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Drug Interactions between Etrafon Forte and trandolapril / verapamil

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

verapamil amitriptyline

Applies to: trandolapril / verapamil and Etrafon Forte (amitriptyline / perphenazine)

MONITOR: Concurrent administration of verapamil may increase tricyclic antidepressant (TCA) serum concentrations. The mechanism appears to be inhibition of CYP450 metabolism. Pharmacologic and toxic effects of TCAs may be increased.

MANAGEMENT: Close monitoring for clinical response and tolerance is recommended whenever verapamil is added to or discontinued from an antidepressant regimen. Patients should be advised to notify their physician if they experience excessive antidepressant effects such as dry mouth, blurry vision, irregular or fast heartbeat, constipation, urinary retention, dizziness, or orthostatic hypotension. Dose adjustments may be necessary.

References

  1. Hermann DJ, Krol TF, Dukes GE, et al. "Comparison of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine." J Clin Pharmacol 32 (1992): 176-83
  2. "Product Information. Calan (verapamil)." Searle PROD (2001):

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Moderate

verapamil perphenazine

Applies to: trandolapril / verapamil and Etrafon Forte (amitriptyline / perphenazine)

MONITOR: Phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents may potentiate the blood pressure lowering capabilities of other drugs with hypotensive effects due to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the phenothiazine, TCA, or neuroleptic. The severity of this interaction may be affected by the agent's affinity for the alpha-1 adrenoceptor. One in vitro study demonstrated an affinity for the alpha-1 adrenoceptor for some of these medications that was similar to, or greater than, those of alpha blocker medications used to treat hypertension. Examples of drugs evaluated in this study with a high affinity included amitriptyline, clomipramine, chlorpromazine, clozapine, doxepin, flupenthixol, lurasidone, nortriptyline, perphenazine, paliperidone, quetiapine, risperidone, sertindole, and ziprasidone. On the other hand, examples of those with lower affinities included aripiprazole, lofepramine, protriptyline, sulpiride, and amisulpride.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines, tricyclic antidepressants (TCAs), or certain antipsychotic (neuroleptic) agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine, TCA, or neuroleptic may be appropriate, especially in the elderly. It may also be advisable to consider using a phenothiazine, TCA, or neuroleptic medication with a lower affinity for the alpha-1 adrenoceptor when possible. Patients should be counseled to avoid rising abruptly from a sitting or recumbent position and to notify their healthcare provider if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References

  1. Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274
  2. White WB "Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril." Arch Intern Med 146 (1986): 1833-4
  3. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals PROD (2001):
  4. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals PROD (2001):
  5. Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30
  6. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  7. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company PROD (2001):
  8. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  9. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals PROD (2001):
  10. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. Proudman RGW, Pupo AS, Baker JG "The affinity and selectivity of alpha-adrenoceptor antagonists, antidepressants, and antipsychotics for the human alpha1A, alpha1B, and alpha1D-adrenoceptors." Pharmacol Res Perspect 8 (2020): e00602
View all 12 references

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Moderate

amitriptyline perphenazine

Applies to: Etrafon Forte (amitriptyline / perphenazine) and Etrafon Forte (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

  1. Loga S, Curry S, Lader M "Interaction of chlorpromazine and nortriptyline in patients with schizophrenia." Clin Pharmacokinet 6 (1981): 454-62
  2. Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
  3. Bock JL, Nelson JC, Gray S, Jatlow PI "Desipramine hydroxylation: variability and effect of antipsychotic drugs." Clin Pharmacol Ther 33 (1983): 322-8
  4. Gram LF, Overo KF "Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man." Br Med J 1 (1972): 463-5
  5. El-Yousef MK, Manier DH "Tricyclic antidepressants and phenothiazines." JAMA 229 (1974): 1419
  6. Hirschowitz J, Bennett JA, Zemlan FP, Garver DL "Thioridazine effect on desipramine plasma levels." J Clin Psychopharmacol 3 (1983): 376-9
  7. Vandel S, Sandoz M, Vandel B, Bonin B, Allers G, Volmat R "Biotransformation of amitriptyline in man: interaction with phenothiazines." Neuropsychobiology 15 (1986): 15-9
  8. Zelman S, Guillan R "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry 126 (1970): 1787-90
  9. Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978): 1097-100
  10. Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
  11. Siris SG, Cooper TB, Rifkin AE, Brenner R, Lieberman JA "Plasma imipramine concentrations in patients receiving concomitant fluphenazine decanoate." Am J Psychiatry 139 (1982): 104-6
  12. Johnson AL, Hollister LE, Berger PA "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry 42 (1981): 313-7
  13. Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
  14. Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
  15. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm 2 (1983): 174-8
  16. Maynard GL, Soni P "Thioridazine interferences with imipramine metabolism and measurement." Ther Drug Monit 18 (1996): 729-31
View all 16 references

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Moderate

amitriptyline trandolapril

Applies to: Etrafon Forte (amitriptyline / perphenazine) and trandolapril / verapamil

MONITOR: Phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents may potentiate the blood pressure lowering capabilities of other drugs with hypotensive effects due to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the phenothiazine, TCA, or neuroleptic. The severity of this interaction may be affected by the agent's affinity for the alpha-1 adrenoceptor. One in vitro study demonstrated an affinity for the alpha-1 adrenoceptor for some of these medications that was similar to, or greater than, those of alpha blocker medications used to treat hypertension. Examples of drugs evaluated in this study with a high affinity included amitriptyline, clomipramine, chlorpromazine, clozapine, doxepin, flupenthixol, lurasidone, nortriptyline, perphenazine, paliperidone, quetiapine, risperidone, sertindole, and ziprasidone. On the other hand, examples of those with lower affinities included aripiprazole, lofepramine, protriptyline, sulpiride, and amisulpride.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines, tricyclic antidepressants (TCAs), or certain antipsychotic (neuroleptic) agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine, TCA, or neuroleptic may be appropriate, especially in the elderly. It may also be advisable to consider using a phenothiazine, TCA, or neuroleptic medication with a lower affinity for the alpha-1 adrenoceptor when possible. Patients should be counseled to avoid rising abruptly from a sitting or recumbent position and to notify their healthcare provider if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References

  1. Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274
  2. White WB "Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril." Arch Intern Med 146 (1986): 1833-4
  3. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals PROD (2001):
  4. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals PROD (2001):
  5. Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30
  6. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  7. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company PROD (2001):
  8. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  9. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals PROD (2001):
  10. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. Proudman RGW, Pupo AS, Baker JG "The affinity and selectivity of alpha-adrenoceptor antagonists, antidepressants, and antipsychotics for the human alpha1A, alpha1B, and alpha1D-adrenoceptors." Pharmacol Res Perspect 8 (2020): e00602
View all 12 references

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Moderate

perphenazine trandolapril

Applies to: Etrafon Forte (amitriptyline / perphenazine) and trandolapril / verapamil

MONITOR: Phenothiazines, tricyclic antidepressants (TCAs), and some antipsychotic (neuroleptic) agents may potentiate the blood pressure lowering capabilities of other drugs with hypotensive effects due to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the phenothiazine, TCA, or neuroleptic. The severity of this interaction may be affected by the agent's affinity for the alpha-1 adrenoceptor. One in vitro study demonstrated an affinity for the alpha-1 adrenoceptor for some of these medications that was similar to, or greater than, those of alpha blocker medications used to treat hypertension. Examples of drugs evaluated in this study with a high affinity included amitriptyline, clomipramine, chlorpromazine, clozapine, doxepin, flupenthixol, lurasidone, nortriptyline, perphenazine, paliperidone, quetiapine, risperidone, sertindole, and ziprasidone. On the other hand, examples of those with lower affinities included aripiprazole, lofepramine, protriptyline, sulpiride, and amisulpride.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines, tricyclic antidepressants (TCAs), or certain antipsychotic (neuroleptic) agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine, TCA, or neuroleptic may be appropriate, especially in the elderly. It may also be advisable to consider using a phenothiazine, TCA, or neuroleptic medication with a lower affinity for the alpha-1 adrenoceptor when possible. Patients should be counseled to avoid rising abruptly from a sitting or recumbent position and to notify their healthcare provider if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References

  1. Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274
  2. White WB "Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril." Arch Intern Med 146 (1986): 1833-4
  3. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals PROD (2001):
  4. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals PROD (2001):
  5. Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30
  6. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  7. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company PROD (2001):
  8. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  9. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals PROD (2001):
  10. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. Proudman RGW, Pupo AS, Baker JG "The affinity and selectivity of alpha-adrenoceptor antagonists, antidepressants, and antipsychotics for the human alpha1A, alpha1B, and alpha1D-adrenoceptors." Pharmacol Res Perspect 8 (2020): e00602
View all 12 references

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Minor

verapamil trandolapril

Applies to: trandolapril / verapamil and trandolapril / verapamil

Calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors may have additive hypotensive effects. While these drugs are often safely used together, careful monitoring of the systemic blood pressure is recommended during coadministration, especially during the first one to three weeks of therapy.

References

  1. Kaplan NM "Amlodipine in the treatment of hypertension." Postgrad Med J 67 Suppl 5 (1991): s15-9
  2. DeQuattro V "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol 14 (1991): iv28-32;
  3. Sun JX, Cipriano A, Chan K, John VA "Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects." Eur J Clin Pharmacol 47 (1994): 285-9
  4. Di Somma S, et al. "Antihypertensive effects of verapamil, captopril and their combination at rest and during dynamic exercise." Arzneimittelforschung 42 (1992): 103
View all 4 references

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Drug and food interactions

Moderate

verapamil food

Applies to: trandolapril / verapamil

GENERALLY AVOID: Consumption of large quantities of grapefruit juice may be associated with significantly increased plasma concentrations of oral verapamil. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. One study reported no significant effect of a single administration of grapefruit juice on the pharmacokinetics of verapamil in ten hypertensive patients receiving chronic therapy. In another study conducted in nine healthy male volunteers, administration of 120 mg oral verapamil twice daily for 3 days following pretreatment with 200 mL grapefruit juice twice daily for 5 days resulted in a 57% increase in S-verapamil peak plasma concentration (Cmax), a 36% increase in S-verapamil systemic exposure (AUC), a 40% increase in R-verapamil Cmax, and a 28% increase in R-verapamil AUC compared to administration following orange juice. Elimination half-life and renal clearance of both S- and R-verapamil were not affected by grapefruit juice, and there were no significant effects on blood pressure, heart rate, or PR interval. A third study reported a 1.63-fold increase in Cmax and a 1.45-fold increase in AUC of (R,S)-verapamil in 24 young, healthy volunteers given verapamil sustained-release 120 mg twice daily for 7 days with 250 mL grapefruit juice four times daily on days 5 through 7. Two subjects developed PR interval prolongation of more than 350 ms during grapefruit juice coadministration. A high degree of interindividual variability has been observed in these studies. The interaction was also suspected in a case report of a 42-year-old woman who developed complete heart block, hypotension, hypoxic respiratory failure, severe anion gap metabolic acidosis, and hyperglycemia following accidental ingestion of three verapamil sustained-release 120 mg tablets over a span of six hours. The patient's past medical history was remarkable only for migraine headaches, for which she was receiving several medications including verapamil. Prior to admission, the patient had a 2-week history of poorly controlled migraine, and the six hours preceding hospitalization she suffered from worsening headache and palpitations progressing to altered sensorium. An extensive workup revealed elevated verapamil and norverapamil levels more than 4.5 times above the upper therapeutic limits. These levels also far exceeded those reported in the medical literature for patients taking verapamil 120 mg every 6 hours, or 480 mg in a 24-hour period. The patient recovered after receiving ventilator and vasopressor support. Upon questioning, it was discovered that the patient had been drinking large amounts of grapefruit juice (3 to 4 liters total) the week preceding her admission due to nausea. No other sources or contributing factors could be found for the verapamil toxicity.

MANAGEMENT: Patients treated with oral verapamil should avoid the consumption of large amounts of grapefruit or grapefruit juice to prevent any undue fluctuations in serum drug levels. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.

References

  1. McAllister RG, Jr "Clinical pharmacology of slow channel blocking agents." Prog Cardiovasc Dis 25 (1982): 83-102
  2. "Product Information. Covera-HS (verapamil)." Searle PROD (2001):
  3. Zaidenstein R, Dishi V, Gips M, Soback S, Cohen N, Weissgarten J, Blatt A, Golik A "The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil." Eur J Clin Pharmacol 54 (1998): 337-40
  4. Ho PC, Ghose K, Saville D, Wanwimolruk S "Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers." Eur J Clin Pharmacol 56 (2000): 693-8
  5. Fuhr U, Muller-Peltzer H, Kern R, et al. "Effects of grapefruit juice and smoking on verapamil concentrations in steady state." Eur J Clin Pharmacol 58 (2002): 45-53
  6. Bailey DG, Dresser GK "Natural products and adverse drug interactions." Can Med Assoc J 170 (2004): 1531-2
  7. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions. 1998." Br J Clin Pharmacol 58 (2004): S831-40; discussion S841-3
  8. Arayne MS, Sultana N, Bibi Z "Review: grape fruit juice - drug interactions." Pak J Pharm Sci 18 (2005): 45-57
  9. Pillai U, Muzaffar J, Sandeep S, Yancey A "Grapefruit juice and verapamil: a toxic cocktail." South Med J 102 (2009): 308-9
View all 9 references

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Moderate

trandolapril food

Applies to: trandolapril / verapamil

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

References

  1. "Product Information. Vasotec (enalapril)." Merck & Co., Inc PROD (2002):
  2. Good CB, McDermott L "Diet and serum potassium in patients on ACE inhibitors." JAMA 274 (1995): 538
  3. Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens 13 (1999): 717-20

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Moderate

verapamil food

Applies to: trandolapril / verapamil

GENERALLY AVOID: Verapamil may increase the blood concentrations and intoxicating effects of ethanol. The exact mechanism of interaction is unknown but may involve verapamil inhibition of ethanol metabolism. In 10 healthy, young volunteers, verapamil (80 mg orally every 8 hours for 6 days) increased the mean peak blood concentration (Cmax) and the 12-hour area under the concentration-time curve (AUC) of ethanol (0.8 g/kg single oral dose) by 17% and 30%, respectively, compared to placebo. Verapamil AUCs were positively correlated to increased ethanol blood AUC values. Subjectively (i.e. each subject's perception of intoxication as measured on a visual analog scale), verapamil also significantly increased the area under the ethanol effect versus time curve but did not change the peak effect or time to peak effect.

MANAGEMENT: Patients treated with verapamil should be counseled to avoid alcohol consumption.

References

  1. Bauer LA, Schumock G, Horn J, Opheim K "Verapamil inhibits ethanol elimination and prolongs the perception of intoxication." Clin Pharmacol Ther 52 (1992): 6-10
  2. "Product Information. Isoptin (verapamil)." Knoll Pharmaceutical Company PROD (2001):

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Moderate

amitriptyline food

Applies to: Etrafon Forte (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

  1. Dorian P, Sellers EM, Reed KL, et al. "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol 25 (1983): 325-31
  2. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol 24 (1983): 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther 43 (1988): 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther 17 (1975): 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol 51 (1990): 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA "Imipramine disposition in alcoholics." J Clin Psychopharmacol 2 (1982): 2-7
View all 7 references

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Moderate

perphenazine food

Applies to: Etrafon Forte (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

  1. Lutz EG "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA 236 (1976): 2422-3
  2. Freed E "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust 2 (1981): 44-5

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Moderate

verapamil food

Applies to: trandolapril / verapamil

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

References

  1. Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6
  2. Moller IW "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth 59 (1987): 522-6
  3. Oszko MA, Klutman NE "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm 6 (1987): 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol 67 (1991): 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy 10 (1990): 247
  6. Woie L, Storstein L "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J 2 (1981): 239-42
  7. Morris DL, Goldschlager N "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA 249 (1983): 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol 27 (1987): 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M "Calcium gluconate in severe verapamil intoxication." N Engl J Med 330 (1994): 718-20
  10. Bar-Or D, Gasiel Y "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed) 282 (1981): 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med 8 (1982): 55-7
  12. McMillan R "Management of acute severe verapamil intoxication." J Emerg Med 6 (1988): 193-6
  13. Perkins CM "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J 2 (1978): 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol 17 (1980): 395-400
View all 14 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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