Cats often resist oral drug administration, possibly resulting in injury to the human or cat and negatively effecting the human–animal bond; however, injectable administration may not be practical for outpatient treatment. Transdermal drug administration can thus be a desirable alternative, especially for long-term treatment. Safety and efficacy of transdermal drugs depends on several factors, including drug molecule characteristics, dosage and indications, safety considerations, evidence of efficacy, and formulation design.
Drug Molecule Characteristics
Transdermal drugs are formulated to facilitate absorption via the skin; however, drug molecule passage through the lipophilic stratum corneum to the hydrophilic dermal layer (where absorption occurs) can be challenging. Certain drug factors (eg, lower molecular weight [ideally, <400 Daltons], balance between hydrophilic and lipophilic characteristics) can increase the likelihood of successful absorption.1
Dosage & Indications
Compounded transdermal drugs are administered via the pinna due to the thin, highly vascular, hairless skin as well as limited access to self-grooming, maximizing the potential for absorption and limiting the risk for ingestion. Larger doses may not be fully absorbed because of the limited surface area of the pinna, and administration more frequent than every 12 hours may result in irritation at the application site. Other factors (eg, drug molecule size and characteristics, skin structure characteristics) may also limit absorption.2
Some drugs may not be ideal therapeutic options. Sucralfate, for example, is intended to have a local effect on the GI tract and should not be administered transdermally. Antimicrobials should never be administered via the transdermal route due to potential resistance and lack of efficacy from drug levels that are lower than intended.
Safety Considerations
Drugs designed to penetrate feline skin can also penetrate human skin; therefore, drugs (eg, cytotoxic medications) with an unacceptable risk to human caregivers may not be appropriate for transdermal administration. In addition, drugs with a narrow therapeutic index or those that cause photosensitivity may pose an increased risk to patients and should not be administered transdermally.
Timeliness and completeness of response to therapy should also be considered. For example, patients given methimazole are slower to return to a euthyroid clinical state with transdermal administration versus oral administration.3 A small prospective study suggested that blood pressure decrease following transdermal administration of amlodipine was less than with oral administration by ≈20 mm Hg.4 Transdermal compounds should therefore be considered only after other routes of administration have been ruled out and evaluated based on each individual patient's needs. A slower return to a euthyroid state in patients receiving transdermal methimazole is unlikely to have a negative impact. Decreased efficacy due to transdermal administration of amlodipine may be harmful, although use in patients that cannot receive oral medication may be warranted to decrease blood pressure.
Evidence of Efficacy
Unknown aspects of transdermal drug delivery can result in an ineffective formulation, even when other criteria for administration are met. Ideal transdermal drugs have quantitative parameters (eg, defined effective therapeutic ranges for serum drug levels and laboratory targets [eg, thyroid levels]) to monitor for efficacy.
In addition, consideration should be given to using the transdermal route only for drugs that have published efficacy (eg, methimazole) or commercial drugs FDA-approved for transdermal administration in cats (eg, mirtazapine).5
Formulation Design
Formulations for FDA-approved drugs are often complex combinations of various penetration enhancers and ingredients to create desirable consistency, high absorption at the intended rate, and long-term drug stability; compounders are often unable to duplicate this complexity. Transdermal formulations are therefore typically prepared with a base (eg, pluronic lecithin organogel, one of many proprietary bases) that contains chemicals known to enhance drug penetration combined with the appropriate amount of active drug powder. Results may vary because of variability among bases. Although there is limited information comparing transdermal compound efficacy when prepared with different bases, transdermal medication refills for an individual patient should be made with the same base when possible.
As with other compounded medications, transdermal drugs may vary in potency from what is stated on the label. The drug concentration of a compounded medication is legally permitted to vary from the stated concentration by ±10%. Batch to batch variability is possible; therefore, choosing a high-quality compounding pharmacy can increase confidence in the desired potency. Compounded medications may lack stability and degrade before the expiration date. Pharmacies should therefore assign conservative expiration dates, and the pet owner should be given monthly refills.6
Conclusion
Safety and efficacy of compounded drugs cannot be guaranteed, as they are not FDA-approved. Efficacy of a transdermal drug may vary among compounding pharmacies due to the impact of the formulation on absorption. Clinicians should discuss the transdermal formulation details with the compounding pharmacy to assess data used to determine stability, safety, and potential efficacy of the product.