Beruflich Dokumente
Kultur Dokumente
OCTOBER 2011
Drug Review
Introduction
Asenapine, a new sublingual second-generation
antipsychotic, received FDA-approval on August
13, 2009 with label indications for the acute
treatment of schizophrenia in adults and for the
acute treatment of manic or mixed episodes
associated with bipolar I in adults.
Pharmacology1-3
Distribution
Absorption
372
Metabolism
Excretion
OCTOBER 2011
Parameter
Metabolism
Elimination
Half-life
Protein Binding
Bioavailability
Asenapine
Hepatic via CYP1A2 oxidation and
UGT1A4 glucuronidation
Urine (~50%), feces (~50%)
~24 Hours
95% (albumin and 1-acid
glycoprotein)
Sublingual: 35%Swallowed: < 2%
(Also decreased if administered with
food/water)
373
OCTOBER 2011
OCTOBER 2011
Asenapine
Asenapine
5 mg twice daily 10 mg twice daily
N = 274
N = 208
All Asenapine
5 or 10 mg twice
daily N=572
Gastrointestinal disorders
Constipation
Dry mouth
Oral hypoesthesia
Salivary hypersecretion
Stomach discomfort
Vomiting
6%
1%
1%
0%
1%
5%
7%
3%
6%
<1%
<1%
4%
4%
1%
7%
4%
3%
7%
5%
2%
5%
2%
2%
5%
General disorders
Fatigue
Irritability
Weight increased
3%
<1%
<1%
4%
2%
2%
3%
1%
2%
3%
2%
3%
Metabolism disorders
Increased appetite
<1%
3%
0%
2%
Akathisia
Dizziness
Extrapyramidal
symptoms
(excluding akathisia)
Somnolence
3%
4%
4%
7%
11%
3%
6%
5%
7%
7%
9%
15%
12%
13%
10%
13%
Psychiatric disorders
Insomnia
13%
16%
15%
15%
Vascular disorders
Hypertension
2%
2%
3%
2%
375
OCTOBER 2011
Placebo
(N = 203)
Asenapine
5 or 10 mg twice daily (N=379)
Gastrointestinal disorders
Dry mouth
Dyspepsia
Oral hypoesthesia
Toothache
1%
2%
<1%
2%
3%
4%
4%
3%
General disorders
Fatigue
Weight increased
2%
<1%
4%
5%
Metabolism disorders
Increased appetite
1%
4%
1%
<1%
3%
2%
Akathisia
Dizziness
Dysgeusia
Headache
Other extrapyramidal symptoms
(excluding akathisia)
Somnolence
2%
3%
<1%
11%
4%
11%
3%
12%
2%
6%
7%
24%
Anxiety
Depression
Insomnia
2%
1%
5%
4%
2%
6%
Psychiatric disorders
Coadministered Drug
Fluvoxamine
(CYP1A2 Inhibitor
Paroxetine
(CYP2D6 Inhibitor)
Imipramine
(CYP1A2 /2C19/3A4 inhibitor)
Cimetidine
(CYP3A4/2D6/1A2 inhibitor)
Carbamazepine
(CYP3A4 inducer)
Valproate (UGT1A2)
376
Asenapine
Effect on Asenapine
CMAX
AUC0-
5 mg single dose
+13%
+29%
5 mg single dose
-13%
-9%
75 mg single dose
5 mg single dose
+17%
+10%
5 mg single dose
-13%
+1%
-16%
-16%
+2%
-1%
5 mg single dose
Recommendation
Coadminister with
caution
No asenapine dose
adjustment
No asenapine dose
adjustment
No asenapine dose
adjustment
No asenapine dose
adjustment
No asenapine dose
adjustment
OCTOBER 2011
377