SIDE EFFECTS

In five clinical studies of depo-subQ provera 104 involving 2,325 women (282 treated for up to 6 months, 1,780 treated for up to 1 year and 263 treated for up to 2 years), 9% of women discontinued treatment for adverse reactions. Among these 212 women, the most common reasons for discontinuation were:

· Uterine bleeding irregularities (35%, n=75)

· Increased weight (18%, n=39)

· Decreased libido (11%, n=23)

· Acne (10%, n=21)

· Injection site reactions (6%, n=12)

Adverse reactions reported by 5% or more of all women in these clinical trials included:

· Headache (9%)

· Intermenstrual bleeding (7%)

· Increased weight (6%)

· Amenorrhea (6%)

· Injection site reactions (5%)

Adverse reactions reported by 1% to <5% of all women in these clinical trials included:

General disorders: fatigue, injection site pain

Gastrointestinal disorders: abdominal distention, abdominal pain, diarrhea, nausea

Infections: bronchitis, influenza, nasopharyngitis, pharyngitis, sinusitis, upper respiratory tract infection, urinary tract infection, vaginal candidiasis, vaginitis, vaginitis bacterial

Investigations: abnormal cervix smear

Musculoskeletal, connective tissue, and bone disorders: arthralgia, back pain, limb pain

Nervous system disorders: dizziness, insomnia

Psychiatric disorders: anxiety, depression, irritability, decreased libido

Reproductive system and breast disorders: breast pain, breast tenderness, menometrorrhagia, menorrhagia, menstruation irregular, uterine hemorrhage, vaginal hemorrhage

Skin disorders: acne

Vascular disorders: hot flushes

Postmarketing Experience

There have been rare cases of osteoporosis including osteoporotic fractures reported postmarketing in patients taking DEPO-PROVERA Contraceptive Injection. In addition, infrequent voluntary reports of anaphylaxis and anaphylactoid reaction have been received associated with use of Depo-Provera CI (150 mg).

The following additional reactions have been reported with Depo-Provera Contraceptive Injection and may occur with use of depo-subQ provera 104:

General disorders: asthenia, axillary swelling, chills, chest pain, fever, excessive thirst

Blood and lymphatic system disorders: anemia, blood dyscrasia

Cardiac disorders: tachycardia

Gastrointestinal disorders: gastrointestinal disturbances, rectal bleeding

Hepato-biliary disorders: jaundice

Immune system disorders: allergic reaction

Infections: genitourinary infections

Investigations: decreased glucose tolerance

Musculoskeletal, connective tissue, and bone disorders: loss of bone mineral density, scleroderma

Neoplasms: breast cancer, cervical cancer

Nervous system disorders: convulsions, facial palsy, fainting, paralysis, paresthesia, somnolence

Psychiatric disorders: increased libido, nervousness

Reproductive system and breast disorders: breast lumps, galactorrhea, nipple discharge or bleeding, oligomenorrhea, prevention of lactation, prolonged anovulation, unexpected pregnancy, uterine hyperplasia, vaginal cyst

Respiratory disorders: asthma, dyspnea, hoarseness

Skin disorders: angioedema, dry skin, increased body odor, melasma, pruritus, urticaria

Vascular disorders: deep vein thrombosis, pulmonary embolus, thrombophlebitis

DRUG INTERACTIONS

No drug-drug interaction studies have been conducted with depo-subQ provera 104.

Aminoglutethimide administered concomitantly with depo-subQ provera 104 may significantly decrease the serum concentrations of MPA.

Laboratory Tests

The pathologist should be advised of progestin therapy when relevant specimens are submitted. The physician should be informed that certain endocrine and liver function tests, and blood components may be affected by progestin therapy:

(a) Plasma and urinary steroid levels are decreased (e.g., progesterone, estradiol, pregnanediol, testosterone, cortisol).

(b) Plasma and urinary gonadotropin levels are decreased (e.g., LH, FSH).

(c) SHBG concentrations are decreased.

(d) T3-uptake values may decrease.

(e) There may be small changes in coagulation factors.

(f) Sulfobromophthalein and other liver function test values may be increased slightly.

(g) There may be small changes in lipid profiles.

---