Dinoprostone, also known as prostaglandin E2 (PGE2), is a naturally occurring prostaglandin that plays various roles in the body. One of its well-known functions is in the female reproductive system, where it helps to induce labor and ripen the cervix.

In medical practice, synthetic forms of dinoprostone are often used in obstetrics to induce labor when it is medically necessary, such as in cases of post-term pregnancy or when there are maternal or fetal health concerns. Dinoprostone can be administered intravaginally or intracervically in the form of a gel, tablet, or suppository. It helps to soften and dilate the cervix, making it easier for labor to progress.

Dinoprostone (Cervidil) is a naturally occurring prostaglandin E2. It stimulates uterine contractions and is used in the induction of labor, postpartum hemorrhage, and termination of pregnancy.

Dinoprostone Uses:

• Cervical ripening for labor induction:
  • Endocervical gel (Prepidil): 
    • Encourage cervical ripening in those sufferers at or near term in whom there is a medical or obstetrical manifestation for the induction of labor.
  • Tablet (oral) (Prostin E-2; [Canadian product]):
    • Elective induction of labor; when indications for induction of labor available (eg, Toxemia of pregnancy, Rh incompatibility, diabetes mellitus, hypertension, postmaturity, premature rupture of amniotic membranes, intrauterine death, or fetal growth retardation)
  • Vaginal gel (Prostin E-2; [Canadian product]):
    • Induction of labor in sufferer at or near term with a singleton pregnancy, vertex presentation, and favorable induction features
  • Vaginal insert (Cervidil):
    • starting and/or continuation of cervical ripening in sufferers at or near term in whom there is a medical or obstetrical manifestation for the induction of labor
• Termination of intrauterine pregnancy:
  • Suppositories (Prostin E2): Terminate pregnancy from 12th through 20th week of gestation;
  • evacuate the uterus in cases of missed abortion or intrauterine fetal death up to 28 weeks of gestation;
  • manage benign hydatidiform mole (nonmetastatic gestational trophoblastic disease)

Dinoprostone (Cervidil) Dose in Adults

Note: Dinoprostone is a medicine that helps pregnant women who need to start labor. In the United States, it comes in different forms like gel (called Prepidil), insert (Cervidil), and suppository (Prostin E2). Each form works differently in the body, so they can't be swapped. Sometimes, people have made mistakes by using the wrong form of this medicine, which can be dangerous.

Dinoprostone (Cervidil) Dose in the Termination of intrauterine pregnancy:

• In terminating a pregnancy, using the Prostin E2 vaginal suppository involves inserting 20 mg (which is one suppository) high up in the vagina.
• You repeat this every 3 to 5 hours until the abortion occurs.
• However, it's not recommended to keep using it for more than 2 days.

Dinoprostone (Cervidil) Dose in the Cervical ripening:

Endocervical gel (Prepidil):

• Use a catheter supplied with the gel to insert 0.5 mg into the cervical canal.
• You can repeat this every 6 hours if necessary.
• The maximum total dose within 24 hours should not exceed 1.5 mg.

Tablet (oral) [Prostin E, Canadian product]:

• Induction: Start with an initial dose of 0.5 mg, then repeat the same dose 1 hour later. Additional 0.5 mg doses can be given hourly if needed for a good uterine response.
• If contractions aren't regular after 8 hours, it suggests failed induction, and other options should be considered.
• If a patient vomits a tablet but it's still intact, repeat the dose. If vomiting occurs after two successive doses, hold off on further dosing until the next scheduled dose.
• For women who have given birth two or more times or have a Bishop Score of 6 or higher: Administer 0.5 mg hourly during induction, but stop the hourly dose if there's excessive uterine activity.
• For women with a Bishop Score lower than 6 and who haven't given birth before, if there's not enough response after 2 hours, the dose can be increased by 0.5 mg increments at hourly intervals up to a maximum single dose of 1.5 mg.
• During labor, a 0.5 mg dose may be given occasionally, and hourly dosing can be paused to assess the need for more doses.

Vaginal gel [Prostin E, Canadian product]:

• Initially, using a prefilled syringe, insert 1 mg into the posterior fornix of the vaginal canal.
• If needed, you can give an additional dose of 1 to 2 mg 6 hours later.

Vaginal insert (Cervidil):

• Insert 10 mg transversely into the posterior fornix of the vagina.
• This insert should be removed either at the onset of active labor or after 12 hours, whichever comes first.

Dinoprostone (Cervidil) Dose in Children

Females of reproductive age: Refer to adult dosing.

Dinoprostone Pregnancy Risk Category: X

• Adverse effects have been seen in studies on animals during reproduction.
• While these effects aren't expected in humans, giving dinoprostone after the organ development stage could still increase risks to the baby due to sustained increased uterine tone.
• Around 3% to 4% of babies exposed to Cervidil in the womb experienced fetal distress without the mother having uterine hyperstimulation.
• However, a follow-up study on exposed babies didn't find any negative effects on their physical or mental development over three years.
• Prepidil gel use has been linked to abnormal fetal heart rates in about 17% of exposed babies, along with deceleration, fetal sepsis, depression, and acidosis.
• Stillbirths, abnormal fetal heart rates, and fetal distress have been reported with Prostin E vaginal gel and oral tablets.
• While dinoprostone isn't considered harmful to the fetus during pregnancy termination due to its ability to trigger uterine contractions, it should not be used if the fetus is viable.
• If a fetus is not yet viable, it might briefly show signs of life when aborted using dinoprostone.
• If dinoprostone fails to terminate pregnancy, another method should be used to complete the termination.

Use of dinoprostone while breastfeeding

• The natural prostaglandin E (PGE) is indeed found in breast milk, as indicated by a study conducted by Shimizu in 1992.
• This suggests that breastfeeding infants can be exposed to small amounts of PGE through breast milk.

Dinoprostone Dose in renal disease:

No dosage recommendations have been mentioned, however, in active renal impairment, the use of vaginal gel, suppository, and tablets are contraindicated.

Dinoprostone Dose in Liver disease:

No dosage recommendations have been mentioned, however, certain forms such as vaginal gel, suppository, and tablets are contraindicated in active liver disease.

Side effects of Dinoprostone Endocervical gel:

• Central nervous system:
  • Localized warm feeling
• Gastrointestinal:
  • Gastrointestinal distress
• Genitourinary:
  • Uterine contractions
• Neuromuscular & skeletal:
  • Back pain

Side effects of Dinoprostone Suppository:

• Cardiovascular:
  • Cardiac Arrhythmia
  • Chest Pain
  • Chest Tightness
  • Hypotension
  • Syncope
• Central Nervous System:
  • Chills
  • Dizziness
  • Headache
  • Paresthesia
  • Shivering
  • Tension
• Dermatologic:
  • Diaphoresis
  • Skin Discoloration
  • Skin Rash
• Endocrine & Metabolic:
  • Dehydration
  • Hot Flash
• Gastrointestinal:
  • Diarrhea
  • Endometritis
  • Nausea
  • Vomiting
• Genitourinary:
  • Breast Tenderness
  • Urinary Retention
  • Uterine Rupture
  • Vaginal Pain
  • Vaginismus
  • Vaginitis
  • Vulvitis
• Neuromuscular & Skeletal:
  • Arthralgia
  • Arthritis
  • Back Pain
  • Leg Cramps
  • Muscle Cramps
  • Myalgia
  • Neck Stiffness
  • Tremor
  • Weakness
• Ophthalmic:
  • Blurred Vision
  • Eye Pain
• Otic:
  • Auditory Impairment
• Respiratory:
  • Cough
  • Dyspnea
  • Laryngitis
  • Pharyngitis
  • Wheezing
• Miscellaneous:
  • Fever

Side effects of Dinoprostone Tablets [Canadian Product]:

• Cardiovascular:
  • Amniotic Fluid Embolism
  • Cardiac Arrest Central Nervous System: Malaise
• Gastrointestinal:
  • Vomiting
• Genitourinary:
  • Hypertonic Uterine Contractions
  • Cervical Dilation
  • Placental Abruption
  • Uterine Contractions
  • Uterine Rupture
• Hypersensitivity:
  • Hypersensitivity Reaction
• Neuromuscular & Skeletal:
  • Back Pain
• Respiratory:
  • Asthma

Side effects of Vaginal Gel [Canadian Product]:

• Cardiovascular:
  • Cardiac Arrest
• Central Nervous System:
  • Localized Warm Feeling
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Vomiting
• Genitourinary:
  • Hypertonic Uterine Contractions
  • Uterine Contractions
  • Uterine Rupture
• Hypersensitivity:
  • Hypersensitivity Reaction Including
    • Anaphylaxis
    • Anaphylactic Shock
    • And Nonimmunologic Anaphylaxis
• Neuromuscular & Skeletal:
  • Back Pain
• Miscellaneous:
  • Fever

Vaginal Insert:

Less Common Side Effects Of Dinoprostone (Cervidil):

• Genitourinary:
  • Hypertonic Uterine Contractions

Contraindications to Dinoprostone (Cervidil):

Labor induction should not be performed whenever spontaneous labor or vaginal delivery is not recommended, as outlined by ACOG guidelines from 2009. Specific contraindications vary depending on the dosage form of the medication:

All dosage forms:

• Contraindicated in individuals with hypersensitivity to prostaglandins or any component of the formulation.

Endocervical gel (Prepidil):

• Contraindicated in patients for whom oxytocic drugs are not recommended, including those with a history of cesarean section or major uterine surgery, cephalopelvic disproportion, fetal distress when delivery isn't imminent, unexplained vaginal bleeding during the current pregnancy, history of difficult labor or traumatic delivery, ≥6 previous term pregnancies with nonvertex presentation, hyperactive or hypertonic uterine patterns, obstetric emergencies where surgical intervention is preferable, placenta previa, or when vaginal delivery is not indicated (e.g., vasa previa, active herpes genitalia).
• Canadian labeling adds contraindications such as epilepsy history, fetal malpresentation, overdistention of the uterus, ruptured amniotic membranes or suspected chorioamnionitis, and concurrent use with other oxytocics.

Suppository (Prostin E2):

• Contraindicated in acute pelvic inflammatory disease, active cardiac, pulmonary, renal, or hepatic disease.

Oral Tablet (Prostin E; Canadian product):

• Contraindications include patients for whom oxytocic drugs are generally not recommended, those with active cardiac, pulmonary, renal, or hepatic disease, simultaneous use with other oxytocics, history of cesarean section or major uterine surgery, presence of cephalopelvic disproportion, history of difficult labor or traumatic delivery, ≥6 pregnancies, suspected or clinically evident preexisting fetal distress, overdistention of the uterus, preexisting uterine hypertonus, situations where a responsible physician is unavailable, engagement of head not yet occurred, unexplained vaginal bleeding during this pregnancy, fetal malpresentation, gynecological, obstetrical, or medical conditions precluding vaginal delivery, pregnancy complicated by abnormal position of the placenta or umbilical cord, history of or existing pelvic inflammatory disease unless adequately treated.

Vaginal gel (Prostin E; Canadian product):

• Contraindications are similar to oral tablets, including simultaneous use with other oxytocics, history of cesarean section or major uterine surgery, presence of cephalopelvic disproportion, history of difficult labor or traumatic delivery, ≥6 term pregnancies, suspected or clinically evident preexisting fetal distress, overdistention of the uterus, preexisting uterine hypertonus, situations where a responsible physician is unavailable, engagement of head not yet occurred, unexplained vaginal bleeding during this pregnancy, fetal malpresentation, gynecological, obstetrical, or medical conditions precluding vaginal delivery, pregnancy complicated by abnormal position of the placenta or umbilical cord, ruptured amniotic membranes or suspected chorioamnionitis.

Vaginal insert (Cervidil):

• Contraindications include patients for whom oxytocic drugs are not recommended, history of cesarean section or major uterine surgery, presence of cephalopelvic disproportion, fetal distress when delivery is not imminent, unexplained vaginal bleeding during this pregnancy, patients already receiving IV oxytocic drugs, or ≥6 previous term pregnancies.

Canadian labeling adds contraindications such as placenta previa, history of difficult labor or traumatic delivery, overdistention of the uterus, fetal malpresentation, and history of uncontrolled epilepsy or pelvic inflammatory disease.

Warnings and precautions

Anaphylactoid pregnancy syndrome:

• Anaphylactoid syndrome of pregnancy is a rare but serious condition that can occur when endocervical gel, vaginal gel, or vaginal insert is placed inside the cervix or vagina.
• This syndrome can lead to severe allergic-like reactions in pregnant individuals.

Disseminated intravascular coagulation

• Disseminated intravascular coagulation (DIC) is a serious condition where blood clots form throughout the body's small blood vessels.
• Postpartum DIC, occurring after childbirth, has been reported in some cases following the use of dinoprostone for labor induction.
• The risk of DIC may be higher in women who are 30 years old or older, those who have pregnancies lasting longer than 40 weeks, or those with complications during pregnancy.

Hypersensitivity reactions

• Hypersensitivity reactions, including severe and life-threatening ones like anaphylaxis and angioedema, have been observed with the use of dinoprostone.
• These reactions can happen shortly after starting the therapy, ranging from minutes to hours.

Cardiovascular disease

• Patients with cardiovascular disease should be treated with caution when considering the use of dinoprostone.
• Some dosage forms may have contraindications for individuals with active cardiovascular disease.
• It's important to carefully review the manufacturer's labeling for specific dosage forms to determine if there are any contraindications related to cardiovascular health.

Epilepsy:

• Dinoprostone should be used cautiously in patients with epilepsy.

Glaucoma:

• Caution should be exercised when using dinoprostone in patients with glaucoma.

Hepatic impairment

• Patients with hepatic impairment should be treated with caution when considering the use of dinoprostone.
• Some dosage forms, such as the suppository, tablet, and vaginal gel, may have contraindications for individuals with active hepatic disease.
• It's important to carefully review the manufacturer's labeling for specific dosage forms to determine if there are any contraindications related to liver health.

Pulmonary disease

• Patients with a history of asthma should be treated with caution when considering the use of dinoprostone.
• Some dosage forms, such as the suppository, tablet, and vaginal gel, may have contraindications for individuals with active pulmonary disease.
• It's important to carefully review the manufacturer's labeling for specific dosage forms to determine if there are any contraindications related to pulmonary health.

Renal impairment

• Patients with renal impairment should be treated with caution when considering the use of dinoprostone.
• Some dosage forms, such as the suppository, tablet, and vaginal gel, may have contraindications for individuals with active renal disease.
• It's important to carefully review the manufacturer's labeling for specific dosage forms to determine if there are any contraindications related to kidney health.

Dinoprostone: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Gel and Insert:

• Fetal Heart Rate: Monitor the baby's heart rate to ensure it remains within a healthy range.
• Uterine Activity: Keep track of contractions to ensure they're progressing labor but not becoming too frequent or intense.
• Cervical Dilation and Effacement: Observe how the cervix is dilating and thinning out to gauge progress in labor.

Tablet:

• Uterine Activity: Monitor contractions to ensure they're occurring at a healthy rate.
• Excessive Uterine Activity: Watch out for contractions happening too frequently or with too much intensity, which can be problematic if they exceed a certain threshold.

Suppository:

• Confirmation of Fetal Death: In cases where the fetus has died, the suppository may be used to help with the delivery process.

How to administer Dinoprostone (Cervidil)?

Endocervical Gel (Prepidil):

• Bring to room temperature before use, avoid forcing warming.
• Avoid skin contact during handling and wash hands thoroughly after administration.
• For cervical ripening, patient should be supine in the dorsal position.
• Choose catheter length based on degree of effacement.
• Patient should remain supine for 15-30 minutes post-administration.
• Wait 6-12 hours after gel administration before starting oxytocin.

Tablet (Oral) [Prostin E, Canadian product]:

• Administer with a small amount of water.
• Avoid using oxytocin until at least 1 hour after the last oral tablet.

Vaginal Gel (Prostin E, Canadian product):

• For intravaginal use only, not intracervical.
• Administer dose in the posterior fornix of the vagina using prefilled syringe.
• Patient should remain in lateral or supine position for 30 minutes to prevent leakage.
• Syringe is for single use only and contains overfill.
• Avoid oxytocin for 12-24 hours post-administration.

Vaginal Insert (Cervidil):

• Keep frozen until use, do not warm prior to use.
• Open package along tear mark without sharp objects.
• Insert one vaginal insert transversely in the posterior fornix of the vagina.
• Patient should remain recumbent for 2 hours post-insertion.
• Avoid excessive lubricant use.
• Wait ≥30 minutes after removal before starting oxytocin.

Vaginal Suppository (Prostin E2):

• Insert high into vagina after removing from foil package.
• Bring to room temperature before use.
• Patient should remain supine for 10 minutes post-insertion.

Mechanism of action of Dinoprostone (Cervidil):

• Dinoprostone, which is a type of prostaglandin E hormone, naturally exists in low levels in various tissues of the body.
• When used to induce abortion, it triggers uterine contractions, mimicking those that occur during natural labor.
• However, when administered for labor induction, it has a different effect.
• It helps to relax the smooth muscle of the cervix, which allows it to dilate and enables the fetus to pass through the birth canal more easily.

Onset of Action (Uterine Contractions):

• Vaginal Suppository: Begins working within 10 minutes.

Duration:

• Vaginal Insert: Lasts for 12 hours, releasing 0.3 mg per hour.
• Vaginal Suppository: Effects can last up to 2-3 hours.

Absorption:

• Vaginal Suppository: Absorption is slow.

Metabolism:

• Metabolized in the lungs; further metabolites are processed in the liver and kidney.

Half-life Elimination:

• Lasts between 2.5 to 5 minutes.

Time to Peak, Plasma:

• Endocervical Gel: Peaks in the bloodstream between 30 to 45 minutes after administration.

Excretion:

• Primarily excreted through urine, with small amounts excreted in feces.

International Brand Names of Dinoprostone:

• Cervidil
• Prepidil
• Prostin E2
• Cervidil
• Cerviprime
• Cerviprost
• Dinoglandin E2
• Glandin E2
• Minprostin
• Minprostin E(2)
• Prandin E2
• Prepidil
• Primigyn
• Primiprost
• Prolisina E2
• Propess
• Propess Vag SR
• Prostaglandina E2
• Prostarmon E
• Prostenon
• Prostin E2
• Prostin E2 Vaginal Cream
• Prostin E2 Vaginal Gel
• Prostin VR
• Prostine

Dinoprostone Brand Names in Pakistan: