Action And Clinical Pharmacology: Micronized progesterone is an oral dosage form of the naturally occurring steroid; it is chemically identical to progesterone of ovarian origin. Micronization of progesterone improves its absorption by the digestive tract by increasing the surface area in contact between the steroid and the mucous membrane. Pharmacokinetic studies indicate that plasma progesterone levels within the luteal range are achieved with peak levels at 2 to 4 hours following administration of progesterone (see Table I).
Progesterone is metabolized primarily by the liver and is excreted mainly in the urine. Patients with illness related to the liver and/or kidneys should be monitored closely.
Progesterone exerts significant antiproliferative effects on the endometrium and suppresses endometrial mitotic activity through suppression of nuclear estradiol receptors, reduction of epithelial and stromal DNA synthesis and induction of 17b-estradiol dehydrogenase and isocitric dehydrogenase.
Indications And Clinical Uses: In women with intact uteruses as an adjunct to postmenopausal estrogen replacement therapy to significantly reduce the risk of endometrial hyperplasia and carcinoma.
Contra-Indications: Severe liver disease such as cholestatic jaundice or hepatitis or a history of severe liver disease, hepatic cell tumors, Rotor syndrome or Dubin-Johnson syndrome.
Unexplained abnormal vaginal bleeding.
Known or suspected breast malignancy or pathology.
Known or suspected progesterone-dependent neoplasia.
Conditions or a history of conditions of rare occurrence which have occurred or have worsened with pregnancy or the use of sex steroids i.e. herpes gestationis, jaundice of pregnancy, otosclerosis, severe pruritus, or porphyria.
Cerebral apoplexy or thrombophlebitis.
Known sensitivity to progesterone capsules or any of its individual components. Prometrium contains peanut oil and should never be used by patients allergic to peanuts.
Manufacturers’ Warnings In Clinical States: Treatment should be discontinued if the results of liver function tests become abnormal or if cholestatic jaundice appears.
Several published epidemiological studies have documented an association between a modest increase in the risk of developing breast cancer and the use of hormone replacement therapy in menopause when given for periods exceeding 10 years. Information is still lacking to show whether the risks of combination estrogen-progestin therapy differ from those of estrogen used alone.
Instruction for breast self-examination should be given to all women.
Precautions: Occupational Hazards: Transient and occasional somnolence or dizziness may occur in some patients 1 to 4 hours after ingestion of progesterone, particularly if administered with food. Activities requiring concentration, good attention, good coordination or reflex action should be avoided when the above-mentioned neurological symptoms occur. In most cases, these problems can be avoided by taking the capsules at the recommended times. The 200 mg dosage should be taken at bedtime. The 300 mg dosage should be divided into 2 doses, 100 mg 2 hours after breakfast and 200 mg at bedtime.
Chloasma is occasionally seen during the use of estrogen and/or progestin-containing preparations, especially in women with a history of chloasma gravidarum. In women with a tendency to chloasma, exposure of the skin to natural or artificial sunlight may induce or aggravate the condition.
There are no indications of an increased cardiovascular risk associated with natural progesterone use. However, a slightly increased risk of these disorders has been reported with estrogen/progestin-containing oral contraceptive preparations, therefore patients with cardiovascular disorders (or a history of this condition) should be kept under close medical supervision.
Pregnancy: If the patient is exposed to progesterone during the first 4 months of pregnancy or if she becomes pregnant while taking this drug she should be appraised of the potential risks to the fetus.
Lactation: Detectable amounts of progesterone have been identified in the milk of mothers receiving progesterone. The possible effects of progesterone on the nursing infant have not been determined.
Abnormal uterine bleeding due to its prolongation, irregularity or heaviness, occurring during therapy, should prompt diagnostic measures such as endometrial biopsy, hysteroscopy or uterine curettage to rule out the possibility of uterine pathology.
The pretreatment physical examination, prior to initiation of hormone replacement therapy, should include blood pressure determination, breast, abdomen and pelvic organ examination as well as Papanicolaou smear. This examination should exclude the presence of genital or breast neoplasia before considering hormone replacement therapy.
Pathologists should be advised of progestin therapy when relevant specimens are submitted.
Adverse Reactions: Adverse events which could be considered to be possibly associated with progesterone therapy are: breakthrough bleeding, spotting, and menstrual irregularity.
Under the recommended conditions of use (200 mg h.s.), dizziness, somnolence, cramps or nausea have been reported occasionally.
Fatigue, headache, vertigo, lightheadedness or migraine have been reported rarely.
Breast: Breast tenderness may occur with the use of progesterone.
Other adverse events which are generally attributed to synthetic progestins and which may possibly occur during progesterone treatment include: chloasma, pruritus, jaundice, rash, fluid retention, mental depression and thrombotic disorders.
The following laboratory results may be altered by the use of progesterone: levels of gonadotropin, plasma progesterone and urinary pregnanediol.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: The toxicity of progesterone is very low. Symptoms that may possibly occur are: nausea, vomiting, somnolence and dizziness. No specific antidote is available. If necessary, symptomatic treatment can be given.
Dosage And Administration: Hormone Replacement Therapy: In general, the dosage is 200 mg daily for the last 14 days of estrogen treatment per cycle (i.e., from day 8 to day 21 for a 28 day cycle, and from day 12 to day 25 for a 30 day cycle). Estrogens should be administered daily at the lowest effective dose. Patients being treated with high dosages of estrogen (equivalent to 1.25 mg conjugated estrogens or higher) should be administered 300 mg daily for the last 12 to 14 days of estrogen treatment.
The 200 mg daily dosage should be taken at bedtime. Patients receiving 300 mg daily should take 1 capsule (100 mg) in the morning and 2 capsules (200 mg) at bedtime. The morning dose should be taken 2 hours after breakfast.
If a patient is treated with 200 mg daily (total dose at bedtime) and she forgets to take this dose, she should take an extra dose of 1 capsule (100 mg) the following morning and continue taking the rest of the capsules as prescribed. If a patient is treated with 300 mg daily, and she forgets to take a morning or evening dose, she should not take the missed dose.
The dosage of progesterone should be proportional to the dosage of estrogen. With adequate adjustment of the dosage of progesterone, patients should experience either regular withdrawal uterine bleeding or cessation of bleeding (amenorrhea).
Abnormal uterine bleeding due to its prolongation, irregularity or heaviness, in any patient receiving hormone replacement therapy, requires institution of prompt diagnostic measures such as endometrial biopsy, hysteroscopy or uterine curettage to rule out uterine pathology.
Availability And Storage: Each capsule contains: micronized progesterone 100 mg. Nonmedicinal ingredients: arachis (peanut) oil, gelatin, glycerin, lecithin; coloring agent: titanium dioxide. Unit dose blister packages of 28, bottles of 100. Store at controlled room temperature 15 to 30°C. Protect from light.
PROMETRIUM Schering Progesterone Progestin