1. Name Of The Medicinal Product
Hemabate Sterile Solution
2. Qualitative And Quantitative Composition
Each 1 ml contains carboprost tromethamine equivalent to carboprost 250 micrograms.
3. Pharmaceutical Form
Colourless, sterile, aqueous solution for intramuscular injection.
4. Clinical Particulars
4.1 Therapeutic Indications
Treatment of post-partum haemorrhage due to uterine atony and refractory to conventional methods of treatment with oxytocic agents and ergometrine used either alone or in combination.
Conventional therapy should usually consist of 0.5 - 1 mg ergometrine with up to 50 units of oxytocin infused intravenously over periods of time from 20 minutes to 12 hours. The dosage and duration of administration should reflect the seriousness of the clinical situation.
4.2 Posology And Method Of Administration
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
An initial dose of 250 micrograms (1.0 ml) of Hemabate should be administered as a deep intramuscular injection.
If necessary, further doses of 250 micrograms may be administered at intervals of approximately 1.5 hours. In severe cases the interval between doses may be reduced at the discretion of the attending physician, but it should not be less than 15 minutes. The total dose of Hemabate should not exceed 2 mg (8 doses).
|
|
| |
|
|
4.3 Contraindications
Hemabate should not be used where the patient is sensitive to carboprost tromethamine or any of the excipients.
Hemabate is not recommended in the following circumstances:
1. Acute pelvic inflammatory disease.
2. Patients with known cardiac, pulmonary, renal or hepatic disease.
4.4 Special Warnings And Precautions For Use
Warnings
This preparation should not be used for induction of labour.
Hemabate, as with other potent oxytocic agents, should be used only with strict adherence to recommended dosages. Hemabate should be used by medically trained personnel and is available only to hospitals and clinics with specialised obstetric units where 24 hour resident medical cover is provided.
Hemabate must not be given intravenously.
Very rare cases of cardiovascular collapse have been reported following the use of prostaglandins. This should always be considered when using Hemabate.
Precautions
Hemabate should be used with caution in patients with a history of glaucoma or raised intra-ocular pressure, asthma, hypertension or hypotension, cardiovascular disease, renal disease, hepatic disease, anaemia, jaundice, diabetes or epilepsy.
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 have received prostaglandin E1 during prolonged treatment. There is no evidence that short-term administration of Hemabate can cause similar bone effects.
Decreases in maternal arterial oxygen content have been observed in patients treated with carboprost tromethamine. A causal relationship to carboprost tromethamine has not been established, however, it is recommended that patients with pre-existing cardio-pulmonary problems receiving Hemabate are monitored during treatment and given additional oxygen if necessary.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Prostaglandins may potentiate the effect of oxytocin
4.6 Pregnancy And Lactation
Hemabate is contra-indicated in pregnancy.
In the unlikely event of a mother breastfeeding her baby whilst receiving Hemabate, no adverse effects to the nursing infant would be anticipated.
4.7 Effects On Ability To Drive And Use Machines
Not applicable
4.8 Undesirable Effects
The adverse effects of Hemabate are generally transient and reversible when therapy ends.
The most frequent side-effects observed with the use of Hemabate are related to its contractile effect on smooth muscle. Thus nausea, vomiting and diarrhoea have been reported as commonly encountered. The incidence of vomiting and diarrhoea may be decreased by pre-treatment and concomitant use during treatment of anti-emetic and antidiarrhoeal agents.
Hyperthermia and flushing have been observed after intramuscular Hemabate, but if not complicated by endometritis, the temperature will usually return to normal within several hours of the last injection.
Asthma and wheezing have been noted with Hemabate treatment.
Less frequent, but potentially more serious adverse effects are elevated blood pressure, dyspnoea and pulmonary oedema. Other less serious adverse effects noted include chills, headache, diaphoresis, dizziness and injection site erythema and pain.
4.9 Overdose
Treatment of overdosage must be symptomatic at this time, as clinical studies with prostaglandin antagonists have not progressed to the point where recommendations may be made.
If evidence of excessive side-effects appears, the frequency of administration should be decreased or administration discontinued.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Carboprost is a synthetic 15-methyl analogue of dinoprost (prostaglandin F2 alpha). It is a uterine stimulant with a more prolonged action than dinoprost and when used in post-partum haemorrhage, it stimulates the uterus to contract in a manner similar to that normally observed in the uterus following delivery. The resulting myometrial contractions provide haemostasis at the site of placentation and hence prevent further blood loss. Whether or not this action results from a direct effect on the myometrium has not been determined with certainty at this time. The fundamental actions of the prostaglandins include inhibition or stimulation of smooth muscle contraction and inhibition of the release of noradrenaline or modulation of its effects at neuroeffector sites. They affect the uterus, the cardiovascular system, the gastro-intestinal system, the nervous system, the urinary system and metabolic processes.
5.2 Pharmacokinetic Properties
The presence of the methyl group delays inactivation by enzymic dehydrogenation.
Peak plasma levels vary depending on the route of administration. In the Rhesus monkey after a single i.m. injection of 20 - 30 micrograms of 15-methyl PGF2 alpha peak levels of 0.4 - 5 nanograms/ml resulted at 30 - 60 minutes, declining to baseline levels 6 - 8 hours after injection. In pregnant women, an i.m. injection of 100 - 400 micrograms resulted in peak plasma levels of 1 - 1.6 nanograms/ml 20 - 30 minutes after injection. Levels declined to 0.2 - 0.4 nanograms/ml after 3 hours. When i.m. doses of 250 micrograms were given every two hours, pre-injection plasma levels stabilised after four injections at 1.2 nanograms/ml.
After administration of 2.5 mg 15-methyl PGF2 alpha intra-amniotically to 5 subjects, plasma levels were from 100 - 580 picograms/ml during the first 15 hours after administration. In three subjects the levels were low and fairly constant, while the two other had higher, but more variable levels.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Benzyl alcohol
Sodium chloride
Tromethamine
Sodium hydroxide
Hydrochloric acid
Water for injections
6.2 Incompatibilities
None known
6.3 Shelf Life
Ampoules: 48 months
Vial: 24 months
6.4 Special Precautions For Storage
The ampoules must be stored in a refrigerator at 2 - 8°C.
The vial must be stored in a refrigerator at 0 - 6°C
6.5 Nature And Contents Of Container
Ampoule: Type 1 glass ampoule containing 1 ml solution, packed in cartons of two or ten ampoules.
Vial: Type 1 glass with butyl rubber closure, containing 10 ml solution, packed individually in a carton.
6.6 Special Precautions For Disposal And Other Handling
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Administrative Data
7. Marketing Authorisation Holder
Pharmacia Limited
Ramsgate Road
Sandwich
Kent CT13 9NJ
UK
8. Marketing Authorisation Number(S)
PL 0032/0152
9. Date Of First Authorisation/Renewal Of The Authorisation
16 August 1990/23 February 1996
10. Date Of Revision Of The Text
May 2007
Legal category:
POM
Company Ref: HM 2_0
No comments:
Post a Comment