Avelumab – Uses, Dosage, Side Effects, Interactions Avelumab is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). It is a fully human anti-PD immunoglobulin G1 (IgG1) lambda monoclonal antibody with antineoplastic actions. It was granted accelerated approval in March 2017 under the name Bavencio. Mechanism of Action PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. The binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen-presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production. Avelumab binds PD-L1 through the FG loops 7 and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth. Indications Avelumab is indicated for the treatment of adult and pediatric patients ≥12 years of age with metastatic Merkel cell carcinoma (MCC). It is also indicated as a maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (UC) which has not progressed with first-line platinum-containing chemotherapy. In addition, it is indicated in patients with locally advanced or metastatic UC who experience disease progression on or after platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Avelumab is additionally indicated as a first-line treatment, in combination with axitinib, in the treatment of advanced renal cell carcinoma (RCC). Associated Conditions Advanced Renal Cell Carcinoma (RCC) Metastatic Urothelial Cancer Locally advanced Urothelial Carcinoma Metastatic Merkel Cell Carcinoma (MCC) First Line Chemotherapy Maintenance therapy Avelumab is approved to treat Merkel cell carcinoma (a type of skin cancer) has spread. It is used in adults and children aged 12 years and older. Renal cell carcinoma (a type of kidney cancer) has spread or cannot be removed by surgery. It is used with axitinib as the first treatment. Urothelial cancer (a type of cancer in the bladder or urinary tract) that has spread or cannot be removed by surgery. It is used: As maintenance therapy in patients whose cancer did not get worse after first-line platinum chemotherapy. In patients whose cancer got worse during or after treatment with platinum chemotherapy. This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, confirmatory trial(s) must show that avelumab provides a clinical benefit in these patients. Contraindications overactive thyroid gland a condition with low thyroid hormone levels low blood sugar decreased function of the adrenal gland a type of inflammation of the lung called interstitial pneumonitis inflammation of the large intestine kidney inflammation abnormal liver function tests pregnancy a patient who is producing milk and breastfeeding Dosage Usual Adult Dose for Merkel Cell Carcinoma 800 mg IV over 60 minutes every 2 weeks Duration of therapy: Until disease progression or unacceptable toxicity Usual Adult Dose for Urothelial Carcinoma 800 mg IV over 60 minutes every 2 weeks Duration of therapy: Until disease progression or unacceptable toxicity Usual Adult Dose for Renal Cell Carcinoma 800 mg IV over 60 minutes every 2 weeks in combination with axitinib 5 mg orally 2 times a day (12 hours apart) with or without food Duration of therapy: Until disease progression or unacceptable toxicity Patients should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions; premedication should be administered for subsequent doses based on clinical judgment and the presence/severity of prior infusion reactions. Usual Pediatric Dose for Merkel Cell Carcinoma 12 years and older: 800 mg IV over 60 minutes every 2 weeks Duration of therapy: Until disease progression or unacceptable toxicity Renal Dose Adjustments Serum creatinine more than 1.5 and up to 6 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper Serum creatinine more than 6 x ULN: Permanently discontinue therapy. Liver Dose Adjustments Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal (ULN) or total bilirubin more than 1.5 and up to 3 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper AST or ALT more than 5 x ULN or total bilirubin more than 3 X ULN: Permanently discontinue therapy. Dosage Adjustments DOSE ADJUSTMENTS FOR ADVERSE REACTIONS PNEUMONITIS: Grade 2: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of pneumonitis after corticosteroid taper Grade 3 or 4 or recurrent Grade 2: Permanently discontinue therapy HEPATITIS Aspartate aminotransferase (AST)/or alanine aminotransferase (ALT) more than 3 and up to 5 times the upper limit of normal (ULN) or total bilirubin more than 1.5 and up to 3 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of hepatitis after corticosteroid taper AST or ALT more than 5 x ULN or total bilirubin more than 3 X ULN: Permanently discontinue therapy COLITIS Grade 2 or 3 diarrhea or colitis: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis: Permanently discontinue therapy You Might Also Read Calaspargase Pegol - Uses, Dosage, Side Effects, InteractionENDOCRINOPATHIES Endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism, adrenal insufficiency, and hyperglycemia): Grade 3 or 4: Withhold therapy; administer corticosteroids as appropriate for adrenal insufficiency; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of endocrinopathies after corticosteroid taper NEPHRITIS AND RENAL DYSFUNCTION: Serum creatinine more than 1.5 and up to 6 x ULN: Withhold therapy; administer prednisone or equivalent at 1 to 2 mg/kg/day followed by a corticosteroid taper; resume therapy in patients with complete or partial resolution (Grade 0 to 1) of colitis or diarrhea after corticosteroid taper Serum creatinine more than 6 x ULN: Permanently discontinue therapy. For moderate or severe signs of an immune-mediated adverse reaction not previously described: Withhold therapy; administer high dose corticosteroids, and if appropriate, initiate hormone replacement; resume therapy in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper For any of the following: Life-threatening adverse reaction (excluding endocrinopathies); recurrent severe immune-mediated adverse reactions; requirement for 10 mg per day or greater prednisone or equivalent for more than 12 weeks; persistent Grade 2 or 3 immune-mediated adverse reactions lasting 12 weeks or longer: Permanently discontinue therapy INFUSION-RELATED REACTIONS: Grade 1 or 2: Interrupt or slow the rate of infusion Grade 3 or 4: Permanently discontinue therapy COMBINATION THERAPY In patients with RCC being treated with this drug in combination with axitinib: If ALT or AST is 3 times the upper limit of normal (ULN) or greater but less than 5 x ULN or total bilirubin is 1.5 x ULN or greater but less than 3 x ULN: Withhold both this drug and axitinib until adverse reactions recover to Grade 0 or 1. If persistent (greater than 5 days), consider corticosteroid therapy (initial dose of 0.5 to 1 mg/kg/day) prednisone or equivalent followed by a taper. Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery. Dose reduction per the axitinib Full Prescribing Information if rechallenging with axitinib. If ALT or AST is 5 x ULN or greater or greater than 3 x ULN with concurrent total bilirubin 2 x ULN or greater or total bilirubin is 3 x ULN or greater, permanently discontinue both this drug and axitinib and consider corticosteroid therapy (initial dose 1 to 2 mg/kg/day prednisone or equivalent followed by a taper). When this drug is administered in combination with axitinib, review the axitinib Full Prescribing Information for recommended dose modifications for axitinib. Administration advice: Do not freeze or shake the diluted solution. Administer the diluted solution over 60 minutes through an IV line containing a sterile, nonpyrogenic, low protein binding in-line filter (pore size of 0.2 microns). Do not coadminister other drugs through the same IV line Reconstitution/preparation techniques: Visually inspect the vial for particulate matter and discoloration; it should be a clear, colorless to slightly yellow solution. Discard vial if the solution is cloudy, discolored, or contains particulate matter. Withdraw the required volume of drug from the vial(s) and inject it into a 250 mL infusion bag containing either 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection. Gently invert the bag to mix the diluted solution and avoid foaming or excessive shearing. Inspect the solution to ensure it is clear, colorless, and free of visible particles. Discard any partially used or empty vials. Side effects The Most Common The most common serious adverse reactions to avelumab are immune-mediated adverse reactions (pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions. Among the 88 patients enrolled in the JAVELIN Merkel 200 trial, the most common adverse reactions were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis.[rx][rx] The most common serious risks are immune-mediated, where the body’s immune system attacks healthy cells or organs, such as the lungs (pneumonitis), liver (hepatitis), colon (colitis), hormone-producing glands (endocrinopathies) and kidneys (nephritis).[rxx] In addition, there is a risk of serious infusion-related reactions.[rx] Patients who experience severe or life-threatening infusion-related reactions should stop using avelumab.[rx] Women who are pregnant or breastfeeding should not take nivolumab because it may cause harm to a developing fetus or a newborn baby.[rx] Drug Interactions This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist. DRUG INTERACTION Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Avelumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Avelumab. Aducanumab The risk or severity of adverse effects can be increased when Avelumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Avelumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Avelumab. Amivantamab The risk or severity of adverse effects can be increased when Avelumab is combined with Amivantamab. Anifrolumab The risk or severity of adverse effects can be increased when Avelumab is combined with Anifrolumab. Ansuvimab The risk or severity of adverse effects can be increased when Avelumab is combined with Ansuvimab. immune globulin human The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Avelumab. antilymphocyte The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Avelumab. Antithymocyte The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Avelumab. Articaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Articaine. Asfotase alfa The risk or severity of adverse effects can be increased when Asfotase alfa is combined with Avelumab. Atezolizumab The risk or severity of adverse effects can be increased when Atezolizumab is combined with Avelumab. Atoltivimab The risk or severity of adverse effects can be increased when Avelumab is combined with Atoltivimab. Bamlanivimab The risk or severity of adverse effects can be increased when Avelumab is combined with Bamlanivimab. Basiliximab The risk or severity of adverse effects can be increased when Basiliximab is combined with Avelumab. Bebtelovimab The risk or severity of adverse effects can be increased when Avelumab is combined with Bebtelovimab. Belantamab mandolin The risk or severity of adverse effects can be increased when Avelumab is combined with Belantamab mandolin. Belimumab The risk or severity of adverse effects can be increased when Belimumab is combined with Avelumab. Benralizumab The risk or severity of adverse effects can be increased when Avelumab is combined with Benralizumab. Benzocaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Benzyl alcohol. Besilesomab The risk or severity of adverse effects can be increased when Avelumab is combined with Besilesomab. Bevacizumab The risk or severity of adverse effects can be increased when Bevacizumab is combined with Avelumab. Bezlotoxumab The risk or severity of adverse effects can be increased when Avelumab is combined with Bezlotoxumab. Bimekizumab The risk or severity of adverse effects can be increased when Avelumab is combined with Bimekizumab. Blinatumomab The risk or severity of adverse effects can be increased when Blinatumomab is combined with Avelumab. Brentuximab The risk or severity of adverse effects can be increased when Brentuximab vedotin is combined with Avelumab. Brodalumab The risk or severity of adverse effects can be increased when Brodalumab is combined with Avelumab. Brolucizumab The risk or severity of adverse effects can be increased when Avelumab is combined with Brolucizumab. Bupivacaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Bupivacaine. Burosumab The risk or severity of adverse effects can be increased when Avelumab is combined with Burosumab. Butacaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Butacaine. Butamben The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Butamben. Canakinumab The risk or severity of adverse effects can be increased when Canakinumab is combined with Avelumab. Caplacizumab The risk or severity of adverse effects can be increased when Caplacizumab is combined with Avelumab. Capromab pendetide The risk or severity of adverse effects can be increased when Capromab pendetide is combined with Avelumab. Capsaicin The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Capsaicin. Casirivimab The risk or severity of adverse effects can be increased when Avelumab is combined with Casirivimab. Catumaxomab The risk or severity of adverse effects can be increased when Catumaxomab is combined with Avelumab. Cemiplimab The risk or severity of adverse effects can be increased when Avelumab is combined with Cemiplimab. Certolizumab pegol The risk or severity of adverse effects can be increased when Certolizumab pegol is combined with Avelumab. Cetuximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Avelumab. Chloroprocaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Chloroprocaine. Cilgavimab The risk or severity of adverse effects can be increased when Avelumab is combined with Cilgavimab. Cinchocaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Cinchocaine. Cocaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Cocaine. Conjugated estrogens Conjugated estrogens may increase the thrombogenic activities of Avelumab. Daratumumab The risk or severity of adverse effects can be increased when Daratumumab is combined with Avelumab. Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Avelumab. Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Avelumab. Dienestrol Dienestrol may increase the thrombogenic activities of Avelumab. Diethylstilbestrol Diethylstilbestrol may increase the thrombogenic activities of Avelumab. Digoxin Immune The risk or severity of adverse effects can be increased when Digoxin Immune Fab (Ovine) is combined with Avelumab. Dinutuximab The risk or severity of adverse effects can be increased when Dinutuximab is combined with Avelumab. Diphenhydramine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Diphenhydramine. Dostarlimab The risk or severity of adverse effects can be increased when Avelumab is combined with Dostarlimab. Dulaglutide The risk or severity of adverse effects can be increased when Dulaglutide is combined with Avelumab. Dupilumab The risk or severity of adverse effects can be increased when Avelumab is combined with Dupilumab. Durvalumab The risk or severity of adverse effects can be increased when Durvalumab is combined with Avelumab. Dyclonine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Dyclonine. Ebola Zaire vaccine The therapeutic efficacy of the Ebola Zaire vaccine (live, attenuated) can be decreased when used in combination with Avelumab. Eculizumab The risk or severity of adverse effects can be increased when Eculizumab is combined with Avelumab. Efalizumab The risk or severity of adverse effects can be increased when Efalizumab is combined with Avelumab. Eflapegrastim The risk or severity of adverse effects can be increased when Avelumab is combined with Eflapegrastim. Eftrenonacog alfa The risk or severity of adverse effects can be increased when Eftrenonacog alfa is combined with Avelumab. Elotuzumab The risk or severity of adverse effects can be increased when Elotuzumab is combined with Avelumab. Emapalumab The risk or severity of adverse effects can be increased when Avelumab is combined with Emapalumab. Emicizumab The risk or severity of adverse effects can be increased when Avelumab is combined with Emicizumab. Eptinezumab The risk or severity of adverse effects can be increased when Avelumab is combined with Eptinezumab. Erenumab The risk or severity of adverse effects can be increased when Avelumab is combined with Erenumab. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Avelumab. Esterified estrogens Esterified estrogens may increase the thrombogenic activities of Avelumab. Estetrol Estetrol may increase the thrombogenic activities of Avelumab. Estradiol Estradiol may increase the thrombogenic activities of Avelumab. Estradiol acetate Estradiol acetate may increase the thrombogenic activities of Avelumab. Estradiol benzoate Estradiol benzoate may increase the thrombogenic activities of Avelumab. Estradiol cypionate Estradiol cypionate may increase the thrombogenic activities of Avelumab. Estradiol valerate Estradiol valerate may increase the thrombogenic activities of Avelumab. Estriol Estriol may increase the thrombogenic activities of Avelumab. Estrone Estrone may increase the thrombogenic activities of Avelumab. Estrone sulfate Estrone sulfate may increase the thrombogenic activities of Avelumab. Ethinylestradiol Ethinylestradiol may increase the thrombogenic activities of Avelumab. Ethyl chloride The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Ethyl chloride. Etidocaine The risk or severity of methemoglobinemia can be increased when Avelumab is combined with Etidocaine. Evolocumab The risk or severity of adverse effects can be increased when Evolocumab is combined with Avelumab. Fanolesomab The risk or severity of adverse effects can be increased when Avelumab is combined with Fanolesomab. Fremanezumab The risk or severity of adverse effects can be increased when Avelumab is combined with Fremanezumab. Galcanezumab The risk or severity of adverse effects can be increased when Avelumab is combined with Galcanezumab. Gemtuzumab The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Avelumab. Golimumab The risk or severity of adverse effects can be increased when Golimumab is combined with Avelumab. Guselkumab The risk or severity of adverse effects can be increased when Guselkumab is combined with Avelumab. Hepatitis B immune globulin The risk or severity of adverse effects can be increased when Hepatitis B immune globulin is combined with Avelumab. Human cytomegalovirus The risk or severity of adverse effects can be increased when Avelumab is combined with Human cytomegalovirus immune globulin. Human immunoglobulin G The risk or severity of adverse effects can be increased when Human immunoglobulin G is combined with Avelumab. Human Rho The risk or severity of adverse effects can be increased when Human Rho(D) immune globulin is combined with Avelumab. Human varicella- The risk or severity of adverse effects can be increased when Human varicella-zoster immune globulin is combined with Avelumab. Ibalizumab The risk or severity of adverse effects can be increased when Avelumab is combined with Ibalizumab. Ibritumomab tiuxetan The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Avelumab. You Might Also Read Misoprostol / Mifepristone - Uses, Dosage, Side Effects Pregnancy and Lactation Pregnancy Receiving this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment and for at least 1 month after the last dose. If you think you have become pregnant while receiving the medicine, tell your doctor right away. There is no or limited data on the use of avelumab in pregnant women. Animal reproduction studies have not been conducted with avelumab. However, in murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and result in increased fetal loss. These results indicate a potential risk, based on its mechanism of action, that administration of avelumab during pregnancy could cause fetal harm, including increased rates of abortion or stillbirth. Human IgG1 immunoglobulins are known to cross the placental barrier. Therefore, avelumab has the potential to be transmitted from the mother to the developing fetus. It is not recommended to use nivolumab during pregnancy unless the clinical condition of the woman requires treatment with avelumab. Lactation It is unknown whether avelumab is excreted in human milk. Since it is known that antibodies can be secreted in human milk, a risk to newborns/infants cannot be excluded. Breast-feeding women should be advised not to breastfeed during treatment and for at least 1 month after the last dose due to the potential for serious adverse reactions in breastfed infants. The effect of avelumab on male and female fertility is unknown. Although studies to evaluate the effect of avelumab on fertility have not been conducted, there were no notable effects on the female reproductive organs in monkeys based on 1-month and 3-month repeat-dose toxicity studies. You Might Also Read Management of Drug Interactions, Types, Guideline References https://pubchem.ncbi.nlm.nih.gov/substance/252827393#section=External-ID https://pubchem.ncbi.nlm.nih.gov/substance/347911260 https://go.drugbank.com/drugs/DB11945 https://www.mayoclinic.org/drugs-supplements/avelumab-intravenous-route/precautions/drg-20406146 https://www.webmd.com/drugs/2/drug-173442/avelumab-intravenous/details/list-contraindications Show More