Combined Injectables

Combined injectable contraceptives give a long-acting progestin ester with a natural oestrogen ester by deep intramuscular injection once every 30 days. They prevent pregnancy mainly by inhibiting ovulation. They are less commonly stocked than progestin-only injectables and are not interchangeable with them.

Products.

Pharmacokinetics. The natural oestrogen is less potent than ethinylestradiol, and intramuscular delivery avoids first-pass hepatic metabolism, so oestrogen effects may differ from those of combined pills.

Effectiveness. First-year pregnancies: 3 in 100 women with typical use and 1 in 100 with perfect use. Risk is greatest when an injection is late or missed.

Onset of protection. Immediate when the first dose is given within 7 days of the start of menses; otherwise 7 days of backup.

Return to fertility. An average of about 5 months after the last injection.

Bleeding pattern. Irregular bleeding in the first months, then usually regular monthly bleeding. Amenorrhoea is uncommon.

Suitable candidates. Patients who want an injectable with regular monthly bleeding and cannot take a daily pill, and who have no category 3 or 4 condition.

Eligibility. Categories are those of every combined method.

• Category 4: breastfeeding under 6 weeks; blood pressure 160/100 or more; ischaemic heart disease, stroke or complicated valvular disease; migraine with aura; current or past breast cancer; current or past deep vein thrombosis or pulmonary embolism, or thrombogenic mutation; diabetes with vascular disease; smoker 35 years or more with 15 or more cigarettes daily; lupus with positive or unknown antiphospholipid antibodies; decompensated cirrhosis; liver adenoma or malignancy.
• Category 3: breastfeeding 6 weeks to under 6 months; not breastfeeding under 21 days postpartum; blood pressure 140/90 to 159/99; rifampicin; rifabutin; enzyme-inducing antiseizure medicines.

Investigations. Blood pressure and body mass index. No routine laboratory tests. A pregnancy test when pregnancy cannot be excluded.

Interactions. Enzyme inducers reduce effectiveness; medroxyprogesterone acetate 150 mg injectable, a copper device or a levonorgestrel intrauterine system is preferred for patients on rifampicin or rifabutin. Efavirenz, nevirapine and ritonavir-boosted regimens are category 2 and need added condoms.

Counselling points for the clinician. The method needs a clinician or trained provider for each dose and does not support self-injection. Do not confuse it with 150 mg medroxyprogesterone acetate or 200 mg norethisterone enanthate injections, which have different intervals. Consent, no coercion, assent from under 18 years.

Regimen line. Medroxyprogesterone acetate 25 mg with oestradiol cypionate 5 mg, or norethisterone enanthate 50 mg with oestradiol valerate 5 mg, by deep intramuscular injection.

First dose within 7 days of the start of menses with no backup; later starts need 7 days of backup after pregnancy is reasonably excluded. Repeat every 30 days. Grace: up to 7 days early or 7 days late, that is between day 23 and day 37. Protection lasts about 30 days from each dose.

Postpartum: not before 21 days if not breastfeeding; breastfeeding from 6 months. Enzyme inducers: do not use.

More than 7 days late. Give the next dose if there has been no intercourse since 7 days after the scheduled date, or if backup or emergency contraception was used after any unprotected sex since then; use backup for 7 days after the injection. If these conditions are not met, take further steps to be reasonably certain the patient is not pregnant before injecting; amenorrhoea does not exclude pregnancy.

Pregnancy exclusion. Reasonably certain when there has been no intercourse since the last menses, a reliable method has been used correctly, menses began within the past 7 days, the patient is within 7 days of abortion, or within 4 weeks of childbirth and not breastfeeding. Otherwise test.

Switching. From a pill, patch or ring used correctly, give the first dose at once. From a progestin-only injectable, give the first dose when the next progestin injection is due. From an intrauterine device, give within 5 days of menses and remove the device then; if later, remove it at the next menses.

Follow up. Review at about 3 months and then yearly: blood pressure, weight, smoking, medicines, bleeding. Reassess from 40 years; at about 50 years a change to a progestin-only or non-hormonal method is usual practice.

Expected effects. Irregular bleeding or spotting in the first months, headache, breast tenderness, nausea and weight change. Effects continue until the dose wears off, which takes about a month.

Management. Unscheduled bleeding: exclude pregnancy, infection, late dosing and interactions; give ibuprofen 800 mg orally three times daily for 5 days with food (maximum 2.4 g daily; avoid in renal impairment, active peptic ulcer or significant liver disease; not used in pregnancy); if bleeding persists after 3 months, change the product or method. Amenorrhoea: exclude pregnancy and reassure. Headache: measure blood pressure and ask about aura; mild headache needs reassurance.

Serious complications. Venous thromboembolism, stroke, myocardial infarction and hypertension.

Red flags. Severe abdominal pain, chest pain or breathlessness, severe or new headache, eye problems and severe calf pain. Give no further injection and arrange urgent evaluation.

When to change method. Category 4 condition, migraine with aura, enzyme-inducing medicines, or unacceptable bleeding.

Referral and escalation. Suspected thrombosis, stroke or myocardial infarction needs emergency transfer. Persistent unexplained bleeding or an undiagnosed breast lump needs evaluation.