Brochure GALVUS

Penurunan nyata A1c sebagai terapi mono atau “add-on” dengan Metformin

GALVUSMET®

Presentation: Vildagliptin/Metformin hydrochloride fixed combination: 50 mg/500 mg, 50 mg/850 mg tablets. Indications: Galvusmet is indicated as an adjunct to diet and exercise to improve glycaemic control in patientswith type 2 diabetes mellitus whose diabetes is not adequately controlled on metformin hydrochloride or vildagliptin alone or who are already treated with the combination of vildagliptin and metformin hydrochloride, as separatetablets. Dosage: Based on the patient’s current dose of metformin, Galvusmet may be initiated at either the 50 mg/500 mg or 50 mg/850 mg tablet strength twice daily, one tablet in the morning and the other in the evening.The recommended daily dose is 100 mg vildagliptin plus 2000 mg metformin hydrochloride. Patients receiving vildagliptin and metformin from separate tablets may be switched to Galvusmet containing the same doses ofeach component. Doses higher than 100 mg of vildagliptin are not recommended. Taking Galvusmet with or just after food may reduce gastrointestinal symptoms associated with metformin. Contraindications: Knownhypersensitivity to vildagliptin or metformin hydrochloride or to any of the excipients • renal failure or renal dysfunction • congestive heart failure • acute or chronic metabolic acidosis including diabetic ketacidosis with orwithout coma • should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials • acute conditions with the potential to alter renal functionsuch as dehydration, severe infection, shock, septicaemia, intravascular administration of iodinated contrast agents • acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recentmyocardial infarction, shock • hepatic impairment • acute alcohol intoxication • lactation. Precautions/Warnings: Risk of lactic acidosis • monitoring of renal function • caution with concomitant use of medications that mayaffect renal function or metformin hydrochloride disposition • should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials • discontinuetreatment in case of hypoxemia • temporary discontinuation in patients undergoing surgical procedure • excessive alcohol intake to be avoided • not recommended in patients with hepatic impairment including patients witha pre-treatment ALT or AST >2.5X the upper limit of normal. Liver function tests (LFT) to be performed prior to treatment initiation, at three-month intervals during the first year and periodically thereafter. Withdrawal of therapywith Galvusmet recommended if an increase in AST or ALT of 3X upper limit normal or greater persist. Following withdrawal of treatment with Galvusmet and LFT normalisation, treatment with Galvusmet should not bereinitiated • risk of decreased vitamin B12 serum levels • should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis • risk of hypoglycaemia • may be temporarily withhold in case of lossof glycaemic control • should only be used in elderly patients with normal renal function • not recommended in paediatric patients. Pregnancy: Should not be used in pregnancy unless the potential benefit justifies the potentialrisk to the foetus. Lactation: Should not be used during breast-feeding. Interactions: Interactions with Vildagliptin: low potential for drug interactions, no clinically relevant interactions with other oral antidiabetics (glibenclamide,pioglitazone, metformin), amlodipine, digoxin, ramipril, simvastatin, valsartan or warfarin were observed after co-administration with vildagliptin. Interactions with Metformin hydrochloride: furosemide, nifedipine, cationicdrugs, drugs tending to produce hyperglycaemia, alcohol. Adverse reactions: • Vildagliptin monotherapy - Common: dizziness, constipation, arthralgia – Uncommon: headache, oedema peripheral. • Metformin monotherapy– Very common: nausea, vomiting, diarrhoea, abdominal pain, loss of appetite. Common: metallic taste. Very rare: decrease of vitamin B12 absorption, lactic acidosis, liver function test abnormalities, hepatitis, skin reactionssuch as erythema, pruritus and urticaria. • Other effects with Combination of Vildagliptin and Metformin - Common: headache, tremor, dizziness, nausea. Packs: Box, 3 strips @ 10 film-coatedtablets. No. Reg.: DKI0967507617A1; DKI0967507617B1. Harus Dengan Resep Dokter. Full information, consult full prescribing information.

GALVUS®

Presentation: Vildagliptin. Tablets: 50 mg. Indications: Galvus is indicated as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes mellitus. It is indicated as monotherapyand in dual combination with metformin, a sulphonylurea, a thiazolidinedione when diet, exercise and a single antidiabetic agent do not result in adequate glycaemic control. Dosage: Monotherapy: The recommendeddose of Galvus is 50 mg or 100 mg daily. Combination therapy: The recommended dose of Galvus is 50 mg or 100 mg daily in dual combination with metformin or a TZD; and 50 mg daily in dual combination withSU. The 50 mg dose should be administered once daily in the morning. The 100 mg dose should be administered as two divided dose of 50 mg given in the morning and evening. Galvus is not recommended inpatients with hepatic impairment including patients with a pre-treatment ALT or AST >2.5X the upper limit of normal. Contraindications: Hypersensitivity to vildagliptin or to any of the excipients. Patientswith moderate or severe renal impairment. Patients with hepatic impairment. Precautions/Warnings: LFTs should be monitored during Galvus treatment at three-month intervals during the first year andperiodically thereafter. Galvus should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Not recommended in patients with rare hereditary problems of galactose intolerance,lactase deficiency or glucose-galactose malabsorption. Should not be used in pregnancy unless the potential benefit justifies the potential risk to the foetus. Should not be used during lactation. Interactions:Vildagliptin has a low potential for drug interactions. No clinically relevant interactions with other oral antidiabetics (glibenclamide, pioglitazone, metformin), amlodipine, digoxin, ramipril, simvastatin, valsartan orwarfarin were observed after co-administration with vildagliptin. Adverse reactions: Monotherapy - Common: dizziness, headache, constipation, nausea, diarrhea, arthralgia, nasopharyngitis, hypertension.Uncommon: skin rash. Additional adverse reactions: Dual oral therapy with metformin, a sulphonylurea or a thiazolidinedione - Common: nasopharyngitis, headache, dizziness, tremor, upper respiratory tractinfections, asthenia. Packs: Box, 2 Blisters @ 14 Tablets. Reg. No.: DKI0767506910A1. Harus Dengan Resep Dokter. Note: Before prescribing, please read full prescribing information.

GA

LM/B

RO

C/S

1-01

12/0

1

Untuk informasi lebih lanjut hubungi :PT Novartis IndonesiaWisma 46-Kota BNI lantai 35. Jl. Jenderal Sudirman Kav. 1,Jakarta 10220 PO Box 1076, Jakarta 10010Telp.: (021) 2513251. Fax.: (021) 2513252

Referensi : 1. Konsensus Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia 2011. 2. Galvus product information Novartis Indonesia, 2007. 3. Pi-Sunyer F, et al. Efficacy and tolerability of vildagliptin monotherapy in drug-naïve patientswith type 2 diabetes. Diabetes Res Clin Pract. 2007; 76: 132–138. 4. Kahn S, Zinman. Counterpoint : A Diabetes Outcome Progression Trial (ADOPT) : Good for Sulfonylureas? Diabetes Care 2007:30(6)1677-1680. 5. Viberti G, et al. A Diabetes outcomeprogression trial (ADOPT). Diabetes Care. 2002; 25:1737-1743. 6. Göke B, et al. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naïve patients with type 2 diabetes: comparison with metformin. Horm Metab Res. 2008;40: 892–895. 7. J Foley & S Sreenan. Efficacy and Safety Comparison Between the DPP-4 Inhibitor Vildagliptin and the Sulfonylurea Gliclazide After Two Years of Monotherapy in Drug-naïve Patients with Type 2 Diabetes. Horm Metabo Res. 2009;41:905-909. 8. Rosenstock J, et al. Long-term 2-year safety and efficacy of vildagliptin compared with rosiglitazone in drug-naïve patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2009; 11: 571–578. 9. Nathan DM, et al. Medical management ofhyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009; 32: 193–203. 10. Bosi E, et al. Effects of Vildagliptin on Glucose Control Over 24 Weeks in Patients with Type 2 DiabetesInadequately Controlled with Metformin. Diabetes Care. 2007; 30 (4) : 890-895. 11. Data on file, Novartis Pharmaceutical, LAF237A2303. 12. Ferrannini et al., Fifty two week efficacy & safety of vildagliptin vs glimepiride in patient with type 2 DMinadequately controlled on metformin montherapy; Diabetes, Obesity & Metabolism. 2009; 11: 157-166. 13. Bolli G, et al. Efficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin : a 24-week, randomized, double blind study.Diabetes, Obesity and Metabolism. 2008:10(1): 82-90. 14. Bolli G, et al. Comparison of vildagliptin and pioglitazone in patients with type 2 diabetes inadequately controlled with metformin. Diabetes, Obesity and Metabolism. 2009;11: 589-595. 15. UKProspective Diabetes Study Group. UK Prospective Diabetes Study. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995; 44: 1249–1258. 16. Bosi E, et al. Effects of vildagliptin on glucose control over 24 weeks inpatients with type 2 diabetes inadequately controlled with metformin. Diabetes Care. 2007; 30: 890–895.

Pada Pasien DM tipe 2 dengan HbA1c 7-8%Konsensus PERKENI 2011: Lakukan GHS + monoterapi OAD1

Studi 24 minggu, buta ganda, acak, multisenter, kontrol plasebo, grup paralel pada 354 pasien drug naïve. Pasiendiacak untuk mendapat terapi vildagliptin 50 mg sekali sehari, 50 mg dua kali sehari, 100 mg sekali sehari atau

plasebo (rata-rata nilai awal HbA1c : 8,4 %)

Monoterapi GALVUS®

MEMPERBAIKI KONTROL GLIKEMIK PADA PASIENDRUG NAÏVE DM TIPE 23

1.Dinyatakan gagal bila denganterapi 2-3 bulan tidakmencapai target HbA1c <7%

2. Bila tidak ada pemeriksaanHbA1c dapat digunakanpemeriksaan glukosa darah.Rata-rata glukosa darah seharidikonversikan ke HbA1cmenurut kriteria ADA2010

Catatan

GALVUS® DPP-4 inhibitor yang mendapatkan indikasi sebagaimonoterapi oleh BPOM RI2

Kadar HbA1c

<7% 7-8% 8-9% >9% 9-10% >10%

GHS GHS

GHS

GHS

GHS

GHS

Gaya HidupSehat

• Penurunan berat badan• Mengatur diit• Latihan Jasmani teratur

+

Monoterapi

Met, SU,AGI, Glinid,TZD, DPP-IV

+

Kombinasi2 obat


+

Kombinasi3 obat


+

Kombinasi2 obat

Met, SU,AGI, Glinid,

TZD

+

Basal Insulin +

InsulinIntensif

Primary intention-to-treat population. *P=0.01; **P <0.001 vs placebo.

9.0

8.6

8.2

7.8

7.4

7.0-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24

Vildagliptin 50 mg sekali sehari (n=84)Vildagliptin 50 mg dua kali sehari (n=79)Placebo (n=88)

Rat

a-ra

ta H

bA1c

(%)

Waktu (Minggu)

***

Studi ADOPT: terjadi glycaemic control losspada terapi jangka panjang dengan Sulfonilurea,

Metformin dan Tiazolidindion 4,5

MONOTERAPI GALVUS®

MEMBERIKAN KONTROL GLIKEMIK YANG STABILDALAM WAKTU YANG PANJANG (2 TAHUN) 6

Studi ini merupakan lanjutan studi 52 minggu yang telah dipublikasikan sebelumnya, multisenter, acak, studi grup paralel.Populasi lanjutan ini terdiri dari 300 pasien yang diacak menerima vildagliptin (100 mg perhari, terbagi menjadi duadosis) dan 158 pasien menerima metformin (2000 mg perhari, terbagi menjadi dua dosis). Nilai awal HbA1c kelompokterapi vildagliptin 8,4 ± 0,1%. * Not NI = Not Non-inferior.

Studi ADOPT, multisenter, acak, buta ganda, pada pasien DM tipe 2 yang mendapat monoterapi rosiglitazone 4 mg,metformin 500 mg atau gliburide 2,5 mg. Dosis ditingkatkan menjadi dosis maksimal bila gula darah puasa ≥ 140 mg/dL

Vildagliptin 50 mg dua kali sehariMetformin 1000 mg dua kali sehari

9.5

9.0

8.5

8.0

7.5

7.0

6.5-20 4 8 12 16 24 32 40 50 64 76 88 104

Waktu (Minggu)

Rat

a-ra

ta H

bA1c

(%)

GA

LV

US

sebagai

mo

no

terapi

Jumlah Pasien

8.0

7.6

7.2

6.8

6.4

6.00

0 1 2 3 4 5

Treatment difference (95% Cl)Rosiglitazone vs metformin,-0.13 (-0.22 to -0.05); P=0.002Rosiglitazone vs glyburide,-0.42 (-0.50 to -0.33); P=0.001

Annualized Slope (95% Cl)Rosiglitazone, 0.07 (0.06 to 0.09)Metformin, 0.14 (0.13 to 0.16)*Glyburide, 0.24 (0.23 to 0.26)*

Waktu (Tahun)

Rat

a-ra

ta H

bA1c

(%)

4012 3308 2991 2583 2197 822* p<0,001 vs Rosiglitazone

* Not NI

Kejadian efek samping saluran cerna lebih rendahdibandingkan metformin6

GALVUS MONOTERAPI DAPAT DITOLERANSIDENGAN BAIK 3

Kejadian hipoglikemia yang rendah7

MONOTERAPI GALVUS®

Memberikan kontrol Glikemik yang baik denganprofil berat badan yang superior dibandingkan

TZD atau SU

Terjadi kenaikan berat badan yang signifikan pada terapi TZDatau SU dibandingkan GALVUS® monoterapi 7,8

Studi 104 minggu, multi senter, buta ganda, acak, kontrol aktif untukmembandingkan efikasi dan keamanan vildagliptin dua kali (n=409)sehari dan glicazide sampai 320 mg perhari (n=402) pada pasienpasien drug-naïve DM tipe 2 . * p<0.01

Studi perpanjangan 80 minggu dari studi 24 minggu, buta ganda,acak, kontrol aktif, grup paralel membandingkan efikasi dan tolerabilitasvildagliptin (50 mg dua kali sehari) dan rosiglitazone (8 mg perhari)pada pasien drug-naïve. 533 pasien diikutisertakan pada populasiintention-to-treat di studi 80 minggu perpanjangan ini (vildagliptinn=354; rosiglitazone n=179). ** P<0.001 dibandingkan data awal*** P=0.99 dibandingkan data awal

Rat

a-ra

ta p

erub

ahan

ber

at b

adan

dari

nila

i aw

al (%

)

GALVUS 50 mgdua kali sehari

Glicazide sampai320 mg perhari

GALVUS 50 mgdua kali sehari

Rosiglitazone 8 mgperhari

-

-

-

-

-

2

1.5

1

0.5

0

_

_

_

_

_

_

_

_

_

_

_

5

4.5

4

3.5

3

2.5

2

1.5

1

0.5

0

0.8

1.6

4.7

0

*

* *

* * *

Bila pasien Diabetes Mellitus tipe 2 gagalmencapai kontrol glikemik dengan

Metformin monoterapi ...

Manajemen DM Tipe 2 menurutkonsensus ADA dan EASD (2009)9 :

Kombinasi Metformin+ SU menimbulkan risiko peningkatanberat badan dan hipoglikemia, meskipun memberikan

penurunan HbA1c yang efektif 9

ADA : American Diabetes AssociationEASD : European Association for Study of DiabetesSU : Sulfonilurea

Gaya hidup sehat +metformin +insulin basal

Gaya hidup sehat +metformin + SU

Gaya hidup sehat +metformin +

insulin intensif

Pasien terdiagnosa DM tipe 2:Gaya hidup sehat

+Metformin

Langkah 1

Langkah 2

Langkah 3

GA

LV

US

‘add

on

to’ m

etform

inG

AL

VU

S‘ad

d o

n to

’ metfo

rmin

Penurunan lebih besar – mencapai 1,3% vs metformin + plasebopada pasien dengan kadar HbA1c yang tinggi (nilai awalHbA1c > 9%). 11

Penelitian selama 24 minggu, multisenter, buta ganda, kontrol dengan plasebo. Pasien DM tipe 2 yang tidak terkontroldengan monoterapi metformin (≥1500 mg sehari) pada 544 pasien secara acak mendapatkan Galvus 50 mg sekalisehari + Metformin (n=177). Galvus 50 mg diberikan dua kali sehari + metformin (n=185) atau plasebo + Metformin(n=182). Rata-rata kadar A1c : 8,3 – 8,4%. Dosis rata-rata metformin pada awal terapi : 2100 mg perhari.

PILIHAN UTAMA KETIKAMONOTERAPI TIDAK CUKUP KUAT

Galvusmet = Galvus + Metformin

Pada pasien yang tidak terkontrol dengan Metformin ≥ 1500 mg sehari (dosis rata-rata: 2100 mg), penambahan Galvus memberikan penambahan penurunan HbA1c. 10

8.5

8.0

7.5

7.0

-

-

-

-

Rat

a-ra

ta H

bA1c

(%

)

PenambahanGalvus®

-4 0 4 8 12 16 20 24Waktu (minggu)

PenurunanA1c

Nyata dalam24 minggu

-1.1%

...ketika Galvus® ditambahkan pada Metformin vs Metformin + plasebo

P<0.001

Metformin + plasebo (n=130) (Rata-rata nilai awal A1c=8.3%)

Galvus® 100 mg perhari* + metformin (n=143) (Rata-rata nilai awal HbA1c=8.4%)


TERBUKTI MEMILIKI EFEKTIFITAS SETARASU + METFORMIN DENGAN TOLERABILITAS

YANG BAIK

Kejadian hipoglikemia yang lebih rendah. 12

Galvus + Metformin memberikan penurunan kadar A1c yangsetara dengan Glimepiride + Metformin pada minggu ke 52 12

Penelitian multisenter selama 52 minggu, buta ganda, pada pasien DM tipe 2 yang tidak terkontrol denganmonoterapi metformin (≥1500 mg perhari) dan kadar A1c antara 6,5% - 8,5%. Pasien (n=2789) secara acakmendapatkan Galvus 50 mg dua kali sehari + Metformin (n=1396) atau Glimepiride sampai 6 mg perhari +Metformin (n=1393).

Perbedaan nyata pada berat badan sebesar 1,8 kg pada mingguke 52 dengan pemberian Galvus + Metformin 12

– Galvus + Metformin : -0.2 kg dan Glimepiride + Metformin : 1.6 kg (p<0.001)

Semua kasus hipoglikemia (%) Kasus hipoglikemia Berat (%)

20

15

10

5

0

-

-

-

-

-

1.7 % 16.2 % 100

10

5

0

-

-

-

Ang

ka k

ejad

ian

Ang

ka k

ejad

ian

(%)

(n=1389) (n=1383) (n=1389) (n=1383)

Galvus 50 mg dua kali sehari+ metforminGlimepiride sampai 6 mg perhari+ metformin

Galvus 50 mg dua kali sehari+ metforminGlimepiride sampai 6 mg perhari+ metformin

TERBUKTI MEMPUNYAI EFEKTIVITAS SETARADENGAN TZD + METFORMIN DENGAN EFEK

STABIL PADA BERAT BADAN 13,14


Galvusmet memberikan penurunan HbA1c setara dengan kombinasipioglitazone + metformin. 13

Penelitian selama 24 minggu, acak, buta ganda, paralel pada pasien diabetes tipe 2 yang tidak terkontrol denganmonoterapi metformin (≥1500 mg perhari). 576 pasien secara random mendapatkan Galvus 50 mg dua kali sehari+ Metformin (n=295) atau pioglitazone 30 mg sekali sehari + Metformin (n=281). Kadar HbA1c : 7,5 - 11%. Padakeseluruhan populasi, terlihat penurunan yang serupa pada Galvus + Metformin dan pioglitazone + metformin(-0,9% vs -1%)

2.4 kg perbedaan penambahan berat badan yang timbul (p<0,001) : 14

– Galvus + Metformin = + 0,2 kg– Pioglitazone + Metformin = + 2,6 kg

-1.5%(n=63)

-1.5%(n=58)

Galvus +metformin

Pioglitazone+ metformin

Penurunan rata-rata HbA1c dari nilai awal

Pada pasien dengan HbA1c awal >9%

Fungsi sel beta menurun walaupun telahditangani oleh obat-obatan diabetes mellitus tipe 2 15

0 1 2 3 4 5 6

Tahun semenjak terdiagnosa

100

75

50

25

0

Fung

si s

el b

eta

(%)*

Sulfonylurea (n=511)Diet (n=376)Metformin (n=110)

Galvusmet meningkatkan fungsi sel betadibandingkan plasebo 16

Studi buta ganda, acak, multisenter, grup paralel, pengobatan 24 minggu dengan 50 mg vildagliptin perhari (n=177), 100 mg vildagliptinperhari (n=185), atau plasebo (n=182) pada pasien yang meneruskan dosis metformin (≥ 1500 mg/hari) tapi tidak mencapai kontrolglikemik (HbA1c 7.5 – 11%). Fungsi sel beta diukur berdasarkan rasio Insulin Secretory Rate (ISR) dengan kadar Area Under The Curve(AUC)/glukosa setelah 2 jam pp.

Data dari the UK Prospective Diabetes Study (UKPDS) 16 . Penelitian kontrol acak, subjek terdiri dari 4209 pasien yang baru terdiagnosadiabetes mellitus tipe 2 yang setelah 3 bulan dari terapi diet memiliki gula darah puasa sebesar 6,0-15,0 mmol/L. Studi terdiri dari2 pembanding utama : (1) pasien obese dan nonobese yang menjalani terapi konvensional (diet) atau terapi intensif dengan penambahansulfonilurea atau insulin; (2) pasien obese yang menjalani terapi konvensional atau terapi intensif dengan metformin. Data yangditampilkan adalah subset pasien pada perbandingan kedua yang masih menjalani terapi inisial pada tahun ke-6. * Fungsi sel beta dinilaidengan homeostasis model assessment (HOMA).

10

8

6

4

2

0

Adj

. Mea

n C

hang

e(p

mol

/min

/m2/

mM

)

* *

Fungsi sel beta

50 mg vildagliptin sekali sehari+ metformin

50 mg vildagliptin dua kali sehari+ metformin

plasebo

* p<0.001

KEAMANANdan

TOLERABILITAS

GALVUSMET®


GALVUS®



DPP4 Inhibitor yang terbukti sama efektif dengan TZD atau SU padakombinasi dengan Metformin

EFEKTIFITAS Penurunan nyata A1c sebagai terapi mono atau “add-on” dengan Metformin

KEAMANANdan

TOLERABILITASProfil penambahan berat badan yang minimalEfek samping hipoglikemia yang rendah

Stabil mengontrol kadar glikemik dalam jangka waktu yang panjangMeningkatkan fungsi sel beta

GALVUSMET®


GALVUS®


GA

LM/B

RO

C/S

1-01

12/0

1

Untuk informasi lebih lanjut hubungi :PT Novartis IndonesiaWisma 46-Kota BNI lantai 35. Jl. Jenderal Sudirman Kav. 1,Jakarta 10220 PO Box 1076, Jakarta 10010Telp.: (021) 2513251. Fax.: (021) 2513252Efficacy you can see

Galvus + Metformin dalam 1 tabletuntuk kenyamanan yang lebih

50 mg Galvus /500 mg metformin BID

50 mg Galvus/850 mg metformin BID

• DPP-4 inhibitor yang mendapatkan indikasisebagai monoterapi oleh BPOM RI 2

• “Add on” terapi untuk :

50 mg BID• Add-on to metformin atau TZD

50 mg QD• Add-on to SU


Documents

Brochure GALVUS