Alogliptin 25 mg tablet (NESINA )

1. : Alogliptin Benzoate

2. : NESINA

3. : film-coated tablets

TAK ALG-25
4. (Category)

4.1 ATC code A10B

: H04
 4.2 : Dipeptidyl peptidase 4 (DPP-4) inhibitors

4.3 : 2-({6-[(3R)-3-aminopiperidin-1-yl]- 3-methyl-

2,4-dioxo-3,4-dihydropyrimidin-1(2H)-

yl}methyl)benzonitrile monobenzoate

C18H21N5O2C7H6O2

461.51 daltons

5. 24 : 143992999003750121781073

TMT code : 1000345

6.

5.1 : (NED)

5.2 :
 - 2

-


5.3 : adjunct to

diet and exercise to improve glycemic control in adults

with type 2 diabetes mellitus.
Limitation of Use: Not for treatment of type 1
diabetes or diabetic
ketoacidosis.
5.4
: -

7. (Rational for therapeutic

approach to disease)
7.1 :
etiology and classification epidemiology

pathogenesis physiologic or clinical presentation

7.2

8. (Pharmacodynamic)/

(Mechanism of action)

DPP-4 inhibitors DPP-4

incretins

incretins GIP GLP-1
incretins


incretins
glucose-dependent
2
9. (Pharmacokinetics)/

(Biopharmaceutical)
Bioavailability 100%
time to peak concentration 1-2 hr
protein biding 20%
half-life (T1/2) 21 hr
60-71%
metabolite 2
14
[ C]alogliptin N-demethylated, M-I ( 1% )

N-acetylated alogliptin, M-II ( 6% ) M-I

metabolite DPP-4

M-II DPP-4

DPP CYP2D6 CYP3A4

metabolism alogliptin
 Alogliptin (R)-enantiomer ( 99%)

chiral conversion chiral conversion

(S)-enantiomer (S)-enantiomer

25 mg

10. scope biopharmaceutical

11. (Clinical trials/Clinical efficacy)
1






Primary outcome
Secondary outcome


2






Primary outcome
Secondary outcome


3






Primary outcome
Secondary outcome


12. (Adverse effect)/

(Adverse events)
1. Common
- Headache (4.3% )
- Nasopharyngitis (4.8% )
- Upper respiratory infection (4.5% )
2. Serious
- Dermatologic: Stevens-Johnson syndrome
 - Gastrointestinal: acute Pancreatitis (0.2%)
- Hepatic: Fulminant hepatic failure
- Immunologic: Anaphylaxis, Hypersensitivity reaction (0.6%)
- Musculoskeletal: Arthralgia
- Other: Angioedema
13. (Contraindications)
- 1 ketoacidosis
-

alogliptin anaphylaxis, angioedema

14. (Precautions)
1. Pancreatitis

significant hazard ratio (HR) of 1.578 (P = .033)

prior pancreatitis, gallstones,

biliary disease, very high triglyceride levels, or high alcohol

consumption pancreatitis
2. Heart Failure EXAMINE trial T2DM acute coronary

events CHF 3.9%

(placebo 3.3%) risks/benefits risk

heart failure heart failure renal

impairment
3. Hypersensitivity Reactions severe

hypersensitivity alogliptin anaphylaxis,

 angioedema Stevens-Johnson syndrome

angioedema DPP-4

inhibitors cross reaction

4. Hepatic failure, including fatalities liver

enzyme elevations
5. Severe and Disabling Arthralgia 1 1

DPP-4 inhibitors

6. hypoglycemia

hypoglycemia
15. (Drug interaction)
metabolism

Cytochrome (CYP) P450

CYP substrate CYP inhibitor

16. (Use in special population)
15.1 Pregnancy Category B
15.2 alogliptin

15.3 /
15.4

alogliptin 18
 15.5

mild to moderate (Child-Pugh

A B) Child-Pugh C

liver disease
15.6
- CrCl 60 mL/min = No dose adjustment
- CrCl 30 - 60 mL/min = 12.5 mg once daily
- CrCl 15 - 30 mL/min = 6.25 mg once daily
- CrCl <15 mL/min or requiring hemodialysis = 6.25 mg once

daily supplement
Dose

PD
17. (Dosage and administration) 1

tablet(25 mg) orally once daily with or without food

18. (Efficacy) (Toxicity)

(Monitoring parameters)
- HbA1c 2
- Blood glucose (self-monitoring) as needed
- Renal function; at baseline and periodically during therapy
- Signs and symptoms of pancreatitis; after treatment

initiation
- Signs and symptoms of heart failure, in patients at risk for

heart failure; during therapy

 19. 30
20. (Patient education and counseling)
- congestive heart failure
- acute pancreatitis hepatic failure
- Stevens-Johnson syndrome

bullous pemphigoid
- severe arthralgia
-

nasopharyngitis, upper respiratory infections

headaches

21. (Summary and conclusion)

Alogliptin Sitagliptin Vildagliptin

Generic name Sitagliptin(Janu Vildagliptin(

(Trade name) via ) GulvatMet )

Alogliptin(Nesin

a )
 Alogliptin Sitagliptin Vildagliptin

Manufacturer/Di Takeda/DKSH MSD/ZPL Novatis/ZPL

stributor

Dosage form film-coated film-coated film-coated

tablets tablets tablets

Strength 25 mg 100 mg 50/1000 mg

Approve -
Indication
& Dosage 2 (monotherapy)
Regimen
2



-
,
2
metformin,

sulfonylurea

(SU)
thiazolidinedio
ne (TZD)
 Alogliptin Sitagliptin Vildagliptin

Classification DPP-4 inhibitor DPP-4 inhibitor DPP-4 inhibitor

Mechanism of
action


dipeptidyl dipeptidyl dipeptidyl
peptidase 4 peptidase 4 peptidase 4
(DPP-4) (DPP-4) (DPP-4)


incretin 2 incretin 2 incretin 2
GLP-1 GLP-1 GLP-1
GIP GIP GIP

insulin - insulin - insulin -
cell cell cell
 Alogliptin Sitagliptin Vildagliptin

glucose- glucose- glucose-

dependent dependent dependent

glucagon - glucagon - glucagon -
cell cell cell

ED/NED NED NED NED

Pharmacokinetic -Bioavailability - Bioavailability: -Bioavailability:

s 100% 87% 85%
-Tmax 1-4 hrs -Tmax 1.7 hours
-Protein binding: 9.3%
-Protein -Vd: 71 L
-half-life (T1/2) 3
-Tmax 1-2 hr binding: 38%
hrs
-protein biding -half-life (T1/2)
-Mostly
20% 12.5 hrs
metabolized in
-half-life (T1/2) -Metabolism:
liver by
21 hr hepatic via
hydrolysis
- Excretion: CYP3A4 and
--Excretion:
urine: 60-71% CYP 2C8
urine: 80%
(unchange) -Excretion:
(inactive
urine: 87%
metabolite)
(79%

16%
metabolites)
 Alogliptin Sitagliptin Vildagliptin

-
hemodialysis

13.5%

Efficacy Selectivity for DPP-4

high high Moderate

>14000-fold vs >2660-fold vs >270-fold vs
DPP-8 DPP-8 DPP-8
>14000-fold vs >5550-fold vs >52-fold vs
DPP-9 DPP-9 DPP-9

monotherapy(*= Statistically
significant)
A1c
achieve A1c
<7% placebo

MFM alogliptin

HbA1C -0.74* HbA1C -0.75* HbA1C -0.67*

OR achieve A1c OR achieve A1c OR achieve A1c
<7% =4.29* <7% =3.64* <7% =4.02*
0.32
OR 0.70* 0.83*
hypoglycemia OR OR
0.27 hypoglycemia hypoglycemia
0.61 0.78

metformin(*= Statistically
 Alogliptin Sitagliptin Vildagliptin

significant)
A1c
achieve A1c
<7% MFM

HbA1C -0.68* HbA1C -0.64* HbA1C -0.59*

OR achieve A1c OR achieve A1c OR achieve A1c
<7% =6.41* <7% =2.87* <7% =2.45*
0.26 0.87
OR -0.28 OR
hypoglycemia OR hypoglycemia
0.24 hypoglycemia 0.78
1.32

SU(*= Statistically significant)

A1c
SU
3 vildagliptin achieve A1c
<7%

HbA1C -0.47* HbA1C -0.68* HbA1C -0.81*

OR achieve A1c OR achieve A1c OR achieve A1c
<7% =2.82 <7% =2.00 <7% =5.81*
0.83 0.68 0.95
OR OR OR
hypoglycemia hypoglycemia hypoglycemia
1.44 4.74 3.69

metformin SU (*= Statistically

significant)
 Alogliptin Sitagliptin Vildagliptin
alogliptin MFM SU
sitagliptin vildagliptin
double therapy(metformin plus SU) sitagliptin
vildagliptin

HbA1C -0.91 HbA1C -0.76

OR achieve A1c OR achieve A1c
<7% - <7% -
1.78 -
OR OR
hypoglycemia hypoglycemia
12.92 9.89

pioglitazone (*= Statistically

significant)
A1c
achieve A1c
<7% pioglitazone

HbA1C -0.64* HbA1C -0.88* HbA1C -0.51*

OR achieve A1c OR achieve A1c OR achieve A1c
<7% = 3.31* <7% = 4.23* <7% = 2.40*
0.54 1.10 0.24
OR OR OR
hypoglycemia hypoglycemia hypoglycemia
20.15 3.22 0.49

insulin(*= Statistically significant)

 Alogliptin Sitagliptin Vildagliptin

alogliptin insulin sitagliptin

vildagliptin

insulin

HbA1C -0.41 HbA1C -0.55

OR achieve A1c OR achieve A1c
<7% - <7% -
0.78
-1.81 OR
OR hypoglycemia
hypoglycemia 7.30
2.74

Risk of heart failure

The findings of this meta-analysis indicate
that, as compared with
placebo or other anti-diabetic regimens,
long-term treatment with
DPP-4is does not affect CV and overall
mortality nor the occurrence of
stroke, but significantly increases the risk
of onset of HF. The analysis
showed that DPP-4is reduce the risk of MI
in the short term but this effect
is lost in the long term while the
increased risk of HF becomes evident
 Alogliptin Sitagliptin Vildagliptin

with chronic treatment, suggesting a time-

dependent effect that
warrants further investigation.

heart
failure
Safety

Renal -GFR 60 -GFR 50 -GFR >50

mL/min, no mL/min, no ml/min, No
dosage dosage dose
adjustment adjustment adjustment
needed needed -moderate,
-GFR 30 to < -GFR 30-50 severe, or
60 mL/minute: mL/min, do not ESRD: 50 mg
12.5 mg once exceed 50 mg orally once
daily daily daily
-GFR 15 to < -GFR < 30
30 mL/minute: mL/min, do not
 Alogliptin Sitagliptin Vildagliptin

6.25 mg once exceed 25 mg

daily daily
-ESRD (GFR < -HD or PD do
15 mL/minute not exceed 25
or requiring mg daily
hemodialysis):
6.25 mg once
daily;administer
ed without
regard to timing
of hemodialysis

Hepatic Hepatic
mild- impairment:
moderate use not
mild to hepatic recommended
moderate impairment.
(Child-Pugh
A B) severe hepatic
impairment
Child-Pugh
C

Pregnancy B B B

Contraindic - T1DM -Serious -

 Alogliptin Sitagliptin Vildagliptin

ations hypersensitivity Hypersensitivity

reaction to to vildagliptin
ketoacidosis sitagliptin such or to any
-Serious as angioedema component of
hypersensitivity or anaphylaxis the product
reaction to
alogliptin
anaphylaxis,
angioedema

Adverse -Headache - Hypoglycemia -Dizziness (1%-

Reactions (4.3% ) (0.6%-12.2% ) <10% )
- -Headache -
Nasopharyngitis (1.1%-5.9% ) Headache(0.1%
(4.8% ) - -12.9%)
-Upper Nasopharyngitis -
respiratory (5.2% -6.3% ) Nasopharyngitis
infection -Upper (3.5%- 13.2%)
(4.5% ) respiratory -
-Dermatologic: infection (4.5%- Gastrointestinal
Stevens- 6.3% ) : Pancreatitis
 Alogliptin Sitagliptin Vildagliptin

Johnson -Cardiovascular: -Acute

syndrome Heart failure Musculoskeleta
- - l: Arthralgia
Gastrointestinal: Gastrointestinal:
acute Pancreatic
Pancreatitis cancer,
(0.2% ) Pancreatitis
-Hepatic: -Immunologic:
Fulminant Anaphylaxis,
hepatic failure Angioedema,
-Immunologic: Generalized
Anaphylaxis, exfoliative
Hypersensitivity dermatitis,
reaction (0.6%) Hypersensitivity
- reaction, Rash,
Musculoskeleta Stevens-
l: Arthralgia Johnson
-Other: syndrome,
Angioedema Urticaria
-
Musculoskeleta
l: Arthralgia,
Rhabdomyolysi
s
 Alogliptin Sitagliptin Vildagliptin

-Renal: Abnorm
al renal
function, Acute
renal failure
-Other: Pancrea
tic cancer

Drug Potential for Potential for Potential for

Interactions drug-drug drug-drug drug-drug
interaction = interaction = interaction =
low low low

-Partly pass CYP3A4, -Mostly metabolized in

substrate CYP2C8 ( liver by hydrolysis (
drug
CYP2D6 CYP ) interaction )
-Undergoes primarily -Renal excretion in
and CYP3A4
renal elimination (~87% inactive metabolite ~
unchanged in urine) 80%
inhibitor
inducer CYP
Adherence
1 1 2
with or without taken with or
food without food

Cost 34.24 // 43 // 42 /2 /

Storage 30 30 30

 Alogliptin Sitagliptin Vildagliptin

Advantage

Disadvantage

Packaging look
alike sound
alike

Clinical () /
Application

Summary and
Formulary
Recommendati
on
DUE