Dinoprostone

(BAN, USAN, rINN)
Dinoprostone Chemical formula
Synonyms: Dinoproston; Dinoprostona; Dinoprostonas; Dinoprostoni; Dinoprostonum; Dinoproszton; PGE 2 ; Prostaglandin E 2 ; U-12062. (5Z,13E)-(8R,11R,12R,15S)-11,15-Dihydroxy-9-oxoprosta-5,13dienoic acid; (Z)-7-{(1R,2R,3R)-3-Hydroxy-2-[(E)-(3S)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl}hept-5-enoic acid.
Cyrillic synonym: Динопростон.

💊 Chemical information

Chemical formula: C20H32O5 = 352.5.
CAS — 363-24-6.
ATC — G02AD02.
ATC Vet — QG02AD02.

Pharmacopoeias.

In Eur. and US.

Ph. Eur. 6.2

(Dinoprostone). A white or almost white, crystalline powder or colourless crystals. Practically insoluble in water; freely soluble in alcohol; very soluble in methyl alcohol. Store at a temperature not exceeding −15°.

USP 31

(Dinoprostone). A white to off-white, crystalline powder. Freely soluble in alcohol, in acetone, in dichloromethane, in ether, in ethyl acetate, in isopropyl alcohol, in methyl alcohol; soluble in diisopropyl ether and in toluene; practically insoluble in hexanes. Protect from light.

💊 Adverse Effects

The incidence and severity of adverse reactions to dinoprostone are dose-related and also depend to some extent on the route; the intravenous route has been associated with a high incidence of adverse effects. Nausea, vomiting, diarrhoea, and abdominal pain are common by all routes. Back pain and rash can occur. Transient cardiovascular (vasovagal) symptoms have included flushing, shivering, headache, dizziness, and hypotension; there have been rare reports of myocardial infarction and cardiac arrest. Hypertension has also been reported. Convulsions and EEG changes have occurred rarely. Local tissue irritation and erythema, as well as pyrexia and raised white cell count, may follow intravenous doses but generally revert to normal after termination of the infusion. Transient pyrexia and raised white cell count may also occur after intravaginal use. Local infection may follow intra- or extra-amniotic therapy. Excessive uterine activity may occur and there have been occasional reports of uterine rupture after the use of prostaglandins to terminate pregnancy or induce labour; fetal distress and, rarely, fetal death have occurred during induction. Disseminated intravascular coagulation has occurred rarely. Dinoprostone, although generally acting as a bronchodilator, may cause bronchoconstriction in some individuals. Hypersensitivity reactions have occurred.

Incidence of adverse effects.

Adverse effects were evaluated in 626 patients1 undergoing abortion (usually in the second trimester), using extra-amniotic or intra-amniotic dinoprost or dinoprostone, often with oxytocin. Vomiting occurred in 291, diarrhoea in 28, pyrexia in 34, transient hypotension (fall in systolic blood pressure of at least 20 mmHg) in 25, transient bronchospasm in 2 patients given extra-amniotic dinoprost, and blood loss exceeding 250 mL in 68 (38 lost more than 500 mL). No patients had convulsions even though 8 were being treated for epilepsy. Three patients sustained lacerations to the cervix. Five patients complained of breast soreness or lactation; these symptoms may have been under-reported. Overall 14 patients were re-admitted; 13 because of excessive vaginal bleeding and 1 because of pelvic infection. A later report describes the cumulative experience in 3313 pregnancies2 in which dinoprostone gel was used for induction of term labour or cervical ripening. Adverse effects were rare. Vomiting, fever, and diarrhoea occurred in about 0.2% of mothers and were difficult to distinguish from the effects of concurrent drug therapy. Detectable myometrial activity was dose-related and more common after intravaginal than after intracervical use. Myometrial activity was reported in 0.6 to 6% of patients following intravaginal application and hyperstimulation was virtually non-existent at an intracervical dose of 500 micrograms. Fetal effects were negligible in the absence of uterine hyperstimulation.
1. MacKenzie IZ, et al. Prostaglandin-induced abortion: assessment of operative complications and early morbidity. BMJ 1974; 4: 683–6
2. Rayburn WF. Prostaglandin E gel for cervical ripening and induction of labor: a critical analysis. Am J Obstet Gynecol 1989; 160: 529–34.

Effects on the bones.

Reversible periosteal reactions of the long bones and bone thickening have occurred in infants receiving long-term therapy with prostaglandins of the E series. In addition, reversible widening of cranial sutures was reported1 in 2 neonates given dinoprostone intravenously for 95 and 97 days respectively.
1. Hoevels-Guerich H, et al. Widening of cranial sutures after longterm prostaglandin E therapy in two newborn infants. J Pediatr 1984; 105: 72–4.

Effects on the cardiovascular system.

Cardiovascular adverse effects are most common after intravenous dinoprostone but may also occur with other routes. Severe cardiovascular disorders reported with the intra-amniotic or intravaginal use of dinoprost or dinoprostone have included: cardiac arrhythmias in 3 patients,1,2 fatal in 2 of them;2 hypotension, tachypnoea, and tachycardia in 3 patients3,4 with associated pyrexias in 2 patients;3 and fatal myocardial infarction in a patient who had several high-risk factors for ischaemic heart disease.5 Severe hypertension occurred in a patient6 who received dinoprostone by direct myometrial injection and by intravenous infusion concomitantly for postpartum haemorrhage. Adverse cardiovascular effects have also been reported with other prostaglandins used in gynaecological or obstetric indications.
1. Burt RL, et al. Hypokalemia and cardiac arrhythmia associated with prostaglandin-induced abortion. Obstet Gynecol 1977; 50: 45S–46S
2. Cates W, Jordaan HVF. Sudden collapse and death of women obtaining abortions induced with prostaglandin F . Am J Obstet Gynecol 1979; 133: 398–400
3. Phelan JP, et al. Dramatic pyrexic and cardiovascular response to intravaginal prostaglandin E . Am J Obstet Gynecol 1978; 132: 28–32
4. Cameron IT, Baird DT. Sudden collapse after intra-amniotic prostaglandin E injection. Lancet 1984; ii: 1046
5. Patterson SP, et al. A maternal death associated with prostaglandin E . Obstet Gynecol 1979; 54: 123–4
6. Veber B, et al. Severe hypertension during postpartum haemorrhage after i.v. administration of prostaglandin E2. Br J Anaesth 1992; 68: 623–4.

Effects on the fetus.

A woman who failed to abort despite receiving carboprost intravaginally 7 weeks after conception gave birth at 34 weeks of gestation to an infant with hydrocephalus and abnormal digits.1 There have been reports of 2 infants born, without congenital abnormality, to women who continued with the pregnancy after attempted mid-trimester termination using intravaginal gemeprost.2,3 However, abnormalities including limb deformities, cleft palate, anencephaly, cerebellar atrophy, and heart malformation were reported in a review4 of 71 cases of pregnancy that were continued after attempted termination using mifepristone either alone or with a prostaglandin. Of the 8 cases of abnormality that were reported, 7 occurred in the group of 10 women who had been given intravaginal gemeprost. A case of cerebellar agenesis has also been described5 after a failed medical termination using mifepristone and gemeprost. For abnormalities reported after the failed misuse of misoprostol alone for termination of pregnancy. For reports of adverse effects on the fetus due to hyperstimulation of the uterus during labour, see under Effects on the Uterus, below.
1. Collins FS, Mahoney MJ. Hydrocephalus and abnormal digits after failed first-trimester prostaglandin abortion attempt. J Pediatr 1983; 102: 620–1
2. Lakasing L, Spencer JAD. Continuation of pregnancy after midtrimester gemeprost administration. Br J Obstet Gynaecol 1999; 106: 1319–20
3. Rolland P, Sinha A. Continuation of pregnancy after mid-trimester gemeprost administration. Br J Obstet Gynaecol 2000; 107: 1184
4. Sitruk-Ware R, et al. Fetal malformation and failed medical termination of pregnancy. Lancet 1998; 352: 323
5. Afadapa FK, Elsapagh K. Isolated one-sided cerebellar agenesis following an attempted medical termination of pregnancy. J Obstet Gynaecol 2006; 26: 581–2.

Effects on the gastrointestinal system.

Necrotising enterocolitis has been associated with the use of intravenous1 or oral2dinoprostone, or intravenous alprostadil,2 in infants with symptomatic congenital heart disease. It has been suggested that induced hypotension and apnoea may be responsible,1 although others3 did not support this view, or that pulmonary vasodilatation may produce systemic to pulmonary shunting, rendering the gastrointestinal tract relatively ischaemic.2
1. Leung MP, et al. Necrotizing enterocolitis in neonates with symptomatic congenital heart disease. J Pediatr 1988; 113: 1044–6
2. Singh GK, et al. Study of low dosage prostaglandin—usages and complications. Eur Heart J 1994; 15: 377–81
3. Miller MJS, Clark DA. Congenital heart disease and necrotizing enterocolitis. J Pediatr 1989; 115: 335–6.

Effects on the neonate.

Aspiration of the undissolved remnants of a dinoprostone vaginal tablet caused neonatal respiratory distress due to mechanical obstruction of the airways; there was no evidence to suggest absorption of dinoprostone from the tablet matrix.1 Inadvertent intramuscular injection of carboprost 250 micrograms caused hypertension, bronchospasm, diarrhoea, and hyperthermia in a neonate. There was also an adverse neurological effect that was either a dystonic reaction or seizure activity. The neonate was treated symptomatically and discharged 24 hours later; neurological and developmental examinations were normal at 3 months of age.2 The authors of this report also learned of 2 other cases that had been reported to the manufacturer, in which neonates given injections of 125 micrograms and 63 micrograms remained asymptomatic.
1. Andersson S, et al. Neonatal respiratory distress caused by aspiration of a vaginal tablet containing prostaglandin. BMJ 1987; 295: 25–6
2. Mrvos R, et al. Carboprost exposure in a newborn with recovery. J Toxicol Clin Toxicol 1999; 37: 865–7.

Effects on the nervous system.

Convulsions and EEG changes have been occasionally reported during the use of prostaglandins for termination of pregnancy. Convulsions occurred1in 5 of 320 women after intra-amniotic dinoprost, but in other large series2-4 of patients given dinoprost or dinoprostone by various routes no problems occurred despite the inclusion of patients with a history of epilepsy. However, convulsions were reported5 in 3 of 4 epileptic patients given sulprostone intramuscularly.
1. Lyneham RC, et al. Convulsions and electroencephalogram abnormalities after intra-amniotic prostaglandin F . Lancet 1973; ii: 1003–5
2. MacKenzie IZ, et al. Convulsions and prostaglandin-induced abortion. Lancet 1973; ii: 1323
3. Thiery M, et al. Prostaglandins and convulsions. Lancet 1974; i: 218
4. Fraser IS, Gray C. Electroencephalogram changes after prostaglandin. Lancet 1974; i: 360
5. Brandenburg H, et al. Convulsions in epileptic women after administration of prostaglandin E derivative. Lancet 1990; 336: 1138.

Effects on the uterus.

Use of prostaglandins to induce labour or to terminate pregnancy is associated with an increased risk of hyperstimulation of the uterus. Uterine rupture has occurred with carboprost,1 dinoprost or dinoprostone,2-7 gemeprost,8-10 misoprostol,11-14 and sulprostone.15-17 These effects have been reported with parenteral, local, and oral dosage. The risk of rupture and associated complications is increased in grand multiparae4 and those with uterine scarring from previous caesarean section.5,7Studies have reported relative risks of between 6 and 10 times those of spontaneous labour after labour induction with dinoprostone in the latter group.5,7 In addition to rupture, with the risk of potentially fatal maternal haemorrhage, hyperstimulation has been associated with fetal distress and death,18-20 and maternal death due to amniotic fluid embolism.18,21
1. Vergote I, et al. Uterine rupture due to 15-methyl prostaglandin F . Lancet 1982; ii: 1402
2. Claman P, et al. Uterine rupture with the use of vaginal prostaglandin E for induction of labor. Am J Obstet Gynecol 1984; 150: 889–90
3. Keller F, Joyce TH. Uterine rupture associated with the use of vaginal prostaglandin E suppositories. Can Anaesth Soc J 1984; 31: 80–2.
4. Larsen JV, et al. Uterine hyperstimulation and rupture after induction of labour with prostaglandin E . S Afr Med J 1984; 65: 615–16
5. Ravasia DJ, et al. Uterine rupture during induced trial of labor among women with previous cesarean delivery. Am J Obstet Gynecol 2000; 183: 1176–9
6. Rabl M, et al. A randomized trial of vaginal prostaglandin E for induction of labor: insert vs tablet. J Reprod Med 2002; 47: 115–19
7. Taylor DR, et al. Uterine rupture with the use of PGE vaginal inserts for labor induction in women with previous cesarean sections. J Reprod Med 2002; 47: 549–54
8. Thavarasah AS, Achanna KS. Uterine rupture with the use of Cervagem (prostaglandin E1) for induction of labour on account of intrauterine death. Singapore Med J 1988; 29: 351–2
9. Byrne P, Onyekwuluje T. Uterine rupture after termination of pregnancy with gemeprost. BMJ 1991; 302: 852
10. Vine SJ, et al. Transverse posterior cervicoisthmic rupture after gemeprost pessaries for termination. BMJ 1992; 305: 1332
11. Blanchette HA, et al. Comparison of the safety and efficacy of intravaginal misoprostol (prostaglandin E ) with those of dinoprostone (prostaglandin E ) for cervical ripening and induction of labor in a community hospital. Am J Obstet Gynecol 1999; 180: 1551–9
12. Mathews JE, et al. Uterine rupture in a multiparous woman during labor induction with oral misoprostol. Int J Gynaecol Obstet 2000; 68: 43–4
13. Khabbaz AY, et al. Rupture of an unscarred uterus with misoprostol induction: case report and review of the literature. J Matern Fetal Med 2001; 10: 141–5
14. Nayki U, et al. Uterine rupture during second trimester abortion with misoprostol. Fetal Diagn Ther 2005; 20: 469–71
15. Larue L, et al. Rupture d’un utérus sain lors d’une interruption de grossesse par prostaglandines au deuxième trimestre. J Gynecol Obstet Biol Reprod (Paris) 1991; 20: 269–72
16. Prasad RNV, Ratnam SS. Uterine rupture after induction of labour for intrauterine death using the prostaglandin E analogue sulprostone. Aust N Z J Obstet Gynaecol 1992; 32: 282–3
17. de Boer MA, et al. Low dose sulprostone for termination of second and third trimester pregnancies. Eur J Obstet Gynecol Reprod Biol 2001; 99: 244–8
18. Stronge J, et al. A neonatal and maternal death following the administration of intravaginal prostaglandin. J Obstet Gynaecol 1987; 7: 271–2
19. Quinn MA, Murphy AJ. Fetal death following extra-amniotic prostaglandin gel: report of two cases. Br J Obstet Gynaecol 1981; 88: 650–1
20. Simmons K, Savage W. Neonatal death associated with induction of labour with intravaginal prostaglandin E : case report. Br J Obstet Gynaecol 1984; 91: 598–9
21. Less A, et al. Vaginal prostaglandin E and fatal amniotic fluid embolus. JAMA 1990; 263: 3259–60.

Overdosage.

Severe adverse effects associated with intraamniotic prostaglandins have been attributed to absorption into the systemic circulation of doses higher than would normally be given systemically. Rigors, vomiting, severe abdominal pain, and an intense desire to urinate and defaecate occurred1 in 3 patients given dinoprostone intra-amniotically for mid-trimester abortion; one patient had peripheral vasoconstriction and a rapid low-volume pulse, with hypotension, and another had peripheral cyanosis. It was suggested2 that this might have been due to displacement of the needle or cannula outside the amniotic sac. In 2 of the patients prior use of urea may have increased the rate of absorption of prostaglandins from the amniotic cavity. In a further report3 flushing, severe headache, and nausea immediately after a test dose of dinoprost 2.5 mg was also thought to be due to incorrect positioning of the needle and consequent injection into the systemic circulation; at least part of the dose might have been injected into the peritoneal cavity.4 Severe reactions have also been reported with prostaglandins given to abort hydatidiform moles. A 20-year-old woman given 20 mg of dinoprostone by injection into the uterine cavity developed profound hypotension, bradycardia, and rigors, followed by nausea, vomiting, suprapubic pain, an increased pulse rate, pyrexia, and generalised flushing.5 Since there are no fetal membranes in a molar pregnancy, intra-uterine administration is similar to extra-amniotic administration and the dose used was 100 times higher than the usual extra-amniotic dose.4 However, in a similar patient6 ‘extra-amniotic’ instillation of dinoprostone 200 micrograms was followed immediately by nausea, retching, severe abdominal pain, dizziness, difficulty in breathing and the production of frothy blood-stained sputum, an imperceptible pulse, and hypotension; the dinoprostone had probably been injected directly into the maternal circulation.
1. Ross AH, Whitehouse WL. Adverse reactions to intra-amniotic urea and prostaglandin. BMJ 1974; 1: 642
2. Craft I, Bowen-Simpkins P. Adverse reactions to intra-amniotic urea and prostaglandin. BMJ 1974; 2: 446
3. Brown R. Adverse reactions to intra-amniotic prostaglandin. BMJ 1974; 2: 382
4. Karim SMM. Adverse reactions to intra-amniotic prostaglandin. BMJ 1974; 3: 347
5. Smith AM. Adverse reactions to intra-amniotic prostaglandin. BMJ 1974; 2: 382–3
6. McNicol E, Gray H. Adverse reaction to extra-amniotic prostaglandin E . Br J Obstet Gynaecol 1977; 84: 229–30.

💊 Precautions

Dinoprostone should not be given to patients in whom oxytocic drugs are generally contra-indicated, because spontaneous labour or vaginal delivery are liable to harm either the mother or the fetus. This includes significant cephalopelvic disproportion or unfavourable presentation of the fetus, placenta praevia, or fetal distress. It should not be used where there is a predisposition to uterine rupture, as in high parity or the presence of a uterine scar from previous caesarean section or major uterine surgery, or in those with a history of pelvic inflammatory disease. Since prostaglandins enhance the effects of oxytocin, use of these drugs together or in sequence should be carefully monitored. Dinoprostone is contra-indicated in active cardiac, pulmonary, renal, or hepatic disease. It should be used with caution in patients with glaucoma or raised intraocular pressure, a history of asthma or epilepsy, hepatic or renal impairment, or cardiovascular disease. In the induction of labour cephalopelvic relationships should be carefully evaluated before use. During use uterine activity, fetal status, and the progress of cervical dilatation should be carefully monitored to detect adverse responses, such as hypertonus, sustained uterine contractions, or fetal distress. In patients with a history of hypertonic uterine contractility or tetanic uterine contractions, uterine activity and the state of the fetus should be continuously monitored throughout labour. Where high-tone myometrial contractions are sustained the possibility of uterine rupture should be considered. Dinoprostone should not be given by the myometrial route, since there is a possible association with cardiac arrest in severely ill patients. The extra-amniotic route should not be used in patients with cervicitis or vaginal infections. Vaginal preparations of dinoprostone should not be used in the induction of labour once the membranes are ruptured. In some countries, intravenous prostaglandins are considered to be contra-indicated in women who smoke. Dinoprostone should be used with caution in women over 35 years of age, those with complications during pregnancy, such as gestational diabetes, hypertension, or hypothyroidism, and in those past the fortieth week of pregnancy as their condition may further enhance the increased risk of disseminated intravascular coagulation in the immediate postpartum period associated with pharmacologically induced labour. In the therapeutic termination of pregnancy, fetal damage has been seen in cases of incomplete termination and the appropriate treatment for complete evacuation of the uterus should therefore be instituted whenever termination is unsuccessful or incomplete. Dinoprostone should not be used for termination in patients with pelvic infection, unless adequate treatment has already been started.

Administration.

For the hazards of unintentional systemic absorption of prostaglandins after intra-uterine use for the termination of pregnancy and abortion of hydatidiform moles, see Overdosage in Adverse Effects, above.

💊 Interactions

Dinoprostone enhances the effects of oxytocin on the uterus. There is a theoretical risk that prostaglandin synthetase inhibitors, such as aspirin and NSAIDs, might alter the efficacy of dinoprostone.

Uterine stimulants.

Marked hypertension, vomiting, and severe dyspnoea occurred after the sequential use of oxytocin, methylergometrine, and dinoprost within the space of 10 minutes to a woman with postpartum haemorrhage.1
1. Cohen S, et al. Severe systemic reactions following administration of different ureotonic [uterotonic] drugs. N Y State J Med 1983; 83: 1060–1.

💊 Uses and Administration

Dinoprostone is a prostaglandin of the E series with actions on smooth muscle; the endogenous substance is termed prostaglandin E 2 and is rapidly metabolised in the body. It induces contraction of uterine muscle at any stage of pregnancy and is reported to act mainly as a vasodilator and as a bronchodilator. In the UK, dinoprostone is used principally in the induction of labour; it may also be used for the termination of pregnancy, missed abortion, hydatidiform mole, and intra-uterine fetal death. Dinoprostone is usually given vaginally. It may also be given intravenously, extra-amniotically, or orally, but the intravenous route has been associated with a high incidence of adverse effects and is generally only used for missed abortion or hydatidiform mole; continuous use for more than 2 days is not recommended. For the induction of labour dinoprostone is used to ripen (soften and dilate) the cervix before the membranes are ruptured and to induce labour at term. The cervical gel used for cervical ripening contains 500 micrograms in 2.5 mL, whereas the vaginal gel used for induction of labour contains 1 or 2 mg in 2.5 mL; the vaginal gel should not be used in the cervical canal. Pessaries are also available for both cervical ripening and labour induction. These are not bioequivalent to the gels and their dosage is different. To soften and dilate the cervix before induction of labour dinoprostone 500 micrograms is given as cervical gel. This dose may be repeated after 6 hours if there was no response to the initial dose; in some cases a third dose may be used to a maximum cumulative dose of 1.5 mg in 24 hours. For induction of labour the dose as vaginal gel is 1 mg (or 2 mg in primigravid patients with unfavourable induction features) followed, if necessary, by a further 1 or 2 mg after 6 hours; a total dose of 3 mg (or 4 mg in unfavourable primigravid patients) should not be exceeded. Alternatively a vaginal pessary containing 3 mg may be used and this may be followed, if necessary, by a further 3 mg after 6 to 8 hours; a total dose of 6 mg should not be exceeded. A modified-release vaginal pessary containing 10 mg and delivering about 300 micrograms/hour can be used for cervical ripening and subsequent labour induction. If satisfactory cervical ripening does not occur within 12 or 24 hours, depending on the preparation, then it should be removed. Dinoprostone may be given orally for the induction of labour in an initial dose of 500 micrograms, repeated hourly, and increased if necessary to 1 mg hourly until an adequate response is achieved; single doses of 1.5 mg should not be exceeded. Oral use has, however, generally been replaced by intravaginal dosage since the latter is associated with fewer gastrointestinal adverse effects. Dinoprostone has been given intravenously for the induction of labour but is no longer recommended for routine use by most authorities. A suggested intravenous dosage has been 250 nanograms/minute infused as a solution containing 1.5 micrograms/mL for 30 minutes, the dose being subsequently maintained or increased according to the patient’s response; in intrauterine fetal death higher doses may be required and an initial rate of 500 nanograms/minute has been used with increases at intervals of not less than 1 hour. For the termination of pregnancy in the second trimester 1 mL of a solution containing dinoprostone 100 micrograms/mL may be instilled extra-amniotically through a suitable Foley catheter, with subsequent doses of 1 or 2 mL given at intervals usually of 2 hours, according to response. Dinoprostone has also been given intravenously for the termination of pregnancy and for missed abortion or hydatidiform mole. A solution containing 5 micrograms/mL may be infused at a rate of 2.5 micrograms/minute for 30 minutes, the infusion then being maintained or increased to a rate of 5 micrograms/minute; this rate should be maintained for at least 4 hours before making further increases. In the USA dinoprostone pessaries are used for the termination of second trimester pregnancy. A dose of 20 mg is given intravaginally and repeated every 3 to 5 hours according to response for up to 2 days; a total dose of 240 mg should not be exceeded. Pessaries are also used in the USA in missed abortion, intra-uterine fetal death, and benign hydatidiform mole. Dinoprostone is used in some centres to maintain the patency of the ductus arteriosus (see below).

Haemorrhagic cystitis.

Dinoprostone instilled into the bladder for 4 hours and repeated for 4 days successfully improved severe cyclophosphamide-induced haemorrhagic cystitis in a bone marrow transplant recipient.1 Similar results were obtained in another series of 10 patients.2
1. Mohiuddin J, et al. Treatment of cyclophosphamide-induced cystitis with prostaglandin E . Ann Intern Med 1984; 101: 142
2. Laszlo D, et al. Prostaglandin E2 bladder instillation for the treatment of hemorrhagic cystitis after allogeneic bone marrow transplantation. Haematologica 1995; 80: 421–5.

Hepatic disorders.

See under Alprostadil, for reference to the use of prostaglandins, including dinoprostone, in the treatment of viral hepatitis.

Patent ductus arteriosus.

Prostaglandins, particularly alprostadil and dinoprostone, may be used to maintain the patency of the ductus arteriosus in infants with congenital heart disease until surgery can be performed to correct the malformation. Treatment for a longer period, especially with oral dinoprostone, may facilitate later surgery by allowing growth of the infants and their pulmonary arteries. Beneficial responses to long-term use of dinoprostone have been reported.1,2 Dinoprostone has been given orally in an initial dose of 20 to 25 micrograms/kg hourly, decreasing the frequency of doses after the first week; it was suggested that treatment should be continued for up to 4 weeks initially and a decision then made whether to proceed with surgery or to plan a longer course of treatment to encourage further growth. When gastrointestinal absorption is expected to be poor or when oral treatment is ineffective, dinoprostone has been given by intravenous infusion. The BNFC recommends an initial dose of 5 to 10 nanograms/kg per minute increased as necessary, in steps of 5 nanograms/kg per minute, to 20 nanograms/kg per minute; further increases may be needed and doses of up to 100 nanograms/kg per minute have been used, however, these are associated with an increased risk of adverse effects.
1. Silove ED, et al. Evaluation of oral and low dose intravenous prostaglandin E in management of ductus dependent congenital heart disease. Arch Dis Child 1985; 60: 1025–30
2. Thanopoulos BD, et al. Prostaglandin E administration in infants with ductus-dependent cyanotic congenital heart disease. Eur J Pediatr 1987; 146: 279–82.

Pemphigus.

Erosive oral lesions in 3 patients1 with pemphigus vulgaris, that had previously been refractory to standard corticosteroid therapy, resolved on sucking oral dinoprostone tablets 1.5 to 3 mg daily. Symptoms recurred within weeks of ceasing dinoprostone but could be controlled by courses of 0.5 to 1 mg daily for 1 to 2 weeks, when required. In a group of 10 patients,2 topical dinoprostone produced similar results in 6 patients, but disease was exacerbated in the others; the dinoprostone was applied twice daily, but details of the dosage form and dose were not reported.
1. Morita H, et al. Clinical trial of prostaglandin E on the oral lesions of pemphigus vulgaris. Br J Dermatol 1995; 132: 165–6
2. Kumaran MS, Kanwar AJ. Efficacy of topical PGE2 in recalcitrant oral lesions of pemphigus vulgaris: a clinical trial. J Eur Acad Dermatol Venereol 2006; 20: 898–9.

Peripheral vascular disease.

Various prostaglandins have been used in the treatment of peripheral vascular disease, particularly in severe Raynaud’s syndrome, but do not constitute mainline therapy.

Postpartum haemorrhage.

Dinoprostone and other prostaglandins have been used to control severe postpartum haemorrhage unresponsive to ergometrine and oxytocin. Beneficial response to continuous intra-uterine irrigation with dinoprostone solution 1.5 micrograms/mL was seen in 22 patients with postpartum haemorrhage unresponsive to other treatment.1Postpartum haemorrhage was controlled in another patient using a dinoprostone 3-mg vaginal suppository held against the uterine wall.2
1. Peyser MR, Kupfermine MJ. Management of severe postpartum hemorrhage by intrauterine irrigation with prostaglandin E . Am J Obstet Gynecol 1990; 162: 694–6
2. Markos AR. Prostaglandin E intrauterine suppositories in the treatment of secondary postpartum hemorrhage. J R Soc Med 1989; 82: 504–5.

💊 Preparations

Proprietary Preparations

Arg.: Prolisina E2; Propess; Austral.: Cervidil; Prostin E2; Austria: Prepidil; Propess; Prostin E2; Belg.: Prepidil; Prostin E2; Canad.: Cervidil; Prepidil; Prostin E2; Cz.: Prepidil; Propess; Prostin E2; Denm.: Minprostin; Fin.: Minprostin; Propess; Fr.: Prepidil; Propess; Prostine E ; Ger.: Minprostin E ; Prepidil; Propess; Gr.: Minprostin; Propess; Prostin E2; Hong Kong: Prostin E2; Hung.: Prepidil; Propess†; Prostin E2; India: Cerviprime; Primiprost; Indon.: Prostin E2; Irl.: Prostin E2; Israel: Prepidil; Propess; Prostin E2; Ital.: Prepidil; Propess; Prostin E2; Malaysia: Prostin E2; Mex.: Prepidil; Propess; Neth.: Prepidil; Propess; Prostin E2; Norw.: Minprostin; NZ: Cervidil; Prostin E2; Pol.: Prepidil; Propess; Port.: Propess; Prostin E2; Rus.: Prepidil (Препидил); Prostin E2 (Простин E2)†; S.Afr.: Prandin E ; Prepidil; Propess; Prostin E2; Singapore: Prostin E2; Spain: Prepidil; Propess; Swed.: Minprostin; Propess; Switz.: Prepidil†; Propess; Prostin E2; Thai.: Prostin E2; UK: Propess; Prostin E2; USA: Cervidil; Prepidil; Prostin E2.
Published October 24, 2018.