[india-drug] Re: Drug Query-Centchroman (3)

["Sampada Patvardhan" <dicmspc@yahoo.co.in>]

Drug Query-Centchroman (3)
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It seems SAHELI - (Centchroman) does not prevent user from ovulating like the pill does. This means that the egg will become fertilized and then be "aborted" because it is unable to attach to the uterus. Maybe it is like aborting each time lady is on this oral contraceptive?
   
  SAHELI - (Centchroman 30 ma Uncoated Tablets)
  Description
  Chemical Name: 3,5 Trans-2, 2-Dimethyl-3 Pheny l - 4 - (p-(Beta-Pyrrolidinoethoxy) Phenyl)- 7 Methoxychroman Hydrochloride.
  Structural Formula

"Saheli is a novel non - steroidal once - a - week* oral contraceptive unrelated to conventional hormonal oral contraceptives that are required to be taken daily for 21 days everymonth (28days) and are known to have typical steroid-related side-effects. Saheli is recommended twice a week for the first 3 months and once a week thereafter and is free from-side effects generally associated with hormonal contraceptives.

  Mode of Action
  Saheli has a weak estrogenic and potent antlestrogenic activity. Contraceptive effects are related to slight acceleration of embryo transport through the oviducts and accelerated blastocyst formation along with suppression of uterine proliferation and decidualisation as well as alteration in biochemical parameters of implantation thus creating an asynchrony between embryo and uterine development, acritical requisite for nidation. Saheli does not affect the hypothalmopituitary-ovarian axis. Administration of Saheli does not inhibit ovulation either.

  Clinical Pharmacology
  Estrogenic action of Saheli is mediated through its estrogen receptor interaction. Little is known about the mechanism of antagonistic activity. Basic studies suggest that a tertaminoethoxy moiety when attached to the p-position on the 4-phenyt substitutent increases their relative binding affinity to estradiol receptors through their interaction with a receptor site which is responsible for their antagonistic action.
  No progestational, androgenic or antiandrogenic properties are exhibited by Saheli at the recommended contraceptive doses. There is also no effect on the pituitary, thyroid or adrenal secretory functions.
  Routine laboratory evaluations were within normal physiological range following administration of Saheli and there has been no abnormal or detetertous effects on any of the body systems. Absorption from the Gl tract is adequate, though somewhat delayed.
  63 ng/mt concentration in the serum was seen following -30 minutes of oral dministration and peak serum concentration over 125 ng/ml is achieved at 4 hours.
  Distribution in the tissues seems to be extensively evidenced by high values of the apparent volume of distribution.
  Saheli manifests little affinity and non-saturable plasma protein binding, and te non competing with both sex hormone-binding and corticoateriod binding globulins. Serum concentration time data has best been described by a two component open model with first order absorption and elimination rate constants. The terminal disposition half-life was evaluated at approximately 170 hours. 

  Indication
  Saheli is a safe non-steroidal oral contraceptive for women of reproductive age group who are desirous of spacing their children.

  Contraindications
  Administration of Saheli is not recommended in the following conditions:
  ·                                 Polycystic ovarian disease. 
  ·                                 Cervical hyperptasia. 
  ·                                 Recent history of clinical evidence of jaundice or liver diseases. 
  ·                                 Administration of Saheli is not advisable in conditions like severe allergic states, chronic illness such as tuberculosis, renal diseases etc.
  Although the experimental studies show that the concentration of Centchroman in the breast milk in lactating mothers from 6 to12 months is below that of any which can have physiological consequences to the suckling baby, as a precautionary measure it is advisable that lactating mothers may not use Centchroman for the first six months.

  Precaution
  Prolongation of menstrual cycles may be experienced by some individuals. Delayed menstruation is inconsequential if dosages have not been missed. In case of delay exceeding 15 days, pregnancy should be ruled out with routine investigations. Administration should be discontinued immediately if pregnancy is confirmed. Animal studies have shown no teratogenic effect. Children born to method failure cases have shown normal growth and development parameters. Women in the untoward event of confirmed pregnancy have the option of MTP or continuing with pregnancy.

  Adverse effects 
  Clinical studies, both animal and human, have confirmed Saheli is safe and free from typical hormorial side effects such as nausea, weight gain, fluid retention, hypertension etc. Drug-induced vaginal discharge, spotting, breakthrough bleeding or menorrhagia have not been reported.
  
Administration
  Regimen should be started with 1 tablet of 30 mg twice a week for 3 months followed by one tablet once a week as long as contraception is desired. The first tablet has to be taken on the first day of the menstrual cycle. Tablet should be taken on fixed days and at fixed times. Dosage should be followed irrespective of subsequent menstrual periods.
  # Caution - Non adherence to usage recommendations may lead to pregnancy.
   

Dr. (Mrs.) Sampada Patvardhan (Ph.D.Tech. Pharmacology)                                         
Director, Maharashtra State Pharmacy Council?s Drug Information Centre  E.S.I.S. Hospital Compound, L.B.S. Marg, Mulund (W), Mumbai-400 080   Phone: 25930607  Telefax: 25684291/25684418  e-mail: dicmspc@yahoo.co.in