Transdermal Medications

Transdermal - what works and what does not work

Dr Rachel Korman, Cat Specialist Services

Compounded medications seem desirable in cats due to difficulties in giving medications, small body size, bitter human formulations and the common requirement for polypharmacy with multiple disease conditions. Compounding options include transdermal medications, flavoured oral suspensions and drug combinations within capsules. In this presentation we briefly discuss drugs compounded for transdermal administration including assessment of evidence where available.

It is important to be mindful that adding flavourings or other vehicles may interfere with drug potency, oral absorption and efficacy. Additionally, pharmacokinetics and therapeutic response data cannot be extrapolated for compounded medications from proprietary formulations. For this reason, the author prefers that medications considered essential for long term survival (e.g. chemotherapy) or any antibiotic are administered as proprietary formulations if possible.

The compounded medication that we use most commonly is mirtazapine, used as an appetite stimulant and antiemetic. It is available in a proprietary formulation as a 15 mg tablet. Mirtazapine toxicity was more likely in cats receiving higher doses of mirtazapine (3.75 mg rather than 1.88 mg).¹ We have prescribed 2 mg compounded mirtazapine oral capsules to over 350 cats in the last 5 years. Increased vocalisation is reported occasionally and rarely, agitation. Overall, the compounded oral capsule formulation appears well tolerated.

Transdermal mirtazapine significantly increased food intake in healthy cats.² Tandem mass spectrometry revealed significant variation from target dose in the transdermal gel preparations. This study demonstrates that transdermal administration is likely to be beneficial for cats not amenable to oral administration. Multiple dose regimes were shown to significantly increase drug exposure compared with a single dose. As the multiple dose regime of 7.5 mg transdermal mirtazapine resulted in more adverse effects of increased vocalisation and food seeking behaviours, a lower dosage (e.g. 3.75 mg) might be more beneficial as a multi dose regime. We have been using 2 mg/0.1 ml syringes. These are obviously more costly than a capsule, but do appear to be effective in some cats.

Transdermal amlodipine administration has been reported following 7 days of oral administration.^3,4 Blood pressure was reduced but not to the same extent as oral administration. As severe hypertension can result in life threatening complications, administration of oral amlodipine would be preferred. In patients where oral administration is impossible for owners, use of a transdermal amlodipine formulation could be considered following stabilisation with oral medication by veterinary staff.

At best, transdermal gel application is an inexact science. A list of the top four requests for transdermal medication compounding was obtained from a large Australian compounding pharmacy. Transdermal formulations of methimazole, gabapentin, tramadol and prednisolone were most commonly requested.

Transdermal methimazole has the most available evidence. Although effective and necessary for medical management in some patients, it may yield highly variable thyroid control over time. A recent study found it difficult to maintain total T4 concentrations within reference intervals and owner compliance was still a concern.⁵ Gastrointestinal side effects may be less when using transdermal methimazole compared with oral methimazole. As hyperthyroidism is now diagnosed at younger age and earlier stage in many patients and given that the longer patients receive medical management, the higher the risk of development of thyroid carcinoma, radioactive iodine treatment remains the most cost effective and safest treatment in many cases.

Transdermal gabapentin was shown to have erratic and poor transdermal absorption despite multiple dose regimes.⁶ The same study found that oral administration of compounded gabapentin (50 mg) was well tolerated. More research is required to assess effects in populations of elderly cats with chronic pain. The author commonly uses compounded gabapentin tablets for chronic pain in cats with a dosing interval of two to three times daily – the frequency dependent on the owner’s ability to medicate and patient requirements. The tablets are small and easy to give in most cases. Some owners have reported that even once daily dosing has resulted in noticeable positive effects.

Oral tramadol has questionable efficacy in cats as an analgesic agent.⁷ The efficacy of transdermal tramadol as an analgesic agent is unknown. Transdermal tramadol has been evaluated in an in vitro feline model and absorption was possible.⁸ Further research in cats is required.

Transdermal prednisolone can result cartilage degeneration (floppy ear syndrome) that is permanent if used over a long period. As oral prednisolone is readily available in a small tablet and liquid form (Redi-Pred) the author has not found it necessary to use a transdermal prednisolone preparation.

1. Ferguson LE et al. Mirtazapine toxicity in cats: retrospective study of 84 cases (2006-2011). J Feline Med Surg. 2016 Nov, 18(11): 868-874

2. Benson KK et al. Drug exposure and clinical effect of transdermal mirtazapine in healthy young cats: a pilot study. J Feline Med Surg. 2017 Oct 19 (10): 998- 1006

3. Mixon W, Helms SR. Transdermal Amlodipine Besylate in Lipoderm for the treatment of Feline Hypertension: A Report of Two Cases. Int. J Pharm Compd. 2008 Sept-Oct; 12(5): 392-7

4. Helms SR. Treatment of feline hypertension with transdermal amlodipine: a pilot study. J Am Anim Hosp Assoc. 2007 May-Jun; 43(3): 149-56

5. Boretti FS et al. Transdermal application of methimazole in hyperthyroid cats : a long term follow-up study. J Feline Med Surg. 2014 Jun; 16(6): 453-9

6. Adrian D. et al. The pharmacokinetics of gabapentin in cats. J Vet Intern Med. 2018 Nov; 32(6): 1996-2002

7. Bortolami E, Love EJ. Practical use of opiods in cats : a state of the art, evidence-based review. J Feline Med Surg. 2015 Apr; 17(4): 283-311

8. Bassani AS et al. In vitro characterization of the percutaenous absorption of tramadol into inner ear domestic feline skin using the Franz skin finite dose model. Vet Med Anim Sci. 2015; 3(3)