Fuzeon

Patient Information Leaflet

Fuzeon 90 mg/ml powder and solvent for injectable solution

Enfuvirtide
Please read this leaflet carefully before using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Fuzeon is and what it is used for
2. What you need to know before using Fuzeon
3. How to use Fuzeon
4. Possible side effects
5. How to store Fuzeon
6. Contents of the pack and other information

7. Step-by-step guide on how to self-inject Fuzeon

1. What Fuzeon is and what it is used for
What Fuzeon is
Fuzeon contains the active substance enfuvirtide and belongs to a group of medicines called
"antiretrovirals".

What Fuzeon is used for
Fuzeon is used in the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral medicines in patients with HIV infection.

• Your doctor has prescribed Fuzeon to help you control HIV infection.
• Fuzeon does not cure HIV infection.

How Fuzeon works
HIV attacks cells in the body known as CD4 cells or T-lymphocytes. In order for the virus to multiply, it must attach to these cells and enter them. Fuzeon helps prevent this process.

2. What you should know before using Fuzeon

Do not use Fuzeon

• if you are allergic to enfuvirtide or to any of the other ingredients of this medicine (listed in section 6). If you are unsure, consult your doctor, pharmacist, or nurse before using Fuzeon.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Fuzeon:

• if you have previously had any type of lung problems,
• if you have previously had any type of kidney problems,
• if you have chronic hepatitis B or C or any other liver disease; there is an increased risk of developing serious liver problems when using this medicine.

Signs of previous infections
In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections,
inflammatory signs and symptoms of previous infections may occur shortly after starting anti-HIV therapy.
These symptoms are believed to result from the recovery of the body's immune system. This improvement enables the body to fight infections that may have been present without clear symptoms. If you notice any signs of infection, inform your doctor immediately.
Signs of autoimmune disorders
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet spreading upwards towards the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive the necessary treatment.
Patients with liver disease
Patients with chronic hepatitis B or C undergoing anti-HIV therapy are at higher risk of developing serious liver problems. If you have previously had a liver disease, consult your doctor.
Bone disease (osteonecrosis)
Some patients taking combination anti-HIV medicines may develop a bone disease called osteonecrosis, in which reduced blood supply leads to bone tissue death (death of bone tissue due to inadequate blood supply to the bone).

• Signs of osteonecrosis include joint stiffness, discomfort, and pain (especially in the hips, knees, and shoulders), and difficulty moving. Consult your doctor if you notice any of these signs.
• Risk factors for developing this disease include: duration of anti-HIV therapy, use of corticosteroids, amount of alcohol consumed, immune system function, and being overweight.

Other medicines and Fuzeon
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines, including those without a prescription and herbal remedies. It has been shown that Fuzeon does not interact with other anti-HIV medicines you are taking or with rifampicin (an antibiotic).
Fuzeon with food and drink
You may use Fuzeon with or without food. However, you should follow the instructions provided in the package leaflets of any other medicines you are taking.
Pregnancy and breastfeeding

• If you are pregnant, think you might be pregnant, or are planning a pregnancy, ask your doctor for advice before taking this medicine. Do not use Fuzeon unless specifically instructed by your doctor.
• Breastfeeding is not recommended for HIV-positive women because HIV infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, you should discuss this with your doctor as soon as possible.

Driving and using machines
The effect of Fuzeon on the ability to drive vehicles or operate tools or machinery has not been studied. If you experience dizziness while using Fuzeon, do not drive or operate tools or machinery.
Fuzeon contains sodium
Fuzeon contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially ‘sodium-free’.

3. How to use Fuzeon

Always use this medicine exactly as instructed by your doctor or pharmacist. Consult your doctor or pharmacist if you have any doubts.
How to prepare and inject Fuzeon
Fuzeon must be administered by injection just beneath the skin, that is, by "subcutaneous" injection. In section 7 you will find instructions on how to prepare Fuzeon and how to self-inject the medicine.
How much Fuzeon to use

• For adults and adolescents (aged 16 years and older), the recommended dose is 90 mg twice daily.
• The dose is administered as a 1 ml injection just beneath the skin.
• It is best to use Fuzeon at the same time each day.
• Try to evenly space the dosing times at convenient times for you, for example, early in the morning and early in the evening.

See further instructions on how to use Fuzeon at the end of this leaflet (see section 7).
You will find instructions on how to prepare Fuzeon and how to self-inject the medicine.
If you use more Fuzeon than you should
If you use more Fuzeon than you should, contact a doctor or go to hospital immediately, taking the medicine pack with you.
If you forget to use Fuzeon

• If you forget to take a dose, take it as soon as you remember. However, if there are less than 6 hours remaining before the next scheduled dose, skip the missed dose.
• Do not take a double dose to make up for a forgotten dose.

If you stop using Fuzeon

• Continue using the medicine until your doctor tells you to stop treatment. Stopping treatment, even temporarily, may increase the likelihood that the HIV virus in your blood becomes resistant to Fuzeon more quickly than if you took the medicine regularly and without interruptions.
• The HIV virus in your blood may become resistant to Fuzeon. In such a case, viral levels in the blood may start to rise. This is when your doctor might decide to discontinue therapy with Fuzeon. Your doctor will discuss this with you should it occur.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you notice any of the following side effects, stop treatment with Fuzeon and
contact a doctor immediately; you may need urgent medical treatment.

• Allergic reaction (hypersensitivity) – signs may include: rash, high temperature or chills, nausea or vomiting, sweating or tremor. This side effect is rare (affects fewer than 1 person in 1,000). These signs do not necessarily mean that you are allergic to the medicine.

Tell your doctor if you experience side effects at the injection site.
The most common side effects (affect more than 1 person in 10) are problems at the site on the body where the injection is given. You are likely to experience one or more of the following reactions, which are generally mild to moderate:

• redness
• swelling
• itching
• bruising
• hardened skin or firm lumps (nodules)
• pain, tenderness or soreness

These reactions may appear during the first week of treatment and usually last no longer than 7 days. After this time, the reactions generally do not worsen. If you experience any of these reactions, do not stop using Fuzeon, but consult your doctor if you have any concerns.

Reactions may worsen if injections are repeatedly given at the same site on the body.
They may also worsen if the injection is administered too deeply (e.g. into the muscle). In rare cases, infection may occur even at a site used for a single injection. To reduce the risk of infection, it is important to follow the instructions provided in section 7.
Fuzeon may cause deposits of a type of protein called amyloid under the skin at the injection site, which may be felt as nodules under the skin. Contact your doctor if this occurs.

Other possible side effects
Very common (affect more than 1 person in 10)

• diarrhoea
• nausea
• weight loss
• pain and numbness or tingling sensations in hands, feet or legs

Common (affect fewer than 1 person in 10)

• pneumonia
• otitis
• enlargement of glands (lymph nodes)
• eye inflammation (conjunctivitis)
• influenza or flu-like symptoms
• sinusitis
• nasal congestion
• anorexia
• heartburn
• inflammation of the pancreas
• decreased appetite
• diabetes
• nightmares
• dizziness
• tremor
• anxiety or irritability
• difficulty concentrating
• reduced sensation
• acne
• skin redness
• eczema
• dry skin
• warts
• muscle pain
• kidney stones
• fatigue
• blood in the urine
• changes observed in blood tests (increased blood lipids)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Fuzeon

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label of the Fuzeon vials or on the vials of water for injectable preparations, following "Exp.". The expiry date refers to the last day of the month.
Keep the vial in the outer packaging to protect it from light.
Once the solution has been prepared for injection, it must be used immediately. If it is not used immediately, it must be stored in a refrigerator (2°C – 8°C) and used within 24 hours.
Do not use this medicine if you notice any particles in the powder or in the solution after adding the water for injectable preparations. Also, do not use the water for injectable preparations if you see any particles in the vial or if the water is cloudy.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Fuzeon contains

• The active substance is enfuvirtide. Each vial contains 108 mg of enfuvirtide. After reconstitution with the solvent supplied, 1 ml of reconstituted solution contains 90 mg of enfuvirtide.
• The excipients are:

Powder
Anhydrous sodium carbonate
Mannitol
Sodium hydroxide
Hydrochloric acid
Solvent
Water for injections
See section 2 “Fuzeon contains sodium”

Description of the appearance of Fuzeon and contents of the pack
Fuzeon powder and solvent for solution for injection is supplied in a box containing:
60 vials of Fuzeon
60 vials of water for injections used to reconstitute the Fuzeon powder
60 3-ml syringes
60 1-ml syringes
180 alcohol swabs.
This pack provides you with everything needed to prepare and administer Fuzeon injections for
30 days.

Marketing Authorisation Holder
Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer responsible for batch release
Roche Pharma AG
Emil-Barell-Str. 1
D-79639 Grenzach-Wyhlen
Germany

For further information about Fuzeon, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
N.V. Roche S.A. UAB “Roche Lietuva”
Tél/Tel: +32 (0) 2 525 82 11 Tel: +370 5 2546799

България Luxembourg/Luxemburg
Рош България ЕООД (Voir/siehe Belgique/Belgien)
Тел: +359 2 474 5444

Česká republika Magyarország
Roche s. r. o. Roche (Magyarország) Kft.
Tel: +420 - 2 20382111 Tel: +36 - 1 279 4500

Danmark Malta
Roche Pharmaceuticals A/S (See Ireland)
Tlf: +45 - 36 39 99 99

Deutschland Nederland
Roche Pharma AG Roche Nederland B.V.
Tel: +49 (0) 7624 140 Tel: +31 (0) 348 438050

Eesti Norge
Roche Eesti OÜ Roche Norge AS
Tel: + 372 6 177 380 Tlf: +47 - 22 78 90 00

Ελλάδα Österreich
Roche (Hellas) A.E. Roche Austria GmbH
Τηλ: +30 210 61 66 100 Tel: +43 (0) 1 27739

España Polska
Roche Farma S.A. Roche Polska Sp.z o.o.
Tel: +34 - 91 324 81 00 Tel: +48 - 22 345 18 88

France Portugal
Roche Roche Farmacêutica Química, Lda
Tél: +33 (0) 1 47 61 40 00 Tel: +351 - 21 425 70 00

Hrvatska România
Roche d.o.o. Roche România S.R.L.
Tel: + 385 1 47 22 333 Tel: +40 21 206 47 01

Ireland Slovenija
Roche Products (Ireland) Ltd. Roche farmacevtska družba d.o.o.
Tel: +353 (0) 1 469 0700 Tel: +386 - 1 360 26 00

Ísland Slovenská republika
Roche Pharmaceuticals A/S Roche Slovensko, s.r.o.
c/o Icepharma hf Tel: +421 - 2 52638201
Sími: +354 540 8000

Italia Suomi/Finland
Roche S.p.A. Roche Oy
Tel: +39 - 039 2471 Puh/Tel: +358 (0) 10 554 500

Kύπρος Sverige
Γ.Α.Σταμάτης & Σια Λτδ. Roche AB
Τηλ: +357 - 22 76 62 76 Tel: +46 (0) 8 726 1200

Latvija United Kingdom (Northern Ireland)
Roche Latvija SIA Roche Products (Ireland) Ltd.
Tel: +371 - 6 7039831 Tel: +44 (0) 1707 366000

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

7. DETAILED GUIDE ON HOW TO INJECT FUZEON

Always use this medicine exactly as instructed by your doctor, pharmacist, or nurse. If you are
unsure, consult your doctor, pharmacist, or nurse.
What to do if you are left-handed
The images in this leaflet show right-handed people. If you are left-handed, act in the way that
feels most natural to you. You may find it more comfortable to:

• hold the syringe with your left hand and
• hold the vial between the thumb and index finger of your right hand.

When to ask for help from another person
At first, it may be difficult to administer the injection into certain areas, such as the upper arm. If you need help, ask your partner, a friend, or a family member. If you wish, you may invite someone to accompany you to the injection training session provided by your doctor or nurse.
Your syringes
The syringes supplied with this medicine are equipped with a colored needle protection device. This device is attached to the needle and covers it after use to reduce the risk of accidentally pricking another person with the needle. Although the syringes are equipped with this safety system, it is important to dispose of used syringes properly. Follow the instructions given to you by your doctor, pharmacist, or nurse.
Safety advice

• Wash your hands thoroughly. This will reduce the risk of bacterial infections.
• After washing your hands, do not touch anything except the medicine and the supplied materials.
• When handling the syringe, do not touch the needle.
• Do not touch the tops of the vials after disinfecting them with alcohol wipes.
• Do not use materials that have already been opened. Ensure that none of the kit components have been opened prior to use.
• Never use or share needles that have already been used.
• Never use a syringe with a bent or damaged needle.
• Never mix the medicine with tap water.
• Never inject the medicine mixed with other injectable medicines.
• Inject Fuzeon only under the skin (“subcutaneously”).
• Do not inject Fuzeon intravenously (“intravenously”) or into the muscles (“intramuscularly”).
• Dispose of all used materials by placing them in the designated container with a lid, even if vials still contain unused amounts of medicine or water for injectable preparations, as these vials are for single use only. Contact your doctor, pharmacist, or nurse if you have any questions regarding the safe disposal of this material.

Below is a basic, step-by-step guide to injecting the medicine.
Step A: Getting started

1. Gather the following materials:
   • One vial of Fuzeon (glass container with white powder inside)
   • One vial of water for injectable preparations (glass container with clear, colorless liquid inside)
   • One 3 ml syringe (larger syringe) with a 25 mm needle
   • One 1 ml syringe (smaller syringe) with a 13 mm needle
   • Three alcohol wipes
   • A designated sharps container with a lid for safe disposal of waste materials.
2. Open the syringe packaging and remove the closure caps from the vials.
   • Dispose of the packaging and closure caps by placing them in the designated container with a lid.
   • Place the syringes and vials on a clean surface.
3. Wash your hands thoroughly.
   • After washing your hands, do not touch anything except the materials needed for the injection and the injection site.
4. Clean the tops of the vials.
   • Wipe the top of each vial with a clean alcohol wipe. Allow the tops to air dry.

• Be careful not to touch the rubber tops after cleaning. If you do touch them, make sure to clean them again.

Step B: How to mix Fuzeon
Draw up the water for injectable preparations

1. Take the large 3 ml syringe. Using your index finger, push back the colored needle protection device away from the needle.

2. To ensure the needle is securely attached to the syringe:
   • hold the plastic closure cap below the needle protection device
   • gently twist the needle and cap clockwise. Do not apply excessive force, as the needle may loosen.
3. To remove the clear plastic closure cap:
   • push toward the syringe and then pull off the closure cap.

4. Draw up 1.1 ml of air.
5. Insert the syringe needle into the rubber top of the vial containing water for injectable preparations and push the plunger. This will inject the air.

6. Gently turn the vial upside down. Check that the needle tip remains below the surface of the water for injectable preparations to prevent air bubbles from entering the syringe.
7. Slowly pull back the plunger until the water reaches the 1.1 ml mark. Be careful, as the vial contains more liquid than needed (2 ml); you should withdraw only 1.1 ml to prepare the injection correctly.

8. Gently tap the syringe to bring any air bubbles to the surface.
   • If too much air enters the syringe, gently press the plunger to push the air back into the vial.
   • Then withdraw the liquid again.
   • Make sure you have 1.1 ml of water for injectable preparations in the syringe.
   • You may repeat this step until the correct amount of water for injectable preparations is in the syringe.
9. Remove the needle from the vial. Be careful never to touch the needle with your fingers or anything else.
10. Dispose of the vial and water for injectable preparations by placing them in the designated container with a lid. The vial is for single use only.

Injecting the water for injectable preparations into the Fuzeon powder

1. Gently tap the Fuzeon vial to loosen the powder.
2. Hold the body of the syringe filled with water and insert the needle into the rubber top of the vial at a slight angle.
3. Slowly push the syringe plunger.
   • Let the water flow slowly down the inside wall of the vial.
   • Be careful not to forcefully inject the water into the powder, as this may cause foaming.
   • If foaming occurs, it may take longer for the powder to dissolve completely.

4. After all the water for injectable preparations has been added to the Fuzeon vial, remove the syringe from the vial.
5. Hold the body of the syringe with one hand and gently press the colored needle protection device against a flat surface until it covers the needle.
   • You will hear a click. Do not use your free hand to press the device onto the needle.

6. Dispose of the syringe in the designated container with a lid.

Mixing the water for injectable preparations with the Fuzeon powder

1. Gently tap the vial with your fingertip until the powder begins to dissolve. Never shake or invert the vial to mix—this would create excessive foam.
2. Once the powder begins to dissolve, set the vial aside to allow the powder to dissolve completely.
   • The powder may take up to 45 minutes to fully dissolve.
   • After adding the water for injectable preparations, the vial may also be gently rotated between your hands until the powder is completely dissolved.
   • This may reduce the time required for the powder to dissolve.
3. After the powder has completely dissolved:
   • Allow any bubbles that may have formed to settle.
   • If bubbles remain, gently tap the side of the vial to help them settle.
4. It is important to examine the liquid for the presence of particles (fragments).
   • If you notice any particles in the liquid, do not use it.
   • Dispose of the vial by placing it in the designated container with a lid or return it to the pharmacy. Then start again with a new vial of Fuzeon powder.
5. If you accidentally touch the rubber stopper, make sure to clean it again with a new alcohol wipe.
6. Once the dose has been mixed with water for injectable preparations, it must be used immediately. Otherwise, store it in the refrigerator and use it within 24 hours.
   • Allow the liquid to return to room temperature before use.
7. If you are preparing both daily doses at the same time, make sure to use new syringes, new water for injectable preparations, and a new Fuzeon vial for each dose.

Step C: Preparing the injection
Drawing up Fuzeon into the 1 ml syringe

1. Wipe the top of the Fuzeon vial again with a new alcohol wipe.
2. Take the small 1 ml syringe. Using your index finger, push back the colored needle protection device away from the needle.

3. To ensure the needle is securely attached to the syringe:
   • hold the plastic closure cap below the needle protection device
   • gently twist the needle and cap clockwise while pressing them toward the syringe.
4. To remove the clear plastic closure cap:
   • push toward the syringe and then pull off the closure cap.

5. Draw up 1 ml of air.
   • Be careful not to pull the plunger too quickly, as it may go past the 1 ml mark or come out of the syringe.
6. Insert the syringe needle into the rubber top of the Fuzeon vial and push the plunger. This will inject the air.
7. Gently turn the vial upside down.

Ensure that the needle tip remains below the surface of the solution to prevent air bubbles from entering the syringe.

8. Slowly pull back the plunger until the solution reaches the 1.0 ml mark.
   • Be careful not to pull the plunger too quickly, as it may go past the 1 ml mark or come out of the syringe.

9. Gently tap the syringe to bring any air bubbles to the surface.
   • If too much air enters the syringe, gently push the plunger to return the air to the vial.
   • Then withdraw the liquid again.
   • Make sure you have 1.0 ml of liquid in the syringe (or the amount prescribed by your doctor, if different).
   • This step may be repeated until the correct amount of solution is in the syringe.
10. Remove the syringe from the vial.

Step D: Injecting Fuzeon
Tip: Your doctor or nurse may suggest different injection techniques that are more suitable for you.
Injection sites

• Fuzeon must be administered as a 1 ml injection just under the skin, i.e., by “subcutaneous” injection.
• The injection can be given in the upper arm, upper thigh, or abdomen (belly).
• Choose a different area from the one used for your last injection.
• Do not inject where a reaction from a previous dose may be present. Check injection sites by pressing on the skin to feel for any hard lumps.
• Do not inject in areas that could be irritated by a belt or waistband.
• Do not inject near moles, scars, bruises, or the navel.

Cleaning the injection site
Clean the injection area with an alcohol wipe, using a circular motion starting from the center and moving outward. Allow it to dry completely in the air.
Inserting the needle and injecting

1. Pinch as much skin as possible between your fingers without causing pain.

2. Insert the needle into the skin at a 45-degree angle.

3. When the needle is inserted:
   • release the skin
   • with your free hand, hold the body of the syringe; this will keep the syringe steady and prevent it from moving.
4. Using the thumb of your other hand, push the plunger to inject the liquid.
   • After the full dose has been injected, remove the needle from the skin.

After removing the needle

1. Hold the body of the syringe with one hand
   • then gently press the colored needle protection device against a flat surface until it covers the needle.
   • you will hear a click. Do not use your free hand to press the safety device onto the needle.

2. Dispose of the syringe by placing it in a designated container with a lid.
3. If there is blood at the injection site, cover the area with an adhesive bandage.

Step E: Disposal of used materials

• Immediately dispose of all used materials by placing them in the designated container with a lid, even if vials still contain unused amounts of medicine or water for injectable preparations, as these vials are for single use only.
• Keep the container lid tightly closed and store it out of the reach of children.
• Ask your doctor, pharmacist, or nurse for the best way to dispose of the container.
• If you have any doubts or questions about the safe disposal of this material, consult your doctor, pharmacist, or nurse.