PROSTIN F2 alpha (dinoprost) is the synthetic or partially synthetic, naturally-occurring prostaglandin, F2 alpha present in this product in the form of its crystalline trometamol (THAM) salt. Its structural formula is The molecular weight of dinoprost is 354.47 and that of its trometamol salt, depicted above, is 475.6. In the form of its trometamol (THAM) salt, it is a white or slightly off-white crystalline powder that is readily soluble in water at room temperature in concentrations up to at least 200 mg/mL. It is supplied as: Sterile Aqueous Solution dinoprost, 5 mg/1 mL. (present as 6.71 mg/mL of dinoprost trometamol salt) containing 0.9% benzyl alcohol as preservative.

PHARMACOLOGY

Although the exact mode of action in pregnancy termination in humans is not fully defined, when PROSTIN F2 alpha is administered by the intrauterine route it initiates rhythmical uterine contractions which, if continued for a sufficient time, are capable of expelling the contents of the uterus. Sensitivity of the pregnant uterus to prostaglandins is lower during early and mid-pregnancy than at term. While PROSTIN F2 alpha has been shown to be luteolytic in several animal species, it is unlikely that this is the mechanism involved when the drug is utilised in therapeutic termination of pregnancy in the human as described in this leaflet. PROSTIN F2 alpha is also capable of inducing contractions of the smooth muscle of the intestinal tract. This action may be the cause of the vomiting and diarrhoea which are associated with the use of PROSTIN F2 alpha. In some animals and in man, large doses of PROSTIN F2 alpha can bring about an increase in blood pressure, probably due to its effect on vascular smooth muscle. At the doses recommended for the therapeutic termination of pregnancy, this effect has not been clinically significant.

INDICATIONS

Therapeutic termination of pregnancy (PROSTIN F2 alpha Sterile Solution 5 mg/1 mL).

PROSTIN F2 alpha is indicated for the therapeutic termination of pregnancy during the first or second trimester.
PROSTIN F2 alpha may be used for evacuation of the uterus in cases of foetal death in utero, missed abortion, as a non-surgical treatment for the evacuation of hydatidiform moles and as an alternative measure to complete therapeutic termination of pregnancy when intra-amniotic saline injections have failed.

NOTE: At the present time, this product should only be used in hospitals or in locations with facilities for emergency obstetric and gynaecological care.

CONTRAINDICATIONS

PRECAUTIONS

There has been some evidence in animals of teratogenic activity, therefore, if termination of pregnancy does not occur or is suspected to be incomplete as a result of prostaglandin therapy, the appropriate treatment for complete evacuation of the pregnant uterus should be instituted in all instances. It has been found that prostaglandins potentiate the effect of oxytocin and it is therefore recommended that use of these drugs simultaneously or in sequence be carefully monitored. Caution should be exercised in the administration of PROSTIN F2 alpha for therapeutic termination of pregnancy in patients with a history of asthma, glaucoma or raised intraocular pressure. The possibility of uterine rupture should be borne in mind where high tone myometrial contractions are sustained. Alcohol and beta stimulants neutralise the effects of PROSTIN F2 alpha and if the patient has taken either of these, this should be considered. In the therapeutic termination of pregnancy, physicians are reminded that a live born foetus may occur particularly as gestational age approaches the end of the second trimester.

ADVERSE EFFECTS

Most common side effects are nausea, vomiting and diarrhoea. Certain rare (less than 1/1000) but serious events should be especially noted: hypersensitivity to the drug, uterine rupture and cardiac arrest. Clinical experience to date indicates that Prostin F2 alpha administered by the intrauterine (extra-amniotic or intra-amniotic) routes is more effective and better tolerated than by the intravenous route. Other adverse events reported in decreasing order of severity were:

Events occurring in approximately one to five percent of cases: Blood loss

Uterine infections Fever Events occurring in approximately 5/10,000 cases: Disseminated intravascular Tachycardia Coagulation Perforation of the cervix Uterine pain Drowsiness Hypovolaemic shock Headache Unspecified pain Syncope or dizziness Bronchospasm Dyspnoea Coughing Chills Hypertension or Urinary tract infections Hypotension Events occurring less frequently than approximately 5/10,000 cases: Pulmonary embolism Paraesthesias Hiccough Backache Perforated uterus-post instrumentation Pruritus Malaise Skin eruption Pelvic thrombophlebitis Petechiae Diplopia Paralytic ileus Hypokalaemia Breast engorgement Polydipsia Weakness Congestive heart failure Sweating Hyperventilation Bradycardia Second degree heart block Nosebleed Burning sensation - eye Urinary incontinence Ventricular arrhythmia Dehydration Burning sensation - breast Dysuria Aggravation of diabetes Excitement Pupil constriction Haematuria Chest pain Cyanosis Convulsions Unspecified muscle spasm Uterine atony or hypertonicity

DIRECTIONS FOR THE PREPARATION OF DILUTE SOLUTIONS FROM THE 5 mg/1 mL STERILE SOLUTION

The neck of the ampoule is prescored at the point of constriction. (No ampoule file is needed to open the ampoules. ). A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards.

For Extra-Amniotic Use (250 mg/mL solution).

Withdraw 1.0 mL from the ampoule, using an aseptic technique and add 19.0 mL of sterile normal saline to make 20 mL of a solution containing 250 mg/mL. Shake to ensure uniformity. Use the dilute solution within 48 hours of preparation.

For Intra-Amniotic Use

The 5 mg/1 mL solution is used as it comes from the ampoule, without dilution. The intravenous administration is not approved in Australia.

DOSAGE AND ADMINISTRATION

A solution containing 250 mg/mL PROSTIN F2 alpha should be prepared. Insert a 12 to 14 French gauge Foley catheter with self-retaining 30 mL balloon through the cervix into the space between the foetal membranes and the uterine wall (extra-ovular or extra-amniotic), so that the balloon passes just beyond the internal os. Fill the balloon with 30 mL sterile water (a fine polyethylene catheter has also been used). The PROSTIN F2 alpha solution should then be instilled through the catheter. After filling the catheter system deadspace with a predetermined quantity of dilute solution, the initial dose should be 1 mL. Subsequent instillations should be 3 mL, unless side effects ensue, when the dose may be reduced to 1 or 2 mL or the interval between doses prolonged. Two hours should usually elapse between each installation and never less than 1 hour.

A transabdominal tap of the amniotic sac should be accomplished with an appropriate sized needle and at least 1 mL of amniotic fluid should be withdrawn, then 40 mg (8 mL) of PROSTIN F2 alpha is slowly injected into the amniotic sac. It is suggested that the first millilitre be injected very slowly to determine possible sensitivity prior to completing the total 40 mg dose. (Do not inject medication in the case of a bloody tap). If within 24 hours of the initial dose the abortion process has not been established or completed (and in the presence of intact membranes), an additional 10-40 mg (2-8 mL) of PROSTIN F2 alpha may be administered.

Other drugs which have been employed during PROSTIN F2 alpha administration for the symptomatic relief of side effects include:

PRESENTATION AND STORAGE CONDITIONS

PROSTIN F2 alpha is available as: Sterile Solution, each millilitre contains 5 mg PROSTIN(r) F2 alpha (dinoprost), as trometamol salt, supplied as: 5 mg/1 mL, 20 mg/4 mL (not marketed) and 40 mg/8 mL (not marketed) ampoules. PROSTIN F2 alpha is stable for five years from date of manufacture if stored below 25C.

NAME OF THE MEDICINE

DESCRIPTION