Missed Combined Pills

Missed combined pills are the commonest cause of pill failure. The risk comes from lengthening the hormone-free interval, because follicles then develop and ovulation can escape. Missing pills at the start or end of a pack is the most dangerous, since it extends the planned 7 day break. Missing pills in the middle of a pack carries little risk because ovarian suppression is already established.

Weeks of the pack. In a 21 active tablet pack, week 1 is tablets 1 to 7, week 2 is tablets 8 to 14 and week 3 is tablets 15 to 21. The 7 inactive tablets of a 28 tablet pack are not counted.

Risk. Pregnancy risk is greatest when a new pack is started 3 or more days late or when 3 or more active pills are missed near the start or end of a pack. Missing 1 or 2 pills, or starting a new pack 1 or 2 days late, carries little or no risk.

Effectiveness. First-year pregnancies: 8 in 100 women with typical use and 0.3 in 100 with perfect use. Most of the difference comes from missed pills.

Absorption failure. Vomiting within 2 hours of a pill and vomiting or diarrhoea lasting more than 2 days reduce absorption and act as missed pills.

Return to fertility. Without delay after stopping.

Assessment. Establish how many active pills were missed, which week of the pack they fell in, whether the pack was started late, the date and number of episodes of unprotected sex in the last 5 days, and the date of the last menses. Ask about vomiting, diarrhoea and interacting medicines.

Pregnancy test. Do a pregnancy test when pills were missed and there has been unprotected sex more than 5 days earlier, when a withdrawal bleed is absent after missed pills in week 3, or when pregnancy symptoms occur. A negative test within 2 weeks of unprotected sex does not exclude pregnancy, so repeat it.

Interactions. Rifampicin, rifabutin, phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, griseofulvin and St John’s wort lower hormone levels, so a patient taking them is effectively a patient with missed pills and needs another method. Efavirenz, nevirapine and ritonavir-boosted regimens are category 2 and need condoms. Lamotrigine levels fall.

Eligibility for continued pill use. Missed pills do not change eligibility. A patient with a category 3 or 4 condition should not be restarted on the pill.

Eligibility for emergency contraception. All patients are eligible, including adolescents, patients who are breastfeeding and patients with conditions that make combined pills unsuitable. Levonorgestrel is less effective at body mass index of 30 or more; ulipristal or a copper intrauterine device is preferred.

Counselling points for the clinician. Ask without blame. Explain that the pill is taken at a fixed time linked to a daily routine, with phone alarms or a spare pack. Offer condoms, advance supply of emergency contraception and a review of the method. Consent, no coercion, assent from under 18 years.

Special groups. Adolescents: higher rates of missed pills, so offer a long-acting method. Postpartum: combined pills start at 21 days if not breastfeeding and from 6 months if breastfeeding. HIV: check the antiretroviral regimen. Epilepsy and tuberculosis treatment: enzyme inducers make the pill unreliable. Patients who vomit or have chronic diarrhoea: use a ring or another method.

Regimen line. Ethinylestradiol 20 to 35 micrograms with a progestin, oral, one tablet daily at about the same time; 21 active tablets then 7 hormone-free days or inactive tablets. Grace: missing 1 or 2 pills, or a new pack 1 or 2 days late, needs no backup. Backup after 3 or more missed pills: condoms or abstinence for 7 days. Enzyme inducers: do not use.

Missed pill rules.

Packs with 24 active and 4 inactive tablets. Missed 1 or 2 active pills: take a pill now and continue; no backup. Missed 3 or more in the first 2 weeks: take a pill now, continue, backup 7 days, consider emergency contraception. Missed 3 or more in the last week of active tablets: finish the active tablets, discard the inactive tablets, start the next pack the next day, backup 7 days, consider emergency contraception.

Multiphasic packs. Count the missed tablets by position in the pack, take the missed tablet now and continue in pack order.

Extended and continuous use. Apply the same rules. If 3 or more pills are missed in the 7 days before a planned break, omit the break, start the next pack straight away and use backup for 7 days.

Emergency contraception.

• Levonorgestrel 1.5 mg orally as a single dose (two 750 microgram tablets together is preferred) as soon as possible within 120 hours; a split dose of 750 micrograms twice, 12 hours apart, is acceptable. No renal or liver adjustment. Compatible with breastfeeding. Not needed if pregnant. Maximum one course for each episode.
• Ulipristal acetate 30 mg orally as a single dose within 120 hours, where available. Avoid in severe liver disease. Wait 5 days before restarting the pill, and use backup for 7 days after restarting.
• Copper intrauterine device inserted within 5 days of unprotected sex: the most effective option.
• Yuzpe regimen, only when no other option exists: combined pills giving ethinylestradiol 100 micrograms with levonorgestrel 500 micrograms, repeated after 12 hours, within 120 hours (for example four 30 microgram pills twice). Least effective.
• Repeat the dose if vomiting occurs within 2 hours of an oral emergency dose.
• After levonorgestrel or the Yuzpe regimen, continue or restart the pill at once and use backup for 7 days.

Follow up. Review in 3 weeks or at the next expected menses. Do a pregnancy test if menses are absent or late. Reassess the method if two or more episodes of missed pills occur in 3 months.

Expected effects of missed pills. Breakthrough bleeding or spotting, early or absent withdrawal bleeding, nausea, and a rise in pregnancy risk.

Effects of emergency contraception. Nausea, vomiting, headache, breast tenderness and a change in the timing of the next menses by a few days. Menses delayed by more than 7 days needs a pregnancy test.

Pregnancy after missed pills. Stop the pill and confirm the pregnancy and its location. Combined hormones are not known to harm the foetus. Pain or bleeding needs assessment for ectopic pregnancy.

Unscheduled bleeding. Exclude pregnancy, infection and interacting medicines. Reinforce timing. Ibuprofen 800 mg orally three times daily for 5 days with food gives short-term relief (maximum 2.4 g daily; avoid in renal impairment, active peptic ulcer or significant liver disease; not used in pregnancy).

Red flags. Severe abdominal pain, chest pain or breathlessness, severe or new headache, eye problems and severe calf pain. Stop the pill and arrange urgent evaluation.

When to change method. Repeated missed pills, vomiting or diarrhoea that keeps recurring, need for an enzyme-inducing medicine, or a category 4 condition.

Referral and escalation. Suspected ectopic pregnancy or thrombosis needs emergency transfer. Offer an intrauterine device or implant to patients with repeated failures.