Download HIV Management in the Primary Care Setting

Management of the transplant patient in the
primary care setting
Katee Lira, PharmD
Ambulatory Care Clinical Pharmacist, St. Vincent Indianapolis
Assistant Professor of Pharmacy Practice, Manchester University
April 20, 2016
I have no actual or potential conflicts of interest to disclose.
 Identify the primary care providers’ role in management of
solid organ transplant patients
 Describe how transplant medications contribute to metabolic
disorders
 Develop a “checklist” for appropriate considerations in primary
care patients with a solid organ transplant
 Identify common adverse effects of transplant medication
 PCPs have an important role in improving outcomes of
transplant recipients
 Outcomes after transplant have improved, with an increasing
number of long-term survivors
 Metabolic syndrome, CVD, renal dysfunction, and malignancies
are leading causes of morbidity/mortality
 Some centers defer management of metabolic syndrome and
medical complications to PCPs
McCashland TM. Liver Transpl 2001; 7:S2.
Steroids
Tacrolimus (CNI)
Cyclosporine (CNI)
Mycophenalate mofetil
Azathioprine
Sirolimus
Triple drug combination:
• Glucocorticoid
• Calcineurin inhibitor (CNIs)
• Purine antagonist (mycophenalate)
Steroid is weaned off or decreased
to lowest dose
Once stable, can sometimes be only
monotherapy
• Typically a calcineurin inhibitor
Neurotoxicity, hair
loss, insomnia
CVD
GERD, nausea
Metabolic
abnormalities
(DM, HLD)
Diarrhea
Reduced bone
mineral density
Nephrotoxicity
Gout
Long-Term Management of Adult Liver Transplant: 2012 Practice Guideline by AASLD and AST
DRUGS
ADVERSE EFFECTS
Steroids
Hypertension, diabetes, hyperlipidemia, bone disease, weight
gain, impaired wound healing, cataracts, psychological changes
Tacrolimus
Tremors, nephrotoxicity, neurotoxicity, diabetes, hypertension,
gout, hyperkalemia, hyperlipidemia
Cyclosporine
Tremors, nephrotoxicity, diabetes, hypertension, gout,
hyperkalemia, hyperlipidemia, neurotoxicity, increased hair/gum
growth
Mycophenolate mofetil
N/V/D, neutropenia, anemia
Azathioprine
Sirolimus
Neutropenia, anemia, liver inflammation, hair loss, acute
pancreatitis
Tremors, hyperlipidemia, thrombocytopenia, neutropenia, anemia,
poor wound healing
 Numerous drugs that interact with immunosuppressants
 Check for drug-interactions before starting new medications
 P-glycoprotein
 Cyclosporine
 Tacrolimus
 CYP 3A4
 Cyclosporine
 Tacrolimus
 Sirolimus
Drug
Pregnancy
Category
Concerns
Steroids
C/D
First trimester use associated with oral clefts; decreased birth
weight; recommended to use lowest dose for shortest duration
Tacrolimus
C
Lower birth weights, fetal mortality, hyperkalemia in infants,
renal toxicity, maternal toxicity
Cyclosporine
C
Not teratogenic. May be used in pregnant transplant patients
Mycophenalate
D
Boxed Warning: increased risk of congenital malformations
and first trimester pregnancy loss. Effective contraception
must be started before and continued for 6 weeks after d/c
Azathioprine
D
Congenital anomalies, hematologic toxicities, and intrauterine
growth retardation. Better alternative than MMF.
Sirolimus
C
Not teratogenic, lower birth weights, fetal mortality. Effective
contraception must be started before therapy and continued
for 12 weeks after d/c
 Pregnancies are considered high risk
 Delay pregnancy for 1-2 year(s) post-transplant
 CNIs should be continued and monitored closely
 Barrier method required with mycophenolate
 IUDs are less effective with azathioprine
A pregnancy registry has been established for pregnant women taking
immunosuppressants following any solid organ transplant.
National Transplantation Pregnancy Registry, 877-955-6877
Long-Term Management of Adult Liver Transplant: 2012 Practice Guideline by AASLD and AST
 65 yoM with a kidney transplant is on cyclosporine and azathioprine.
He also has T2DM, HTN, OA and depression.
 ASCVD 10-year risk of 21.5%, LDL 107
 Is a statin indicated in this patient? If so, what regimen would you
initiate?
AYES
Initiate
atorvastatin 40
mg daily
B YES
Initiate
simvastatin
40 mg daily
CYES
Initiate
rosuvastatin
mg daily
5
 Per the lipid guidelines, this patient qualifies for a high intensity
statin
 However, atorvastatin is contraindicated with cyclosporine
 Your patient develops rhabdomyolysis and is hospitalized
Dagnabbit Doctor! Here’s to better luck next time…
 Per the lipid guidelines, this patient qualifies for a high intensity
statin
 However, simvastatin is contraindicated with cyclosporine
 Your patient develops rhabdomyolysis and is hospitalized
Dagnabbit Doctor! Here’s to better luck next time…
 Per the lipid guidelines, this patient qualifies for a high intensity
statin
 However, the max dose of rosuvastatin is 5 mg/day in patients
who are also on cyclosporine
 The patient presents to your next visit in 3 months and her LDL is
68. She has no complaints or concerns.
Congratulations Doctor! Continue to the next adventure…
Statin
Cyclosporine
Tacrolimus
Atorvastatin
CONTRAINDICATED
No dose adjustment, monitor
Fluvastatin
Limit fluvastatin to 20 mg BID
Lovastatin
CONTRAINDICATED
Pitavastatin
CONTRAINDICATED
Pravastatin
Limit pravastatin to 20 mg/day
Rosuvastatin
Limit rosuvastatin to 5 mg/day
Simvastatin
CONTRAINDICATED
No dose adjustment, monitor
No dose adjustment, monitor
 65 yoM with a kidney transplant is on cyclosporine and azathioprine.
He also has T2DM, HTN, OA and depression.
 ASCVD 10-year risk of 21.5%, LDL 107
 Is a statin indicated in this patient? If so, what regimen would you
initiate?
AYES
Initiate
atorvastatin 40
mg daily
B YES
Initiate
simvastatin
40 mg daily
CYES
Initiate
rosuvastatin
mg daily
5
 Incidence of HLD: 40-66%
 Significant elevations in total cholesterol are typical
 Changes seen 3-6 months after transplantation
 Annual fasting lipid profile
 Treatment is similar to treatment in non-transplant patient
 Statins are safe and effective
 Complicated by drug interactions
BioDrugs 2001; 15 (4)
Long-Term Management of Adult Liver Transplant:2012 Practice Guideline by AASLD and AST
Pretransplantation CVD
Hyperlipidaemia
Hyperhomocysteinemia
Hypertension
Diabetes mellitus
Smoking
Acute rejection episodes
Graft failure
Direct effects of immunosuppressive agents
BioDrugs 2001; 15 (4)
BioDrugs 2001; 15 (4)
 Incidence of CAD 9-25%
 ALL agents require close follow-up
 Strict management of CVD risk factors is recommended
 Annual rate of fatal or nonfatal CVD events in kidney
transplant patients is 2x higher than general population
Fouad T. Transplantation. 2009;87(5):763
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54 yo AA male s/p liver transplantation
Antirejection regimen tacrolimus and mycophenalate
Patients BP is 148/92 despite steroids being weaned
What antihypertensive agent would you start in this patient?
A ACEI
Initiate lisinopril
10 mg daily
B HCTZ
Initiate HCTZ 25
mg daily
C DHPCCB
Initiate
amlodipine 5mg
daily
 Patient is started on lisinopril 10mg and BP reaches goal with no
complications
 ACEIs/ARBs can be used but with caution
 May have problematic effects on renal function and hyperkalemia
 After early post-transplant, ACEIs/ARBs may be beneficial
 Nephroprotective effect
 Antifibrotic effect
 Close monitoring for hyperkalemia is recommended for both
ACEIs/ARBs when used in association with CNIs
Congratulations Doctor! Continue to the next adventure…
 Hydrochlorothiazide 25mg daily is started and patient develops
hyperuricemia causing a gout flare
 Diuretics are not used as primary therapy for hypertension in
transplant patients
 Concerns:
 Excerbate electrolyte disturbances
 Risk for hyperuricemia
 Renal dysfunction
 If thiazides or loop diuretics must be used, close follow-up is required
Dagnabbit Doctor! Here’s to better luck next time…
 Patient is started on amlodipine 5mg and BP reaches goal with
no complications
 DHP-CCBs are the preferred first-line agents
 Amlodipine
 Nifedipine
 Cause vasodilation of renal afferent arterioles
 Minimally interact with CNIs, and have limited side effects
Congratulations Doctor! Continue to the next adventure…
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54 yo AA male s/p liver transplantation
Antirejection regimen tacrolimus and mycophenalate
Patients BP is 148/92 despite steroids being weaned
What antihypertensive agent would you start in this patient?
A ACEI
Initiate lisinopril
10 mg daily
B HCTZ
Initiate HCTZ 25
mg daily
C DHPCCB
Initiate
amlodipine 5mg
daily
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

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Incidence 40-85%
Target blood pressure is <140/90
Up to 30% of patients require 2 or more agents
Monitoring: weekly home monitoring and monthly office
readings x6 months post-transplant, then Q6 months
 Preferred agents
 DHP CCBs (amlodipine, nifedipine)
 ACEIs/ARBs
 Use with caution
 Non-DHP CCBs (diltiazem, verapamil)
 Diuretics (hydrochlorothiazide, furosemide)
Ann Pharmacother 2010;44:1259-70
Long-Term Management of Adult Liver Transplant:2012 Practice Guideline by AASLD and AST.
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38 yo Hispanic female s/p kidney transplantation
Antirejection regimen tacrolimus and mycophenalate
Family history is not significant for DM and her BMI is 24.1
Do you need to screen her for diabetes? If so, what is the most
appropriate frequency?
A YES
Screen every 3
years
B NO
Does not have
risk factors for
diabetes
screening
C YES
Screen every
year
 The patient is screened for diabetes and does not have newonset diabetes mellitus after transplantation (NODAT) upon
initial screening
 Patient is not screened for three years and within that time she
develops new-onset diabetes mellitus after transplantation
(NODAT) that is unrecognized
 Her uncontrolled diabetes leads to graft failure
Dagnabbit Doctor! Here’s to better luck next time…
 The patient is not screened for diabetes until she is 45
 She develops new-onset diabetes mellitus after transplantation
(NODAT) that is unrecognized
 Her uncontrolled diabetes leads to graft failure
Dagnabbit Doctor! Here’s to better luck next time…
 The patient is screened and found to have new-onset diabetes
mellitus after transplantation (NODAT)
 She is started on appropriate treatment and does not develop
complications of uncontrolled diabetes
Congratulations Doctor! Continue to the next adventure…


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38 yo hispanic female s/p kidney transplantation
Antirejection regimen tacrolimus and mycophenalate
Family history is not significant for DM and her BMI is 24.1
Do you need to screen her for diabetes? What is the most
appropriate frequency?
A YES
Screen every 3
years
B NO
She does not
have risk factors
for diabetes
screening
C YES
Screen every
year
 Incidence 30-40%
 Negatively affects graft and patient survival
 Annual screening is recommended
 Management is similar to general population
 Insulin may be required in the early post-txp period
 Oral hypoglycemic agents are safe and effective later
2008 European Society for Organ Transplantation 22 (2009) 519–530
Long-Term Management of Adult Liver Transplant: 2012 Practice Guideline by AASLD and AST
 More common with the current obesity epidemic
 Associated with CVD, graft failure, and death
2008 European Society for Organ Transplantation 22 (2009) 519–530
 Common among patients who have transplants
 Incidence of 50-60%
 Combination of
 Hypertension
 Insulin resistance/diabetes
 Dyslipidemia
 Obesity
 Immunosuppressant use is associated with all aspects of the
metabolic syndrome
2008 European Society for Organ Transplantation 22 (2009) 519–530
Long-Term Management of Adult Liver Transplant: 2012 Practice Guideline by AASLD and AST
 The risk of fractures following transplantation is high
 DEXA scan
 Pre-transplant
 6 months to 1 year after transplantation
 Then recommended every 2-3 years post transplant
 Management of osteoporosis is similar to that for the nontransplant general population
 Weight-bearing exercises
 Supplementation with calcium and vitamin D
 Bisphosphonates
Long-Term Management of Adult Liver Transplant: 2012 Practice Guideline by AASLD and AST
 63 yo Caucasian male with HCV due to IVDA received a liver
transplant
 Anti-rejection regimen of mycophenolate/tacrolimus
 He is complaining of GERD symptoms. What PPI would you start?
A Protonix B
Initiate
pantoprazole
40mg daily
Dexilant
Initiate dexlansoprazole
30mg daily
C Nexium
Initiate
esomeprazole
40mg daily
 This patient begins pantoprazole as directed and his GERD
symptoms are relieved
 Patient has no interaction with tacrolimus and does not develop
complications
Congratulations Doctor! Continue to the next adventure…
 This patient begins dexlansoprazole as directed and his GERD
symptoms are relieved
 Dexlansporazole interacts with tacrolimus and causes increased
tacrolimus levels
 Patient develops tremors
Dagnabbit Doctor! Here’s to better luck next time…
 This patient begins esomeprazole as directed and his GERD
symptoms are relieved
 Esomeprazole interacts with tacrolimus and causes increased
tacrolimus levels
 Patient develops tremors
Dagnabbit Doctor! Here’s to better luck next time…
 63 yo caucasian male with HCV due to IVDA received a liver
transplant
 Anti-rejection regimen of mycophenolate/tacrolimus
 He is complaining of GERD symptoms. What PPI would you start?
A Protonix B
Initiate
pantoprazole
40mg daily
Dexilant
Initiate dexlansoprazole
30mg daily
C Nexium
Initiate
esomeprazole
40mg daily
 Diarrhea
 Caused by mycophenolate and tacrolimus
 May treat with loperamide
 Switching CellCept  Myfortic (specialist to manage)
 GERD
 Antacids
 May decrease the absorption of mycophenolate
 Separate mycophenolate and antacids by at least 2 hours
 PPIs
 May decrease the absorption of mycophenolate
 May increase concentration of tacrolimus
 Use of pantoprazole preferred
 H2RAs
 Use of ranitidine or famotidine preferred
 Incidence 10% to 20%
 Hyperuricemia occurs in a larger number of CNI-treated patients
 Acute attacks may be treated with colchicine or steroids
 Avoid NSAIDs due to risk of nephrotoxicity
 Allopurinol should be avoided/used with caution in patients who are
taking azathioprine
 Colchicine and allopurinol require dose adjustments in patients with
reduced renal function
Shibolet O. Transplantation 2004; 77:1576.
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58 yo white female with liver transplant due to hx of alcoholism
Antirejection regimen includes tacrolimus
PPV23 (Pneumovax) received 10/15/2012
Does the patient require further pneumococcal vaccination?
A NO
She is already
adequately
protected
against
pneumococcal
disease
B YES
One dose of
PCV13 today,
then second
PPSV23 5 years
from first
C YES
Another dose of
PPSV23 five
years after the
original dose
 It is recommended that this patient receive a dose of PCV13
one year after the original PPSV23 vaccination
 It is also recommended that she be revaccinated with PPSV23 5
years from the first dose
 Without further vaccinations, this patient is not appropriately
immunized and is at risk for pneumococcal infection
Dagnabbit Doctor! Here’s to better luck next time…
 After receiving the PCV13 vaccination today, the patient is
appropriately immunized against pneumococcal infection
 The patient receives the second dose of PPSV23 in 5 years, and
has a reduced risk of pneumococcal infections
Congratulations Doctor! Continue to the next adventure…
 Recommended that this patient receive a dose of PCV13 one
year after the original PPSV23 vaccination
 Revaccinated with PPSV23 5 years from the first dose
 Without the PCV13 vaccination, this patient is not appropriately
immunized and is at risk for pneumococcal infection
Dagnabbit Doctor! Here’s to better luck next time…
 If no previous pneumococcal vaccination:
PCV13
now
PPSV23
in 8 weeks
PPSV23 5
years later
 If previous pneumococcal vaccination with PPSV23:
PCV13 after
at least 1
year
PPSV23
5 years later
ACIP 2016 Adult Immunization Schedule
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58 yo white female with liver transplant due to hx of alcoholism
Antirejection regimen includes tacrolimus
PPV23 (Pneumovax) received 10/15/2012
Does the patient require further pneumococcal vaccination?
A NO
She is already
adequately
protected
against
pneumococcal
disease
B YES
One dose of
PCV13 today,
then second
PPSV23 5 years
from first
C YES
Another dose of
PPSV23 five
years after the
original dose
Pre-Transplant
Post-Transplant
Influenza-inactivated
Influenza-live attenuated
Recommended
X (may be given ≥2 weeks prior)
Recommended
X
PCV13
PPSV23
Recommended
Recommended
Recommended*
Recommended*
Hep B
Recommended
Recommended*
Hep A
Recommended
Recommended*
Tdap, Td
If indicated
If indicated
HPV
If indicated
If indicated
Meningiococcal
If indicated
If indicated
Polio
If indicated
If indicated
MMR
If indicated
X
Rotavirus
If indicated
X
Varicella
If indicated and ≥4 weeks prior
X
Zostavax
If indicated and ≥4 weeks prior
X
*if not vaccinated prior to transplant
ACIP 2016 Adult Immunization Schedule
 If possible, vaccinate prior to transplant
 Delay until prednisone dose is <20 mg/day
 Live-attenuated vaccines should be avoided after transplant
 Prophylactic pneumococcal and influenza vaccine for all
American Journal of Transplantation 2013; 13: 311–317
 Many of these patients die with functioning grafts
 Primary care providers have an important role in improving
outcomes of transplant recipients
 Important items to monitor in the primary care setting:
Metabolic abnormalities
Cardiovascular risks
Contraceptive
GI complaints
Drug interactions
Osteoporosis
Vaccinations
Management of the transplant patient in the
primary care setting
Katee Lira, PharmD
Ambulatory Care Clinical Pharmacist, St. Vincent Indianapolis
Assistant Professor of Pharmacy Practice, Manchester University
April 20, 2016
I have no actual or potential conflicts of interest to disclose.