Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
ZYNYZ contains the active substance retifanlimab, a monoclonal antibody (a protein that recognises and attaches to a specific target substance in the body). ZYNYZ helps your immune system fight your cancer. ZYNYZ is used in adults to treat Merkel cell carcinoma, a rare type of skin cancer. It is given when the cancer has spread or returned and cannot be treated with surgery or radiation.
Package leaflet: Information for the patient
ZYNYZ 500 mg concentrate for solution for infusion
Tell your doctor immediately if you have any of the following symptoms during treatment or if they get worse: • lung inflammation (pneumonitis) such as breathing difficulties, chest pain or new or worsening cough. • bowel inflammation (colitis) such as frequent diarrhoea often with blood and/or mucus, more bowel movements than usual, stools that are bloody, black or tarry and severe abdominal pain or tenderness. • liver inflammation. Symptoms include persistent nausea or vomiting, loss of appetite, pain on the right side of your stomach, eye and/or skin yellowing, drowsiness, dark-coloured urine, bleeding or bruising more easily than normal. • hormone gland problems (including the pituitary, thyroid and adrenal glands) that may affect how these glands work. Symptoms include fast heartbeat, dizziness, fainting, extreme tiredness, persistent or unusual headaches, weight change, hair loss, feeling cold or constipation. • type 1 diabetes or diabetic ketoacidosis. Symptoms of diabetes include feeling more hungry or thirsty than usual, frequent urination, weight loss, feeling tired or sick. Symptoms of diabetic ketoacidosis include difficulty thinking clearly, sleepiness, stomach pain, fast and deep breathing, breath that smells sweet or fruity, sweet or metallic taste in the mouth or a different odour to urine or sweat. • kidney inflammation. Symptoms include decreased volume of urine, foamy urine, passing blood or traces of blood in the urine that may change its colour, swollen ankles or loss of appetite. • skin problems that can lead to a severe skin reaction known as toxic epidermal necrolysis and Stevens-Johnson syndrome. Symptoms include rash, itching, skin blistering or ulcers in the mouth or in the lining of the nose, throat or genital area. • inflammation in other parts of the body such as eyes (changes in eyesight), joints, muscles, nerves, pancreas (symptoms include abdominal pain, nausea or vomiting), or of the heart muscle. • infusion-related reactions such as chills, shaking, rigor, fever, itching, rash, flushing or swollen face, shortness of breath or wheezing, feeling dizzy or faint. If you have any of the above-mentioned symptoms during treatment, do not try to treat your symptoms with other medicines on your own. Your doctor may: • give you other medicines to prevent complications and reduce your symptoms, • monitor you, • withhold the next dose of ZYNYZ, • stop your treatment or • slow or stop your infusion depending on the severity of the reaction, if you have an infusion-related reaction when you receive ZYNYZ. Please note that the above listed symptoms are sometimes delayed and may occur weeks or months after your last dose. Complications of solid organ transplant rejection, including graft-versus-host disease, in patients who have received a bone marrow (stem cell) transplant that uses donor stem cells can lead to death. They may occur if you undergo transplantation either before or after treatment with ZYNYZ. Your doctor will monitor you for these complications. Children and adolescents ZYNYZ should not be given to children and adolescents under 18 years of age because it has not been studied in this patient group. Other medicines and ZYNYZ Tell your doctor or nurse if you are using, have recently used or might use any other medicines. This applies in particular to medicines that suppress your immune system, such as corticosteroids, which may disrupt the effect of ZYNYZ. Once you are treated with ZYNYZ, your doctor may prescribe corticosteroids to reduce side effects that you may have during treatment. This will not impact the effect of the medicine.
Contraception Women who could become pregnant must use effective contraception during treatment and for minimum 4 months after the last ZYNYZ dose. Pregnancy You must not be given ZYNYZ if you are pregnant unless your doctor specifically recommends it. ZYNYZ can cause harmful effects or death to your unborn baby. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine. Breast-feeding It is not known if ZYNYZ passes into breast milk. A risk to the breast-feeding newborns/infants cannot be excluded. Ask your doctor for advice if you are breast-feeding. Driving and using machines ZYNYZ may have a minor influence on the ability to drive and use machines. If you feel tired, do not drive or use machines until you feel better. ZYNYZ contains sodium This medicine contains less than 1 mmol sodium (23 mg) per dose unit, that is to say essentially 'sodium-free.' However, before ZYNYZ is given to you, it is mixed with a solution that may contain sodium. Talk to your doctor if you are on a low-salt diet. ZYNYZ contains polysorbate 80 This medicine contains 2 mg of polysorbate 80 (E433) in each 20 mL of concentrate which is equivalent to 0.1 mg/mL. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.
Like all medicines, this medicine can cause side effects, although not everybody gets them. ZYNYZ can have serious side effects, which can sometimes become life-threatening and can lead to death. These side effects may happen at any time during treatment, or even after your treatment has ended. You may get more than one side effect at the same time (See section 2, "Warnings and precautions" for symptoms). Tell your doctor immediately if you have any of the following serious side effects: Common (may affect up to 1 in 10 people): • lung inflammation (pneumonitis) • bowel inflammation (colitis) • liver inflammation (hepatitis) • liver cell injury (hepatocellular injury) • sudden kidney damage (acute kidney failure) • kidney failure (renal failure) • infusion-related reactions that can cause symptoms such as chills, shaking or fever, itching or rash, flushing or swollen face, being short of breath or wheezing, feeling dizzy or nausea. Uncommon (may affect up to 1 in 100 people) • inflammation of the pituitary gland in the base of the brain (hypophysitis) • acid in the blood produced from diabetes (diabetic ketoacidosis) • damage to nerves causing numbness and weakness (polyneuropathy) • pinched nerve caused by damage to the root of the nerve(s) in the spine (radiculopathy) • nerve damage to voice box which is used for breathing, swallowing and talking (vocal cord paralysis) • inflammation of the eyes (uveitis) • inflammation of the cornea or the clear tissue on the front of the eye (keratitis) • inflammation of the covering of the heart which often causes sharp chest pain (pericarditis) • inflammation of the heart muscle (myocarditis) • inflammation of the pancreas (pancreatitis) Other side effects may occur with the following frequencies: Very common (may affect more than 1 in 10 people): • decrease in the number of red blood cells (anaemia) • decreased appetite • diarrhoea • nausea • constipation • rash • itching of the skin (pruritus) • joint pain (arthralgia) • tiredness (fatigue) • fever (pyrexia) Common (may affect up to 1 in 10 people): • underactive thyroid gland (hypothyroidism) • overactive thyroid gland (hyperthyroidism) • abnormal sensation such as tingling or numbness of the hands or feet (paraesthesia)
• increased blood level of liver enzymes, including alanine aminotransferase, aspartate aminotransferase • increased blood levels of bilirubin • increased blood levels of creatinine • increased blood levels of thyroid stimulating hormone • increased level of amylase, an enzyme that breaks down starch • increased levels of lipase, an enzyme that breaks down fats Uncommon (may affect up to 1 in 100 people): • decreased secretion of hormones produced by the adrenal glands (adrenal insufficiency) • thyroid gland inflammation (thyroiditis) • inflammation of the bile ducts (cholangitis) • increased blood levels of bilirubin causing yellowing of the eyes and skin (hyperbilirubinaemia) • joint inflammation (arthritis) • muscle inflammation (myositis) • inflammation of the tissue between the muscle and skin which may cause skin swelling (eosinophilic fasciitis) • inflammation of the muscles causing pain or stiffness (polymyalgia rheumatica) • decreased blood levels of thyroid stimulating hormone Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed below: Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.
This leaflet was last revised in 03/2026. Other sources of information Detailed information on this medicine is available on the Medicines and Healthcare products Regulatory Agency web site: www.gov.uk/mhra ------------------------------------------------------------------------------------------------------------------------ The following information is intended for healthcare professionals only:
Preparation and administration • Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. Retifanlimab is a clear to slightly opalescent, colourless to pale yellow solution, free of visible particles. Discard the vial if the solution is cloudy, discoloured or visible particles are observed. • Do not shake the vial. • Withdraw 20 mL (500 mg) of retifanlimab concentrate from the vial and transfer into an intravenous infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection to prepare a diluted solution with a final concentration between 1.4 mg/mL to 10 mg/mL. Use polyvinylchloride (PVC) and di-2-ethylhexyl phthalate (DEHP), polyolefin copolymer, polyolefin with polyamide, or ethylene vinyl acetate infusion bags. • Mix the diluted solution by gentle inversion. Do not shake the infusion bag. • From a microbiological point of view, the diluted solution, once prepared, should be used immediately. If not used immediately, chemical and physical in-use stability has been demonstrated: − For 8 hours at room temperature (20 °C to 25 °C) (including infusion time).
OR − For 24 hours under refrigeration at (2 °C to 8 °C). If refrigerated, allow the diluted solution to come to room temperature prior to administration. The diluted solution must be administered within 4 hours (including infusion time) once it is removed from the refrigerator. Do not freeze. • Discard if the diluted solution is discoloured or contains extraneous particulate matter other than trace amounts of translucent to white particles. • Administer the retifanlimab solution by intravenous infusion over 30 minutes using a sterile, non-pyrogenic, low-protein binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2 micron to 5 micron in-line or add-on filter or 15 micron mesh in-line or add-on filter. • Do not coadminister other medicinal products through the same infusion line. Disposal • Retifanlimab is for single use only; discard any unused portion left in the vial. • Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
ZYNYZ 500 mg concentrate for solution for infusion comes as solution containing 500 mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in ZYNYZ 500 mg concentrate for solution for infusion is retifanlimab.
This leaflet reproduces the patient information leaflet approved for ZYNYZ 500 mg concentrate for solution for infusion, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
ZYNYZ is indicated as monotherapy for the first‑line treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) not amenable to curative surgery or radiation therapy.
Treatment should be initiated and supervised by a physician experienced in the treatment of cancer.
Posology
The recommended dose is 500 mg retifanlimab every 4 weeks administered as an intravenous infusion over 30 minutes. Treatment should continue until disease progression or unacceptable toxicity for up to 2 years.
Dose modifications
Dose escalation or reduction of retifanlimab is not indicated.
Recommended dose modifications to manage immune‑related adverse reactions are provided in Table 1 (see also sections 4.4 and 4.8).
Table 1: Recommended dose modifications
| Adverse reaction | Severitya | Dose modification |
| Pneumonitis | Grade 2 | Withhold until adverse reactions recover to Grades 0‑1. |
| Grades 3 or 4 | Permanently discontinue. | |
| Colitis | Grades 2 or 3 | Withhold until adverse reactions recover to Grades 0‑1. |
| Recurrent Grade 3 or Grade 4 | Permanently discontinue. | |
| Hepatitis with no tumour involvement of the liver OR Increased total bilirubin | Grade 3 with AST or ALT greater than 3 but no more than 8 times ULN OR TB increases to more than 1.5 and up to 3 times ULN | Withhold until adverse reactions recover to Grades 0‑1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. |
| Grade 4 with AST or ALT increases to more than 8 times ULN OR TB greater than 3 times ULN | Permanently discontinue. | |
| Hepatitis with tumour involvement of the liver OR Increased total bilirubin | Grade 3 with AST or ALT more than 5 and up to 10 times ULN OR TB greater than 1.5 but no more than 3 times ULN | Withhold until adverse reactions recover to Grades 0‑1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. |
| Grade 4 with AST or ALT increase to more than 10 times ULN OR TB greater than 3 times ULN | Permanently discontinue. | |
| Endocrinopathies • Adrenal insufficiency • Hypothyroidism • Hyperthyroidism • Type 1 diabetes mellitus • Hyperglycaemia • Hypophysitis | Grade 2 adrenal insufficiency | Withhold until adverse reactions recover to Grades 0‑1 or otherwise clinically stable. |
| Grades 3 or 4 adrenal insufficiency | Withhold until adverse reactions recover to Grades 0‑1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. | |
| Grades 3 or 4 hypothyroidism | Withhold until adverse reactions recover to Grades 0‑1 or is otherwise clinically stable. | |
| Grades 3 or 4 hyperthyroidism | Withhold until adverse reactions recover to Grades 0‑1 or is otherwise clinically stable. | |
| Grades 3 or 4 type 1 diabetes mellitus (or hyperglycaemia) | Withhold until adverse reactions recover to Grades 0‑1 or is otherwise clinically stable. | |
| Grade 2 hypophysitis (asymptomatic) | Withhold until adverse reactions recover to Grades 0‑1. May restart after controlled by hormone replacement therapy. | |
| Grade 2 hypophysitis (symptomatic e.g., headaches, visual disturbances) | Withhold until adverse reactions recover to Grades 0‑1. May restart after controlled by hormone replacement therapy, if indicated and steroid taper is complete. | |
| Grade 3 or 4 hypophysitis (symptomatic) | Withhold until adverse reactions recover to Grades 0‑1. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids. | |
| Nephritis with renal dysfunction | Grade 2 increased blood creatinine | Withhold until adverse reactions recover to Grades 0‑1. |
| Grade 3 or 4 increased blood creatinine | Permanently discontinue.b | |
| Skin reactions | Grade 3 or suspected SJS or suspected TEN Persistent Grade 2 (≥ 2 weeks) | Withhold until adverse reactions recover to Grades 0‑1. |
| Grade 4 or confirmed SJS or confirmed TEN | Permanently discontinue. | |
| Myocarditis | Confirmed Grades 2, 3 or 4 | Permanently discontinue. |
| Other immune‑related adverse reactions (including myositis, encephalitis, demyelinating neuropathy, Guillain Barré syndrome, sarcoidosis, autoimmune haemolytic anaemia, pancreatitis, uveitis, diabetic ketoacidosis, arthralgia) | Grade 3 | Withhold until adverse reactions recover to Grades 0‑1. |
| Grade 4 | Permanently discontinue. | |
| Persistent Grade 2 or 3 immune‑related adverse reactions (excluding endocrinopathies) | Grade 2 or 3 (≥ 12 weeks after last dose) Recurrent Grade 3 or 4 Recurrent Grade 2 pneumonitis | Permanently discontinue. |
| Infusion‑related reactions | Grade 1 | Interrupt or slow the rate of infusion. |
| Grade 2 | First occurrence: Interrupt infusion and resume at 50% of the original rate if symptoms resolve within 1 hour. Subsequent occurrences: Permanently discontinue after recommended prophylaxis. | |
| Grade 3 | Permanently discontinue. If rapidly responsive to symptomatic management and/or to brief interruption of infusion, retifanlimab does not need to be permanently discontinued. | |
| Grade 4 | Permanently discontinue. |
AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limit of normal; TB = total bilirubin; SJS = Stevens‑Johnson syndrome; TEN = toxic epidermal necrolysis.
a Toxicity graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.
b Permanently discontinue only if retifanlimab is directly implicated in renal toxicity.
Patient card
All prescribers of ZYNYZ should be familiar with and inform the patients about the patient card explaining what to do should they experience any symptom of immune‑related adverse reactions. The patient card will be provided to each patient treated with retifanlimab.
Special populations
Elderly
No dose adjustment is needed for patients who are aged 65 years or over (see sections 5.1 and 5.2).
Renal impairment
No dose adjustment is needed for patients with mild or moderate renal impairment. There is insufficient data in patients with severe renal impairment (creatinine clearance < 30 mL/min) and no data for patients with end‑stage renal disease and therefore no dosing recommendation can be made (see section 5.2).
Hepatic impairment
No dose adjustment is needed for patients with mild hepatic impairment. There are insufficient data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment and therefore no dosing recommendations can be made (see section 5.2).
Paediatric population
There is no relevant use of retifanlimab in children and adolescents below the age of 18 years with Merkel cell carcinoma.
Method of administration
ZYNYZ is for intravenous use. It must be diluted and administered by intravenous infusion over 30 minutes.
ZYNYZ must not be administered as an intravenous push or bolus injection.
ZYNYZ can only be administered through an intravenous line containing a sterile, non‑pyrogenic, low‑protein binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2 micron to 5 micron in‑line or add‑on filter or 15 micron mesh in‑line or add‑on filter. Other medicinal products should not be co‑administered through the same infusion line.
For instructions on dilution of the medicinal product before administration, see section 6.6.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
No formal pharmacokinetic drug interaction studies have been conducted with retifanlimab. Since retifanlimab is cleared from the circulation through catabolism, no metabolic drug‑drug interactions are expected.
The use of systemic corticosteroids or immunosuppressants before starting retifanlimab, except for physiological doses of systemic corticosteroids (≤ 10 mg/day prednisone or equivalent), should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of retifanlimab. However, systemic corticosteroids or other immunosuppressants can be used after starting retifanlimab to treat immune‑related adverse reactions (see sections 4.2 and 4.4).
Retifanlimab is not expected to be a victim or perpetrator of drug‑drug interactions involving drug transporters or CYP enzymes.
Women of childbearing potential/Contraception
Women of childbearing potential should use effective contraception during treatment with retifanlimab and for at least 4 months after the last dose of retifanlimab.
Pregnancy
There are no data from the use of retifanlimab in pregnant women. Animal reproduction studies have not been conducted with retifanlimab. Animal studies have demonstrated that inhibition of the PD‑1/PD‑L1 pathway can lead to increased risk of immune‑mediated rejection of the developing foetus resulting in foetal death. Therefore, based on its mechanism of action, retifanlimab can cause foetal harm when administered to a pregnant woman. Human IgG4 immunoglobulins are known to cross the placenta; therefore, retifanlimab has the potential to be transmitted from the mother to the developing foetus. ZYNYZ is not recommended during pregnancy and in women of childbearing potential not using effective contraception (see section 5.3).
Breast‑feeding
It is unknown whether retifanlimab is excreted in human milk. There is insufficient information on the excretion of retifanlimab in animal milk.
Human IgGs are known to be excreted in breast milk during the first few days after birth; which decreases to low concentrations soon afterwards; consequently, a risk to the breast‑fed infant cannot be excluded during this short period. For this specific period, a decision should be made whether to discontinue/abstain from retifanlimab therapy, taking into account the benefit of breast‑feeding to the child and the benefit of therapy to the woman. Afterwards, retifanlimab could be used during breast‑feeding if clinically needed.
Fertility
No clinical data are available on the possible effects of retifanlimab on fertility. Animal reproduction studies to evaluate the effect of retifanlimab on fertility have not been conducted.
ZYNYZ has minor influence on the ability to drive and use machines. Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that retifanlimab does not adversely affect them.
In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.
Ask anything about ZYNYZ 500 mg concentrate for solution for infusion. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
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