Has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.

 Do not start any new patients on 80 mg of simvastatin.
 Avoid prescribing methylene blue or linezolid to patients on serotonergic drugs
 Do not prescribe doses of Citalopram > 40 mg



Retrospective, cohort study of 1166 patients with an initial diagnosis of C Difficile infection (CDI)
Patients who received a PPI within 14 days after their
C diff dx were defined as PPI exposed.
 45% of patients with CDI were PPI exposed.
Recurrent CDI was more common in PPI exposed patients (25% vs 18%) HR 1.42,95% CI 1.11-1.82
 Arch Intern Med 2010;170:772-778.
 Also W J Gastroenterology 2010;16 (28):3573- 3577.

 Statins and cognitive impairment, increased risk of diabetes (worry level-low)
 Sitagliptan (Januvia) and pancreatitis (worry level- moderate)

PPI’s and Clostridia difficile (worry levelmoderate)









Decreased Ca absorption
Decreased iron absorption
Increased fracture risk
Decreased thyroid absorption
Poor Magnesium absorption
Poor B12 absorption
Decreased Ketoconazole/Itraconazole absorption
Increased risk of C. difficile, and recurrent C Diff and more severe C diff. FDA warning 2/12


A)
B)
C)
D)
Pharmacist calls to tell you that you are prescribing a triptan for a patient who is on an SSRI (citalopram 20 mg a day). She is on no other meds. What should you do?
Switch to another migraine treatment
Have patient not take citalopram for 24 hours after taking the triptan
Cut the dose of triptan by 50 %
Don’t worry

 Concern for serotonergic syndrome
 Extremely unlikely if only a triptan + SSRI
(especially at lower doses of SSRI)
 Beware of patients on multiple drugs that can trigger serotonergic syndrome ( tramadol, linezolid,meperidine, dextromethorphan, TCA,
MAOI, buspirone, trazadone)


A)
B)
C)
D)
Pharmacist calls you to tell you that she did not fill the Tadalafil (10mg) prescription you wrote for your patient because he is on tamsulosin. What do you do?
Switch Tamsulosin to Finaseride
Switch Tamsulosin to Alfuzosin
Switch Tadalafil to Sidenafil
Ask that the prescription be filled

 .4 mg of tamsulosin was given for 7 days in healthy volunteers, then tadalafil 10mg,20 mg or placebo were given two hours after tamsulosin dose
 No significant difference in standing SBP with either dose of tadalafil and placebo, no one had a SBP < 85, no dizziness.
 J Urol 2004; 172: 1935-1940.

 Nitrates
Ok to give NTG > 4 hours after sildenafil use, 24 hours after vardenafil use and 48 hours after tadalafil use
 Alpha Blockers
Ok to use in patients who are on stable alpha blocker therapy. For patients on doxazosin or terazosin, should not take within 4 hours of a dose to avoid potential drop in BP





National Electronic Injury Surveillance System –Cooperative
Adverse Drug Event Surveillance project (2007 through 2009) was used to estimate the frequency of emergency hospitalization for adverse drug events in patients 65 and older
Almost 100,000 admissions annually in adults >65 due to adverse drug events occurred during the study period
Four drug classes causes 67% of the mayhem- warfarin 33%,
Insulins 13.9%, oral antiplatelet drugs 13.3% and oral hypoglycemics 10.7%.
N Engl J Med 2011;365:2002-2012.

A 72 y.o. male S/P AVR replacement two years ago for aortic stenosis presents with wide spread bruising on his back/legs and some bruising on the back of both hands. His last INR was three weeks ago and was 3.0. He states he saw an
M.D. six days ago for a cough and was put on a medication described as a “white tablet.” His chronic medications include: Coumadin 5 mg qd,
Albuterol inhaler 2 puffs 4 times a day and
Nortryptiline 25 mg qhs.

What medication was he placed on?
a) Amoxicillin b) Codeine c) Cefixime d) Azithromycin e) TMP/Sulfa

Most Severe Possible*
TMP/Sulfa Quinolones
Erythromycin Omeprazole
Amiodarone Clarithromycin
Propafenone Azithromycin
Ketoconazole/fluconazole
Itraconazole
Metronidazole * Especially in elderly and polypharmacy

 Retrospective cohort study 104 patients on stable warfarin therapy. Effect on INR of Terazocin (control),
Azithromycin (32 patients), Levofloxacin (27) and
TMP/Sulfa (16)
 Mean change in INR: Terazocin -.15, Azithromycin +
.51 , Levofloxacin + .85, TMP/Sulfa +1.76


Percent patients having a INR > 4: Terazocin 5%,
Azithromycin 31%, Levofloxacin 33%, TMP/Sulfa
69%
JGIM 2005;20 (7);653-6.



Nested case control study of 38,000 elderly warfarin users (on medicare D)
Cases were patients hospitalized for bleeding/each matched with 3 control patients taking warfarin
 Exposure to any antibiotic in the 15 days prior to admission was a risk, greatest risk with azoles (aOR
4.57), Cotrimoxazole (aOR 2.70).
Am J Med.
2012 Feb;125(2):183-9

 Penicillins/cephalosporins ok
 Nitrofurantion ok
 Quinolones- be worried

TMP/Sulfa don’t use

A 39 y.o. woman with a prosthetic aortic valve presents with bruising. Her last INR 6 weeks ago was 2.4, today’s INR is 6.5. She has not taken any extra Coumadin. Which of the following when taken on a daily basis could explain her increased INR?
a) Acetaminophen b) Calcium carbonate c) OCP d) Ranitidine e) DOSS


3 studies suggest increased INR with
Acetaminophen + Warfarin


> 9100 mg/week led to 10 x risk of having INR > 6*
In double blind crossover trial patients on Warfarin
+ 4 g/d of Acetaminophen had PT 1.75
control +
 Patients received 2 gm or 4 gm acetaminophen or placebo with warfarin, 54% of those receiving acetaminophen overshot INR goal vs 17% of placebo #.
*JAMA 1998;279:657-662
+ Clin Res 1984;32:698a
# Pharmacotherapy 2007; 27 (5):675-83.

 A 76 yo man is admitted with increasing SOB. He has a long history of COPD and has had a recent productive cough. He is admitted to the hospital and treated with amoxicillin, prednisone, codeine, and albuterol. PMH: A fib, Hypertension, COPD, GERD.
Outpatient meds: Metoprolol, coumadin, pantoprazole, lisinopril. His recent INR 2 weeks ago was 2.2, on hospital day 6 it is 4.3. What is the most likely interaction with coumadin?



A) Prednisone
B) Amoxicillin
C) Codeine
 D) Amoxicillin + Pantoprazole

 Retrospective review of patients in ACC who received oral corticosteroids. Patients were excluded if they were treated with any drug with a known interaction with warfarin.


Mean difference between pre steroid INR and the INR when patients on steroids was 1.24, p<.001. 62% of the patients had an INR above their targeted range.
Mean time to INR elevation was 6.7 days after starting steroids.
Ann Pharmacother 2006;40:2101-6.

 A 65 yo man presents with cough and fever. He has had severe diarrhea for 2 days. He was on a cruise with a friend who was diagnosed with Legionella yesterday. PMH – diabetes, hyperlipidemia,hypertension. Meds: Lisinopril, simvastatin, amlodipine, gemfibrozil,metformin.
Chest Xray shows patchy bilateral infiltrates. WBC
17,000 Na 125. What is the most appropriate treatment?
A)Amoxicillin/clavulanate
B)Clarithromycin
C)Levofloxacin
D)Cefuroxime
E)Trimethoprim/sulfa

 Fibrates (Gemfibrozil 15X >> Fenofibrate)
 Azole antifungals
 Amiodarone
 Erythromycin/Clarithromycin
 Protease inhibitors
 Verapamil/Diltiazem
 Least drug interactions with pravastatin, most with simvastatin and lovastatin







Your 5 o’clock add on patient is a 55 yo man with DM who has been having myalgias. His baseline LDL cholesterol is 125 . He started having myalgias when he took atorvastatin 3 months ago. The myalgias stopped when he stopped the med. He was switched to pravastatin 3 weeks ago and the myalgias started again, What do you recommend?
 A) Start ubiquinone (Conenzyme Q10)
 B) Switch to simvastain
 C) Add an NSAID
 D) Stop pravastatin and start red yeast rice

 PRIMO study 10.5 % had muscle symptoms on statins
 For those receiving the highest doses of statins rates of myalgia were
Fluvastatin XL 5.1%
Pravastatin 10.9%
Atorvastatin 14.9%
Simvastatin 18.2%
Cardiovasc Drugs Ther. 2005 Dec;19(6):403-14.









Appears to be dose and possibly drug related
Check TSH level
More common inpatients with low body mass
More common in Asian patients
? Role of vitamin D
? Benefit of coenzyme Q10 (low ubiquinone levels?)
Biopsy of muscle in statin treated patients with myalgia and normal CPK levels have shown myopathy
Biopsy of muscle in statin treated patients with no symptoms have shown muscle cell damage.



62 patients with hyperlipidemia and discontinuation of statin therapy due to myalgias
Randomly assigned to red yeast rice (RYR) 1800 mg
BID or placebo
 In RYR group LDL decreased by 35 mg/dl compared to 15 mg/dl in placebo group (p=.01).


Pain severity scores were no different between groups
Ann Intern Med 2009;150: 830-839.

Approach to Management of Myalgias on Statins
 Check CK ,TSH.


Stop statin, when symptoms disappear restart statin at lower dose or change statin
If recurrent symptoms try Fluvastatin 80mg XL QD or alternate day or 2X weekly 10mg atorvastatin, or low dose rosuvastatin daily,QOD or weekly
 If symptoms continue try ezetimibe or colesevelam or red yeast rice
 Adapted from Harper and Jacobson Curr Atheroscler Rep.
2010 Sep;12(5):322-30.

 Major interaction with grapefruit juice
 Mild interaction with warfarin
 Major interaction with amiodarone
 Usual statin concern with fibrates/clarithromycin/azoles
 Red flags should go off when prescribing for A fib patients, where they might be on both warfarin and amiodarone (and a Ca channel blocker)
 June 2011 FDA advisory to not put new patients on
80mg of simvastatin

 A 36 yo man with a history of gout returns for follow up. He has had a 2 day history cough and today fevers. Chest xray shows a RLL infiltrate. PMH: CRI baseline Cr 2.0. Meds : Allopurinol 200 mg a day, colchicine .6 mg a day, citalopram 20 mg a day.
Which drug would be most dangerous to prescribe?
A)
Azithromycin
B)
Clarithromycin
C)
Levofloxacin
D)
Erythromycin
E)
Chloramphenicol

 Higher risk in patients with renal insuff
 Many (over 100) reports of death with interaction with clarithromycin, a strong
CYP3A4 inhibitor
 Avoid clarithromycin, protease inhibitors, itraconazole and ketoconazole

A 85 yo man is brought to the ED for evaluation of weakness and nausea. He was diagnosed 10 days ago with prostatitis. His other problems include hypertension, CHF and CRI. Meds: Carvedilol, furosemide, TMP/Sulfa, verapamil, digoxin. Exam-
BP 100/60 P-100 T 36.9 cardiac- grade 2/6 SEM lower extremity edema present. Lab: Na- 132 K -6.8
BUN 37 Cr- 2.3. What is the most likely cause of his hyperkalemia?
A) Chronic renal insufficiency
B) Carvedilol
C) TMP/Sulfa
D) Verapamil
E) Digoxin

 More common in elderly and patients with renal impairment
 More likely if patient is on an ACEI or ARB
 More likely if patient is receiving high doses of steroids
 Mechanism is that trimethoprim acts like amiloride, a potassium sparing diuretic, and reduces urinary potassium excretion by 40%

 Patient taking warfarin
 Patient taking methotrexate
 Allergy
 Elderly patients with renal insufficiency


A)
B)
C)
D)
E)
78 yo man is brought to the ED with hypotension.
His BP is 70/50. He has a history of atrial fibrillation and CAD and was diagnosed with pneumonia 3 days ago. Medications: Isosorbide mononitrate,
Lisinopril, Diltiazem, clarithromycin and linezolid.
What is the most likely cause of his hypotension?
Isosorbide-clarithromycin interaction
Lisinopril-clarithromycin interaction
Diltiazem-clarithromycin interaction
Linezolid- clarithromycin interaction
Linezolid- isosorbide interaction






Nested, case-crossover study of patients age 66 and older prescribed a CCB over a 15 year period.
Study group was those admittd to the hospital with hypotension/shock
Compared risk of exposure to macrolide in 7 days before hospitalization with 7 day control interval the month prior
RR of hypotension 5.8 for erythromycin, 3.7 for clarithromycin. Azithromycin was not associated with hypotension
CMAJ 2011;183 (3):303-307.

 Major statin interaction (especially simvastatin/lovastatin)
 Major interaction with CCB
 Increase levels of glypizide/glyburide
(hypoglycemia)
 Major interaction with colchicine
 82 Major drug interactions reported!



85 yo woman is brought to the ED after a syncopal episode.
Her care givers report a similar episode 2 weeks ago,but she recovered so quickly they did not seek evaluation for her.
Meds: Omeprazole 20 mg, pravastatin 40 mg, citalopram 10 mg, albuterol, donepezil 10 mg, isosorbide mononitrate 60mg and calcium. On exam BP 100/60 P 55. ECG Bradycardia with normal intervals. What drug most likely caused of her syncope?





A) Citalopram
B) Pravastatin
C) Donepezil
D) Isosorbide
E) Calcium

 Cholinesterase inhibitors and bradycardia
 ChE-I

RR bradycardia

1.4 (95% CI, 1.1
–1.6)
 Dose effect: donepezil > 10mg

2.1
 risk
J Am Geriatr Soc 2009;57:1997
 Clinical significance: ChE-I use associated with


Syncope: HR

1.76 (95% CI, 1.57-1.98)
ED visits for bradycardia: HR

1.69


Pacemaker placement: HR

1.49
Hip Fx: HR

1.18 (95% CI, 1.03-1.34)
Arch Intern Med 2009;169:867


s
A

A)
B)
C)
D)
E)
A 66 yo woman presents with symptoms of severe muscle pain and joint pain. This has been present for the past 3 weeks. She has had no fevers, chills or trauma. She has a past history of
HTN,Hypothyroidism, CAD, Osteoporosis , GERD and depression. Meds: Omeprazole, Metoprolol,
Alendronate, Citalopram, Levothyroxine . What is the most likely cause of her pain?
Citalopram
Omeprazole
Alendronate
Metoprolol
Hypothyroidism

 612 consecutive patients treated in an osteoporosis clinic with oral alendronate or residronate were evaluated for side effects
 The frequency of severe musculoskeletal side effects was 5.6%. All severe side effects occurred in once weekly treated patients- 20.1% of alendronate treated patients and 25% of risedronate treated patients
 J Musculoskelet Neuronal Interact 2007; 7(2):144-
148.

 Strongly consider bisphosphonate as cause for musculoskeletal pain in patients who are taking them who have severe pain
 Strongly consider temporarily or permanently stop the medication
 Much more likely with weekly or monthly dosing

e
A 66 yo woman presents with hypotension and confusion. She was in her usual state of health until 4 hours prior when she felt ill and vomited a small amount of bloody material. She did not seek medical attention for 2 additional hours . She had another episode of emesis this time of a large amount of bloody material. She has also had one episode of maroon stool. PMH-
HTN, Osteoporosis and depression. Meds: fluoxetine, benazapril, hydrochlorathiazide, acetominophen, and estrogen/progestin.
What medication has the the strongest association with UGI bleeding?
A) Fluoxetine
B) Benazapril
C) Hydrochlorathiazide
D) Acetominophen
E) Estrogen





Multiple retrospective studies show relative risk for UGI bleeding of 34 with the use of SSRI’s
Risk is further increased with concurrent use of a nonsteroidal,
Odds ratio 6.33 if SSRI combined with NSAID
Risk is highest in the elderly
Strongly consider gastroprotection if combination used in patients with history of UGI bleeding, in patients taking NSAIDS or the elderly




Arch Intern Med 2003;163:59-64
BMJ 1999; 319 (7217):1106-9.
Aliment Pharmacol Ther 2008; 27: 31-40. Meta-analysis
Clin Gastroenterol Hepatol. 2009 Dec;7(12):1314-21.

A 66 yo woman presents with fatigue. She has a history of bipolar disorder and reflux disease. She has felt well the past few months until the last few weeks.
Medications: Rabeprazole, lithium, paroxetine, calcium.
Physical exam is normal. As part of her workup she is found to have the following labs: Na 120, K 3.6 Bun 3 Cr
0.7 What is the most likely cause of her low sodium?
A) Hyperlipidemia
B) Lithium
C) Acute psychosis
D) Rabeprazole
E) Paroxetine

 Older age
 Female
 Concomitant diuretic use
 Low body weight

 Dose dependent QT prolongation




Maximum dose recommended for citalopram 40 mg
(maximum dose 20 mg for age >65)
Contraindicated in patients with congenital long QT syndrome
Important interaction with CYP2C19 inhibitors
(fluvoaxamineluvox, fluoxetine, PPI’s, cimetidine, clopidogrel)
Avoid use with other QT prolonging drugs

 Probable increased risk of UGI bleed
 Often overlooked cause of hyponatremia
 Sexual dysfunction (20-50%)
 QT prolongation with citalopram

 Watch carefully for interactions with
TMP/Sulfa , simvastatin and clarithromycin.
 You can use PDE5 inhibitors with tamsulosin
 Statin myalgias are common