Update on clinically significant drug interactions in dermatology

Barranco, Vincent P

doi:10.1016/j.jaad.2003.10.678

« Previous Next »Journal of the American Academy of Dermatology
Volume 51, Issue 2 , Pages E1-E4, August 2004

Update on clinically significant drug interactions in dermatology☆

Clinical Professor of Dermatology and Family Medicine, Vice-Chairman Department of Dermatology, The University of Oklahoma, Schusterman Health Sciences Center, College of Medicine—Tulsa USA

To the Editor: This update of clinically significant drug interactions (DI) in dermatology updates the information published in the Journal of the American Academy of Dermatology in 2002.^1., ^2., ^3., ^4., ^5., ^6., ^7. It incorporates information available up to December 31, 2002. This is an attempt to focus on clinically significant DIs and is not intended to be an encyclopedic collection of all reported interactions. There are thousands of reported DIs which are either inconsequential or not scientifically substantiated. Clinicians may be distracted by unimportant information and fail to take note of significant interactions that can lead to significant morbidity and mortality. Table I is a useful peer-reviewed tool designed to keep dermatologists abreast of the growing list of significant DIs. These include high-risk drugs with narrow therapeutic index^8., ^9., ^10. and drugs that cause sudden death from prolongation of the QT interval leading to a cardiac arrhythmia termed torsades de pointes (TdP).^11., ^12., ^13., ^14. Interactions involving 27 important or frequently used dermatologic drugs or categories of drugs are included in Table I. Drugs with a narrow therapeutic index are listed in Table II Drugs that can induce a prolonged QT interval at high serum concentrations, leading to TdP, are listed in Table III

Table IV. Summary of generic and brand name drugs

Generic name	Brand name
Amprenavir	Agenerase
Azathioprine	Imuran
Azole antifungal agents^∗
Fluconazole	Diflucan
Itraconazole	Sporonox
Ketoconazole	Nizoral
Buspirone	BuSpar
Carbamazepine^∗	Tegretol (eg)^†
Cilostazol	Pletal
Corticosteroids	Deltasone (eg)^†
Cyclosporine^∗	Neoral
Diltiazem	Cardizem (eg)^†
Dofetilide	Tikosyn
Haloperidol	Haldol (eg)^†
HMG-CoA reductase inhibitors
Atorvastatin	Lipitor
Lovastatin	Mevacor
Simvastatin	Zocor
Lamotrigine	Lamictal
Macrolide antibiotics^∗
Erythromycin	Emycin (eg)^†
Clarithromycin	Biaxin
Methadone	Dolophine
Modafinil	Provigil
Oral contraceptives^∗	Ortho Tri-Cyclen (eg)^†
Orlistat	Xenical
Pimozide	Orap
Phenothiazine
Perphenazine	Trilafon
Thioridazine	Mellaril
Quinolones^∗
Levofloxacin	Levaquin
Moxifoxacin	Avelox
Repaglinide	Prandin
Rifamycins^∗	Rifadin, Rimactane
Risperidone	Risperdal
Ropivacaine	Naropin
Serotonin reuptake inhibitors^∗
Fluvoxamine	Luvox
Fluoxetine	Prozac
Nefazodone	Serzone
Proxetine	Paxil
Sertraline	Zoloft
Sirolimus	Rapamune
Tacrolimus	Prograf
Tamoxifen	Nolvadex (eg)^†
Theophylline^∗	Theo-Dur (eg)^†
Toremifine	Fareston
Trimethoprim^∗	Trimpex
Voriconazole	Vfend
Warfarin^∗	Coumadin
Ziprasidone	Geodon

∗ Red flag drugs.

† Brand name given is representative; others are available.

. A committee of experts should be convened to consider this information, and any additional drugs that should be added to the short list of truly significant DIs in dermatology.

Table I. Updated clinically significant drug interactions in dermatology

Interacting drugs
Dermatologic agent	Significant interacting drug	Significance rating	Mechanism	Effect
Azathioprine	Warfarin^∗	2	Unknown	Decreased plasma warfarin
Azole antifungal agents^∗	Carbamazepine^∗	2	Decreased metabolism	Increased plasma carbamazepine
Azole antifungal agents^∗	Haloperidol	2	Decreased metabolism	Increased plasma haloperidol and risk of TdP
Azole antifungal agents^∗	Sirolimus	2	Decreased metabolism	Increased plasma sirolimus
Corticosteroids	Diltiazem	2	Decreased metabolism	Increased plasma corticosteroids
Corticosteroids	Grapefruit juice	2	Decreased metabolism	Increased plasma corticosteroids
Cyclosporine^∗	HMG-CoA reductase inhibitors	1	Decreased metabolism	Increased plasma HMG-CoA reductase inhibitors
Cyclosporine^∗	Orlistat	1	Decreased GI absorption	Decreased plasma cyclosporine
Cyclosporine^∗	St. John's wort	1	Increased metabolism	Decreased plasma cyclosporine
Cyclosporine^∗	Sirolimus	2	Unknown	Increased plasma sirolimus
Macrolide antibiotics^∗; clarithromycin, erythromycin (not azithromycin)	HMG-CoA reductase inhibitors	1	Decreased metabolism	Increased plasma HMG-CoA reductase inhibitors with myopathy and/or rhabdomyolysis
Macrolide antibiotics^∗; clarithromycin, erythromycin (not azithromycin)	Cilostazol	2	Decreased metabolism	Increased plasma cilostazol
Macrolide antibiotics^∗; clarithromycin, erythromycin (not azithromycin)	Repaglinide	2	Decreased metabolism	Increased plasma repaglinide
Oral contraceptives^∗	Lamotrigine	2	Increased metabolism	Decreased plasma lamotrigine
Oral contraceptives^∗	Modafinil	2	Increased metabolism	Decreased plasma oral contraceptives
Pimozide	Phenothiazines^#, specifically thioridazine	1	Synergistic prolongation of the QT interval	Life-threatening cardiac arrhythmias, including TdP
Pimozide	Ziprasidone	1	Synergistic prolongation of the QT interval	Life-threatening cardiac arrhythmias including TdP
Quinolones^∗^# (moxifloxacin and less likely with levofloxacin)	Ziprasidone	1	Synergistic prolongation of the QT interval	Life-threatening cardiac arrhythmias including TdP
Rifamycins^∗	Tacrolimus	1	Increased metabolism	Decreased plasma tacrolimus and decreased immunosuppression
Rifamycins^∗	Amprenavir	2	Increased amprenavir; decreased rifamycin metabolism	Decreased plasma amprenavir; increased plasma rifamycin
Rifamycins^∗	HMG-CoA reductase inhibitors	2	Increased metabolism	Decreased plasma HMG-CoA reductase inhibitors
Rifamycins^∗	Lamotrigine	2	Increased metabolism	Decreased plasma lamotrigine
Rifamycins^∗	Tamoxifen	2	Increased metabolism	Decreased plasma tamoxifen
Rifamycins^∗	Toremifene	2	Increased metabolism	Decreased plasma toremifene
Rifamycins^∗	Voriconazole	2	Increased metabolism	Decreased plasma voriconazole
Serotonin reuptake inhibitors^∗	Phenothiazines^#, specifically thioridazine and trilafon	1	Decreased metabolism	Increased plasma phenothiazines and risk of TdP
Serotonin reuptake inhibitors, specifically fluvoxamine^∗^#	Methadone	1	Decreased metabolism	Increased plasma methadone and risk of TdP
Serotonin reuptake inhibitors, specifically fluvoxamine^∗^#	Ropivacaine	2	Decreased metabolism	Increased plasma ropivacaine
Serotonin reuptake inhibitors, specifically fluvoxamine^∗^#	St. John's wort	2	Possible additive serotonin reuptake inhibition	Increased sedative-hypnotic effect
Serotonin reuptake inhibitors, specifically fluvoxamine^∗^#	Theophyllines^∗	2	Decreased metabolism	Increased plasma theophylline
Serotonin reuptake inhibitors, specifically paroxetine^∗^#	Risperidone	2	Decreased metabolism	Increased plasma risperidone
Serotonin reuptake inhibitors^∗	Beta-blockers	2	Decreased metabolism	Increased plasma beta-blockers with excessive bradycardia
Serotonin reuptake inhibitors, specifically fluvoxamine^∗^#	Buspirone	3	Decreased metabolism	Increased plasma buspirone
Trimethoprim^∗	Dofetilide	1	Decreased renal excretion	Increased plasma dofetilide and risk of TdP

GI, Gastrointestinal.

Drugs that appear in bold were not included in the original 27 commonly prescribed drugs.

# Recent report involving a specific drug within a family of drugs. Over time, other or all drugs withing the family may be incriminated.

∗ Red flag drugs.

Narrow therapeutic index.

Prolonged QT interval with torsades de pointes (TdP).

Table II. Drugs inclined to produce toxicity because of a narrow therapeutic index

Carbamazepine^∗

Cyclosporine^∗

Digoxin

Lithium

Phenytoin^∗

Theophylline^∗

Warfarin^∗

∗ Red flag drugs.

Table III. Prolonged QT interval with risk for torsades de pointes (TdP) associated with overdose, drug interactions, or hereditary prolonged QT interval

Amiodarone^∗

Bepridil

Disopyramide^∗

Dofetilide

Haloperidol

Isradipine

Levomethadyl

Methadone

Pimozide

Procainamide

Quinidine^∗

Serotonin reuptake inhibitors^∗

Sotalol

Tacrolimus

Thioridazine

Tricyclic antidepressants

Trimethoprim-sulfamethoxazole^∗

Ziprasidone

∗ Red flag drugs.

As in the two previous reports, the overwhelming majority of clinically significant DIs involve either activation or inhibition of the cytochrome P-450 isoenzymes. At least 26 drugs so commonly involve drug metabolism that I have called them “red flag drugs.”^1., ^2. In this update, there are 32 new clinically significant drug interactions. Twenty-seven involve one of the twenty-six red flag drugs. As in the previous papers, these numbers further support the red flag concept, which continues to be a most helpful and practical aid to my practice.

As in previous reports, I have used the quarterly updated scheme developed by “Drug Interaction Facts.”³ In their scheme, DIs may have a significance rating of 1, 2, 3, 4, or 5. A rating of 1 is severe and well documented, whereas a rating of 5 is, at worst, unlikely and only partially or not documented. DIs that are well documented or at least reasonably well documented have a significance rating of 1, 2, or 3. It is unlikely that a patient would be harmed or a physician considered negligent except in cases of DI with a significance rating of 1, 2, or possibly 3.

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☆ Secretarial support was provided by Tulsa Dermatology Clinic.

PII: S0190-9622(04)01051-5

doi:10.1016/j.jaad.2003.10.678

« Previous Next »Journal of the American Academy of Dermatology
Volume 51, Issue 2 , Pages E1-E4, August 2004

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Update on clinically significant drug interactions in dermatology☆

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Article Outline

Table IV. Summary of generic and brand name drugs

Table I. Updated clinically significant drug interactions in dermatology

Table II. Drugs inclined to produce toxicity because of a narrow therapeutic index

Table III. Prolonged QT interval with risk for torsades de pointes (TdP) associated with overdose, drug interactions, or hereditary prolonged QT interval

References

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