Medroxyprogesterone acetate (Depo-Provera)

1. Health Canada Product Monograph — Medroxyprogesterone acetate

• Medroxyprogesterone acetate injectable suspension (Depo-Provera) is used for long-acting contraception (prevention of pregnancy).
• Medroxyprogesterone acetate oral tablets are used, together with estrogen, as hormone replacement therapy to protect the uterine lining from overgrowth in women with an intact uterus.
• Medroxyprogesterone acetate oral tablets are used to treat functional menstrual disorders, such as secondary amenorrhea and dysfunctional uterine bleeding, caused by a hormone imbalance without an underlying structural cause.
• High-dose medroxyprogesterone acetate oral tablets are used as adjunctive or palliative treatment for recurrent or metastatic endometrial cancer.
• High-dose medroxyprogesterone acetate oral tablets are used as adjunctive or palliative treatment for hormone-sensitive, recurrent metastatic breast cancer in postmenopausal women.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Medroxyprogesterone acetate is contraindicated in women who are or may be pregnant, whether given by injection or by tablet.
• Use of medroxyprogesterone acetate is not recommended during pregnancy, and it should not be used as a test for pregnancy.
• If a patient is exposed to medroxyprogesterone acetate during pregnancy, or becomes pregnant while taking it, she should be told about the potential risk to the fetus.
• Because the injectable form has a long-acting effect, a delayed or missed follow-up injection can allow ovulation to resume, so patients relying on Depo-Provera for contraception should be counselled about this possibility.

• Small amounts of medroxyprogesterone acetate pass into breast milk; children who were breastfed while their mothers used the drug have not shown developmental or behavioural problems through puberty in available studies.
• If breastfeeding and using Depo-Provera, discuss the risks of pregnancy and the possible risks of the injection with a healthcare provider to determine the best approach.

• In large hormone therapy trials, oral medroxyprogesterone acetate combined with estrogen has not shown a difference in cardiovascular risk between women 70 to 79 years old and younger postmenopausal women, though women 75 and older showed a higher relative risk of stroke and breast cancer.
• Depo-Provera has not been specifically studied in women over 65, and dose selection in older adults in general should take into account other health conditions and medications.

• Medroxyprogesterone acetate oral tablets are not authorized for use in patients under 16 years of age, since no data are available to Health Canada for this age group.
• Depo-Provera should not be used before a girl's first menstrual period (menarche).
• In adolescent females who use Depo-Provera, loss of bone mineral density during treatment may not fully recover, which is of particular concern during this critical period of bone growth.

• For contraception, Depo-Provera is given as a deep intramuscular injection of 150 mg once every 3 months (every 10 to 13 weeks), with the first injection timed to the first 5 days of a normal menstrual period to help confirm the patient isn't already pregnant.
• If Depo-Provera is given later in the cycle, or if a follow-up injection is delayed beyond 13 weeks, an additional non-hormonal method of contraception is needed and a pregnancy test may be required before continuing.
• For hormone replacement therapy, oral medroxyprogesterone acetate is typically given at 5 to 10 mg daily for 12 to 14 days per cycle, alongside estrogen, in women with an intact uterus; the tablets should be swallowed with a full glass of water.
• For secondary amenorrhea, the usual oral dose is 5 to 10 mg daily for 12 to 14 days each month, after pregnancy has been ruled out.
• For dysfunctional uterine bleeding, the usual oral dose is 5 to 10 mg daily for 10 to 14 days, started around day 12 to 16 of the cycle and typically repeated for at least two more cycles.
• For endometrial cancer, the usual oral dose is 200 to 400 mg daily; if there's no improvement within 2 to 3 months, treatment is usually stopped.
• For breast cancer, the usual oral dose is 400 mg daily in divided doses, continued as long as the patient is responding; a response may not be apparent for 8 to 10 weeks.
• If a dose of the oral tablets is missed, it should be taken as soon as remembered unless it is almost time for the next dose, in which case the missed dose should be skipped; doses should never be doubled.
• The lowest effective dose for the shortest necessary duration should be used for hormone replacement therapy in general; no specific dose adjustment guidance is provided for kidney or liver impairment.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Overdose of medroxyprogesterone acetate, whether by injection or tablet, may cause a period of amenorrhea (absent periods) of variable length, sometimes followed by irregular menstrual bleeding for several cycles.
• Very high doses (500 mg or more daily) have been associated with corticosteroid-like effects, including a rounded ("moon") face and elevated blood pressure.
• Oral doses as high as 1000 mg daily have been used for cancer therapy without reports of acute overdose toxicity.
• There is no specific antidote for medroxyprogesterone acetate overdose; management is supportive and based on symptoms.

• Irregular, unpredictable, or breakthrough vaginal bleeding or spotting is common, especially with Depo-Provera, and tends to lessen the longer the injections continue.
• Complete absence of periods (amenorrhea) is common with continued use of Depo-Provera.
• Headache may occur.
• Nervousness, dizziness, or fatigue may occur.
• Breast tenderness or swelling may occur.
• Weight gain may occur.
• Fluid retention (edema) may occur.
• Bloating or abdominal discomfort may occur.
• Nausea may occur.
• Acne or increased facial/body hair (hirsutism) may occur.
• Hair thinning (alopecia) may occur.
• Mood changes, including symptoms similar to premenstrual syndrome, may occur.
• Decreased sex drive may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Depo-Provera can cause loss of bone mineral density that increases with longer use and may not fully recover after stopping, particularly of concern in teenagers and young women.
• Combined estrogen and medroxyprogesterone acetate hormone replacement therapy has been shown in large clinical trials to increase the risk of heart attack, stroke, blood clots (including deep vein thrombosis and pulmonary embolism), and invasive breast cancer.
• Serious blood clots (thromboembolic events), including in the legs, lungs, brain, or eyes, can occur with either the injection or the tablets.
• Severe allergic (anaphylactic) reactions can occur, ranging from rash and hives to a life-threatening reaction.
• Liver problems, including cholestatic jaundice, can occur; treatment should be stopped if jaundice develops.
• Gallbladder disease requiring surgery has been reported more often in women using estrogen-containing hormone therapy.
• Worsening of glucose tolerance, and in some cases new or worsening diabetes, can occur.
• Elevated blood pressure can develop or worsen during treatment.
• Vision problems, including sudden partial or complete loss of vision, double vision, or optic nerve inflammation, can occur and require immediate discontinuation.
• Migraine headaches may develop or worsen; a new-onset severe headache warrants evaluation.
• Combined estrogen plus progestin hormone therapy has been linked to an increased risk of probable dementia in women 65 years of age and older.
• Rare cases of meningioma (a type of brain tumor) have been reported with long-term progestin use, including medroxyprogesterone acetate.
• Depression, including a worsening of pre-existing depression, has been reported.
• Ectopic pregnancy should be considered in a Depo-Provera user who develops severe abdominal pain.
• Seek urgent medical attention for sudden vision changes, sudden severe headache, chest pain, coughing up blood, sudden shortness of breath, leg swelling or pain, or signs of a stroke such as weakness or difficulty speaking.

• Use with caution in women who smoke, especially those over 35, because of an increased risk of serious cardiovascular events.
• Use with caution in women with diabetes or risk factors for diabetes, since medroxyprogesterone acetate can worsen blood sugar and lipid control.
• Use with caution in women with a history of depression, since symptoms can worsen during treatment.
• Use with caution in women with cardiac or kidney dysfunction or asthma, since the drug can cause fluid retention that may worsen these conditions.
• Use with caution in women with a history of migraine, epilepsy, or liver or gallbladder disease.
• Use with caution in women with risk factors for blood clots, including obesity, a personal or family history of blood clots, or prolonged immobility; hormone therapy should generally be stopped several weeks before major surgery.
• Use with caution in women with pre-existing uterine fibroids or endometriosis, since estrogen-containing therapy can cause these conditions to grow or worsen.
• Use with caution in women with a strong family history of breast cancer or an abnormal breast finding, who need closer monitoring.

• Contraindicated in women who are or may be pregnant.
• Contraindicated in women with known or suspected breast cancer or a history of breast cancer, unless the drug is specifically being used to treat breast cancer.
• Contraindicated in women with known or suspected hormone-sensitive cancers, unless the drug is specifically being used to treat that cancer.
• Contraindicated in women with undiagnosed abnormal vaginal or genital bleeding.
• Contraindicated in women with active liver disease or a history of liver tumors.
• Contraindicated in women with a current or past history of blood clots, stroke, heart attack, or other arterial or venous thromboembolic disease.
• Contraindicated in women with vision loss or other eye problems caused by blood vessel disease of the eye.
• Contraindicated in the presence of hypersensitivity to medroxyprogesterone acetate or any ingredient in the formulation.
• Depo-Provera specifically should not be used before a girl's first menstrual period.

• Aminoglutethimide can significantly reduce medroxyprogesterone acetate blood levels, potentially reducing its effectiveness; patients should be warned of this possibility.
• Rifampin and other liver-enzyme-inducing drugs, such as barbiturates, phenytoin, carbamazepine, and phenylbutazone, can speed up the breakdown of medroxyprogesterone acetate and reduce its effectiveness.
• Herbal products such as St. John's wort may also speed up hormone metabolism and reduce effectiveness.
• Medroxyprogesterone acetate can alter the results of certain endocrine and liver function laboratory tests; the laboratory should be told a patient is on this therapy.
• Medroxyprogesterone acetate may affect blood clotting test results, so this should be considered when interpreting coagulation studies.

• Depo-Provera is given by injection, so food has no effect on it.
• The oral tablets can be taken with or without food; taking a dose with or right after a meal increases how much medroxyprogesterone acetate the body absorbs, but this does not require any specific timing around meals, so patients can choose whichever is more convenient.

• Depo-Provera injections are scheduled every 3 months (10 to 13 weeks) by a healthcare professional and are not related to time of day or meals.
• Oral tablets can be taken at any time of day, with or without food; taking them at the same time each day can help with remembering the dose, especially for the 12 to 14 day cyclic regimens used for hormone replacement therapy or menstrual disorders.

• Store Depo-Provera injectable suspension and oral tablets at controlled room temperature, 15°C to 30°C.
• Protect the injectable suspension from freezing, and shake it well immediately before use to ensure a uniform suspension.
• Keep out of the reach and sight of children.

• Medroxyprogesterone acetate is a progestin hormone available as an injection (Depo-Provera) for contraception, and as tablets for hormone replacement therapy, menstrual disorders, or certain cancers.
• If using Depo-Provera for birth control, keep every 3-month injection appointment, since being late can reduce protection against pregnancy and require a backup method or pregnancy test.
• Irregular bleeding or a complete stop in periods is common and expected, especially with the injection.
• Tell your healthcare provider about any personal or family history of blood clots, stroke, heart disease, liver disease, or breast cancer before starting this medicine.
• Seek urgent care for sudden vision changes, severe headache, chest pain, leg swelling, or shortness of breath while using this medicine.
• If you smoke, ask your healthcare provider about the added cardiovascular risks of hormone therapy.