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FDA Consumer magazine
July-August 2000
by Tamar Nordenberg
Two thousand years ago, according to Christian belief, three wise men traveled to Bethlehem to worship the Christ child, bringing with them the gifts of gold, frankincense and myrrh. The aromatic resin myrrh, historically treasured for its medical and cosmetic usefulness, is still used in medicine today, mostly to treat inflammation of the mouth and pharynx.
Myrrh is not approved by the Food and Drug Administration to treat these or any other conditions. But the medical use of this unapproved drug may become legally acceptable under a new pharmacy compounding law that allows pharmacists and doctors to tailor-make some drugs for specific patients.
Considering the Alternatives
Health professionals are compounding when they prepare a specialized drug product to fill an individual patient's prescription when an approved drug can't fill the bill.
Compounding sometimes involves nothing more than crushing a pill into a powder with a mortar and pestle and then mixing it into a liquid, says Wayne Mitchell, an FDA regulatory counsel and member of the agency's internal pharmacy compounding steering committee. On the other hand, some types of compounding involve sophisticated scientific operations. Preparing sterile drug products, for example, can require complex steps to ensure a germ-free work environment.
The pharmacy compounding law, which is part of the FDA Modernization Act of 1997, defines the limits of legitimate compounding. By limiting the scope of the practice, the law aims to protect patients from the unnecessary use of compounded drugs, which carry intrinsic risks. Patients are often better served by taking commercially manufactured drugs that have been scientifically tested, approved by FDA, and manufactured under controlled conditions.
Compounded drugs can be "a great alternative when nothing is commercially available," says Randy Juhl, Ph.D., dean of the University of Pittsburgh's pharmacy school and chair of FDA's pharmacy compounding advisory committee, a group that includes non-government doctors, pharmacists, and consumer advocates. "But," Juhl says, "as a rule of thumb, if there is a commercially available drug, that's always better because of the quality controls that we as pharmacists can't provide for something we make up as a single-patient batch."
No Seal of Approval
The pharmacy compounding law carves out a limited exception to the requirement that prescription drugs be approved by FDA based on studies demonstrating their safety and effectiveness. Because pre-approval drug studies are performed on a very specific drug formula and dosage, even relatively small compounding changes can convert an approved drug (a product tested as a tablet, for example) into an unapproved one (such as a liquid form made by the pharmacist).
As unapproved drugs manufactured without FDA oversight, compounded medications involve an extra risk factor compared to approved ones. "Any time you make a change to a drug, there is the potential for reactions between ingredients or other problems," says Fred Richman, an FDA compounding expert. "You could end up with something that is less effective and that, at worst, could harm the patient."
Patients have been injured and have even died after taking pharmacy-prepared drug products. Examples include three infants who died after receiving an intravenous solution incorrectly prepared in a pharmacy, and a patient who became blind in one eye from pharmacy-prepared eyedrops that weren't sterile.
Taking the Risk
So why would a doctor choose to prescribe a compounded drug for a patient despite the inherent risks? A doctor may determine, in his or her professional judgment, that the compounded drug's benefits over any approved alternative justify the risk for a particular patient.
Drugs for certain conditions just aren't made by manufacturers. But even if a drug is mass-produced for a medical condition, patients might need a custom-made version for a variety of reasons.
Sometimes a patient can't use the standard version of a drug because of an allergy to one of its ingredients. If that ingredient is "inactive," meaning it has no therapeutic role, a compounder might make a similar drug minus that ingredient--say, without the dye used for coloring; or without lactose, a filler in many classes of drugs, from decongestants to antibiotics to chemotherapy medicines.
In other cases, the right dosage strength is not readily available for every patient. A child, for example, would usually need a smaller dosage than an adult. Commercial products are often not available in kid-sized portions, and sometimes it's not practical to break up the adult drug product.
And, commercially available drug products often need to be transformed into a different form for children and the elderly. For people in these age groups who can't swallow tablets or capsules, compounders can make a drug in a powder, liquid, lozenge, suppository, or other form for them.
Children may refuse to swallow a medicine, even in liquid form, if it tastes bad. Compounders can customize a drug in a kid's favorite flavor--cherry, orange, or raspberry, for example--to increase its appeal.
While flavoring a medicine may seem innocuous, it can alter a drug's makeup to the point of diminishing its effectiveness, scientists caution, so health professionals should not underestimate the potential downside of prescribing these drugs.
The risks of prescribing a compounded drug, along with the benefits, should be weighed in the context of a specific patient's medical condition, emphasizes the University of Pittsburgh's Juhl. It's "unfortunate," he says, that some pharmacists--including, for example, some makers of hormone replacement drugs--"are insisting that compounded drugs are better for you in all times and all places because they're 'all natural.' To generalize that these are necessarily best for everyone is, in my mind, a weak point in terms of credibility."
Proceeding With Caution
To encourage what quality control is possible for compounded drugs, the compounding law calls for certain federal requirements. (See "The Law Laid Out.") Some of these requirements, including a list of acceptable compounding ingredients, were developed by FDA's steering committee in consultation with Juhl and others on the external advisory committee.
Even with the law's restrictive provisions, however, pharmacist and former FDA pharmacy compounding steering committee member Robert Tonelli cautions consumers, "Whenever possible, FDA would recommend that patients use an approved drug. We have more data and reporting requirements on those to assure us of their safety and effectiveness."
More information on pharmacy compounding is available on FDA's Website at www.fda.gov/cder/pharmcomp/.
Tamar Nordenberg is a staff writer for FDA Consumer
The pharmacy compounding law offers some protections against unsafe and ineffective compounded products, including the following main provisions:
Also, to protect consumers from the excessive use of these unapproved drugs and to prevent compounders from profiting from the research and development efforts of drug manufacturers, the law places limits on the compounding of copies of manufactured drugs.
"It's a hard line to draw between legitimate compounding and manufacturing," says recently retired FDA pharmacist Robert Tonelli, "but we want to draw that line so manufacturers can't use the guise of compounding to avoid the approval process."
--T.N.
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