Herz Mechanism of Action

Pharmacology: Pharmacodynamics: HERZ is combination oral contraceptives that inhibit ovulation by suppressing the gonadotropins, FSH and LH. Additionally, alteration in the cervical mucus (which inhibits sperm penetration) and the endometrium (which reduces the likelihood of implantation), may contribute to contraceptive effectiveness.
Drospirenone has beneficial properties in addition to contraception. Drospirenone has antimineralocorticoid activity that can prevent weight gain and other symptoms caused by fluid retention. It counteracts the estrogen-related sodium retention, providing for a very good tolerance and has positive effects on the premenstrual syndrome (PMS). Originator product was studied in PMDD. PMDD is a severe form of PMS. In two placebo controlled phase 3 studies including over 500 subjects, originator product showed clinical superiority in relief of symptoms of PMDD. In combination with ethinylestradiol, drospirenone displays a favorable lipid profile with an increase in HDL. Drospirenone exerts antiandrogenic activity leading to a positive effect on the skin and to a reduction in acne lesions and sebum production. In addition, drospirenone does not counteract the ethinylestradiol - related SHBG increase which is useful for binding and inactivating the endogenous androgens.
In two multicenter, double blind, randomized, placebo controlled studies on the efficacy and safety of originator product as an acne therapy in women with moderate acne vulgaris, it produced clinically and statistically significant anti-acne effects on all the primary efficacy variables (inflammatory lesion, non-inflammatory lesion, total lesion counts, and the number and percentage of subjects with a 'clear' or 'almost clear' rating on the Investigator's Stated Global Assessment (ISGA) scale) and on the majority of secondary efficacy variables. Drospirenone is devoid of any androgenic, estrogenic, glucocorticoid, and antiglucocorticoid activity. This, in combination with the antimineralocorticoid and antiandrogenic properties, gives drospirenone a biochemical and pharmacological profile closely resembling the natural hormone progesterone. Apart from this, there is evidence of a reduced risk of endometrial cancer and ovarian cancer. Furthermore, the higher dosed COCs (0.05 mg ethinylestradiol) have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Whether this also applies to lower-dosed CPCs remains to be confirmed.
More about the Pill: The combined pill may also have non-contraceptive health benefits.
The period may be lighter and shorter. As a result, the risk of anemia may be lower. The period pains may become less severe or may completely disappear.
In addition, some serious disorders have been reported as occurring less frequently in users of Pills containing 50 microgram ethinylestradiol ('high-dose Pills'). These are benign breast disease, ovarian cysts, pelvic infections (pelvic inflammatory disease or PID), ectopic pregnancy (pregnancy in which the embryo implants outside of the womb) and cancer of the endometrium (lining of the womb) and ovaries. This may also be the case for low-dose Pills but so far this has only been confirmed for endometrial and ovarian cancer.
One of the hormones in HERZ, drospirenone, has special properties leading to beneficial effects in addition to contraception. Drospirenone can prevent weight-gain, and other symptoms such as bloating or swelling, related to fluid retention and caused by hormones both in oral contraceptives and occurring at certain times in the menstrual cycle.
Drospirenone also has antiandrogenic activity which can help to reduce acne (pimples) and greasiness of the skin and hair. These special properties make drospirenone similar to the natural progesterone hormone produced by the body.
In a large study of originator product, the specific pill intake scheme with 24 tablets containing hormones as compared to 21 in conventional combined oral contraceptives showed a very high contraceptive efficacy.
Pharmacokinetics: Absorption: Orally administered drospirenone is rapidly and almost completely absorbed.
Peak serum concentrations of drospirenone are reached 1 to 3 hours after administration. Ethinylestradiol is rapidly absorbed with peak concentrations attained within 2 hours.
Distribution: Drospirenone is about 97% protein bound, presumably to albumin. Ethinylestradiol is about 98% protein bound, mainly to albumin. But it is non-specifically binding Drospirenone and ethinylestradiol do not appear to bind to sex hormone binding globulin (SHBG).
Metabolism: Drospirenone is metabolized to 2 major inactive metabolites, which formed without involvement of the P450 system.
Ethinylestradiol appears to undergo extensive first-pass metabolism. Ethinylestradiol is mainly metabolized via aromatic hydroxylation by hepatic microsomal isoenzyme cytochrome P-450 (CYP) 3A4. The major hydroxylated metabolite of ethinylestradiol is 2-hydroxyethinylestradiol, which is thought to contribute to some of the adverse cardiovascular effects of the drug. The hydroxylated metabolite is further metabolized by methylation and glucuronidation prior to urinary and fecal excretion. Ethinylestradiol and its metabolites undergo glucuronide and sulfate conjugation. Ethinylestradiol undergoes extensive enterohepatic circulation as glucuronide and sulfate conjugation.
Excretion: The elimination half-life has been reported to be 30 hours for drospirenone. Drospirenone is excreted only in trace amounts in unchanged form. The metabolites of drospirenone are excreted with the feces and urine. The elimination half-life has been reported to be 6-45 hours for ethinylestradiol. Ethinylestradiol is not excreted in unchanged form to any significant extent. The metabolites of ethinylestradiol are excreted at a urinary to biliary ratio of 4:6.