Dinoprostone

Aka: Dinoprostone, PGE2 Gel, Cervidil, Prepidil, Prostin E2

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II. Indications

  1. Cervical Ripening in Labor Induction
    1. Bishop Score <6
    2. Membranes intact
    3. No active contraction pattern
      1. Less than 10 mild contractions per hour
  2. Evacuation of Uterine Contents after Fetal Death
    1. Up to 28 weeks gestation

III. Contraindications

  1. Uterine Contractions >3 in 10 minutes prior to placement
  2. Factors increasing the risk for Uterine Rupture
    1. Prior Cesarean Section
    2. Major uterine surgery with scar dehiscence risk

IV. Mechanism

  1. See Prostaglandin
  2. Dinoprostone is a synthetic Prostaglandin E2 (PGE2) analog
    1. Prostaglandin E2 (PGE2) is the most common and the most biologically active Prostaglandin
  3. Dinoprostone induces smooth Muscle Contraction in the Uterus (myometrium) and Stomach
    1. Increases cAMP levels, activating adenylate cyclase, and increasing Calcium Ion transport across cell membranes

V. Precautions

  1. Monitor Fetal Heart Rate and tocometry in Cervical Ripening
    1. Start 15 to 30 minutes before
    2. Vaginal Gel monitoring should continue for 30-120 minutes after gel placement
    3. Vaginal Insert monitoring should continue while inserted, and for 15 min after removal

VI. Medications

  1. Cervical Ripening Agents for Labor Induction
    1. Dinoprostone Gel (PGE2 Gel, Prepidil): 0.5 mg per 3 g syringe
    2. Dinoprostone Pessary or Vaginal Insert (PGE2, Cervidil): 10 mg
  2. Evacuation of Uterine Contents after Fetal Death or Termination of Pregnancy
    1. Dinoprostone Vaginal Suppository (Prostin E2): 20 mg

VII. Dosing: Dinoprostone Gel (PGE2 Gel, Prepidil) for Cervical Ripening

  1. Initiate Fetal Heart Rate and tocometry
    1. Start 15-30 minutes before gel inserted
    2. Continue monitoring for 30-120 minutes after placement
  2. Insertion Technique
    1. Use one syringe of gel (0.5 mg in 3cc KY)
    2. Patient remains supine for 30 minutes after insertion
    3. Introduce gel into Cervix
      1. Cervix not effaced: Use 20 mm catheter
      2. Cervix effaced 50% or greater: Use 10 mm catheter
      3. Intracervical is preferred over posterior fornix
        1. Perry (2004) Obstet Gynecol 103:13-7 [PubMed]
  3. Dosing
    1. May repeat every 6 hours up to 3 doses in 24 hours
  4. End points
    1. Bishop Score of 8 or greater
    2. Strong uterine contractions
  5. Drug Interactions
    1. Wait 6-12 hours before starting Oxytocin

VIII. Dosing: Dinoprostone Pessary or Vaginal Insert (PGE2, Cervidil) for Cervical Ripening

  1. Dinoprostone 10 mg vaginal insert releases Dinoprostone at 0.3 mg/hour for 12 hours
  2. Insert Pessary into posterior fornix (adjacent to Cervix)
  3. Monitor Fetal Heart Tones and tocometry
    1. Start 15 to 30 minutes before insertion
    2. Continue monitoring for 15 minutes after removal
  4. Patient remains recumbent for 2 hours after insertion
  5. Pull Pessary out via string if hyper-stimulated

IX. Dosing: Dinoprostone Vaginal Suppository (Prostin E2) in Evacuation of Uterine Contents

  1. Indicated in up to 28 weeks gestation for Fetal in utero death
  2. Insert 20 mg intravaginal suppository
  3. May repeat up to every 3 to 5 hours (maximum use 2 days) as needed until uterine contents expelled

X. Adverse Effects

  1. Uterine Tachysystole
    1. Criteria: >10 contractions in 20 minutes (or >5 contractions in 10 minutes)
    2. Dinoprostone Tachysystole Incidence: 33%
  2. Uterine Hyperstimulation
    1. Criteria
      1. Exaggerated uterine response (i.e. Tachysystole)
      2. Concerning Fetal Heart Rate tracing
        1. Late Decelerations
        2. Fetal Tachycardia >160 beats per minute
    2. Dinoprostone Hyperstimulation Incidence: 17%
    3. Hyperstimulation Management
      1. Remove Dinoprostone
      2. Consider Terbutaline SQ
  3. Uterine Rupture in VBAC
    1. Risk: 2.5% in Trial of Labor after Cesarean
  4. References
    1. Crane (2001) Obstet Gynecol 97:926-31 [PubMed]
    2. Ravasia (2000) Obstet Gynecol 183:1176-9 [PubMed]

XI. Safety

  1. Unknown safety in Lactation
  2. Pregnancy use only in peripartum (or intended evacuation of Uterus)

XII. Resources

  1. Dinoprostone Vaginal Insert (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3bc9031-0620-4a50-b440-f661cadfeb1d
  2. Dinoprostone Gel (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ab03de5b-782c-4f81-a8dc-7ef9969dd0cf

XIII. References

  1. Adair (2000) Clin Obstet Gynecol 43:447-54 [PubMed]
  2. Crane (2001) Obstet Gynecol 97:926-31 [PubMed]
  3. Sanchez-Ramos (1997) Obstet Gynecol 89:633-4 [PubMed]
  4. Tenore (2003) Am Fam Physician 67(10):2123-8 [PubMed]
  5. Wheeler (2022) Am Fam Physician 105(2): 177-86 [PubMed]

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