Cardiac drug-psychotropic drug update

Cardiac Drug-P&chotropic Drug Update

James J. Strain, MD, Anwarul Karim, MD, Gina Caliendo, PharmD, RPh, Jeffrey D. Alexis, MD,

R. Sandlin Lowe III, MD and Valentin Fuster, MD, PhD

This is an update from the report-Cardiac Drug and Psychotropic Drug Interactions: Signifkance and Recom- mendations-published in this journal in November- December 1999. As mentioned in that article there has been an explosion of new drugs both in psychiatry and cardiology without a sufficient understanding of their potential interactions. Also there is a need for methods to update drug interactions on an ongoing basis. This report describes: 1) examples of actual adverse interactions from clinical cases that move beyond some of the hypothesized contraindications included in the 2000 millennium publication; 2) confirmation of previous adverse interactions reported if they strengthen the earlier fhulings; 3) listing of new drugs, e.g., sildenafil (viagra) now commonly prescribed by psychiatrists and cardiologists; 4) reports explaining and/or refining mechanisms of adverse interactions; and 5) cautions and important associated phenomenon of either a cardiac or a psychotropic drug, e.g., valproic acid and cases of life-threatening pancreatitis. Methods of publicizing the new knowledge of cardiac drug-psychotropic drug interactions, e.g., the Internet and web sites are described.

Reprinted from Strain JJ, Karim A, Caliendo G, et al. Cardiac Drug-Psychotropic Drug Update. Gen Hosp Psychiatry 2002;24:283-289 with permission.

This work was funded by the Malcolm Gibbs Foundation, Inc., New York, NY, USA. Dis Mon 2003;49:312-325 doi:l0.1067/mda.2003.24

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TABLE 1. Commonly Prescribed Cardiac Drugs

Adenosine Amiloride Amiodarone Amlodipine Aspirin Atenolol Atorvastatin Atropine Benazepril Bisoprolol Bretylium Bumetanide Candesartan Captopril Carvedilol Cerivastatin Cholestyramine Clonidine Clopidogrel Colestipol Coumadin Digoxin Diltiazem Disopyramide Enalapril Felodipine Flecainide Flolan Fluvastatin Furosemide Gemfibrozil

,Heparin Hydralazine Hydrochlorothiazide

lbutilide lsordil Labetalol Levophed Lidocaine Lisinopril Losartan Lovastatin Metolazone Metoprolol Mexiletine Minoxidil Nadolol Neosynephrine Nicardipine Nifedipine Nimodopine Nitroglycerin Pravastatin Prazosin Procainamide Propafenone Propranolol Quinidine Simvastatin Sotalol Spironolactone Terazosin Ticlopidine Tocainide Torsemide Triamterene Verapamil

Introduction

Q A

large percentage of symptoms in patients are related to drug interactions and toxicity. Better identification and understanding of these effects will lead to improved patient care. With the

ongoing development of new drugs, new interactions are surely to be seen. In December 1999 our group published Cardiac Drug and Psych- otropic Drug Interactions: SigniJcance and Recommendations.’ This article was sent to every medical school in the world by the authors assisted by grants from the Malcolm Gibbs Foundation, Inc. and donors to the Liaison Psychiatry Research Fund at the Mount Sinai School of Medicine, NY, USA. During the last year, new drugs were approved for

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TABLE 2. Commonly Prescribed Psychotropic Medications

Amantadine Amitriptyline Amphetamine Alprazolam Amobarbitai Benztropine Bupropion Buspirone Butalbital Carbamazepine Choral Hydrate Chlordiazepoxide Chlorpromazine Citalopram Clomipramine Clonazepam Clozapine Desipramine Dextroamphetamine Diazepam Diphenhydramine Divalproex sodium Donepezil Fluoxetine Fluphenazine Fluvoxamine Gabapentin Haloperidol lmipramine Lamotrigine Lithium Lorazepam Loxapine

Meprobamate Methylphenidate Mirtazapine Molindone Nefazadone Nortriptyline Olanzapine Oxazepam Pargyline Paroxetine Pemoline Perphenazine Phenobarbital Quetiapine Risperidone Sertindole Sertraline Sildenafil Sodium Amytal Tacrine Temazepam Thioridazine Thiothixene Trazodone Tranylcypromine Triazolam Trifluperazine Trihexyphenydil Valproic acid Venlafaxine Zaleplon Zolpidem

clinical use, new interactions were identified, and data confirming hypothesized interactions were described. The study group examined the updates of key reference sources from the last quarter of 1999 until the present to discern the interactions between a group of commonly employed cardiac drugs and psychotropic medications (Tables 1 and 2).

The drugs selected for review were from: 1) the 1999 Redbook list of the 200 most often prescribed drugs in the United States; and 2) those most commonly employed by the Cardiovascular Institute and the Division of Behavioral Medicine and Consultation Psychiatry (Mount Sinai-NYU Medical Center/Health System). The disciplines of the investigators were: cardiologists (JA, VF), pharmacist-drug information specialist (GC), psychiatrists (JJS, RSL), and a research assistant (AK). The search strategy utilized: 1) MEDLINE (PubMed) employing the

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cardiac drug name, the psychotropic drug name, and the term “interaction;” 2) Hanston’s Drug Interaction Analysis and Management Text (July 2001 quarterly updated version)2; 3) Drug Interactions Facts (quarterly updated version)3’4; 4) MICROMEDEX Drug-dex’; 5) Ameri- can Hospital Formulary Service Drug Information [6]; and 6) Food and Drug Administration (MedWatch) (Dear Doctor Letters and new labeling) (www.fda.gov/medwatch) for (1999, 2000 and 2001, July). (Citations regarding children, reports in foreign languages or about food, animals, in-vitro experiments, analgesics and naturalistic treatment interactions were excluded). Obviously, these sources do not necessarily include all information regarding drug-drug interactions.

This communication reports examples of actual adverse interactions from clinical cases that move beyond some of the hypothesized contraindications included in the 2000 millennium publication. r Second, confirmation of previous adverse interactions are reported if they strengthen the earlier findings. Third, new drugs, e.g., sildenafil (viagra), now commonly prescribed by psychiatrists and cardiologists, and its interactions are reported. Fourth, reports explaining mechanisms of adverse interactions or refinement of mechanisms of action of a specific drug are included in this update. And, jijlh, reports of cautions and important associated phenomenon or side effects of either a cardiac or a psychotropic drug, e.g., valproic acid and cases of life-threatening pancreatitis reported in both children and adults receiving this medication (Abbot letter to physicians-FDA MedWatch, July 2000).7

Significance Levels: Rating Systems The first three levels of the Drug Znteractions Facts rating system was

employed3s4: “ 1 = Major: The effects are potentially life-threatening or capable of causing permanent damage; 2 = Moderate: The effects may cause a deterioration in a patient’s status. Additional treatment, hospital- ization or extension of hospital stay may be necessary; and 3 = Minor: The effects are usually mild; consequences may be bothersome or unnoticeable, but should not significantly affect the therapeutic outcome. Additional treatment is usually not required.“354

Significance level 1 requires the clinician to document why he/she is prescribing this combination, and to use both drugs only if there is no other way to manage the patient. Drug combinations producing an interaction with a Significance level 1 are combinations that result in serious and potentially life threatening adverse effects such as arrhythmia. Obviously, if this combination is to be used the drug(s) in question must be prescribed with an explanation as to the need for their concurrent use and cautious monitoring employed. The optimum choice, if possible, is to

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use another drug to avoid Significance level 1 interactions. With Signif- icance level 2, the potential interaction must be documented and the clinical outcome(s) must be monitored carefully so that unacceptable, pernicious reactions may be halted as soon as possible. Again, it is often better to use another drug when possible. In any event, it is incumbent upon the clinician to provide careful documentation that adverse effects were considered when using this drug combination and the physician had knowledge of potential adverse consequences. It is also mandatory to communicate to the patient’s health care providers the potential interactions and adverse outcomes. Significance level 3 may not preclude the use of a specific drug, but clinical decision-making needs to consider whether the untoward side effects, (e.g., nausea, rash, etc.) could be avoided by another drug choice. Again, the potential interaction and its mechanism should be documented in the patient’s medical chart and patient’s health care providers need to be informed.

Facts and Comparisons utilizes a five point significance classification?

1. Avoid combination-risk always outweighs benefit. 2. Usually avoid combination-use combination only under special

circumstances. 3. Minimize risk-take action as necessary to reduce risk. 4. No action needed-risk of adverse outcomes appears small. 5. No interaction-evidence suggests no interaction.

For this communication level 4 and level 5 were not used, and only levels l-3 were employed.

Cardiac Drug-Psychotropic Drug Interactions

Case Support of Previously (7 999) Hypothesized (Potential) /nfefuctions

ChoZestyrumine/VuZproic Acid. Significance level 2: Moderate Advice to Practitioner: Cholestyramine interferes with the gastrointes-

tinal absorption of valproic acid, which reduces the concentration and therapeutic effects of valproic acid.

Action: Administer valproic acid at least three hours before, but not within three hours following cholestyramine. Monitor the patient’s clinical response and adjust the dose of valproic acid accordingly.

Confirmation of Previously Reported Adverse Interactions ( 7 999)

Nifedipine/Fluoxetine. Significance level 2: Moderate

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Advice to Practitioner: Occasionally, there are increased calcium blocker effects when fluoxetine is administered simultaneously. Although there are no clinical data available, since nefazodone is a more potent inhibitor of cytrochrome P3A4 than fluoxetine, it could also inhibit the metabolism of nifedipine, verapamil, and other calcium blockers. There is a question if this interaction would apply to other SSRIs.

Action: monitor for increased effects of calcium blockers if fluoxetine is also prescribed.

Propafenone/Fluoxetine. Significance level 2: Moderate Advice to Practitioner: Fluoxetine increases the concentration of

propafenone, and thereby markedly delays cardiac conduction leading to increased likelihood of pro-arrhythmia. Since fluoxetine inhibits the cytrochrome P2D6 enzyme system, which is the metabolic pathway for propafenone, its concentration may be increased. Given fluoxetine’s and its active metabolite, norfluoxetine long half-life, their effects may appear only after a period of time with the concomitant administration of propafenone. Similarly, it is necessary to observe and monitor the patient for a sufficient period of time after fluoxetine is withdrawn because propafenone’s concentration would decrease.

Action: Select antidepressants that do not inhibit cytochrome P2D6, for example, citalopram, nefazadone, venlafaxine. At the least, if this combination is prescribed, the patient should be monitored for heart rate and increased QRS duration.

Quinidine/Fluvoxamine. Significance level 2: Moderate Advice to Practitioner: Fluvoxamine coadministered with quinidine

produces a modest increase in quinidine concentration with possible toxicity by fluvoxamine’s inhibition of the cytochrome P3A metabolism of quinidine. For the same reason nefazodone would be expected to have an even greater effect on quinidine than fluvoxamine.

Action: Alternative antidepressants should be considered that do not affect cytochrome P3A4 metabolism, e.g., venlafaxine, paroxetine. Or, another antiarrhythmic could be employed, e.g., procainamide that is not metabolized by the cytochrome P3A4 enzyme system. Monitor EKG for prolonged QT and increased quinidine concentrations. Due to marked pro-arrhythmia quinidine should be avoided if possible.

Newly Reported Drug Interactions Since 7 999 Amiloride/Lithium. Significance level 2: Moderate

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Advice to Practitioner: Caution is needed when lithium and diuretics are combined because the sodium loss may reduce the renal clearance of lithium leading to toxicity.

Action: monitor lithium levels during the first week after starting amiloride or discontinuing it.

AtenoloUVerapamil. Significance level 2: Moderate Advice to Practitioner: It is reported that the effects of both drugs can

be decreased by their concomitant use. It is uncertain if the mechanism(s) is an additive or synergistic occurrence. It is known that verapamil can diminish oxidative metabolism for certain beta blockers.

Action: it is essential to monitor cardiac functioning and adjust (decrease) the dose of both drugs as required.

AtorvastatNHydantoins (Phenytoin). Significance level 2: Moderate Advice to Practitioner: The therapeutic effect of atorvastatin may be

decreased resulting in its diminished therapeutic efficacy. The possible mechanism for the reduction in atorvastatin is its increased metabolism as a result of the presence of hydantoins.

Action: The patient should be monitored for clinical response and if the atorvastatin appears to be decreased with diminished clinical effectiveness, then a change to pravastatin is suggested since it is less likely to interact with phenytoin.

Atorvastatin/Nefazodone. Significance level: 1 Major Advice to Practitioner: Nefazodone is a known inhibitor of cytrochrome

P3A4 and atorvastatin is a substrate of the same enzyme. Myopathy and rhabdomyolysis have occurred in patients with HMG-CoA reductase inhibitors alone, or in conjunction with nefazodone.

Action: Monitor for signs and symptoms of myopathy and rhabdomyolysis. Monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis occurs.

CarvediloUFluoxetine. Significance level 2: Moderate Advice to Practitioner: Fluoxetine increases the plasma concentrations

of carvedilol; although the clinical significance is uncertain, increased hypotension or bradycardia may result. Since fluoxetine is a cytrochrome 2D6 inhibitor and can diminish the metabolism of R-carvedilol greater than the S form, an increase of carvedilol’s alpha and /3-blocking effects may be seen.

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Action: First an alternative SSRI should be considered, e.g., citalopram or nefazodone which do not inhibit cytochrome P2D6. Or, a beta blocker that does not employ cytochrome P2D6 metabolism, e.g., metoprolol could be considered. Monitor alpha or P-blocking effects if carvedilol and fluoxetine are administered simultaneously.

ClopidogreUPhenobarbital. Significance level: Non specified Advice to Practitioner: There are no data to predict the reaction from

the concomitant administration of these two drugs. However, since clopidogrel may interfere with CYP2C9 enzymes, and phenobarbital is partially metabolized by the same enzyme system, an adverse reaction may one day be reported and this is a potential reaction to be cognizant of.

Action: observe for changes that may occur from coadministration.

DigoxidFluoxetine. Significance level 2: Moderate Advice to practitioner: the mechanism for increased digoxin toxicity

when fluoxetine was added to a previously stabilized patient is unknown. Action: Although this is from one case report in a 93 year old

female, the increased use of SSRI for depression in the elderly should be cautiously undertaken when the patient is on digoxin.

Diltiazem/Buspirone. Significance level 2: Moderate Advice to Practitioner: Diltiazem increases the concentration of buspi-

rone. Diltiazem inhibits CYP3A4 enzymes that may result in an increase in the bioavailability of buspirone and enhance its plasma concentration. In studies the increase in buspirone varied from 3.3 to 7.4 times. Coadminis- tration of buspirone with verapamil, diltiazem, erythromycin and itraconazole substantially increased the plasma concentration of busprione.

Action: The use of dihydropyridine calcium channel blockers could prevent this reaction, or the use of an anxiolytic drug that does not employ cytochrome P3A4 enzymes, e.g., lorazepam, diazepam. Mon- itor for increased buspirone effects, e.g., sedation.

Flecainide/Paroxetine. Significance level 2: Moderate Advice to Practitioner: Although there are no data available related to

the combined use of flecainide and paroxetine, concern does prevail in that paroxetine is a potent inhibitor of cytochrome P2D6 which is how flecainide is metabolized. Therefore, it would not be surprising that at some point an adverse reaction will be reported by their concomitant use.

Action: Monitor QRS duration. Doses may have to be reduced. Caution should prevail in the concomitant use of these two drugs. DM, May 2003 319

Exercise testing can be used to assess increased cardiac effects of flecainide. Prolongation of QRS duration with exercise indicates high risk of proarrhythmia.

Lovastatin (Pravastatin)/Nefazodone. Significance level 2: Moderate Advice to Practitioner: Myopathy and rhabdomyolysis have occurred in

patients treated with lovastatin and nefazodone simultaneously. Nefaz- odone is a potent inhibitor of cytrochrome P3A4 and lovastatin is a substrate of cytrochrome P3A4. Elevated CPK levels have also been reported with the simultaneous use of nefazodone and pravastatin, which is also, a substrate of cytochrome P3A4.

Action: Carefully monitor serum CPK levels if nefazodone is used in combination with lovastatin or pravastatin. This combination should be discontinued if there is a significant rise in CPK, or if rhabdomyolsis occurs.

Mibefradil/Triazolum. Significance level 2: Moderate Advice to Practitioner: Mibefradil markedly increases the plama con-

centrations of triazolam probably secondary to its potent inhibition of cytochrome P3A4. Thus the pharmcokinetic effects on triazolam are to enhance and prolong its effects.

Action: prescribe another hypnotic and try to avoid using mibefradil and triazolam concomitantly.

Nefazodone/SildenafX Significance level 2: Moderate Advice to Practitioner: Nefazodone and Sildenafil use the same cyto-

chrome P450 metabolic pathways. Therefore, the practitioner must know that either drug may have less effect than expected for the dosage administered.

Action: Attempt to use an alternative antidepressant. If you need to employ nefazodone with sildenahl, insure blood levels and/or effectiveness is monitored routinely to achieve expected result.

Nitrates/SiZdenafiZ. Significance level 1: Major Advice to Practitioner: Current warnings advise that sildenafil should

not be taken with any nitrate containing drugs, e.g., nitroglycerin. Sildenafil inhibits phosphodiesterase-5 (PDE-5) that is found in the corpus cavernosum and in the systemic vasculature. Sildenafil causes a decrease in systemic arterial pressure and a synergistic and often major decrease in systemic arterial pressure in the presence of organic nitrates (nitric oxide donors).

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Action: Do not concomitantly administer nitrate containing medications and sildenafil. Although other vasodilating agents have different pharmacology, it may be prudent to avoid agents that cause vasodilation when administering sildenafil until more information is available. In addition, patients’ cardiac status needs to be evaluated when administering any erectile dysfunction treatment that may have systemic vasodilatory properties that may potentially lower blood pressure. Patients may require exercise treadmill testing to determine if erectile dysfunction patients with coronary artery disease may achieve the physiologic work load (4-6 metabolic equivalents) associated with sexual intercourse.14

Verapamil/Oxcarbazepine. Significance level 2: Moderate Advice to Practitioner: Co-administered verapamil and oxcarbazepine

has resulted in a 20% reduction in the plasma level of the lo-monohy- droxy metabolite of oxcarbaxzeine that possesses pharmacological activity. The clinical significance of this interaction has not been determined as yet.

Action: monitor clinical effectiveness of oxcarbazepine when coadministered with verapamil.

WarfaridBarbiturates. Significance level 1: Major Advice to Practitioner: Warfarin’s clinical efficacy is reduced with the

addition and concomitant utilization of barbiturates. The mechanism may be the enhanced metabolic rate from the induction of hepatic microsomal enzymes by the barbiturates. Addition of barbiturates to war-far-in will decrease its clinical effectiveness, while the withdrawal of barbiturates from the anticoagulant will increase its effectiveness and produce toxicity.

Action: It is necessary to monitor anticoagulant therapy when adding or discontinuing barbiturates as either insufficient or exces- sive anticoagulation activity may occur. It is important to monitor patients for several weeks. Benzodiazepines would have less effect on warfarin.

WarfaridFluvoxamine. Significance level 2: Moderate Advice to Practitioner: Low dose fluvoxamine can interact significantly

with war-farm in the elderly and the effect may persist for up two weeks after stopping the antidepressant.

Action: monitor the effects on warfarin, e.g., increase of international normalized ration, when it is combined with fluvoxamine. DM, May 2003 321

Warfarin/Quetiapine. Significance level 2: Moderate Advice to Practitioner: A recent case report suggests that quetiapine

may competitively inhibit cytochrome ~450 3A4 and cytochrome 2C9, resulting in increased warfarin activity. Interactions of this type present problems when the enzyme-altering drugs are added to a previously stable patient. Interactions due to this mechanism may take a few days to two weeks to become evident or dissipate, as it may take some time before the enzyme alteration occurs or resolves.

Action: When quetiapine is added to a previously stable regimen of warfarin, warfarin activity may be increased. When warfarin is added to a regimen containing quetiapine, no intervention would be required, as the dose of warfarin would be determined by prothrombin times or international normalized ratios. Monitor prothrombin times and/or international normalized ratios.

Exp/cmatory Mechanisms for Drug or Drug-Drug heractions

Angiotensin Converting Enzyme Inhibitors (Ace)/Desipramine. Sig- nificance level 2: Moderate

Advice to Practitioner: Tricyclic antidepressants decrease ACE function, especially desipramine that displaces ACE from its receptors. Fluoxetine or tranycypromine do not change ACE levels.’

Action: monitor carefully if ace and desipramine are used concomitantly.

AtenoZoUFZuvoxamine. Significance level: Not applicable Advice to Practitioner: Because atenolol is renally excreted fluvoxam-

ine added to it did not affect the plasma concentration of atenolol. In contrast fluvoxamine does have an impact upon metoprolol and propran- 0101 (both of which are metabolized hepatically).

Action: note the difference in reaction when fluvoxamine administered concomitantly with atenolol then when it is with metoprolol and propanolol.

MetoproloUDiphenhydramine. Significance level 2: Moderate Advice to Practitioner: Diphenhydramine inhibits the metabolism of

metoprolol because of the alteration of metabolizers of cytochrome P2D6. Consequently the negative chronotropic and inotropic effects of the drug are prolonged”.

Action: monitor the combined use of metroprolol and diphenhydramine for adverse chronotropic and inotropic effects.

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Cautions and Important Associated Phenomenon Vulproic Acid. “Cases of life-threatening pancreatitis have been reported

in both children and adults receiving depakote. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death” (Dear Doctor Letter, Abbott Laboratories, July 2000).7

Thioridazine. “Mellaril has been shown to prolong the QTc interval in a dose related manner, and drugs with this potential, including mellaril, have been associated with torsade de pointes-type arrthymias and sudden death. Mellaril is indicated only for schizophrenic patients who fail to show an acceptable response to adequate courses of treatment with other antipsychotic drugs. Mellaril is contraindicated with certain other drugs, including fluvoxamine, propranolol, pindolol, any drug that inhibits the cytochrome ~450 2D6 isoenzyme, e.g., fluoxetine and paroxetine and agents known to prolong the QTc interval. Mellaril is contraindicated in patients with reduced levels of the cytochrome-P450 2D6 isozyme as well as in patients with congenital long QT syndrome or a history of cardiac arrhythmias. A baseline EKG is suggested, and serum potassium should be normalized before starting treatment and patients with a QTc interval greater than 450 msec should not receive mellaril and it should be discontinued in patients with a QTc interval over 500 msec. . . . . ” (Novartis Dear Doctor Letter July 7, 2000; FDA/MedWatch 2000).”

Sildenufil. Sildenafil and the interactions with the SSRIs has been reviewed, including the psychopharmacology of sildenafil, possible interactions with SSRIs, side effects, risks, and the need for concomitant psychological counseling.i2 Important papers address the issues of management of sexual dysfunction in patients with cardiovascular disease: Recommendations of the Princeton Consensus Panel,i3 American College of Cardiology/American Heart Association.‘4

ZaZepZon. Zaleplon the newest benzodiazepine receptor agonist, has the shortest half-life of available agents. Zaleplon improves sleep latency, duration and sleep quality, particularly in the elderly. It does not appear to cause rebound insomnia, residual sedation, or adversely affect psychomotor function. Patients should be ready to go to sleep immediately upon the drug’s ingestion. Zaleplon appears to be helpful to those with difficulty falling asleep, and those who experience next-day drowsiness with the more long acting hypnotic agents. There were no interactions noted from the search strategies employed with the cardiac drugs listed (Table 1).

Ziprasidone. “QT Prolongation and Risk of Sudden Death. A study directly comparing the QT/QTc prolonging effect of ziprasidone

with several other drugs effective in the treatment of schizophrenia was

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conducted in patient volunteers. In the first phase of the trial, ECGs were obtained at the time of maximum plasma concentration when the drug was administered alone. In the second phase of the trial, ECGs were obtained at the time of maximum plasma concentration while the drug was coadministered with an inhibitor of the CYP450 3A4 metabolism of the drug. . . .

Nevertheless, ziprasidone’s larger prolongation of QTc length com- pared to several other antipsychotic drugs raises the possibility that the risk of sudden death may be greater for ziprasidone than for other available drugs for treating schizophrenia. This possibility needs to be considered in deciding among alternative drug products. . . .

Ziprasidone use should be avoided in combination with other drugs that are known to prolong the QTc interval. Ziprasidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.“”

Conclusion We have previously reported several methods to keep up-to-date,

including the instruments that are currently available to accomplish this (see introduction)‘. As this update illustrates new drugs have appeared, new interactions have been reported, and confirmatory data on previously described hypotheses are now known. This unfolding of knowledge of cardiac drug-psychotropic drug interactions illustrates the importance of methods of surveillance to ensure that new information is current, accurate, and available. It is our intent to have the earlier interactions as well as those described in this paper available on the Internet on a web site (www.microcares.com), and as a part of the dictionaries in a computer- ized medical record-MICROCARES. l5 This would allow medical students, house officers, fellows, and attendings in psychiatry, cardiology and primary care to have immediate access to this essential information.

Non psychiatric physicians, e.g., cardiologists, primary care physicians, internists, would be expected to have their patients on medical drugs. They are also frequent prescribers of psychotropic medications for behavioral and mental disorders as well. Psychiatrists often consult with medically ill patients on a variety of medications and to which they are adding a psychotropic prescription. It is incumbent that physicians of all disciplines know the interactions listed above, (and those in the previous article) before they prescribe psychotropic medications to the medically ill where concomitant medication use may lead to adverse and at times life threatening interactions.’

Although there is a new journal to be launched in 2001-American Journal of Cardiovascular Drugs: Drugs, Devices and Other Interven-

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tions-it does not necessarily include or emphasize cardiac drug- psychotropic drug interactions.8”6

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Cardiac drug-psychotropic drug update