September 21, 2018
The U.S. Food and Drug Administration (FDA) recently approved Mirataz (mirtazapine transdermal ointment), a new animal drug used to manage undesired weight loss in cats. Mirataz is the first transdermal product to receive FDA approval for use in cats. FDA-approved drugs have been demonstrated to be safe and effective for their intended use and manufactured in a consistent manner.
FDA wants to remind you of the benefits of using FDA-approved drugs in your clinic and inform you of the bioavailability concerns associated with mirtazapine formulations compounded from bulk drug substances. Manufactured for Kindred Biosciences Inc., Mirataz is a prescription animal drug that is intended to be applied topically on the inner pinna of the cat’s ear once daily for 14 days. Each 5 g tube contains 100 mg (0.1 g) of mirtazapine. Please refer to the Freedom of Information Summary and package insert for Mirataz before using it.
Because Mirataz is administered transdermally, gloves should be worn when handling the drug to prevent accidental topical exposure to humans. After application, people should dispose of used gloves and wash hands with soap and water. Appropriate safety measures should be taken so that people or other animals in the household do not come in contact with the treated cat for at least two hours.
Mirataz must be prescribed by a licensed veterinarian because a trained professional is needed to correctly diagnose the cause of weight loss in cats and determine whether Mirataz is an appropriate treatment.
Benefits of FDA Approval
FDA rigorously evaluates an animal drug before determining whether to issue an approval. As part of the approval process, the drug company must prove to FDA that:
- The drug is safe and effective for a specific use in a specific animal species;
- The manufacturing process is adequate to preserve the drug’s identity, strength, quality, and purity from lot to lot for a consistent product; and
- The drug’s labeling is truthful and not misleading.
FDA’s role does not stop after the agency approves an animal drug. As long as the drug company markets the animal drug, the agency continues to monitor:
- The drug’s safety and effectiveness. Sometimes, the agency’s post-approval monitoring uncovers safety and effectiveness issues that were unknown at the time of approval;
- The manufacturing process to ensure quality and consistency are maintained;
- The drug’s labeling to make sure the information remains truthful and not misleading; and
- The company’s marketing communications related to the drug to make sure the information is truthful and not misleading.
Adverse Drug Events and Drug Interactions Associated with Mirataz
Mirataz is contraindicated in cats with a known hypersensitivity to mirtazapine or to any of the excipients. Mirataz should not be given in combination, or within 14 days before or after treatment with a monoamine oxidase inhibitor (MAOI) [e.g. selegiline hydrochloride (L-deprenyl), amitraz], as there may be an increased risk of serotonin syndrome.
Upon discontinuation of Mirataz monitor the cat’s food intake. The cat should be re-evaluted if food intake diminishes >75% for several days.
In the clinical field study, 115 cats received 2 mg Mirataz every day for 14 days. The most common adverse reactions included application site reactions (erythema, dermatitis or irritation, residue, crust/scabs), behavioral abnormalities (vocalization and hyperactivity), and vomiting. Please see Table II.3 of the Freedom of Information Summary for more information.
Safety and Effectiveness of Mirataz Compared to Compounded Transdermal Forms of Mirtazapine
Animal drugs compounded from bulk drug substances are not FDA-approved drugs, nor are they FDA-approved generic drugs, therefore their safety and effectiveness has not been established.
Unlike FDA-approved Mirataz, compounded formulations of transdermal mirtazapine have not been reviewed by FDA for safety or effectiveness, and may vary in quality and potency.
Mirataz is formulated for transdermal absorption. The absorption and effectiveness of this product have been demonstrated. In contrast, like many compounded transdermal drugs, the absorption and bioavailability of compounded transdermal mirtazapine are unknown and may be inadequate or variable, making treatment outcomes unpredictable.
Pharmacokinetic data in healthy cats demonstrated that Mirataz was well absorbed after topical administration to the cat’s inner pinna as directed. Maximum plasma concentrations were achieved within 2 - 6 hours after administration. The mean plasma half-life was long, ranging from 11.2 hours in cats who were allowed to rub their ears and lick their paws (both oral and transdermal absorption) to 20.7 hours in cats wearing Elizabethan collars (transdermal absorption only).
The effectiveness of Mirataz was demonstrated in one adequate and well-controlled clinical field study. Mirataz was administered to 115 client-owned cats and a vehicle control was administered to another 115 client-owned cats. All cats had a history of weight loss. The mean percent body weight increase at Week 2 compared to Day 1 was 3.94% in the Mirataz group compared to 0.41% in the vehicle control group and showed statistical significance. This clinical field study demonstrated that the topical administration of Mirataz to the inner pinna of the ear at a dose of 2 mg/cat for 14 days was effective for the management of weight loss in cats.
FDA’s Center for Veterinary Medicine (CVM) is committed to promoting and protecting animal health by ensuring safe and effective drugs are available for animals. For more information, please contact CVM’s Education & Outreach Staff at 240-402-7002 or AskCVM@fda.hhs.gov.
FDA’s Center for Veterinary Medicine