Pembrolizumab Drugbank ID :DB09037 Half life : 28 days. Molecular Weight (Daltons):146286.29 Chemical Formula :C6504H10004N1716O2036S46 Description : Pembrolizumab is an antibody drug that targets the cell surface receptor programmed cell death protein 1 (PD-1) found on T cells. By preventing the binding of its ligands (PD-L1 and PD-L2), pembrolizumab induces an antitumor immune response. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Its use is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following therapy with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Due to its success in clinical trials, pembrolizumab was approved early to allow quick patient access and was given breakthrough therapy and orphan drug designation. Pembrolizumab (as Keytruda) was approved by the U.S. Food and Drug Administration to treat advanced cases of the most common type of lung malignancy, non-small cell lung cancer (NSCLC) on Oct. 2, 2015.

Indication : For the treatment of patients with unresectable or metastatic melanoma and disease progression following therapy with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It is also for the treatment of patients with metastatic NSCLC (non-small cell lung cancer) whose tumors express PD-L1 (as determined by an approved test) and who have disease progression on or after platinum-containing chemotherapy. Pharmacodynamics : In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. Mechanism of action : Pembrolizumab is an antibody drug that targets the cell surface receptor programmed cell death protein 1 (PD-1) found on T cells. By preventing the binding of its ligands (PD-L1 and PD-L2), pembrolizumab induces an antitumor immune response. Upregulation of PD-1 ligands is a mechanism for tumours to evade antitumor immune response; when PD-1 binds its ligand, the T cell receives an inhibitory signal leading to T cell anergy and blockade of anti tumour immune response. Instead of directly targeting tumor tissue to induce tumor cell death, pembrolizumab acts as a checkpoint inhibitor to stimulate immune responses to eliminate cancer cells.

Metabolism : Since therapy with pembrolizumab induces tumour regression by stimulation of immune responses, side effects may be caused by activating potentially self-reactive T cells. This includes immune-mediated pneumonitis, colitis, hypophysitis, nephritis and renal failure, hyperthyroidism and hypothyroidism, and hepatitis. Other adverse events such as myasthenic syndrome, optic neuritis, uveitis, arthritis, pancreatitis, partial seizures, and rhabdomnyolysis were reported to occur in less than 1% of patients during clinical trials. Female patients are advised to use highly effective contraception during and for 4 months following treatment due to the risk of fetal harm. Clearance : 0.22 L/day

Categories : Antineoplastic and Immunomodulating Agents Patents : US2012135408 Brands : Keytruda Company : Merck Sharp & Dohme Corp. Formulation : 100 mg of pembrolizumab in 4 mL of solution. Form : lyophilized powder Route of administration : Intravenous infusion

Dosage : The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. Contraindication : NA Side effects : Immune-mediated pneumonitis; Immune-mediated colitis; Immune-mediated hepatitis; Immune-mediated endocrinopathies; Immune-mediated nephritis and renal dysfunction; Other immune-mediated adverse reactions; Infusion-related reactions.

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