Formulations and methods for providing progestin-only contraception while minimizing adverse side effects associated therewith

Abstract

Formulations and methods for providing progestin-only contraception to a woman including transdermally administering to a woman a formulation having a contraceptively effective amount of progestin-only hormonal agents as part of a contraceptive regimen.

What is claimed is: 
     
         1 . A method of providing progestin-only contraception to a woman while minimizing adverse side effects associated with the progestin-only contraception, comprising the steps of:
 a) applying a transdermal patch to the outer skin surface of a woman and allowing the patch to remain applied to the outer skin surface of the woman for at least seven days; and   b) removing the transdermal patch from the outer skin surface after about seven days wherein the transdermal patch comprises a drug formulation comprising (i) norethindrone and/or norethindrone acetate as the only active hormonal agents in an amount of from about 1% w/w to about 15% w/w of the drug formulation and (ii) a permeation enhancer in an amount from about 3% w/w to about 15% w/w of the drug formulation wherein the permeation enhancer is selected from the group consisting of isopropyl myristate as the sole permeation enhancer, a combination of isopropyl myristate and sorbitan monooleate or a combination of isopropyl myristate and dipropylene glycol; and   the norethindrone and/or norethindrone acetate are administered from the transdermal patch at a rate and amount that provides a minimum norethindrone serum level of at least 300 pg/ml from about 24 hours to about 168 hours following application of the patch to the outer skin surface and a maximum norethindrone serum level of less than 1200 pg/ml about 24 to 96 hours following application of the patch to the outer skin surface.   
     
     
         2 . The method described in  claim 1  wherein the application step and removal step are conducted once a week for 4 to 12 weeks. 
     
     
         3 . The method described in  claim 2  wherein the application step and removal step are conducted once a week for 4 weeks. 
     
     
         4 . The method described in  claim 2  wherein the application step and removal step are conducted once a week for 12 weeks. 
     
     
         5 . The method described in  claim 1  wherein at least 0.35 mg/day of norethindrone and/or norethindrone acetate is delivered from the transdermal patch. 
     
     
         6 . The method as described in  claim 1  wherein the minimum norethindrone serum level is at least 350 pg/ml and is sustained from about 24 hours to about 168 hours following application of the transdermal patch to the outer skin surface. 
     
     
         7 . The method as described in  claim 1  wherein the maximum norethindrone serum level is less than 1100 pg/ml and is obtained about 24 to 96 hours following application of the transdermal patch to the outer skin surface. 
     
     
         8 . The method as described in  claim 1  wherein the norethindrone and/or norethindrone acetate is present in an amount of from about 2.5% w/w to about 12% w/w of the drug formulation. 
     
     
         9 . The method as described in  claim 1  wherein the adverse side effect is selected from the group consisting of strokes, myocardial infarctions, embolisms, breakthrough bleeding, and combinations thereof. 
     
     
         10 . The method as described in  claim 1  wherein the drug formulation further comprises diluents, emollients, plasticizers, skin irritation reducing agents, or a mixture thereof. 
     
     
         11 . The method as described in  claim 10  wherein the drug formulation includes a skin irritation reducing agent and wherein the skin irritation reducing agent is glycerin. 
     
     
         12 . The method as described in  claim 1  wherein the only active hormonal agent is a combination of norethindrone and norethindrone acetate, which are present in an amount of from 2.5% to 12% w/w of the drug formulation. 
     
     
         13 . The method as described in  claim 1  wherein the transdermal patch is a matrix patch and the drug formulation further comprises an acrylic polymer adhesive. 
     
     
         14 . The method as described in  claim 1  wherein the permeation enhancer is isopropyl myristate as the sole permeation enhancer. 
     
     
         15 . The method as described in  claim 1  wherein the permeation enhancer is a combination of isopropyl myristate and sorbitan monooleate. 
     
     
         16 . The method as described in  claim 1  wherein the permeation enhancer is a combination of isopropyl myristate and dipropylene glycol. 
     
     
         17 . A method of providing progestin-only contraception to a woman while minimizing adverse side effects associated with the progestin-only contraception, comprising the steps of:
 a) applying a transdermal patch to the outer skin surface of a woman and allowing the patch to remain applied to the outer skin surface of the woman for at least seven days; and   b) removing the transdermal patch from the outer skin surface after about seven days wherein the transdermal patch is a matrix patch comprising a drug formulation comprising (i) a combination of norethindrone and norethindrone acetate as the only active hormonal agents in an amount of from about 1% w/w to about 15% w/w of the drug formulation; (ii) a permeation enhancer in an amount from about 3% w/w to about 15% w/w of the drug formulation wherein the permeation enhancer is selected from the group consisting of isopropyl myristate as the sole permeation enhancer, a combination of isopropyl myristate and sorbitan monooleate or a combination of isopropyl myristate and dipropylene glycol; (iii) an acrylic adhesive; (iv) one additional ingredient selected from the group consisting of comprises diluents, emollients, plasticizers, skin irritation reducing agents, or a mixture thereof; and   the norethindrone and/or norethindrone acetate are administered from the transdermal patch at a rate and amount that provides a minimum norethindrone serum level of at least 300 pg/ml from about 24 hours to about 168 hours following application of the patch to the outer skin surface and a maximum norethindrone serum level of less than 1200 pg/ml about 24 to 96 hours following application of the patch to the outer skin surface.   
     
     
         18 . The method as described in  claim 17  wherein the permeation enhancer is isopropyl myristate as the sole permeation enhancer. 
     
     
         19 . The method as described in  claim 17  wherein the permeation enhancer is a combination of isopropyl myristate and sorbitan monooleate. 
     
     
         20 . The method as described in  claim 17  wherein the permeation enhancer is a combination of isopropyl myristate and dipropylene glycol.