那他珠单抗(Natalizumab)的注意事项和药物相互作用？

Natalizumab was originally developed by Biogen (in collaboration with Elan) and needs to be used under the guidance of a professional physician.

Natalizumab (Natalizumab) Precautions

1. Progressive multifocal leukoencephalopathy (PML)

PML is a severe brain infection caused by JC virus, with a high mortality rate. Risk factors include:

(1) Positive anti-JCV antibodies: patients need to regularly detect antibody status.

(2). Long medication time: especially if it exceeds 2 years, the risk increases significantly.

(3) Past use of immunosuppressants: such as azathioprine, methotrexate, etc.

Perform brain MRI examinations before and regularly during medication. If neurological symptoms (such as limb weakness, blurred vision, cognitive impairment) occur, the medication should be discontinued and evaluated immediately. Monitoring is still required for at least 6 months after discontinuation of medication.

2. Risk of infection

(1) Herpes virus infection: may cause encephalitis, meningitis or acute retinal necrosis, and severe cases may cause blindness.

(2) Other opportunistic infections: such as pulmonary fungal infection, recurrence of tuberculosis, etc.

Avoid live vaccinations during medication, and seek medical attention promptly if symptoms of infection occur.

3. Hepatotoxicity

Rare but serious cases of liver injury have been reported, even requiring liver transplantation. Liver function should be monitored during medication. If symptoms such as jaundice, fatigue, and darkened urine occur, the medication must be discontinued.

4. Hypersensitivity reaction

About 1% of patients may experience severe allergic reactions, such as urticaria, dyspnea, hypotension, etc. Observation is required for 1 hour after the first infusion, and the observation time for subsequent infusions should be adjusted according to the situation.

5. Thrombocytopenia

Rare but may cause bleeding tendencies, such as ecchymosis, epistaxis, etc. Platelet count needs to be monitored during treatment.

Natalizumab drug interactions

Be careful when using it in combination with other drugs, especially immunomodulatory drugs:

1. Contraindicated combined use

(1) Patients with Crohn's disease: It is prohibited to use it in combination with immunosuppressants (such as azathioprine, 6-mercaptopurine, methotrexate) or TNF-α inhibitors (such as infliximab) to avoid increasing the risk of PML and infection;

(2) Patients with multiple sclerosis: Combination with immunosuppressants or immunomodulators is generally not recommended.

2. Adjustment of glucocorticoids

If patients with Crohn's disease are taking glucocorticoids, they should reduce the dose as soon as possible after taking effect. If they cannot be stopped within 6 months, natalizumab needs to be stopped.

3. Vaccine related

There is no data to support the safety of live vaccines during medication and their use should be avoided.

Natalizumab pharmacokinetics

1. Absorption and distribution

(1). Administration method: intravenous infusion of 300 mg, once every 4 weeks.

(2) Time to reach peak: The peak will be reached after the infusion is completed.

(3). Distribution volume: about 5.2–5.7L, indicating that it is mainly distributed in plasma and extracellular fluid.

2. Metabolism and clearance

(1). Half-life: about 10–11 days.

(2). Clearance rate: MS patients are about 16mL/h, CD patients are about 22mL/h.

(3). Steady state time: about 16-24 weeks.