Prometrium (Progesterone Oral) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug/Laboratory Test Interactions

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 determination.
• Thyroid function: increase in PBI, and butanol extractable protein bound iodine and decrease in T3 uptake values.

Fasting and 2-hour plasma insulin and glucose levels following an oral glucose tolerance test (OGTT) and fibrinogen levels were measured in patients receiving PROMETRIUM Capsules at a dose of 200 mg/day for 12 days per 28-day cycle in combination with conjugated estrogens 0.625 mg/day (n=120). Table 7 summarizes these data. Plasma insulin levels 2 hours post-OGTT were decreased from baseline. The fasting plasma glucose and fasting plasma insulin levels were also decreased from baseline. Glucose levels 2 hours post-OGTT were increased slightly. There was no effect on fibrinogen levels.

For information on changes in lipid profile, see the Clinical Studies subsection, Table 5.

TABLE 7 Mean Changes from Baseline in Insulin and Glucose Levels After 36 Months of Treatment

Parameter		Treatment Group Mean (Mean % Change)
		Conjugated Estrogens 0.625 mg + PROMETRIUM Capsules 200 mg (cyclical) a		Conjugated Estrogens 0.625 mg (only)		Placebo
		n= 173 to 176b		n=170 to 172b		n=171
		Mean Change	Mean % Change	Mean Change	Mean % Change	Mean Change	Mean % Change
a There are no significant changes (p<0.05) from conjugated estrogens values.
b Number of subjects (n) varies by parameter.
OGTT    Insulin     (pmol/L)	fasting 2 hours	-2.2 -45.2	-6.2 -14.5	-1.1 -23.9	-3.2 -7.9	5.1 -29.7	14.2 -9.1
Glucose     (mg/dL)	fasting 2 hours	-3.0 3.6	-2.9 5.2	-2.7 5.0	-2.7 7.8	-1.0 2.1	-0.9 3.9

OVERDOSAGE

No studies on overdosage have been conducted in humans. In the case of overdosage, PROMETRIUM Capsules should be discontinued and the patient should be treated symptomatically.

CONTRAINDICATIONS

PROMETRIUM Capsules should not be used in women with any of the following conditions:

1. PROMETRIUM Capsules should not be used in patients with known hypersensitivity to its ingredients. PROMETRIUM Capsules contain peanut oil and should never be used by patients allergic to peanuts.
2. Undiagnosed abnormal genital bleeding.
3. Known, suspected, or history of cancer of the breast.
4. Active deep vein thrombosis, pulmonary embolism or history of these conditions.
5. Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction).
6. Liver dysfunction or disease.
7. Known or suspected pregnancy. There is no indication for PROMETRIUM Capsules in pregnancy. There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins from oral contraceptives inadvertently during early pregnancy. (See PRECAUTIONS.)