Dr. Aby Abraham, MD, DM
Assistant Professor
Dr. Alok Srivastava, MD, FRACP, FRCPA, FRCP
Professor of Medicine
&
Dr. Sukesh C. Nair, MD, FRCPA (Haematology),
Professor, Department of Haematology and Department of
Transfusion Medicine & Immuno Haematology,
Christian Medical College,
Vellore-632004.
Why NICE Registry?
Off label uses >> Evidence-based indications
No consensus in dose and duration
Practice-based collection of data
NovoSeven® in Critical care Evaluation (NICE Registry)
in April 2006
NovoSeven® Advisory Board –
Dr. Alok Srivastava, MD, FRACP, FRCPA, FRCP
Dr. M.B.Agarwal, MD, MNAMS,
Dr. Palepu Gopal, MD, FRCA, CCST,
Dr. Rajesh Pande, MD, PDCC.
Aim: To see would it be possible to gather new
information?
09/04/2011
NICE Registry 2011
2
Acknowledgements
DR. A.C.SHUKLA
DR. A.SATISH
DR. AMITAVA SAHA
DR. ANAND KATKAR
DR. ARIJIT BOSE
DR. C.K.AURANGABADKER
DR. H. GADHIKAR
DR. KAYANOOD KADAGNATT
DR. KULDEEP A.DALAL
DR. MITUL P. CHARDA
DR. M.BHATTACHARYA
DR. OMENDER SINGH
DR. PRABHAKAR. S
DR. PIYUSH RANJAN
DR. RANJIT DESHMUKH
DR. RAJESH PANDE
DR. ROGESH BHURAT
DR. ROHINI SRIDHAR
DR. SAMEER PALTEWAR
DR. SHASHIKANT J. APTE
DR. SHAILESH R. SINGI
DR. SHIVINDER SINGH
DR. VILAS E. TAMBE
DR. VIJAY RAMANAN
DR. VINODAN
DR. COL.SUDHIR MEHROTRA
DR. A.R. BASU
DR. A.N. JHA
DR. ADARSH CHAUDHRY
DR. MRINAL SIRCAR
DR. P.AGARWAL
DR. SAMUEL SYLVESTER
09/04/2011
MATA CHANAN DEVI HOSPITAL, DELHI.
ABHAYA HOSPITAL, BANGALORE.
B.P.PODDAR HOSPITAL, KOLKATA.
BHARATI VIDHYAPEETH UNIVERSITY MEDICAL COLLEGE &
HOSPITAL, PUNE.
AMRI, KOLKATA.
VIVEKANAND HOSPITAL, NAGPUR.
DEENANATH MANGESHKAR HOSPITAL, PUNE.
JEHANGIR HOSPITAL & MEDICAL CENTRE, PUNE.
JASLOK HOSPITAL, MUMBAI.
APOLLO HOSPITAL, CHENNAI.
KOLKATA MEDICAL COLLEGE HOSPITAL, KOLKATA.
MAX SUPER SPECIALITY HOSPITAL, SAKET.
APOLLO HOSPITAL, HYDERABAD.
SIR GANGA RAM HOSPITAL, DELHI.
RUBY HALL CLINIC, PUNE.
FORTIS HOSPITAL, NOIDA.
LOKMANYA HOSPITAL, PUNE.
APOLLO SPECIALITY HOSPITAL, MADURAI.
SURETECH HOSPITAL & RESEARCH INSTITUTE, NAGPUR
SAHYADRI SPECIALITY HOSPITAL, PUNE.
FERNANDEZ HOSPITAL, HYDERABAD.
BASE HOSPITAL, DELHI.
CRITICAL CARE UNIT, NAGPUR.
RUBY HALL CLINIC, PUNE.
MEDICAL TRUST HOSPITAL, COCHIN.
MH AMBALA MILITARY HOSPITAL
COMMAND HOSPITAL, EASTERN COMMAND, KOLKATTA.
MEDANTATHE MEDICITY HOSPITAL, GURGAON.
MEDANTA THE MEDICITY HOSPITAL, GURGAON.
FORTIS HOSPITAL, NOIDA.
MAX SUPER SPECIALITY HOSPITAL, SAKET.
FRONTIER LIFELINE HOSPITAL, CHENNAI.
NICE Registry 2011
Contd…
3
Acknowledgements
DR. BALACHANDRAN NAIR. P
DR. NARENDRANATHAN. M
DR. RAJALAKEHMI. A
DR. SATISH. B
DR. AJITH K. NAIR
DR. VIJAYAN. K.N
DR. MATHEW THOMAS
DR. REVATHI RAJ
DR. ZAHEER AHMED SAYEED
DR. RAMNATH.S
DR. VIJAYA SHANKAR
DR. SOMNATH CHATERJEE
DR. VIJAYA MANOHAR
DR. KIRTHIVASAN
DR. BHARESH DEDHIA
DR. PRAVEEN MENON
DR. MOHAN MATHEW
DR. KHALEEL
DR. MADANMOHAN RAO
DR. HARISH
DR. VASUDEV
DR. ABHIJIT SARKAR
DR. S.K.SINGH
DR. MANASH GHOSH
DR. NITIN.K / DR.ARUN AGARWAL
DR. VISHAL SINGH
DR. NIRMALA AGARWAL
DR. CHIRAG SHAH
DR. CHIRAG MATRAVADIA
DR. SELVAKUMAR.
09/04/2011
KIMS, TRIVANDRUM.
KIMS, TRIVANDRUM.
KIMS, TRIVANDRUM.
KIMS, TRIVANDRUM.
KIMS, TRIVANDRUM.
KIMS, TRIVANDRUM.
KIMS, TRIVANDRUM.
APOLLO HOSPITAL, CHENNAI.
APOLLO HOSPITAL, CHENNAI.
APOLLO HOSPITAL, CHENNAI.
APOLLO HOSPITAL, CHENNAI.
MANIPAL HOSPITAL, BANGALORE.
AGADI HOSPITAL, BANGALORE.
FRONTIER LIFELINE HOSPITAL, CHENNAI.
WOCKHARDT HOSPITAL, MUMBAI.
LOURDES HOSPITAL, ERNAKULAM.
LAKESHORE HOSPITAL & RESEARCH CENTRE, COCHIN.
MEDICAL TRUST HOSPITAL, COCHIN.
HOPE HOSPITAL, HYDERABAD.
KRISHNA CHILDREN’S HOSPITAL, HYDERABAD.
MAX BALAJI HOSPITAL, DELHI.
PEERLESS HOSPITAL, KOLKATA.
AMRI HOSPITAL, KOLKATA.
GNRC, GOUHATI.
BMC HOSPITAL & RESEARCH CENTRE, JAIPUR.
FORTIS ESCORTS HOSPITAL, OKHLA.
SANT PARMANAND HOSPITAL, DELHI.
APOLLO HOSPITAL, AHMEDABAD.
STERLING HOSPITAL, RAJKOT.
MADRAS MEDICAL MISSION HOSPITAL, CHENNAI.
NICE Registry 2011
Contd…
4
Acknowledgements
DR. SHABBAR H.K JOAD
DR. A.K. MANDAL
DR. BHARDWAJ / DR. BETTY ELIZABETH
DR. SELVA KUMAR / DR. MANOHAR
DR. VIMALA / DR. ROY/ DR. UDAY
DR. NEVILLA AG SOLOMON
DR. THANGARAJ / DR. PAUL JUDE
DR. VIJAYSHANKAR
DR. M. RAJA
DR. JAYASHREE GAJRAJ
DR. WAHIDA SURESH
DR. SRINIVAS
DR. LT. COL. P. MUKERJI
DR. COL TVSP MURTHY
DR. BRIG M LUTHRA
DR. RAJESH PANDE
DR. DEEPA DAS
DR. VIVEK SINGH
DR. YATIN METHA
DR. RAJESH SHARMA
DR. VINEET SANKHLA
DR. SIBABRATA BANNERJEE
DR. SHOBHA / DR.SATISH KRISHNA
DR. MAMMEN CHANDY
DR. ALOK SRIVASTAVA
DR. AURO VISWABANDYA
DR. VIKRAM MATHEWS
DR. ARUNA KEKRE
DR. NAGAMANI SEN
DR. SUBRAMANIAN
DR. BIJU GEORGE
09/04/2011
FORTIS ESCORTS HOSPITAL, JAIPUR.
FORTIS HOSPITAL, MOHALI.
MADRAS MEDICAL MISSION HOSPITAL, CHENNAI.
MADRAS MEDICAL MISSION HOSPITAL, CHENNAI.
MADRAS MEDICAL MISSION HOSPITAL, CHENNAI.
APOLLO CHILDRENS HOSPITAL, CHENNAI.
APOLLO SPECIALITY HOSPITAL, CHENNAI.
APLLO SPECIALITY HOSPITAL, CHENNAI.
APOLLO SPECIALITY HOSPITAL, CHENNAI.
APOLLO SPECIALITY HOSPITAL, CHENNAI.
APOLLO SPECIALITY HOSPITAL, CHENNAI.
APOLLO CHILDRENS HOSPITAL, CHENNAI.
ARMY HOSPITAL(R&R), DELHI.
COMMAND HOSPITAL, LUCKNOW.
ARMY HOSPITAL (R&R), DELHI.
B.L KAPOOR MEMORIAL HOSPITAL, NEWDELHI.
PARAS HOSPITAL, GURGOAN.
COLUMBIA ASIA HOSPITAL, GURAGOAN.
MEDANTA INSTITUTE OF NEUROSCIENCES, GURAGAON.
ESCORTS HEART HOSPITAL, NEWDELHI.
APOLLO HOSPITALS, AHMEDABAD.
MISSION OF MERCY, KOLKATA.
SREE UTHRADOM THIRUNAL HOSPITAL,TRIVANDRUM.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
CHRISTIAN MEDICAL COLLEGE, VELLORE.
NICE Registry 2011
5
Registry outline
Both web-based (www.niceindia.net) and nonweb based
Components of Registry
Demographic data
Clinical History and Indication of NovoSeven®
Laboratory parameters
Dose of NovoSeven® and Response to this complication
Outcome
09/04/2011
NICE Registry 2011
6
19/04/2009
Christian Medical College, Vellore.
NICE Registry 2011
7
7
19/04/2009
09/04/2011
Christian Medical College, Vellore.
NICE Registry 2011
8
8
19/04/2009
09/04/2011
Christian Medical College, Vellore.
NICE Registry 2011
9
9
Collection of data
NICE Registry in April 2006 to Feb 2011
Distribution of demographic data (n=380)
Age
n
Median
Range
(in years)
Overall
380
40
1–91
Age ≤15
53
3
1–15
Age > 15
327
46
16–91
Sex
n
%
Male
Female
247
133
65
35
Indications (n=380)
Milliliter
Blood loss prior to the usage of
NovoSeven®
* Number of patients
Haematological parameters
Hb – Haemoglobin, PT – Prothrombin time, aPTT – activated partial thromboplastin time
Other parameters
P = 0.132
Mean
Mean
P=0.004
N
84
54
54
N
09/04/2011
38
p=0.212
Mean
Mean
p=0.054
37 10
38
p = 0.396
P = 0.373
N
69
17 8
17
N
8
NICE Registry 2011
42 17
23 8
23
8
15
Abnormal LFT (n=46)
p=0.494
p=0.569
Median
p=0.455
N
25
19
29
20
24
17
SGOT - Serum glutamic oxaloacetic transaminase; SGPT - Serum glutamic pyruvic transaminase
Median
Dosage of NovoSeven® used (µg/kg)
(Based on body weight)
N
380
98
23
14
9
Patients received 3 doses of NovoSeven®
Median
Range
2
42
24–60
Anticoagulant-associated bleed
1
90
90
UGI & LGI bleed
2
75
70–80
Cardiac
1
86.67
87
Thrombocytopenia/Coag/IC/Platelet
1
66
66
IC/Platelet
2
41
16–66
IC
3
30.76
16–66
Liver disease/UGI/Platelet
1
70
70
Indication
(3 doses=9)
Obstetric bleeding
(µg/kg)
(µg/kg)
Patients received >3 doses of NovoSeven®
Indication
(>3 doses=14)
Median
Range
(µg/kg)
(µg/kg)
Other surgery, Thrombocytopenia,
Other Coagulopathies
1
40
40
Liver disease, UGI
1
90
90
Anticoagulate
1
90
90
Other coagulopathies
6
66.18
39–80
Thrombocytopenia, Dengue
1
67.5
68
IC
1
41.16
41
Obstetric bleeding
1
53
53
Platelet
1
150
150
Other Coagulopathies,
Thrombocytopenia, Liver disease
1
80
80
Cardiac
1
26.6
27
Dengue
2
48.75
30–68
NovoSeven® – Indication and doses
Medical causes of bleeding
NovoSeven® – Indication and doses
Median Dose
(ug/kg)
Surgical causes of bleeding and trauma
Blood products usage in different
medical/surgical condition before
and after the usage of NovoSeven®
Blood products usage in liver disease
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in UGI/LGI bleed
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in thrombocytopenia
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in dengue
haemorrhagic fever
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in anti-coagulopathies
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in intracerebral
haemorrhage
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in trauma
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in other
coagulopathies
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in obstetric bleeding
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in cardiac surgery
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in other surgery
R = RBCs, W = WBCs, P = Platelet, C = Cryoprecipitate, F = Fresh frozen plasma
Blood products usage in different medical
condition after the usage of rFVIIa
After the administration of rFVIIa, most of the
patients received ≤ 3 units of RBCs
Transfusion of all blood products was substantially
reduced
Response
50
42.7
42.3
41.4
38.3
Percentage
40
28.3
30
20.3
20
0N
19.5
12
10.1
10
98
67
48
24
1 hr (237)
Bleeding stopped
28
27.9
26
25.5
20.2
9.8
7.8
159
76
96
45
6 hrs (376)
Minimal Bleeding
40
59
43
12
12 hrs (154)
Bleeding reduced
35
23
16
Day 2 (82)
Bleeding not reduced
8
Overall efficacy of NovoSeven®
Overall survival rate with usage of
NovoSeven®
Usage of NovoSeven® in different
medical and surgical bleeding
Usage of NovoSeven®
in anticoag-associated bleeding
n= 11; Median dose – 60 µg/kg
Efficacy
Survival rate
Usage of NovoSeven®
in intra-cerebral haemorrhage
n= 70; Median dose – 46.5 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in cardiac surgery
n= 66; Median dose – 40 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in trauma
n= 44; Median dose – 55 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in obstetric bleeding
n= 48; Median dose – 60 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in other surgery
n= 31; Median dose – 60 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in UGI/LGI
n= 40; Median dose – 60 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in liver disease
n= 46; Median dose – 60 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in other
coagulopathies
n= 42; Median dose – 60 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in thrombocytopenia
n= 39; Median dose – 60 µg/kg
Efficacy
Survival rate
Usage of NovoSeven® in dengue
haemorrahagic fever
n= 15; Median dose – 75 µg/kg
Efficacy
Survival rate
Adverse events
Adverse events
Number of events
CVA
1
DVT
2
Multi-organ failure
4
ARDS
7
Others
3
Causes of death [n=112]
ACUTE FULMINANT HEPATIC FAILURE, SEPSIS, ARDS
DHF/DIC/MODS.
ACUTE RENAL FAILURE, METABOLIC ACIDOSIS,
ANTRODUODENAL ULCER BLEED, CHRONIC LIVER
DISEASE, CIRRHOSIS, PHT, DUODENAL VARICES
DIC, MULTI ORGAN FAILURE - 2
ADVANCE METASTATIS CARCINOMA OF URETER WITH
SEPSIS, MOF
DIC, INTRACEREBRAL BLEEDING, ESRD, CHRONIC
LIVER DISEASE
APLASTIC ANAEMIA, DIFFUSE ALVEOLAR
HAEMORRHAGE, GI BLEED, MODS, ARDS & ARF
DISSEMINATED INTRAVASCULAR COAGULATION
ARDS, CARDIORESPIRATORY ARREST
END STAGE HF, ORTHOTOPIC HEART
TRANSPLANTATION, SEPTICAEMIA, MODS
ARDS, SHOCK, MULTI ORGAN FAILURE
FEVER + DIC + DIFFUSE ALVEOLAR HAEMORRHAGE
ASPIRATION
FUNGAL PNEUMONIA & SEPTICEMIA
BRADYCARDIA,HYPOTENSION, DILATED
CARDIOMYOPATHY
FUNGAL SEPSIS, SEPTIC SHOCK, SEVERE DIC
BRAIN STEM DYSFUNCTION, EVANS SYNDROME, POST
SPLENECTOMY - 2
HAEMORRAGIC SHOCK - 2
BLUNT TRAUMA ABDOMEN WITH MULTIPLE MESENTRIC
TEARS, WITH SEPSIS WITH MOF.
HEMORRHAGIC SHOCK / PPH
CARDIAC ARREST, CARDIOGENIC SHOCK - 3
HYPOTENSIVE SHOCK
CHRONIC LIVER DISEASE - 3
HYPOVOLEMIC SHOCK
CMV PNEUMONIA WITH ARDS
HYPOXIC ISCHAEMIC ENCEPHALOPATHY
Causes of death [n=112] (Contd.)
DECOMPENSATED LIVER DISEASE, MOF
MODS
DENGUE HAEMORRHAGIC SHOCK - 2
ICH
DHF & CARDIAC ARREST
HYPOVOLUEMIA SECONDARY TO SEVERE BLOOD LOSS
WITH MULTIPLE LIVER LACERATIONS TO BLUNT
TRAUMA ABDOMEN & CHEST
ARDS & ARF
INTRACEREBRAL HAEMORRHAGE
INTRACRANIAL HAEMORRAGE
MULTISYSTEM ORGAN FAILURE
INTRACEREBRAL HAEMORRHAGE
PATIENT DIED FROM OTHER COMPLICATIONS,
BLEEDING WAS STOPPED AFTER rFVIIa
INTRACTABLE VENTRICULAR ARRHYTHMIA WITH LOW
CARDIO OUTPUT, POST CABG
PERI AMPULLARY & PANCREATIC CARCINOMA
PATIENT EXPIRED AFTER 8 DAYS BECAUSE OF ACUTE
INTRACTABLE CARDIO RESPIRATORY FAILURE DUE TO
FATTY
LIVER OF PREGNANCY, THOUGH HER BLEEDING
SEVERE PAH CRISIS, S/P TRUNCUS ARTERIOSUS REPAIR
STOPPED AFTER rFVIIa
(VSD CLOSURE, RV TO PA CONDUIT)
INTRACTABLE RESPIRATORY FAILURE DUE TO RECURRENT
PNEUMONIA WITH SEPSIS
PULMONARY HAEMORRHAGE AND SEPSIS
LIVER DAMAGED – 4
POLY TRAUMA, COLLAPSE OF RIGHT LUNG
LOW CARDIAC OUTPUT,SEVERE PULMONARY ARTERIAL
HYPERTENSION
POLYTRAUMA
LOW CARDIAC OUTPUT, MODS, AV CANAL DEFECT, VSD
POST-OP SEPSIS
LUNG BRONCHOPNEUMONIA, RENAL TRANSPLANT
IMMUNOSUPPRESION, TYPE II DIABETES MELLITUS
PPH WITH MULTIORGAN FAILURE
MASSIVE BLEEDING/SEPSIS/ARDS
MALIGNANT HYPERTHERMIA, RHABDOMYOLYSIS, ARF,
SEPTICEAMIA, RESPIRATORY DISTRESS, DIC
Causes of death [n=112] (Contd.)
METABOLIC ACIDOSIS, SEVERE ANEMIA, SHOCK
PULMONARY HAEMORRHAGE / ARDS
MLC CARE
REFRACTORY ACUTE CARDIAC ALLOGRAFT REJECTION
MODS
RTA, LIVER LACERATION, FULMINANT HEPATIC
FAILURE, DIC
MODS DUE TO DHF, IC BLEED
MODS, ACS, REFRACTORY SHOCK
MSOF, AML
S/P ARTERIAL SWITCH OPERATION FOR D-TGA, ASD, PDA WITH
HYPOXIC ENCEPHALOPATHY
S/P ARTERIAL SWITCH OPERATION, VENTRICULAR TACHYCARDIA
DEGENERATING TO CARDIAC ASYSTOLE
SDH WITH MIDLINE SHIFT BRIANSTEM CONTUSION,
RESPIRATORY ARREST
MULTI-ORGAN FAILURE -3
SEPSIS DUE TO IMMUNOCOMPROMISED STATE
MULTI-ORGAN FILURE WITH DIC
SEPSIS WITH ARDS WITH ARF - 4
MULTI-ORGAN FAILURE WITH BLEEDING DIATHESIS
SEPSIS, LIVER DAMAGED
SEPSIS, MULTI-ORGAN FAILURE
SEPTICAEMIA, LEFT LOWER LIMB, DIC, ARF
SEPSIS, CHRONIC LIVER DISEASE, UPPER GI BLEED
SEPTICEMIA,CARDIOGENIC SHOCK
SEPSIS, MODS WITH UNCONTROLLED BLEEDING
SEVERE CALCIFIC AORTIC STENOSIS
SEPSIS/MODS/ARF/MOF - 3
SEVERE HYPOTENSION & EXCESS OF BLEEDING
SDH, INTRACEREBRAL HAEMORRHAGE, DM, HTN, CRF
SUB-ARACHNOID HAEMORRHAGE, BRAIN STEM DYSFUNCTION,
CARDIO-RESPIRATORY ARREST
SEPTIC SHOCK, MULTI-ORAGAN FAILURE, ACUTE RENAL
FAILURE
TERMINAL CARDIO-RESPIRATORY ARREST IN C/O HEPATO -RENAL
SHUT DOWN, SEPTICEMIA, DIC, SHOCK, THROMBOCYTOPENIA IN
K/C/O CIRRHOSIS OF LIVER
SEPTIC SHOCK
VENTRICULAR FIBRILLATION DEGENERATING TO ASYSTOLE
SEPTICAEMIA WITH MOF WITH DIC - 3
UNKNOWN – 5
Limitations
Not all cases reported
Data incomplete
No independent check of data
No definite conclusions can be drawn
Impact of NovoSeven® outcome
Conclusion
No significant variation in dose of rVIIa between those
who responded vs. those who did not in medical causes
of bleeding
All patients with IC bleed who survived
received a median dose of 48 µg/kg
The median dose of rVIIa used was maximum
in Dengue haemorrhagic fever though no
difference in outcome
Median dose correlated with outcome both in surgical
and obstetric cases of bleeding was 60 µg/kg and 40
µg/kg, respectively
There was no correlation with outcome and dose of
rVIIa in trauma-related bleeding
Conclusion (Contd.)
1st step towards collection of data in off-label use in India
Wide variation in practice
At present, a larger data is needed to substantiate any
specific dose recommendation in off-label use