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Logo DEPO-PROVERA™ 150 (Injection)
SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

DEPO-PROVERA™ 150 (Injection)

COMPOSITION:
Each mL contains:
Medroxyprogesterone Acetate         150 mg
Preservatives:        Methylparaben 0,014% m/v
        Propylparaben 0,015% m/v

PHARMACOLOGICAL CLASSIFICATION:
A 21.8.2 Progesterone with or without oestrogens

PHARMACOLOGICAL ACTION:
DEPO-PROVERA has progestational effects. It suppresses the secretion of pituitary gonadotropins which, in turn, prevents follicular maturation, producing long-term anovulation in the reproductive woman. DEPO-PROVERA suppresses the Leydig cell function in the male, i.e. suppresses endogenous testosterone production. A single dose of 50 mg of parenteral medroxyprogesterone acetate has the equivalent effect of 20 mg of parenteral progesterone given daily for 10 days in producing an optimal secretory change in an oestrogen-primed endometrium. This steroid also produces typical progestational changes in the cervical mucus (inhibits ferning), increases the viscosity of cervical mucus, thereby increasing the difficulty of sperm penetration; and increases the intermediate cell count in the maturation index of the vaginal epithelium.
The anti-cancer activity of DEPO-PROVERA at high doses is unexplained and may be dependent on its effect on the hypothalamic/pituitary/gonadal axis, oestrogen receptors or the metabolism of steroids at the tissue level. At the high dose levels used in the treatment of certain cancers, corticoid-like activity may be manifested.
PHARMACOKINETICS:
Parenteral medroxyprogesterone acetate is a long-acting progestational steroid. The 100 mg/mL formulation reaches half its initial concentration in about 27 days. Its long duration of action results from its slow absorption from the injection site.
The principal metabolite of medroxyprogesterone acetate that has been identified is a 6alpha-methyl-6beta,17alpha,21-trihydroxy-4-pregnene-3,20-dione-17-acetate, which is excreted in the urine.

INDICATIONS:
1. Endometriosis
2. Contraception (ovulation suppression)
3. Endometrial Cancer: As adjunctive and/or palliative therapy in inoperable, recurrent or metastatic endometrial carcinoma.
4. Renal Cancer: As adjunctive and/or palliative therapy in recurrent and/or metastatic adenocarcinoma of the kidney.

CONTRA-INDICATIONS:
1. Known sensitivity to medroxyprogesterone acetate.
2. Undiagnosed vaginal bleeding.
3. Undiagnosed urinary tract bleeding.
4. Undiagnosed breast pathology.
5. Thrombophlebitis, or a history of thrombophlebitis.

WARNINGS:
1. Any patient who develops signs and/or symptoms consistent with a thromboembolic disorder while undergoing therapy with DEPO-PROVERA should have her status and need for treatment carefully assessed before continuing therapy.
2. In any patient who develops an acute impairment of vision, proptosis, diplopia, or migraine headache, DEPO-PROVERA should be discontinued and the patient carefully evaluated ophthalmologically to exclude the presence of papilloedema or retinal vascular lesions before continuing medication.
3. The use of progestational agents during pregnancy is not recommended. Progestational agents are not recommended as a diagnostic test for pregnancy.
4. Following repeated injections, amenorrhoea and anovulation may persist for periods up to 18 months and, in rare instances, for longer periods.
5. Anaphylactic and anaphylactoid reactions have occasionally been reported in patients treated with DEPO-PROVERA.
6. Clinical suppression of adrenocortical function has not been observed at the dose levels employed for contraception. However, at very high doses (500 mg daily or more) used in the treatment of certain cancers, corticoid-like activity has been reported.

DOSAGE AND DIRECTIONS FOR USE:
The sterile aqueous suspension of DEPO-PROVERA should be vigorously shaken just before use to ensure that the dose being administered represents a uniform suspension of DEPO-PROVERA.
ENDOMETRIOSIS:
The recommended dose of DEPO-PROVERA in this condition is 50 mg weekly or 100 mg every 2 weeks intramuscularly for at least 6 months. It should be noted that return of ovulation may be delayed following this therapy due to the depot properties of the medicine (See WARNINGS).
CONTRACEPTION:
The recommended dose is 150 mg DEPO-PROVERA every three months administered by deep intramuscular injection. To increase assurance that the patient is not pregnant at the time of the first administration, it is recommended that this injection be given during the first 5 days after the onset of a normal menstrual period or before the sixth week postpartum.
ENDOMETRIAL AND RENAL CARCINOMA:
Doses of 400 mg to 1000 mg of DEPO-PROVERA intramuscularly 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.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
PRECAUTIONS:
1. It is recommended that physicians or others directly responsible for these patients advise them at the beginning of treatment that their menstrual cycle may be disrupted, that irregular and unpredictable bleeding or spotting are produced, but that this usually decreases to the point of amenorrhoea as treatment with DEPO-PROVERA continues, without other therapy being required.
  Restoration of normal menstrual cycling may take from 5 to 28 months after the last injection of DEPO-PROVERA.
  In cases of abnormal bleeding, appropriate investigation should first be instituted to rule out the possibility of organic pathology before continuing treatment with DEPO-PROVERA.
2. All patients should be physically examined before treatment with special reference to breast and pelvic organs as well as a Papanicolaou smear.
3. In cases of breakthrough bleeding, as in all cases of irregular bleeding per vaginum, organic causes should be excluded. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures are indicated.
4. Patients who have a history of mental depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree. Some patients may complain of premenstrual like depression while on DEPO-PROVERA therapy.
5. A decrease in glucose tolerance has been observed in patients on progestogens. The mechanisms of this decrease is obscure. For this reason diabetic patients should be carefully observed while receiving progestogen therapy.
6. The use of DEPO-PROVERA may mask the onset of the climacteric.
7. Certain endocrine and possibly liver function tests may be affected by treatment with DEPO-PROVERA. Therefore, if such tests are abnormal in a patient taking DEPO-PROVERA, it is recommended that they be repeated after the drug has been withdrawn.
8. Because of the prolonged action and the resulting difficulty in predicting the time of withdrawal bleeding following injection, DEPO-PROVERA is not recommended for treatment of secondary amenorrhoea or dysfunctional uterine bleeding.
9. Weight gain may be associated with use of DEPO-PROVERA.
10. The pathologist should be advised of progestogen therapy when relevant specimens are submitted.
11. The following laboratory tests may be affected by the use of DEPO-PROVERA:
 a. Gonadotropin levels
 b. Plasma progesterone levels
 c. Urinary pregnanediol levels
 d. Plasma testosterone levels (in the male)
 e. Plasma oestrogen levels (in the female)
 f. Plasma cortisol levels
 g. Glucose tolerance test
 h. Metyrapone test
12. Hypercalcaemia
13. Liver disease or dysfunction
14. Pulmonary embolism.
15. Because progestogens may cause fluid retention, conditions which might be influenced by this factor, such as epilepsy, migraine, asthma, cardiac or renal dysfunction, require careful observation.
16. The high dose of DEPO-PROVERA used in the treatment of cancer patients may, in some cases produce Cushingoid symptoms, e.g. moon faces, fluid retention, glucose intolerance, and blood pressure elevation.
17. Aminoglutethimide administered concomitantly with DEPO-PROVERA may significantly depress the bioavailability of DEPO-PROVERA.

SIDE-EFFECTS:
The following events have been associated with the use of progestogens:
1. Anaphylaxis and anaphylactoid-like reactions.
2. Thromboembolic disease: thrombophlebitis and pulmonary embolism.
3. Central nervous system: nervousness, insomnia, somnolence, fatigue, depression, dizziness and headache.
4. Skin and mucous membranes: urticaria, pruritus, rash, acne, hirsutism, and alopecia.
5. Gastro-intestinal: nausea, abdominal discomfort, diarrhoea.
6. Breast: tenderness and galactorrhoea.
7. Cervix: changes in erosion and secretions.
8. Miscellaneous: pyrexia, change in weight and moon face.
9. Local reactions: pain, residual lumps and change in skin colour at the injection site.
10. Amenorrhoea, prolonged irregular bleeding, loss of libido, dysmenorrhoea, hot flushes, acne.
11. Increased sweating, muscle cramps, virilisation, feminisation, impotence.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Nausea, vomiting, somnolence, lower abdominal discomfort, insomnia, fullness and tenderness of the breasts, headache have been attributed to therapeutic doses. Treatment should be symptomatic and supportive.

IDENTIFICATION:
White injectable suspension.

PRESENTATION:
DEPO-PROVERA 150 is available in 1 mL vials.

STORAGE INSTRUCTIONS:
Store at room temperature (15°C - 30°C).
Keep out of reach of children.

REGISTRATION NUMBER:
DEPO-PROVERA 150: E/21.8.2/114

NAME AND ADDRESS OF APPLICANT:
Pharmacia South Africa (Pty) Limited
Alphen West G
George Street
Midrand 1685

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
25-01-93

™ = TRADEMARK

New addition to this site: February 2005
Source: Pharmaceutical Industry

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