Table 2.
Available hormonal contraceptive products and potential routes of drug-drug interactions.
| Enzymes that metabolize and/or are inhibited or induced by contraceptive hormones | ||||||
|---|---|---|---|---|---|---|
| Contraceptive Hormone | Available Delivery Routes | CYP substrate | CYP inhibitor | CYP inducer | UGT1A1 | Other major routes of metabolism |
| Estrogen | ||||||
|
Ethinyl estradiol [95–98] Estradiol valerate [99] |
COC Transdermal patch Vaginal ring |
3A4 (61%) 2C9 (23%) Minor (<20% total): 1A2, 2C19, 3A5 |
In vitro: 2B6, 2C19, 3A4 | 2A6 (proposed) | Substrate Inducer |
Sulfate conjugation |
| Progestins | ||||||
| 1st Generation – derived from 17-hydroxyprogesterone or from testosterone | ||||||
| Medroxyprogesterone acetate [98, 100–102] | IM injection SC injection |
3A4 | … | 3A4 (by 25%) | None | … |
| Norethindrone (U.S.)/Norethisterone (international) [103, 104] | COC POP |
3A4 | In vitro: 2C9 (weak) | … | Substrate | Sulfate conjugation |
| 2nd Generation – derived from testosterone | ||||||
| Levonorgestrel [22, 24, 98] | COC POP (emergency) IUD Subdermal implant |
3A4 | In-vitro: 3A4 (weak) | … | Substrate (minor) | Sulfate conjugation |
|
Norgestrel [98] Includes levonorgestrel and its inactive isomer, dextronorgestrel |
COC | 3A4 | … | … | … | … |
| 3rd Generation – derived from levonorgestrel | ||||||
|
Desogestrel [20, 105, 106] Prodrug, rapidly and extensively converted to etonogestrel |
COC | In-vitro: 2C9 (not supported by in-vivo data) | … | … | Substrate | … |
| Etonogestrel [24] | Vaginal ring Subdermal implant |
3A4 | In-vitro: 3A4 (weak) | … | Substrate | … |
| Gestodene [20, 24] | COC | 3A4 | In-vitro: 3A4(potent), not clinically significant at low doses | … | … | … |
|
Norgestimate [20, 24] Prodrug, rapidly and extensively converted to norelgestromin and norgestrel |
COC | 3A4 | In-vitro: 3A4 (weak) | … | … | … |
|
Norelgestromin [107] Metabolized to norgestrel |
Transdermal patch | … | … | … | … | Undergoes hepatic metabolism to norgestrel |
| 4th Generation | ||||||
| Drospirenone [98, 108] | COC | 3A4 (minor) | In-vivo: inhibition of 2C19 and 3A4 were not significant | Reduction, then sulfate conjugation | ||
Abbreviations: CYP, cytochrome P450; COC, combination (estrogen/progestin) oral contraceptive; IM: intramuscular; SC: subcutaneous; POP, progestin-only oral contraceptive; IUD, intrauterine device.