FDA Question and Answers Regarding Compounded Memopausal Hormone Therapy

Compounded Menopausal Hormone Therapy Questions and Answers

Pharmacy CompoundingMenopausal Hormone Therapy and “Bio-identical” HormonesFDA’s Enforcement Action Against Compounded “BHRT” drugsFDA’s Response to Wyeth’s Citizen Petition

     

Pharmacy Compounding 

1. What is pharmacy compounding?

FDA regards traditional pharmacy compounding as the combining or altering of ingredients by a pharmacist, in response to a licensed practitioner’s prescription, to produce a drug tailored to an individual patient’s special medical needs. In its simplest form, traditional compounding may involve reformulating a drug, for example, by removing a dye or preservative in response to a patient allergy. In the case of menopausal hormone therapy, an FDA approved progesterone product contains peanut oil. Progesterone compounded without peanut oil in response to a prescription for a specific patient who is allergic to this ingredient might allow the patient to safely use the drug.

2. Is combining two or more drugs considered compounding?

FDA would consider the combining of two or more FDA-approved drugs into a single medication, in a manner not described in a drug’s FDA-approved labeling, to be compounding if it is done by a pharmacist in response to a licensed practitioner’s prescription and produces a medication tailored to an individual patient’s special medical needs.

3.  Is pharmacy compounding beneficial for patients?

It can be.  Traditional pharmacy compounding enhances patient treatment with individually-tailored drugs when a physician deems that an FDA-approved drug may not be available or appropriate for that patient's care.  Thus, traditional compounding is an important component of patient care.

  

4. What are the risks associated with compounded drugs?

Compounded drugs can pose both direct and indirect health risks. Direct health risks include unsafe compounded products. Compounded drugs may be unsafe and compounded drugs made using poor quality compounding practices may be sub- or super‑potent, contaminated, or otherwise adulterated. Indirect health risks include the possibility that patients will use ineffective compounded drugs instead of FDA-approved drugs that have been shown to be safe and effective.  

Some pharmacists are well-trained and well-equipped to compound certain medications safely. But not all pharmacists have the same level of skills and equipment, and some drugs may be inappropriate for compounding. In some cases, compounders may lack sufficient controls (e.g., equipment, training, testing, or facilities) to ensure product quality or to compound complex drugs like sterile or extended-release drugs. The quality of the drugs that these pharmacists compound is unknown and these drugs pose potential risks to the patients who take them.

When pharmacy compounders both operate like drug manufacturers and engage in high‑volume distribution, the risk of patient harm increases. Over the past several years, FDA has become aware of serious adverse events, including deaths, associated with compounded drugs. For example:

• In December 2006, FDA issued warning letters to five firms about their standardized compounded, high‑strength topical anesthetic creams. Two deaths were connected to the topical anesthetics compounded by two of the pharmacies.
• In August 2006, FDA warned three firms to stop manufacturing and distributing thousands of doses of unapproved inhalation drugs under the guise of compounding. Warning letters to these firms identify a range of serious concerns including inadequate quality control, concerns about potency, and compounding copies of FDA-approved drugs.
• In March 2006, FDA issued a warning letter to a Maryland firm regarding its compounding of cardioplegia solutions – used in open-heart surgery – that were contaminated. The contaminated solutions caused severe systemic infections in five patients at a hospital in Virginia. Three of the five patients died from their infections.

5. Does FDA want to prevent pharmacy compounding?

No. FDA believes that pharmacists engaging in traditional compounding provide a valuable medical service that is important to patient health. FDA has no interest in ending traditional pharmacy compounding and focuses instead on the subset of inappropriate compounding described in FDA’s Pharmacy Compounding CPG. The CPG is available on FDA’s pharmacy compounding Web page.

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Menopausal Hormone Therapy and “Bio-identical” Hormones

1. What is hormone therapy for menopause?

During menopause, women may have lower levels of some hormones and experience hot flashes, vaginal dryness, and thin bones. To help with these symptoms, some physicians prescribe hormones like estrogen or estrogen with a progestin or progesterone. FDA has approved drugs for use in hormone therapy for menopause symptoms, and advises women who choose to use hormones to use them at the lowest dose that helps, for the shortest time needed.

2. What does the term “bio-identical” mean?  

The term “bio-identical” has no defined meaning in any medical or conventional dictionary, and FDA does not recognize the term. Even different medical groups define the term differently. The Endocrine Society, for example, defines “bio-identical” hormones as “compounds that have the exact same chemical and molecular structure as hormones that are produced in the human body,” while the American College of Obstetricians and Gynecologists (ACOG) defines “bio-identical” hormones as “plant-derived hormones that are biochemically similar or identical to those produced by the ovary or body.”  

Many compounding pharmacies use “Bio-identical” as a marketing term to imply that drugs are natural, or have effects identical to those from hormones made by the body. FDA is not aware of credible scientific evidence to support these claims. Compounded products that have identical chemical structures to synthetic hormones can be expected to have the same benefits—and risks— associated with FDA-approved hormone therapy.

3. How widespread is the marketing of compounded “BHRT” drugs?  

“BHRT” compounding appears to be widespread and growing. Many compounding pharmacies have established internet websites to promote and sell their compounded “BHRT” drugs. But compounding pharmacies generally are not required to register with FDA, or to report the products that they produce. Thus, it is impossible for us to accurately gauge the volume of “BHRT” compounding.

4. Has FDA purchased or tested any compounded “BHRT” drugs as part of its enforcement efforts?  

In 2001, FDA collected and analyzed 29 compounded drugs, including eight hormone drugs such as progesterone, estrogen, and estradiol. Ten of the 29 drugs failed analytical testing. Two of those ten drugs were hormone drugs. The results of this survey are available on FDA’s website.  

Under FDA’s ongoing surveillance sampling program, the agency continues to sample compounded drugs – including compounded “BHRT” drugs – to assess their quality.

5. Is saliva testing helpful for people taking menopausal hormone therapy?  

Some compounding pharmacies and other promoters of “BHRT” claim that estrogen levels in a person’s saliva can be tested by practitioners to help practitioners estimate the amount of hormone a person needs and purportedly to “customize” the hormone therapy for individual patients. There is no scientific basis for using saliva testing to adjust hormone levels. Instead, practitioners should adjust hormone therapy dosages based on a patient’s symptoms.

6. Is there “BHRT” available for men?  

Some pharmacies promote hormone therapy for men in the form of testosterone to treat a decline in the level of testosterone in older men, sometimes referred to as andropause. There are currently no FDA-approved products for the treatment of andropause. In addition, there are no FDA-approved testosterone drugs for women.

7. What are the FDA-approved hormone therapies for menopause?  

There are three major categories of FDA-approved menopausal hormone therapy products: products containing only estrogen, products containing only progestin, and products containing estrogen and progestin. Complete list of the FDA-approved medications for menopause.

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 FDA’s Enforcement Action Against Compounded “BHRT” drugs

1. What enforcement action is FDA taking today against compounded “BHRT” drugs?

FDA issued several Warning Letters today notifying certain compounding pharmacies about unlawful practices related to their compounded “BHRT” drugs. FDA’s letters warned the pharmacies that they make false and misleading claims about their “BHRT” drugs, including claims that compounded “BHRT” drugs are safer or more effective than FDA approved hormone therapy drugs and claims that compounded “BHRT” drugs can prevent or treat serious illnesses such as Alzheimer’s disease and certain forms of cancer. In addition, FDA warned a number of pharmacies that they may not compound drugs containing the estrogen substance estriol without a valid investigational new drug application. Firms that do not properly address violations identified in Warning Letters risk further enforcement, including injunctions that prevent additional violations and seizure of violative drugs.

2. Why is FDA concerned about compounded “BHRT” drugs?

FDA is aware that a growing number of pharmacies compound hormone drugs for treatment of the symptoms of menopause. These pharmacies often promote their compounded drugs as “bio-identical” to the hormones produced by a woman’s body, and the phrase “bio-identical hormone replacement therapy” has been used to describe these drugs.  

Some pharmacy compounders claim that their compounded “BHRT” drugs are a “natural” alternative to FDA-approved drugs, because the compounded hormones are purportedly identical to the hormones produced in the body. These pharmacies may also claim that their “natural” compounded drugs are safer and more effective than FDA-approved menopausal hormone therapy drugs. FDA is not aware of any credible scientific evidence supporting these claims. Nor is FDA aware of sound evidence showing that the side effects and risks of compounded "BHRT" drugs that use estrogen and progesterone as active ingredients are different than those of similarly formulated FDA-approved menopausal hormone therapy drugs. Because many claims regarding the safety, efficacy, and superiority of compounded “BHRT” drugs have not been proven, FDA is concerned that these claims mislead patients and practitioners. Compounded products that have identical chemical structures to synthetic hormones can be expected to have the same benefits—and risks— associated with FDA-approved hormone therapy.

3. Can “BHRT” drugs be used to prevent or treat Alzheimer’s disease, depression, breast cancer, colon cancer, or other serious illnesses?  

A number of pharmacies claim that compounded “BHRT” drugs can prevent or treat serious illnesses including: heart disease, stroke, depression, Alzheimer’s disease, and breast cancer. FDA is not aware of scientific evidence that “BHRT” drugs can be used to prevent or treat of any of these illnesses.  

The National Institutes of Health Women’s Health Initiative (WHI) conducted several studies, including a large study to determine the effects of estrogen with the progestin medroxyprogesterone acetate on the prevention of heart disease. Results from the WHI study showed that postmenopausal women taking estrogen with a progestin had an increased risk of heart attack, stroke, breast cancer, and blood clots.

4. What is estriol and why is FDA concerned about “BHRT” drugs that contain it?  

Some compounded “BHRT” drugs contain an estrogen component called estriol. No drug containing estriol has been approved by FDA and the safety and effectiveness of estriol is unknown. Pharmacies may not compound drugs containing estriol unless they have an FDA-sanctioned investigational new drug application.

5. Will compounded hormone therapy drugs still be available to patients?

FDA believes that pharmacists engaging in traditional compounding provide a valuable medical service, and the Agency respects and takes seriously a licensed practitioner’s decision that an FDA-approved drug may not be appropriate for his or her patient’s medical needs. When a licensed practitioner decides that his or her patient’s specific medical needs will be best served by a compounded hormone therapy drug, FDA would expect to exercise enforcement discretion towards the compounding of that drug, consistent with FDA’s policy described in the Compounding CPG.  

Estriol, however, is not a component of an FDA-approved drug and, consistent with FDA policy, pharmacies may not compound drugs containing estriol unless they have a valid investigational new drug application.

6. What should a patient do if they are currently taking a compounded “BHRT” drug?  

Anyone who is currently receiving compounded menopausal hormone therapy for symptoms of menopause should discuss hormone therapy options with their health-care provider to determine if compounded drugs are the best option for their particular medical needs.

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 FDA’s Response to Wyeth’s Citizen Petition

1. What did Wyeth request in its Citizen Petition?

In October 2005, Wyeth filed a Citizen Petition asking FDA to:

Initiate enforcement actions against pharmacists compounding “BHRT” drugs, or in promoting “BHRT” drugs, whose facilities or practices violate the Federal Food, Drug and Cosmetic Act; Commence investigations to determine whether firms involved in dispensing  are providing patient package inserts when dispensing each package and are including material facts and risk information in product labeling and advertisements;Require pharmacists compounding “BHRT” drugs to make certain labeling and advertising disclosures; and Issue an FDA Alert or Talk Paper addressing concerns relating to compounded “BHRT” drugs.

2. What was FDA’s answer to the Wyeth Citizen’s Petition?  

FDA was considering issues related to compounded “BHRT” drugs prior to the receipt of Wyeth’s petition. FDA has granted the petition in part and denied the petition in part. FDA denied those petition requests that FDA initiate activities related to enforcement actions, because such requests for the Agency to initiate enforcement actions are not within the scope of FDA’s citizen petition procedures. FDA has developed a public-awareness campaign about the risks and benefits of hormone therapy for the treatment of menopausal symptoms and other conditions.

3. Where can people find more information regarding menopausal hormone therapy?

        

        For more information, please see the following websites:

• FDA News Release: FDA Takes Action Against Compounded Menopause Hormone Therapy Drugs (1/9/2008)  
• Testimony of Dr. Steven Galson at Congressional Hearing: Pharmacy Compounding/Compounding of Bio-identical Hormone Replacement Therapies (4/19/2007)
• FDA Office of Women’s Health “Menopause and Hormones” Web sit

Information provided above is found here.