ATOSIBAN IN PRETERM LABOR by Dr Sharda Jain

1. …Caring hearts, healing hands
DR. SHARDA JAIN

2. • Great Teacher & surgeon ,taught for 2 decades in medical college (PGI Chandigarh , LHMC, Delhi )
• ETHICAL COMMITTEE MEMBER OF MEDICAL COUNCIL OF INDIA
• “TEACHER OF THE TEACHER AWARD” by Delhi Gynaecologist forum 2018
• Life time achievement Award from FOGSI (national organisation of Gynaecologists )
*IMA medical Association
*Lady Harding Medical Collage
*Delhi gynaecologist forum
• *ISAR ( Delhi)
• Founder chairman (for a decade )PushpanjaliCrosslayHospital now Max vaishali
• Founder & director of Lifecare Centre & IVF which is serving east Delhi for last 27 year for GYNAE
care , IVF ,Bariatric surgery , Advanced Lap / Hyst Surgery
• FOUNDER & SECRETARY GENERAL OF DELHI GYNAECOLOGIST FORUM ( 2000 )
• Recognised as Great Medical social worker is behind National movements of Female foeticide ,
Anamia Free India , Adolescent Health , Save uterus, Save girl child etc
NOW HER PASSION 360 * CARE ,DOCTORS TRAINING & SAFETY OF DOCTORS
DR. SHARDA JAIN
M.D. (PGIMER), MNAMS,FICOG,FIMSA,
DHM, QM &AHO
PGDMLS (SYMBIOSIS)
PRESENTED ON 28/11/2018 IN GAZIABAD OBS/GYNAE SOCIETY

4. U have to learn
8
+
8
+
8
LIFE
3F
3H
3S

5. One of the earliest descripting of PRETERM BIRTH
On December25,1642when awidowgave birthprematurelytoamale child ,his mother Hannah
Ayscoughreportedlydescribed thatchild as
“So small that he could have been put into a quart mug” (-1.3 liters)
The infant survived & grew up to be” sir isaac newton”
“However , a significant proportion of preterm births do not survive ,
let alone grow to become Newton”

6. INDIA SCENARIOWHO2012
1/4
1/6

7. PRETERM BIRTH
• Approximately 0.5% of all births occur before of
third trimester of pregnancy contributing
majority of NND.
• Most infants born at or above 26 weeks have a
high likelihood of survival ( policy of resusitation ).
However few of these children also have high
risk of permanent disability.

8. Complications of Preterm Delivery
• 75% of neonatal mortality occurs in Infants. Preterm
• The long-term sequelae of PTB include:
• – CNS complications, such as cerebral palsy,seizures
• – Neurodevelopmental delay
• – Respiratory complications
• – bronchopulmonary dysplasia,RDS
• – Blindness & deafness
• – GIT: Necrotising enterocolitis
• – Cardiovascular: PDA, persistent fetal circulation
• – Metabolic: hypoglycemia, hypocalcemia, jaundice .
Highest incidence of complications in births
occurring at <30 weeks gestation

9. OUTCOME OF PRETERM BIRTHS
Potentially modifiable factors that influence the outcome are
•ANTEPARTUM CORTICOSTEROIDS (betamethasone
>dexamethasone ).Repeat dose not needed
(.C.I…INFECTION)
• ANTIBIOTICS IN PPROM ( B haemolytic streptococus
• CERCLAGE (controvertial )
• MAGSULPH FOR NEUROPROTECTION.(25 33wks
• TOCOLYSIS (short period unless contra indicated )
• PLACE & METHOD OF DELIVERY ( vaginal prefered )
• POSTNATAL MANAGEMENT INCLUDES INITIATING &
CONTINUING CARE IN NICU

10. Delivery is recommended at a Centre with
level 111- IV NICU
Delivery is recommended at a Centre with
level 111- IV NICU is ideal.
Utero transfer is associated with improved
neonatal outcome but in some cases,
circumstances may preclude antenatal maternal
transport
then neonatal transport after delivery may be
needed .
Protocols also should be in place to facilitate
postpartum consultation & transfer.

11. Rationale for Tocolysis
• To prolong pregnancy and to aim for term delivery
(This is still what women and the lay public expect from us.)
• This idea -superseded by recent dogma : tocolytics are
given to delay delivery for 48 hours,
• * To allow Ante partum glucocorticoids to induce lung maturation
• * Utero transfer to a tertiary care centre with NICU facilities –
Delay
• of delivery just for 48 hrs to permit growth, maturation of
LUNGS & to reduce mortality & morbidity
• Ronald F Lamont. Expert Rev. Obstet. Gynecol. 3(2), 163–174 (2008).

12. SPECTRUM OF TOCOLYTIC AGENTS
Gr. tokos: childbirth, lytic: capable of dissolving
• β-mimetics 1 & 2
• MgSO4
• Ca Channel Blockers
• Oxytocin antagonist
• Progesterone

13. Tocolytic Therapy: Historical Perspective
1960s- the management - bed rest, hydration, opiate analgesia & iv alcohol.
1970s- β1-agonists (isoxuprine) were introduced. FDA approval ritodrine
1980s- “decade of β 2-agonists” (salbutamol, terbutaline, orciprenaline,
fenoterol & Other- MgSO4,indomethacin. Expert Opin. Pharmacother.
(2014) 15(5):585-588.
1990s- Reappraisal of the use of β2-agonists due to concerns about serious
adverse effects e.g. pulmonary edema.
• Subsequently, a gradual drift away from -β2-agonists
• to ATOSIBAN & Nifedipine

14. AN IDEAL TOCOLYTIC AGENT
• • Modes of Action: Uterospecific
• • Efficacy: Short term as well as long term
• • Safety: Maternal & neonatal
• • Cost: Affordable
• • Licensing for use: Approved /off label
• • Evidence: Cochrane, RCOG, RCT

15. U R USING ??
Which Drug

16. Most of the Currently used Tocolytics acts
on Non-myometrial Tissues
Agent Non-myometrial Tissues Responsive
β-adrenergic receptor agonists
Myocardium, Smooth muscles, Juxtaglomerular cells, Skeletal muscle,
Liver
Calcium channel blockers Vascular smooth muscle, Cardiac conduction
Magnesium sulphate Smooth muscle, Brain NMDA receptor, Neuromuscular junction blockage
Nitric oxide donors Vascular smooth muscle
BJOG. 2005 Mar;112 Suppl 1:74-8.
The primary target of tocolytics is the myometrial cell
The wide distribution of responsive tissue is major
determinant of NUMEROUS UNDESIRED SIDE EFFECTS
with these agents.

17. As a result, no other tocolytic is utero specific and, therefore, all other tocolytics
have multi-organ side effects.
Class of drugs Primarily licensed for
Beta-adrenergic agonists Bronchial asthma
Cyclooxygenase inhibitors Inflammation, pain, fever
Gestagens/Progestogens Hormonal substitution, contraception
Magnesium sulphate Hypomagnesaemia, Eclampsia in pregnancy
CCBs (DHPs) Hypertension
Oxytocin antagonists (ATOSIBAN) Tocolysis
APART FROM THE OXYTOCIN RECEPTOR ANTAGONIST
ATOSIBAN, NO TOCOLYTIC HAS BEEN SPECIFICALLY
DEVELOPED FOR THE TREATMENT OF SPTL.
1.Ronald F Lamont. Expert Rev. Obstet. Gynecol. 3(2), 163–174 (2008).

18. CHOICE OF TOCOLYTICS
• Specifically developed to be
UTEROSPECIFIC
- Oxytocin receptor antagonist –
ATOSIBAN
• Not specifically developed (Not
uterospecific)
- Beta-agonists
- Nifedipine
- NSAIDs
- MgSO4
• Licensed preparations
- Oxytocin receptor antagonist –
Atosiban
- Beta agonist – Ritodrine, isoxsuprine,
Terbutaline, salbutamol, fenoterol
• Unlicensed preparations/not
approved by regulatory
authority
- Calcium channel blockers [CCBs] -
Nifedipine, Nicardipine
- Nitric oxide donors (No donors)-
glyceryl trinitrate [GTN]
- PG synthetase inhibitors –
Indomethacin, sulindac, COX-2
inhibitors
- MgSO4 (magnesium sulfate)

19. Atosiban: A novel Tocolytic Agent

20. USP OF ATOSIBAN
• Oxytocin receptors are crucial for the onset of human labor.
• Plays two important roles in :
 the initiation of labour &
 the expulsive phase of labour
• Atosiban acts only on myometrium/myoepithelial tissue (most
uterospecific).
* Best maternal and fetal safety profile
*Only tocolytic drug without serious ADR
• Atosiban was developed specifically to treat preterm labor
• NOW FIRST-LINE TOCOLYTIC for the management of spontaneous
preterm labour.2
2. Experimental Physiology (2001) 86.2, 297–302. 1. Science.
1982 Mar 12;215(4538):1396-8.

21. ATOSIBAN: Is an advance in currently
available TOCOLYTICS
• Safest choice In:
*Multiple pregnancies,
*Expanded blood volume &
*Anemia
Di Renzo GC. J Perinat Med. 2006; 34(5):359-66.
WHERE USE OF
OTHER
TOCOLYTICS
PREDISPOSE TO
PULMONARY
EDEMA.

23. Recommended
atosiban in the
management of
Preterm labor. [3,4]
Atosiban
1. Presented at Ninth World Conference in Perinatal Medicine. Symposium on Uterine
Contractility, [Berlin] 2009).
2. Lamont CD. Expert Opin Drug Saf. 2016 Sep;15(9):1163-73.
3. Rcog. Tocolytic drugs for women in preterm labour: Royal College of Obste-
tricians and Gynaecologists (RCOG). 2002.
4. Expert Opin Pharmacother. 2014 Apr;15(6):787-97.
Atosiban as a first-line tocolytic for the management of
Spontaneous Preterm Labor.[1,2]
International Preterm Labour Guidelines and Tocolytic
Treatment Recommendations advocate

24. Atosiban: International Preterm Labour Guidelines &
Tocolytic Treatment Recommendations
Countries Guidelines &
Organizations
Recommendations
United
Kingdom
Royal College of Obstetricians
and Gynaecologists (R.C.O.G.)
If tocolytics are to be used, atosiban or
nifedipine are preferable.
Atosiban is licensed and nifedipine is not.
β2-agonists should not be used.
Spain PTL guideline No 10-S.E.G.O.
(Spanish Society of Gynecology and
Obstetrics)
Atosiban to be used as first choice
Austria O.E.G.G.G.
(Austrian Society GYN/OB)
Atosiban or β-agonists.
Atosiban first line for certain patient groups.
Belgium G.G.O.L.F.B. & V.V.O.G. Atosiban 1st line treatment (treatment of
choice)
Netherlands Dutch Gynecology Society
(N.V.O.G.)
Atosiban a ‘first choice’ for tocolysis.
1. Ref: Presented at Ninth World Conference in Perinatal Medicine. Symposium on Uterine Contractility, [Berlin] 2009.
2. Lamont CD. Expert Opin Drug Saf. 2016 Sep;15(9):1163-73.

25. Countries Guidelines & Organizations Recommendations
France PTL Guidelines C.N.G.O.F.
(College National des
Gynecologues et Obstetriciens
Francais)
Atosiban, first line of treatment.
In multiple pregnancies
recommended
first line: atosiban or nifedipine
Portugal No National Guidelines Atosiban or nifedipine are the
most prescribed tocolytic drug.
Atosiban recommended for diabetic
patients, multiple pregnancies and
women with cardiac pathology.
Italy S.L.O.G. Atosiban first line for “risk patient”
Atosiban: International Preterm Labour Guidelines &
Tocolytic Treatment Recommendations
Ref: Presented at Ninth World Conference in Perinatal Medicine. Symposium on Uterine Contractility, [Berlin] 2009

26. Countries Guidelines & Organizations Recommendations
Denmark Danish Society of Obstetrics
and Gynecology (D.S.O.G.)
Recommendation of Atosiban as first line
of treatment
Sweden No national guidelines. Work
in Progress
80% of the guidelines at level III
hospitals are recommending atosiban as
1st line.
Germany D.G.G.G.
(German Society of Gynecologists &
Obstetricians)
Atosiban, fenoterol, nifedipine are
recommended.
Atosiban has less side effects.
Norway Norwegian Society of
Obstetrics and Gynaecology
(N.G.F.)
1.Atosiban 2. Nifedipine
3. Indomethicin 4. Terbutaline
Atosiban: International Preterm Labour Guidelines &
Tocolytic Treatment Recommendations
1. Ref: Presented at Ninth World Conference in Perinatal Medicine. Symposium on Uterine Contractility, [Berlin] 2009.
2. Lamont CD. Expert Opin Drug Saf. 2016 Sep;15(9):1163-73.

27. THERAPEUTIC PREREQUESITES
• Indicated to delay imminent pre-term birth in
pregnant adult women with:
• * Regular uterine contractions of at least 30 seconds
• duration at a rate of ≥ 4 per 30 minutes
• * Cervical dilation of 1 to 3 cm (0-3 for nulliparas) and
• effacement of ≥ 50%.
• * GESTATIONAL AGE FROM 24 UNTIL 33 COMPLETED
WEEKS
• * Normal foetal heart rate
• Tractocile International prescribing information.

28. PHARMACO-DYNAMICS
• Decreases the frequency & tone of uterine
contractions.
• Antagonizes uterine contractions & induces
uterine quiescence.
• The onset of uterine relaxation is rapid,
contractions significantly reduced within 10
min to achieve stable uterine quiescence (≤ 4
contractions/hour) for 12 hours.
Ronald F Lamont.. Expert Rev. Obstet. Gynecol. 3(2), 163–174 (2008).

29. Standard Dosing Regimen for Atosiban
Administered Intravenously in Three Successive Stages
Step Regimen Infusion rate Duration
1 0.9 ml I.V.
injection
Bolus (6.75 mg) Given over 1 minute
2
I.V.
loading
infusion
300µg/min 3 hr
3
I.V.
infusion.
100 µg/min
Up to 45 hours

31. CONTRAINDICATIONS
• Intrauterine foetal death
• Suspected intrauterine infection
(chorioamnionitis)
• Placenta praevia, Abruptio placenta
• Any other conditions of the mother or
foetus, in which continuation of
pregnancy is hazardous
• Hypersensitivity to the atosiban or
excipients
• Gestational age : < 24 or > 33
completed wks.
• PROM >30 wks of gestation
• Abnormal foetal heart rate −
• Antepartum uterine hemorrhage
• Eclampsia & severe pre-eclampsia
Tractocile International prescribing information.

32. ADVERSE REACTIONS
• ADRs were generally of a mild severity.
• The most commonly reported adverse
reaction in the mother is Nausea (11 %).
• No specific ADR in newborn.
• Di Renzo GC, Roura LC; European Association of Perinatal Medicine-Study Group on Preterm Birth. Guidelines for the management of spontaneous
preterm labor. J Perinat Med. 2006; 34(5):359-66. Adverse Reactions

33. INFANT: LONG TERM SAFETY
• According to a current meta-analysis of 9
randomized no fetal side effects have been
reported.
A follow-up study of infants born after tocolysis
with atosiban revealed NO ILL EFFECT on their
psychosocial and motor development up to the
age of two years.
• The Worldwide Atosiban versus Beta-agonists
Study Group. BJOG. 2001 Feb;108(2):133-42.

34. ATOSIBAN SAFETY: NO BAD EFFECT ON
PLACENTAL & FETAL CIRCULATION.
Grzesiak M, Wilczynski J. Preliminary report of 48-hours Atosiban administration in spontaneous preterm labor - Doppler blood flow assessment of
placental and fetal circulation. Neuro Endocrinol Lett. 2013;34(7):681-6.
Atosiban doesn't alter
uterine nor fetal arterial
blood flow pattern.
Hemodynamic cardiac
activity in fetuses remains
unaffected.

35. NO EFFECT ON BREAST FEEDING (LACTATION)
• The administration of atosiban during
pregnancy has no effect on the type of
lactation in term newborns
• Studies showed that betamimetics
reduced mammary gland tissue &
decreased milk production.
•
However this has not been observed in the case of
atosiban
López Gómez L,. Breastfeed Med. 2018 Jan 22. doi: 10.1089/bfm.2017.0206.

36.  Patients with renal or hepatic impairment
a) Renal impairment is not likely to warrant a dose adjustment.
b) Should be used with caution in impaired hepatic function
 Paediatric population
a) The safety and efficacy in pregnant women < 18 yrs have not been
established.
 Atosiban is not involved in CYP450 mediated drug-drug interactions.
 No clinically relevant interaction was found between atosiban and
bethamethasone or labetalol
Tractocile International prescribing information.
EFFECT ON KIDNEY, LIVER ,
< 18 YRS

37.  Jan. 2000 :Atosiban approved in the European Union.
 On 30 May 2013 The EMA granted a marketing authorisation for
atosiban SUN (Sun Pharmaceutical) a generic of Tractocile.
 Oct. 2014 : Approved In India.(Zuventus health care ltd)
 As of June 2007 atosiban is approved in 67 countries, excluding
the USA, Japan.
Ronald F Lamont. Expert Rev. Obstet. Gynecol. 3(2), 163–174 (2008).
REGULATORY AFFAIRS

39. The Clinical Experience of Atosiban
in Preterm Labour
• Aims: To evaluate the efficacy, safety and tolerability of atosiban in delaying
preterm labour.
• Study design: A prospective, open label, non comparative study
• Place of Study: Lokmanya Tilak Municipal Medical College Mumbai, India.
• Methodology:
• Pregnant women (N=110) between the gestational age of 24 to 34 wks,
presenting with signs of preterm labour were enrolled in the study.
• Efficacy, safety & tolerability of atosiban were assessed for a period of 72 hrs.
Dewan B, Shah D. BJMMR.2016;13(7):1-9. Article no.BJMMR.23823.

40. Efficacy analysis based on duration of tocolysis
89.09% 89.09% 88.18%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
48 hrs 72 hrs At discharge
Figure 1: Percentage of patients remaining undelivered at 48 hrs, 72 hrs and at
discharge (≤7 day)
1. No alternative tocolytics were required during the entire study
2. Atosiban retreatment not required by any patient (upto 7days)
3. 100% Successful in multiple birth pregnancy (7 out of 7
patients)
4. No Fetal or Maternal Side effects observed.
5. All patients tolerated Atosiban well Dewan B, Shah D. BJMMR.2016;13(7):1-9. Article no.BJMMR.23823.

41. LIFECARE CENTRE ,S EXPRIENCE
• 5 CASES---- ALL I.V.F. PREGNANCIES
• 1. 28 WEEKS..,41 YRS ----DELIVERED AT 39 WK
• 2.29 WEEKS –37 YRS---LSCS AT 39.4 WKS
• 3. 32 WEEKS -30 YRS….LSCS AT 40 WKS
• 4.30 WEEKS,S.PET ..31 YRS…CONTD..TILL
TERM.. ( DELIVERED AT AMBALA )
• 5.27 WEEKS TWINS…..CONTINUED TILL 34
WKS..BOTH BABY ARE ALIVE

42. The strong evidence base for atosiban in SPTL
 >350 research articles, earliest 1985 compared to nifedipine (poor
quality evidence) & β-agonist (ritodrine, Isoxsuprine, Terbutaline, fenoterol).
From its clinical introduction in open-label pilot studies through Phase
II, Phase III, worldwide comparative studies and Phase IV studies a
robust evidence base for atosiban has established.
Lyndrup J, Lamont RF. The choice of a tocolytic for the treatment of preterm labor: a critical evaluation of nifedipine versus atosiban.
Expert Opin Investig Drugs. 2007 Jun;16(6):843-53.

43. SN Title Test
&compara
tor drug
Study design n Remark
1. Hadar E.
Am J Obstet Gynecol. 2013
Jun 15. pii: S0002-
9378(13)00542-5.
Atosiban Open label
Comparative
21 atosiban (Tractocile) reduces uterine electrical activity in women with
preterm labor.
2.
Wu MY.Taiwan J Obstet
Gynecol. 2010 Dec;49(4):495-
9.
Atosiban Case report 1
Atosiban has few side effects and assisted in prolonging a pregnancy
involving twins that experienced extremely preterm premature
rupture of membranes.
3.
Moraloglu O. Reprod Biomed
Online. 2010 Sep;21(3):338-
43.
atosiban RCT 180 Results have indicated that atosiban increases the implantation rate
and pregnancy rate after IVF-embryo transfer.
4. Maagaard M. Ugeskr Laeger.
2009 Mar 9;171(11):907.
Case report Long-term treatment with a combination of tocolytics, Atosiban and
diclofenac inhibited labour until week 26 + 3 where both babies were
born.
5. Pierzynski P. Fertil Steril. 2007
Jul;88(1):213.e19-22.
Atosiban Case report. The treatment decreased the uterine contractile activity and resulted
in successful embryo implantation and a normal twin diamniotic
pregnancy.
6 Husslein P. BJOG. 2006 Dec;
113 Suppl 3:105-10.
Atosiban open-label, RCT 105 The use of atosiban was effective for the delay of preterm labour and
presented no safety concerns irrespective of the time it was
administered.

44. SN Title Test
&compara
tor drug
Study design n Remark
7 Richter ON. Arch Gynecol
Obstet. 2005 Jun;272(1):26-30.
Epub 2004 Jul 23.
Atosiban prospective,
randomized
pilot study
20 In summary, atosiban showed itself to be effective for tocolytic
treatment for premature labor, even during 18 and 24 weeks of
pregnancy, while exhibiting its known, favorable profile of side
effects.
8 Lurie S. J Perinat Med.
2004;32(2):137-9.
Atosiban prospective
observational
study
15 Atosiban may be an effective treatment of uterine hyperactivity
during active labor.
9 Helmer H. BJOG. 2003 Apr;110
Suppl 20:113-5.
atosiban retrospective
study
208 Atosiban is an effective tocolytic drug in the treatment of preterm
labour and preterm rupture of the membranes. It has significantly
less side effects due to its lack of cardiovascular activity.
10 Herbst A. Eur J Obstet Gynecol
Reprod Biol. 2003 May
1;108(1):109-10.
atosiban Case report 1 Tocolytic therapy with a continuous infusion of the oxytocin
antagonist, atosiban, during 154 h. The delivery was postponed for 12
days. The prolonged treatment was not associated with maternal or
fetal side effects.
11 Coomarasamy A. Med Sci
Monit. 2002 Nov;8(11):RA268-73.
atosiban Meta-analysis
Cochrane
Oxytocin antagonists appear to be effective and safe for tocolysis in
preterm labour.

45. SN Title Test
&compara
tor drug
Study design n Remark
12 Goodwin TM. Am J Obstet
Gynecol. 1994 Feb;170(2):474-8.
atosiban RCT 120 A 2-hour infusion of the oxytocin antagonist atosiban resulted in a
significantly greater decline in contraction frequency compared with
controls.
13 Valenzuela GJ. Am J Obstet
Gynecol. 1995 Apr;172(4 Pt
1):1304-6.
atosiban Open label 8 Our results show minimal placental transfer of atosiban.
Administration of atosiban even at high doses up to the time of
delivery did not increase maternal blood loss at cesarean section.
14 Am J Perinatol. 1996
Apr;13(3):143-6.
Goodwin TM.
atosiban. An open-
labeled
62 Successful tocolysis was noted in 43 of 61 (70.5%). A decrease in
uterine contraction frequency of 50% or more was noted in 50 of 61
patients (82.0%).

46. ATOSIBAN IN TWIN PREGNANCY
• 60 twin pregnancy pts. who experienced late abortion & preterm labour,
randomly divided into 2 groups:
- The first group-30 cases of a short course - Atosiban for 18 hours, &
- The second group - 30 cases of a long course of Atosiban for 45 hours
Group n
(case)
48 h Efficacy
n
7 d efficacy
n
Short course of treatment
(18 hr)
30 22 ( 73.3%) 14 (46.7%)
Long course of treatment
(45 hr)
30 29 (96.7%) 24 (80%)
P-value 0.030 0.007
Comparison of the treatment efficacy between the two groups
Atosiban can effectively extend the pregnancy time for twin pregnancy with late abortion
and preterm labour.
Ya-Juan Xu. Int J Clin Exp Med 2016;9(2):3946-3952.

47. Atosiban:
Role in IVF/Embryo Transfer

48. Atosiban
Vs
Nifedipine
(CCBs)

49. Atosiban V/s Nifedipine
• ATOSIBAN AS EFFECTIVE AS NIFEDIPINE with fewer
cardiovascular side effects.
• NIFEDIPINE IS NOT UTEROSPECIFIC and hence have multiorgan
side effects.
• NIFEDIPINE HAS NO LICENCE OR APPROVAL for use in
pregnancy or spontaneous preterm labour. Pregnancy category C
by the Food and Drug Administration (FDA) so is not
recommended before 20 weeks, or in the first trimester.
Husslein P,.Atosiban versus usual care for the management of preterm labor. J Perinat Med. 2007;35(4):305-13..
Wu MY, Chen SU, Yang YS. J Formos Med Assoc. 2011 Dec;110(12):800.

50. NIFEDIPINE
• DOSAGE –20 mg ORAL ( NOT SUBLINGUAL )
STAT FOLLOWED BY 10 mg 4—6 HOURLY
UNTIL UTERINE CONTRACTIONS CEASE ,
FOLLOWED BY 10 mg 8 hourly for about a
week.
• COMMONLY USED IN INDIA
• NOT COMBINED WITH BETAMIMETICS OR
MAGSULPH ( bcs enhances neuromuscular
blocking effects of Magsulph. )

51. • Nifedipine can be administered orally but rapid onset preparations
compromise safety and slow-release preparations compromise efficacy and
lead to the use of additional tocolytics such as magnesium sulfate or β -
agonists, which further compromise safety .
• Increasing number of reports of fetomaternal adverse effects with the use
of nifedipine.
• Nifedipine: not useful in multiple pregnancies, expanded
blood volume , anemia & patients with heart disease.
• Poor quality of clinical evidence. [mostly retrospective, small sample size]
ATOSIBAN VS NIFEDIPINE

52. Atosiban Vs nifedipine for the treatment of preterm labor
83
75
17.5
75
65
40
0
10
20
30
40
50
60
70
80
90
Efficacy Rate for 48 hours(
%)
Efficacy Rate at 7 days (%) Maternal side effects (%)
Atosiban
Nifedipine
Int J Gynaecol Obstet. 2005 Oct;91(1):10-4.
Percentageofpatients

53. SN Title Test
&comparator
drug
Study design n Remark
1. Saleh SS.
J Obstet Gynaecol. 2013 Jan;
33(1):43-5.
Atosiban
Vs.
Nifedipine
Retrospective
study
comparing the
efficacy and
safety
75 A total of 68.3% of women in the atosiban group remained
undelivered, Vs. 64.7% in the nifedipine group at 7 days .
Only the nifedipine group showed flushing, palpitation and
hypotension.
2. Salim R.
Obstet Gynecol. 2012 Dec;
120(6):1323-31.
Atosiban
Vs.
Nifedipine
Randomized
Controlled
Trial
145 Atosiban has fewer failures within 48 hours.
68.6% women in atosiban Vs 52% to nifedipine did not deliver and
did not require an alternate agent at 48 hours.
3. de Heus R. J Matern Fetal
Neonatal Med. 2009
Jun;22(6):485-90.
Atosiban or
nifedipine
RCT 31 Tocolysis with either atosiban or nifedipine combined with
betamethasone administration appears to have no direct fetal
adverse effects.
4. de Heus R, BMJ. 2009 Mar
5;338:b744.
Atosiban,
Indometacin,
Nifedipine,
Beta agonists.
Prospective
cohort study. 1920
Atosiban & Indometacin were the only drugs not associated with
serious adverse drug reactions.
5. Kam KY. Expert Opin
Pharmacother. 2008
May;9(7):1153-68.
Nifedipine,
or Atosiban,
Review The evidence to support atosiban is much superior to that of
nifedipine and there have been recent safety concerns over
nifedipine.

54. SN Title Test
&comparator
drug
Study
design
n Remark
6 Al-Omari WR. Eur J Obstet
Gynecol Reprod Biol. 2006
Sep-Oct;128(1-2):129-34.
atosiban
or
nifedipine
RCT 63
Both drugs are equally effective and efficacious in acute tocolysis. The
maternal side effects were higher with nifedipine.
7 Kashanian M. Int J Gynaecol
Obstet. 2005 Oct;91(1):10-4.
atosiban
and nifedipin
randomized
controlled
trial
80 Atosiban is an effective and safe drug for the acute treatment of
preterm labor with minimal side effects, and it can be an option in the
treatment of preterm labor, especially in patients with heart disease
and multi-fetal pregnancies.
8 Thornton JG. BJOG. 2005
Mar;112 Suppl 1:118-21.
beta-agonists
and magnesium
sulphate
nifedipine,
atosiban.
systematic
reviews
The only tocolytic that has been shown to prolong gestation when
used as maintenance therapy is atosiban.
9 Husslein P. J Perinat Med.
2007; 35(4):305-13.
atosiban or
beta-agonists,
CCBs,
magnesium
sulphate,
and/or bed rest
open-label,
RCT
295 Atosiban was associated with fewer maternal and fetal adverse
events compared with other tocolytics, and presented no safety
concerns for either the mother or the unborn baby.
10. Vercauteren M. Acta
Anaesthesiol Scand. 2009
Jul;53(6):701-9.
Atosiban,
CCB,
Magnesium
sulphate,
Nitroglycerin.
Review
Atosiban and CCB are at least as effective tocolytic agents as beta-
mimetics but have significantly less side effects.

55. RITODRINE HYDROCLORIDE
100mg in 500 ml 5 % dextrose
• Drops / mt mg /mt
• 5 0.05
• 10
• 15 0.15( usual dose )
• 20
• 25
• 30 0.30 ( maximum dose )

56. ISOXSUPRINE REGIMEN
• 60 mg in 500 of 5 % dextrose
• ________________________
• 8 drops ( 60 ugm )
• Maintenance dose of 60 mg /day
• Oral /i/m
• STOP---
• PULSE > 140
• HYPOTENSION
• PULMONARY ODEMA
• CONTINUED LABOR

57. MAGNESIUM SULPHATE
• Mgso4 given for FETAL
NEUROPROTECTION
from 25 to 32 weeks of gestation
• 4g iv loading dose in 30 minutes &
maintenance dose of 1g/1hr until
delivery .
• In PTB - it is started 4 hrs ideally before
birth.

58. PPROM
• PPROM: CHORIOAMNIONITIS complicates 8 – 77%
of < 30 weeks PPROM .
• Prophylactic antibiotics ARE AMPICILIN 2 GM I/V
INITIAL DOSE,followed by 1gm 4-6 hourly for 48 hrs
,then oral for 5 days
• If allergic..VANCOMYCIN 1gm i/v 12 hourly
Delayed cord clamping is recommended.
Role of emergency encerclage in
defined cases improves outcome

59. Take Home Messages

60. Take Home Messages

61. G
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V
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U
P
N
E
G
A
T
I
V
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T
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62. Thanks

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