Prescribing Compounded Drugs: Manage the Risk

Compounded medicines have been in use since the sixth century BC. As recently as the 1950s, long after the creation of the U.S. Food and Drug Administration (FDA), almost all physician-prescribed medications were compounded by a pharmacist. Today, most medications are mass produced by pharmaceutical companies that are subject to FDA oversight and regulation. However, the demand for customized, tailored drug therapies persists as evidenced by the recent surge in sales of compounded glucagon-like peptide-1 (GLP-1) agonists during periods of shortage. According to some estimates, compounded medications currently account for about 1-3% of all prescriptions written.
 
Two types of compounding pharmacies are subject to state and federal regulation:

• Traditional compounding pharmacies. Also known as “503A” pharmacies, traditional compounding pharmacies can compound medications only in response to a written prescription for a particular patient and are limited in the amount of medication they can distribute across state lines. Traditional compounding pharmacies are not subject to FDA regulation but are regulated by state pharmacy boards. 503A pharmacies are not required to abide by FDA-enforced Current Good Manufacturing Practices (CGMP). 
• Outsourcing facilities. Also known as “503B” pharmacies, outsourcing pharmacies can both compound in bulk in anticipation of receiving a prescription and distribute compounded medications across state lines. Although the FDA provides primary regulatory oversight, states can impose additional requirements on outsourcing pharmacies. Unlike traditional compounding pharmacies, outsourcing facilities are required to follow CGMP. 

Compounded medications play an important role in pharmacotherapy. They may be prescribed when FDA-approved drugs are inappropriate for or unavailable to the patient. Compounded medications may be appropriate when: 

• The patient is allergic to an ingredient in an FDA-approved medication.
• The patient cannot swallow a pill and needs the medication in a different form.
• The medication is not palatable in its FDA-approved form.
• The drug dosage needs to be customized.
• The medication is not available due to shortage.

While compounded drugs may be the right choice for a patient, they can also expose the patient to risk. Compounded drugs are not FDA approved, which means that the safety, effectiveness, or quality of the medication has not been evaluated by the FDA prior to marketing. As a result, the prescriber and the patient, must rely on the individual pharmacist and the compounding pharmacy to evaluate and assess the safety and quality of the medication being provided. Quality standards for compounded drugs may differ depending on the type and location of the compounding pharmacy that produces them. The major risks associated with compounded drugs are infection/contamination or dosage/concentration issues.
 
While compounded medication can be an important addition to a patient’s treatment plan, it can also pose patient safety risks when prescribed or prepared improperly. Consider the following when collaborating with compounding pharmacies:

• Do your homework. Become familiar with the compounding pharmacies in your area and with the outsourcing facilities they contract with. Ensure that pharmacies are accredited, properly licensed, and follow quality control standards. Monitor the FDA website to check the status of drug shortages, compounding risk alerts and recalls.
• Review contracts. If you contract with an outsourcing facility to supply compounded medication for use in your organization, work with an attorney to ensure that contracts address essential elements, such as expectations regarding quality standards and control, licensure, accreditation, supply chain, and pricing.
• Know the medications you prescribe. Adverse events related to medication therapy—regardless of whether the medication administered is compounded or mass produced—are often associated with a lack of practitioner knowledge about the medication being prescribed. Encourage prescribers to understand and acknowledge the importance of familiarity with the medications they prescribe in their practice. 
• Educate the patient. Prior to prescribing compounded medication, discuss with the patient the reasons for prescribing compounded medication, the benefits of prescribing it, the risks associated with it, and the alternatives to using it. Obtain the patient’s informed consent and document the consent discussion in the medical record. As with all medications, ensure that the patient understands how to recognize, report, and manage potential side effects and expected treatment response.
• Communicate with the pharmacist. Provide relevant clinical information to the compounding pharmacist such as other medications (prescription medications, over-the-counter medications, and supplements) the patient is taking, allergies or past adverse reactions to drugs, or other medical information that may be important.
• Understand reimbursement issues. Insurance plans may not reimburse costs or may require higher co-pays for compounded medications. If possible, confirm reimbursement prior to prescribing a compounded medication to avoid surprises at the pharmacy counter. Encourage patients to contact their health plan directly with questions about insurance coverage for prescribed medication. 
• Report adverse events. Report all adverse events related to compounded medications through the incident reporting system in your organization and the FDA’s MedWatch reporting system.

Compounding pharmacies can provide additional treatment options to patients who require customized medications or who have special needs, but they can also expose the patient to risk. Safe prescribing practices can help minimize those risks.