Transcript addyi

AddyiTM - flibanserin
Manufacturer:
Sprout Pharmaceuticals Inc.
FDA Approval Date: August 18, 2015
AddyiTM - flibanserin
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend AddyiTM
(flibanserin)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of AddyiTM (flibanserin)
AddyiTM - flibanserin
Clinical Application
• Indications:
• Treatment of generalized, acquired
hypoactive sexual desire disorder
(HSDD) in premenopausal women
• Place in therapy:
• Treatment of a rare disorder in
premenopausal women (~10%)
AddyiTM [package insert].
BEGONIA Trial
AddyiTM - flibanserin
Clinical Application
• Contraindications:
• Alcohol intake, hepatic impairment, and concomitant use with
moderate or strong CYP3A4 inhibitors
• Black Box Warning:
• Hypotension and syncope in specific situations:
• Contraindicated with alcohol
• Contraindicated with strong or moderate CYP3A4 inhibitors
• Contraindicated in patients with hepatic impairment
• Precautions:
• Hypotension and syncope with AddyiTM alone
• CNS depression (i.e. somnolence and sedation)
AddyiTM [package insert].
AddyiTM - flibanserin
Clinical Application
• Pregnancy:
• Unknown
• Lactation:
• NOT recommended
AddyiTM [package insert].
AddyiTM - flibanserin
Drug Facts
• Pharmacology:
• Agonist of 5-HT1A
• Antagonist of 5-HT2A, 5-HT2B, 5-HT2C, and
dopamine D4 receptor
• Exact mechanism of action is unknown
AddyiTM [package insert].
AddyiTM - flibanserin
Drug Facts
• Pharmacokinetics:
A
F: 33%, Tmax: 0.8 hours, steady state:
reached after 3 days
D
98% protein binding
M
Primarily CYP3A4 metabolism (lesser
extent CYP2C19) into two inactive
metabolites
E
T1/2: 11 hours
AddyiTM [package insert].
AddyiTM - flibanserin
Drug Interactions
• Drug Interactions – Object Drugs:
AddyiTM Increases
• Digoxin 2-fold
• Simvastatin 1-3 fold
• Oral contraceptives
100%
• PGP substrates
AddyiTM Decreases
• Bupropion
(hydroxybupropion)
9%
AddyiTM [package insert].
AddyiTM - flibanserin
Drug Interactions
• Drug Interactions – Precipitant Drugs:
Increases AddyiTM
• Strong CYP3A4 inhibitors:
fluconazole 7-fold,
ketoconazole 4.5-fold,
itraconazole 2.6-fold,
GFJ 1.4-fold
• Strong CYP2C19 inhibitors
• Oral contraceptives 1.4-fold
Decreases AddyiTM
• CYP3A4 inducers:
Rifampin 95%
• Paroxetine 4%
• Etravirine 21%
AddyiTM [package insert].
AddyiTM - flibanserin
Adverse Effects
Common ADES
•CNS depression (21%) [8%]
•Dizziness (11.4%) [2.2%]
•Somnolence (11.2%) [2.9%]
•Nausea (10.4%) [3.9%]
•Fatigue (9.2%) [5.5%]
•Insomnia (4.9%) [2.8%]
•Dry mouth (2.4%) [1.0%]
•Syncope (0.4%) [0.2%]
•Hypotension (0.2%) [<0.1%]
AddyiTM [package insert].
AddyiTM - flibanserin
Monitoring Parameters
• Efficacy Monitoring:
• Increase in sexual desire
• Toxicity Monitoring:
• Hypotension, syncope, and CNS
depression
AddyiTM [package insert].
AddyiTM - flibanserin
Prescription Information
• Dosing:
• Initial/Usual: 100mg PO HS
• Maximum: 200mg PO HS
• Renal adjustment: 50mg PO HS
• Cost: $400 for 30 day supply
AddyiTM [package insert].
Forbes Accessed 8/18/15
AddyiTM - flibanserin
Literature Review
Efficacy of Flibanserin in Women with
Hypoactive Sexual Desire Disorder:
Results from the BEGONIA Trial
Purpose: To access the safety and
efficacy of flibanserin in premenopausal
women with HSDD
Design: multi-center, randomized,
double-blind, placebo-controlled
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
• Methods:
• 4-week baseline period, followed by a 24week treatment period, and a 1-week
post-treatment period
• Randomized to receive either flibanserin
100mg QHS (n = 543) or placebo (n = 547)
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
Inclusion Criteria
• > 18 years old
• Premenopausal women
• Diagnosed with acquired,
generalized HSDD
• Heterosexual monogamous
relationship for > 1 year with a
sexually functioning partner
physically present for > 50% of
every month during the trial
• Willing to engage in sexual
activity at least once monthly
Exclusion Criteria
• Medications that may
affect sexual function
• Diagnosed with
depression (> 14 score
on Beck Depression
scale)
• Gynecological issues
including endometriosis
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
• General Baseline Characteristics:
• Avg. age ~36
• ~74% Caucasian
• Avg. 74.7 kg (164 lbs)
• Avg. length of relationship 11 years
• Avg. duration of HSDD 49 months
• Avg. baseline FSFI total score 19
• Avg. baseline SSE standardized to 28days 2.6
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
• Intervention: Compare the safety and
efficacy of flibanserin to placebo
• Co-primary Endpoints:
• Change from baseline to week 24 in FSFI
score
• Number of SSE standardized to 28-days
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
• Secondary Endpoints:
• Change from baseline to week 24 in the
FSDS-R Item 13
• FSDS-R total scores
• FSFI total scores
• PGI-I score
• Patient benefit evaluation (PBE) at week
24
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
• Safety Assessment
• Evaluation of ADES
• Clinical laboratory parameters
• Vital signs
• Physical exam
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
Coprimary Endpoints
Results
Flibanserin
PBO
P value
Change from baseline
to week 24 in FSFI
desire domain score
1.0
0.7
<0.001
Number of SSE
standardized to 28 days
2.5
1.5
<0.001
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
Results
Secondary Endpoints
Change from baseline to
week 24 FSDS-R Item 13
Change from baseline to
week 24 FSDS-R total
score
Change from baseline to
week 24 PGI-I score
PBE at week 24
Flibanserin
PBO
P value
-1.0
-0.7
<0.001
-9.4
-6.1
<0.001
3.2
3.5
<0.001
44.7%
34.8%
0.001
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
• Adverse Events:
• Somnolence (14.4%) [3.5%]
• Dizziness (10.3%) [1.1%]
• Nausea (7.6%) [2.2%]
• Fatigue (5.7%) [3.3%]
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Literature Review
• Conclusions: results from this trial,
“indicate that flibanserin 100mg QHS
has the potential to improve sexual
desire and sexual function and
reduce distress related to loss of
sexual desire in premenopausal
women with HSSD.”
Katz et al. BEGONIA trial. J Sex Med. 2013;10(7):1807-15.
AddyiTM - flibanserin
Summary
• First-in-class for HSDD in
premenopausal women
• Dosing is 100mg PO daily at bedtime or
50mg for any renal impairment
• Most common ADEs: dizziness, CNS
depression, nausea, and sleep issues
• BBW: hypotension, syncope, and CNS
depression (REMS program)
AddyiTM - flibanserin
References
1.
AddyiTM [package insert]. Raleigh, NC: Sprout
Pharmaceuticals Inc.; 2015.
2.
Katz M, Derogatis LR, Ackerman R, et al. Efficacy
of flibanserin in women with hypoactive sexual
desire disorder: results from the BEGONIA trial. J
Sex Med. 2013;10(7):1807-15.