Combined oral contraceptive pill

Is the combined pill safe?

For most healthy women who do not smoke, yes. The combined pill pairs an estrogen (almost always ethinyl estradiol) with one of several progestins, and taken correctly it is more than 99% effective at preventing pregnancy (NHS). It has 60 years of data behind it, no misuse potential, and overdoses are not dangerous.

The real risk is blood clots. Every combined pill raises the chance of a clot in the legs or lungs, the size of the rise depends on the progestin, and smoking, age, obesity and some migraines push the risk of stroke and heart attack up. We score the class 77, level with estradiol for menopause (77).

This page covers combined pills as a class. Brands differ in their progestin, estrogen dose and pack schedule, so the leaflet in your own pack is the final word.

How much does the pill raise the risk of blood clots?

The US labels put the risk of a venous clot at 3 to 9 per 10,000 women a year on the pill, against 1 to 5 in women who are neither pregnant nor on the pill. The risk is highest in the first months of use, and again when restarting after a break of 4 weeks or more. It fades after stopping.

The progestin matters. After a European review completed on 21 November 2013, the MHRA published this table:

Progestin in the pill	Clots per 10,000 women a year
None (not pregnant, no hormonal contraception)	About 2
Levonorgestrel, norethisterone, norgestimate	5 to 7
Etonogestrel, norelgestromin (ring, patch)	6 to 12
Gestodene, desogestrel, drospirenone	9 to 12
Dienogest, nomegestrol	Not yet estimated in 2014

The Yaz label says drospirenone pills may carry up to three times the clot risk of levonorgestrel pills in some studies, while others found no difference. Both regulators stressed the absolute risk is small and lower than in pregnancy and the weeks after birth. The MHRA advised that no woman needs to change pills because of the review.

Warning signs need urgent care: pain or swelling in one leg, sudden breathlessness or chest pain, coughing blood, a sudden severe headache, weakness on one side or loss of vision.

The smoking warning

All US combined pills carry the same boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary. Smoking raises the risk of serious cardiovascular events on the pill, the risk grows with age and with the number of cigarettes, and the pill must not be used by women over 35 who smoke.

The labels also rule it out after a clot, stroke or heart attack, with heart valve or rhythm disease that forms clots, an inherited clotting disorder, uncontrolled high blood pressure, diabetes with blood vessel damage, migraine with aura (or any migraine over 35), breast cancer, liver tumours or liver disease, and unexplained vaginal bleeding. Drospirenone pills are also not for women with kidney or adrenal problems, because drospirenone can raise potassium.

Other rare label risks: liver adenomas (about 3.3 cases per 100,000 users), gallbladder disease, a rise in blood pressure, and mood changes in women with a history of depression.

Interactions that can make the pill fail

The most practical risk is not a side effect but an unplanned pregnancy. Drugs and herbs that speed up liver enzymes lower hormone levels. The labels name rifampin, rifabutin, carbamazepine, oxcarbazepine, phenytoin, barbiturates, topiramate, felbamate, griseofulvin, bosentan, efavirenz and St John's wort, and advise a backup method while taking them and for 28 days after stopping. Most ordinary antibiotics have not shown a consistent effect.

It works the other way too. The pill can lower lamotrigine levels enough to affect seizure control, and women on levothyroxine may need a higher dose. Strong CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary blockers such as ketoconazole or clarithromycin raise hormone levels. Acne treatment with isotretinoin usually requires reliable contraception, so the pill is often prescribed alongside it.

Missed pills and overdose

Missed-pill rules depend on the brand and pack. As one example, the Yaz label says: one missed active tablet, take it as soon as you remember and the next at the usual time (two in one day is fine), with no backup needed. Two or more missed active tablets need extra tablets or a new pack, depending on the week, plus condoms for 7 days. Missed inactive tablets can be thrown away. Your own leaflet may differ; a pharmacist can tell you what applies.

Swallowing extra tablets is not dangerous. The labels describe nausea and withdrawal bleeding, and no serious ill effects even when children swallowed them. Call Poison Help on 1-800-222-1222 in the US or NHS 111 in the UK if a child gets into a pack.

Who should be careful

Talk to your doctor, nurse or pharmacist before starting or restarting the pill if you smoke, are over 35, have migraines, high blood pressure, diabetes, a BMI in the obese range, a family history of clots before 45, or have just had a baby. Tell any surgeon you take it, as labels suggest stopping 4 weeks before major surgery. The NHS says a pharmacist may be able to supply it without a prescription in England; in the US every combined pill still needs one.

How we scored it

Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (95), dependence (95) and track record (95) are strong. Interactions (68) lose points because common seizure drugs, rifampin and St John's wort can make the pill fail. Regulatory warnings (45) reflect the boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary on every US product, and serious side effects (65) the rise in clot risk. A lower score does not mean you should stop; talk to your prescriber first.