Kygevvi provides significant survival benefits for patients with the rare disease TK2 deficiency, but the treatment may be accompanied by various adverse effects, with gastrointestinal reactions and liver function impairment being the most prominent.

I. Common and Serious Adverse Effects of Kygevvi

1. Common Adverse Reactions (Incidence ≥ 5%)

According to clinical trial data, the most frequently reported adverse reactions in patients receiving Kygevvi include:

(1) Diarrhea: Occurring in up to 72% of patients, it is the most common side effect.

(2) Abdominal Pain: Including upper abdominal pain, with an incidence of approximately 23%.

(3) Vomiting: Having an incidence of about 21%, it is more common in pediatric patients (28%).

(4) Increased Liver Transaminases: Elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occur in 21% and 17% of patients respectively, which may also be a potential manifestation of the disease itself.

2. Serious Adverse Effects Requiring Vigilance

Certain side effects may lead to treatment interruption, dose reduction, or even hospitalization, and require high attention:

(1) Liver Function Impairment: Increased liver enzymes may result in permanent treatment discontinuation (accounting for approximately 3% in clinical trials). Symptoms such as decreased appetite, right upper quadrant pain, jaundice (yellowing of the skin or sclera), dark urine, and pruritus may indicate potential liver injury.

(2) Severe Gastrointestinal Reactions: Severe or persistent diarrhea and vomiting may lead to dehydration and electrolyte imbalance, and have required hospitalization in some patients (including pediatric patients). In clinical trials, 3% of patients discontinued treatment permanently due to diarrhea or increased liver enzymes, and 21% required dose reduction due to diarrhea.

II. Ways to Mitigate and Manage Adverse Effects

1. Management of Liver Function Abnormalities

(1) Baseline Monitoring: Baseline levels of ALT, AST, and total bilirubin must be measured prior to the initiation of treatment.

(2) Regular Re-examination: Liver function should be monitored at least annually during treatment, and the frequency may be increased based on clinical indications.

(3) Prompt Intervention: Immediately discontinue treatment if symptoms related to liver injury or a significant increase in liver enzymes occur. Upon the return of liver function indicators to baseline or stabilization at a new baseline, treatment may be resumed at the previously tolerated dose under the guidance of a physician, with careful dose titration. If liver injury persists or worsens, permanent discontinuation should be considered.

2. Management of Gastrointestinal Reactions

(1) Dose Adjustment: Reduce the dose or suspend medication based on the severity of diarrhea/vomiting.

(2) Supportive Care: Closely monitor for signs of dehydration (e.g., decreased urine output, dry mouth, dizziness). In case of diarrhea or vomiting, promptly replenish fluids and electrolytes through oral rehydration salts or similar means. For persistent or recurrent severe gastrointestinal reactions, permanent discontinuation should be considered.

(3) Special Considerations for Pediatric Patients: Children are at higher risk of vomiting and severe diarrhea; caregivers should provide close observation and care.

3. General Principles

(1) All dose adjustments and treatment decisions must be conducted under the guidance of the attending physician.

(2) Patients and caregivers should be aware of the early signs of side effects, communicate promptly with the medical team, and never manage symptoms independently or ignore them.

III. Correct Storage Conditions of Kygevvi

1. Storage of Drug Powder (Unopened Packaging)

(1) Storage Temperature: Store at room temperature between 20°C to 25°C (68°F to 77°F).

(2) Allowable Range: For short-distance transportation or temporary storage, the temperature may fluctuate between 15°C to 30°C (59°F to 86°F).

(3) Precautions: Keep the packaging intact and store in a dry place out of reach of children.

2. Storage and Disposal of Reconstituted Oral Solution

(1) Storage Options: The reconstituted Kygevvi solution has two storage methods:

(2) Room Temperature Storage: Control at 20°C to 25°C (68°F to 77°F).

(3) Refrigerated Storage: In a refrigerator at 2°C to 8°C (36°F to 46°F).

(4) Key Time Limit: Regardless of the storage method, the solution must be used within 16 hours of reconstitution. If the daily 3-dose regimen is completed during this period, discard any remaining solution immediately.

(5) Storage Requirements: When storing, tightly screw the dosing cup onto the mixing bottle and keep the bottle upright to prevent leakage.

(6) Prohibited Actions: Never use household containers to store the solution, and do not save leftover solution for the next day's use to avoid waste.