Transcript Medication related changes in the post

Medication related changes in
the post-bariatric surgery
population
Christopher Giuliano, Pharm.D.
Assistant Professor, Internal Medicine Clinical
Specialist
Medication absorption after gastric
surgery could
A.
Increase
B.
Decrease
C.
Not change
D.
B or C
E.
All of the above
Objectives
 Distinguish the differences between
restrictive and restrictive-malabsorptive
bariatric surgeries
 Identify medication related changes in
patients after bariatric surgery
 Create a medication regimen based off
suspected pharmacokinetic changes in a
patient case
 Identify nutritional deficiencies associated
with bariatric surgery
Case
FC is a 45 yof that presents with a chief
complaint of feeling dizzy. She has a
PMH of DM, HTN, HLD, atrial fibrillation,
roux-en-y gastric bypass (RYGB) surgery
(4 months prior) , and major depression.
Vitals temp 98.6°, HR 115, BP 102/70,RR 20
Physical Exam: Tachycardic, irregularly
irregular pulse, all else WNL
Case
 EKG- Afib
 Labs (In ER in am)
 Na 135, K 4.3, CL 101, CO2 26, Cr 1.0, BUN
13, Ca 8.6, Glucose 65
 Hgb 9, Hct 33, MCV 55, WBC 7, Platelets
325
 Iron 20, Ferritin 10, B12 600, folate 15
 LDL 40
Case
 Medications (been on for “years”)
 Insulin glargine 30 units qhs
 Insulin aspart 10 units with meals
 Diltiazem XR 360 mg daily
 Hydrochlorothiazide 25 mg daily
 Lisinopril 20 mg daily
 Atorvastatin 80 mg qhs
 Sertraline 20 mg qhs
 Multivitamin qd, B12 1 mg PO daily, Ca/VitD
500/400 BID
Normal anatomy
http://www.nlm.nih.gov/medlineplus/ency/imagepages/8940.htm. Accessed 12/1/14
Restrictive procedures
Vertical Banded
Gastroplasty
Adjustable Gastric
Banding
Sleeve Gastrectomy
Miller A, et al. AJHP. 2006;63:1852-7
Malabsorptive procedures
Jejunoileal bypass
Miller A, et al. AJHP. 2006;63:1852-7
Restrictive-malabsorptive
Roux-en-y*L
Biliopancreatic diversion
Miller A, et al. AJHP. 2006;63:1852-7
Gastric mixing,
volume, ph,
residence time
What if my
PgP increases
active significantly in
transporter
jejunum
is in and
the duodenum?
ileum
No duodenal
absorption!
What if the drug
undergoes
enterohepatic
recirculation?
Giuliano et al. Adv Pharmacoepidem Drug Safety. 2012; S1-6
Remember the
grapefruit juice
interaction with
intestinal
CYP3A4?
Drug disintegration and dissolution
Disintegration
 Gastric mixing
 Clinical pearl- give liquid formulation
 Dissolution and solubility
 Gastric ph
 Clinical pearl- avoid extended release products, if
PPI interacts be careful
Gastric emptying
Which medication could be switched to
another dosage form?
A.
Sertraline
B.
Atorvastatin
C.
Diltiazem XR
D.
Lisinopril
Drug disintegration and dissolution
The role of bile acids
 Lipophilicity
 Tacrolimus
 Enterohepatic recirculation
 Cyclosporine, rifampin, phenytoin, levothyroxine, oral
contraceptives
http://www.nlm.nih.gov/medlineplus/ency/imagepages/8940.htm. Accessed 12/1/14
Mucosal exposure
Length of bypassed segment
Transit time
Intestinal adaptation
Miller A, et al. AJHP. 2006;63:1852-7
Absorption across intestines
Metabolism (CYP3A4)
Active transport (OAT)
Efflux (P-glycoprotein)
 E.g. cyclosporine
The evidence: jejunoileal bypass
Decreased Absorption
No Change
 Phenytoin (9)
 Isoniazid (9)
 Ethosuximide (1)
 Ethambutol (7)
 Rifampin (6)
 Phenazone (17)
 Ethambutol (2)
 Acetaminophen (3)
 Cyclosporine (2)
 Digoxin (7)
 Tacrolimus (1)
 Propylthiouracil (3)
 Levothyroxine (2)
 Ampicillin (6)
 HCTZ (4)
 Digoxin (9)
Padwal R, et al. Obesity Reviews. 2010;11:41-50
Gastric surgery: contraceptives
 71% of 98 anovulatory women achieved
normal menstrual cycles
2 pharmacokinetic studies in JIB patients
 Lower levels of NET and LNG
 No reduced levels of D-norgesterol or estrogens
2 observational studies
 2 out of 9 BPD women using oral contraceptives became
pregnant
 Of 215 patients, no LAP-band patient on OC became pregnant
Teitelman M, et al. Obes Surg. 2006;16:1457–63.
Gerrits E, et al. Obes Surg 2003;13:378–82.
Weiss HG, et al. Obes Surg 2001;11: 303–6.
Victor A, et al. Gastroenterol Clin North Am 1987;16:483–91
Andersen AN, et al. Int J Obes 1982;6:91–6.
Nutritional deficiencies
RYGB
Sleeve
B12
42.1%*
5%
Iron
30%
36.4%
Folic acid
20%
18.4%
Vitamin D
56.3%
39.6%
Alexandrou E, et al. Surgery for Obesity and Related Diseases. 2014; 10(2): 183-203
RYGB: iron
67 RYGB women were followed over 18
months
 1.5% anemic at baseline compared to 38.8%
 7.5% low ferritin at baseline compared to 37.3%
Ruz M, et al. Am J Clin Nutr. 2009;90: 527-32
Other nutritional deficiencies
Thiamine
Copper
Zinc
Vitamin A, D, E, K
Saltzman E, et al. Annu Rev Nutr. 2013; 33: 183-203
What type of anemia does our patient
have?
A.
Iron deficiency
B.
B12 deficiency
C.
Folate deficiency
D.
Anemia of chronic disease
RYGB case reports
Magee et al.
 29 year old woman with RYGB who failed treatment with
amoxicillin and nitrofurantoin, required IV abx
 Sobieraj et al.
 71 year old women with RYGB and complete gastrectomy
who needed larger doses of warfarin
Wills et al.
 3 cases of women with RYGB who had subtherapeutic
tamoxifen levels
Magee SR, et al. J Am Board Fam Med 2007; 20: 310–313
Sobieraj, et al. Pharmacotherapy 2008; 28(12):1537-41
Adami GF et al. Obes Surg 1991; 1: 293–294
RYGB case reports
Fuller et al.
 51 year old female with RYGB who required transient
increase in haloperidol dosage
Tripp et al
 1 Case of lithium toxicity after RYGB in patient on for 10 years
Fuller AK, et al. J Clin Psychopharmacol. 1986; 6: 376–377
Wills, SM, et al. Pharmacotherapy. 2010; 30(2):217
Tripp, AC. Journal of Clinical Physcopharmacology. 2011;31(2):261-2
RYGB case reports
Michelak et al.
 27 year old female with RYGB with lower levels of HIV
medications (lamivudine, zidovudine, lopinavir, ritonavir)
Knoll BM
 Isavuconazole in patient with RYGB required twice normal
dose to achieve therapeutic levels
Michelak DE, et al. J Int Ass of AIDS care. 2014; 1: 1-4
Knowll EM. Journal of Antimicrobial Chemotherapy. 2013; 3441- 43
RYGB: Alcohol
5 RYGB patients (no control)
Cmax
 After 2 minutes over driving limit of 0.08%
 Cmax was 0.138%
Tmax
 5.4 minutes
Steffen KJ, et al. Surgery for Obesity and Related Diseases. 2013; 9: 470-3
Steffen KJ, et al. Surgery for Obesity and Related Diseases. 2013; 9: 470-3
RYGB: Sertraline
5 matched RYGB patients
Excluded
 Ultra-rapid and poor metabolizers
 Drug interactions
AUC0-10.5
 RYGB vs. control (124 vs. 314, p 0.043)
 Range (62-198 vs. 195-508)
Roerig JL, et al. Surgery for Obesity and Related Diseases. [Epub ahead of print on
12/15/2014]
RYGB: Duloxetine
10 matched RYGB patients
Excluded
 Ultra-rapid and poor metabolizers
 Drug interactions
AUC0-∞
 RYGB vs. control (646.7 vs. 1191.9, p 0.017)
 Range (539-791 vs. 415 - 2426)
Roerig JL, et al. Journal of Clinical Psychopharmacology. 2013; 3: 479-84
RYGB: Azithromycin
14 matched RYGB patients
AUC0-24
 RYGB vs. control (1.41 vs. 2.07, p 0.008)
Peak
 RYGB vs. control (0.26 vs. 0.36, p 0.08)
Padwal R, et al. Journal of Antimicrobial Chemotherapy. 2012;67:2203-6
RYGB: Linezolid
4 patients before and 3 months after
RYGB
AUC0-∞
 After vs. before (98.9 vs. 41.6, p <0.05)
No change in bioavailability
Peak
 After vs. before (7.3 vs. 9.2)
Hamilton R, et al. Journal of Antimicrobial Chemotherapy. 2013;68:666-73
RYGB: Moxifloxacin
12 RYGB patients (crossover between IV
and oral)
 No change in bioavailability
 AUC and peak 50% higher than reference
De Smet J, et al. Journal of Antimicrobial Chemotherapy. 2012;67:226-9
RYGB: Atorvastatin
12 patients 5 weeks post RYGB
8 patients had increased atorvastatin
levels
3 patients with highest levels pre-surgery
had 2.6 fold decrease in levels
Why?
Skottheim IB, et al. Clinical Pharmacology and Therapeutics. 2009;86(3): 311-17
You should consider making what
change to the atorvastatin dose?
A.
Increase
B.
Decrease
C.
Discontinue
D.
No change
RYGB: Metformin
16 patients post RYGB versus match
controls
AUC0-∞ was calculated
 AUC0-∞ was increased by 21%
 Bioavailability increased by 50%
 A difference was seen in AUC glucose of
5.9ug/ml/hr over 8 hours
Padwal RS, et al. Diabetes Care. [Epub ahead of print on 04/08/2011]
RYGB: Pain medication
Morphine solution
 30 patients before and 6 months after RYGB
 AUC0-24
 After vs. before (54.7 vs. 44.8, p <0.05)
 Peak
 After vs. before (38.1 vs. 11.3, p<0.05)
Oxycodone
 Total gastrectomy
 No change in AUC; although compared to reference
Szalek R, et al. European Review for Medical and Pharmacological Sciences. 2014;18:3126-33
RYGB: Immunosuppresants
6 gastric bypass patients with ESRD
 Tacrolimus AUC0-∞ decreased 20%
 Sirolimus AUC0-∞ decreased 37%
 MMF AUC0-∞ decreased 38%
Rogers CC, et al. Clin Transplant. 2008; 22: 281–291
Other medication changes
Decreased need for medications for:
 Hypertension
 Diabetes
 Hyperlipidemia
One study conducted in 298 VA
patients found
 52% of patients discontinued DM medications
 40% discontinued HLD medications
Maciejewski ML, et al. Surgery for Obesity and Related Diseases. 2010;6:601-07
Our patients blood pressure and diabetes medications
may need to be
A.
Decreased
B.
Increased
C.
No change
General rules
 If efficacy or safety is a major concern
 Choose something that you can monitor
 Drugs most likely to display absorption issues
 Low bioavailability, high lipophilicity, and enterohepatic
circulation
 Avoid ER, EC, DR products if possible
 Administer medication via a different route
 Monitor patients clinically
Questions?
The most commonly used restrictivemalabsorptive bariatric surgery procedure is
A.
Roux-en-Y gastric bypass
B.
Vertical banded gastroplasty
C.
Adjustable gastric banding
D.
Biliopancreatic diversion
Post bariatric surgery patients have shown
decreased need for
A.
Antidepressants
B.
Gastric suppressant agents
C.
Diabetes medications
D.
Contraceptives
A post RYGB patient is likely to experience
decreased medication absorption if the
medication has/is
A.
Low bioavailability
B.
High lipophilicity
C.
Extended release
D.
All of the above
Common nutritional deficiencies in patients
undergoing gastric bypass surgery include
A.
Vitamin B12
B.
Iron
C.
Folate
D.
Vitamin A,D, E, K
E.
All of the above