Transcript veltassa

Veltassa® - Patiromer
Manufacturer: Relypsa Inc.
FDA Approval Date: October 21, 2015
Veltassa®- Patiromer
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Veltassa® -
Patiromer
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Veltassa® - Patiromer
Veltassa®- Patiromer
Clinical Application
• Indications:
• Treatment of hyperkalemia
• Place in therapy:
• Patients who are receiving RAAS therapy
and have hyperkalemia
Veltassa® [package insert].
Veltassa®- Patiromer
Clinical Application
• Contraindications:
• Known hypersensitivity to patiromer or
any of its components
• Precautions:
• Hypomagnesemia
• Worsening of gastrointestinal motility
Veltassa® [package insert].
Veltassa®- Patiromer
Clinical Application
• Black Box warnings
• Patiromer binds to many orally
administered medications, which could
decrease their absorption and reduce their
effectiveness
• Administer other oral medications at least
6 hours before or 6 hours after patiromer
• Choose patiromer or the other oral
medication if adequate dosing separation
is not possible
Veltassa® [package insert].
Veltassa®- Patiromer
Clinical Application
• Pregnancy:
• Patiromer is not absorbed systemically
following oral administration and maternal
use is not expected to result in fetal risk
• Lactation:
• Patiromer is not absorbed systemically by
the mother, so breastfeeding is not
expected to result in risk to the infant
Veltassa® [package insert].
Veltassa®- Patiromer
Drug Facts
• Pharmacology:
• A cation exchange polymer that
increases fecal potassium excretion
through binding of potassium in the
lumen of the gastrointestinal tract,
resulting in a reduction of serum
potassium levels
Veltassa® [package insert].
Veltassa®- Patiromer
Drug Facts
• Pharmacokinetics:
•
•
•
•
A–
D–
M–
E–
N/A
N/A
N/A
N/A
• In radiolabeled ADME studies in rats and
dogs, patiromer was not systemically
absorbed and was excreted in the feces
Veltassa® [package insert].
Veltassa®- Patiromer
Drug Interactions
• Drug Interactions – Object Drugs:
• No formal drug studies have been
conducted in humans
• In in vitro binding studies, patiromer was
shown to bind about half of the oral
medications that were tested
• Administer other oral medications at
least 6 hours before or 6 hours after
patiromer
Veltassa® [package insert].
Veltassa®- Patiromer
Adverse Effects
• Common Adverse Effects:
• Constipation (7.2%)
• Hypomagnesemia (5.3%)
• Diarrhea (4.8%)
• Nausea (2.3%)
• Common Laboratory Abnormalities:
• Hypomagnesemia < 1.4mg/dL (9%)
• Hypokalemia < 3.5mEq/L (4.7%)
Veltassa® [package insert].
Veltassa®- Patiromer
Monitoring Parameters
• Efficacy Monitoring:
• Serum potassium at least weekly until
desired serum potassium target range
• Toxicity Monitoring:
• Serum potassium
• Serum magnesium
Veltassa® [package insert].
Veltassa®- Patiromer
Prescription Information
• Dosing:
• 8.4g by mouth daily; may titrate > 1 week
intervals to a max dose of 25.2g
• Administer with food 6 hours apart from
oral medications
• Mix the powder with water and consume
all of the powder
• Cost: – $714 - $1071
• UpToDate.com – accessed 3/13/15
Veltassa® [package insert].
Veltassa®- Patiromer
Literature Review
• Patiromer in Patients with Kidney
Disease and Hyperkalemia Receiving
RAAS Inhibitors
• Purpose: To assess the safety and
efficacy of patiromer in patients with
chronic kidney disease and
hyperkalemia that are receiving at
least one RAAS inhibitor
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Design: multinational, single-blind,
two-phase study
• Conducted at sites in:
Eastern Europe, European Union,
United States
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Initial treatment phase:
• N = 243 (4 weeks)
• 5.1 - <5.5mmol/L – mild hyperkalemia
(4.2g of patiromer twice daily)
• 5.5 - <6.5mmol/L – moderate-to-severe
hyperkalemia (8.4g of patiromer twice
daily)
• The dose could be adjusted to reach and
maintain a target potassium level
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Randomized withdrawal phase:
• N = 107 (8 weeks)
• > 5.5mmol/L at baseline of the initial
treatment phase and if their potassium
level was within 3.8 - <5.1mmol/L at the
end of the initial treatment phase
• Randomized in 1:1 ratio to continue the
same daily dose they were receiving at
the end of the initial treatment phase or
to receive placebo
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
Inclusion Criteria
Exclusion Criteria
• 18 – 80 years old
• Had stage 3 or stage 4 CKD
(15 - <60 mL/min/1.73m2)
• Serum potassium of 5.1 <6.5mmol/L at two
screenings
• Receiving a stable dose of
one or more RAAS inhibitors
for >28 days
• Doses of antihypertensives
had to be stable for >28
days
• Potassium-related EKG
changes
• Severe GI disorders
• Uncontrolled or unstable
arrhythmias
• Recent cardiac surgery
• Kidney or heart transplant
• ACS
• TIA or stroke within the past 2
months
• T1DM
• >180 or <110 systolic BP
• >110 or < 60 diastolic BP
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Initial treatment phase baseline characteristics:
• 58% male
• 64 years old
• 98% white
• 57% T2DM
• Serum potassium 5.6mmol/L
• eEGF 35.4 mL/min/1.73m2
• 54% using a non-RAAS-inhibitor diuretic
• 70% using ACE inhibitor
• 38% using an ARB
• 44% receiving maximal dose of RAAS inhibitor
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Results: Initial treatment phase
Dose group 1 Dose group 2
(5.1 (5.5 <5.5mmol/L)
<6.5mmol/L)
N=92
N=151
Primary
Endpoint:
Mean change
in serum
potassium
from baseline
to week 4
Mean daily
dose
Total
(5.1 <6.5mmol/L)
N=243
-0.64mmol/L
-1.23mmol/L
-1.01mmol/L
(95% CI,
-0.74 to -0.54)
(95% CI,
-1.31 to -1.15)
(95% CI,
-1.07 to -0.94)
12.8g/day
21.4g/day
N/A
Pvalue
<0.001
N/A
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Results: Initial treatment phase
• 76% of patients had serum potassium within
target range (3.8 – <5.1mmol/L) at end of
week 4
• To note, this phase 3 trial and the phase 2
trial both used BID dosing, yet the FDA
approved once daily dosing based off of the
total daily dose given to patients in the trials
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Results: Withdrawal treatment phase
Patiromer
Placebo
P-value
Start of phase to
week 4 of the phase
median change in
serum potassium
0mmol/L
0.72mmol/L
<0.001
>1 serum potassium
>5.5mmol/L through
week 8
15%
60%
<0.001
>1 serum potassium
>5.1mmol/L through
week 8
43%
91%
<0.001
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Adverse Events
Initial
Treatment
Withdrawal Treatment
Placebo (N=52)
Patiromer (N=55)
>1 Adverse event
47%
50%
47%
Constipation
11%
0%
4%
Diarrhea
3%
0%
4%
Nausea
3%
0%
4%
Hypomagnesemia
3%
N/A
N/A
Anemia
3%
N/A
N/A
Headache
N/A
8%
4%
Chronic renal failure
3%
N/A
N/A
Supraventricular extrasystoles
N/A
2%
4%
>1 Serious adverse event
1%
2%
0%
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Literature Review
• Conclusions:
• Patients with chronic kidney disease who
were taking RAAS inhibitors and who had
hyperkalemia, treatment with patiromer
was associated with reductions in serum
potassium levels and maintenance of
normal potassium levels
Weir, MR et al. N Engl J Med. 2015;Vol372:Pages 211-21.
Veltassa®- Patiromer
Summary
• Veltassa, patiromer, is a potassium binder indicated to
treat hyperkalemia. It is not to be used as emergency
treatment for life-threatening hyperkalemia because of
its delayed onset of action.
• Black box warning for patiromer binding to other oral
medications. The administration of other oral
medications should be given 6 hours before or 6 hours
after the administration of patiromer.
• Patiromer has 3 different doses (8.4 g, 16.8 g, 25.2 g
once daily) that can be adjusted at > 1 week intervals
based on the patient’s serum potassium levels.
• Most common adverse drug effects include:
constipation, hypomagnesemia, diarrhea, and nausea.
Veltassa®- Patiromer
References
1. https://www.veltassa.com
2. Veltassa package insert. Relypsa Inc. Oct. 2015.
3. Bakris, GL et al. Effect of patiromer on serum
potassium level in patients with hyperkalemia and
diabetic kidney disease: The AMETHYST-DN
Randomized Clinical Trial. JAMA. 2015 Jul
14;314(2):151-61.
4. Weir, MR et al. Patiromer in patients with kidney
disease and hyperkalemia receiving RAAS
inhibitors. N Engl J Med. 2015 Jan 15;372(3):21121.