Dinoprostone
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Prostaglandin E2Stimulant, Therapy Class:
Synthetic prostaglandin, Approved Countries
The United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Dinoprostone is a synthetic prostaglandin belonging to the pharmacological class of Prostaglandin E2 Stimulant.
The FDA has approved Dinoprostone for the induction of abortion for fetal death in utero at or near term, the management of nonmetastatic gestational trophoblastic disease, and the ripening of the cervix before induction of labour.
Dinoprostone gradually absorbs via vaginal suppositories, peaking in 30-45 minutes with cervical gel. It enters the bloodstream instantly with IV administration, later found in breast milk, undergoing rapid metabolism and quick elimination via urine and occasionally faeces.
The most common side effects of Dinoprostone include vomiting, diarrhoea, back pain, and flushing of the skin.
Dinoprostone is available in the form of vaginal inserts, gel and suppositories.
The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Dinoprostone is a synthetic prostaglandin belonging to the pharmacological class of Prostaglandin E2 Stimulant.
The intravaginal administration of Dinoprostone induces contractions in the gravid uterus' myometrium that resemble those of the term uterus during labour, which causes the uterine products to be expelled. Although the precise mode of action of Dinoprostone is unknown, it is thought to influence the uterus by direct myometrial stimulation. Moreover, methods are proposed to control intracellular concentrations of cyclic 3',5'-adenosine monophosphate, and calcium transport across cellular membranes. Local cervical effects such as dilatation, softening, and effacement appear to be caused by Dinoprostone. The precise mechanism of action underlying this effect remains unclear; however, it has been proposed that it could be linked to the breakdown of collagen resulting from the enzyme collagenase being secreted in reaction to locally given Dinoprostone.
Peak plasma time occurs within 0.5 to 0.75 hours.
In most first and second-trimester pregnancies, slight uterine contractions commence within 10 minutes.
After inserting a dinoprostone suppository vaginally, the duration of contractions persists for 2 to 3 hours, aiding cervical changes during labour.
Dinoprostone is available in the form of vaginal inserts, gel and suppositories.
Administer Dydrogesterone vaginal inserts, gels, or suppositories using an applicator by inserting them into the vagina and lying down for 30 minutes as directedby the physician.
- It is used to initiate labour or to stimulate contractions when pregnancy needs to be induced.
- Dinoprostone is employed to evacuate the uterine contents in cases of missed abortion or intrauterine fetal death.
- Dinoprostone is also used in pregnancy termination for the induction of labour during the second trimester (from the 12th to the 20th week of pregnancy).
- Induction of labour: During pregnancy, Dydrogesterone, a naturally occurring substance, readies the cervix for labour by facilitating cervical ripening. It softens and widens the womb's opening and boosts uterine contractions. This aids in childbirth by enabling the baby's easier passage from the mother's womb, reducing potential complications associated with delivery.
- Dinoprostone assists in evacuating uterine contents in missed abortion or intrauterine fetal death cases. Additionally, it induces labor in the second trimester (from the 12th to the 20th week of pregnancy) for pregnancy termination.
Dinoprostone is indicated for the following conditions:
- In the second trimester, dinoprostone effectively ends pregnancies (12–20 gestational weeks).
- Up to 28 weeks after the previous menstrual cycle, it removes the contents of the uterus due to misplaced abortion or fetal death.
- Dinoprostone also effectively treats gestational trophoblastic illness that is not metastatic.
- When a pregnant woman needs labor induction or is experiencing postpartum hemorrhage, it promotes cervical inducibility.
Administer Dinoprostone Vaginal inserts, gels, and suppositories intravaginally. The vaginal insert, a controlled-release system, is inserted deep into the vagina using an applicator. The gel, applied with an applicator, is also inserted into the vagina. Suppositories, solid moulded shapes, are manually inserted into the vagina. Healthcare providers advise patients to abstain from sexual intercourse or use tampons for a specified duration after administration.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Vaginal insert: 10 mg
Endocervical gel: 0.5mg/3g (3g)
Vaginal suppository: 20mg
Dinoprostone is available in the form of vaginal inserts, gel and suppositories.
Dose Adjustment in Adult Patients:
Cervical Ripening
Dydrogesterone: One insert in the posterior fornix; remove it 12 hours later or when active labour starts.
Dydrogesterone gel: use a syringe and catheter to inject 2.5 mL (0.5 mg) into the cervical canal; repeat after 6 hours; the maximum cumulative dose is 1.5 mg/24 hours.
Termination of Pregnancy
Dydrogesterone: Take one 20 mg suppository intravaginally (high in the vagina) every three to five hours until an abortion happens; do not take more than two days to administer continuously.
Administering Dinoprostone intravaginally to induce labour typically doesn't come with specific dietary restrictions. Staying hydrated is crucial, permitting water and clear fluids unless advised otherwise. Avoiding caffeine, alcohol, and spicy foods, known to provoke hot flushes, is advisable. Quitting smoking reduces hot flushes and risks of conditions like heart disease, stroke, and cancer, aiding symptom management. Embracing a diet abundant in fruits, vegetables, whole grains, lean proteins, and healthy fats promotes well-being. Rest, stress reduction, and increased warm fluid intake are suggested to alleviate discomfort during menstruation.
The dietary restriction should be individualized as per patient requirements.
Dinoprostone may be contraindicated in the following conditions:-
- History of cesarean delivery, a disproportion in the head and pelvis, hard labour, grand multiparae, non-vertex presentation, hyperactive uterine patterns, fetal distress without impending delivery, and obstetric emergencies that require immediate surgical intervention, oxytocic medications should not be used.
- Hypersensitivity to prostaglandins or constituents of the gel
- Placenta previa or unexplained vaginal bleeding during this pregnancy.
- Patients for whom vaginal delivery is not indicated, such as vasa previa or active herpes genitalia.
- Administer in a hospital setting equipped with obstetric care facilities. Exercise caution in patients with epilepsy, glaucoma, hepatic/renal impairment, or pulmonary disease. Wait 30 minutes post-insert removal or 6-12 hours after gel application before using other oxytocic drugs.
- Monitor patients for signs of amniotic fluid embolism syndrome (AFES) post-dinoprostone use, such as hypotension, hypoxemia, DIC, coma, or seizures, and provide necessary supportive care; AFES can be fatal.
- Avoid inserting gel above the internal os and remove before amniotomy. Patients with cervical laceration and severe haemorrhage may need blood transfusions. Monitor closely for various conditions, including acute vaginitis, anaemia, cardiovascular disease, cervical stenosis, and more.
- Women over 30, those with pregnancy complications, or gestational age over 40 weeks are at higher risk of postpartum disseminated intravascular coagulation; monitor closely postpartum. Rarely, inadvertent tissue disruption and embolization can cause an anaphylactoid syndrome of pregnancy.
- Exercise caution in women at high risk of postpartum disseminated intravascular coagulation (DIC) when using physiologic or pharmacologic induction of labour, as it is associated with increased postpartum DIC risk. Immediately initiate therapy by removing procoagulant sources, replacing depleted clotting factors, and, in certain situations, administering heparin for anticoagulation.
- Life-threatening hypersensitivity reactions like anaphylaxis and angioedema have occurred shortly after initiating dinoprostone gel; if suspected, remove the gel, consider other causes, and provide symptomatic therapy.
- Therapy may induce uterine tachysystole, with or without fetal heart rate changes. Monitor uterine activity, fetal status, and cervical progress carefully during treatment. Discontinue therapy if signs of uterine tachysystole, fetal distress, or labour onset appear.
- Monitor patients for signs of amniotic fluid embolism syndrome (AFES) post-dinoprostone use, such as hypotension, hypoxemia, DIC, coma, or seizures, and provide necessary supportive care; AFES can be fatal.
Alcohol Warning
It is unsafe to consume alcohol.
Breast Feeding Warning
Probably unsafe to use during breastfeeding as it may pass into the breastmilk and harm the baby.
Pregnancy Warning
It is generally considered to be safe when used during pregnancy. Animal studies indicate minimal fetal risks; human data is limited.
Food Warning
Limit caffeine intake, avoid fried foods, and limit alcohol intake.
The adverse reactions related to Dinoprostone can be categorized as
Common Adverse Effects: Nausea, vomiting, diarrhoea, fever, chills, tachycardia, and headaches.
Less Common Adverse Effects: Changes in blood pressure (both hypotension and hypertension), uterine rupture or hypertonus, fetal distress, and allergic responses.
Rare Adverse Effects: Anaphylactoid reactions, amniotic fluid embolism, cardiac arrhythmias, or pulmonary oedema.
Reports on Postmarketing
Hypersensitivity reactions, such as anaphylactic shock and reaction.
Diseases of the nervous system: headache
Cardiovascular disorders: Women who have already experienced myocardial infarction may also experience it.
The clinically relevant drug interactions of Dinoprostone are briefly summarized here.
- Oxytocic agents: Dinoprostone, when used concurrently with other oxytocic agents, can potentiate uterine contractions, increasing the risk of uterine hyperstimulation or tachysystole. Concomitant use with oxytocin should be approached cautiously due to the potential for an intensified effect on uterine activity.
- Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs may diminish the effects of Dinoprostone. Additionally, administering Dinoprostone alongside other prostaglandins might heighten adverse effects or excessive uterine activity.
The common side effects of Dinoprostone include:-
Flushing of skin
Diarrhea
Chills
Vomiting
Nausea
Fever
Wheezing
Uterine tachysystole
Uterine hyperstimulation
- Pregnancy
Pregnancy Category C: Use caution if the benefits outweigh the risks.
There is a lack of relevant animal reproductive evidence about Dinoprostone, and the scant research on its use in pregnant people does not indicate a negative correlation with developmental outcomes.
Withdraw therapy in the event of persistent tachysystole with or without fetal heart rate changes and follow established institutional guidelines in patient management. When medication was stopped for fetal distress, there was a return to normal rhythm and no neonatal sequelae.
Animal data
Dinoprostone has been demonstrated to be embryotoxic in rats and rabbits, although there is no evidence from animal research that it is teratogenic. Nevertheless, any dosage that raises uterine tone may harm the developing embryo or baby.
- Nursing Mothers
Combining this with breastfeeding isn't recommended; no data exists on its impact on the nursing child. Limited information is accessible regarding its effects on milk production when taken by the mother.
- Pediatric Use
As per the FDA, Dinoprostone is not intended for use in this population.
- Geriatric Use
As per the FDA, Dinoprostone is not intended for subjects aged 65 and over.
Dose Adjustment in Kidney Impairment Patients:
Mild to severe impairment: No dosage adjustment required.
Dose Adjustment in Hepatic Impairment Patients:
Hepatic impairment: No dosage adjustment is required.
The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Dinoprostone.
Signs and Symptoms
Overconsumption of Dinoprostone could lead to nausea, vomiting, and abdominal discomfort.
Management
There is no specific antidote or treatment for excessive Dinoprostone, so treatment typically involves symptomatic and supportive measures. If ingestion is recent, gastric lavage or activated charcoal might limit absorption. Close monitoring of the patient's vital signs, electrolytes, and fluid balance is essential.
Furthermore, if severe hypersensitivity reactions such as anaphylaxis occur, the discontinuation of Dinoprostone and prompt administration of appropriate treatments, including epinephrine and antihistamines, are necessary.
Pharmacodynamics:
Dinoprostone is a prostaglandin E2 (PGE2) substitute. Stimulating the uterus terminates the pregnancy and promotes labour and delivery. Additionally, Dinoprostone can produce the smooth muscle of the human gastrointestinal tract. The vomiting and/or diarrhoea that frequently occur when Dinoprostone is used to end pregnancy may be caused by this activity.
Pharmacokinetics:
Absorption
Dinoprostone gradually absorbs through vaginal suppositories and reaches peak plasma concentration within 30 to 45 minutes with cervical gel application.
Distribution
It disperses immediately into the mother's bloodstream during IV administration, eventually entering breast milk.
Metabolism
Rapid metabolism occurs in surrounding tissues, primarily in the mother's lungs, with secondary clearance in the liver and kidneys.
Elimination
Excretion primarily happens via urine and occasionally faeces, with a relatively short elimination half-life of 2.5–5 minutes.
- Anh ND, Duc TA, Ha NT, Giang DT, Dat DT, Thuong PH, Toan NK, Duc NT, Duc NM. Dinoprostone Vaginal Insert for Induction of Labor in Women with Low-Risk Pregnancies: A Prospective Study. Med Arch. 2022 Feb;76(1):39-44. doi: 10.5455/medarh.2022.76.39-44. PMID: 35422562; PMCID: PMC8976886.
- Shirley M. Dinoprostone Vaginal Insert: A Review in Cervical Ripening. Drugs. 2018 Oct;78(15):1615-1624. doi:10.1007/s40265-018-0995-2. PMID: 30317521.
- Hughes EG, Kelly AJ, Kavanagh J. Dinoprostone vaginal insert for cervical ripening and labor induction: a meta-analysis. Obstet Gynecol. 2001 May;97(5 Pt 2):847-55. doi: 10.1016/s0029-7844(00)01216-3. PMID: 11336776.
- Buser D, Mora G, Arias F. A randomized comparison between misoprostol and dinoprostone for cervical ripening and labor induction in patients with unfavorable cervices. Obstet Gynecol. 1997 Apr;89(4):581-5. doi: 10.1016/S0029-7844(97)00015-X. PMID: 9083316.
- https://www.ncbi.nlm.nih.gov/books/NBK545279/
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/017810s019lbl.pdf
- KD Tripathi. [link]. Seventh Edition. New Delhi, India: Jaypee Brothers Medical Publishers; 2013: Page No 189.
- https://dailymed.nlm.nih.gov/dailymed/lookup.cfm
Published on: 5 Dec 2023 5:51 AM GMT
