CinnaFact®


(Buserelin Acetate)

A Big triumph for medical society


Description

Buserelin acetate is a synthetic peptide analog of the natural gonadotropin releasing hormone (GnRH/LHRH) with enhanced biological activity. After repeated administration of this drug, the secretion of gonadotrophin release and gonadal steroids is significantly inhibited. The pharmacological effect is attributable to the down- regulation of pituitary LHRH receptors.

In male individuals the elimination of gonadotrophin release results in a reduction in the synthesis and secre- tion of testosterone.

In female individuals the elimination of pulsatile gonadotrophin release inhibits the secretion of estrogen. Clinical Pharmacology The substitution of glycine in position 6 by D-serine, and that of glycinamide in posi- tion 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LHRH effect. The effects of buserelin on FSH and LH release are 20 to 170 times greater than those of LHRH. Buserelin also has a longer duration of action than natural LHRH.

Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours.

Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to

castration level, was found when large pharmacologic doses (50-500 mcg SC/day) were administered for periods greater than 1 to 3 months. Chronic administration of such doses of buserelin results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis for buserelin use in patients with hormone-dependent metastatic carcinoma of the prostate gland as well as in patients with endometriosis.

CinnaFact is supplied at a concentration of 1 mg/mL buserelin as acetate (5.5 ml) multiple use vial.  Each mL of sterile aqueous injection solution contains: 1.05 mg buserelin acetate (equivalent to 1.00 mg pure  anhydrous buserelin free base), benzyl alcohol as preservative, monobasic sodium phosphate buffer, sodium  chloride for tonicity adjustment and sodium hydroxide for pH adjustment.

Indication and Usage

Prostate cancer

 Palliative treatment in patients with hormone-dependent advanced prostate cancer (stage D)

Endometriosis

 Treatment of endometriosis in women who do not require surgical intervention as first-line therapy (length of therapy is usually 6 months, but no longer than 9 months)

FAQs

A

CinnaGen has sponsored four clinical trials with Cinnal-f® so far. In these clinical trials efficacy and safety of Cinnal-f® was compared with the reference product (Gonal-f®). In a randomized, phase III, triple-blind study that was conducted in patients referring to Vali-e-Asr Hospital (A referral infertility hospital, Tehran, Iran) Cinnal-f® proved to be non-inferior to Gonal-f® in terms of efficacy and safety.

 

A
  • Conventional (Fixed dose): I) Starting a constant daily dose of 75–150 IU of FSH from day 2-3. II) Monitoring USG and E2 levels. III) Continuing FSH until a follicle >18 mm is observed
  • Step-Up Protocol: I) Starting with 75–150 IU of FSH on day 2-3 and continuing that dose for 5–7 days. II) If the follicular and estradiol response are inadequate; the dose is increased by 37.5–75 IU for another 5–7 days. III) If necessary, another 37.5 IU incremental increase can be used until an appropriate response obtained.
  • Step-Down Protocol: I) beginning with 150 IU of FSH on day 2-3 which is continued for 2-3 days. II) The dose is reduced to 75 IU for another 3 days. III) Monitoring USG and E2 levels. If follicles >10 mm are observed on TVS, the dose is decreased in two steps. The last dose is then continued till the day of hCG injection
  • Chronic Low-Dose Step-Up (Low-Slow): I) Starting dose: 37.5–75 units/day of FSH and a stepwise increase in subsequent doses. II) Serum E2 and USG are monitored on day 7. If Serum E2>200 pg/ml or follicle size> 10 mm, the same dose is continued. III) Otherwise, if E2 and follicle size were lower than the above-mentioned cut-offs, the daily dose is increased by an increment of 37.5 units/week, till the serum E2 level rises adequately.
  • Sequential: I) start with 37.5–75 IU/day of FSH which is increased by 50 % or 37.5 IU after 14 days in case of no ovarian response. II) Thereafter, any further FSH increment is made by 37.5–75 IU at weekly intervals to a maximum of 225 IU/day. III) Once dominant follicle emerges and reaches a diameter of 14 mm, the dose is reduced by 50 %
A

Patients with porphyria or a family history of porphyria should be closely monitored during treatment with Cinnal-f®. Deterioration or a first appearance of this condition may require cessation of treatment.

A

Cinnal-f® should be administered subcutaneously at a 90° angle. The best areas for administration of Cinnal-f® are:

  • Front of the thighs (at least 7.5 cm below the hip and above the knees).
  • Belly (below the ribs and above the hip bones, at least 5 cm away from the belly button).
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