● Pharmacological effects

is a non amphetamine appetite inhibitor with antidepressant properties. Sibutramine acts mainly through its secondary (M1) and primary (M2) amine metabolites. Its mechanism of action is to inhibit the Reuptake of norepinephrine, 5-hydroxytryptamine and dopamine, increase satiety and accelerate energy consumption, but has no significant effect on the release of norepinephrine, 5-hydroxytryptamine and dopamine. The study also showed that Sibutramine and its amine Active metabolite had no significant anticholinergic, antihistamine and monoamine oxidation enzyme inhibition.

● Pharmacokinetics

Sibutramine took effect 8 weeks after oral administration, the weight loss reached the maximum value at 6 months, and the effect of repeated administration lasted for 12 months. The peak time of Sibutramine after oral administration was 1.2 h, and the peak time of metabolites M1 and M2 was 3~4 h. The oral bioavailability is 77%. Food can reduce the maximum concentration of metabolites M1 and M2 and delay the peak time, but there is no significant change in the area under the curve of M1 and M2, so the impact of food on drugs can be ignored. The protein binding rates of Sibutramine, M1 and M2 were 97%, 94% and 94% respectively. The highest concentration was observed in the liver and kidneys after administration. Sibutramine undergoes a large number of first pass metabolism in the liver to form two Active metabolite, M1 and M2. M1 and M2 are further metabolized into inactive M5 and M6. The oral clearance rate is 1750L per hour. The clearance half-life of the parent drug is 1.1 hours, and the half-life of metabolites M1 and M2 is longer, about 14-16 hours. 77% is excreted through the kidneys, about 8% is excreted through feces, and metabolites M5 and M6 are mainly excreted through the kidneys. It is not yet clear whether it is secreted through milk.

● Indications

Sibutramine is applicable to obesity that cannot be reduced and controlled by exercise and diet control, and can reduce weight and maintain the weight that has been lost. Treatment should be combined with a low calorie diet and exercise. The body mass index of obesity patients recommended for medication should be greater than or equal to 30kg/m or greater than or equal to 27kg/m and other risk factors (such as hypertension, diabetes, Dyslipidemia, etc.).

● Contraindications

1. Allergies to Sibutramine and drug ingredients;

2. Patients with Anorexia nervosa;

3. Patients receiving treatment with monoamine oxidase inhibitors;

4. Patients receiving treatment with other central nervous appetite suppressants;

5. Uncontrolled or poorly controlled hypertension patients;

6. Patients with coronary heart disease, palpitations, and arrhythmia;

7. Patients with Cerebrovascular disease, stroke or Transient ischemic attack;

8. Severe liver and kidney dysfunction;

9. Pregnant women (Sibutramine has teratogenic effect but no carcinogenic or mutagenic effect is observed in Animal testing);

10. Breastfeeding women;

11. Organic obesity.

Precautions:

The treatment of obesity should be based on dietary control and exercise.

2. Obese individuals caused by Cushing’s syndrome and hypothyroidism should be excluded from the scope of using this product.

3. Patients with a history of hypertension should use it with caution.

4. Because it may increase or aggravate the formation of gallstones, patients with Gallstone should use this product with caution.

5. This product can cause pupil dilation and should be carefully used in patients with angle closure glaucoma.

6. Patients with epilepsy history should use it with caution, and patients with Seizure should stop using it.

7. It may affect judgment, thinking, or motor skills.

Medication for pregnant and lactating women:

In Animal testing, it is observed that this product has teratogenic effects, but no carcinogenic and mutagenic effects are observed. It is recommended that pregnant women or women preparing for pregnancy and lactation should not take this product.

Children’s medication:

The safety and effectiveness of using this product for children under the age of 16 have not been established, so it is not recommended for children under the age of 16.

Elderly medication:

Due to the increased likelihood of reduced heart, kidney, and liver function in the elderly, as well as concomitant treatment with other diseases, caution should be exercised in the dosage selection for the elderly.

Interactions with other drugs

1. The combination of Sibutramine and other central appetite inhibitors may cause severe hypertension and tachycardia. Therefore, the combination of Sibutramine and other central appetite inhibitors is prohibited.

2. When Sibutramine is used in combination with Dextromethorphan, dihydroergotoxine, Ergotamine, fentanyl, lithium, Pethidine, Pentazocine, selective serotonin reuptake inhibitor, serotonin agonist, Tryptophan, etc., it can cause high serotonin status and serotonin syndrome (hypertension, hypothermia, myoclonus and mental disorders, etc.).

3. When Sibutramine is used together with cytochrome P4503A4 enzyme inhibitor, the plasma concentration of Sibutramine increases. Therefore, caution should be exercised when using drugs that affect the activity of cytochrome P4503A4 enzyme simultaneously. Inhibitors of cytochrome P4503A4 enzyme include Ketoconazole, Erythromycin, Troleandomycin and Ciclosporin; Inducers include Rifampicin, Macrolide antibiotics, phenytoin sodium, Carbamazepine, Phenobarbital and dexamethasone.

4. When Sibutramine is used in combination with monoamine oxidation enzyme inhibitor, it may cause central nervous system toxicity or 5-hydroxytryptamine syndrome. It is prohibited to use it in combination with sibutramine.

5. Sibutramine can affect blood pressure and heart rate, so it should be carefully used in combination with other drugs that affect blood pressure and heart rate (such as drugs containing Phenylpropanolamine, Ephedrine or Pseudoephedrine).

6. Sibutramine has no effect on ovulation inhibition caused by oral contraceptives. Since there is no obvious clinical interaction, women taking Sibutramine and oral contraceptives do not need to use other contraceptives.