Dinoprostone

Registered South African indications:

• Cervical ripening

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Labour has started
• When strong, prolonged uterine contraction would be inappropriate such as in:
  - Previous major uterine surgery (e.g. caesarean section, myomectomy)
  - Rupture to the cervix of the uterus (other than biopsies and cervical abrasion) (South African manufacturer recommendations)
  - Previous major uterine cervix surgery (e.g. other than biopsies and cervical abrasion) or rupture of the uterine cervix) (International manufacturer recommendations)
  - Cephalopelvic disproportion
  - Foetal malpresentation
  - Suspicion or evidence of foetal distress
• Current pelvic inflammatory disease, unless adequate prior treatment has been instituted
• Placenta praevia or unexplained vaginal bleeding during the current pregnancy
• Coadministration with oxytocic medicines and /or other labour induction agents

Cautions 

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Lung disease
• Ruptured membranes
• History of uterine hypertonus
• History of glaucoma
• History of asthma
• Prolonged or excessive uterine contractions
• Multiple pregnancy
• >3 full-term deliveries
• Second dose of dinoprostone
• Risk factors for developing disseminated intravascular coagulation (DIC)
  - Women 35 years or older
  - Complications during pregnancy (gestational diabetes, arterial hypertension and hypothyroidism)
  - Gestational age over 40 weeks
• Coadministration with anti-inflammatory agents, including acetylsalicylic acid

Forms avail. in SA and covered in this monograph: vat

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Cervical ripening
- Initiation and/or continuation at term (from 37 completed weeks of gestation)

• Vaginal delivery system: 10mg, administered high into the posterior vaginal fornix

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The vaginal delivery system should be removed after 24 hours irrespective of whether cervical ripening has been achieved

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A dosing interval of at least 30 minutes is recommended for the sequential use of oxytocin following the removal of the vaginal delivery system. Only one application of dinoprostone is recommended

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Method of administration: See additional prescribing points

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Removal: See additional prescribing points

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International manufacturer recommendations

Cervical ripening
- Initiation at term (from 37 completed weeks of gestation)

Dinoprostone should only be administered by qualified healthcare personnel in hospitals and clinics with specialised obstetric units with facilities for continuous fetal and uterine monitoring

• Vaginal delivery system: 10mg, administered high into the posterior vaginal fornix

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After insertion, uterine activity and foetal condition must be carefully and regularly monitored

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The vaginal delivery system should be removed after 24 hours irrespective of whether cervical ripening has been achieved

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A dosing interval of at least 30 minutes is recommended for the sequential use of oxytocin following the removal of the vaginal delivery system. Only one application of dinoprostone is recommended

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Method of administration: See additional prescribing points

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Removal: See additional prescribing points

Not established for use in children below 18 years

Pregnancy

• Caution
• Dinoprostone should not be used during pregnancy prior to 37 completed weeks of gestation. Dinoprostone should be used with caution when there is a multiple pregnancy. No studies in multiple pregnancy have been performed. Dinoprostone is used in pregnancy to induce labour

Breastfeeding

• Caution 
• No studies have been performed to investigate the amount of dinoprostone in colostrum or breast milk following the use of dinoprostone
• Dinoprostone may be excreted in colostrum and breast milk, but the level and duration is expected to be very limited and should not hinder breastfeeding. No effects on the breastfed new-borns have been observed in the clinical studies conducted with dinoprostone

Fertility

• Not relevant

Renal Impairment

• Caution; no information available 
  The use of dinoprostone is not recommended

Hepatic Impairment

• Caution; no information available 
  The use of dinoprostone is not recommended

Elderly

• Not indicated for use in geriatric patients 

Porphyria Information

• Probably not porphyrinogenic (PNP) 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache

Cardiovascular Disorders 

• Foetal heart rate disorder
  - Abnormalities in foetal heart rate
  - Foetal bradycardia
  - Foetal tachycardia
  - Unexplained absence of normal variability
  - Decreased foetal heart rate
  - Foetal heart rate deceleration
  - Early or late decelerations
  - Variable decelerations
  - Prolonged decelerations
• Hypotension 

Respiratory Disorders 

• Neonatal respiratory distress-related conditions

Gastrointestinal Disorders 

• Abdominal pain
• Diarrhoea
• Nausea and vomiting

Hepatobiliary Disorders 

• Neonatal hyperbilirubinaemia

Genitourinary Disorders

• Abnormal labour affecting foetus
  - Uterine tachysystole
  - Late decelerations
  - Foetal bradycardia
  - Prolonged decelerations
• Abnormal uterine contractions
• Uterine tachysystole
• Uterine hyperstimulation
• Uterine hypertonus
• Meconium in amniotic fluid
• Premature separation of placenta
• Arrested labour
• Chorioamnionitis
• Uterine atony
• Vulvovaginal burning sensation
• Genital oedema
• Uterine rupture
• Postpartum haemorrhage

Skin and Subcutaneous Tissue Disorders 

• Pruritus

Immune, Blood and Lymphatic System Disorders 

• Hypersensitivity
• Anaphylactoid syndrome of pregnancy
• Anaphylactic reaction
• Febrile disorders
• Disseminated intravascular coagulation

Others

• Foetal distress syndrome
  - Foetal acidosis
  - Pathological cardiotocography (CTG)
  - Foetal heart rate abnormalities
  - Intrauterine hypoxia
  - Threatening asphyxia
• Foetal death
• Stillbirth
• Neonatal death
• Low Apgar score

• Oxytocic agents

• Foetal heart rate
• Uterine activity
• Progression of cervical dilation and effacement

Additional observations

• Signs of amniotic fluid embolism
  - Coma
  - Disseminated intravascular coagulation (evolving fibrinolysis)
  - Hypotension
  - Hypoxemia
  - Respiratory failure
  - Seizures

Method of administration

• Dinoprostone should be removed from the freezer just prior to the insertion. No thawing is required prior to use
• There is a “tear mark” on the side of the foil sachet. Open the package along the tear mark across the top of the sachet. Do not use scissors or other sharp objects which may cut the retrieval system
• The vaginal delivery system should be inserted high into the posterior vaginal fornix using only small amounts of water-soluble lubricants to aid insertion. After the vaginal delivery system has been inserted, the withdrawal tape may be cut with scissors always ensuring there is sufficient tape outside the vagina to allow removal
• No attempt should be made to tuck the end of the tape into the vagina as this may make retrieval more difficult
• The patient should be recumbent for 20-30 minutes after insertion. As prostaglandin E2 (PGE2) will be released continuously over a period of 24 hours, it is important to monitor uterine contractions and foetal condition at frequent regular intervals

Removal

• The vaginal delivery system can be removed quickly and easily by gentle traction on the retrieval tape. Remove the vaginal delivery system to terminate drug administration when cervical ripening is judged to be complete or for any of the reasons listed below
• Onset of labour, for the purpose of induction of labour with dinoprostone, the onset of labour is defined as the presence of regular, painful uterine contractions occurring every 3 minutes irrespective of any cervical change. There are two important points to note
  - Once regular, painful contractions have been established with dinoprostone, they will not reduce in frequency or intensity as long as dinoprostone remains in situ because PGE2 is still being administered
  - Patients, particularly multigravidae, may develop regular, painful contractions without any apparent cervical change. Effacement and dilation of the cervix may not occur until uterine activity is established. Because of this, once regular, painful uterine activity is established with dinoprostone in situ, the vaginal delivery system should be removed irrespective of cervical state to avoid the risk of uterine hyperstimulation
• Spontaneous rupture of the membranes or amniotomy
• Any suggestion of uterine hyperstimulation or hypertonic uterine contractions
• Evidence of foetal distress
• Evidence of maternal systemic PGE2 adverse effects such as nausea, vomiting, hypotension or tachycardia
• At least 30 minutes prior to starting an intravenous infusion of oxytocin, as there is a much greater risk of hyperstimulation if the dinoprostone source is not removed before administration of oxytocin
• The opening on one side of the retrieval device is present only to allow the manufacturer to enclose the vaginal delivery system into the retrieval device during manufacture. The vaginal delivery system should never be removed from the retrieval device
• On removal of the product from the vagina, the vaginal delivery system will have swollen to 2-3 times its original size and be pliable. The whole product should be disposed of as clinical waste

Special warnings and precautions for use

• Use of dinoprostone may result in inadvertent abruption of placenta and subsequent embolization of antigenic tissue causing in rare circumstances the development of anaphylactoid syndrome of pregnancy (amniotic fluid embolism)

Prostaglandin E2 (PGE2) is a naturally occurring compound found in low concentrations in most tissues of the body. It functions as a local hormone. Prostaglandin E2 plays an important role in the complex set of biochemical and structural alterations involved in cervical ripening. Cervical ripening involves a transformation of the uterine cervix which must be transformed from a rigid structure to a soft, dilated configuration to allow passage of the fetus through the birth canal. This process involves activation of the enzyme collagenase which is responsible for the breakdown of the collagen. Local administration of dinoprostone to the cervix results in cervical ripening which then induces the subsequent events which complete labour.

Vaginal delivery system 10mg

• Propess (Ferring) originator

Also available in the following forms: gel and tablet.