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Mirtazapine Ointment (trade name Mirataz) is a white to off white transdermal ointment, with Mirtazapine as the active ingredient and a content of 2% (w/w). Each gram of ointment contains 20 milligrams of mirtazapine, and each 5-gram pack contains 100 milligrams of active ingredient. Its matrix is composed of ingredients such as polyethylene glycol 400 (PEG 400), polyethylene glycol 3350 (PEG 3350), diethylene glycol monoethyl ether, PEG-8 caprylic/caprylic acid glycerides, oleyl alcohol, butyl hydroxytoluene, dimethyl silicone oil, and Dry Flo TS, ensuring drug stability and skin permeability. This substance is the first FDA approved transdermal mirtazapine formulation for cats, designed specifically for the treatment of unexpected weight loss. Clinical studies have shown that daily administration of 2 milligrams per cat to the inner ear for 14 consecutive days can increase the average weight of cats by 5.7% and significantly improve appetite scores. Its therapeutic effect is superior to oral preparations, as transdermal administration can avoid first pass effects and reduce liver metabolic burden.
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Mirtazapine COA
Medication plan and operating procedures
Mirtazapine Ointment is a four ring antidepressant that enhances the neurotransmission of norepinephrine and serotonin (5-HT) by blocking central nervous system alpha 2 adrenergic receptors, while antagonizing 5-HT2 and 5-HT3 receptors, reducing side effects such as nausea and anxiety. Its sedative effect is mainly achieved by blocking the histamine H1 receptor. In veterinary medicine, mirtazapine ointment (such as Mirataz) ®) Developed as a transdermal drug formulation, it is mainly used to stimulate the appetite of cats and treat weight loss and malnutrition caused by diseases, surgeries, or psychological factors.
Drug characteristics&indications
Dosage form: White to off white ointment containing 2% mirtazapine (20 milligrams per gram).
Accessories: Polyethylene glycol (PEG) 400, PEG 3350, diethylene glycol monoethyl ether, PEG-8 caprylic/decanoic acid glyceride, oleyl alcohol, butyl hydroxytoluene, dimethyl silicone oil, Dry Flo TS, etc.
Mechanism of action: By stimulating the hypothalamic feeding center, increasing the release of neuropeptide Y, while antagonizing 5-HT2C receptors, reducing the transmission of satiety signals, thereby promoting appetite.
Weight loss in cats due to chronic kidney disease, cancer, oral diseases, postoperative recovery, or psychological anorexia.
Cases that require rapid improvement of nutritional status to support treatment or surgery.
Medication Regimen
Dose and treatment course
Standard dose: Once daily, apply a 1.5 inch (approximately 3.8 cm) ointment strip (equivalent to 2 milligrams of mirtazapine) to the inner side of the cat's ear canal.
Course of treatment: Use continuously for 14 days, apply alternately to the left and right ears to reduce the risk of local irritation.
Adjustment principle:
Cats weighing less than 2 kilograms or aged less than 6 months are prohibited.
Patients with liver and kidney dysfunction need to adjust the dose after veterinary evaluation.
Repetitive treatment should be conducted at least 14 days apart and only after veterinary assessment that the benefits outweigh the risks.
Administration method
Operation steps:
Preparation: Wear disposable gloves and open the ointment tube (rotate the tube cover counterclockwise).
Measurement: Squeeze out 3.8 centimeters of ointment to the fingertips according to the scale on the tube or the ruler attached to the packaging.
Application: Gently apply to the inner side of the cat's ear canal (not the ear canal), avoiding contact with hair or damaged skin.
Cleaning: Immediately seal the ointment tube after use, store it out of reach of children, discard gloves, and wash hands.
Alternating medication: Use the left ear on the first day, the right ear on the second day, and so on to reduce local tolerance.
Medication monitoring
Efficacy evaluation:
Record the cat's food intake, weight changes, and behavioral status daily.
If there is no improvement in appetite after 3-5 days of medication, it is necessary to contact a veterinarian to adjust the plan.
Indications for discontinuation of medication:
Cats refuse to eat for 48 consecutive hours or their food intake decreases by more than 75%.
Severe vomiting, diarrhea, dehydration, or abnormal behavior (such as overexcitement or aggression) may occur.
Local skin reactions (erythema, scabbing, desquamation) lasting for more than 3 days.
Operating standards and safety measures
Personnel protection
Glove use: Disposable gloves (such as nitrile rubber or latex gloves) must be worn to avoid drowsiness, dizziness, or allergic reactions caused by transdermal absorption of drugs.
Post contact handling: Discard gloves immediately after medication, wash hands thoroughly with soap and warm water, and avoid hand mouth and hand eye contact.
Taboo population: Pregnant women, lactating women, and those allergic to mirtazapine are prohibited from contacting the medication.
Animal management
Isolation period: Avoid contact between humans and cats or other pets within 2 hours after medication to prevent drug transfer.
Behavioral observation: During medication, cats may exhibit hyperactivity, vocalization, or drowsiness. It is important to ensure a safe environment and avoid falling or injury.
Skin care: If there is redness, swelling, or peeling in the ear, medication can be temporarily suspended and a veterinarian can be consulted. Local use of pet specific moisturizer is recommended.
Drug storage and disposal
Storage conditions: Store in a sealed container below 25 ℃ and use within 30 days after opening.
Expired processing:
Mix coffee grounds or cat litter, seal in a plastic bag, and dispose of as regular garbage.
Do not flush into the toilet or sewer.
Child protection: Store medication in locked drawers or high places to avoid accidental ingestion.
Adverse reactions and treatment
1.Common reactions (incidence rate>10%)
Local reactions: erythema, scabbing, and desquamation of the ear (usually self resolving within 7-10 days).
Behavioral abnormalities: increased vocalizations, hyperactivity, and disorientation (commonly seen 2-4 hours after medication, lasting<12 hours).
Digestive system: vomiting, soft stools (related to drug stimulation of gastric mucosa or 5-HT3 receptor antagonism).
Handling principle:
Local reactions: Suspend medication for 1-2 days and resume medication after symptoms have improved.
Abnormal behavior: Ensure a quiet environment and avoid stimulation. If it persists for more than 24 hours, seek medical attention.
Vomiting: Feeding small amounts of easily digestible food multiple times a day, if>2 times/day, discontinue medication.
2.Serious reaction (requiring immediate discontinuation of medication)
Serotonin syndrome: tremors, high fever, diarrhea (rare but potentially fatal).
Allergic reactions: facial swelling, difficulty breathing, shock.
Hepatotoxicity: jaundice, vomiting, loss of appetite (increased risk of long-term medication or liver disease in cats).
Emergency Measure:
Immediately rinse the contact area with warm water to remove any residual medication.
Bring the medication packaging to the nearest veterinary clinic and inform them of the medication history.
Monitor vital signs (respiration, heart rate, body temperature) and provide supportive treatment if necessary.
Medication for special populations and disease states
Pregnant and lactating cats
Taboo: Not evaluated for safety, prohibited for use in pregnant, lactating, or breeding cats.
Alternative solution: Prioritize the treatment of primary diseases (such as pyometra and mastitis), and nutritional support therapy can be used for appetite stimulation.
Cats with chronic kidney disease
Monitoring indicators: Blood urea nitrogen (BUN), creatinine, and electrolytes are tested before medication.
Dose adjustment: If BUN>50mg/dL or if polyuria or dehydration occurs, reduce to 1mg/day.
diabetes cats
Blood glucose monitoring: Fasting blood glucose should be measured daily during medication. If it exceeds 300mg/dL, medication should be stopped.
Insulin adjustment: After improving appetite, it may be necessary to reduce insulin dosage to avoid hypoglycemia.
Drug interactions
Taboo combination therapy
Monoamine oxidase inhibitors (MAOIs), such as selegiline and promethazine, can cause serotonin syndrome when used in combination.
Saiheptadine: an antihistamine that increases the risk of central inhibition when used in combination.
Tramadol: an analgesic that, when used in combination, may cause high fever and convulsions.
Be cautious when using combination drugs
5-HT reuptake inhibitors (SSRIs), such as fluoxetine, may enhance the 5-HT effect when used in combination, leading to diarrhea and tremors.
Benzodiazepines, such as diazepam, can be used in combination to enhance sedation and increase the risk of falls.
Warfarin: Mirtazapine Ointment may slightly increase INR values, and coagulation function needs to be monitored.
Key points of patient education
Medication compliance
Fixed time: Take medication at the same time every day (such as before bedtime) to reduce the risk of missed doses.
Recording tool: Use a calendar or mobile reminder to mark the date of medication use.
Family environment adjustment
Dietary management: Provide high calorie, easily digestible foods (such as prescription food, chicken breast puree), and feed in small amounts multiple times.
Reduce stress: Avoid unfamiliar visitors, noise stimulation, and provide a hidden resting place.
Emergency situation identification
Red warning signal:
Cats refuse to eat for more than 48 hours.
Vomit with blood or coffee color.
Abnormal behavior (such as hitting a wall or falling into a coma).
Contact information: Save 24-hour veterinary emergency phone number and prepare for transportation.
Frequently Asked Questions
Why is it considered to make a topical "ointment" for the treatment of oral antidepressants, such as rice nitrogen plain?
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The main goal is to avoid the central nervous system side effects (such as drowsiness and weight gain) caused by oral administration, while utilizing its local antihistamine and anti-inflammatory properties to explore the possibility of "old drugs for new use" in the treatment of specific skin diseases.
What is the core treatment scenario envisioned (non depression)?
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Mainly targeting chronic itching, especially nodular itching, atopic dermatitis, or uremic itching that are resistant to other treatments. The mechanism is to block the histamine H1 receptor and 5-HT2 receptor in the skin, directly inhibiting the generation and transmission of itch signals.
As a ointment, can it achieve the ideal goal of "local effectiveness without entering the systemic circulation"?
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In theory, there are advantages, but the challenges are enormous. Transdermal administration aims to achieve local high concentration and reduce systemic exposure. However, mirtazapine itself has high lipophilicity and is easy to penetrate the skin. Its molecular weight (~265) is also suitable for transdermal use, so it still needs to be closely monitored to prevent systemic absorption.
What are the theoretical advantages compared to topical anesthetics (such as lidocaine) or steroid ointments that are also used for itching relief?
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The advantage lies in multi-target action and non hormonal mechanisms. It also has antihistamines, regulates inflammation, and does not pose long-term risks such as hormone induced skin atrophy and capillary dilation. It is suitable for use in thin and tender skin areas or situations that require long-term maintenance treatment.
Are there any approved or clinically advanced topical formulations of mirtazapine currently available?
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None at the moment. As of October 2024, there are no regulatory agencies worldwide that have approved the marketing of topical formulations of mirtazapine. It is still in the early preclinical or exploratory clinical research stage and belongs to a highly experimental treatment concept.
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