Buserelin, sold under the brand name Suprefact among others, is a drug which is used primarily in the treatment of prostate cancer and endometriosis.
of buserelin are related to sex hormone hypogonadism and include of hypoandrogenism and hypoestrogenism such as , sexual dysfunction, vaginal atrophy, and osteoporosis.
Buserelin was first patented in 1974 and approved for medical use in 1985.
Medical uses
Buserelin is approved for the treatment of hormone-responsive cancers including
prostate cancer and
premenopause breast cancer,
sex hormone-dependent
including endometrial hyperplasia,
endometriosis, and
uterine fibroids, and in assisted reproduction for female infertility.
It is also used
off-label use for the treatment of precocious puberty, as a
puberty blocker in transgender children, and as a component of transgender hormone therapy.
In ovulation induction, buserelin is used for
pituitary gland suppression as an
adjunct therapy to
gonadotropin administration.
It has also been assessed as a nasal spray for use as a hormonal contraceptive in women, with a 96%
anovulation rate.
Dosages
For prostate cancer, the dosage of buserelin by subcutaneous injection is 500 μg three times per day (once every 8 hours, 1,500 μg/day total) for one week and then 200 μg once daily thereafter.
If buserelin is used as a
nasal spray, the dosage for prostate cancer is 800 μg sprayed into the nostrils three times per day (once every 8 hours, 2,400 μg/day total) for one week followed by 400 μg sprayed into the nostrils three times per day (once every 8 hours, 1,200 μg/day total) thereafter.
For endometriosis, buserelin is used specifically as a nasal spray and the dosage is the same as that used for prostate cancer.
These dosages of buserelin for both subcutaneous injection and nasal spray have been found to decrease
testosterone levels to near-
castration levels in men with prostate cancer, although suppression was more complete with subcutaneous injection presumably due to suboptimal absorption with intranasal administration.
Available forms
Buserelin is available in the form of a 1 mg/mL solution for use as a
nasal spray or subcutaneous injection once every 8 hours (three times per day) and as 6.3 mg and 9.45 mg implants for subcutaneous injection once every two and three months, respectively.
Contraindications
of buserelin include the following:
-
Hypersensitivity to buserelin or any of the other components of the medication (case reports of anaphylaxis exist)
-
Prostate cancer that is not hormone-dependent (as there will be no benefit from testosterone suppression)
-
Individuals who have undergone gonadectomy (as hormone levels will not be affected)
-
Pregnancy and breastfeeding (unknown whether buserelin might be )
-
Undiagnosed abnormal vaginal bleeding
Side effects
During the initial phase of the therapy, before GnRH receptors have been significantly
downregulation,
testosterone levels are increased.
This can lead to transient
tumor activation with
bone pain (in patients with
cancer metastasis) and urinary retention.
Side effects that occur later during the treatment are mainly due to
hypogonadism and include reduced
libido, erectile dysfunction,
,
vaginal dryness,
vaginal atrophy,
menorrhagia,
osteoporosis, depression,
asthenia, emotional lability,
headache,
dizziness, and application site reactions.
Overdose
Buserelin appears to be safe in the event of an
overdose.
Pharmacology
Pharmacodynamics
Buserelin is a GnRH agonist, or an
agonist of the
GnRH receptor.
It is a
superagonist of the GnRH receptor with potency for induction of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
secretion of about 20 to 170 times that of GnRH itself.
By activating the GnRH receptor in the
pituitary gland, buserelin induces the secretion of LH and FSH from the
of the anterior pituitary, which travel to the
through the
bloodstream and activate gonadal
sex hormone biosynthesis as well as stimulate
spermatogenesis in men and induce ovulation in women.
With chronic administration of buserelin however, the GnRH receptor becomes desensitized and completely stops responding both to buserelin and to endogenous GnRH.
In men, approximately 95% of circulating testosterone is produced by the testicle, with the remaining 5% being derived from the .
Buserelin has been found to suppress testosterone levels in men with prostate cancer from 426 ng/dL to 28 ng/dL (by 93.4%) with 200 μg by subcutaneous injection once per day and from 521 ng/dL to 53 ng/dL (by 89.8%) with 400 μg by nasal spray once every 8 hours (1,200 μg/day total).
Pharmacokinetics
Buserelin is ineffective via oral administration due to first-pass metabolism in the gastrointestinal tract.
Its
bioavailability is 2.5 to 3.3% by intranasal administration and 70% by subcutaneous injection.
The plasma protein binding of buserelin is approximately 15%.
The
metabolism of buserelin occurs in the
liver,
, and gastrointestinal tract and is mediated by
, specifically pyroglutamyl peptidase and chymotrypsin-like endopeptidase.
The elimination half-life of buserelin regardless of route of administration is about 72 to 80 minutes.
Buserelin and its
are eliminated in
urine and
bile, with approximately 50% of buserelin
excretion in urine unchanged.
Chemistry
Buserelin is a
GnRH analogue, or a synthetic analogue of GnRH.
It is a
nonapeptide and is also known as
D-Ser(tBu)
6,des-Gly-NH
210GnRH ethylamide or as
D-Ser(tBu)
6EA
10-GnRH.
Buserelin is marketed for medical use in both its
free base (buserelin) and
acetate salt (buserelin acetate) forms.
History
Buserelin was first described in 1976 and was introduced for medical use in 1984.
Intranasal buserelin was the first GnRH agonist demonstrated to achieve medical castration in humans.
This was initially observed via a marked decrease in circulating testosterone levels in a single patient in 1980.
Society and culture
Generic names
Buserelin is the
generic term of the drug and its and , while
buserelin acetate is its , , and ,
buséréline is its , and
buserelina is its .
While under development by
Hoechst AG, buserelin was also known as
HOE-766.
Brand names
Buserelin is marketed by
Sanofi-Aventis primarily under the brand names Suprefact, Suprefact Depot, and Suprecur.
It is also available under a number of other brand names including Bigonist, Bucel, Buserecur, Fuset, Metrelef, Profact, Profact Depot, Supremon, and Zerelin.
CinnaFact is a generic version of the medication that is produced by
CinnaGen.
Buserelin is marketed for use in veterinary medicine primarily under the brand name Receptal, but is also available under the brand names Buserol, Busol, Porceptal, and Veterelin.
Availability
Buserelin is marketed in the
United Kingdom,
Ireland, other
countries,
Canada,
New Zealand, and
South Africa, as well as in
Latin America,
Asia, and elsewhere in the world.
It is not available in the
United States or
Australia.
Research
The steroidal antiandrogen cyproterone acetate has been studied for blocking the testosterone flare at the start of buserelin therapy in men with prostate cancer.
While cyproterone acetate for two weeks eliminates the biological and biochemical signs of the flare, no benefits on prostate cancer outcomes were observed.
Very low doses of buserelin nasal spray have been assessed for increasing testosterone levels and fertility in men with Oligozoospermia and hypogonadotropic hypogonadism.
See also
-
Gonadotropin-releasing hormone receptor § Agonists
Further reading
External links
