Agamree

Package leaflet: Information for the patient

AGAMREE 40 mg/mL oral suspension

vamorolone
▼ This medicinal product is under additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicinal product. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before taking 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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What AGAMREE is and what it is used for

AGAMREE is a corticosteroid anti-inflammatory medicine containing the active substance vamorolone.
AGAMREE is indicated for the treatment of patients aged 4 years and older with Duchenne muscular dystrophy (DMD). DMD is a genetic disease caused by defects in the dystrophin gene, which normally produces a protein that keeps muscles healthy and strong. In patients with DMD, this protein is not produced, and the body is unable to grow new muscle cells or replace damaged muscle. This causes the body's muscles to become weaker over time.
AGAMREE is used to stabilise or improve muscle strength in patients with DMD.

2. What you should know before taking AGAMREE

Do not take AGAMREE

• if you are allergic to vamorolone or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe liver problems;
• if you are planning to receive, or have received within the last 6 weeks, vaccination with live or live-attenuated vaccines (for example, against measles, mumps, rubella, or varicella). Please consult your doctor if you are already being treated with AGAMREE and plan to receive such vaccination.

Warnings and precautions
Talk to your doctor before taking AGAMREE.

Endocrine function disturbances: adrenal insufficiency
AGAMREE reduces the amount of a hormone called cortisol that your body can produce. This is known as adrenal insufficiency.

• Do not reduce or stop taking AGAMREE without speaking to your doctor first. If you reduce or abruptly stop taking AGAMREE for several days, you may develop symptoms of acute adrenal insufficiency, such as excessive fatigue, dizziness, or confusion, which could be life-threatening. Your doctor may need to monitor your treatment more closely if your dose is changed.
• If you experience unusual stress (due to acute infection, traumatic injury, or major surgery), you may need to take an additional corticosteroid medicine to prevent acute adrenal insufficiency. Discuss with your doctor what to do in case of unusual stress before starting treatment with AGAMREE.
• If you are currently being treated with another corticosteroid such as prednisone, you may switch directly to AGAMREE, but your doctor will prescribe the appropriate dose of AGAMREE for you.
• If you have a type of tumor of the adrenal glands called a pheochromocytoma, your doctor may need to monitor your treatment more closely.

IMPORTANT WARNING: The AGAMREE packaging contains a patient alert card providing important safety information in case of adrenal crisis. Keep this card with you at all times.

Weight gain

• AGAMREE may increase your appetite and therefore your weight, especially during the first months of treatment. Your doctor or nurse will provide you with dietary advice before and during treatment.

Patients with altered thyroid function

• If you have hypothyroidism (reduced thyroid activity) or hyperthyroidism (overactive thyroid), your doctor may need to monitor your treatment more closely or adjust your dose.

Ophthalmic effects

• If you or someone in your family has glaucoma (increased pressure in the eye), your doctor may need to monitor your treatment more closely.

Increased risk of infections
AGAMREE may reduce your natural resistance to infections.

• If you have a weakened immune response (due to an immunodeficiency syndrome, an illness, or other medicines that suppress the immune system), your doctor may need to monitor your treatment more closely.
• If you develop an infection while being treated with AGAMREE, your doctor may need to monitor you more closely, and you may need to take an additional corticosteroid medicine.

Diabetes mellitus

• Long-term use of AGAMREE may increase the likelihood of developing diabetes mellitus (a condition related to blood sugar); your doctor may need to regularly check your blood sugar levels.

Vaccination

• If you plan to be vaccinated with live or live-attenuated vaccines, vaccination should occur at least 6 weeks before starting treatment with AGAMREE.
• If you have never had chickenpox or have not been vaccinated against it, discuss the possibility of vaccination with your doctor before starting AGAMREE therapy.

Thromboembolic events

• If you have had thromboembolic events (a blood clot inside the body) or a disease that increases the risk of blood clotting, your doctor may need to monitor your treatment more closely.

Hepatic impairment

• If you have liver disease, your doctor may need to adjust your dose.

Children
Do not administer AGAMREE to children under 4 years of age, as it has not been studied in this patient group.

Other medicines and AGAMREE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Tell your doctor if you are taking any of the following medicines:

• medicines used to treat epileptic seizures and neuropathic pain, such as carbamazepine or phenytoin, as they may affect the medicine’s action;
• antifungal medicines (including candidiasis and aspergillosis) known as triazoles, such as itraconazole and voriconazole, as they may affect the medicine’s action;
• antibiotics known as macrolides (such as clarithromycin) or "ketolides" (such as telithromycin), as they may affect the medicine’s action;
• antibiotics known as rifamycins, such as rifampicin, as they may affect the medicine’s action;
• spironolactone or eplerenone, known as potassium-sparing diuretics (treatments that increase urine production), which may be prescribed to lower blood pressure and protect cardiovascular function, as they may have effects similar to those of AGAMREE. Your doctor may need to monitor your potassium levels and adjust the dose of these medicines;
• St. John’s wort (Hypericum perforatum), a herbal medicine used to treat depression and emotional disorders, as it may affect the medicine’s action.

If you need to be vaccinated, consult your doctor first (see section 2: “Do not take AGAMREE”). You should not receive certain types of vaccines (live or live-attenuated vaccines) up to 6 weeks before starting treatment with AGAMREE, as in such combination these vaccines could cause the infection they are intended to prevent.

AGAMREE with food and drinks
Avoid grapefruit and grapefruit juice during treatment with AGAMREE, as they may affect the medicine’s action.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.
You should not take AGAMREE during pregnancy unless clearly indicated by your doctor.
Women of childbearing potential must use an effective method of contraception during treatment with AGAMREE.
Animal studies have shown that long-term treatment with AGAMREE may impair male and female fertility.

Driving and using machines
Ask your doctor whether your condition allows you to drive vehicles, including bicycles, and to use machinery safely. AGAMREE should not affect your ability to drive vehicles, ride a bicycle, or use machinery.

AGAMREE contains sodium benzoate and sodium
AGAMREE contains 1 mg of sodium benzoate (E 211) per mL.
AGAMREE contains less than 23 mg of sodium per 7.5 mL and is therefore essentially "sodium-free".

3. How to take AGAMREE

Take this medicine exactly as directed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose of AGAMREE depends on your body weight and age.
If you are 4 years of age or older and weigh less than 40 kg, the dose is generally 6 mg per kg of body
weight, taken once daily.
If you are 4 years of age or older and weigh 40 kg or more, the dose is generally 240 mg, taken
once daily.
If you experience certain adverse effects while taking AGAMREE (see section 4),
your doctor may reduce the dose or temporarily or permanently discontinue treatment. If
you have liver disease, your doctor may reduce the dose.
This medicine is taken orally. AGAMREE may be taken with or without food (see
section 2 “AGAMREE with food and drink”).
To withdraw the medicine, use one of the oral dosing syringes provided in the
package. Use only these oral dosing syringes to measure the dose. Your doctor will tell you how much
medicine to withdraw with the syringe for your daily dose.
Caregivers should assist in administering AGAMREE, particularly in the use of the oral dosing
syringes to correctly measure and administer the prescribed dose.
Shake the bottle well before withdrawing the medicine with the syringe. Withdraw the dose using the
oral dosing syringe, then immediately empty the syringe slowly and directly into the mouth.
Read the instructions below for more information on how to correctly measure and take the dose. If you
have any doubts about how to use the oral dosing syringe, consult your doctor or pharmacist.
After taking the prescribed dose, disassemble the oral dosing syringe, rinse the syringe and plunger with
cold tap water, and allow to air dry. Store the cleaned oral dosing syringe in the package until the next
use. An oral dosing syringe should be used for no more than 45 days. After this time,
discard it and use the second oral dosing syringe provided in the package. If you have any
doubts about the use of this medicine, consult your doctor or pharmacist.
HOW TO PREPARE THE DOSE OF AGAMREE ORAL SUSPENSION
Before taking/administering
AGAMREE
Step 1 Ensure the child-resistant cap of the bottle is securely fastened
and shake the bottle well.
Step 2 Remove the child-resistant cap by firmly pushing it down and
rotating it counterclockwise.
Step 3 Firmly insert the adapter into the
bottle.
This step should be performed the first time the bottle is opened. The adapter
must remain in the bottle thereafter.
If the bottle adapter falls on the ground, clean it with cold running water and allow it to air dry for at least 2 hours.
Preparing the dose of
AGAMREE
Step 4 Hold the bottle in an upright position.
Before inserting the tip of the oral dosing syringe
into the bottle adapter, push the plunger fully towards the tip of the oral dosing
syringe. Firmly insert the tip into the opening of the bottle adapter.

Step 5	Firmly hold the oral syringe and carefully invert the bottle. Slowly pull the plunger outward until the desired amount of medicine has been drawn into the oral syringe. If large air bubbles are present in the oral syringe (see figure on the left) or if the drawn dose of AGAMREE is incorrect, firmly insert the tip of the syringe into the bottle adapter while the bottle is in an upright position. Push the plunger down so that AGAMREE flows back into the bottle, then repeat steps 4 to 6.
Step 6	Check that the dose corresponds to the millilitres (mL) prescribed by the doctor. To identify the marking indicating the dose in millilitres (mL) on the plunger, refer to the figure on the right. On the scale marked on the syringe, each line corresponds to 0.1 mL. In the example shown, a dose of 1 mL is indicated. Do not take a dose higher than the daily dose prescribed.
Step 7	Place the bottle upright and carefully remove the oral syringe from the bottle. Do not hold the oral syringe by the plunger, as it may come out.

Administration of AGAMREE
Step 8 Do not mix the medicine with any type of liquid before administration.
The patient should be in an upright sitting position during administration of the medicine.
Empty the syringe directly into the mouth.
Gently push the plunger to empty the syringe. Do not force the plunger.
To avoid the risk of choking, do not spray the medicine onto the back of the mouth or into the throat.
After administration of AGAMREE
Step 9 Close the vial with the child-resistant cap after each use.
Step 10
Disassemble the oral syringe, rinse it under cold running water, and allow it to air dry before the next use.
The oral syringes supplied with AGAMREE may be used for up to 45 days each.
Enteral feeding tube
AGAMREE may be administered via an enteral feeding tube, following the instructions provided with the feeding tube kit. Administer the prescribed dose of AGAMREE without dilution. Do not mix with nutritional formulas or other products. The feeding tube must be flushed before and after administration of AGAMREE using the syringe provided in the enteral feeding tube kit. Flush the tube with at least 20 mL of water.
If you take more AGAMREE than you should
If you take more AGAMREE than prescribed, contact your doctor or hospital for advice. Show them the AGAMREE packaging and this patient information leaflet. You may require medical treatment.
If you forget to take AGAMREE
Do not take a larger dose of AGAMREE and do not repeat the dose.
Take the next dose as usual.
If you are concerned, consult a healthcare professional.
If you stop treatment with AGAMREE
Take AGAMREE for the entire duration prescribed by your doctor. Consult your doctor before stopping treatment with AGAMREE, as your dose should be gradually reduced to avoid adverse effects.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Treatment with AGAMREE causes adrenal insufficiency. Consult your doctor before starting therapy with AGAMREE (see section 2 for further information).
The following side effects have been reported with AGAMREE at a very common frequency (may affect more than 1 in 10 people):

• more rounded and swollen facial appearance (Cushingoid)
• increased body weight (weight gain)
• increased appetite
• irritability
• vomiting

The following side effects have been reported at a common frequency (may affect up to 1 in 10 people):

• abdominal pain (stomach ache)
• upper abdominal pain (pain in the upper part of the abdomen)
• diarrhoea
• headache

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

5. How to store AGAMREE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the
vial after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
After the first opening of the AGAMREE vial, store it in the refrigerator (2 °C – 8 °C) in an upright position.
The medicine can be stored in the refrigerator for up to 3 months.
Discard any unused medicine within 3 months after first opening the vial.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What AGAMREE contains
The active substance is vamorolone. Each mL of suspension contains 40 mg of vamorolone.
The other components are: citric acid (monohydrate) (E 330), disodium phosphate (E 339), glycerol (E 422), orange flavour, purified water, sodium benzoate (E 211) (see section 2, "AGAMREE contains sodium benzoate"), sucralose (E 955), xanthan gum (E 415), and hydrochloric acid (for pH adjustment). See section 2 "AGAMREE contains sodium benzoate and sodium".
Description of the appearance of AGAMREE and contents of the pack
AGAMREE is an oral suspension, white to off-white in colour. The medicinal product is supplied in an amber glass bottle with a child-resistant tamper-evident closure made of polypropylene and a low-density polyethylene liner. The bottle contains 100 mL of oral suspension.
Each pack contains one bottle, one bottle adapter, and two identical oral dosing syringes. The oral dosing syringes are graduated from 0 to 8 mL in 0.1 mL increments.
Marketing Authorisation Holder and Manufacturer
Santhera Pharmaceuticals (Deutschland) GmbH
Marie-Curie-Straße 8
D-79539 Lörrach
Germany
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu