Serious Safety Concerns With Unapproved Pharmacy-Compounded Topical Anesthetics and Other Drugs

The Food and Drug Administration (FDA) is taking action against several pharmacies that produce compounded anesthetic products, citing concerns about the safety of the drugs.

On December 6, 2006, the FDA issued warning letters to five pharmacies who were found producing, distributing and selling unapproved high-strength topical anesthetics, copies of some FDA-approved drugs, and drugs that have never been approved for marketing in the United States. (A warning letter generally represents the FDA’s first official notification of a violation of the Food, Drug, and Cosmetic Act to a firm.)

These pharmacies, called “compounding pharmacies,” combine raw ingredients and/or drugs produced by pharmaceutical companies to create an alternate drug preparation that is not available commercially. Traditional pharmacy compounding is rarely medically necessary and generally involves breaking down FDA-approved tablets and capsules and making solutions or suspensions for patients who have difficulty swallowing.

The drugs that pharmacists compound are not produced in facilities meeting Good Manufacturing Practice (GMP) guidelines, which are regulations established by the FDA that ensure the quality of final finished products. In addition, compounded drugs are not evaluated by the FDA for safety and effectiveness and are not FDA-approved. Instead, compounding pharmacies are overseen, with varying degrees of success, by state regulatory bodies.

Once a compounding pharmacy begins selling a product to the general public as opposed to preparing it for one individual, it becomes a standardized product that the FDA views as a “new drug.” These pharmacists are not authorized to compound and sell “standardized” drug preparations. New drugs must be approved through a specific and rigorous FDA process.

Compounding pharmacies are not authorized to sell copies of FDA-approved drugs or sell products made with drugs that have not been approved for marketing in the United States.

Some compounding pharmacists attempt to bypass these rules, and this practice has turned compounding pharmacies into a lucrative niche industry that acts upon the same economic incentives as large drug companies, using many similar marketing strategies.

Two deaths have been tied to the compounded high-strength topical anesthetic creams made by Triangle Compounding Pharmacy of Cary, N.C., and University Pharmacy located in Salt Lake City, UT. Each of the other products produced by these compounding pharmacies poses its own specific serious risk to consumers. These risks are discussed later in detail.

The five compounding pharmacies that the FDA found violated the Food, Drug and Cosmetic Act are:

Custom Scripts Pharmacy
4600 North Habana Ave., Suite 16A
Tampa, Fla. 33614

Hal’s Compounding Pharmacy Inc.
3825 32nd Street
San Diego, Calif. 92104

New England Compounding Center
697 Waverly Street
Framingham, Mass. 01702

Triangle Compounding Pharmacy
550 New Waverly Place, Suite 110
Cary, N.C. 27511

University Pharmacy
1320 East 200 South
Salt Lake City, Utah 84102

The full text of the FDA warning and links to the five warning letters to these pharmacies can be found on the agency’s Web site at http://www.fda.gov/bbs/topics/NEWS/2006/NEW01516.html.

Custom Scripts Pharmacy
This pharmacy developed and patented its own standardized line of topical anesthetics called Betacaine LA Ointment (containing lidocaine, prilocaine and phenylephrine) and Betacaine Plus Ointment (containing lidocaine and prilocaine).

The ingredients in local anesthetic products, such as Betacaine, can cause seizures and heart rhythm disturbances. The risk of toxicity is greatest in small children and in patients with pre-existing heart disease. The use of large doses of prilocaine is related to a decrease in the oxygen-carrying capacity of red blood cells. Also, phenylephrine, which narrows blood vessels, can cause serious health complications related to high blood pressure at the large dose present in the Betacaine LA ointment.

In addition, patients with severe liver problems are at greater risk of developing toxic blood levels from any of these local anesthetics because of their inability to or break down anesthetics.

Custom Scripts Pharmacy also offers to compound two drugs that are not approved for use in the United States: polidocanol injections to treat varicose veins and dinitrochlorobenzene (DNCB) for warts.

Polidocanol is associated with the development of blood clots, tissue death and ulcers at the treatment site.

DNCB is highly toxic and may be fatal if inhaled, swallowed or absorbed through the skin. High concentrations of DNCB are also extremely destructive to tissues of the mucous membranes and upper respiratory tract, eyes and skin.

Hal’s Compounding Pharmacy
This pharmacy compounds several standardized products that contain high concentrations of the local anesthetics lidocaine and/or tetracaine, alone or in combination with other local anesthetics such as prilocaine and benzocaine.  

Some of the names used for these products are: Anesthetic Skin Lotion (containing lidocaine and prilocaine), Tetracaine in DMSO Gel (tetracaine and dimethyl sulfoxide) and Triple Kwick Anesthetic Gel (benzocaine, lidocaine and tetracaine), N*E*W* topical anesthetic (lidocaine, prilocaine and tetracaine), Kwick Anesthetic Gel (benzocaine, lidocaine, tetracaine and dimethyl sulfoxide), Lidocaine and Tetracaine Demi Gel and Anesthetic Skin Gel 3+ (lidocaine, prilocaine and tetracaine).

Hal’s Compounding Pharmacy also manufactures products that appear to be copies of commercially available FDA-approved drugs. These include progesterone 100mg capsules (PROMETRIUM), tretinoin 0.05 percent and 0.1 percent cream (RENOVA, RETIN-A).

New England Compounding Center
This pharmacy developed a standardized anesthetic drug product that it sells under the name Extra Strength Triple Anesthetic Cream (containing benzocaine, lidocaine and tetracaine). Also like a drug company, the New England Compounding Center generates sales by giving doctors “courtesy prescriptions” (a fancy way of saying “free samples”) of its product.  

The New England Compounding Center may also be copying commercially available FDA-approved drugs such as VisionBlue and aminolevulinic acid (LEVULAN). VisionBlue is a selective tissue-staining agent for use as a medical aid in ophthalmic (eye) surgery. Aminolevulinic acid is used in the treatment of dry, scaly, rough textured patches or lesions that form on the outermost layer of the skin after years of exposure to ultraviolet light, such as sunlight (considered the earliest stage in the development of skin cancer).  

Additionally, the FDA has received a complaint that the New England Compounding Center was repackaging the cancer drug bevacizumab (AVASTIN) into syringes for subsequent promotion and sale to ophthalmologists (eye doctors). Bevacizumab is approved for lung and colorectal cancers, but it has no FDA-approved use for the eye.

In this specific case, the center’s practice of repackaging can be dangerous because the bevacizumab does not contain a preservative to prevent the growth of bacteria and fungus once the single-use glass vial in which it is packaged is opened. Opening the vial in order to repackage the material can compromise the sterility and stability of the product.

Triangle Compounding Pharmacy
This pharmacy produces its own standardized line of topical anesthetic products sold under the names Lasergel and Lasergel Plus 10/10. In some cases, Triangle Compounding Pharmacy provides samples of these products to encourage future sales.

Triangle Compounding Pharmacy compounds and sells lollipops containing the local anesthetic tetracaine. This is a dangerous practice because the rapid absorption of local anesthetics through the mouth and nose may lead to convulsions.

The FDA is concerned about two problems with these anesthetic lollipops: that rapid absorption of tetracaine may be toxic, and that the anesthetic may cause food or vomit to “go down the wrong pipe” of a patient (aspirate). This may happen if the drug relaxes the reflexes that protect a patient’s airway, leading to the inhalation of food or vomit into the lungs or trachea. Children who are recovering from surgery involving the mouth or nose, such as having their tonsils removed, have an additional risk of the latter complication since post-operative bleeding can be swallowed and lead to stomach irritation and vomiting.

The FDA’s inspection also found that this pharmacy offers to compound products containing polidocanol, a substance not approved for use in the United States. Known adverse reactions of polidocanol include blood clots, tissue death and ulcers at the treated site. Additionally, the FDA has received reports of reversible cardiac arrest after using polidocanol in the treatment of varicose veins.

University Pharmacy
This pharmacy manufactures its own standardized brand-name product called Photocaine Gel. The product contains the local anesthetic tetracaine, which is associated with a higher incidence of allergic reactions than other anesthetics, such as lidocaine.

Factors that may increase systemic toxicity (poisoning that affects the entire body rather than a localized area) of local anesthetics are length of time and surface area of the exposure, particularly when the area of application is covered by a bandage used to keep in moisture.  

Patients with severe liver disease are at greater risk of developing toxic blood levels of local anesthetics because of their inability to break down these drugs. The risk of toxicity from using this product is greatest in small children and in patients with pre-existing heart disease.

The University Pharmacy also lists copies of commercially available FDA-approved progesterone products as drugs it produces.

Public Citizen denounces compounding pharmacies
Public Citizen has written previously about pharmacy-compounded drugs that are not approved by the FDA, including bioidentical hormone replacement drugs (see Worst Pills, Best Pills News August 2006), domperidone, promoted on the flimsiest of evidence to increase milk production in new mothers (see Worst Pills, Best Pills News August 2004), and unapproved drugs to treat attention deficient hyperactivity disorder (see Worst Pills, Best Pills News December 2001).  

The FDA is rightfully troubled about the safety of counterfeit and unapproved prescription drugs being sold to uninformed consumers. The agency has only recently taken notice of serious problems that unapproved drugs manufactured by compounding pharmacies pose to the public’s health. 

What You Can Do
You should avoid products produced by compounding pharmacies.