Veterinary compounding is the process of creating customized medications to meet specific needs of individual patients and has critical nuances that can differ from human medicine. Compounded medications do not replace FDA-approved medications but provide a potentially lifesaving alternative option when FDA-approved products are not suitable or available.
Compounding effective and safe medications requires significant education, training, and hands-on practice. Making informed decisions is critical, as some compounded preparations may not be as effective as FDA-approved products or may increase risk for toxicosis. Improved education on drug compounding and administration could help prevent negative patient outcomes.
Patient Outcomes
Veterinary compounding is complex and potentially dangerous. Just because a drug can be compounded does not mean it should. For example, in one anecdotal case, a male dog with myasthenia gravis was effectively managed with a commercially manufactured pyridostigmine syrup. Due to pet owner financial concerns, the referring clinician switched to a compounded version of pyridostigmine, which was assumed to have equal efficacy. The patient slipped out of remission, and his condition continued to deteriorate despite receiving escalated doses of the compounded medication until eventual euthanasia. Compounded pyridostigmine was suspected to not have the same efficacy of the FDA-approved product, contributing to the patient's decline; however, predisposing factors could have also played a role.
In a contrasting anecdotal case, a 2-lb (0.9-kg) female Yorkshire terrier crossbreed without a lower jaw was successfully treated and managed for a severe cardiovascular condition with compounded liquid formulations of enalapril and sildenafil. These formulations allowed a precise dose that was appropriate for the patient’s small size, as other drug forms could not be administered.
How to Help Clients Feel Confident About Giving Medication
When prescribing a medication, ask the client whether they feel comfortable and confident administering it. Ask about potential challenges, and create space for them to be honest and forthcoming. They may respond with:
I'm usually comfortable giving my dog pills, but I recently had surgery and am unable get down on the floor to give her medication right now.
I have a family member in the hospital and don't have any time to pick that medication up from the pharmacy.
I'm willing to try medicating my cat, but I never learned how to give pills to animals. I could use some help.
Once you know the client's concerns and can help address them, administering medication may feel more manageable for the client and less likely to cause anxiety, missed doses, and treatment failure.
Compounding Challenges
Compounding certain medications, particularly those with complex formulations, can be challenging beyond finding alternatives to commercially manufactured products. These challenges include addressing unique release mechanisms, complex salt forms, and physiologic differences among products that can result in metabolic variations. Quality control is also a consideration, as FDA-approved drugs undergo rigorous testing for potency, purity, and stability, which can be logistically and financially unfeasible for compounding pharmacies to replicate. Ensuring consistency among batches can be difficult and lead to variability in efficacy. For example, compounded formulations like itraconazole, trilostane, pimobendan, budesonide, and cyclosporine can be pharmacologically stable yet still produce different clinical effects as compared with their FDA-approved counterparts.
Compounded Itraconazole
Compounded itraconazole has complex formulation requirements. Cyclodextrin, an ingredient in the commercially available oral solution, aids in oral absorption and influences whether food is required with administration. Cyclodextrin is absent from many compounded oral suspension formulations, resulting in differences in bioavailability. Creating a stable itraconazole–cyclodextrin complex is possible but labor-intensive and often not financially viable.1 Compounding itraconazole with cyclodextrin requires specialized knowledge and techniques not typically employed in routine compounding and therefore is not standard practice for most compounders.
A study involving 8 female dogs given compounded itraconazole (5 mg/kg PO) from the same compounding pharmacy revealed significant variability in serum concentrations, underscoring the unpredictable bioavailability and absorption associated with compounded versions of the drug.2 In addition, compared with commercial counterparts, compounded itraconazole preparations have pharmacokinetic differences, inconsistent absorption, and treatment failure in various species.3-7
Compounded Trilostane
Compounded trilostane is frequently prescribed because it can be cost-effective; however, cost should not drive the decision to compound a medication. Compounded trilostane can pose significant risk when not prepared correctly. In a study that analyzed trilostane capsules from 8 pharmacies, 38% of compounded batches were below the acceptable criteria for active pharmaceutical ingredient content.8 Potential deficiency was revealed when compounding from the bulk active pharmaceutical ingredient as compared with a compounded control derived from FDA-approved trilostane capsules. The significant variance in failure rate among compounding pharmacies emphasizes the need for compounding via a reputable pharmacy.
Compounded Pimobendan
Pimobendan has historically been compounded during drug shortages for treatment of conditions like congestive heart failure and degenerative mitral valve disease, but stability and efficacy, particularly in aqueous suspensions, remain a concern.9 Education among compounders is crucial; for example, substantial amounts of citric acid are needed to stabilize pimobendan, but this may be overlooked by or unknown to some compounders.10 Engaging with compounding pharmacies (eg, asking whether the compounder knows the formulation will be effective) is important. Proactive communication can help ensure compounded medications meet therapeutic expectations.
Additional Compounded Medications & Increased Risk for Toxicosis
Similar issues with stability and efficacy have been identified with other compounded medications, including fluconazole, cyclophosphamide, and lomustine.11-13 These compounded medications may exhibit variable potency or dosage inaccuracies, which can significantly increase risk for toxicosis, especially in drugs with narrow therapeutic indexes. Patients receiving compounded medications may be particularly vulnerable to these risks. Verifying the compounding pharmacy adheres to rigorous quality control standards is therefore essential. Checking for accreditation, reviewing professional experience, and investigating any disciplinary actions by the National Association of Boards of Pharmacy or the FDA may help ensure high standards of the compounding pharmacy.
Conclusion
Compounded medications are essential, particularly when a suitable FDA-approved product is unavailable, but their use should be approached judiciously, with a thorough understanding of potential efficacy and safety challenges. Actively engaging with compounding pharmacies, including asking questions to verify effectiveness of formulations, ensuring compounded medications are prepared by reputable pharmacies, and holding facilities to high standards, can improve patient outcomes without compromising safety.