Drug Interactions between amitriptyline / perphenazine and Lexapro
This report displays the potential drug interactions for the following 2 drugs:
- amitriptyline/perphenazine
- Lexapro (escitalopram)
Interactions between your drugs
amitriptyline escitalopram
Applies to: amitriptyline / perphenazine and Lexapro (escitalopram)
MONITOR CLOSELY: Concomitant use of agents with serotonergic activity including selective serotonin reuptake inhibitors, tricyclic antidepressants, and other antidepressants may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.
MONITOR CLOSELY: Escitalopram can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval including tricyclic antidepressants and other antidepressants (e.g., trazodone) may result in additive effects and increased risk of ventricular arrhythmias such as torsade de pointes and sudden death. In a double-blind, placebo-controlled ECG study consisting of 113 healthy subjects, the change from baseline in QTc (Fridericia-corrected) was 4.3 msec for escitalopram 10 mg/day and 10.7 msec for the supratherapeutic dosage of 30 mg/day. Based on the established exposure-response relationship, the predicted QTc change from placebo under the Cmax for 20 mg/day is 6.6 msec. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Also, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures. Due to the potential for additive effects on the QT interval, ECG monitoring may also be appropriate when escitalopram is used with tricyclic antidepressants or other antidepressants like trazodone. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
References
- Nierenberg DW, Semprebon M (1993) "The central nervous system serotonin syndrome." Clin Pharmacol Ther, 53, p. 84-8
- Metz A (1990) "Interaction between fluoxetine and buspirone." Can J Psychiatry, 35, p. 722-3
- Goldberg RJ, Huk M (1992) "Serotonin syndrome from trazodone and buspirone." Psychosomatics, 33, p. 235-6
- Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
- Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol, 10, p. 213-7
- Ciraulo DA, Shader RI (1990) "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol, 10, p. 48-50
- (2001) "Product Information. Zoloft (sertraline)." Roerig Division
- (2001) "Product Information. Prozac (fluoxetine)." Dista Products Company
- Insel TR, Roy BF, Cohen RM, Murphy DL (1982) "Possible development of the serotonin syndrome in man." Am J Psychiatry, 139, p. 954-5
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2001) "Product Information. Paxil (paroxetine)." GlaxoSmithKline
- Ruiz F (1994) "Fluoxetine and the serotonin syndrome." Ann Emerg Med, 24, p. 983-5
- (2001) "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc
- Reeves RR, Bullen JA (1995) "Serotonin syndrome produced by paroxetine and low-dose trazodone." Psychosomatics, 36, p. 159-60
- Harvey AT, Preskorn SH (1995) "Interactions of serotonin reuptake inhibitors with tricyclic antidepressants." Arch Gen Psychiatry, 52, p. 783-4
- Fischer P (1995) "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol, 15, p. 440-2
- Corkeron MA (1995) "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust, 163, p. 481-2
- George TP, Godleski LS (1996) "Possible serotonin syndrome with trazodone addition to fluoxetine." Biol Psychiatry, 39, p. 384-5
- Skop BP, Finkelstein JA, Mareth TR, Magoon MR, Brown TM (1994) "The serotonin syndrome associated wtih paroxetine, an over-the-counter cold remedy, and vascular disease." Am J Emerg Med, 12, p. 642-4
- John L, Perreault MM, Tao T, Blew PG (1997) "Serotonin syndrome associated with nefazodone and paroxetine." Ann Emerg Med, 29, p. 287-9
- Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
- Bhatara VS, Magnus RD, Paul KL, Preskorn SH (1998) "Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms." Ann Pharmacother, 32, p. 432-6
- (2001) "Product Information. Celexa (citalopram)." Forest Pharmaceuticals
- Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
- Manos GH (2000) "Possible serotonin syndrome associated with buspirone added to fluoxetine." Ann Pharmacother, 34, p. 871-4
- Nijhawan PK, Katz G, Winter S (1996) "Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission." Crit Care Med, 24, p. 1086-9
- Margolese HC, Chouinard G (2000) "Serotonin syndrome from addition of low-dose trazodone to nefazodone." Am J Psychiatry, 157, p. 1022
- Mackay FJ, Dunn NR, Mann RD (1999) "Antidepressants and the serotonin syndrome in general practice." Br J Gen Pract, 49, p. 871-4
- Smith DL, Wenegrat BG (2000) "A case report of serotonin syndrome associated with combined nefazodone and fluoxetine." J Clin Psychiatry, 61, p. 146
- (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
- Dougherty JA, Young H, Shafi T (2002) "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother, 36, p. 1647-1648
- Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
- Lane R, Baldwin D (1997) "Selective serotonin reuptake inhibitor--induced serotonin syndrome: review." J Clin Psychopharmacol, 17, p. 208-21
- Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S (2006) "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther, 13, p. 550-552
- Castro VM, Clements CC, Murphy SN, et al. (2013) "QT interval and antidepressant use: a cross sectional study of electronic health records." BMJ, 346, f288
perphenazine escitalopram
Applies to: amitriptyline / perphenazine and Lexapro (escitalopram)
MONITOR CLOSELY: Escitalopram can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a double-blind, placebo-controlled ECG study consisting of 113 healthy subjects, the change from baseline in QTc (Fridericia-corrected) was 4.3 msec for escitalopram 10 mg/day and 10.7 msec for the supratherapeutic dosage of 30 mg/day. Based on the established exposure-response relationship, the predicted QTc change from placebo under the Cmax for 20 mg/day is 6.6 msec. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking escitalopram with certain other drugs that cause these effects, especially in elderly or debilitated patients.
MANAGEMENT: Caution is recommended if escitalopram is used in combination with other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. When escitalopram is used in combination with other drugs that cause CNS and/or respiratory depression, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their doctor if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References
- (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- Health Canada (2012) Antidepressant Cipralex (escitalopram): Updated information regarding dose-related heart risk. http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2012/2012_63-eng.php
- Castro VM, Clements CC, Murphy SN, et al. (2013) "QT interval and antidepressant use: a cross sectional study of electronic health records." BMJ, 346, f288
- EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
amitriptyline perphenazine
Applies to: amitriptyline / perphenazine and amitriptyline / perphenazine
MONITOR: Coadministration of a phenothiazine with a tricyclic antidepressant (TCA) may result in elevated plasma concentrations of one or both drugs as well as additive adverse effects. Most phenothiazines and TCAs have been found to undergo metabolism by CYP450 2D6, thus competitive inhibition of the enzyme may occur when more than one of these agents are administered. Although these drugs have been used together clinically, the possibility of increased risk of serious adverse effects such as central nervous system depression, tardive dyskinesia, hypotension, and prolongation of the QT interval should be considered, as many of these agents alone can and have produced these effects. In addition, excessive anticholinergic effects may occur in combination use, which can result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of anticholinergic intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures.
MANAGEMENT: Concurrent use of phenothiazines and TCAs should be approached with caution, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication (e.g., abdominal pain, fever, heat intolerance, blurred vision, confusion, hallucinations) or cardiovascular toxicity (e.g., dizziness, palpitations, arrhythmias, syncope). Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A dosage reduction in one or both drugs may be necessary if excessive adverse effects develop.
References
- Loga S, Curry S, Lader M (1981) "Interaction of chlorpromazine and nortriptyline in patients with schizophrenia." Clin Pharmacokinet, 6, p. 454-62
- Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
- Bock JL, Nelson JC, Gray S, Jatlow PI (1983) "Desipramine hydroxylation: variability and effect of antipsychotic drugs." Clin Pharmacol Ther, 33, p. 322-8
- Gram LF, Overo KF (1972) "Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man." Br Med J, 1, p. 463-5
- El-Yousef MK, Manier DH (1974) "Tricyclic antidepressants and phenothiazines." JAMA, 229, p. 1419
- Hirschowitz J, Bennett JA, Zemlan FP, Garver DL (1983) "Thioridazine effect on desipramine plasma levels." J Clin Psychopharmacol, 3, p. 376-9
- Vandel S, Sandoz M, Vandel B, Bonin B, Allers G, Volmat R (1986) "Biotransformation of amitriptyline in man: interaction with phenothiazines." Neuropsychobiology, 15, p. 15-9
- Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
- Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
- Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
- Siris SG, Cooper TB, Rifkin AE, Brenner R, Lieberman JA (1982) "Plasma imipramine concentrations in patients receiving concomitant fluphenazine decanoate." Am J Psychiatry, 139, p. 104-6
- Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
- Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
- Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
- Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
- Maynard GL, Soni P (1996) "Thioridazine interferences with imipramine metabolism and measurement." Ther Drug Monit, 18, p. 729-31
Drug and food interactions
escitalopram food
Applies to: Lexapro (escitalopram)
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
amitriptyline food
Applies to: amitriptyline / perphenazine
GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.
MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.
References
- Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
- Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
- Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
- Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
- Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7
perphenazine food
Applies to: amitriptyline / perphenazine
GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.
MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.
References
- Lutz EG (1976) "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA, 236, p. 2422-3
- Freed E (1981) "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust, 2, p. 44-5
Therapeutic duplication warnings
Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.
Antidepressants
Therapeutic duplication
The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antidepressants' category:
- amitriptyline/perphenazine
- Lexapro (escitalopram)
Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.
See also
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Check Interactions
To view an interaction report containing 4 (or more) medications, please sign in or create an account.
Save Interactions List
Sign in to your account to save this drug interaction list.