Buserelin

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

  • GnRH Structure: Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2
  • Buserelin Structure: Glu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHEt (substitution of glycine in position 6 by D-serine, and of glycinamide in position 10 by ethylamide)

[edit] MECHANISM OF ACTION

Buserelin is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH), with enhanced biological activity.

Normally, the hypothalamus controls the pituitary production of gonadotropins through secretion of GnRH. The hypothalamus releases GnRH in a pulsatile fashion every 90–120 min into the portal circulation connecting the hypothalamus and anterior pituitary. When the pulsatile GnRH binds to the gonadotropes in the anterior pituitary, it stimulates release of LH and FSH into the general circulation.

Buserelin acts like GnRH by binding to the gonadotropin releasing hormone receptor; following an initial stimulation of gonadotropins release, long-term exposure to constant levels of buserelin interrupt the normal pulsatile stimulation of GnRH receptors by GnRH, and thus desensitize the GnRH receptors and indirectly downregulates the secretion of gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to hypogonadism and thus a dramatic reduction in estradiol and testosterone levels in both sexes.

This causes the ovaries to enter a state of rest, putting the woman in a temporary “menopausal state” and, in males, androgens are reduced to castrate or pre-pubertal levels. These decreases occur within a month of initiating treatment and are maintained as long as treatment continues.

This effect is reversible on discontinuation of therapy.

Antiandrogens like Bicalutamide (Casodex) is strongly recommended as adjunctive therapy before starting and during the first weeks of GnRH agonist therapy in order to prevent the initial and temporary rise in serum testosterone (flare up effect)

[edit] INDICATIONS

  • Palliative treatment of advanced Prostate Cancer
  • Treatment of endometriosis in patients who do not require surgery as primary therapy
  • Buserelin is indicated for downregulation and prevention of premature LH surges that is associated with stimulation with gonadotropins in women undergoing assisted reproduction (In vitro fertilisation protocols). Prevention of the LH surge can reduce the cycle cancellation rate, increases the pregnancy rate and facilitates cycle control

[edit] DOSAGE

  • Prostate Cancer
    • Initial treatment: For the first seven days 500 mcg (0.5 mL) every 8 hours by subcutaneous injection
    • Maintenance treatment: 400 mcg (200 mcg into each nostril) three times daily. Each pump action delivers 100 mcg
      Goserelin is entended for long-term administration
  • Endometriosis: 400 mcg (200 mcg into each nostril) three times daily. Each pump action delivers 100 mcg. . The treatment duration is usually six months and should not exceed nine months.
  • IVF, Long Down Regulation Protocol (LDR): In a woman having a regular 28-day menstrual cycle, ovarian suppression will begin on the 21st day by administering Buserelin, 100 mcg (One pump) into each nostril three times daily. Administration will last for approximately 2-3 weeks.

[edit] DOSAGE FORMS AND STRENGTHS

  • Subcutaneous Injection solution 1mg/mL
  • Intranasal solution 1mg/mL

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Buserelin
  • Pregnancy and e breastfeeding
  • Patients with nonhormone-dependent prostate cancer
  • Patients who have undergone orchiectomy (Castration)
  • Patients with undiagnosed abnormal vaginal bleeding

[edit] WARNINGS AND PRECAUTIONS

  • Transient worsening of tumor symptoms may occur during the first few weeks of treatment in men, which may include bone pain, ureteral obstruction and spinal cord compression.
  • Increased risk of myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH analogs in men. Physicians should consider whetherthe benefits of androgen deprivation therapy outweigh the potential cardiovascular risk
  • Anaphylactoid reactions: Reactions including allergic asthma with dyspnea as well as rare anaphylactic shock have been observed.
  • Diabetes: Reduced glucose tolerance has been noted in rare cases.

[edit] INTERACTIONS

[edit] PREGNANCY AND LACTATION

  • Buserelin is contraindicated in pregnant women

[edit] SIDE EFFECTS

Most common: Headache (nasal solution), libido decreased, hot flushes, vaginal dryness, menorrhagia, impotence, nasal irritation (nasal solution).

[edit] RELATED LINKS

Hormone Therapy for Prostate Cancer

[edit] BIBLIOGRAPHY

[edit] REFERENCES