Sawai

]

2. Pregnant women or women who may become pregnant [Safety during pregnancy has not been determined. ]

For patients with endocrine abnormalities, clinical symptoms need to be observed and blood hormone levels (TSH, prolactin, etc.) measured as needed.

This drug has not been investigated to clarify the incidence of side effects, such as an outcome survey.

1. Convulsions may occur. If such symptoms occur, appropriate measures should be taken, such as discontinuing administration.

2. Malignant syndromes such as fever, immobility, muscle stiffness, weakness, tachycardia and blood pressure fluctuations may occur. If such symptoms occur, discontinue administration, lower body temperature, and take appropriate measures such as hydration. In addition, at the onset of the disease, an increase in leukocytes and serum CK (CPK) often occurs, and decreased renal function accompanied by myoglobinuria may occur.

3. Increases in AST (GOT), ALT (GPT), Al-P, LDH, γ-GTP, etc. may lead to liver insufficiency or jaundice. Stop management and take appropriate action.

1. Shock-like symptoms may occur, such as transient hypotension and loss of consciousness.

2. When administered to patients with pituitary adenoma, pituitary apoplexy accompanied by headache, vision, visual field disturbance, etc. may occur. If such symptoms occur, appropriate treatment such as surgery should be performed.

3. Thrombocytopenia may occur. Patients should be carefully monitored. If any abnormalities are detected, appropriate measures should be taken, such as discontinuing administration.

Frequency unknown Decreased red blood cells, decreased hemoglobin Changes in circulating blood pressure and pulse, palpitations Gastrointestinal nausea, vomiting, diarrhea, loss of appetite, stomach discomfort, gastritis, abdominal pain, dry mouth, constipation, glossitis Increased liver AST (GOT), ALT (GPT), γ-GTP, Al-P, LDH, triglycerides, total cholesterol Increased renal BUN Mental and nervous system headaches, dizziness, lightheadedness, tremors, numbness, drowsiness, lightheadedness, insomnia Allergy rash, so itchy Endocrine TSH fluctuations, elevated thyroid hormones (T3, T4), elevated prolactin, gynecomastia Otherwise, elevated CK (CPK), elevated blood sugar, fever, fatigue, frequent urination, hair loss

If any side effects are observed, appropriate measures should be taken, such as discontinuing administration.

This drug is primarily excreted by the kidneys, but because kidney function is often impaired in the elderly, high blood pressure may persist.

1. Administer to pregnant women or women who may become pregnant only when the benefits of treatment are considered to outweigh the risks. [The safety of use during pregnancy has not been established. ]

2. Women who breastfeed only when the benefits of treatment are believed to outweigh the risks. [It has been reported in animal experiments that it passes into milk. ]

Safety has not been established in low birth weight infants, neonates, infants, or children (no experience with use in low birth weight infants, neonates, infants, infants, or children).

During drug delivery: Instruct the patient to place the drug into the PTP package after removing it from the PTP sheet. (It has been reported that due to accidental ingestion of PTP tablets, the steep acute angle penetrates the esophageal mucosa and further leads to perforation causing serious complications such as mediastinal sinusitis)

Pharmacokinetics

1. Bioequivalence studies of Taltilelin tablets 5 mg "Sawai" and the standard formulation were measured in fasting single oral administration (crossover method) in healthy adult males (5 mg as tartilelin hydrate). As a result of the statistical analysis of the obtained pharmacokinetic parameters (AUC, Cmax), the bioequivalence of the two agents was confirmed.

Plasma concentrations and parameters such as AUC and Cmax can vary depending on test conditions, such as subject selection and the number and timing of body fluid collections.

2. Dissolution behavior, it has been confirmed that this preparation meets the dissolution standards set by the Japanese Pharmacopoeia.

Pharmacokinetic parameters when administering one tablet

Cmax (ng/mL) Tmax (hour) T1/2 (hour) AUC0-12 hour (ng·hr/mL) Tartilelin Tablet 5 mg "Sawai" 3.28±3.38 3.6±1.2 2.2±0.4 18.71±16.52 Standard formula (tablet, 5 mg) 2.99±1.88 4.2±1.7 2.6±1.0 17.68±7.22

(mean±SD)

Medicinal Pharmacology

Tartilelin is a derivative of thyroid stimulating hormone-releasing hormone (TRH). It is believed that ataxia in spinocerebellar degeneration can be improved by activating the acetylcholine, dopamine, norepinephrine, and serotonin nervous systems upon binding to TRH receptors that are widely distributed in the central nervous system. In addition, spinal reflex-enhancing effects, neurotrophic factor-like effects, and local glucose metabolism promotion are also thought to be related to drug efficacy. 2)

Physical and chemical knowledge about the active ingredient

Common name Taltirelin hydrate

Chemical name N - [(4S)-1-methyl-2,6-dioxohexahydropyrimidine-4-carbonyl] -L-Histidyl-L-prolinamide tetrahydrate

Molecular formula C17H23N7O5·4H2O.

Molecular weight 477.47

Structural formula

Properties Tartilelin hydrate is white crystal or crystalline powder. Easily soluble in water, ethanol (99.5) or acetic acid (100), slightly soluble in methanol. Dissolve in 1 mol/L hydrochloric acid test solution.