Uterotonics

to reduce postpartum blood loss

Prevention/Treatment
Prevention/Treatment
  • PREVENTION
  • DIAGNOSTIC
  • TREATMENT
  • OVERVIEW
  • TECHNOLOGY Characteristics
  • Uterotonics
    Representative Product

    GLOBAL ANNUAL DEATHS ASSOCIATED WITH HEMORRHAGE

    PERCENT (%)
    NUMBER

    Maternal

    45%
    115,000

    Neonatal

    N/A
    N/A

    Stillbirth

    *
    *
    *Estimates under development

    Condition
    Postpartum hemorrhage (PPH) is blood loss greater than 500 ml within 24 hours after delivery. This condition accounts for approximately 125,000 deaths per year and 35% of all maternal deaths.  Uterine atony, retained placenta, inverted or ruptured uterus, cervical, vaginal, or perineal lacerations are all common causes of PPH. Uterine atony is the primary target of uterotonic drugs though it also helps with delivery of the placenta and other uterine bleeding. Untreated, PPH can lead to shock and death within hours.

    Mechanism of Action
    Oxytocics, prostaglandin analogues, and ergot derivatives are the most common uterotonic agents. All produce the rhythmic uterine contractions characteristic of labor. These contractions help deliver the placenta during the third stage of labor and additionally help slow the bleeding of the uterus.

    Uterotonics require injection after the delivery of the baby as part of the active management of the third stage of labor. Oxytocin and ergometrine must be refrigerated at 2- 8°C, though some versions can spend up to three months in room temperature conditions. 

    Current use in High-Resource settings
    Oxytocin and its synthetic equivalents (e.g. Pitocin, Syntocinon) are routinely administered to prevent PPH. Preventative dosing is typically 10 IU intramuscularly for the active management of the third stage of labor. Oxytocin is available on a generic basis at relatively low cost and is commonly used to slow bleeding after birth.

    Application in Low-Resource settings
    Where refrigeration and a skilled attendant are available, oxytocin is the drug of choice for the prevention of PPH. Packaging oxytocin in the Uniject system has been demonstrated to improve its correct use. In home settings, where refrigeration and means of injection are less common, misoprostol is more viable. Several studies have shown that minimally trained attendants have the ability to successfully administer therapeutic doses. A growing body of literature add credibility to misoprostol’s proponents who believe it is the single most promising technology to reduce maternal mortality due to PPH in the home setting. Where registered for specific obstetric and gynecologic indications, misoprostol can be procured as a generic for less than $0.14 per 200 mcg tablet.
     

    Related Technologies in Development

    Dry Powder Oxytocin, Ergometrine, Oxytocin Uniject Device, Prostoglandin F2a

    REPRESENTATIVE DEVICES

    DRUG
    DOSE
    PRICE*
    STATUS
    NOTES

    Oxytocin/Uniject

    10 IU
    $0.80-$1.00
    Limited
    Undergoing market expansion

    Oxytocin alone

    10 IU
    $0.25-$0.50
    Marketed
    Widely used, requires refrigeration

    Ergometrine

    1mg
    $0.35-$0.60
    Marketed
    Requires refrigeration

    Synometrine

    5 IU + 0.5mg
    $0.45-$0.70
    Marketed
    Syntheic oxytocin + ergometrine

    Misoprostol

    600 mcg
    $0.42-$3.60
    Marketed
    Potentially self-administrated

    *Prices are approximated. Actual pricing can, and will vary by marketplace and market conditions.

  • CHARACTERISTICS OF REPRESENTATIVE PRODUCT

    TECHNOLOGY CHARACTERISTICS

    OPERATIONAL PARAMETERS

    POTENTIAL OPPORTUNITIES FOR IMPROVEMENT

    SKILLS

    REQUIRED

    Intended end user
    Training required
    Time required per use
    Patient, TBA, nurse, doctor
    Hours
    Minutes

    Patient aids, in the form of smart packaging can help to lower the skill barrier. Several are under development.

    ENVIRONMENT/ INFRASTRUCTURE

    Power required
    Waste collection
    Complementary technologies required
    Temperature and storage
    Maintenance
    None
    None
    None
    If loose, low humidity
    None

    Loose tablets can be easily compromised. Aluminum blisters are commonly used, often marked with 18 month shelf lives.

    COST

    Device Cost (Approx)
    Cost/course (Approx)
    $0.10-$3.50
    $0.10-$3.50

    Cost is unlikely to be an issue.

    OTHER

    Portability
    Regulatory
    Efficacy
    <100g
    Registration can be a hurdle in countries that may wish to block potential abortifacients.
    >50% reduction in risk

    The WHO recommends the use of misoprostol where oxytocin (and other injectables) are not practical. However, availability varies by country. In some cases, where misoprostol is not approved for obstetric use, it is available as a gastric ulcer drug and used off label.

    Additional devices required for impact: Technique to approximate blood loss, (frequently a cloth of known absorptive capacity), alternative therapeutic approaches, depending on the cause of hemorrhage

Sources: WHO Report "Oxytocin in prefilled auto-disable injection system". Slegiman, Barbara and Xingzhu Liu. 2006 Tsu Intl Gynec Obstet. 2004 Hemmerling A .A Textbook of Postpartum Hemorrhage. 2006 POPPHI. Pilot use of oxytocin in a Uniject™ device for AMTSL in Mali: evaluation of the safety and feasibility of a new delivery technology. Seattle: PATH; 2008