Depo-Provera ® medroxyprogesterone acetate injectable suspension, USP

DEPO-PROVERA Sterile Aqueous Suspension contains medroxyprogesterone acetate, which is a derivative of progesterone and is active by the parenteral and oral routes of administration. It is a white to off-white, odorless crystalline powder, stable in air, melting between 200° and 210° C. It is freely soluble in chloroform, soluble in acetone and in dioxane, sparingly soluble in alcohol and methanol, slightly soluble in ether and insoluble in water.

The chemical name for medroxyprogesterone acetate is Pregn-4-ene-3,20-dione, 17-(acetyloxy)-6-methyl-, (6α)-. The structural formula is:

DEPO-PROVERA for intramuscular injection is available as 400 mg/mL medroxyprogesterone acetate. Each mL of the 400 mg/mL suspension contains:

Medroxyprogesterone acetate .............400 mg
Polyethylene glycol 3350.....................20.3 mg
Sodium sulfate anhydrous ......................11 mg
  with
Myristyl-gamma-picolinium
  chloride ............................................1.69 mg
  added as preservative

When necessary, pH was adjusted with sodium hydroxide and/or hydrochloric acid.

Medroxyprogesterone acetate, administered parenterally in the recommended doses to women with adequate endogenous estrogen, transforms proliferative endometrium into secretory endometrium.

Medroxyprogesterone acetate inhibits (in the usual dose range) the secretion of pituitary gonadotropin which, in turn, prevents follicular maturation and ovulation.

Because of its prolonged action and the resulting difficulty in predicting the time of withdrawal bleeding following injection, medroxyprogesterone acetate is not recommended in secondary amenorrhea or dysfunctional uterine bleeding. In these conditions oral therapy is recommended.

Adjunctive therapy and palliative treatment of inoperable, recurrent, and metastatic endometrial or renal carcinoma.

1. Known or suspected pregnancy or as a diagnostic test for pregnancy
2. Undiagnosed vaginal bleeding
3. Known or suspected malignancy of breast
4. Active thrombophlebitis, or current or past history of thromboembolic disorders, or cerebral vascular disease
5. Liver dysfunction or disease
6. Known sensitivity to DEPO-PROVERA (medroxyprogesterone acetate or any of its other ingredients).

–(See WARNINGS for possible adverse effects on the fetus)
–breakthrough bleeding
–spotting
–change in menstrual flow
–amenorrhea
–headache
–nervousness
–dizziness
–edema
–change in weight (increase or decrease)
–changes in cervical erosion and cervical secretions
–cholestatic jaundice, including neonatal jaundice
–breast tenderness and galactorrhea
–skin sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash
–acne, alopecia and hirsutism
–rash (allergic) with and without pruritis
–anaphylactoid reactions and anaphylaxis
–mental depression
–pyrexia
–fatigue
–insomnia
–nausea
–somnolence

In a few instances there have been undesirable sequelae at the site of injection, such as residual lump, change in color of skin, or sterile abscess.

A statistically significant association has been demonstrated between use of estrogen-progestin combination drugs and pulmonary embolism and cerebral thrombosis and embolism. For this reason patients on progestin therapy should be carefully observed. There is also evidence suggestive of an association with neuro-ocular lesions, e.g. retinal thrombosis and optic neuritis.

The following adverse reactions have been observed in patients receiving estrogen-progestin combination drugs:

–rise in blood pressure in susceptible individuals
–premenstrual syndrome
–changes in libido
–changes in appetite
–cystitis-like syndrome
–headache
–nervousness
–fatigue
–backache
–hirsutism
–loss of scalp hair
–erythema multiforma
–erythema nodosum
–hemorrhagic eruption
–itching
–dizziness

The following laboratory results may be altered by the use of estrogen-progestin combination drugs:

–increased sulfobromophthalein retention and other hepatic function tests
–coagulation tests: increase in prothrombin factors VII, VIII, IX, and X
–metyrapone test
–pregnanediol determinations
–thyroid function: increase in PBI, and butanol extractable protein bound iodine and decrease in T₃ uptake values

The suspension is intended for intramuscular administration only.

Endometrial or renal carcinoma— doses of 400 mg to 1000 mg of DEPO-PROVERA Sterile Aqueous Suspension per week are recommended initially. If improvement is noted within a few weeks or months and the disease appears stabilized, it may be possible to maintain improvement with as little as 400 mg per month. Medroxyprogesterone acetate is not recommended as primary therapy, but as adjunctive and palliative treatment in advanced inoperable cases including those with recurrent or metastatic disease.

When multi-dose vials are used, special care to prevent contamination of the contents is essential (See WARNINGS).

DEPO-PROVERA Sterile Aqueous Suspension is available as 400 mg/mL in 2.5 mL vials   NDC 54868-3348-1.

The text of the patient insert for progestational drugs is set forth below.

DEPO-PROVERA Sterile Aqueous Suspension is a progestational drug. The information below is required by the U.S. Food and Drug Administration to be provided to all patients taking such products. This information relates only to the risk to the unborn child associated with use of progestational drugs during pregnancy. For further information on the use, side effects, and other risks associated with this product, ask your doctor.

WARNING FOR WOMEN

Progesterone or progesterone-like drugs have been used to prevent miscarriage in the first few months of pregnancy. No adequate evidence is available to show that they are effective for this purpose. Furthermore, most cases of early miscarriage are due to causes which could not be helped by these drugs.

There is an increased risk of minor birth defects in children whose mothers take this drug during the first 4 months of pregnancy. Several reports suggest an association between mothers who take these drugs in the first trimester of pregnancy and genital abnormalities in male and female babies. The risk to the male baby is the possibility of being born with a condition in which the opening of the penis is on the underside rather than the tip of the penis (hypospadias). Hypospadias occurs in about 5 to 8 per 1000 male births and is about doubled with exposure to these drugs. There is not enough information to quantify the risk to exposed female fetuses, but enlargement of the clitoris and fusion of the labia may occur, although rarely.

Therefore, since drugs of this type may induce mild masculinization of the external genitalia of the female fetus, as well as hypospadias in the male fetus, it is wise to avoid using the drug during the first trimester of pregnancy.

These drugs have been used as a test for pregnancy but such use is no longer considered safe because of possible damage to a developing baby. Also, more rapid methods for testing for pregnancy are now available.

If you take DEPO-PROVERA Sterile Aqueous Suspension and later find you were pregnant when you took it, be sure to discuss this with your doctor as soon as possible.

Rx only

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LAB-0143-3.0
May 2006

2.5 mL Vial
Rx only

Depo-Provera^®
medroxyprogesterone acetate
injectable suspension, USP

400 mg/mL