Transcript New Drug Update

New Drug Update
2014-2015
Deborah Sturpe, PharmD, MA, BCPS
[email protected]
The speaker has no actual or potential disclosures to report.
Objectives
Focusing on drugs likely to be used outpatient and already
on the market:
1. Identify basic package insert information (e.g. indication,
dosing, drug interactions) for each drug presented;
2. Compare and contract each new drug to any existing
drugs in the same therapeutic class; and
3. Determine place in therapy of each new drug as
compared to currently available modalities for the indicated
condition(s).
2
Starting with the Toes…
JUBLIA® (efinaconazole)
KERYDIN® (tavaborole)
3
Efinaconazole (Jublia®) & Tavaborole (Kerydin®)
Efinaconazole
Indication(s)
Tavaborole
Onychomycosis (T. rubrum & T. mentagrophytes)
Class
Azole antifungal
Oxaborole antifungal
How Supplied
10% solution, 4 mL & 8 mL
5% solution, 4 mL & 10 mL
Dosing
How to Apply
Competing Agents
Daily x 48 weeks

Squeeze one drop onto toenail and (for big toe) second
drop to end of toenail

Spread with brush or tip to cover entire toenail, cuticle,
folds of skin, and underneath nail
 Ciclopirox (Penlac®) – topical
 Terbinafine HCl – oral
4
Onychomycosis Treatment: Cure Rate vs. Cost
Treatment
Course
Cure Rate
Relapse Rate
Course of
Treatment AWP
Terbinafine
12 weeks
46%
21%
$1170
Efinaconazole
48 weeks
17%
na
$5200
Tavaborole
48 weeks
<10%
na
$4720
Ciclopirox
48 weeks
7%
40%
$125

Cost-benefit favors systemic therapy

Topical advantages – no systemic absorption or drug interactions.
Mild, local skin adverse reactions

Topical disadvantages – high cost and lower efficacy

Topical agent with strongest data to support use = efinaconazole
Pharmacists Letter Detail Document #300807
5
Moving to the Lungs…
STRIVERDI® RESPIMAT® (olodaterol)
STIOLTO™ RESPIMAT® (olodaterol-tiotropium)
6
COPD Treatment Guidelines (GOLD 2015)
 First line = bronchodilators
 No preference for anticholinergic vs beta-agonist
 Long-acting formulations preferred over short-acting
 Combination beta-agonist + anticholinergic reasonable in
patients with severe SOB
 Inhaled steroids indicated for patients with more severe
disease that is unresponsive to bronchodilators alone
http://www.goldcopd.org/uploads/users/files/GOLD_Report_2015_Apr2.pdf
7
Olodaterol (Respimat®)
Indication(s)
COPD
Class
Long-acting beta2-adrenergic agonist
How Supplied
60 or 28 metered actuations
Dosing
2 inhalations (5 mcg) once-daily
Contraindications
Asthma
Drug Interactions
MOA inhibitors; TCAs; Beta-blockers
Competing Agents
arformoterol (nebulized solution)
formotrol (Aerolizer®)
indacaterol (Neohaler™)
salmeterol (Diskus®)
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Olodaterol-Tiotropium (Respimat®)
Indication(s)
COPD
Class
Long-acting beta2-adrenergic agonist and
long-acting anticholinergic combination
How Supplied
60 or 28 metered actuations
Dosing
2 inhalations (5-5 mcg) once-daily
Contraindications
Asthma
Drug Interactions
MOA inhibitors; TCAs; Beta-blockers; Strong
anticholinergics
Competing Agents
umeclidinium/vilanterol (Anoro Ellipta®)
9
Olodaterol Products – OTHER TIDBITS
 Dispense with medication guide
 Inhaler must be discarded 3 months after assembly
 Inhaler must be primed
 Pneumonic for inhaler use is TOP
 Twist the clear base
 Open the cap
 Press the dose release button
 Dose release button will not work if base not twisted
 Inhaler will “lock” when empty (base cannot be twisted)
10
Olodaterol vs. Placebo1
Olodaterol vs. Formoterol vs. Placebo2
Olodaterol vs. Tiotropium vs. Combo3
 Versus placebo:
 Significant improvements in lung function
 Reductions in COPD exacerbations (~7-10% absolute)
 Improved patient global ratings and quality of life
scores
 Versus formoterol = No difference
 Combination therapy better than monotherapy
 No noteworthy ADRs
1. Ferguson GT et al. Int J COPD. 2014;9:629-645.
2. Koch A et al. Int J COPD. 2014;9:697-714.
3. Buhl R et al. Eur Respir J. 2015;45:869-871.
11
Olodaterol Products – PLACE IN THERAPY
Selections between and within anticholinergic and betaagonist classes will primarly be driven by:
 Ability of patient to use device
 Cost and insurance coverage
AWP pricing per month

Olodaterol = $186.84

Indacaterol = $241.82

Formoterol = $291.55

Salmeterol = $326.62

Vilanterol/umeclidinium = $357.37

Olodaterol/tiotropium
= $378.82 (Tiotropium alone = $378.82)
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Onto the GI system:
MOVANTIK™ (naloxegol)
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Naloxegol (Movantik™)
Indication(s)
Opioid-induced constipation (chronic non-cancer pain)
Class
Peripherally-acting µ-opioid receptor antagonist
Pegylated derivative of naloxone
How Supplied
12.5 mg and 25 mg tablets
Dosing
25 mg q AM (reduce to 12.5 mg if unable to tolerate)
CrCl < 60 mL/min: 12.5 mg q AM (increase if able)
Contraindications
GI obstruction, strong CYP3A4 inhibitors
Drug Interactions
Moderate CYP3A4 inhibitors, including grapefruit (reduce)
CYP3A4 inducers (avoid due to possible lack of effect)
Competing Agents
Relistor® (methylnaltrexone) – Subcutaneous injection
Amitiza® (lubiprostone) – Oral
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Naloxegol (Movantik®) – OTHER TIDBITS
 Requires medication guide
 Take on empty stomach around first meal of day
(at least 1 hour before or 2 hours after)
 Discontinue maintenance laxative therapy
 Laxative rescue indicated if suboptimal response after
three days
15
KODIAC Clinical Trials – Efficacy Results
KODIAC-04
KODIAC-05
Placebo
Naloxegol
12.5 mg
Naloxegol
25 mg
Placebo
Naloxegol
12.5 mg
Naloxegol
25 mg
Response Rate*
%
29.4
40.8
44.4
29.3
34.9
39.7
p-value
--
0.02
0.001
--
0.2
0.02
NNT
--
8.8
6.7
--
N/A
9.7
*Response rate definition: ≥ 3 spontaneous bowel movements per week for at least 9 of 12 treatment weeks and at least 3 of
the final 4 treatment weeks.
Other findings:

Response seen regardless of previous laxative failure

Average time to first BM 6-12 hours after dose

Improved severity of straining and stool consistency

Effect seen across opioid doses without loss of pain control
Chey WD, et al. NEJM. 2014;370:2387-96.
16
KODIAC Clinical Trials – Safety Data
KODIAC-04
% of patients
KODIAC-05
KODIAC-08
Placebo
Naloxegol
Placebo
Naloxegol Usual Care
Naloxegol
Any AE
46.9
61.2
58.9
69.0
72.2
81.8
Abdominal pain
3.3
12.6
7.8
19.0
3.3
17.8
Diarrhea
4.2
9.3
4.3
9.1
5.9
12.9
Nausea
4.7
7.5
4.3
8.6
4.1
9.4
Back pain
2.3
3.3
1.7
5.2
8.9
9.0
Headache
1.9
3.7
3.5
5.2
4.8
9.0
Flatulence
1.9
5.6
3.0
6.0
1.1
6.9
Upper abd. pain
1.9
5.1
1.3
2.6
1.1
5.1
Chey WD, et al. NEJM. 2014;370:2387-96.
Webster L, et al. Aliment Pharmacol Ther. 2014;40:771-79.
17
Naloxegol (Movantik®) – PLACE IN THERAPY
 AWP pricing per month

Lubiprostone
= $ 377.40

Methylnaltrexone
= $2,594.10

Naloxegol
= $ 299.40
AFTER stimulant or osmotic failure:
•
•
Probably best to try lubriprostone or naloxegol first
•
Naloxegol may be slightly more effective
•
Lubiprostone lacks drug interations
Reserve methylnaltrexone due to cost, subQ route, and higher
incidence of opioid withdrawal
18
Don’t forget the heart…
CORLANOR® (ivabradine)
ENTRESTO™ (sacubitril-valsartan)
19
HFrEF Guidelines for Symptomatic Patients
 ACE inhibitor
• ARB if ACE intolerant
• Hydralazine-Nitrates if ACE and ARB intolerant
 Evidence-based beta-blockers
 Aldosterone antagonist for NYHA class II-IV
 Loop diuretic if volume overload present
 Hydralazine-Nitrates for African Americans with NYHA class III-IV if
persistent symptoms despite the above
ACCF/AHA Guideline. Circulation 2013;128:e240-e327. 20
Ivabradine (Corlanor®)
Indication(s)
HFrEF (provided in sinus rhythm, HR ≥ 70, and on or intolerant to max
beta-blocker)
Class
Hyperpolarization-activated cyclic nucleotide-gated channel blocker
MOA: binds funny current channels in SA node to slow depolarization
How Supplied
5 mg and 7.5 mg tablets
HR > 60: increase to 7.5 mg BID
HR 50-60: maintain 5 mg BID
HR < 50: decrease to 2.5 mg BID
Dosing
5 mg po BID x 14 days
Contraindications
Acute decompensated disease
BP < 90/50
HR < 60
Severe hepatic impairment
Strong CYP3A4 inhibitors
Drug Interactions
Moderate CYP3A4 inhibitors and any 3A4 inducer (avoid)
Competing Agents
None
21
Ivabradine (Corlanor®) – OTHER TIDBITS
 Requires medication guide
 Take with meals
 Not compatible with pregnancy or breastfeeding
22
Ivabradine – Efficacy & Safety
SHIFT (Swedberg K, et al. Lancet 2010;376:875-85.)
Selected Baseline Characteristics
Age 60
Male 76%
Baseline HR 80
Caucasian 89%
Asian 8%
Other 3%
Previous MI 56%
HTN 67%
DM 30%
NYHA Class
Class I – 0%
Class II – 49%
Class III – 50%
Class IV – 2%
Other Medications
ACE or ARB 93%
Beta-blocker 89%
Outcomes
Ivabradine (n=3241)
Placebo (n=3264)
p-value
All-cause mortality
16%
17%
0.092
Death from HF
3%
5%
0.014 (NNT 50)
HF hospitalizations
16%
21%
<0.001 (NNT 20)
Aldosterone antagonist 60%
Potential Harms:

Atrial fibrillation (NNH ranges 100-208)

Sudden change in brightness of light (usually resolves)
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Sacubitril-Valsartan (Entresto™ aka LCZ696)
Indication(s)
HFrEF
Class
Neprilysin inhibitor (combined with ARB)
MOA: increases levels of natriuretic peptides (as well as bradykinin
and adrenomedullin) which leads to vasodilation, diuresis, natriuresis,
and antiproliferative effects and decreased ATII production
How Supplied
24/26 mg, 49/51 mg, and 97/103 mg tablets
49/51 mg po BID, then double q 2-4 weeks to 97/103 mg BID target
Dosing
Start at 24/26 mg if:
• ACE or ARB naïve or only on low dose previously
• eGFR < 30
• Moderate hepatic impairment (avoid use if severe)
Contraindications
Previous ACE or ARB angioedema
Concurrent therapy with ACE inhibitor or aliskiren in DM patients
Competing Agents
None
24
Sacubitril-Valsartan (Entresto™)
Efficacy & Safety
PARADIGM-HF (McMurray JJV et al. NEJM 2014;317:993-1004.)
Selected Baseline
Characteristics
Age 64
Male 78%
White 66%
Asian 18%
Black 5.1%
NYHA Class
Class I – 4.5%
Class II – 70%
Class III – 24%
Other Medications
Previous ACE or ARB 90%
Beta-blocker
93%
HTN 71%
DM 35%
Previous MI 43%
Class IV – 5%
Aldosterone antagonist 55%
Sacubitril-Valsartan
(n=4187)
Enalapril
(n=5212)
p-value
17%
19.8%
<0.001 (NNT 36)
CV death
13.3%
16.5%
<0.001 (NNT 31)
HF hospitalizations
12.8%
15.6%
<0.001 (NNT 36)
Symptomatic hypotension
14%
9.2%
<0.001 (NNH 21)
Scr ≥ 2.5
3.3%
4.5%
0.007
Angioedema
0.2%
0.1%
NS
Outcomes
All-cause mortality
25
Ivabradine and Sacubitril-Valsartan:
PLACE IN THERAPY
 Anticipate adoption of sacubitril-valsartan combination by many
cardiologists due to impressive NNT and relative safety
 Ivabradine less impressive – no impact on mortality and concern
over new Afib. Unsure if worth the cost.
AWP pricing per month

Generic HF regimen with ACE or ARB, beta blocker, aldosterone
antagonist and diuretic is under $150

Sacubitril-Valsartan = $225

Ivabradine
(valsartan alone = $150)
= $225
26
There’s always diabetes…
FARXIGA® (dapagliflozin)
JARDIANCE® (empagliflozin)
TANZEUM® (albiglutide)
TRULICITY™ (dulaglutide)
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5/29/09
Presentation Title
28
ADA Guidelines. Diabetes Care 2015. Suppl 1.
Sodium-Glucose Co-Transporter 2 (SGTL2) Inhibitors
Dapagliflozin
(Farxiga®)
Empagliflozin
(Jardiance®)
Canagliflozin
(Invokana®)
How Supplied
5 mg & 10 mg tabs
10 mg & 25 mg tabs
100 mg & 300 mg tabs
Dosing
5-10 mg po q AM
10-25 mg po q AM
100-300 mg po q AM
Renal
Considerations
Do not use eGFR < 60
Do not use eGFR < 45
Do not use eGFR < 45
Max 100 mg if 45-60
A1c Lowering
0.5-1%
Other Benefits
Low rates of hypoglycemia
Weight loss (3-6 kg)
Reduced blood pressure (up to 10 mmHg)
Pharmacists Letter Detail Document #310601
Facts and Comparisons eAnswers 30
Sodium-Glucose Co-Transporter 2 (SGTL2) Inhibitors
Dapagliflozin
(Farxiga®)
New Warning
Empagliflozin
(Jardiance®)
Ketoacidosis
Dehydration
Genital fungal infections
UTI
Increased LDL
Side Effects &
Risks
Bladder cancer
AWP per Month
CoFormulations
Canagliflozin
(Invokana®)
Stroke
$410
$410
$410
With metformin
With linagliptin
With metformin
Pharmacists Letter Detail Document #310601
Facts and Comparisons eAnswers 31
Glucagon-like Peptide-1 (GLP-1) Receptor Agonists
Albiglutide
(Tanzeum®)
Route
Dulaglutide
(Trulicity™)
Exenatide
(Byetta®)
(Bydureon®)
Liraglutide
(Victoza®)
Subcutaneous injections
How Supplied
Single-dose
pen*
Single-dose
pen
Multi-dose
pen
Single dose
pen*
Multi-dose
pen
Dosing
30-50 mg
once weekly
0.75-1.5 mg
once weekly
5-10 mcg
BID
2 mg
once weekly
1.2-1.8 mg
once daily
A1c Lowering
1-1.5%
Other Benefits
Weight loss (1-2.5 kg)
* Pen device requires mixing process prior to use
Pharmacists Letter Detail Documents #310601 and #301204
Facts and Comparisons eAnswers 32
Glucagon-like Peptide-1 (GLP-1) Receptor Agonists
Exenatide
Albiglutide
(Tanzeum®)
Dulaglutide
(Trulicity™)
(Byetta®)
(Bydureon®)
Liraglutide
(Victoza®)
Nausea rate
11%
12.5-21%
8%
11%
28%
Injection site
reaction rate
18%
0.5%
13%
17%
2%
$610
$510-770
Diarrhea
Headache
Pancreatitis
Thyroid cancer concern
Other Side
Effects & Risks
AWP per
Month
$425
$640
$620
* Pen device requires mixing process prior to use
Pharmacists Letter Detail Documenst #310601 and #301204
Facts and Comparisons eAnswers 33
Ending with the CNS:
BELSOMRA® (suvorexant)
34
Suvorexant (Belsomra®)
Indication(s)
Insomnia (onset and maintenance)
Class
Orexin receptor antagonist
How Supplied
5 mg, 10 mg, 15 mg, and 20 mg tablets
Dosing
10 mg q HS (usual dose)
Contraindications
Narcolepsy
Drug Interactions
Strong CYP3A4 inhibitors (avoid)
Moderate CYP3A4 inhibitors, including grapefruit (5 mg)
Strong CYP3A4 inhibitors (may reduce effect)
Competing Agents
Benzodiazepines (various)
GABA-acting hypnotics (eszopiclone, zaleplon, zolpidem)
Ramelteon
35
Suvorexant (Belsomra®) – OTHER TIDBITS
 C-IV designation
 Medication guide required
 Take within 30 minutes of going to bed and assure 7 hours
remain before awakening
 Food delays time to effect
 AUC and Cmax are highest in obese females. No labeled
dose adjustments, but use caution.
Belsomra® [package insert]. 2014. Merck 7 Co., Inc.
Pharmacists Letter Detail Document #310211
36
Comparative Kinetics
Onset (minutes)
Half-life (hours)
Suvorexant
30
12
Temazepam
30 - 60
3.5 - 18.4
Eszopiclone
30
6
Zaleplon
30
1
30
30
20-40
1.4 - 4.5
1.6 - 4.1
1.4 - 3.6
30
2-5
Zolpidem IR
CR
Sublingual
Ramelteon
Pharmacists Letter Detail Document #310211
37
Suvorexant Safety
 Somnolence
 6.7% suvorexant vs. 3% placebo
 8% female vs. 3% male
 Some impairment of next-drive driving performance at 20 mg
 No complex sleep behaviors reported at doses up to 20 mg
 No rebound insomnia or withdrawal after 3 and 12 months
 Side effect incidence similar across age ranges
Citrome L. Int J Clin Pract 2014;68:1429-1441.
38
Suvorexant– PLACE IN THERAPY
My recommendation is to stick with known agents
until more “real world” experience is available with
this new agent
Redbook AWP pricing per dose (as of 9/1/15)

Suvorexant (brand)
= $10.52

Eszopiclone (brand)
= $11.66

Zaleplon (generic)
= $3.60

Zolpidem (generic)
= $4.50

Temazepam (generic) = $0.80
39
Questions?
40
Olodaterol is delivered through what type
of inhaler formulation?
a. Diskus
b. HandiHaler
c. Metered dose inhaler
d. Respimat
d
41
Patients taking naloxegol are at increased
risk of naloxegol-related adverse
reactions when concurrently taking what
type of drugs?
a. p-glycoprotein inhibitors
b. p-glycoprotein inducers
c. strong CYP3A4 inhibitors
d. strong CYP3A4 inducers
c
42
For healthy adult patients in whom sleep
hygeine has failed to correct insomnia, which
of the following medications represents the
most reasonable first-line treatment option?
a. suvorexant
b. temazepam
c. trazodone
d. zolpidem
b
43
Assuming no contraindications, which of the
following patients with HFrEF would be the best
candidate for initiation of ivabradine?
d
a. taking lisinopril 20 mg po daily and carvedilol 6.25 mg po BID; BP
120/64; HR 78
b. taking lisinopril 20 mg po daily and furosemide 20 mg po daily; BP
130/80; HR 90
c. taking lisinopril 20 mg po daily, furosemide 20 mg po d. daily, and
carvedilol 12.5 mg po BID; BP 40/84; HR 82
d. taking lisinopril 20 mg po daily, furosemide 40 mg po daily,
carvedilol 25 mg po BID, and spironolactone 25 mg po daily; BP
110/60; HR 72
44
Use of dapagliflozin should be avoided in
patients with an eGFR below what level?
a. Less than 15 mL/min/1.73m2
b. Less than 30 mL/min/1.73m2
c. Less than 45 mL/min/1.73m2
d. Less than 60 mL/min/1.73m2
d
45