- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Concentrate for infusion of pembrolizumab.
Advanced renal cell carcinoma
Locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC)
Relapsed/refractory classical Hodgkin lymphoma (cHL) after ASCT and BV
Squamous cell carcinoma of head and neck
Urothelial carcinoma: Treatment
Advanced unresectable or metastatic melanoma in adult patients.
As monotherapy the adjuvant treatment of adults with Stage III melanoma and lymph node involvement who have undergone complete resection.
First-line treatment as monotherapy of metastatic non-small cell lung cancer in adults whose tumours express PD-L1 with a tumour proportion score of 50% or greater and no EGFR or ALK positive tumour mutations.
In combination with pemetrexed and platinum chemotherapy as first-line treatment of metastatic non-squamous non-small cell lung cancer in adults whose tumours have no EGFR or ALK positive mutations.
Locally advanced or metastatic non-small cell lung cancer in adults whose tumours express PD-L1 with a tumour proportion score of 1% or greater and have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received approved therapy for these mutations prior to receiving pembrolizumab.
In combination with carboplatin and either paclitaxel or nab-paclitaxel, as first-line treatment of metastatic squamous NSCLC in adults.
Relapsed or refractory classical Hodgkin lymphoma (cHL) in adults who have failed autologous stem cell transplant (ASCT) and brentuximab vedotin (BV), or who are transplant -ineligible and have failed BV.
As monotherapy for locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy.
As monotherapy for locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with a combined positive score (CPS) equal to or greater than 10.
As monotherapy or in combination with platinum and 5-fluorouracil chemotherapy for fist line treatment of unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS greater than or equal to 1.
As monotherapy for the recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with tumour proportion score of 50% or greater and progressing on or after platinum-containing chemotherapy.
In combination with axitinib as first line treatment of advanced renal cell carcinoma (RCC) in adults.
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
200mg every 3 weeks, or 400mg every 6 weeks, administered as an intravenous infusion.
200mg every 3 weeks as an intravenous infusion
Treatment should continue until unacceptable toxicity or confirmed disease progression. Clinically stable patients with initial disease progression should continue treatment until disease progression has been confirmed.
For the adjuvant treatment of melanoma, treatment should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year.
Additional Dosage Information
Suspend treatment in any of the following:
Grade 2 pneumonitis
Grade 2 or 3 colitis
Grade 2 nephritis with serum creatinine between 1.5 and 3 times upper limit of normal (ULN)
Grade 2 hepatitis (AST/ALT between 3 and 5 times ULN or total bilirubin between 1.5 and 3 times ULN)
Renal cell carcinoma (RCC): AST/ALT greater than or equal to 3 and less than 10 times ULN without concurrent total bilirubin greater than or equal to 2 times ULN
Type 1 diabetes with grade 3 hyperglycaemia or ketoacidosis
Grade 3 hyperthyroidism
Grade 3 or suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
Suspend treatment and initiate corticosteroids. Restart treatment within 12 weeks of last dose if adverse reactions remain less than or equal to grade 1 and corticosteroid dose has been reduced to less than or equal to 10mg prednisone or equivalent per day.
For endocrinopathies treatment may be resumed when symptoms resolve to grade 2 or lower and are controlled by hormone replacement therapy.
Discontinue treatment in any of the following:
Grade 3 or 4 pneumonitis or recurrent grade 2 pneumonitis
Grade 4 colitis or recurrent grade 3 colitis
Grade 3 or 4 myocarditis, encephalitis or Guillain-Barre syndrome
Grade 3 nephritis with serum creatinine greater than or equal 3 times ULN
Grade 3 hepatitis (AST/ALT greater than 5 times ULN or total bilirubin greater than 3 times ULN)
If liver metastases are present grade 2 elevations in AST/ALT or hepatitis with increases in AST/ALT greater than or equal to 50% which persist for longer than 1 week
Renal cell carcinoma (RCC): AST/ALT greater than or equal to 10 times ULN
Renal cell carcinoma (RCC): AST/ALT greater than 3 times ULN with concurrent total bilirubin greater than or equal to 2 times ULN
Grade 3 or greater infusion reactions
Any grade 4 toxicity excluding endocrinopathies that are controlled by hormone replacement or haematological toxicity in patients with cHL where pembrolizumab should be withheld until adverse reactions recover to Grade 1
Grade 4 or confirmed Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)
If corticosteroids cannot be reduced to less than or equal to 10mg/day prednisone or equivalent within 12 weeks
Any grade 3 toxicity that occurs a second time
Any toxicity which does not resolve to grade 1 or baseline within 12 weeks of last pembrolizumab dose
For intravenous infusion over 30 minutes.
Children under 18 years
Precautions and Warnings
History of progenitor cell transplantation
Solid organ transplant recipients
Moderate hepatic impairment
Severe renal impairment
Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Consider pre-medication with antihistamines and/or antipyretics
Consider use of corticosteroids if adverse reactions occur
NSCLC: Confirm PD-L1 expression of tumour prior to treatment
Risk of serious transplant-related complications
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
UC: Confirm PD-L1 expression of tumour prior to treatment
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
Advise patient to report signs of gastrointestinal perforation immediately
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor thyroid function prior to and periodically during treatment
Monitor blood glucose
Monitor for signs and symptoms of colitis
Monitor for signs and symptoms of pneumonitis
Monitor hepatic enzymes
Monitor patients for endocrinopathies
Monitor pituitary function regularly
Advise patient to report breathlessness or cough immediately
Advise patient to seek medical advice if severe skin reaction occurs
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Prophylactic antiemetic recommended before each dose
Suspend treatment if grade 2 adrenal insufficiency occurs
Suspend treatment if grade 3 or worse skin reaction occurs
Discontinue if grade 3 myocarditis occurs
Discontinue if grade 3 or 4 encephalitis or Guillain-Barre syndrome
Discontinue if grade 3 or greater adverse reaction that recurs/persists
Discontinue if grade 3 or higher infusion reaction occurs
Discontinue if grade 4 skin reaction occurs
Discontinue permanently if grade 4 colitis occurs
Discontinue treatment if AST/ALT >5 times upper limit of normal
Discontinue treatment if grade 3 or greater nephritis occurs
Discontinue treatment if grade 3 or greater pneumonitis occurs
Discontinue treatment if total bilirubin >3 times upper limit of normal
RCC: Discontinue if AST/ALT > 3 x ULN and bilirubin > or equal to 2 x ULN
RCC: Discontinue permanently if AST/ALT levels exceed 10 times ULN
RCC: Suspend treatment if AST/ALT is 3-10 times ULN
Suspend treatment if AST/ALT is 3-5 times upper limit of normal
Suspend treatment if grade 2 hypophysitis 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 hyperthyroidism occurs
Suspend treatment if grade 3 or greater adverse reaction occurs
Suspend treatment if total bilirubin between 1.5 and 3 times ULN
Not licensed for use in children under 18 years
Female: Contraception required during and for 4 months after treatment
Advise patient to seek medical advice if adverse reactions occur
Remind patient of importance of carrying Alert Card with them at all times
Upon improvement of immune related reactions to grade 1 or baseline the corticosteroid taper should be initiated and continued for at least 1 month.
Cases of hypophysitis (including hypopituitarism and secondary adrenal insufficiency) have been reported in patients receiving pembrolizumab. Patients should be monitored for signs and symptoms of hypophysitis and corticosteroids and hormone replacement therapy initiated to manage symptoms. Treatment should be suspended for symptomatic hypophysitis until controlled by hormone replacement therapy and after the corticosteroid taper. Monitoring of pituitary function and hormone levels should be carried out to ensure appropriate hormone replacement.
Patients with prior exposure to pembrolizumab have reported cases of graft-versus-host-disease (GVHD) and veno-occlusive disease (VOD) when undergoing allogeneic haematopoietic stem cell transplant (HSCT) due to classical hodgkin lymphoma. The benefits of HSCT should be weighed against the risks of transplant-related complications.
Patients with a history of allogeneic HSCT have also reported acute GVHD (including fatal GVHD) after treatment with pembrolizumab. The benefits of pembrolizumab should be weighed against the risks of GVHD.
Pregnancy and Lactation
Pembrolizumab is contraindicated during pregnancy.
The manufacturer recommends pembrolizumab should not be used during pregnancy unless treatment is necessary. At the time of writing, there is limited data on the use of pembrolizumab during pregnancy. Potential risks are unknown, however pembrolizumab has the potential to cross the placenta.
Animal studies have shown an increased risk of foetal loss.
Pembrolizumab is contraindicated during breastfeeding.
The manufacturer recommends a decision should be made whether to discontinue breastfeeding or pembrolizumab. At the time of writing, it is unknown whether pembrolizumab is excreted in breast milk. Pembrolizumab is a large protein molecule (molecular weight of around 149,000), therefore the expected amount found in milk is likely to be very low. A risk to neonates cannot be excluded.
Acute adrenal insufficiency
Graft versus host disease
Hepatic veno-occlusive disease
Hyperpigmentation of skin
Increases in hepatic enzymes
Myasthenic syndrome (transient)
Palmar-Plantar Erythrodysaesthesia syndrome
Prolongation of QT interval
Solid organ graft rejection
Toxic epidermal necrolysis
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 ).
Last Full Review Date: August 2019
Summary of Product Characteristics: Keytruda 25 mg/ml concentrate for solution for infusion. Merck Sharp and Dohme Limited. Revised November 2019.
Summary of Product Characteristics: Keytruda 50 mg powder for concentrate for solution for infusion. Merck Sharp and Dohme Limited. Revised June 2020.
MHRA Drug Safety Update July 2017
Available at: https://www.mhra.gov.uk
Last accessed: 26 July 2017
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Pembrolizumab. Last revised: 03 December 2018
Last accessed: 08 August 2019
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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.