Key Learning Points: Drug Interactions with Contraception

Dr Toni Hazell Provides Six Key Learning Points from the Faculty of Sexual & Reproductive Healthcare Guidance on Interactions Between Hormonal Contraception and Other Medications

In 1996, the average person in England was prescribed 10 items of medication per year by the NHS.^1,2 By 2016, this had doubled to 20,^1,3 and by 2021, 15% of the population in England were taking five or more medicines a day.¹ This rise in medication use increases the risk of drug interactions, and must be considered when prescribing any medication, including contraception.

Polypharmacy tends to increase with age, and many women of child-bearing age will not be taking medicines other than hormonal contraception; for those who are, the consequences of interactions with contraception can be significant.⁴ If another medicine reduces the effectiveness of their contraception, an unwanted pregnancy may result. Conversely, contraception can reduce the efficacy of medications for other conditions. If contraception reduces the effectiveness of an antiepileptic, for example, a seizure may result, causing both medical and social problems related to the loss of a driving licence or employment.

This article discusses the key recommendations of the new Faculty of Sexual & Reproductive Healthcare (FSRH) guidance on drug interactions with hormonal contraception.⁴ Where the data are unclear (as is often the case), the FSRH guidance tends to err on the side of caution in assuming an interaction.

1. Don’t Start Hormonal Contraception at the Same Time as Giving Ulipristal Acetate

Ulipristal acetate (UPA) was approved for use in Europe in May 2009,⁵ and was a welcome addition to the emergency contraception (EC) armoury. It can be used up to 120 hours after unprotected sexual intercourse, and is more effective than the alternative EC levonorgestrel (although both are less effective than the copper intrauterine device [IUD], which should always be offered first line).⁶ However, UPA has a significant interaction that levonorgestrel does not—its efficacy may be reduced if a progestogen is taken in the 7 days before or 5 days after administration.⁶ This is because UPA is a selective progesterone receptor modulator that may compete with progestogens at the progestogen receptor.^4,6

The practical consequence of this is that a hormonal contraceptive method cannot be ‘quick started’ at the same time as giving UPA.⁴ A woman who wants a contraceptive implant will have to come back 5 days after taking EC, and although a prescription for the contraceptive pill can be issued, she will have to delay starting to take it for 5 days.⁴ If a progestogen has been taken in the preceding 7 days (for example, by a woman needing EC who has forgotten to take several of her contraceptive pills) and a copper IUD is not wanted, then consider using levonorgestrel as EC instead of UPA.⁶

2. Be Aware that Women Using Enzyme-inducing Drugs Have Limited Contraceptive Options

Drugs that induce liver enzymes increase the hepatic clearance of contraceptive hormones, reducing the effectiveness of many contraceptive methods and limiting a woman’s choice of contraception.⁴ Several contraceptive options are unavailable to women using enzyme inducers, including all combined hormonal contraception (CHC), the contraceptive implant, and the progestogen-only pill (POP).⁴ This group of women is limited to IUDs (both the copper IUD and the hormonal intrauterine system [IUS] are suitable) or the depot injection. Their use of EC is also affected, and it is especially important that this population is offered a copper IUD if they need EC.⁴ If that is refused or unavailable, then a double dose (3 mg) of levonorgestrel should be given, although the effectiveness of this is unknown.⁴ Use of UPA is not recommended in this situation.^4,6

Some women will consider the side effects of an IUD or depot injection unacceptable, and will not be willing to try them. The FSRH advises that, in users of enzyme-inducing drugs ‘for whom alternative effective contraception is not acceptable [we may], in exceptional circumstances, consider use of two ethinylestradiol [EE] monophasic combined oral contraceptive pills together containing a total of 50 μg of EE (30 μg + 20 μg)’.⁴ This choice is far from ideal: we cannot guarantee its effectiveness, and it may confer an increased risk of thrombosis.⁴ Also, it can only be done with tablets, and not with the contraceptive patch or ring.⁴ If you are at the point of considering this, then good documentation is essential, and it may be worth a discussion with the woman’s consultant as to whether her enzyme inducer can be changed to another drug.

3. Understand the Complex Relationship Between Epilepsy Drugs and Contraception

There are multiple issues to consider in women who have epilepsy and need contraception. Some antiepileptic drugs are enzyme inducers at any dose—the list includes carbamazepine and phenytoin.⁷ Antiepileptics that do not induce liver enzymes include levetiracetam, sodium valproate, and lacosamide.⁷ For more information, see Box 1.

Topiramate, which is indicated for epilepsy and migraine,⁸ is probably only enzyme inducing at a dose greater than or equal to 200 mg daily.⁷ However, given that it is a teratogen,⁹ and in view of the fact that rates of metabolism of contraceptives vary widely, the FSRH suggests that clinicians err on the side of caution and consider topiramate to be a potential enzyme inducer at all doses.⁴

In terms of interations with hormonal contraception, the most complicated antiepileptic medication is lamotrigine, as there are three possible interactions:⁴

• oestrogen can reduce the serum level of lamotrigine and, in turn, its effectiveness, risking a seizure; this may also lead to lamotrigine toxicity during pill-free intervals, when serum lamotrigine can increase
• the progestogen desogestrel can increase serum lamotrigine, risking lamotrigine toxicity; the evidence for this effect with use of other progestogens is limited
• lamotrigine appears to reduce exposure to progestogens, risking contraceptive failure.

The most straightforward option is to avoid prescribing lamotrigine in women of child-bearing age. However, this is not always possible, so the FSRH suggests the following good practice points:⁴

• if CHC use is unavoidable, consider increasing the dose of lamotrigine and using CHC in a continuous fashion to avoid cyclical fluctuations; serum lamotrigine levels should be monitored to avoid a reduction in the effectiveness of lamotrigine
• patients who use lamotrigine and start a progestogen-only contraceptive should be alert to signs of lamotrigine toxicity (for example, dizziness, ataxia, and diplopia)
• discuss with the patient’s neurologist or psychiatrist when starting or stopping hormonal contraception in a woman taking lamotrigine
• the available data do not exclude reduced effectiveness of CHC, the POP, and the contraceptive implant; erring on the side of caution means advising additional reliable use of condoms, or changing to the depot injection, an IUD, or an IUS.

4. Be Vigilant for Women with Hypothyroidism Who Start Taking Oestrogen

Oral oestrogens (as part of contraception or hormone-replacement therapy) can increase the requirement for levothyroxine by elevating the amount of thyroid-binding globulin.⁴ There are limited data to support this, but women who are stable on a dose of levothyroxine may need their dose to be increased if they start taking CHC. The FSRH advises clinicians to check thyroid function 6 weeks after initiating any form of CHC.⁴

5. Know Where to Look for HIV-related Interactions

Many antiretrovirals are enzyme inducing, and FSRH guidance on interactions between hormonal contraceptives and HIV drugs is in the pipeline. The key resource for this situation is the University of Liverpool HIV drug interactions checker,^4,10 into which you can easily enter the antiretroviral medication and the suggested contraception to check if interactions are likely.

6. Don’t Let a Fungal Infection or Gastro-oesophageal Reflux Cause an Unwanted Pregnancy

There is uncertainty around the interactions between the antifungal agent griseofulvin and hormonal contraception.⁴ There is no known mechanism for interaction, but case reports describe changes in menstrual bleeding patterns and unplanned pregnancies in women on hormonal contraception taking griseofulvin.⁴ Griseofulvin is also a potential teratogen.⁴ For safety, the FSRH therefore advises that users of oral contraception or the etonogestrel implant should use condoms reliably while taking griseofulvin;⁴ those treating the fungal infection could also choose a different drug.

There is similar uncertainty around the use of proton-pump inhibitors and how this may affect the effectiveness of UPA for EC, with one small study showing reduced UPA levels during use of esomeprazole.^4,11 A copper IUD should always be offered, and if this is not appropriate or acceptable, then use of levonorgestrel as EC is preferred over UPA if the unprotected intercourse was within the preceding 96 hours.⁴

Summary

In general, women have many contraceptive options, some with failure rates as low as 0.05%,¹² but women affected by drug interactions can find that their options dramatically decrease. If providing contraception turns out to be impossible, it is always worth a discussion with the patient’s consultant to see if their drug regimen can be altered.

Dr Toni Hazell

Portfolio GP, Tottenham, London