PREMARIN Vaginal Cream (conjugated estrogens) Drug Interactions

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No formal drug interactions studies have been conducted in Premarin® Vaginal Cream.


In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John's wort (Hypericum perforatum) preparations, phenobarbital, phenytoin, carbamazepine, rifampicin, and dexamethasone may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4, such as cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase plasma concentrations of estrogens and may result in side effects.

Drug-Drug Interactions

No formal drug-drug interactions studies with Premarin® Vaginal Cream have been conducted (see Drug Interactions – Overview)

Drug-Food Interactions

No formal drug-food interactions studies with Premarin® Vaginal Cream have been conducted (see Drug Interactions – Overview) CYP3A4 inhibitors such as grapefruit juice may increase plasma concentrations of 17 ß-estradiol and may result in side effects.

Drug-Herb Interactions

It was found that some herbal products (e.g. St. John’s wort) which are available as over-the-counter (OTC) products might interfere with steroid metabolism and therefore alter the efficacy and safety of estrogen/progestin products.

Physicians and other health care providers should be made aware of other non-prescription products concomitantly used by the patient, including herbal and natural products obtained from the widely spread health stores.

Drug-Laboratory Test Interactions

There are no studies investigating drug-laboratory test interactions with Premarin® Vaginal Cream.

The results of certain endocrine and liver function tests may be affected by estrogen-containing products:

  • increased prothrombin time and partial thromboplastin time; increased levels of fibrinogen and fibrinogen activity, increased coagulation factors VII, VIII, IX, X; increased norepinephrine-induced platelet aggregability; decreased antithrombin III;
  • impaired glucose tolerance;
  • increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentrations, increased serum triglycerides and phospholipids concentration.
  • increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone (T4), as measured by column or radioimmunoassay;T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered.
  • other binding proteins may be elevated in serum i.e., corticosteroid binding globulin (CBG), sex-hormone binding globulin (SHBG), leading to increased circulating corticosteroids and sex steroids respectively, free or biologically active hormone concentrations are unchanged;
  • The response to metyrapone may be reduced.
  • The pathologist should be informed that the patient is receiving hormone replacement therapy (HRT) when relevant specimens are submitted.

The results of the above laboratory tests should not be considered reliable unless therapy has been discontinued for two to four weeks.

Drug-lifestyle interactions
Acute alcohol ingestion during HRT may lead to elevations in circulating estradiol levels.