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 active significantly in transporter is in the duodenum?
No duodenal absorption!
What if the drug undergoes enterohepatic recirculation?
Remember the grapefruit juice interaction with intestinal
Giuliano et al. Adv Pharmacoepidem Drug Safety. 2012; S1-6
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
Phenytoin (9)
Ethosuximide (1)
Rifampin (6)
Ethambutol (2)
Cyclosporine (2)
Tacrolimus (1)
Levothyroxine (2)
Ampicillin (6)
HCTZ (4)
Digoxin (9)
Padwal R, et al. Obesity Reviews. 2010;11:41-50
No Change
Isoniazid (9)
Ethambutol (7)
Phenazone (17)
Acetaminophen (3)
Digoxin (7)
Propylthiouracil (3)
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
B12
Iron
Folic acid
Vitamin D
RYGB
42.1%*
30%
20%
56.3%
Sleeve
5%
36.4%
18.4%
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
AUC 0-∞
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
AUC 0-24
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
AUC 0-∞
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
AUC
0-∞
was calculated
AUC
0-∞ 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
AUC 0-24
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 AUC
0-∞ decreased 20%
Sirolimus AUC
0-∞ decreased 37%
MMF AUC
0-∞ 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
