那他珠单抗(Natalizumab)的注意事项和药物相互作用

Natalizumab is a recombinant humanized anti-α4-integrin monoclonal antibody available through prescription plans only.

Indications of Natalizumab

1. Multiple sclerosis (MS)

It is used as a monotherapy for the treatment of adult patients with relapsing forms of multiple sclerosis (including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease).

2. Crohn's disease

Indicated to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease and evidence of inflammation who are inadequately responsive to or intolerant to conventional therapies and tumor necrosis factor (TNF; TNF-alpha) inhibitors.

Due to the possible increased risk of PML and other infections, talizumab should not be used in combination with immunosuppressants (such as mercaptopurine, azathioprine, cyclosporine, methotrexate) or TNF inhibitors in patients with Crohn's disease.

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Natalizumab (Natalizumab) Precautions

1. Progressive multifocal leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy usually occurs in immunocompromised patients (such as HIV-infected patients) and often leads to death or severe disability.

Use is not recommended in patients receiving chronic immunosuppressive or immunomodulatory therapy, or in patients with systemic disease resulting in clinically important immune compromise.

2. Herpes infection

Natalizumab increases the risk of encephalitis and meningitis caused by herpes simplex and varicella-zoster viruses. Monitor patients for signs and symptoms of meningitis and encephalitis. If herpetic encephalitis or meningitis occurs, discontinue natalizumab and initiate appropriate treatment.

3. Hepatotoxicity

Elevated transaminase levels accompanied by elevated bilirubin (without evidence of obstruction) are generally considered important predictors of severe liver injury that may lead to death or require liver transplantation.

Discontinue natalizumab in patients who develop jaundice or other clinically significant evidence of liver injury (e.g., laboratory evidence).

4. Hypersensitivity reaction/antibody formation

If a hypersensitivity reaction (such as allergic reaction, urticaria, dizziness, fever, rash, chills, itching, nausea, flushing, hypotension, difficulty breathing, chest pain) occurs, stop the infusion immediately and start appropriate treatment. It should not be used again in anyone who has had a hypersensitivity reaction to this drug. In patients who develop a hypersensitivity reaction, consider the possibility of anti-natalizumab antibodies.

5. Immunosuppression and infection

May increase the risk of infection, including opportunistic infections (such as PML).

Concomitant use of natalizumab with antineoplastic agents, immunosuppressants, or immunomodulators may further increase the risk of infections, including PML and other opportunistic infections. The safety and effectiveness of natalizumab in combination with antineoplastic agents, immunosuppressives, or immunomodulators have not been established.

6. Abnormal laboratory tests

Natalizumab can cause an increase in circulating lymphocytes, monocytes, eosinophils, basophils and nucleated red blood cells. Observed changes persisted during exposure but were reversible, typically returning to baseline levels within 16 weeks of the last dose.

Natalizumab also causes a mild, often transient, drop in hemoglobin levels.

7. Hematological abnormalities

Thrombocytopenia has been reported, including immune thrombocytopenic purpura (ITP). Symptoms may include easy bruising, abnormal bleeding, and petechiae. If thrombocytopenia is suspected, discontinue natalizumab.

Neonatal thrombocytopenia and anemia have been reported in neonates exposed to natalizumab in utero. Perform a complete blood count (CBC) on newborns exposed in utero.

8. Immunization

There are no data on the efficacy of vaccination or secondary transmission of live vaccine infection in patients receiving natalizumab.

Drug interactions of Natalizumab

1. Patients with Crohn's disease

It should not be used in combination with immunosuppressants (such as 6-mercaptopurine, azathioprine, cyclosporine, methotrexate) or TNF-α inhibitors; patients using chronic corticosteroids need to gradually reduce the dosage.

2. Patients with multiple sclerosis

Usually should not be combined with chronic immunosuppressants or immunomodulators because they may increase the risk of PML and other infections.

The safety and effectiveness of natalizumab in combination with antineoplastic agents, immunosuppressants, or immunomodulators have not been established.

Special population use of natalizumab

1. Pregnancy

There are insufficient data on the risk of major birth defects, miscarriage, or other adverse maternal outcomes associated with the use of natalizumab during pregnancy; adverse fetal outcomes have been reported, including neonatal thrombocytopenia, sometimes accompanied by anemia. Perform a complete blood count (CBC) on newborns exposed to natalizumab in utero.

2. Lactation

Natalizumab is secreted into human milk; the effects of the drug on nursing infants or breast milk are unknown.

Consider the benefits of breastfeeding and the woman's clinical need for talizumab, as well as any potential adverse effects on the breastfed infant from this drug or the underlying maternal disease.

3. Pediatric use

The safety and effectiveness have not been determined in patients with MS or Crohn's disease under the age of 18.

4. Medication in the elderly

There is insufficient experience in patients ≥65 years old to determine whether the response of elderly patients is different from that of young adults.

5. Hepatic insufficiency

Clinically significant liver function abnormalities have been reported in patients receiving natalizumab.

6. Renal insufficiency

This product has not been studied in patients with renal insufficiency.