Durvalumab parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of durvalumab.
Drugs List
Therapeutic Indications
Uses
Extensive stage small cell lung cancer (ES-SCLC): adjunctive treatment
Locally advanced unresectable non-small cell lung cancer (NSCLC)
Locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on equal or greater than 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy.
In combination with etoposide and either carboplatin or cisplatin for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Locally advanced non-small cell lung cancer
10mg per kg every 2 weeks or 1500mg every 4 weeks, continued until disease progression or unacceptable toxicity, or a maximum of 12 months.
Patients with bodyweight of 30kg or less must receive weight based dosing, equivalent to 10mg per kg every 2 weeks or 20mg per kilogram every 4 weeks as monotherapy until weight increases to greater than 30kg.
It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression confirmed.
Extensive-stage small cell lung cancer
1500mg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 1500mg every 4 weeks as monotherapy.
Patients with bodyweight of 30kg or less must receive weight based dosing, equivalent to 20mg per kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 20mg per kg every 4 weeks as monotherapy until weight increases to greater than 30kg.
Durvalumab is administered prior to chemotherapy on the same day.
Additional Dosage Information
Dose modifications
Immune-mediated pneumonitis or interstitial lung disease
Grade 2: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 3 or 4: Permanently discontinue. Initiate 1 to 2mg per kg per day prednisone or equivalent followed by a taper.
Immune-mediated hepatitis
Grade 2 with alanine aminotransferase (ALT) or aspartate transaminase (AST) above 3 times and up to and including 5 times the upper limit of normal (ULN), and/or total bilirubin above 1.5 times and up to and including 3 times ULN: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 3 with alanine aminotransferase (ALT) or aspartate transaminase (AST) above 5 times and up to and including 8 times the upper limit of normal (ULN), or total bilirubin above 3 times and up to and including 5 times ULN: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 3 with ALT or AST above 8 times the upper limit of normal (ULN), or total bilirubin above 5 times ULN: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Concurrent ALT or AST above 3 times ULN and total bilirubin above 2 times ULN with no other cause: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Immune-mediated colitis or diarrhoea
Grade 2 or 3: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 4: Permanently discontinue. Initiate 1 to 2mg per kg per day prednisone or equivalent followed by a taper.
Immune-mediated hyperthyroidism, thyroiditis
Grade 2 to 4: Withhold dose until clinically stable, and treat symptomatically.
Immune-mediated hypothyroidism
Grade 2 to 4: Initiate thyroid hormone replacement as clinically indicated.
Immune-mediated adrenal insufficiency or hypophysitis or hypopituitarism
Grade 2 to 4: Withhold dose until clinically stable, and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper and hormone replacement as clinically indicated.
Immune-mediated type 1 diabetes mellitus
Grade 2 to 4: No change to dose. Initiate insulin treatment as clinically indicated.
Immune-mediated nephritis
Grade 2 with serum creatinine above 1.5 and up to and including 3 times ULN (or baseline): Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 3 with serum creatinine above 3 times baseline, or above 3 times and up to and including 6 times ULN: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 4 with serum creatinine above 6 times ULN: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Immune-mediated rash or dermatitis (including pemphigoid)
Grade 2 persisting for more than one week: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 3: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 4: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Immune-mediated myocarditis
Grade 2: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper. If no improvement within 2 to 3 days despite corticosteroids, promptly start additional immunosuppressive therapy. Upon resolution (Grade 0), corticosteroid taper should be initiated and continued over at least 1 month, after which durvalumab can be resumed based on clinical judgement.
Grade 3 or 4, or any grade with positive biopsy: Permanently discontinue, and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Immune-mediated myositis or polymyositis
Grade 2 or 3: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper. Permanently discontinue if not resolved to equal to or less than Grade 1 within 30 days or if their are signs of respiratory insufficiency.
Grade 4: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Infusion-related reactions
Grade 1 or 2: Interrupt or slow infusion rate, and consider prophylactic medication for subsequent infusions.
Grade 3 or 4: Permanently discontinue.
Infection
Grade 3 or 4: Withhold dose until clinically stable.
Myasthenia gravis
Grade 2: Withhold dose and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Any grade with signs of respiratory or autonomic insufficiency: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 3 or 4: Permanently discontinue and initiate 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Other immune-mediated adverse reactions
Grade 3: Withhold dose and consider initiating 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Grade 4: Permanently discontinue and consider initiating 1 to 2mg per kg per day of prednisone or equivalent followed by a taper.
Administration
For administration as an intravenous infusion over 60 minutes.
Contraindications
Children under 18 years
Within 4 weeks of live viral or bacterial vaccination
Breastfeeding
Pregnancy
Precautions and Warnings
Autoimmune disease
History of autoimmune disorder
Hepatitis
Hepatitis B
Hepatitis C
Immunodeficiency syndromes
Positive HIV status
Severe renal impairment
Tuberculosis
Live vaccines not recommended during or within 30 days of treatment
NSCLC: Confirm PD-L1 expression of tumour prior to treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
Must be diluted before use
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Monitor renal and hepatic function before and during treatment
Monitor thyroid function prior to and periodically during treatment
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor for adrenal insufficiency during and after treatment
Monitor for signs and symptoms of colitis
Monitor for signs and symptoms of hypophysitis
Monitor for signs and symptoms of hypopituitarism
Monitor for signs and symptoms of pancreatitis
Monitor for signs and symptoms of pneumonitis
Monitor for signs and symptoms of type 1 diabetes mellitus
Monitor for signs of immune related hepatitis
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs and symptoms of myocarditis
Suspected pneumonitis should be confirmed by radiographic imaging
Advise patient to report diarrhoea
Advise patient to report signs and symptoms of immune thrombocytopenia
Discontinue if myasthenia gravis or myasthenic syndrome occurs
Permanently discontinue treatment if severe respiratory symptoms occur
Consider dose modification in non-haematological toxicity
Female: Contraception required during and for 3 months after treatment
Certain patient populations were not included in durvalumab drug trials, and as such the drug should be used with caution in populations with the following: active or prior autoimmune disease within 2 years, a history of immunodeficiency or severe immune-mediated adverse reactions, conditions requiring systemic immunosuppression (except physiological doses of systemic corticosteroids), uncontrolled intercurrent illness, active tuberculosis, HIV or hepatitis B or C infection or patients receiving live attenuated vaccine within 30 days.
In patients with extensive-stage small cell lung cancer (ES-SCLC), the safety of concurrent prophylactic cranial irradiation (PCI) is unknown.
Pregnancy and Lactation
Pregnancy
Durvalumab is contraindicated during pregnancy.
Use of durvalumab during pregnancy is contraindicated by the manufacturer. Animal studies did not indicate reproductive toxicity, but do show an increase in foetal loss. At the time of writing there is limited published information regarding the use of durvalumab during human pregnancy. Durvalumab is known to cross the placenta. The potential risk are unknown.
Lactation
Durvalumab is contraindicated during breastfeeding.
Use of durvalumab during breastfeeding is contraindicated by the manufacturer. Animal studies have shown low levels of durvalumab in breast milk, however presence in human breast milk is unknown. Effects on exposed infants are unknown.
Side Effects
Abdominal pain
Adrenal insufficiency
Alanine aminotransferase increased
Alopecia
Anaemia
Arthralgia
Aspartate aminotransferase increased
Asthenia
Candidiasis (mouth or throat)
Colitis
Constipation
Cough
Cystitis
Decreased appetite
Dermatitis
Diabetes insipidus
Diabetes mellitus
Diarrhoea
Dysphonia
Dysuria
Encephalitis
Fatigue
Febrile neutropenia
Graves' disease
Guillain-Barre syndrome
Hepatitis
Hepatocellular damage
Hepatotoxicity
Hyperthyroidism
Hypophysitis
Hypothyroidism
Increase of liver transaminases
Increases in hepatic enzymes
Influenza
Infusion related reaction
Interstitial lung disease
Leukopenia
Meningitis
Myalgia
Myasthenia
Myasthenia gravis-like syndrome
Myocarditis
Myositis
Nausea
Nephritis
Neutropenia
Night sweats
Oral infection
Pancreatitis
Pancytopenia
Pemphigoid reaction
Peripheral oedema
Pituitary disorder
Pneumonia
Pneumonitis
Polymyositis
Pruritus
Psoriasis
Pyrexia
Rash
Reduced neutrophil count
Reduced platelet count
Serum creatinine increased
Stomatitis
Thrombocytopenia
Thyroiditis
Upper respiratory tract infection
Vomiting
White blood cell count decreased
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: January 2023.
Reference Sources
Summary of Product Characteristics: Imfinzi 50mg per ml concentrate for solution for infusion. AstraZeneca UK Limited. Revised October 2022.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Durvalumab Last revised: 30 November 2022
Last accessed: 16 December 2022.
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.