(British Approved Name, rINN)
Drug Nomenclature
International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish):
Busereliini; Buserelina; Buserelinas; Busereline; Buserelinum; Buszerelin; S74-6766.
(6-O-tert-Butyl-D-serine)-des-10-glycinarnideg-onadorelin ethylamide; 5-Oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-O-tert-butyl-D-seryl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide.
C60H86Nl6Ol3 = 1239.4.
CAS — 57982-77-1.
ATC — L02AE01.
Pharmacopoeias. In Europe.
European Pharmacopoeia, 6th ed. (Buserelin). A white or slightly yellowish hygroscopic powder. Sparingly soluble in water and in dilute acids. Store at 2° to 8°. Protect from light and moisture.
Buserelin Acetate
Drug Approvals
(BANM, US Adopted Name, rINNM)
Acetato de buserelina; Buserelin Asetat; Busereline, Acetate de; Buserelini Acetas; Hoe-766
D-Ser (But)6 Pro9 NEt LHRH acetate.
C60H86Nl6Ol3,C2H4O2= 1299.5.
CAS — 68630-75-1.
ATC — L02AE01.
Adverse Effects and Precautions
As for Gonadorelin.
Interactions
As for Gonadorelin.
Pharmacokinetics
Buserelin is completely absorbed after subcutaneous injection, with peak plasma concentrations occurring about 1 hour after a dose. It accumulates in liver and kidneys as well as in the anterior pituitary. It is metabolised by tissue peptidases and is excreted in urine and bile as unchanged drug and metabolites. The half-life after injection is stated to be about 80 minutes.
Uses and Administration
Buserelin is an analogue of gonadorelin with similar properties. It is used for the suppression of testosterone in the treatment of malignant neoplasms of the prostate it is also used in the treatment of endome-triosis and as an adjunct to ovulation induction with go-nadotrophins in the treatment of infertility. It has been used in precocious puberty and tried in the treatment of uterine fibroids (see below). Buserelin is usually given as the acetate but doses are expressed in terms of the base 105 micrograms of buserelin acetate is equivalent to about 100 micrograms of buserelin. In advanced prostatic carcinoma doses of 500 micrograms are injected subcutaneously every 8 hours for 7 days.
On the eighth day treatment is changed to the nasal route 100 micrograms is sprayed into each nostril 6 times daily (usually before and after meals). An acceptable response should be achieved within 4 to 6 weeks. Since there is an initial increase in circulating testosterone, an anti-androgen such as cy-proterone acetate may be given for at least 3 days before beginning buserelin therapy, and continued for at least 3 weeks, to avoid the risk of a disease flare. Long-acting subcutaneous depot preparations that release buserelin over a 2- or 3-month period are also available.
In endometriosis a dose of 150 micrograms is sprayed into each nostril three times daily. The usual duration of therapy is 6 months, which should not be exceeded.
In infertility, pituitary desensitisation before ovulation induction with gonadotrophins is achieved by giving 150 micrograms intranasally four times daily, beginning either in the early follicular phase (day 1) or midluteal phase (day 21) of the menstrual cycle. Alternatively, 200 to 500 micrograms may be given daily as a subcutaneous injection. Therapy should be continued until pituitary downregulation occurs, which normally takes 1 to 3 weeks if necessary 300 micrograms four times daily intranasally, or 500 micrograms twice daily subcutaneously may be given. Gonadotrophin treatment is then added to buserelin therapy until an appropriate stage of follicular development, when both are withdrawn and chorionic gonadotrophin is given to induce ovulation.
Endometriosis
Gonadorelin analogues such as buserelin have a role in the management of endometriosis, but the need for long-term therapy limits their value because of the risk of osteoporosis ‘add-back’ therapy (hormone replacement) can be used to prevent this. References.
Fibroids
Like other gonadorelin analogues buserelin has been used to reduce the volume of uterine fibroids. References.
Infertility
Buserelin is given with gonadotrophic hormone therapy for induction of ovulation and as an aid to improving IVF procedures. Buserelin with gonadotrophic hormones has been found to result in pregnancies in women previously unresponsive to clomifene citrate, although there may be a greater risk of multiple births.
The regimens used in IVF may be characterised according to how long the gonadorelin analogue is given for:
- long, 2 weeks or more
- short, 8 to 10 days
- ultrashort, 3 days
A comparative study of such regimens found that the best results in all age groups were consistently associated with the long buserelin protocol The timing of buserelin dosage may also be important. Starting buserelin in the midluteal phase of the cycle has been reported to produce more rapid pituitary down regulation and higher pregnancy rates from IVF than when buserelin was begun in the early follicular phase.
For a general discussion of the management of infertility.
Malignant neoplasms
The long-term use of buserelin in men decreases the testicular concentration of testosterone. For this reason it is used in the treatment of prostatic cancer, which is androgen-dependent. Gonadorelin analogues are an effective alternative to orchidectomy, sometimes combined with an anti-androgen for enhanced effect, and play a maj or role in the management of advanced, incurable disease.
Other reports of malignant neoplasms treated with buserelin include its use in metastatic breast cancer.
Porphyria
Buserelin given with medroxyprogesterone acetate suppressed cyclic and premenstrual exacerbations of porphyria in 2 patients. Doses used were 300 micrograms buserelin intranasally in the evenings of days 1 to 21 of the menstrual cycle and 10 mg medroxyprogesterone acetate daily by mouth from day 12 to 21. Both patients were free from porphyric attacks during the reported 11 months of treatment. Intranasal buserelin has also been used in 1 patient to prevent premenstrual exacerbation of coproporphyria. The initial dose of 900 micrograms daily could be tapered to 150 micrograms daily, with only 1 minor attack in 5 years of treatment. The authors of this report also noted a number of case reports of buserelin used in acute intermittent porphyria.
Premenstrual syndrome
For reference to the use of buserelin or other gonadorelin analogues (with HRT to prevent menopausal symptoms) in women unresponsive to other drug treatment, see under Gonadorelin.
Preparations
Proprietary Preparations
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Jennifer is a clinical pharmacologist. She helps doctors of all medical specialties choose medications. Jennifer consults about drug dosage, interactions, and side effects.