Felycin-CA1 Tablets for Cats: FDA-Approved Sirolimus Treatment for Subclinical HCM

What Are Felycin-CA1 Tablets? (Sirolimus for Cats)

Felycin®-CA1 is the first veterinary-specific brand of Sirolimus (Rapamycin). It is formulated as an enteric-coated tablet for cats, which delays release until the tablet reaches the small intestine to prevent the acid-labile drug from degrading in the stomach. This ensures consistent absorption but does not provide a sustained or gradual release; its pharmacokinetic profile is bioequivalent to other immediate-release sirolimus products. The key innovation is its small size and precise dosing for veterinary use, enabling an intermittent dosing schedule (e.g., once weekly). This pharmacodynamic strategy aims to inhibit specific cellular pathways (mTORC1) beneficial for heart disease while limiting inhibition of others (mTORC2) linked to side effects. It is specifically designed to help manage chronic conditions such as Hypertrophic Cardiomyopathy (HCM) in cats by modulating cellular growth and reducing inflammation.

Active Ingredient: Sirolimus (Rapamycin)

Sirolimus (Rapamycin) is a macrocyclic lactone produced by the bacterium Streptomyces hygroscopicus.

Felycin-CA1 Uses: Treating Subclinical HCM in Cats

Indication and FDA Approval

• Felycin®-CA1 (Sirolimus) is used to treat Subclinical Hypertrophic Cardiomyopathy (HCM) in cats.

• On March 14, 2025, the FDA granted Conditional Approval to Felycin-CA1 (Sirolimus delayed-release tablets). It is the world’s first FDA-approved drug for treating subclinical HCM in cats.

Understanding Hypertrophic Cardiomyopathy (HCM)

Hypertrophic Cardiomyopathy (HCM) is a common and serious heart disease in cats. It occurs when the muscular wall of the heart—particularly the left ventricle—becomes abnormally thickened. This thickening interferes with the heart’s ability to pump blood efficiently, potentially leading to heart failure if left untreated.

When this wall thickens:

• The heart has a harder time filling with blood.
• Blood pressure builds up in the heart and lungs.
• This can lead to breathing problems, fluid in the lungs, or even heart failure.
• In some cases, it can cause sudden death, especially if it’s not diagnosed and treated.

Some cats with HCM also have a valve problem that makes it harder for blood to flow out of the heart to the rest of the body.

Felycin-CA1 Tablet Specifications

Active Ingredient

• Sirolimus (Rapamycin)

Available Strengths & Color Coding

• 0.4 mg: Orange tablet
• 1.2 mg: Blue tablet
• 2.4 mg: White tablet

Physical Characteristics

• Enteric film-coated tablet: This special coating ensures the drug dissolves in the intestines.

Subclinical HCM in Cats: Diagnosis Criteria

What is Hypertrophic Cardiomyopathy (HCM) in Cats?
Hypertrophic Cardiomyopathy (HCM) is a common and serious heart disease in cats. It occurs when the muscular wall of the heart—particularly the left ventricle—becomes abnormally thickened. This thickening interferes with the heart’s ability to pump blood efficiently, potentially leading to heart failure if left untreated. A preliminary stage of heart disease with no visible symptoms, detectable only via laboratory tests.

Inclusion Criteria (Diagnosis Requirements)

• Left ventricular wall must be thickened.
• Measured via echocardiography (2D or M-mode).
• Left ventricular thickness ≥6 mm indicates subclinical HCM.

Exclusion Criteria (Conditions to Rule Out)

1. Systemic Hypertension: Ensure normal blood pressure (high BP can cause wall thickening).
2. Other Causes of Myocardial Thickness: e.g., natural thickening in athletes or other diseases.
3. History Exclusion:
   • Congestive Heart Failure (fluid buildup due to heart weakness).
   • Arterial Thromboembolism (artery blockage by clots).
   • Severe LV Outflow Obstruction (critical blood flow blockage).

Sirolimus Tablet for Cat Dosage & Administration

Recommended Rapamycin Dosage for Cats

• Administer 0.3 mg/kg of body weight orally once weekly.

How to Administer

• Give the tablet whole—do not cut, crush, or chew.
• Always administer with food.

Rapamycin Dosage for Cats

Sirolimus Tablet for Cat Side Effects & Contraindications

Critical Contraindications

• ❌ Do NOT use in diabetic cats.
• ❌ Discontinue immediately if diabetes develops during treatment.
• ❌ Avoid in cats with pre-existing liver disease.

Risk of Diabetic Ketoacidosis (DKA)

• Using FELYCIN®-CA1 in diabetic cats may trigger life-threatening Diabetic Ketoacidosis (DKA).

Diabetic Ketoacidosis (DKA) in Cats

What Is DKA?
A metabolic emergency caused by insulin deficiency/resistance, disrupting glucose metabolism. Cells cannot use glucose for energy, forcing the body to break down fat into ketone bodies.

Hormonal Role in Glucose Balance

• Glucagon: Secreted by pancreatic α-cells → raises blood glucose.
• Insulin: Secreted by pancreatic β-cells → lowers blood glucose.
  Imbalance (e.g., insulin deficiency) causes diabetes.

Consequences of DKA
Excess ketones disrupt acid-base balance (pH), leading to:

• Dehydration
• Electrolyte imbalances (e.g., potassium/phosphorus deficiency)
• Organ dysfunction (heart, brain, kidneys).

DKA Treatment Protocol

1. IV Fluid Therapy: Rehydrate and improve circulation.
2. Regular/Short-Acting Insulin: Regulate blood glucose.
3. Electrolyte Supplementation: Restore potassium/phosphorus.
4. Continuous Monitoring:
   • Blood glucose
   • Ketone levels
   • Acid-base status (pH)

Sirolimus Tablet for Cat Side Effects & Safety Warnings

Critical User Safety Warnings

• 🚫 Not for human use – Keep out of children’s reach.
• 🚫 If accidentally ingested by humans, seek immediate medical attention.

Handling & Administration Precautions

• ❌ Do NOT administer to pregnant or lactating cats.
• ❌ Use cautiously in cats with known Sirolimus allergy.
• ✅ Always store tablets in original packaging – Remove from blister pack ONLY at dosing time.
• ❌ If a cat refuses the tablet, destroy it immediately.
• 🧤 Wear gloves when cleaning vomit/saliva/tablet residue → Wash hands thoroughly afterward.

Note: The enteric coating protects against direct Sirolimus exposure during normal use. Chewing, vomiting, or tablet damage compromises this barrier.

Drug Interactions & Special Risks

Sirolimus and Other Medications
Sirolimus is metabolized by enzymes/proteins (CYP3A4, P-glycoprotein). High-risk interactions with:

• Calcium channel blockers (blood pressure meds)
• Amiodarone (heart rhythm regulator)
• Azole antifungals (e.g., Ketoconazole)
• Cyclosporine (immunosuppressant)
  → May cause toxic Sirolimus buildup.

High-Risk Cats: MDR1 Gene Mutation
Cats with MDR1 gene mutations have reduced drug-elimination capacity → Higher sensitivity to FELYCIN®-CA1. Use extreme caution with:

• Eprinomectin
• Emodepside

Effect on Vaccinations
FELYCIN®-CA1 may suppress immune response to vaccines:

• 🟢 Rabies (killed virus): No significant impact observed.
• 🔴 Other vaccines: Efficacy uncertain for:
  • FHV-1 (Feline Herpes)
  • FCV (Calicivirus)
  • FPV (Panleukopenia)
  • FeLV (Leukemia)

Sirolimus Tablet for Cat Side Effects: Clinical Study Findings

Pilot Field Study Overview

• *180-day controlled trial with 43 subclinical HCM cats:*

Cardiac Side Effects

Most common in medicated cats (linked to HCM progression):

• ⚠️ Arrhythmia (irregular heartbeat)
• ⚠️ Congestive Heart Failure (fluid buildup)
• ⚠️ Syncope (sudden fainting)
• ⚠️ Pericardial Effusion (fluid around heart)

Critical High-Dose Cases (0.6 mg/kg):
3 cats experienced:

• Sudden death or severe heart failure
• 2 had pre-existing advanced heart disease
• 1 showed elevated biomarker NTproBNP (1344 pmol/L; normal <100) indicating high progression risk.
  Note: Causality not confirmed due to small sample size and variable HCM progression.

Non-Cardiac Side Effects

Common across treatment groups:

• Lethargy
• Vomiting
• Diarrhea
• Inappetence

Diabetes Mellitus Risk

• One cat (0.3 mg/kg group) developed:
  • Hypercholesterolemia
  • Hyperglycemia
  • Glucosuria
  • UTI symptoms
    → Progressed to fatal Diabetic Ketoacidosis (DKA) → Cardiac arrest.

Liver Disease Complications

• Pre-existing elevated liver enzymes (ALP/ALT/AST):
  • Worsened anorexia
  • Further enzyme elevation
  • Icterus (jaundice)
    → Euthanized 4 months post-study due to irreversible decline.

Conclusion: Managing Risks with Sirolimus for Cats

Key Safety Recommendations

1. ❗ Contraindicated in cats with:
   • Pre-existing diabetes
   • Liver disease
2. ⚠️ High-risk patients:
   • Advanced HCM (NTproBNP >100 pmol/L)
   • MDR1 gene mutation
3. ✅ Mandatory protocols:
   • Weekly cardiac monitoring
   • Blood glucose checks
   • Liver enzyme panels every 4-6 weeks
4. 🚨 Immediate discontinuation if:
   • Hyperglycemia symptoms appear
   • Appetite loss persists >48 hrs

*FELYCIN®-CA1 requires vigilant risk-benefit assessment—reserve for early-stage HCM with no comorbidities.*

Contact Information

Report adverse events or seek assistance:

• 🏥 PRN Pharmacal: 1-800-874-9764
• ⚕️ FDA Veterinary Adverse Events:
  • ☎ 1-888-FDA-VETS
  • 🌐 www.fda.gov/reportanimalae

Clinical Pharmacology of Felycin-CA1 Tablets

Mode of Action: How Sirolimus Works in Cats
Sirolimus is an immunosuppressant drug primarily used in human organ transplants to prevent antibody rejection. It inhibits the protein complex mTORC1 (mammalian Target of Rapamycin Complex 1), which regulates:

• Cell growth
• Nutrient response

Observed effects in studies:

• ↓ Cardiac hypertrophy (abnormal heart muscle thickening)
• ↑ Autophagy (cellular self-cleaning via lysosomes)
• ↓ Oxidative stress
• ↓ Inflammatory responses
  → Sirolimus improves cardiac outcomes in cats.

Sirolimus Pharmacokinetics in Cats

Drug Absorption, Distribution & Elimination
Pharmacokinetics describes how a drug is:

1. Absorbed
2. Distributed
3. Metabolized
4. Eliminated

*24-week study in healthy cats (once-weekly dosing):*

Key Findings :

1. Saturation Effect:
   • Higher doses DO NOT increase absorption → Body absorbs only up to a threshold.
   • *Implication: Exceeding 0.3 mg/kg/week provides no added benefit.*
2. Non-Linear Kinetics:
   • Drug effects vary over time → Repeated dosing alters response patterns.

Sirolimus Pharmacokinetics at 0.38 mg/kg Dose

Drug Accumulation Findings
*147-day observation in cats revealed significant drug accumulation:*

Conditional FDA Approval: Reasonable Expectation of Effectiveness

What This Means
FELYCIN®-CA1 holds conditional FDA approval (March 2025), not full approval. This indicates:

• ✅ Preliminary studies show therapeutic promise for feline HCM.
• ⚠️ Large-scale validation required for conclusive evidence.

Evidence Supporting Sirolimus Effectiveness in Cats

Published Preclinical Studies

1. Rat Models:
   • ↓ Left Ventricular Hypertrophy (LVH)
   • ↑ Cardiac function improvement
2. Human Transplant Patients:
   • Enhanced cardiac remodeling post-surgery

Results (180 Days):

• Withdrawals: 6 cats (5 high-dose, 1 placebo) due to:
  • Worsening heart disease
  • Accidental death
  • Owner decision

Conclusions & Future Needs

• FELYCIN®-CA1 demonstrates potential efficacy in:
  • Reducing cardiac muscle thickness
  • Improving heart structure
• ❗ Mandatory next steps:
  • Large-scale, long-term clinical trials
  • Ongoing safety monitoring

Source By : FDA & DAILYMED