Enfortumab vedotin parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of enfortumab vedotin
Drugs List
Therapeutic Indications
Uses
Advanced/metastatic transitional cell carcinoma of the urothelial tract
Monotherapy for adults with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a programmed death receptor-1 or programmed death-ligand 1 inhibitor.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
1.25mg/kg (up to a maximum of 125mg for patients greater than or equal to 100kg) over 30 minutes on Days 1, 8 and 15 of a 28 day cycle until disease progression or unacceptable toxicity.
Additional Dosage Information
Dose reductions for adverse reactions
Starting dose: 125mg/kg up to 125mg.
First dose reduction: 1mg/kg up to 100mg.
Second dose reduction: 0.75mg/kg up to 75mg.
Third dose reduction: 0.5mg/kg up to 50mg.
Dose interruption, reduction and discontinuation in patients with locally advanced or metastatic urothelial cancer
Adverse Reaction:
Skin reactions
Suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) or bullous lesions: Immediately withhold and refer to specialised care.
Confirmed SJS or TEN; Grade 4 or recurrent Grade 3: Permanently discontinue.
Grade 2 or worsening, Grade 2 with fever or Grade 3: Withhold until Grade 1 or less. Referral to specialised care should be considered. Resume at the same dose level or consider dose reduction by one dose level as suggested above.
Hyperglycaemia
Blood glucose greater than 13.9mmol/L (greater than 250mg/dL): Withhold until elevated blood glucose has improved to less than 13.9mmol/L (less than or equal to 250mg/dL), resume treatment at the same dose level.
Peripheral neuropathy
Grade 2: Withhold until less than or equal to Grade 1. For first occurrence, resume treatment at the same dose level. For a reccurence, withhold until Grade 1 or less then, resume treatment reduced by one dose level.
Grade 3+: Permanently discontinue.
Administration
For intravenous infusion over 30 minutes.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Obese patients with a BMI equal or greater than 30kg/m2
Diabetes mellitus
End stage renal disease
Hyperglycaemia
Moderate hepatic impairment
Give pre-treatment counselling and consideration of sperm cryopreservation
Treatment to be initiated and supervised by a specialist
Contains polysorbate
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Ensure negative pregnancy test in week preceding initiation of treatment
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor blood glucose in high risk patients
Monitor closely for signs and symptoms of toxic epidermal necrolysis
Monitor for ocular disorders
Monitor for symptoms of peripheral neuropathy
Monitor visual status
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patient to seek medical advice if severe skin reaction occurs
Discontinue if Grade 3 peripheral neuropathy occurs
Discontinue if recurrent Grade 3 skin reaction occurs
Discontinue treatment if Stevens-Johnson syndrome is confirmed
Discontinue treatment if toxic epidermal necrolysis is confirmed
Withhold if Grade 2 skin reaction worsening or with fever
Discontinue if grade 4 skin reaction occurs
Withhold if blood glucose greater than 13.9mmol/L
Advise patient not to take St John's wort concurrently
Female: Contraception required during and for 1 year after treatment
Male: Contraception required during and for 9 months after treatment
Breastfeeding: Do not breastfeed during & for 6 months after treatment
Hyperglycaemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with enfortumab vedotin. Hyperglycaemia occurred more frequently in patients with pre-existing hyperglycaemia or high body mass index.
Ocular disorders predominately dry eye, have occurred in patients treated with enfortumab vedotin. Consider artificial tears for prophylaxis of dry eye and referral for ophthalmologic evaluation if ocular symptoms do not resolve or worsen.
Pregnancy and Lactation
Pregnancy
Enfortumab vedotin is contraindicated during pregnancy.
The manufacturer does not recommend using enfortumab vedotin during pregnancy and in women of childbearing potential not using effective contraception.
Animal studies have shown that enfortumab vedotin can cause foetal harm when administered to pregnant women based upon findings from animal studies. Embryo foetal development studies in female rats have shown that intravenous administration of enfortumab vedotin resulted in reduced numbers of viable foetuses, reduced litter size, and increased early resorptions.
Lactation
Enfortumab vedotin is contraindicated during breastfeeding.
The manufacturer does not recommend breastfeeding whilst taking enfortumab vedotin and for at least 6 months after last dose.
It is unknown whether enfortumab vedotin is excreted in human milk. A risk to breastfed children cannot be excluded.
Side Effects
Alopecia
Anaemia
Blistering
Bullous dermatoses
Burning sensation (local)
Conjunctivitis
Decreased appetite
Demyelinating polyneuropathy
Dermatological disturbances
Diarrhoea
Dry eyes
Dry skin
Dysaesthesia
Dysgeusia
Eczema
Epidermal necrolysis
Erythema
Erythema multiforme
Fatigue
Febrile neutropenia
Gait abnormality
Hyperglycaemia
Hypoaesthesia
Increase in ALT level
Increase in AST level
Infusion site leakage
Intertrigo
Maculopapular rash
Motor disturbances
Muscle weakness
Muscular atrophy
Nausea
Neuralgia
Neurotoxicity
Neutropenia
Palmar-Plantar Erythrodysaesthesia syndrome
Paraesthesia
Pemphigoid reaction
Peripheral motor neuropathy
Peripheral neuropathy
Peripheral sensory neuropathy
Peroneal nerve palsy
Polyneuropathy
Pruritus
Rash
Reduced neutrophil count
Sensory loss
Skin exfoliation
Stevens-Johnson syndrome
Stomatitis
Vomiting
Weight loss
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: October 2022
Reference Sources
Summary of Product Characteristics: Padcev 20 mg powder for concentrate for solution for infusion. Astellas Pharma Ltd. Revised April 2022.
Summary of Product Characteristics: Padcev 30 mg powder for concentrate for solution for infusion. Astellas Pharma Ltd. Revised April 2022.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 12 October 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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