Drug interactions: a look at timing, genetic interplay and tips for
recognizing and preventing them in clinical practice
Presented by Brian Hocum, PharmD
Personalized Prescribing Clinical Pharmacist, Genelex Corporation
Washington State University College of Pharmacy Adjunct Faculty Member
Learning Objectives
1.
2.
3.
4.
Examine the time component involved in drug interactions
Recognize the interplay between drugs and genetics
Identify a drug interaction in a patient with a problem
Predict a drug interaction in a patient that you want to prescribe for
Commitment to change
When I suspect drug interactions in my practice I will consider inter-individual
variation of the CYP450 enzyme system and the timing involved when evaluating
the patient.
Pre-assessment
Case Study: Drug Interaction-Induced Anxiety
Chief Complaint: A 72-year-old male with no known drug allergies presented to
the ER with a chief complaint of feeling “lightheaded, panicky and slight difficulty
breathing.” The panic-like onset first developed three days earlier, reoccurred a
couple of times throughout the day, and seemed to be getting more frequent.
When the physician entered the exam room, the patient was pacing back and
forth and in apparent discomfort. He had normal vital signs except slight
tachycardia. The patient had no prior history of panic attacks.
At the time of admittance, the patient was taking the following medications:
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Methadone 20 mg po q 6 hours prn
Promethazine 25 mg po q 6 hours
Trazodone 50 mg po QHS
Zolpidem 10 mg po QHS
Simvastatin 40 mg po QHS
Lisinopril/HCTZ 20/12.5 mg po QAM
ASA 81 mg po QAM
Tamsulosin 0.4 mg po QAM
History of Present Illness: Ten days earlier the patient was changed from
hydrocodone/acetaminophen to methadone because hydrocodone was no longer
working well. After several days on methadone, the patient requested medication
for nausea and promethazine was prescribed. The patient began feeling
“different” and stopped the promethazine for a day only to start again because
stopping didn’t seem to help.
Plan: After a complete history and exam, the physician diagnosed the patient
with possible mild serotonin syndrome and akathisia as a result of an unknown
drug interaction. Lorazepam IV was prescribed for acute panic relief and
promethazine was discontinued.
Discussion: The speaker, a clinical pharmacist who specializes in drug
interactions discussed this case with the ER physician and used drug interaction
software (YouScript®) to identify the suspected drug interaction. YouScript
predicted that both methadone and promethazine inhibited the metabolism of
trazodone’s metabolite, m-chlorophenylpiperazine (mcPP), through the CYP2D6
enzyme. mcPP is known to have hallucinogenic and dysphoric effects. 1,2,3
Image Source: www.youscript.net
Questions
1. What drug interaction pattern is represented in this case? (circle one)
a. Pharmacodynamic
b. Pharmacokinetic: immediate
c. Pharmacokinetic: 1 to 5 days
d. Pharmacokinetic: Weeks
2. Inhibition based interactions present more quickly than induction based
interactions?
a. True
b. False
3. Since mcPP is metabolized by CYP2D6, a patient with the CYP2D6 Poor
Metabolizer phenotype may have similar problems with trazodone?
a. True
b. False
References
1. Hocum MD, Brian (Emergency Medicine, St. Joseph Regional Hospital,
Lewiston, Idaho). Conversation with: Brian Hocum, PharmD (Genelex,
Seatte, WA). 2013 Spring.
2. Logan BK, Constantino AG, Rieders EF, Sanders D. Trazodone, metachlorophenylpiperazine (an hallucinogenic drug and trazodone
metabolite), and the hallucinogen trifluoromethylphenylpiperazine crossreact with the EMIT®II ecstasy immunoassay in urine. J Anal Toxicol.
2010 Nov;34(9):587-9. PMID: 21073812.
3. Kast RE. Trazodone generates m-CPP: in 2008 risks from m-CPP might
outweigh benefits of trazodone. World J Biol Psychiatry. 2009;10(4 Pt
2):682-5. PMID: 19384678.
Answer key (pre-assessment)
1. C
2. A
3. A