Avelumab parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Intravenous infusions of avelumab.
Drugs List
Therapeutic Indications
Uses
Advanced renal cell carcinoma
Metastatic merkel cell carcinoma
Urothelial carcinoma: Treatment
Monotherapy for patient with metastatic Merkel cell carcinoma (MCC).
Monotherapy for first-line treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) who are progression-free following platinum-based chemotherapy.
Combination therapy with axitinib for first-line treatment of patients with advanced renal cell carcinoma (RCC).
Dosage
Adults
800mg once every 2 weeks.
Additional Dosage Information
Premedication with an antihistamine and paracetamol should occur on first 4 infusions.
Corticosteroids should be administered for grade 2 or greater IRRs, initial dose of 1 to 2mg/kg per day and ensuring corticosteroid dose tapering.
Escalating or reducing dose is not recommended.
Doses may be delayed or discontinued due to tolerability and safety. Below states the guidelines for delaying or discontinuing avelumab as a result of treatment related adverse reactions:
Infusion related reactions (IRR)
Grade 1 IRR, reduce infusion rate by 50%.
Grade 2 IRR, withhold until resolution to grade 0 to 1 and restart treatment reducing infusion rate by 50%.
Grade 3 or 4 IRR, permanently discontinue.
Pneumonitis
Grade 2 pneumonitis, withhold until resolution to grade 0 to 1.
Grade 3 or 4 or recurrent grade 2 pneumonitis, permanently discontinue.
Hepatitis
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 and up to 5 times upper limit of normal (ULN), withhold until resolution to grade 0 to 1.
Total bilirubin greater than 1.5 and up to 3 times ULN, withhold until resolution to grade 0 to 1.
Colitis
Grade 2 or grade 3 colitis or diarrhoea, withhold until resolution to grade 0 to 1.
Grade 4 colitis or diarrhoea or recurrent grade 3 colitis, permanently discontinue.
Pancreatitis
If suspected, withhold treatment.
If confirmed, permanently discontinue treatment.
Myocarditis
If suspected, withhold treatment.
If confirmed, permanently discontinue treatment.
Endocrinopathies
Grade 3 or 4 endocrinopathies, withhold until resolution to grade 0 to 1.
Grade 3 or greater hyperglycaemia, withhold until resolution to grade 0 to 1. and treat with antihyperglycaemics. Resume treatment when metabolic control is achieved via insulin replacement therapy.
Nephritis
Serum creatinine more than 1.5 and up to 6 times ULN, withhold until resolution to grade 0 to 1.
Serum creatinine more than 6 times ULN, permanently discontinue.
Other immune related adverse reactions
Any grade 2 or grade 3 IRR not described as above, withhold until resolution to grade 0 to 1.
Serious grade 4 adverse reactions excluding endocrinopathies controlled by hormone replacement therapy, permanently discontinue.
Recurrent grade 3 IRR, permanently discontinue.
Requirement of 10mg per day or greater prednisone or equivalent for greater than 12 weeks, permanently discontinue.
Persistent grade 2 or 3 immune mediated adverse reactions lasting 12 weeks or longer, permanently discontinue.
Treatment modifications when used in combination with axitinib.
If ALT and AST are 3 times ULN up to 5 times ULN, or bilirubin is 1.5 times ULN up to 3 times ULN, both the avelumab and the axitinib should be withheld until these recover to grades 0 to 1.
If persistent for more than 5 days, corticosteroid therapy with prednisone or equivalent followed by tapering should be considered. Rechallenge with avelumab or axitinib or sequential rechallenge both after recovery should be considered. If rechallenging with axitinib, dose reduction should be considered according to the axitinib product information.
If ALT or AST are equal to or greater than 5 times ULN, or greater than 3 times ULN with concurrent total bilirubin equal to or greater than 2 times ULN, or total bilirubin equal to or greater than 3 times ULN, both avelumab and axitinib should be permanently discontinued and corticosteroid therapy should be considered.
Administration
Intravenous infusion.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Predisposition to diabetes mellitus
Adrenal insufficiency
Hyperglycaemia
Hyperthyroidism
Hypothyroidism
Moderate hepatic impairment
Severe renal impairment
Type 1 diabetes mellitus
Consider use of corticosteroids if adverse reactions occur
Premedicate with an antihistamine and paracetamol
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Suspend treatment or reduce rate until infusion reactions resolve
Monitor serum creatinine prior to and during treatment
Monitor thyroid function prior to and periodically during treatment
Monitor for adrenal insufficiency during and after treatment
Monitor for signs and symptoms of colitis
Monitor for signs and symptoms of pancreatitis
Monitor for signs and symptoms of pneumonitis
Monitor for signs of immune related hepatitis
Monitor hepatic function
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for endocrinopathies
Monitor patients for signs and symptoms of myocarditis
Monitor periodically for signs or symptoms of hyperglycaemia
Suspected pneumonitis should be confirmed by radiographic imaging
Discontinue permanently if acute pancreatitis occurs
Interrupt therapy/reduce infusion rate if infusion-related reactions occur
Consider discontinuing if severe infusion reactions occur
Discontinue if diagnosis of myocarditis is confirmed
Discontinue if grade 3 or greater adverse reaction that recurs/persists
Discontinue if grade 3 or higher diarrhoea or colitis occurs
Discontinue if grade 3 or higher immune related reactions occur
Discontinue if grade 3 or higher infusion reaction occurs
Discontinue permanently if grade 4 colitis occurs
Discontinue treatment if grade 3 or greater pneumonitis occurs
Discontinue treatment if grade 4 nephritis occurs
Permanent discontinuation if > grade 2 immune related hepatitis occurs
Permanent discontinuation if AST/ALT >5 x ULN or total bilirubin >3 x ULN
Permanent discontinuation if grade 3 recurrent colitis occurs
Permanent discontinuation if serum creatinine >6 times ULN
Permanent discontinuation in recurrent grade 2 immune related pneumonitis
RCC: Discontinue if AST/ALT > 3 x ULN and bilirubin > or equal to 2 x ULN
RCC: Permanently discontinue if grade 3 or higher hepatotoxicity occurs
RCC: Suspend if grade 2 hepatotoxicity occurs
Suspend treatment if AST/ALT is 3-5 times upper limit of normal
Suspend treatment if grade 2 diarrhoea occurs
Suspend treatment if grade 2 immune related hepatitis occurs
Suspend treatment if grade 2 nephritis occurs
Suspend treatment if grade 2 or 3 colitis occurs
Suspend treatment if grade 2 pneumonitis occurs
Suspend treatment if grade 3 or greater endocrinopathies occur
Suspend treatment if grade 3 or greater hyperglycaemia occurs
Suspend treatment if total bilirubin between 1.5 and 3 times ULN
Withhold if myocarditis is suspected
Withhold if pancreatitis is suspected
Female: Contraception required during and for 1 month after treatment
Breastfeeding: Do not breastfeed during & for 1 month after treatment
Pregnancy and Lactation
Pregnancy
Avelumab is contraindicated during pregnancy.
The manufacturer states that avelumab is not recommended during pregnancy unless the clinical condition requires treatment.
At the time of writing there is no or limited published information regarding the use of avelumab in pregnancy.
Human IgG1 immunoglobulins are known to cross the placental barrier. Avelumab is not recommended in pregnancy as there is a potential for avelumab to be transmitted from the mother to foetus.
In murine models, blocking the PD-L1 signalling has been shown to increase foetal loss. Indicating a potential risk of administration of avelumab during pregnancy causing increased rate of stillbirth or abortion.
Lactation
Avelumab is contraindicated during breastfeeding.
The manufacturer states that women are advised not to breastfeed during treatment and for at least 1 month after the last dose.
It is unknown if avelumab is excreted in human milk and the risk to newborns/infants cannot be excluded.
Side Effects
Abdominal pain
Acute adrenal insufficiency
Acute renal failure
Alanine aminotransferase increased
Altered liver function tests
Anaemia
Anaphylactic reaction
Arthralgia
Aspartate aminotransferase increased
Asthenia
Autoimmune hepatitis
Back pain
Chills
Colitis
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Dermatitis
Dermatitis acneiform
Diabetes mellitus
Diarrhoea
Dizziness
Dry mouth
Dry skin
Dysphonia
Dyspnoea
Eczema
Elevated amylase levels
Elevated serum lipase
Enterocolitis
Eosinophilia
Erythema
Erythema multiforme
Erythematous rash
Exfoliative dermatitis
Fatigue
Flushing
Gamma glutamyl transferase (GGT) increased
Guillain-Barre syndrome
Headache
Hepatic disorders
Hepatic failure
Hepatitis
Hepatotoxicity
Hyperglycaemia
Hypersensitivity reactions
Hypertension
Hyperthyroidism
Hypophysitis
Hypotension
Hypothyroidism
Ileus
Increase in alkaline phosphatase
Increase in serum transaminases
Influenza-like syndrome
Infusion related reaction
Interstitial nephritis
Ketoacidosis
Lymphopenia
Macular rash
Maculopapular rash
Myalgia
Myasthenia gravis-like syndrome
Myocarditis
Myositis
Nausea
Pancreatitis
Pemphigoid reaction
Peripheral neuropathy
Peripheral oedema
Pituitary disorder
Pneumonitis
Pruritus
Psoriasis
Pustular rash
Pyrexia
Rash
Serum creatinine increased
Skin eruption
Systemic inflammatory response syndrome (SIRS)
Thrombocytopenia
Thyroid stimulating hormone decreased
Thyroiditis
Transient adrenocortical insufficiency
Urticaria
Uveitis
Vomiting
Weight loss
Wheezing
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: May 2019.
Reference Sources
Summary of Product Characteristics: Bavencio 20mg/ml concentrate for solution for infusion. Revised January 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.