jan, 2010.
Product Information: NUEDEXTA(TM) oral capsules, dextromethorphan hydrobromide and quinidine sulfate oral capsules. Avanir Pharmaceuticals, Inc, Aliso Viejo, CA, Oct, 2010.
Concurrent use of VILAZODONE and SEROTONERGIC AGENTS may result in increased risk for serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes).
Serotonin syndrome has been reported with vilazodone monotherapy and in combination with other serotonergic drugs; coadministration with another serotonergic drug may increase risk for serotonin syndrome. Therefore, exercise caution with concomitant use and monitor for serotonin syndrome. Discontinue use of vilazodone and concomitant serotonergic agents immediately if symptoms of serotonin syndrome emerge (Prod Info VIIBRYD® oral tablets, 2015).
additive serotonergic effects
Serotonin syndrome has been reported with vilazodone monotherapy and in combination with other serotonergic drugs; coadministration with another serotonergic drug may increase risk for serotonin syndrome (Prod Info VIIBRYD® oral tablets, 2015). Increased serotonin levels which may produce additive serotonergic effects can occur if serotonergic agents are taken concurrently. Symptoms of serotonin syndrome include neuromuscular abnormalities (including hyperreflexia, tremor, muscle rigidity, clonus, peripheral hypertonicity, and shivering), autonomic hyperactivity (including tachycardia, mydriasis, diaphoresis, the presence of bowel sounds, and diarrhea), and mental status changes (including agitation and delirium). Serotonin syndrome can be life-threatening (Boyer & Shannon, 2005). Therefore, exercise caution with concomitant use of vilazodone and this drug. Monitor for serotonin syndrome and discontinue use of both vilazodone and the concomitant serotonergic agent immediately if symptoms of serotonin syndrome emerge (Prod Info VIIBRYD® oral tablets, 2015).
Boyer EW & Shannon M: The serotonin syndrome. N Eng J Med 2005; 352(11):1112-1120.
Product Information: VIIBRYD(R) oral tablets, vilazodone HCl oral tablets. Forest Laboratories, Inc. (per manufacturer), Cincinnati, OH, Mar, 2015.