Medroxyprogesterone Side Effects

Brand Names: Provera, Depo-Provera, depo-subQ provera 104, Depo-SubQ Provera 104

Please note - some side effects for Medroxyprogesterone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Medroxyprogesterone - for the consumer

Medroxyprogesterone

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Medroxyprogesterone:

Acne; changes in menstrual flow, including breakthrough bleeding, spotting, or missed periods; dizziness; drowsiness; fever; headache; hot flashes; nausea; nervousness; pain; rash; sleeplessness; stomach pain; weakness; weight gain or loss.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; depression; lumps in the breast or under the armpits; partial or complete loss of vision or changes in vision; shortness of breath; slurred speech; sudden loss of coordination; sudden or severe headache; swelling of fingers or ankles; tenderness, pain, or swelling of the calf; weakness, numbness, or pain in the arms or legs; yellowing of the skin or eyes.

Medroxyprogesterone Injectable Suspension

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Medroxyprogesterone Injectable Suspension:

Acne; dizziness; drowsiness; fever; headache; hot flashes; nausea; nervousness; pain, redness, and swelling at injection site; sleeplessness; weakness.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood clots; changes in menstrual flow, including breakthrough bleeding, spotting, or missed periods; chest pain; mental or mood changes; partial or complete loss of vision or changes in vision; severe dizziness or fainting; severe stomach pain; shortness of breath; slurred speech; sudden loss of coordination; sudden or severe headache or vomiting; swelling of fingers or ankles; unusual weight gain or loss; weakness, numbness, or pain in the arms or legs; yellowing of the skin or eyes.

Medroxyprogesterone Injectable Suspension (subcutaneous)

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Medroxyprogesterone Injectable Suspension (subcutaneous):

Acne; changes in menstrual flow, including breakthrough bleeding, spotting, or missed periods; dizziness; drowsiness; fever; headache; hot flashes; nausea; nervousness; pain; rash; sleeplessness; stomach pain; weakness; weight gain or loss.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood clots; chest pain; depression; partial or complete loss of vision or changes in vision; shortness of breath; slurred speech; sudden loss of coordination; sudden or severe headache; swelling of fingers or ankles; weakness, numbness, or pain in the arms or legs; yellowing of the skin or eyes.

For the professional

Medroxyprogesterone

See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reactions have been reported in women taking progestins, including Medroxyprogesterone acetate tablets, without concomitant estrogens treatment:

1. Genitourinary System

Abnormal uterine bleeding (irregular, increase, decrease), change in menstrual flow, breakthrough bleeding, spotting, amenorrhea, changes in cervical erosion and cervical secretions.

2. Breasts

Breast tenderness, mastodynia or galactorrhea has been reported.

3. Cardiovascular

Thromboembolic disorders including thrombophlebitis and pulmonary embolism have been reported.

4. Gastrointestinal

Nausea, cholestatic jaundice.

5. Skin

Sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash have occurred. Acne, alopecia and hirsutism have been reported.

6. Eyes

Neuro-ocular lesions, for example, retinal thrombosis, and optic neuritis.

7. Central Nervous System

Mental depression, insomnia, somnolence, dizziness, headache, nervousness.

8. Miscellaneous

Hypersensitivity reactions (for example, anaphylaxis and anaphylactoid reactions, angioedema), rash (allergic) with and without pruritus, change in weight (increase or decrease), pyrexia, edema/fluid retention, fatigue, decreased glucose tolerance.

The following additional adverse reactions have been reported with estrogen and/or progestin therapy.

1. Genitourinary System

Abnormal uterine bleeding/spotting, or flow; breakthrough bleeding; spotting; dysmenorrheal/pelvic pain; increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer.

2. Breasts

Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

3. Cardiovascular

Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction; stroke; increase in blood pressure.

4. Gastrointestinal

Nausea, vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence of gallbladder disease; pancreatitis; enlargement of hepatic hemangiomas.

5. Skin

Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism; pruritus, rash.

6. Eyes

Retinal vascular thrombosis, intolerance to contact lenses.

7. Central Nervous System

Headache; migraine; dizziness; mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation of epilepsy, dementia.

8. Miscellaneous

Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaplylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.

By body system

Endocrine side effects

Cushing's syndrome is uncommon and appears to be associated with a long duration of therapy and moderate to high doses of medroxyprogesterone. Doses used for hormonal replacement therapy and for long-term contraception are not associated with Cushing's syndrome.

Medroxyprogesterone has mild glucocorticoid activity. In cases of medroxyprogesterone-induced Cushing's syndrome, low cortisol and adrenocorticotrophic hormone (ACTH) levels with a reduced pituitary-adrenal reserve have been documented. Acute adrenal insufficiency may ensue following withdrawal of medroxyprogesterone.

Endocrine side effects have included breast tenderness, galactorrhea with or without hyperprolactinemia, prevention of lactation, hirsutism, and Cushing's syndrome.

Metabolic side effects

Weight gain is more frequently encountered than weight loss during medroxyprogesterone therapy. In women using intramuscular medroxyprogesterone for contraception, the mean weight gain after one year of therapy is 2.5 kg. After two, four, and six years, patients gain a mean of 3.7, 6.3, and 7.5 kg, respectively.

Data regarding the effect of medroxyprogesterone on lipid profiles have been conflicting. Some studies report possible negative effects on lipid profiles while others have documented a reduction in total and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol levels.

Metabolic side effects have included weight changes (increases and decreases), glucose intolerance, and changes in serum cholesterol concentrations.

Genitourinary side effects

Genitourinary side effects have been relatively common and included primarily menstrual changes such as amenorrhea, irregular bleeding, spotting, and heavy bleeding. Vaginal cysts, dyspareunia, and changes in cervical erosion and secretions have also been reported. While endometrial hyperplasia has been reported, medroxyprogesterone tended to have a favorable effect on the endometrium. Changes in libido and anorgasmia have also occurred.

Withdrawal bleeding is a common complaint among postmenopausal women receiving sequential (10 to 14 days per cycle) medroxyprogesterone therapy. In postmenopausal women receiving continuous medroxyprogesterone and estrogen therapy, 75% or more are amenorrheic by one year of therapy.

In women receiving medroxyprogesterone for contraception, more than 50% are amenorrheic by one year of therapy.

In women on estrogen replacement therapy, the addition of medroxyprogesterone or other progestin for at least 10 to 14 days of each cycle significantly reduces the risk of endometrial hyperplasia and, thus, the risk of endometrial carcinoma. Low-dose continuous medroxyprogesterone therapy also reduces the risk of endometrial hyperplasia associated with the use of unopposed estrogen.

In patients in whom abnormal bleeding persists or is severe, the possibility of an organic pathology should be considered and ruled out.

Oncologic side effects

Oncologic side effects possibly associated with medroxyprogesterone have been the topic of considerable debate. Data from some animal studies suggested an increased risk of breast and endometrial cancer. The current consensus is that the carcinogenic potential of medroxyprogesterone is no greater than that of other hormonal contraceptives.

A significant increase in the incidence of breast cancer in beagle dogs in addition to an apparent increase in the incidence of endometrial cancer in rhesus monkeys was noted in early animal carcinogenicity studies.

International long-term studies designed to assess the risk of medroxyprogesterone in humans, sponsored by the World Health Organization, failed to find an increased risk of cancer in users of medroxyprogesterone. Overall, there was no significant increase in the risk of breast cancer, cervical cancer, or epithelial ovarian cancer. Data from these studies did, however, support a significant (8-fold) reduction in the incidence of endometrial cancer among medroxyprogesterone users.

A study from New Zealand has suggested that women taking depot medroxyprogesterone acetate may be at higher risk for breast cancer during the first 5 years, but therapy for more than 5 years confers no increased risk of breast cancer.

Cardiovascular side effects

Cardiovascular side effects have included thromboembolic disorders such as thrombophlebitis, deep vein thrombosis, pulmonary embolism, cerebrovascular accidents, and retinal thrombosis. In addition, edema, hypertension, tachycardia, and syncope have been noted.

The majority of cases of thromboembolic disease during hormonal therapy have been attributed to estrogens and not to progestins. However, it has been demonstrated that medroxyprogesterone, at least at high doses, can produce a hypercoagulable state. Whether or not this contributes to the development of thrombotic events remains unknown.

Because medroxyprogesterone can cause edema, it should be used cautiously in patients with underlying disease (like migraine headaches, asthma, heart disease, renal dysfunction, or seizure disorders) which may be exacerbated by edema or fluid retention.

Musculoskeletal side effects

Musculoskeletal side effects have included changes in bone mineral density and leg cramps.

Reductions in bone mineral density and osteoporosis have been attributed to medroxyprogesterone. Such effects are probably due to medroxyprogesterone-induced estrogen deficiency.

Conflicting data concerning the effects of medroxyprogesterone on bone mineral density have been reported.

In one study, women 25 to 51 years of age receiving medroxyprogesterone 150 mg intramuscularly every three months for five or more years for long-term contraception had a reduction in bone mineral density compared with premenopausal controls. However, bone mineral density in the treatment group was still significantly greater than that observed in postmenopausal controls.

A study of 200 women who received medroxyprogesterone 150 mg intramuscularly every three months for a median duration of 12 years (range 2 to 26 years) reported that bone density was significantly reduced in medroxyprogesterone users. However, bone mineral density in women starting depot medroxyprogesterone after the age of 20 years and using it for 15 or fewer years was greater than the remainder of the cohort.

A study to determine the potential for postmenopausal fracture due to residual effects of depot medroxyprogesterone in former users reported the risk to be small and unlikely to have substantial impact in postmenopausal women. No significant differences in bone density were found, however, women who had used depot medroxyprogesterone for >2 yeas had a trend toward lower bone densities.

Bone density in 185 women receiving long-term depot medroxyprogesterone for a mean of 5 years (range of 1-16 years) was only minimally below the normal population despite decreased estrogen levels.

Dermatologic side effects

Dermatologic side effects have included acne, reduced hair growth, alopecia, melasma, chloasma, rash, excessive sweating, dry skin, scleroderma, erythema multiforme, and erythema nodosum.

Nervous system side effects

Nervous system side effects have included headache, asthenia, dizziness, depression, somnolence, and insomnia. Paresthesias, convulsions, and facial palsy have been reported although causality is unknown.

Gastrointestinal side effects

Gastrointestinal side effects have occurred in up to 5% of patients and included nausea, abdominal pain, bloating, and anorexia.

Hepatic side effects

Hepatic side effects have included elevations in liver function tests, jaundice, cholestatic jaundice, and cholelithiasis.

Hematologic side effects

Hematologic side effects have included rare reports of hypercoagulability with and without thromboembolic activity.

Hypersensitivity side effects

Hypersensitivity side effects have been uncommon but have included urticaria, angioneurotic edema, and anaphylaxis or anaphylactoid reactions.

Local side effects

Local side effects associated with intramuscular administration of medroxyprogesterone have included pain, change in skin color, residual lumps, and sterile abscesses at the injection site.

Ocular side effects

Ocular side effects have included visual disturbances such as sudden loss of vision (partial or complete), sudden onset of proptosis, diplopia, or migraine have been reported. Therapy should be withdrawn in the presence of papilledema or retinal vascular lesions.

Psychiatric side effects

Psychiatric side effects have included dysphoric symptoms similar to premenstrual syndrome (PMS).

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