Prostin E2 Sterile Solution 10mg/Ml
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Prostin E2 Sterile Solution 10mg/ml.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains 10mg dinoprostone.
3 PHARMACEUTICAL FORM
Colourless, sterile solution, which after appropriate dilution is intended for intravenous administration to human beings.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxytocic agent. Therapeutic termination of pregnancy, missed abortion and hydatidiform mole by the intravenous route.
4.2 Posology and method of administration
Adults: Ampoule contents must be diluted before use and full instructions on method of dilution and dosage are given on the package insert which should be consulted prior to initiation of therapy. The following is a guide to dosage:
Dilute with normal saline or 5 % dextrose according to the package insert to produce a 5 micrograms/ml solution. The 5 micrograms/ml solution is infused at 2.5 micrograms/minute for 30 minutes and then maintained or increased to 5 micrograms/minute. The rate should be maintained for at least 4 hours before increasing further.
Elderly: Not applicable
Children: Not applicable.
4.3 Contraindications
Prostin E2 Sterile solution should not be used where the patient is sensitive to prostaglandins.
Prostin E2 sterile solution 10mg/ml is not recommended in the following circumstances:
1 For patients in whom oxytocic drugs are generally contraindicated or where prolonged contractions of the uterus are considered inappropriate such as: Cases with a history of caesarean section or major uterine surgery.
Cases where there is evidence of a potential for obstructed labour.
2 Patients with a past history of, or existing, pelvic inflammatory disease, unless adequate prior treatment has been instituted.
3 Patients with active cardiac, pulmonary, renal or hepatic disease.
4.4 Special warnings and precautions for use
This product is only available to hospitals and clinics with specialised obstetric units and should only be used where 24-hour resident medical cover is provided_
Use caution in handling this product to prevent contact with skin. Wash hands thoroughly with soap and water after administration.
It is advised that Prostin E2 Sterile Solution should not be administered by the intramyometrial route since there have been reports of a possible association between this route of administration and cardiac arrest in severely ill patients.
Caution should be exercised in the administration of Prostin E2 Sterile Solution in patients with:
(i) asthma or a history of asthma;
(ii) epilepsy or a history of epilepsy;
(iii) glaucoma or raised intra-ocular pressure;
(iv) compromised cardiovascular, hepatic, or renal function;
(v) hypertension.
As with any oxytocic agent, Prostin E2 Sterile Solution should be used with caution in patients with compromised (scarred) uteri.
Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone. Such effects have also been noted in newborn infants who received prostaglandin E1 during prolonged treatment. There is no evidence that short-term administration of prostaglandin E2 can cause similar bone effects.
Women aged 35 years or older, those with complications during pregnancy and those with a gestational age over 40 weeks have been shown to have an increased risk of post-partum disseminated intravascular coagulation. In addition, these factors may further increase the risk associated with labour induction (see section 4.8 Undesirable Effects). Therefore, in these women, use of dinoprostone should be undertaken with caution. Measures should be applied to detect as soon as possible an evolving fibrinolysis in the immediate post-partum phase.
4.5 Interaction with other medicinal products and other forms of interaction
Since it has been found that prostaglandins potentiate the effect of oxytocin, it is not recommended that these drugs are used together. If used in sequence, the patient's uterine activity should be carefully monitored.
4.6 Fertility, Pregnancy and lactation
Pregnancy Code D
Prostin E2 Sterile Solution 10 mg/ml is only used during pregnancy for therapeutic termination of pregnancy, missed abortion and hydatidiform mole. There has been some evidence in animals of a low order of teratogenic activity, therefore, if abortion does not occur or is suspected to be incomplete as a result of prostaglandin therapy, (as in spontaneous abortion, where the process is sometimes incomplete), the appropriate treatment for complete evacuation of the pregnant uterus should be instituted in all instances.
Prostaglandins are excrete in breast milk This is not expected to be a hazard given the circumstances in which the product is used.
4.7 Effects on ability to drive and use machines
Not applicable.
4.8 Undesirable effects
Cardiac disorders: Cardiac arrest Vascular disorders: Hypertension Gastrointestinal disorders: Diarrhoea, nausea, vomiting
General disorders and administration site conditions: Fever, local tissue irritation / erythema (injection site), temporary pyrexia, local infections
Immune system disorders: Hypersensitivity reactions such as anaphylactoid reactions and anaphylactic reactions including anaphylactic shock.
Investigations: Elevated WBC
Musculoskeletal and connective tissue disorders: Back pain
Nervous system disorders: Transient vasovagal symptoms (flushing, shivering, headache, dizziness)
Pregnancy andpuerperium conditions
Maternal-related conditions: uterine hypertonus, uterine rupture, abruptio placenta, pulmonary amniotic fluid embolism, rapid cervical dilatation
Respiratory, thoracic and mediastinal disorders: Asthma, bronchospasm
Blood and lymphatic system disorders: An increased risk of post-partum disseminated intravascular coagulation has been described in patients whose labour was induced by pharmacological means, either with dinoprostone or oxytocin (see section 4.4 Special Warnings and Special Precautions for Use). The frequency of this adverse event, however, appears to be rare (<1 per
1,000 labours).
4.9 Overdose
Overdosage may be expressed by uterine hypercontractility and uterine hypertonus. During use, uterine activity and the progression of cervical dilation should be carefully monitored to detect possible evidence of undesired responses, e.g. hypertonus or sustained uterine contractions. Because of the transient nature of PGE2-induced myometrial hyperstimulation, non-specific, conservative management should be used (rate of infusion should be decreased or discontinued, maternal position change and administration of oxygen) If conservative management is not effective, a tocolytic agent may be used in appropriate patients as a treatment of hyperstimulation following administration of PGE2 or appropriate measures should be considered.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Dinoprostone is a prostaglandin of the E series with actions on smooth muscle. It induces contraction of uterine muscle at any stage of pregnancy.
5.2 Pharmacokinetic properties
General characteristics of active substance
Dinoprostone is rapidly metabolised in the body. Intravenous administration results in very rapid distribution and metabolism, with only 3% of unchanged drug remaining in the blood after 15 minutes. At least nine prostaglandin E2 metabolites have been identified in human blood and urine.
Characteristics in patients
No special characteristics. See "Special warnings and special precautions for use" for further information.
5.3 Preclinical safety data
In mice and rats, the oral LD50 values were >500mg/kg and 141-5 13 mg/kg respectively.
Three month oral administration to rats resulted in significantly heavier stomach weights for treated compared with untreated rats, which effect was reversible on treatment cessation. Treated rats had a dose related acanthotic squamous glandular junction and thickened glandular gastric mucosal epithelium. No significant alterations were recognised in routine evaluation of the stemebrae and the femur.
A fourteen day oral toxicity study in dogs showed a maximum tolerated dose of 6-20 mg/kg/day. All treated dogs had microscopic evidence of increased fundic and pyloric mucus. The fundic and pyloric mucosa were thickened, having a cobblestone appearance and had an increased gastric mucus in both 20 mg/kg/day treated dogs and the 60 mg/kg/day male dog. These were the only gross and microscopic drug related changes observed.
Satisfactory results were obtained in intravenous and intramuscular tolerability tests performed in dog and monkey.
Teratogenic effects were observed in rats injected subcutaneously with 0.5 mg/animal. No teratogenic effects were seen in the rabbit at dosage levels of up to 1.5 mg/kg day.
No evidence of mutagenicity was obtained using the Ames Assay, the DNA Damage/Alkaline Elution Assay and the micronucleus test.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Dehydrated alcohol BP.
6.2 Incompatibilities
None known.
6.3 Shelf life
24 months.
6.4 Special precautions for storage
Store in a refrigerator at 4°C. Once diluted, the diluted solution should be stored in a refrigerator at 4°C and used within 24 hours.
6.5 Nature and contents of container
Ph. Eur. Type I glass ampoule, containing 0.5 ml sterile solution, packed in a carton.
Special precautions for disposal
6.6
Use caution in handling this product to prevent contact with skin. Wash hands thoroughly with soap and water after administration.
7 MARKETING AUTHORISATION HOLDER
Pfizer Limited Ramsgate Road Sandwich Kent
CT13 9NJ UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 00057/1027
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
27/06/1986 / 28/10/2004
10 DATE OF REVISION OF THE TEXT
15/12/2014