What Is Premphase 28 Day?

Premphase 28 Day is a prescription hormone replacement therapy (HRT) that combines Conjugated Estrogens and Medroxyprogesterone Acetate in a 28-day oral tablet kit to treat moderate to severe menopause symptoms and help prevent postmenopausal osteoporosis.

If you're experiencing hot flashes, night sweats, vaginal dryness, or other symptoms of menopause, Premphase 28 Day may be a treatment option your doctor considers. Here's everything you need to know about this medication in 2026 — what it is, how it works, what it costs, and who should (and shouldn't) take it.

Brand Name, Generic, and Classification

• Brand name: Premphase
• Generic name: Conjugated Estrogens and Medroxyprogesterone Acetate
• Drug class: Estrogen/Progestin Combination (Hormone Replacement Therapy)
• Manufacturer: Pfizer (formerly Wyeth)
• Controlled substance: No — Premphase 28 Day is not a controlled substance
• Generic available: No direct generic equivalent of the Premphase 28 Day kit is currently available, though the individual components can be prescribed as separate generics

What Is Premphase 28 Day Used For?

The FDA has approved Premphase 28 Day for three indications:

1. Treatment of moderate to severe vasomotor symptoms (hot flashes) due to menopause — This is the most common reason it's prescribed. Hot flashes, night sweats, and flushing can significantly impact quality of life.
2. Treatment of moderate to severe vulvar and vaginal atrophy due to menopause — Declining estrogen levels can cause vaginal dryness, itching, and discomfort during intercourse.
3. Prevention of postmenopausal osteoporosis — Estrogen helps maintain bone density. For women at risk of osteoporosis, Premphase 28 Day can help slow bone loss. However, non-estrogen medications should be carefully considered first.

Some doctors may also prescribe it off-label for managing irregular menstrual bleeding during perimenopause or for hormone therapy in premature ovarian insufficiency.

How Is Premphase 28 Day Taken?

Premphase 28 Day comes as a kit with two types of tablets taken in sequence over a 28-day cycle:

• Days 1 through 14: Take one maroon tablet daily — this contains 0.625 mg of Conjugated Estrogens only.
• Days 15 through 28: Take one light-blue tablet daily — this contains 0.625 mg Conjugated Estrogens plus 5 mg Medroxyprogesterone Acetate.

Key instructions:

• Take one tablet by mouth at the same time each day
• Swallow whole with water
• Can be taken with or without food
• Use the lowest effective dose for the shortest duration consistent with your treatment goals
• After finishing the 28-day kit, start a new one the next day

The two-phase design is intentional: the first 14 days provide estrogen alone, while the second 14 days add a progestin to protect your uterine lining. For more on why this matters, see our article on how Premphase 28 Day works.

Who Should Not Take Premphase 28 Day?

Premphase 28 Day is not safe for everyone. It is contraindicated in women with:

• Undiagnosed abnormal genital bleeding
• Known or suspected breast cancer, or a history of breast cancer
• Known or suspected estrogen-dependent tumors
• Active or past deep vein thrombosis (DVT) or pulmonary embolism (PE)
• Active or past stroke or heart attack
• Known allergic reaction or angioedema to Premphase
• Liver impairment or liver disease
• Known clotting disorders (Protein C, Protein S, or Antithrombin deficiency)
• Pregnancy

Premphase 28 Day also carries a boxed warning about increased risks of cardiovascular disease, breast cancer, endometrial cancer (with unopposed estrogen), and probable dementia in women 65 and older. Discuss these risks thoroughly with your doctor. For more on side effects, read our Premphase 28 Day side effects guide.

How Much Does Premphase 28 Day Cost?

Here's what you can expect to pay in 2026:

• Brand-name cash price: $280 to $320 for a 28-day supply without insurance
• With insurance: Many plans cover Premphase 28 Day, though some require prior authorization or step therapy (trying a lower-cost option first). Your copay will depend on your plan's formulary tier.
• Medicare Part D: May cover Premphase 28 Day with varying copays depending on the plan.
• Component generics: If cost is a barrier, your doctor can prescribe generic Conjugated Estrogens and generic Medroxyprogesterone Acetate separately for approximately $15 to $40 each per month — potentially saving you over $200.

Pfizer doesn't currently offer a specific co-pay savings card for Premphase, but eligible patients may apply through Pfizer RxPathways (pfizerrxpathways.com) for assistance. Additional programs are listed on NeedyMeds and RxAssist.

For more ways to lower your cost, check out our guide on how to save money on Premphase 28 Day.

How Does Premphase 28 Day Compare to Similar Medications?

Several other estrogen-progestin combination HRT products are available:

• Prempro: Same active ingredients (Conjugated Estrogens + Medroxyprogesterone Acetate) but taken as a single continuous-combination tablet every day — no phase change. Simpler dosing, but some women prefer the cyclic approach of Premphase.
• Activella: Combines Estradiol with Norethindrone Acetate. A different estrogen-progestin combination for continuous HRT.
• Angeliq: Combines Estradiol with Drospirenone. May also provide mild blood pressure benefits.
• FemHRT (Jinteli): Ethinyl Estradiol plus Norethindrone Acetate for menopausal HRT.

If you can't find or afford Premphase 28 Day, our guide on alternatives to Premphase 28 Day covers your options in detail.

Final Thoughts

Premphase 28 Day is an effective hormone replacement therapy for postmenopausal women dealing with hot flashes, vaginal atrophy, and osteoporosis risk. Its two-phase design provides estrogen throughout the cycle while adding progestin in the second half to protect the uterus. While it's a brand-name product with a higher price tag and limited availability, tools like Medfinder can help you find it in stock near you. Always work with your doctor to determine whether Premphase 28 Day is the right choice for your individual health needs.