Contraindications and Mechanism of Pembrolizumab

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Contraindications and Mechanism of Pembrolizumab

Journal of pharmacy practice and education is an open access, peer reviewed journal that focuses on the interdisciplinary research offering therapeutic solutions to various neurological, genetics, psychological, and respiratory issues affecting the human beings.

Pembrolizumab (formerly lambrolizumab, trade name Keytruda) is a humanized antibody used in cancer immunotherapy. This includes to treat melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, and stomach cancer. It is given by slow injection into a vein.

Common side effects include itchiness, rash, cough, fever, nausea, and constipation. It is an IgG4 isotype antibody that blocks a protective mechanism of cancer cells and thereby, allows the immune system to destroy them. It targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes.

Pembrolizumab was approved for medical use in the United States in 2014. In 2017 the FDA approved it for any unresectable or metastatic solid tumor with certain genetic anomalies

Contraindications

If a person is taking corticosteroids or immunosuppressants, those drugs should be stopped before starting pembrolizumab because they may interfere with pembrolizumab; they may be used after pembrolizumab is started to deal with immune-related adverse effects.

Women of child-bearing age should use contraception when taking pembrolizumab; it should not be administered to pregnant women because animal studies have shown that it can reduce tolerance to the fetus, increasing the risk of miscarriage. It is not known whether pembrolizumab is present in breast milk.

As of 2017, the drug had not been tested in people with active infections (including any HIV, hepatitis B or hepatitis C infection), kidney or liver disease, active CNS metastases, active systemic autoimmune disease, interstitial lung disease, prior pneumonia, and people with a history of severe reaction to another monoclonal antibody.

Mechanism of action

Pembrolizumab is a therapeutic antibody that binds to and blocks PD-1 located on lymphocytes. This receptor is generally responsible for preventing the immune system from attacking the body's own tissues; it is a so-called immune checkpoint. Many cancers make proteins that bind to PD-1, thus shutting down the ability of the body to kill the cancer on its own. Inhibiting PD-1 on the lymphocytes prevents this, allowing the immune system to target and destroy cancer cells; this same mechanism also allows the immune system to attack the body itself, and checkpoint inhibitors like pembrolizumab have immune-dysfunction side effects as a result.

Tumors that have mutations that cause impaired DNA mismatch repair, which often results in microsatellite instability, tend to generate many mutated proteins that could serve as tumor antigens; pembrolizumab appears to facilitate clearance of any such tumor by the immune system, by preventing the self-checkpoint system from blocking the clearance.

Rutherford

Editorial Manager

Journal of pharmacy Practice and Education