DRUG INTERACTIONS AND

HORMONAL CONTRACEPTION
Concomitant use of hormonal contraceptives with other drugs may alter the serum levels of contraceptive hormones or
concomitant drugs leading to a risk of contraceptive failure or other adverse effects. Thus, it is important to consider the
possible drug interactions when prescribing hormonal contraception along with other drugs to women. Drug interactions
with hormonal contraceptives are of concern, especially when metabolism of the steroid is induced, as this may decrease
the efficacy of contraceptive. This article discusses about the prediction of drug interactions and the interpretation of
pharmacokinetic interaction studies of combined hormonal contraceptives (Table 1).1

Table 1: Quick reference for non-enzyme-inducing drugs and contraception2

Drug Type Lamotrigine Griseofulvin Drugs that alter gastric pH Drugs that cause Progestogen
(antiepilectic; (antifungal; (e.g. antacids,H2 antagonist, severe diarrhoea receptor
non-enzyme- non-enzyme- or vomiting proton pump (e.g. UPA) modulators
inducer) inducer) inhibitors) (e.g. orlistat)

CHC

POP

IMP

DMPA

LNG-IUS

Cu-IUD
(EC)

LNG-EC

UPA-EC

HORMONAL CONTRACEPTIVES

The clinically relevant examples of established drug-interactions which affect hormonal contraceptives are mediated
generally via alteration of the metabolism of the contraceptive steroids.1

Ethinyloestradiol:
Drugs which act as enzyme inducers can increase the clearance of the contraceptive steroids and thus increase
chances of breakthrough bleeding and decrease efficacy of contraceptive. This is because the metabolism of
ethinyloestradiol occurs by hydroxylation via Cytochrome P450 isoenzyme CYP3A4 and CYP2C9 and by conjugation
via sulphation and glucuronidation via UDP-glucuronosyl transferase 1A1. Antifungals such as voriconazole and
fluconazole are specific inhibitors of CYP3A4 and 2C9 and hence cause only modest increase in ethinyloestradiol
levels. Drugs which increase ethinyloestradiol levels by 35% may increase the incidence of adverse effects such as
nausea, breast tenderness and headache.1
 Progestogens:
The extent of first-pass metabolism depends on the drug (for example it is high for norethisterone, desogestrel and
norgestimate whereas none for levonorgestrel).They are metabolized possibly by CYP3A4 and also undergo conjuga-
tion reactions. Most interaction studies including combined oral contraceptive have shown that effect of enzyme
inhibitors or inducers on progestogens is less compared to ethinyloestradiol though there are few exceptions. The
antiepileptic drug felbamate produced a modest decrease in gestodene levels whereas just a slight decrease in
ethinyloestradiol levels.1

DRUG INTERACTION OF HIV PROTEASE INHIBITOR AND ANTIBACTERIALS WITH

HORMONAL CONTRACEPTIVES

Based on in vitro assessment, it was predicted that ritonavir increases the levels of contraceptive steroids but it
was found that it actually decreases them. Most probably ritonavir increases metabolism of ethinyloestradiol by
inducing glucuronidation. Some other HIV protease inhibitors like atazanavir increases ethinyloestradiol levels
when used alone.1

Several pharmacokinetic drug interaction studies have shown that any class of antibacterial does not cause
alteration in the levels of the contraceptive steroids (except rifamycin).1

EFFECT OF CONTRACEPTIVES ON OTHER DRUGS

Lamotrigine:
Evidence suggests that contraceptives decrease lamotrigine levels and efficacy and hence it is advisable to
increase the dose of lamotrigine when used as monotherapy. Also, ethinyloestradiol increases metabolism of
lamotrigine by inducing glucuronidation.1 When ethinyloestradiol is used in combination with lamotrigine, the
concentrations of lamotrigine fall by 50%–60% and lead to seizure aggravation. Women using combined oral
contraceptive (COC) may witness large fluctuations of the lamotrigine serum concentration during the menstrual
cycle. Thus, the combination of lamotrigine with ethinyloestradiol (COCs, patch, or vaginal ring) appears as unfa-
vorable and should be avoided.3

Tizanidine:
Oral contraceptives seem to markedly increase tizanidine levels which result in an increase in the
blood-pressure-lowering effect. This is because contraceptive steroids probably are modest inhibitors of tizanidine
metabolism via CYP1A2.

References:
1. Lee RC, et al. Drug interactions and hormonal contraception. Trends in urology Gynecology
and Sexual Health.2009; 23-26.
2. The Faculty of Sexual and Reproductive Healthcare (FSRH). Clinical Guidance: Drug
Interactions with Hormonal Contraception. Available from:
https://www.fsrh.org/standards-and-guidance/documents/ceu-clinical-guidance-drug-inter
actions-with-hormonal/. Accessed on: June 27, 2018.
3. Reimers A. Contraception for women with epilepsy: counseling, choices, and concerns.
Open Access J Contracept. 2016; 7: 69–76.