Transdermal drug administration is often used in cats to avoid difficulties associated with oral administration (eg, patient resistance to administration, GI adverse effects); however, drug absorption through the skin is complex, and not all drugs are suitable for transdermal delivery. Although studies do not generally support reliable use of many compounded transdermal drugs, some may be effective.1
Transdermal products may typically be considered compounded medications, but there are FDA-approved options. When available, FDA-approved transdermal products provide significantly more reliability than compounded transdermal medications. Obtaining FDA approval requires providing sufficient evidence of safety and efficacy. FDA-approved drugs are therefore expected to function according to approved labeling. Reliability decreases when these drugs are used extra-label, as data for safety and efficacy have not been evaluated under those conditions. For example, because canine skin differs significantly from feline skin,2 a drug labeled for transdermal use in cats cannot be assumed to also perform reliably in dogs.
Although FDA-approved topical drugs (eg, mirtazapine, buprenorphine, topical heartworm preventives) have been proven effective when administered transdermally, compounded drugs with the same active ingredients may not perform comparably to commercial drugs. Several factors (eg, the base used during compounding, proprietary inactive ingredients that may be present in commercial products) can alter the efficacy of a transdermal drug and cause compounded versions to be ineffective despite known efficacy of the approved commercial products.
Commercial products should be used if possible over compounded options, regardless of route of administration. Compounded medications (transdermal or otherwise) should only be used when they provide a clinically significant advantage over FDA-approved products.
Despite the benefits of commercially approved products, compounded transdermal medications may appear to be preferable in some cases. Following are the top 3 compounded drugs that can be reliably administered transdermally in cats according to the author.
Compounded transdermal methimazole is safe and effective when administered transdermally,3-6 and methimazole is often used extra-label (ie, compounded, transdermal) for treatment of feline hyperthyroidism. This drug can be easily monitored for efficacy. Monitoring thyroid hormone levels with a known target measurement can provide quantitative proof of efficacy in cats with hyperthyroidism.
Gastric distress is a well-documented adverse effect of oral methimazole, and transdermal administration of this drug can decrease the incidence of GI adverse effects in cats.5
All compounded drugs have possible adverse effects, and adverse effects (eg, irritation at the site of application) should be considered before transdermal methimazole is selected in place of the oral formulation. Communal grooming in feline housemates can result in accidental drug ingestion by other cats. Drugs designed to penetrate feline skin can also penetrate human skin, possibly resulting in accidental absorption by the pet owner during administration. Methimazole is considered a hazardous drug by the National Institute for Occupational Safety and Health (NIOSH) because of its risk to pregnant women and those trying to conceive. Owners should be instructed on safe handling (eg, wearing gloves) of the compounded product and concerns associated with unintentional absorption.
Phenobarbital is considered a first-line treatment for seizures in cats. The transdermal route may be preferred in some patients due to ease of administration, as phenobarbital is a long-term medication.
In a study of healthy cats administered transdermal phenobarbital, therapeutic serum concentrations were reached in patients given 9 mg/kg every 12 hours for 14 days but not in patients given 3 mg/kg every 12 hours, which is the oral dosage.7 Another study also found administration of 3 mg/kg every 12 hours to be ineffective at reaching therapeutic serum concentrations.8
Although transdermal phenobarbital may be effective, the combination of hepatic enzyme autoinduction and larger general doses needed to achieve therapeutic levels may result in doses that exceed the carrying capacity of the base compound and/or the amount of drug that can be effectively absorbed. Therapeutic monitoring is therefore essential to ensure therapeutic levels are maintained without toxicosis and to facilitate potential adjustments due to variability that may occur from compounding in bases other than the one studied.
There is not good support for the efficacy of fluoxetine, possibly due to lack of quantitative variables for assessing efficacy. Unlike methimazole and phenobarbital, which have defined quantitative factors to evaluate for efficacy, fluoxetine is used for treatment of behavioral modifications that are difficult to quantify.
One study found relative bioavailability of the transdermal formulation to be only ≈10% of that of the oral formulation.9 In a study in which fluoxetine was administered either transdermally or orally daily for 2 months, serum concentrations were achieved with transdermal administration, but patients given 5 mg/kg transdermally had significantly lower serum concentrations after 10 days than patients given 1 mg/kg PO.10 A serum level for efficacy has not been defined, however, and neither study addressed clinical effects.
Fluoxetine can be absorbed transdermally, and transdermal doses should likely be higher than oral doses. Determining efficacy of transdermal fluoxetine likely requires a trial period of multiple months due to the delayed onset of selective serotonin reuptake inhibitors. Transdermal efficacy may also be unclear when fluoxetine is given in conjunction with other behavioral drugs (eg, amitriptyline, buspirone); therefore, goals of therapy, how to identify whether therapy is successful, and appropriate expectations for time to effect should be determined with the owner.
An FDA-approved drug should always be the first-line treatment when selecting a dosage form, but a compounded drug can be considered if an FDA-approved version that meets the needs of the patient is not available. When selecting a product, a commercially available product should be the first choice if possible. If a compounded product is needed, oral formulations should generally be considered first, with transdermal administration reserved for patients in which oral administration is not possible. Further studies regarding transdermal absorption are needed.
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Dr. Forsythe joins us to dive deeper into the transdermal use of these 3 drugs.