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carbetocin ppt.pptx
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FOGSI 2014. Consensus Statement for Prevention of PPH. Accessed online on dated 23 July 2021 from https://www.fogsi.org/wp-content/uploads/2015/11/pph.pdf
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Oxytocin
• Requires special
storage conditions: 2-
8°C
• Multiple dosing
regimen
• Short acting; multiple
doses may be required
• Overdose or prolonged
use can cause water
intoxication
• Prolonged use can
itself lead to uterine
atony
Ergometrine
• Requires special
storage conditions: 2-
8°C
• Associated with
significant increase in
side effects like
nausea, vomiting and
HT
• Needs to be avoided in
HDP, including chronic
HT
Misoprostol
• Less effective in
preventing PPH*
• More side effects, such
as shivering and
pyrexia*
• Associated with a
higher risk of severe
PPH and increased use
of additional
uterotonics*
• Use with caution in
patients with
cardiovascular disease*
Carboprost
• Requires special
storage conditions: 2-
8°C
• Associated with side
effects like vomiting,
diarrhea and
bronchospasm
• Needs to be avoided in
patients with asthma
or significant renal,
hepatic, or cardiac
disease
Syntometrine (Oxytocin+Ergometrin)- Combines the concerns of respective drugs
HT, hypertension; HDP, hypertensive disorders of pregnancy; * compared to oxytocin
Evensen A, et al. Am Fam Physician. 2017;95(7):442-449. Gulmezoglu AM, et al. Lancet. 2001 Sep 1;358(9283):689-95. Practice Bulletin No. 183: Postpartum Hemorrhage. Obstet Gynecol. 2017
Oct;130(4):e168-e186. FOGSI 2014. Consensus Statement for Prevention of PPH. Accessed online on dated 23 July 2021 from https://www.fogsi.org/wp-content/uploads/2015/11/pph.pdf
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Threats to Oxytocin Quality
Occur throughout the Supply
Chain for Oxytocin.
Threats to oxytocin quality
occur throughout
manufacturing,
procurement, distribution,
and storage
Lambert et al. Journal of Pharmaceutical Policy and Practice (2020) 13:14
7. Approved globally for medical use since last 2 decades; lately introduced in India
Long-acting synthetic analogue of oxytocin with agonist properties
Molecular structure different from oxytocin can lead to
Enhanced stability (avoid the cleavage of aminopeptidase and disulfide compounds)
Lower affinity for vasopressin V2 receptor
Rapid onset of action (within 1–2 min)
Prolonged duration of action (approximately 1 h)
Safety profile comparable to oxytocin
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Liu et al., Maternal-Fetal Medicine 2020;2:2. Holleboom et al., Arch Gynecol Obstet 2013:287:1111–1117
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Oxytocin: Drawbacks
Antidiuretic effects/water intoxication
Multiple dosing regimen
Short acting; repeat doses required
Failure of PPH prophylaxis
Stability and quality issues
Can be addressed by
carbetocin
9. Carbetocin was as effective as oxytocin in prevention of PPH
Carbetocin showed lesser mean blood loss in some studies
Carbetocin enhanced early postpartum uterine involution in some studies
Carbetocin showed fewer women requiring additional uterotonics in some studies
Carbetocin showed fewer women requiring uterine massage in some studies
Carbetocin showed lower blood transfusion rates in some studies
Carbetocin showed lower incidence of post partum anemia in some studies
10. Carbetocin showed lesser mean blood loss in some studies
Carbetocin showed fewer women requiring additional uterotonics in some studies
Carbetocin showed lower incidence of post partum anemia in some studies
Carbetocin was associated with lesser incidence of nausea and vomiting
Syntometrine was associated with increase in systolic and diastolic blood pressure
11. Carbetocin was more effective than misopristol in prevention of PPH
Carbetocin was associated with lower duration of 3rd stage of labour in some studies
Carbetocin showed lesser mean blood loss in some studies
Carbetocin showed fewer women requiring additional uterotonics in some studies
Carbetocin showed fewer women requiring uterine massage in some studies
Carbetocin showed lower blood transfusion rates in some studies in some studies
Adverse effects were more common in the misoprostol group
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Long acting; does not require prolonged IV infusion
Administered via a single IV injection, with no need for repeated injections
Well established dose; validated for the prevention of PPH
Lower affinity to the vasopressin V2 receptor compared with oxytocin
Possibly less blood loss & requirement of additional oxytocics
Stable at room temperature
Seems like an ideal uterotonic, but lacks room temperature stability
Carbetocin
13. Novel room temperature stable formulation of carbetocin
Same active ingredients, but differs in its excipients in order to increase stability
Devoid of need for cold chain maintenance and storage issues
Shelf-life of 24-36 months at 30oC and 75% humidity
Provided in a vial
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Characteristic Description
Onset of action • Within 2 minutes
Half-life • 33 minutes (IV)
• 55 minutes (IM)
Duration of action • 60 minutes (IV)
• 119 minutes (IM)
Dosage and mode of
administration
• 100 mcg administered IV (slowly over 1 minute) or IM
• Must only be administered after delivery of the infant, and as soon
as possible after delivery, preferably before the delivery of the
placenta
• Single use only (No further doses should be administered)
Storage Room temperature, ≤30°C and 75% relative humidity
Pabal Summary of Product Characteristics 2019. As accessed on dated 23 July 2021 from https://www.medicines.org.uk/emc/product/172/smpc#POSOLOGY
Pabal RTS Monograph. As accessed on dated 23 July 2021 from https://www.ferring.de/assets/Bilddaten-und-verlinkte-Dateien-www.ferring.de/Arzneimittel/PABAL/PABAL-RTS-Monograph-5.6.15.pdf
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Long acting; does not require prolonged IV infusion
Administered via a single IV injection, with no need for repeated injections
Well established dose that has been validated for the prevention of PPH
Lower affinity to the vasopressin V2 receptor compared with oxytocin
Possibly less requirement of additional oxytocics
Stable at room temperature
Provides all advantages of Carbetocin with further benefits of room temperature stability
17. Conducted by the WHO*
Randomized, multicentric, double- blind, active-controlled, noninferiority trial
23 sites in 10 countries
Primary outcomes:
Proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and
Proportion of women with blood loss of at least 1000 ml
CHAMPION TRIAL
N = 29645 women
RTS Carbetocin 100
mcg administered
immediately after
vaginal birth
N = 14823
Oxytocin 10 IU
administered
immediately after
vaginal birth
N = 14822
*in collaboration with Ferring and MSD for Mothers
(Carbetocin HAeMorrhage PreventION)
18. 14.5
1.51
10.4
1.6
14.4
1.45
10.4
1.3
0
2
4
6
8
10
12
14
16
Blood loss
>500ml or use of
additional
uterotonic agent
Blood loss > 1000
ml
Use of additional
uterotonic
agents
Blood
transfusion
Primary and secondary outcomes
Carbetocin Oxytocin
N Engl J Med. 2018 Aug 23;379(8):743-752
RTS carbetocin was non-inferior to oxytocin for
the prevention of blood loss of at least 500 ml
or the use of additional uterotonic agents
No significant differences between the two
groups in other measures of bleeding or in
adverse effects
These data inform care of women in parts of
the world where a lack of heat stability is a
barrier to the effective prevention of
postpartum hemorrhage
19. Advantages1
Clinical data generated in Indian
population
RTS carbetocin has shown efficacy and
tolerability at par with oxytocin
Limitations2
The trial may underestimate the benefit
expected with heat-stable carbetocin use
in real-life settings where oxytocin may
have degraded due to exposure to higher
temperatures.
1. N Engl J Med. 2018 Aug 23;379(8):743-752 2. https://www.who.int/news/item/27-06-2018-who-study-shows-drug-could-save-thousands-of-women%E2%80%99s-lives
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RTS carbetocin has been added to 21st WHO Essential Medicines List (2019)
WHO Model List of Essential Medicines. https://list.essentialmeds.org/?query=carbetocin
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The GDG noted that both heat-stable and non-heat-stable formulations of
carbetocin are available.
The heat-stable formulation differs from the non-heatstable formulation only in
its excipients.
Heat-stable carbetocin does not require refrigeration and therefore eliminates
the costs associated with refrigerated storage and transport for non-heat-stable
uterotonics.
GDG, Guideline Development Group
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FIGO, The International Federation of Gynecology and Obstetrics
ICM, The International Confederation of Midwives
FIGO and ICM launch joint statements of recommendation for the prevention and treatment of PPH. As accessed on 23 July 2021 from https://www.figo.org/figo-icm-pph-statements
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A similar sort of pharmacoeconomic evaluation should be considered in Indian set-up taking into account
costs of additional uterotonics, blood transfusion, extended hospital stay and resultant morbidities in
Carbetocin versus Oxytocin recipients for PPH prevention
Luni Y, et al. Journal of Obstetrics and Gynaecology, 2017. DOI: 10.1080/01443615.2017.1284188
28. Stability of uterotonics requiring cold storage is a grave concern in India
Carbetocin addresses most of the concerns with oxytocin; but still requires storage condition of 2-8°C
RTS Carbetocin provides all the advantages associated with heat labile carbetocin while overcoming the
limitation of cold storage requirement
Clinical data on RTS Carbetocin in Indian population is available from WHO’s CHAMPION trial
Meta-analysis has shown potential benefits of Carbetocin vs Oxytocin
Reduced blood loss
Reduced requirement of additional uterotonics
Reduced requirement of blood transfusion
Lesser reduction in Hb levels
RTS has been included in WHO essential medicine list and various guidelines
RTS Carbetocin has added useful tool in the arsenal for PPH prevention in India
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