KEYTRUDA (Pembrolizumab)

What Is KEYTRUDA and What Is It Used For?

KEYTRUDA (pembrolizumab) is an immunotherapy medicine that contains a humanised monoclonal antibody. It works by helping your immune system fight cancer by blocking the PD-1 protein on T cells, thereby releasing the immune system's natural ability to recognise and destroy tumour cells.

Pembrolizumab belongs to a class of drugs known as immune checkpoint inhibitors. Cancer cells often exploit immune checkpoint pathways to evade detection by the immune system. Specifically, many tumours express proteins called PD-L1 and PD-L2 on their surface. When these proteins bind to the PD-1 receptor on T cells (a type of white blood cell), they send an “off” signal that prevents the T cell from attacking. Pembrolizumab binds to PD-1, blocking this interaction and thereby restoring the T cell’s ability to recognise and kill cancer cells.

KEYTRUDA has transformed the treatment landscape for many types of cancer. It is used in adults to treat the following cancers:

• Melanoma – a serious type of skin cancer. KEYTRUDA is used for advanced melanoma that has spread or cannot be surgically removed, as well as after surgery to prevent recurrence (adjuvant therapy)
• Non-small cell lung cancer (NSCLC) – the most common type of lung cancer. KEYTRUDA is used both as initial treatment (often with chemotherapy) and after surgery (adjuvant and neoadjuvant therapy)
• Malignant pleural mesothelioma – a cancer affecting the lining around the lungs and chest wall
• Classical Hodgkin lymphoma – a cancer of the lymphatic system
• Urothelial cancer (bladder cancer) – cancer of the bladder and urinary tract lining
• Head and neck squamous cell carcinoma – cancer of the mouth, throat, or larynx
• Renal cell carcinoma (kidney cancer) – often in combination with axitinib or lenvatinib, and as adjuvant therapy after surgery
• MSI-H or dMMR cancers – cancers with high microsatellite instability or deficient mismatch repair, including colorectal cancer, endometrial cancer, gastric cancer, small intestine cancer, and biliary tract cancer
• Oesophageal cancer – cancer of the food pipe
• Triple-negative breast cancer (TNBC) – an aggressive form of breast cancer that does not express hormone receptors or HER2
• Endometrial cancer – cancer of the uterine lining
• Cervical cancer – cancer of the cervix
• Gastric adenocarcinoma – stomach cancer and cancer of the gastroesophageal junction
• Biliary tract cancer – cancer of the bile ducts or gallbladder

KEYTRUDA is given to patients whose cancer has spread (metastatic disease) or cannot be removed by surgery (unresectable disease). For some cancers, it is also used before surgery (neoadjuvant) to shrink the tumour and after surgery (adjuvant) to reduce the risk of recurrence. It may be administered as monotherapy or in combination with chemotherapy, targeted therapy, and/or radiation therapy, depending on the specific cancer type and treatment setting.

What Should You Know Before Receiving KEYTRUDA?

Before starting KEYTRUDA, inform your doctor about all your medical conditions, especially autoimmune diseases, organ transplant history, liver or kidney problems, and any other medications you are taking. KEYTRUDA should not be given if you are allergic to pembrolizumab or any of its ingredients.

Contraindications

You should not receive KEYTRUDA if:

• You are allergic to pembrolizumab or any of the other ingredients in this medicine, including recombinant hyaluronidase alfa, L-histidine, L-methionine, sucrose, polysorbat 80, or water for injections. Talk to your doctor if you are unsure.

Warnings and Precautions

Talk to your doctor or nurse before receiving KEYTRUDA if you:

• Have an autoimmune disease (a condition where the body attacks its own cells) – KEYTRUDA may worsen autoimmune conditions or cause flare-ups
• Have lung inflammation (pneumonia or pneumonitis)
• Have previously been treated with ipilimumab (another immunotherapy for melanoma) and experienced serious side effects from that treatment
• Have had an allergic reaction to other monoclonal antibody treatments
• Have a chronic viral liver infection, including hepatitis B (HBV) or hepatitis C (HCV)
• Have HIV infection or acquired immunodeficiency syndrome (AIDS)
• Have liver or kidney damage
• Have undergone an organ transplant or an allogeneic stem cell (bone marrow) transplant using donor cells

KEYTRUDA works by activating your immune system. This can cause inflammation in various parts of the body. The risk of these side effects may be higher if you already have an autoimmune disease. You may also experience flares of your existing autoimmune condition, although most flares are mild.

These immune-mediated adverse reactions can occur at any time during treatment and even after treatment has ended. You may experience more than one side effect simultaneously. Your doctor may delay your next dose or discontinue KEYTRUDA treatment and may prescribe corticosteroids or other medications to manage symptoms.

Use in Children and Adolescents

KEYTRUDA solution for injection is not recommended for use in children under 18 years of age. Other formulations of pembrolizumab may be more suitable for paediatric patients where approved – consult your doctor for advice.

Pregnancy and Breastfeeding

You should not receive KEYTRUDA if you are pregnant unless your doctor specifically recommends it. KEYTRUDA can cause harm to the unborn baby, including foetal death, because of its mechanism of blocking the PD-1 pathway, which plays a role in maintaining pregnancy tolerance.

If you are a woman of childbearing potential, you must use effective contraception during KEYTRUDA treatment and for at least 4 months after your last dose. Tell your doctor if you are pregnant, think you might be pregnant, or are planning to become pregnant.

Do not breastfeed during treatment with KEYTRUDA. It is not known whether pembrolizumab passes into breast milk, but because of the potential for serious adverse effects in the nursing infant, breastfeeding should be avoided.

Driving and Operating Machinery

KEYTRUDA may have a minor effect on your ability to drive or operate machinery. Fatigue, dizziness, and weakness are possible side effects. Do not drive or use machines after receiving KEYTRUDA until you are sure you feel well.

Important Information About KEYTRUDA Ingredients

KEYTRUDA solution for injection contains polysorbat 80 (0.2 mg per mL), which may cause allergic reactions in some people. Tell your doctor if you have known allergies to polysorbates. This medicine also contains less than 1 mmol (23 mg) sodium per dose, meaning it is essentially “sodium-free”.

How Does KEYTRUDA Interact with Other Drugs?

The most important interaction to be aware of is with systemic corticosteroids and other immunosuppressants, which may reduce KEYTRUDA's effectiveness. However, corticosteroids can be used to manage immune-mediated side effects after treatment has started. KEYTRUDA is also commonly combined with specific chemotherapy and targeted therapy regimens.

Unlike many conventional drugs, pembrolizumab is a monoclonal antibody and is not metabolised by cytochrome P450 enzymes. Therefore, traditional pharmacokinetic drug interactions are generally not a concern. However, the following drug interactions are clinically important because they affect KEYTRUDA’s immunological mechanism of action.

Major Interactions

Approved Combination Therapies

KEYTRUDA is frequently combined with other cancer treatments as part of approved regimens. The specific combination depends on the cancer type:

When KEYTRUDA is given in combination with other medicines, it is important to also read the patient information leaflets for those medications. Ask your doctor if you have any questions about these other medicines.

What Is the Correct Dosage of KEYTRUDA?

The recommended dose for adults is 395 mg given as a subcutaneous injection every 3 weeks, or 790 mg every 6 weeks. KEYTRUDA is always administered by a healthcare professional experienced in cancer treatment. The injection takes 1–2 minutes.

You will receive KEYTRUDA in a hospital or specialist clinic under the supervision of a doctor experienced in treating cancer. Your doctor will decide how many treatments you need based on the type and stage of your cancer, your response to treatment, and any side effects you experience.

Adults – Subcutaneous Injection

Treatment Duration

The duration of KEYTRUDA treatment depends on the type and stage of cancer:

• Advanced/metastatic cancers: Treatment typically continues for as long as the cancer responds and side effects remain manageable, often for up to 2 years (35 cycles at 3-week intervals)
• Adjuvant therapy (after surgery): Treatment is usually given for up to 1 year (approximately 18 cycles at 3-week intervals) to prevent cancer recurrence
• Neoadjuvant + adjuvant therapy: Treatment before and after surgery follows specific protocols determined by your oncologist

Intravenous Administration

Your doctor may change the way your treatment is given, from a subcutaneous injection to an intravenous (IV) infusion into a vein. When given intravenously, KEYTRUDA is administered as a 30-minute infusion at doses of 200 mg every 3 weeks or 400 mg every 6 weeks.

Missed Dose

If you miss an appointment for your KEYTRUDA injection, contact your doctor immediately to reschedule. It is very important not to miss a dose of this medicine. Do not try to make up for a missed dose by doubling the next one.

Stopping Treatment

Stopping KEYTRUDA may mean that the medicine’s effect ceases. Do not stop treatment with KEYTRUDA unless you have discussed it with your doctor. Your doctor may discontinue treatment if you develop severe immune-mediated side effects, if your cancer progresses, or if the maximum treatment duration has been reached.

What Are the Side Effects of KEYTRUDA?

The most common side effects of KEYTRUDA given alone include fatigue, musculoskeletal pain, rash, diarrhoea, nausea, decreased appetite, itching, cough, shortness of breath, constipation, headache, and fever. KEYTRUDA can also cause immune-mediated side effects that may be serious or life-threatening, requiring prompt medical attention.

Like all medicines, KEYTRUDA can cause side effects, although not everybody gets them. Because KEYTRUDA works by activating the immune system, it can cause the immune system to attack healthy tissues in addition to cancer cells. These immune-mediated adverse reactions are a distinct and important class of side effects described in detail in the warnings section above.

Injection site reactions have been reported when KEYTRUDA is given as a subcutaneous injection. These are common (may affect up to 1 in 10 people) and typically include redness, swelling, pain, or itching at the injection site.

Side Effects When KEYTRUDA Is Used Alone

Additional Side Effects in Combination with Chemotherapy

When KEYTRUDA is given together with chemotherapy, additional or more frequent side effects may occur. These include:

• Very common: decreased red and white blood cells (anaemia, neutropenia), decreased platelets, low potassium, sleep problems, nerve inflammation, hair loss, increased liver enzymes (ALT, AST)
• Common: neutropenia with fever (febrile neutropenia), adrenal insufficiency, acute kidney injury, increased bilirubin

Additional Side Effects in Combination with Axitinib or Lenvatinib

When KEYTRUDA is combined with axitinib or lenvatinib for kidney cancer or endometrial cancer, additional common side effects include:

• Urinary tract infection, high blood pressure, altered taste, increased lipase levels, abnormal kidney function
• Diarrhoea, nausea, vomiting, and abdominal pain may be more frequent

If you experience any side effects not listed here, or if any side effect becomes severe, contact your doctor or nurse. Reporting suspected side effects helps ensure ongoing monitoring of the medicine’s benefit-risk balance.

How Should KEYTRUDA Be Stored?

Unopened KEYTRUDA vials must be stored in a refrigerator at 2–8°C, protected from light, in the original packaging. Do not freeze. Once prepared in a syringe, use promptly or store under controlled conditions as specified below.

KEYTRUDA is stored and handled by healthcare professionals in the hospital or clinic. Patients do not typically store this medication at home. However, it is useful to know the following storage requirements:

Unopened Vials

• Store in a refrigerator at 2°C to 8°C
• Do not freeze
• Keep in the original packaging to protect from light
• Do not use after the expiry date (EXP) printed on the carton and vial

Prepared Syringe

Once the solution has been transferred from the vial to the syringe, chemical and physical stability has been demonstrated for up to 30 days at 2–8°C (protected from light) and up to 24 hours at room temperature (in ambient light). The 24-hour room temperature period may include up to 8 hours at up to 25°C. Refrigerated filled syringes must reach room temperature for at least 30 minutes before use. The filled syringe must not be frozen.

Do not save any leftover solution for reuse. Unused medicine and waste should be disposed of in accordance with local regulations.

What Does KEYTRUDA Contain?

Each vial of KEYTRUDA contains pembrolizumab as the active ingredient, co-formulated with recombinant hyaluronidase alfa to facilitate subcutaneous delivery. It is a clear to slightly opalescent, colourless to slightly yellow solution.

Active Ingredient

The active substance is pembrolizumab. Each millilitre of solution for injection contains 165 mg pembrolizumab.

• 2.4 mL vial: contains 395 mg pembrolizumab
• 4.8 mL vial: contains 790 mg pembrolizumab

Inactive Ingredients (Excipients)

The other ingredients are: recombinant hyaluronidase alfa, L-histidine, L-histidine hydrochloride monohydrate, L-methionine, sucrose, polysorbat 80, and water for injections.

Appearance and Packaging

KEYTRUDA solution for injection is a clear to slightly opalescent, colourless to slightly yellow solution with a pH of 5.3–5.9. It is supplied in cartons containing one glass vial.

Sodium Content

This medicine contains less than 1 mmol (23 mg) sodium per dose, meaning it is essentially “sodium-free”.

How Does KEYTRUDA Work in the Body?

KEYTRUDA works by blocking the PD-1 receptor on T cells, removing the “off switch” that cancer cells exploit to hide from the immune system. This restores the ability of T cells to recognise, attack, and kill cancer cells. It is part of a revolutionary approach to cancer treatment known as immune checkpoint inhibition.

The human immune system is equipped with a complex network of checkpoints that regulate its activity. These checkpoints exist to prevent the immune system from attacking the body’s own healthy cells – a state known as immune tolerance. However, cancer cells have evolved to exploit these checkpoints, effectively disguising themselves from immune detection.

One of the most important immune checkpoints involves the PD-1 (programmed death-1) receptor, which is found on the surface of T cells. When PD-1 binds to its ligands, PD-L1 and PD-L2, which are expressed on many types of cancer cells, the T cell receives a signal to stand down and not attack. This is how tumours evade immune destruction.

Pembrolizumab is a humanised IgG4 kappa monoclonal antibody that binds to PD-1 with high affinity, blocking it from interacting with PD-L1 and PD-L2. By occupying the PD-1 receptor, pembrolizumab prevents the “off” signal from being transmitted to the T cell. The result is a reinvigorated immune response against tumour cells, leading to tumour regression and, in many cases, durable anti-tumour immunity.

Pharmacokinetic Profile

Pembrolizumab is administered subcutaneously and is co-formulated with recombinant hyaluronidase alfa, an enzyme that temporarily increases the permeability of subcutaneous tissue, facilitating absorption of the large antibody molecule. Pembrolizumab exhibits linear pharmacokinetics across the therapeutic dose range.

The terminal elimination half-life of pembrolizumab is approximately 22 days. Steady-state concentrations are reached by approximately 16 weeks of repeated dosing on a 3-week cycle (approximately 5.3 half-lives). As a monoclonal antibody, pembrolizumab is catabolised through general protein degradation pathways rather than cytochrome P450 metabolism, which minimises the potential for conventional drug-drug interactions.

The development of pembrolizumab and other PD-1/PD-L1 inhibitors represents one of the most significant advances in cancer treatment in recent decades. James P. Allison and Tasuku Honjo were awarded the 2018 Nobel Prize in Physiology or Medicine for their discovery of immune checkpoint therapy, which laid the scientific foundation for drugs like KEYTRUDA.

Frequently Asked Questions About KEYTRUDA