Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Pharmacy Guide
Patient leaflets and SmPCs, drug interaction checker, official dosages and NHS pharmacy opening hours — all in one place.
Plegridy 125 micrograms solution for injection in pre-filled pen
⚠ This medicine appears to have been discontinued
The electronic medicines compendium (emc) no longer publishes a Summary of Product Characteristics for this product, which usually means it is no longer marketed in the UK. The patient leaflet below is kept for reference, but the product may not be available.
If you were prescribed this medicine, other products containing Peginterferon beta-1a may still be available. Do not stop your treatment — ask your pharmacist or GP what to use instead.
What it is and what it is used for
for
What Plegridy is The active substance in Plegridy is peginterferon beta-1a. Peginterferon beta-1a is a modified long-acting form of interferon. Interferons are natural substances made in the body to help protect from infections and diseases. What Plegridy is used for This medicine is used to treat relapsing-remitting multiple sclerosis (MS) in adults aged 18 or over. MS is a long term illness that affects the central nervous system (CNS), including the brain and spinal cord, in which the body's immune system (its natural defences) damages the protective layer (myelin) that surrounds the nerves in the brain and spinal cord. This disrupts the messages between the brain and other parts of the body, causing the symptoms of MS. Patients with relapsing-remitting MS have periods when the disease is not active (remission) in between flare-ups of symptoms (relapses). Everyone has their own set of MS symptoms. These can include: Feeling off-balance or light headed, walking problems, stiffness and muscle spasms, tiredness, numbness in the face, arms or legs Acute or chronic pain, bladder and bowel problems, sexual problems and problems with vision Difficulty thinking and concentrating, depression.
How Plegridy works Plegridy seems to work by stopping the body's immune system from damaging your brain and spinal cord. This can help to reduce the number of relapses that you have and slow down the disabling effects of MS. Treatment with Plegridy can help to prevent you from getting worse, although it will not cure MS.
2.
What you need to know before you take it
e Plegridy
Do not use Plegridy If you are allergic to peginterferon beta-1a, interferon beta-1a or any of the ingredients of this medicine (listed in section 6). See section 4 for the symptoms of an allergic reaction. If you have severe depression or think about committing suicide. Warnings and precautions Talk to your doctor if you have ever had: Depression or problems affecting your mood Thoughts about committing suicide
- Your doctor may still prescribe Plegridy for you, but it's important to let your doctor know if you have had depression or any similar problems affecting your mood in the past. Talk to your doctor, pharmacist or nurse before injecting Plegridy if you have any of the conditions listed below. They may get worse while using Plegridy: Serious liver or kidney problems Irritation at an injection site, which can lead to skin and tissue damage (injection site necrosis). When you are ready to inject, carefully follow the instructions in section 7 "Instructions for injecting Plegridy pre-filled pen", at the end of this leaflet. This is to reduce the risk of injection site reactions. Epilepsy or other seizure disorders, not controlled by medicine Heart problems, which can cause symptoms such as chest pain (angina), particularly after any activity; swollen ankles, shortness of breath (congestive heart failure); or an irregular heartbeat (arrhythmia). Thyroid problems A low number of white blood cells or platelets, which can cause an increased risk of infection, or bleeding Other things to consider when using Plegridy You will need blood tests to determine your numbers of blood cells, blood chemistry and your levels of liver enzymes. These will be performed before you start using Plegridy, regularly after treatment with Plegridy has been initiated and then periodically during treatment, even if you have no particular symptoms. These blood tests will be in addition to the tests which are normally done to monitor your MS. The functioning of your thyroid gland will be checked regularly or whenever thought necessary by your doctor for other reasons. Blood clots in the small blood vessels may occur during your treatment. These blood clots could affect your kidneys. This might happen several weeks to several years after starting Plegridy. Your doctor may want to check your blood pressure, blood (platelet count) and the function of your kidneys.
If you accidentally prick yourself or someone else with the needle in Plegridy, the area affected should be washed immediately with soap and water and a doctor or nurse should be contacted as soon as possible. Children and adolescents Plegridy should not be used in children and adolescents because it is yet to be established whether it would work for them and whether it would be safe. Other medicines and Plegridy Plegridy should be used carefully with medicines that are broken down in the body by a group of proteins called "cytochrome P450" (e.g. some medicines used for epilepsy or depression). Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, especially those used to treat epilepsy or depression. This includes any medicines obtained without a prescription. Sometimes you will need to remind other healthcare professionals that you are being treated with Plegridy. For example, if you are prescribed other medicines, or if you have a blood test. Plegridy may affect the other medicines or the test result. Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. No harmful effects on the breastfed newborn/infant are anticipated. Plegridy can be used during breastfeeding. Driving and using machines Plegridy has no or negligible influence on the ability to drive and use machines. Plegridy contains sodium This medicine contains less than 1 mmol sodium (23 mg), that is to say it is essentially "sodium-free".
3.
How to take it
Plegridy
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. The usual dose One injection of Plegridy 125 micrograms every 14 days (every two weeks). Try to use Plegridy at the same time on the same day, every time you inject. Starting Plegridy If you are new to Plegridy, your doctor may advise you to gradually increase your dose so that you can adjust to the effects of Plegridy before taking the full dose. You will be provided with an Initiation Pack containing your first 2 injections: one orange pen with Plegridy 63 micrograms (for day 0) and one blue pen with Plegridy 94 micrograms (for day 14).
After that you will be provided with a maintenance pack containing grey pens with Plegridy 125 micrograms (for day 28 and then every two weeks). Read the instructions in section 7 "Instructions for injecting Plegridy pre-filled pen" at the end of this leaflet before you start using Plegridy. Use the record table printed on the inside of the lid of the Initiation Pack to keep a track of your injection dates. Injecting yourself Plegridy is to be injected under the skin (subcutaneous injection). Alternate the sites you use for injections. Do not use the same injection site for consecutive injections. You can inject Plegridy yourself without the help of your doctor, if you have been trained how to do this.
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Read and follow the advice given in the instructions in section 7 "Instructions for injecting Plegridy pre-filled pen" before you start. If you have trouble handling the pen, ask your doctor or nurse who may be able to help.
How long to use Plegridy Your doctor will tell you how long you need to keep using Plegridy. It is important to continue using Plegridy regularly. Do not make changes unless your doctor tells you. If you use more Plegridy than you should You must only inject Plegridy once every 2 weeks. If you have used more than one injection of Plegridy in a 7-day period, contact your doctor or nurse straight away. If you forget to use Plegridy You need to inject Plegridy once every 2 weeks. This regular schedule helps to deliver the treatment as evenly as possible. If you do miss your usual day, inject as soon as you can and carry on as usual. However, do not inject more than once in a 7-day period. Do not use two injections to make up for a missed injection. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
4.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. Serious side effects
- Liver problems (common – may affect up to 1 in 10 people) If you get any of these symptoms: Yellowing of your skin or the whites of your eyes Itching all over Feeling sick, being sick (nausea and vomiting) Easy bruising of the skin Contact a doctor immediately. They may be signs of a possible liver problem.
- Depression (common – may affect up to 1 in 10 people) If you: Feel unusually sad, anxious or worthless or Have thoughts about suicide Contact a doctor immediately.
- Serious allergic reaction (uncommon – may affect up to 1 in 100 people) If you get any of these:
- Difficulty breathing
- Swelling around the face (lips, tongue or throat)
- Skin rashes or redness Contact a doctor immediately.
- Seizures (uncommon – may affect up to 1 in 100 people) If you have a seizure or a fit Contact a doctor immediately. Injection site damage (rare – may affect up to 1 in 1,000 people) If you get any of these symptoms: Any break in the skin together with swelling, inflammation or fluid leaking around the injection site Contact a doctor for advice. Kidney problems including scarring that may reduce your kidney function (rare – may affect up to 1 in 1,000 people) If you get some or all of these symptoms: Foamy urine Fatigue Swelling, particularly in the ankles and eyelids, and weight gain. Contact a doctor as they may be signs of a possible kidney problem. Blood problems (rare – may affect up to 1 in 1,000 people) The following may occur: Blood clots in the small blood vessels that can affect your kidneys (thrombotic thrombocytopenic purpura or haemolytic uremic syndrome). Symptoms may include increased bruising, bleeding, fever, extreme weakness, headache, dizziness or light-headedness. Your doctor may find changes in your blood and the function of your kidneys. If you get some or all of these symptoms: Increased bruising or bleeding Extreme weakness Headache, dizziness or light-headedness Contact a doctor immediately. Other side effects Very common side effects
(may affect more than 1 in 10 people) Flu-like symptoms. These symptoms are not really flu, see below. You can't pass it on to anyone else. Headache Muscle pain (myalgia) Pain in your joints, arms, legs or neck (arthralgia) Chills Fever Feeling weak and tired (asthenia) Redness, itching or pain around the place you have injected If any of these effects trouble you, contact a doctor. Flu-like symptoms Flu-like symptoms are more common when you first start using Plegridy. They gradually get less as you keep using your injections. See below for simple ways to manage these flu-like symptoms if you get them. Three simple ways to help reduce the impact of flu-like symptoms: 1. Consider the timing of your Plegridy injection. The start and end of flu-like symptoms are different for every patient. On average, flu-like symptoms begin approximately 10 hours after injection and last between 12 and 24 hours. 2. Take paracetamol or ibuprofen half an hour before your Plegridy injection and continue to take paracetamol or ibuprofen for the duration of your flu-like symptoms. Speak to your doctor or pharmacist about how much to take and how long to take it. 3. If you have a fever, drink plenty of water to keep you hydrated. Common side effects (may affect up to 1 in 10 people) Feeling or being sick (nausea or vomiting) Hair loss (alopecia) Itchy skin (pruritus) Increase in body temperature Changes around the place you have injected such as swelling, inflammation, bruising, warmth, rash or colour change Changes in your blood which might cause tiredness or reduced ability to fight infection Increases in liver enzymes in the blood (will show up in blood tests) If any of these effects trouble you, talk to your doctor. Uncommon side effects (may affect up to 1 in 100 people) Hives Changes in your blood which might cause unexplained bruising or bleeding. If any of these effects trouble you, talk to your doctor. Frequency not known (frequency cannot be estimated from the available data) Pulmonary arterial hypertension: A disease of severe narrowing of the blood vessels in the lungs resulting in high blood pressure in the blood vessels that carry blood from the heart to the lungs. Pulmonary arterial hypertension has been seen at various time points during treatment, including several years after starting treatment with interferon beta-products.
Children (10 years of age and above) and adolescents In clinical trials, some side effects were reported very commonly in both adults and children, e.g., redness at the injection site, flu-like symptoms, headache, and fever. Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the 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. In order to improve the traceability of this medicine, your doctor or pharmacist should record the name and the lot number of the product you have been given in your patient file. You may also wish to make a note of these details in case you are asked for this information in the future.
5.
How to store it
Plegridy
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the carton and the label after "EXP". The expiry date refers to the last day of that month. –
Store in the original package in order to protect from light. Only open the pack when you need a new pen.
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Store in a refrigerator (fridge), 2o-8oC.
- Do not freeze. Throw away any Plegridy that is accidentally frozen.
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Plegridy can be kept outside a fridge at room temperature (up to 25°C) for up to 30 days but it must be kept away from light.
- Packs can be taken out of the fridge and then put back in a fridge more than once if you need to.
- Make sure the time the pens spend out of a fridge is no more than 30 days in total.
- Throw away any pen that is kept out of the fridge for more than 30 days.
- If you are unsure of the number of days you have kept a pen out of the fridge, throw the pen away.
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Do not use this medicine if you notice any of the following:
- If the pen is broken.
- If the solution is coloured, cloudy or you can see particles floating in it.
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Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6.
Contents of the pack and other information
What Plegridy contains The active ingredient is peginterferon beta-1a. Each 63 microgram pre-filled pen contains 63 micrograms of peginterferon beta-1a in 0.5 mL solution for injection. Each 94 microgram pre-filled pen contains 94 micrograms of peginterferon beta-1a in 0.5 mL solution for injection. Each 125 microgram pre-filled pen contains 125 micrograms of peginterferon beta-1a in 0.5 mL solution for injection. The other ingredients are: Sodium acetate trihydrate, acetic acid glacial, arginine hydrochloride, polysorbate 20 and water for injections (see Section 2 "Plegridy contains Sodium"). What Plegridy looks like and contents of the pack Plegridy is a clear and colourless solution for injection in a glass pre-filled pen with an attached needle. Pack sizes:
- The Plegridy Initiation Pack contains one orange pre-filled pen of 63 micrograms and one blue pre-filled pen of 94 micrograms.
- The 125 micrograms grey pens are provided in a pack containing either two or six pre-filled pens. Not all pack sizes may be marketed. Marketing Authorisation Holder Biogen Netherlands B.V. Prins Mauritslaan 13 1171 LP Badhoevedorp The Netherlands Manufacturer FUJIFILM Diosynth Biotechnologies Denmark ApS Biotek Allé 1 DK-3400 Hillerød Denmark Biogen Netherlands B.V. Prins Mauritslaan 13 1171 LP Badhoevedorp The Netherlands
This leaflet was last revised in January 2026
7.
Instructions for injecting Plegridy pre-filled pen Caution! Do not remove the cap until you are ready to inject.
How to Inject Plegridy Read the instructions for use before you start using Plegridy and each time you get a refill of your prescription. There may be new information. This information does not take the place of talking to your doctor or nurse about your medical condition or your treatment. Note: Before you use the pen for the first time, your doctor or nurse should show you or your carer how to prepare and inject the pen. The pen is for use under the skin only (subcutaneous). Each pen can be used once only. Do not share the pen with anyone else to avoid giving an infection to them or getting an infection from them. Do not use more than 1 pen every 14 days (every 2 weeks). Do not use the pen if it has been dropped or is visibly damaged. Dosage schedule The Initiation Pack contains your first two injections to gradually adjust your dose. Choose the correct pen from a pack. When Day 0 (63 micrograms) Day 14 (94 micrograms)
Day 28 and then every two weeks after that (125 micrograms)
Which dose First injection: 63 micrograms, choose orange pen Second injection: 94 micrograms, choose blue pen Full dose injection: 125 micrograms, choose grey pen
Do not use more than one pen per 14-day period (every 2 weeks). Supplies needed for your Plegridy Pen injection: 1 Plegridy Pen (see Figure A)
Which pack
Before use – Parts of Plegridy Pen (Figure A)
Caution! Do not remove the cap until you are ready to inject. If you remove the cap, do not re-cap the pen. Re-capping could cause the pen to lock. Additional supplies which are not included in the pack (see Figure B):
Preparing for your injection Step 1: Remove your pen from the fridge. a. b. c.
Remove your Plegridy pack from the fridge and select the appropriate pen (dosage) from the pack. Close the pack and put back in the fridge after removing one pen. Let the pen warm to room temperature for at least 30 minutes. Do not use external heat sources, such as hot water, to warm your pen.
Step 2: Collect your supplies and wash your hands. a. b.
Find a well-lit, clean, flat surface to work on like a table. Collect all the supplies you will need to give yourself, or receive, an injection. Wash your hands with soap and water.
Step 3: Check your Plegridy pen (see Figure C) a. Check the injection status window. You should see green stripes. b. Check the expiry date. c. Check the medicine window and make sure the Plegridy medicine is clear and colourless. Do not use the pen if: You do not see the green stripes in the injection status window. It is expired. The liquid is coloured, cloudy or contains floating particles. Note: You might see air bubbles in the medicine window. This is normal and will not affect your dose. Do not use the pen if it has been dropped or is visibly damaged. Step 4: Choose and clean your injection site a. Choose an injection site in your thigh, abdomen, or the back of your upper arm (see highlighted areas in Figure D). If some areas are too difficult for you to reach, ask a carer who has been trained to help you. Do not inject into an area of your body where the skin is irritated, red, bruised, tattooed, infected, or scarred. Do not inject directly into your belly button. b. Wipe your skin with an alcohol wipe. Note: Do not touch or blow on this area again before giving your injection. c. Let your injection site dry on its own before injecting your dose.
Giving your injection Step 5: Remove the Plegridy pen cap a. Pull the pen cap straight off and set it aside (see Figure E). Your pen is now ready to inject. Warning! Do not touch, clean, or manipulate the needle cover. You could get a needle injury or the pen may lock. Caution! Do not re-cap your pen. This could lock the pen
Step 6: Give the injection a. Hold the pen over your injection site. Make sure you can see the green stripes in the injection status window (see Figure F). You should hold the pen over your injection site at 90o angle. Warning! Do not rest the pen on the injection site until you are ready to inject. This may cause the pen to accidently lock.
b. Firmly press and hold down the pen on your injection site. You will hear the clicking sounds start. This tells you that the injection is happening (see Figure G).
c. Continue to hold the pen firmly down on your injection site until the clicking sounds have stopped (see Figure H). Do not lift your pen off your injection site until the clicking sounds stop and you see green ticks in the injection status window. Warning! If you do not hear clicking sounds or you do not see green ticks in the injection status window after attempting to inject, the pen may have locked and you may not have received your injection. You should then contact your doctor, nurse or pharmacist.
Step 7: Remove the Plegridy pen from your injection site a. After the clicking sound has stopped, lift the pen from your injection site. The needle cover will extend to cover the needle and will lock (see Figure I). If you see blood at your injection site, wipe it off with the gauze pad and apply an adhesive bandage or plaster
Step 8: Check to make sure you received your full dose of Plegridy (see Figure J) a. Check the injection status window. You should see green ticks. b. Check the medicine window. You should see a yellow plunger.
After the injection After Use – Parts of your Plegridy pen (see Figure K):
Note: After the pen has been removed from the injection site, the needle cover will lock to protect against needle injury. Do not re-cap the pen. Step 9: Dispose of used Plegridy pen Check with your doctor, pharmacist or nurse about the right way to throw away the used pen. Do not re-cap the pen. Step 10: Care for your injection site If needed, apply a gauze pad or adhesive bandage or plaster to the injection site.
Step 11: Check injection site After 2 hours, check the injection site for redness, swelling, or tenderness. If you have a skin reaction and it does not clear up in a few days, contact your doctor or nurse. Record date and location Record the date and location of each injection. For the Initiation Pack injections, you can use the record table printed on the inside of the lid of the Initiation Pack. General warnings Do not reuse your Plegridy pen. Do not share your Plegridy pen. Keep Plegridy pen and all medicines out of reach of children. Storage
Recommended storage is controlled refrigeration 2°C to 8°C in the closed original carton to protect from light. If needed, Plegridy may be stored in the closed original carton without refrigeration up to 25°C for up to 30 days. Plegridy can be removed from and returned to the refrigerator if necessary. The total combined time out of refrigeration at a temperature up to 25°C, should not exceed 30 days. Do not freeze or expose to high temperatures.
Frequently asked questions about Plegridy 125 micrograms solution for injection in pre-filled pen
How do I take Plegridy 125 micrograms solution for injection in pre-filled pen?
Plegridy 125 micrograms solution for injection in pre-filled pen comes as injection containing 125mcg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
What is the active substance in Plegridy 125 micrograms solution for injection in pre-filled pen?
The active substance in Plegridy 125 micrograms solution for injection in pre-filled pen is peginterferon beta-1a.
Are there equivalent medicines to Plegridy 125 micrograms solution for injection in pre-filled pen?
Medicines with the same active substance, strength and form include: Plegridy 125 micrograms solution for injection in pre-filled syringe. They are interchangeable only if your prescriber or pharmacist says so.
Where does this information come from?
This leaflet reproduces the patient information leaflet approved for Plegridy 125 micrograms solution for injection in pre-filled pen, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Can I get Plegridy 125 micrograms solution for injection in pre-filled pen without a prescription?
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.
About this leaflet
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
- Source: electronic medicines compendium (emc), Datapharm
- Active substance: peginterferon beta-1a
- Official document: view the original leaflet on emc →
⚕For healthcare professionals — Summary of Product Characteristics (SmPC)Full SmPC: dosage, interactions, contraindications, warnings+
4.1. Therapeutic indications
Plegridy is indicated in adult patients for the treatment of relapsing remitting multiple sclerosis (see section 5.1).
4.2. Posology and method of administration
Treatment should be initiated under supervision of a physician experienced in the treatment of multiple sclerosis.
Plegridy may be administered subcutaneously (SC) using a single-use pre-filled pen or pre-filled syringe or intramuscularly (IM) using a single use pre-filled syringe.
Efficacy of peginterferon beta-1a administered subcutaneously has been demonstrated over placebo. Direct comparative data for peginterferon beta-1a versus non-pegylated interferon beta or data on efficacy of peginterferon beta-1a after switching from a non-pegylated interferon beta are not available. This should be considered when switching patients between pegylated and non-pegylated interferons (see section 5.1).
Posology
The recommended dose of Plegridy is 125 micrograms injected SC or IM every 2 weeks (14 days).
Treatment initiation
It is generally recommended that patients start SC or IM treatment with 63 micrograms at dose 1 (on day 0), increasing to 94 micrograms at dose 2 (on day 14), reaching the full dose of 125 micrograms by dose 3 (on day 28) and continuing with the full dose (125 micrograms) every 2 weeks (14 days) thereafter (see Table 1a for SC use or Table 1b for IM use).
Subcutaneous route
An initiation pack is available containing the first 2 doses (63 micrograms and 94 micrograms).
Table 1a: Titration schedule at initiation via SC route
Dose
Time*
Amount (micrograms)
Syringe label
Dose 1
Day 0
63
Orange
Dose 2
Day 14
94
Blue
Dose 3
Day 28
125 (full dose)
Grey
*Dosed every 2 weeks (14 days)
Intramuscular route
An administration dose pack contains the full 125 microgram dose in 1 pre-filled syringe.
The Plegridy titration clips, designed for use with the pre-filled syringe are intended to limit the dose that is administered to 63 micrograms (dose 1 (1/2 dose), yellow titration clip) and 94 micrograms (dose 2 (3/4 dose), purple titration clip), for day 0 and day 14 respectively. Each Plegridy titration clip should be used once, and then discarded along with any remaining medicinal product. Patients should use the full dose of 125 micrograms (no clip required) from day 28 onwards (dosing every 14 days).
Table 1b Titration schedule at initiation via IM route
Dose
Time*
Amount (micrograms)
Titration clip
Dose 1
Day 0
63
Yellow
Dose 2
Day 14
94
Purple
Dose 3
Day 28
125 (full dose)
No clips needed
*Dosed every 2 weeks (14 days)
Dose titration at the initiation of treatment may help to ameliorate flu-like symptoms that can occur at treatment initiation with interferons. Prophylactic and concurrent use of anti-inflammatory, analgesic and/or antipyretic treatments may prevent or ameliorate flu-like symptoms sometimes experienced during interferon treatment (see section 4.8).
Switching between the SC and IM routes of administration and vice versa has not been studied. Based upon bioequivalence demonstrated between the two routes of administration it is not expected that dose titration will be required if switching between SC and IM, or vice versa (see sections 5.1 and 5.2).
If a dose is missed, it should be administered as soon as possible.
• If 7 days or more to the next planned dose: Patients should administer their missed dose immediately. Treatment can then continue with the next scheduled dose as planned.
• If less than 7 days to the next planned dose: Patients should begin a new 2 week dosing schedule starting from when they administer their missed dose. A patient should not administer two doses of peginterferon beta-1a within 7 days of each other.
Special populations
Elderly population
The safety and efficacy of peginterferon beta-1a in patients over the age of 65 have not been sufficiently studied due to the limited number of such patients included in clinical trials.
Renal impairment
No dosage adjustments are necessary in patients with renal impairment based on study data in mild, moderate, and severe renal impairment and end stage renal disease (see sections 4.4 and 5.2).
Hepatic impairment
Peginterferon beta-1a has not been studied in patients with hepatic impairment (see section 4.4).
Paediatric population
The safety and efficacy of peginterferon beta-1a in children and adolescents aged 10 to less than 18 years have not been established in multiple sclerosis. Currently available data are described in section 4.8, 5.1 and 5.2, but no recommendation on a posology can be made.
The safety and efficacy of peginterferon beta-1a in children below 10 years of age have not been established. No data are available.
Method of administration
It is recommended that a healthcare professional trains patients in the proper technique for self—administering SC injections using the SC pre-filled syringe/pre-filled pen or IM injections using the IM pre-filled syringes as appropriate. Patients should be advised to rotate sites for SC or IM injections every two weeks. The usual sites for subcutaneous injections include abdomen, arm, and thigh. The usual site for intramuscular injection is the thigh.
Each Plegridy pre-filled pen/syringe for SC is provided with the needle pre-attached. Plegridy prefilled syringe for IM use is supplied as a prefilled syringe with a separate needle for IM use.
Both IM and SC pre-filled syringes and SC pre-filled pens are for single use only and should be discarded after use.
Precautions to be taken before handling or administering the medicinal product
Once removed from the refrigerator, Plegridy should be allowed to warm to room temperature (up to 25 oC) for about 30 minutes prior to injection. External heat sources such as hot water must not be used to warm the medicinal product.
Plegridy pre-filled syringe must not be used if the liquid is coloured, cloudy, or contains floating particles. The liquid in the syringe must be clear and colourless.
Plegridy pre-filled pen must not be used unless the green stripes are visible in the pen injection status window. Plegridy pre-filled pen must not be used if the liquid is coloured, cloudy, or contains floating particles. The liquid in the medicinal product window must be clear and colourless.
4.3. Contraindications
- Hypersensitivity to natural or recombinant interferon beta or peginterferon or to any of the excipients listed in section 6.1.
- Patients with current severe depression and/or suicidal ideation (see sections 4.4 and 4.8).
4.4. Special warnings and precautions for use
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hepatic injury
Elevated serum hepatic transaminase levels, hepatitis, autoimmune hepatitis and rare cases of severe hepatic failure have been reported with interferon beta medicinal products. Elevations in hepatic enzymes have been observed with the use of peginterferon beta-1a. Patients should be monitored for signs of hepatic injury (see section 4.8).
Depression
Peginterferon beta-1a should be administered with caution to patients with previous depressive disorders (see section 4.3). Depression occurs with increased frequency in the multiple sclerosis population and in association with interferon use. Patients should be advised to immediately report any symptoms of depression and/or suicidal ideation to their prescribing physician.
Patients exhibiting depression should be monitored closely during therapy and treated appropriately. Cessation of therapy with peginterferon beta-1a should be considered (see section 4.8).
Hypersensitivity reactions
Serious hypersensitivity reactions including cases of anaphylaxis have been reported as a rare complication of treatment with interferon beta, including peginterferon beta-1a. Patients should be advised to discontinue treatment with peginterferon beta-1a and seek immediate medical care if they experience signs and symptoms of anaphylaxis or severe hypersensitivity. Treatment with peginterferon beta-1a should not be restarted (see section 4.8).
Injection site reactions
Injection site reactions, including injection site necrosis, have been reported with the use of subcutaneous interferon beta. To minimise the risk of injection site reactions patients should be instructed in the use of an aseptic injection technique. The procedure for the self-administration by the patient should be reviewed periodically especially if injection site reactions have occurred. If the patient experiences any break in the skin, which may be accompanied by swelling or drainage of fluid from the injection site, the patient should be advised to speak with their doctor. One patient treated with peginterferon beta-1a in clinical trials experienced an injection site necrosis with SC peginterferon beta-1a. Whether to discontinue therapy following a single site of necrosis is dependent on the extent of necrosis (see section 4.8).
Decreased peripheral blood counts
Decreased peripheral blood counts in all cell lines, including rare pancytopenia and severe thrombocytopenia, have been reported in patients receiving interferon beta. Cytopenias, including rare severe neutropenia and thrombocytopenia, have been observed in patients treated with peginterferon beta-1a. Patients should be monitored for symptoms or signs of decreased peripheral blood counts (see section 4.8).
Renal and urinary disorders
Nephrotic syndrome (class effects)
Cases of nephrotic syndrome with different underlying nephropathies including collapsing focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranoproliferative glomerulonephritis (MPGN) and membranous glomerulopathy (MGN) have been reported during treatment with interferon-beta products. Events were reported at various time points during treatment and may occur after several years of treatment with interferon beta. Periodic monitoring of early signs or symptoms, e.g. oedema, proteinuria and impaired renal function is recommended, especially in patients at higher risk of renal disease. Prompt treatment of nephrotic syndrome is required and discontinuation of treatment with peginterferon beta-1a should be considered.
Severe renal impairment
Caution should be used when administering peginterferon beta-1a to patients with severe renal impairment.
Thrombotic microangiopathy (TMA) (class effects)
Cases of TMA, manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS), including fatal cases, have been reported with interferon beta products. Events were reported at various time points during treatment and may occur several weeks to several years after starting treatment with interferon beta. Early clinical features include thrombocytopenia, new onset hypertension, fever, central nervous system symptoms (e.g. confusion, paresis) and impaired renal function. Laboratory findings suggestive of TMA include decreased platelet counts, increased serum lactate dehydrogenase (LDH) due to haemolysis and schistocytes (erythrocyte fragmentation) on a blood film. Therefore if clinical features of TMA are observed, further testing of blood platelet levels, serum LDH, blood films and renal function is recommended. If TMA is diagnosed, prompt treatment is required (considering plasma exchange) and immediate discontinuation of peginterferon beta-1a is recommended.
Laboratory abnormalities
Laboratory abnormalities are associated with the use of interferons. In addition to those laboratory tests normally required for monitoring patients with multiple sclerosis, complete blood and differential blood cell counts, platelet counts, and blood chemistries, including liver function tests (e.g. aspartate aminotransferase (AST), alanine aminotransaminase (ALT)), are recommended prior to initiation and at regular intervals following introduction of peginterferon beta-1a therapy and then periodically thereafter in the absence of clinical symptoms.
Patients with myelosuppression may require more intensive monitoring of complete blood cell counts, with differential and platelet counts.
Hypothyroidism and hyperthyroidism have been observed with the use of interferon beta products. Regular thyroid function tests are recommended in patients with a history of thyroid dysfunction or as clinically indicated.
Seizure
Peginterferon beta-1a should be administered with caution to patients with a history of seizures, to those receiving treatment with anti-epileptics, particularly if their epilepsy is not adequately controlled with anti-epileptics (see section 4.8).
Cardiac disease
Worsening of cardiac disease has been reported in patients receiving interferon beta. The incidence of cardiovascular events was similar between peginterferon beta-1a (125 micrograms every 2 weeks) and placebo treatment groups (7% in each group). No serious cardiovascular events were reported in patients who received peginterferon beta-1a in the ADVANCE study. Nevertheless, patients with pre-existing- significant cardiac disease, such as congestive heart failure, coronary artery disease or arrhythmia should be monitored for worsening of their cardiac condition, particularly during initiation of treatment.
Immunogenicity
Patients may develop antibodies to peginterferon beta-1a. Data from patients treated up to 2 years with peginterferon beta-1a administered SC suggests that less than 1% (5/715) developed persistent neutralising- antibodies to the interferon beta-1a portion of peginterferon beta-1a. Neutralising antibodies have the potential to reduce clinical efficacy. However, the development of antibodies against the interferon moiety of peginterferon beta-1a had no discernible impact on safety or clinical efficacy, although the analysis was limited by the low immunogenicity incidence.
Three percent of patients (18/681) developed persistent antibodies to the PEG moiety of peginterferon beta-1a. In the clinical study conducted, the development of antibodies against the PEG moiety of peginterferon beta-1a had no discernible impact on safety, or clinical efficacy (including annualised relapse rate, magnetic resonance imaging (MRI) lesions, and disability progression).
Hepatic impairment
Caution should be used and close monitoring considered when administering peginterferon beta-1a to patients with severe hepatic impairment. Patients should be monitored for signs of hepatic injury and caution exercised when interferons are used concomitantly with other medicinal products associated with hepatic injury (see sections 4.8 and 5.2).
Sodium content
This medicinal product contains less than 1 mmol (23 mg) sodium, that is to say it is essentially “sodium-free”.
4.5. Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed. The clinical studies indicate that multiple sclerosis patients can receive peginterferon beta-1a and corticosteroids during relapses. Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when peginterferon beta-1a is administered in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance, e.g. some classes of antiepileptics and antidepressants.
4.6. Fertility, pregnancy and lactation
Pregnancy
A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited.
Based on animal data (see section 5.3), there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far.
If clinically needed, the use of peginterferon beta-1ay may be considered during pregnancy.
Breast-feeding
Limited information available on the transfer of interferon beta-1a/peginterferon beta-1a into breast milk, together with the chemical / physiological characteristics of interferon beta, suggests that levels of interferon beta-1a/peginterferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated.
Peginterferon beta-1a can be used during breast-feeding.
Fertility
There are no data on the effects of peginterferon beta-1a on human fertility. In animals, anovulatory effects were observed at very high doses (see section 5.3). No information is available on the effects of peginterferon beta-1a on male fertility in animals.
4.7. Effects on ability to drive and use machines
Peginterferon beta-1a has no or negligible influence on the ability to drive and use machines.
4.8. Undesirable effects
Summary of safety profile
The most common adverse drug reactions (ADR) (at a higher incidence than placebo) for Peginterferon beta-1a 125 micrograms subcutaneously every 2 weeks were injection site erythema, influenza like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia.
The most commonly reported adverse reaction leading to discontinuation in patients treated with peginterferon beta-1a 125 micrograms subcutaneously every 2 weeks was influenza-like illness (<1%).
Tabulated list of adverse reactions via subcutaneous route of administration
In clinical studies, a total of 1,468 patients received peginterferon beta-1a SC for up to 278 weeks with an overall exposure equivalent of 4,217 person -years. 1,285 patients received at least 1 year, 1,124 patients have received at least 2 years, 947 patients received at least 3 years, and 658 patients received at least 4 years of treatment with peginterferon beta-1a. The experience in the randomised, uncontrolled phase (year 2) of the ADVANCE study and in the extension study ATTAIN (treatment received for up to 4 years) was consistent with the experience in the 1 year placebo-controlled phase of the ADVANCE study.
Table 2 summarizes ADRs (incidence above placebo and with a reasonable possibility of causality) from 512 patients treated with peginterferon beta-1a 125 micrograms SC every 2 weeks and 500 patients who received placebo for up to 48 weeks and post-marketing data.
The ADRs are presented as MedDRA preferred terms under the MedDRA System Organ Class. The incidence of the adverse reactions below are expressed according to the following categories:
- Very common (≥1/10)
- Common (≥1/100 to <1/10)
- Uncommon (≥1/1,000 to <1/100)
- Rare (≥1/10,000 to <1/1,000)
- Very rare (<1/10,000)
- Not known (cannot be estimated from the available data)
Table 2 Tabulated summary of adverse drug reactions
MedDRA system organ class
Adverse reaction
Frequency category
Blood and lymphatic system disorders
Thrombocytopenia
Uncommon
Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome*
Rare
Immune system disorders
Angioedema
Uncommon
Hypersensitivity
Anaphylaxis1
Not known
Psychiatric disorders
Depression
Common
Nervous system disorders
Headache
Very common
Seizure
Uncommon
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension┼
Not known
Gastrointestinal disorders
Nausea
Common
Vomiting
Skin and subcutaneous tissue disorders
Alopecia$
Common
Pruritus
Urticaria
Uncommon
Musculoskeletal and connective tissue disorders
Myalgia
Very common
Arthralgia
Renal and urinary disorders
Nephrotic syndrome, glomerulosclerosis
Rare
General disorders and administration site conditions
Influenza like illness
Very common
Pyrexia
Chills
Injection site erythema
Injection site pain
Injection site pruritus
Asthenia
Hyperthermia
Common
Injection site inflammation
Pain
Injection site haematoma
Injection site swelling
Injection site oedema
Injection site rash
Injection site warmth
Injection site discolouration
Injection site necrosis
Rare
Investigations
Alanine aminotransferase increased
Common
Aspartate aminotransferase increased
Gamma-glutamyltransferase increased
White blood cell count decreased
Haemoglobin decreased
Body temperature increased
Platelet count decreased
Uncommon
*Class label for interferon beta products (see section 4.4).
┼ Class label for interferon products, see below Pulmonary arterial hypertension
$ Class label for interferon products
1 Adverse reactions derived only during post marketing experience
Description of selected adverse reactions via subcutaneous route of administration
Flu-like symptoms
Influenza -like illness was experienced by 47% of patients receiving peginterferon beta-1a 125 micrograms every 2 weeks and 13% of patients receiving placebo. The incidence of flu-like symptoms (e.g. influenza -like illness, chills, hyperpyrexia, musculoskeletal pain, myalgia, pain, pyrexia) was highest at the initiation of treatment and generally decreased over the first 6 months. Of the patients who reported flu-like symptoms 90% reported them as mild or moderate in severity. None were considered serious in nature. Less than 1% of patients who received peginterferon beta-1a during the placebo-controlled phase of the ADVANCE study discontinued treatment due to flu-like symptoms. An open -label study in patients switching from interferon beta therapy to peginterferon beta-1a evaluated the onset and duration of prophylactically treated flu-like symptoms. In patients experiencing flu-like symptoms, the median time to onset was 10 hours (interquartile range, 7 to 16 hours) after injection, and the median duration was 17 hours (interquartile range, 12 to 22 hours).
Injection site reactions (ISRs)
ISRs (e.g. injection site erythema, pain, pruritus, or oedema) were reported by 66% of patients who received peginterferon beta-1a 125 micrograms every 2 weeks compared to 11% of patients receiving placebo. Injection site erythema was the most commonly reported injection site reaction. Of the patients who experienced injection site reactions 95% reported them as mild or moderate in severity. One patient out of 1,468 patients who received peginterferon beta-1a in clinical studies experienced an injection site necrosis which resolved with standard medical treatment.
Hepatic transaminase abnormalities
The incidence of hepatic transaminase increases was greater in patients receiving peginterferon beta-1a compared to placebo. The majority of enzyme elevations were <3 times the upper limit of normal (ULN). Elevations of alanine aminotransferase and aspartate aminotransferase (>5 times ULN), were reported in 1% and <1% of placebo-treated patients and 2% and <1% of patients treated with peginterferon beta-1a respectively. Elevations of serum hepatic transaminases combined with elevated bilirubin were observed in two patients who had pre-existing liver test abnormalities prior to receiving peginterferon beta-1a in the clinical trials. Both cases resolved following discontinuation of the medicinal product.
Haematological disorders
Decreases in white blood cell (WBC) counts of <3.0 x 109/L were observed in 7% of patients receiving peginterferon beta-1a and in 1% receiving placebo. Mean WBC counts remained within normal limits in patients treated with peginterferon beta-1a. Decreases in WBC counts were not associated with an increased risk of infections or serious infections. The incidence of potentially clinically significant decreases in lymphocyte counts (<0.5 x 109/L) (<1%), neutrophil counts (≤1.0 x 109/L) (<1%) and platelet counts (≤100 x 109/L) (≤1%) was similar in peginterferon beta-1a-treated patients compared to placebo-treated patients. Two serious cases were reported in patients treated with peginterferon beta-1a: one patient (<1%) experienced severe thrombocytopenia (platelet count <10 x 109/L), another patient (<1%) experienced severe neutropenia (neutrophil count <0.5 x 109/L). In both patients, cell counts recovered after discontinuation of peginterferon beta-1a. Slight decreases in mean red blood cell (RBC) counts were observed in peginterferon beta-1atreated patients. The incidence of potentially clinically significant decreases in RBC counts (<3.3 x 1012/L) was similar in peginterferon beta-1a treated patients compared to placebo- treated-patients.
Hypersensitivity reactions
Hypersensitivity events were reported in 16% of patients treated with peginterferon beta-1a 125 micrograms every 2 weeks and 14% of patients who received placebo. Less than 1% of peginterferon beta-1a treated patients experienced a serious hypersensitivity event (e.g. angioedema, urticaria) and they recovered promptly after treatment with anti-histamines and/or corticosteroids. In post marketing experience, serious hypersensitivity events including cases of anaphylaxis (frequency not known) have been reported following peginterferon beta-1a administration.
Pulmonary arterial hypertension
Cases of pulmonary arterial hypertension (PAH) have been reported with interferon beta products. Events were reported at various time points including up to several years after starting treatment with interferon beta.
Intramuscular route of administration
An open-label, crossover study enrolled 136 subjects to assess the bioequivalence of single doses of 125 micrograms of peginterferon beta-1a administered SC and IM injection in healthy volunteers. The most commonly reported AEs (with >10% incidence in either arm) across both treatment periods were chills (35.6% in IM vs 26.9% in SC ), pain (22.0% in IM vs 14.2% in SC), injection site pain (11.4% in IM vs 14.9% in SC), injection site erythema (2.3% in IM vs 25.4% in SC ), and headache (35.6% in IM vs 41.0% in SC). Injection site reactions were reported with a lower frequency in IM (14.4%) compared to SC (32.1%).
Abnormal urine protein was reported in 1/130 (0.8%) for the SC arm and 4/131 (3.1%) in the IM group without any associated adverse drug reactions.
Paediatric population
The safety of peginterferon beta-1a in paediatric patients aged 10 to less than 18 years was studied in an open-label randomized active controlled paediatric trial with 152 paediatric patients with RRMS (peginterferon beta-1a n=75; interferon beta-1a n=77). 66 patients in the peginterferon beta-1a group completed 48 weeks of this study. The following adverse events which are very common in the adult population were also reported as very common in the paediatric population: injection site erythema, influenza-like illness, headache and pyrexia.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
In case of over-dose, patients may be hospitalized for observation and appropriate supportive treatment should be given.
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