Samyr

Package leaflet: Information for the patient or user

SAMYR 400 mg/5ml powder and solvent for injectable solution, 400 mg gastro-resistant tablets

Ademetionine
Please read this leaflet carefully before using this medicine because 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 their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What SAMYR is and what it is used for

This medicinal product contains an active substance called ademetionine. Ademetionine is a compound
naturally present in the body, which participates in many processes occurring within the body.
SAMYR is used in adults for the treatment of depression, which may cause sadness, loss of pleasure and
interest in daily activities, fatigue, and a feeling of malaise.

2. What you should know before using SAMYR

Do not use SAMYR if:

• you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• you have genetic disorders causing abnormalities in certain protein components such as methionine or homocysteine (e.g. cystathionine beta-synthase deficiency, vitamin B12 metabolism disorders).

Warnings and precautions
Talk to your doctor or pharmacist before using SAMYR.
Inform your doctor if:

• you have previously experienced elevated blood ammonia levels after taking medications containing ademetionine by mouth;
• you have liver or kidney disease;
• you suffer from bipolar disorder or other psychiatric conditions;
• you have a reduced number of red blood cells (anaemia);
• you have vitamin deficiency due to medical conditions or dietary habits (e.g. if you are vegan);
• you are pregnant or breastfeeding (see "Pregnancy and breastfeeding").

IN ALL THESE CASES, YOUR DOCTOR WILL ASSESS WHETHER BLOOD TESTS OR
THERAPY MODIFICATIONS ARE NECESSARY.
BE CAREFUL
Depression is frequently associated with suicidal thoughts, self-harm, and suicide. For this reason:

• patients being treated with antidepressant medicines such as SAMYR should be closely monitored, especially during the initial stages of treatment or when dose adjustments are made, particularly if such symptoms have already occurred;
• your doctor will assess whether additional supportive therapy (e.g. psychiatric support) should be associated with drug treatment.

PATIENTS (OR THEIR CAREGIVERS) SHOULD CONTACT THEIR DOCTOR IMMEDIATELY IF THEY NOTICE ANY WORSENING OF SYMPTOMS, BEHAVIOURAL CHANGES, OR SUICIDAL THOUGHTS.
Contact your doctor if, during treatment with SAMYR:

• you develop anxiety or your anxiety worsens, as this may require reassessment of your treatment;
• you experience elevated levels of homocysteine in the blood, which may be caused by SAMYR therapy (false positive);
• you experience dizziness.

Children and adolescents
SAMYR is not indicated for use in children and adolescents.
Other medicines and SAMYR
Inform your doctor or pharmacist if you are currently taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking:

• other antidepressant medicines known as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (e.g. clomipramine);
• medicines or supplements containing the amino acid tryptophan (a protein component).

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning a pregnancy, or breastfeeding, consult your doctor before using this medicine.
During the first three months of pregnancy and during breastfeeding, SAMYR should only be used when clearly necessary and under strict medical supervision.
Driving and using machines
SAMYR may cause dizziness: ensure you do not experience this side effect before driving or operating machinery.
SAMYR 400 mg/5 ml powder and solvent for injectable solution contains less than 1 mmol of sodium (23 mg) per dose, i.e. it is practically "sodium-free".
SAMYR 400 mg gastro-resistant tablets contain less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".

3. How to use SAMYR

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
SAMYR powder and solvent for injectable solution: 1 vial of powder per day for 15–20 days.
Your doctor may prescribe repeating the treatment and/or continuing therapy with tablets.
or
SAMYR tablets: 2–3 tablets (800–1200 mg) daily, for the duration indicated by your doctor.
Elderly patients: your doctor may determine a lower dose than those indicated above.
Patients with renal impairment:
If you have kidney problems, your doctor may decide to administer SAMYR with particular caution.

Method of administration
SAMYR tablets: must be taken by mouth (oral route). Swallow the tablets whole, without chewing, and away from meals. The tablets must be removed from the blister pack (aluminum wrapper) immediately before use. Do not take SAMYR if the tablets appear different from white/yellowish in color (due to the presence of holes in the aluminum wrapping).

SAMYR powder and solvent for injectable solution: must be administered via injection into a vein (intravenous route) or into a

muscle (intramuscular route).
Administration into a vein must be performed slowly and exclusively by medical personnel.
The solution for injection must be prepared immediately before use by dissolving the powder contained in the vial with the clear liquid (solvent) provided in the ampoule within the package. In case of intravenous administration, the dose must be further diluted in 250 ml of saline solution.

To prepare the solution for injection:

• On the neck of the ampoule, there is a small colored spot. Gently tap the top of the ampoule to remove any liquid residue in the tip; position the ampoule as shown in Figure 1;
• To open the ampoule, apply pressure with your thumb on the colored spot as shown in Figure 2;
• Draw up the solvent with a syringe and inject it into the vial containing the powder;
• Once the powder has dissolved, draw up the solution.

Use each vial only once and discard any remaining solution. Do not mix other medicines into the solution. This is particularly important for alkaline solutions or those containing calcium ions. Do not use the powder if it has a color different from white/yellowish (due to damage to the vial or exposure to heat).

If you take more SAMYR than you should, contact your doctor immediately, as appropriate measures may be required.

If you forget to use SAMYR
Do not take a double dose to make up for the missed dose.

If you stop using SAMYR
It is important that you continue taking this medicine for the full duration prescribed by your doctor. Do not stop treatment just because you feel better, as your symptoms may recur or worsen.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Stop taking SAMYR immediately and contact your doctor if you experience any of the following:

• allergic reactions, even severe ones, presenting as more or less sudden onset of skin lesions, for example skin discoloration with spots or widespread rash (rash, erythema), itching, hives, swelling (angioedema) of the face, eyes, lips, and breathing difficulties (dyspnea, bronchospasm), back pain, chest pain or tightness, changes in blood pressure and/or heart rate (tachycardia, bradycardia);
• breathing difficulties due to swelling of the throat (laryngeal edema).

Inform your doctor if, during treatment with SAMYR, you notice the following:
Common side effects (may affect up to 1 in 10 people)

• itching;
• headache;
• abdominal pain, diarrhoea, nausea;
• anxiety, sleep disturbances (insomnia).

Uncommon side effects (may affect up to 1 in 100 people)

• dry mouth, indigestion (dyspepsia), presence of intestinal gas (flatulence), pain or bleeding or other disturbances in the stomach or intestines, vomiting;
• fatigue (asthenia), swelling (oedema), fever, chills, reactions at the injection site;
• urinary tract infection;
• joint pain or muscle spasms, excessive sweating;
• dizziness, disturbances in sensation (paraesthesia) or taste (dysgeusia), agitation, confusion;
• hot flushes, low blood pressure (hypotension), inflammation of the veins (phlebitis).

Rare side effects (may affect up to 1 in 1,000 people)

• abdominal distension, inflammation of the oesophagus (oesophagitis);
• malaise, suicidal thoughts/behaviour;
• severe pain in the upper abdomen, radiating to the right side and back, occurring suddenly after a fatty meal or during the night (biliary colic).

Side effects not known (frequency cannot be estimated from the available data)

• liver problems due to a disease called cirrhosis;
• heart or blood vessel problems (cardiovascular disorders);
• influenza-like symptoms.

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 at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store SAMYR

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
SAMYR tablets: no special storage precautions are necessary.
SAMYR powder and solvent for injectable solution: store at a temperature not exceeding 30°C.
Use SAMYR immediately after preparing the solution.
Do not dispose of any medicine 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 SAMYR contains
The active substance is: ademetionine.
SAMYR 400 mg/5 ml powder and solvent for injectable solution
One vial of powder 400 mg contains: 400 mg of ademetionine.
The other components are:

• solvent vial: water for injections, L-lysine, sodium hydroxide.

SAMYR 400 mg tablets
One tablet contains: 400 mg of ademetionine.
The other components are: microcrystalline cellulose, magnesium stearate, polyethylene glycol 6000,
polymethacrylates, polysorbates, colloidal silica, emulsified silicone, sodium glycolate starch, talc, sodium hydroxide.
Description of the appearance of SAMYR and contents of the pack
SAMYR 400 mg/5 ml powder and solvent for injectable solution: available in a pack containing 5 powder vials and 5 solvent vials of 5 ml.
SAMYR 400 mg tablets: available in a pack containing 20 tablets.
Marketing Authorization Holder
Mylan Italia S.r.l., Via Vittor Pisani 20, 20124 Milan
Manufacturer
SAMYR 400 mg/5 ml powder and solvent for injectable solution
Delpharm Saint Remy - Rue de l'Isle Saint Remy Sur Avre, 28380 - France
AbbVie S.r.l. – S.R. 148 Pontina km 52 s.n.c. - Campoverde (LT)
Biologici Italia Laboratories S.r.l., Via F. Serpero 2, 20060 Masate (MI)
SAMYR 400 mg tablets
AbbVie S.r.l. - S.R. 148 Pontina km 52 s.n.c. Campoverde (LT)

Patient or user information leaflet

SAMYR 100 mg/5ml powder and solvent for injectable solution, 200 mg/5ml powder and solvent for injectable solution, 200 mg gastro-resistant tablets

Ademetionine
Please read this leaflet carefully before using this medicine because 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 other people, 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 or pharmacist. See section 4.

Contents of this leaflet:

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

1. What SAMYR is and what it is used for

This medicinal product contains an active substance called ademetionine. Ademetionine is a compound naturally present in the body and involved in many processes occurring within the body.
SAMYR is used in adults for the treatment of depression, which may cause sadness, loss of pleasure and interest in daily activities, fatigue, and a feeling of malaise.

2. What you should know before using SAMYR

Do not use SAMYR if:

• you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• you have genetic disorders causing abnormalities in certain protein components such as methionine or homocysteine (e.g. cystathionine beta-synthase deficiency, defects in vitamin B12 metabolism).

Warnings and precautions
Talk to your doctor or pharmacist before using SAMYR.
Inform your doctor if:

• you have previously experienced increased blood ammonia levels after taking medications containing ademetionine by mouth;
• you have liver or kidney disease;
• you suffer from bipolar disorder or other psychiatric illnesses;
• you have a reduced number of red blood cells (anemia);
• you have vitamin deficiency due to medical conditions or dietary habits (e.g. if you are vegan);
• you are pregnant or breastfeeding (see "Pregnancy and breastfeeding"); IN ALL THESE CASES, YOUR DOCTOR WILL ASSESS WHETHER CONTROL TESTS OR THERAPY MODIFICATIONS ARE NECESSARY.

BE CAREFUL
Depression is frequently associated with suicidal thoughts, self-harm, and suicide. For this reason:

• patients being treated with antidepressant medicines such as SAMYR should be closely monitored, especially if such symptoms have already occurred, during the initial stages of therapy or when dose adjustments are made;
• your doctor will assess whether supportive therapy (e.g. psychiatric support) should be added to drug treatment. PATIENTS (OR THEIR CAREGIVERS) MUST CONTACT THEIR DOCTOR IMMEDIATELY IF THEY NOTICE ANY WORSENING OF SYMPTOMS, BEHAVIORAL CHANGES, OR SUICIDAL THOUGHTS.

Contact your doctor if, during treatment with SAMYR:

• you develop anxiety or your anxiety worsens, as your therapy may need to be re-evaluated;
• you experience elevated levels of homocysteine in the blood, which could be caused by SAMYR therapy (false positive);
• you experience dizziness.

Children and adolescents
SAMYR is not indicated for use in children and adolescents.
Other medicines and SAMYR
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking:

• other antidepressant medicines known as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (e.g. clomipramine);
• medicines or supplements containing the amino acid tryptophan.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor before using this medicine.
During the first three months of pregnancy and during breastfeeding, SAMYR should only be used when clearly necessary and under direct medical supervision.
Driving and using machines
SAMYR may cause dizziness: ensure you do not experience this adverse effect before driving or operating machinery.
SAMYR 100 mg/5 ml powder and solvent for injectable solution contains less than 1 mmol of sodium (23 mg) per dose, i.e. practically "sodium-free".
SAMYR 200 mg/5 ml powder and solvent for injectable solution contains less than 1 mmol of sodium (23 mg) per dose, i.e. practically "sodium-free".
SAMYR 200 mg gastro-resistant tablets contain less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".

3. How to use SAMYR

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.

Initial dose
SAMYR powder and solvent for injectable solution: 1–2 vials of powder per day for 15–20 days
or
SAMYR tablets: 2 tablets (400 mg), 2–3 times a day for 15–30 days.

Maintenance therapy dose
SAMYR tablets: 1 tablet (200 mg), 2–3 times a day.

Elderly patients: Your doctor may prescribe a lower dose than those indicated above.

Patients with renal impairment:
If you have kidney problems, your doctor may decide to administer SAMYR with particular caution.

Method of administration
SAMYR tablets: must be taken orally. Swallow the tablets whole, without chewing, and away from meals. The tablets should be removed from the blister pack (aluminum wrapper) immediately before use. Do not take SAMYR if the tablets appear brownish in color (due to the presence of holes in the aluminum packaging).

SAMYR powder and solvent for injectable solution: must be administered by injection into a vein (intravenous route) or into a muscle (intramuscular route). Intravenous administration must be performed slowly and only by medical personnel.

The solution for injection must

be prepared immediately before use by dissolving the powder contained in the vial with the clear liquid (solvent) provided in the ampoule inside the package. In case of intravenous administration, the dose must be further diluted in 250 ml of saline solution.

To prepare the solution for injection:

• On the neck of the ampoule, there is a small colored spot. Gently tap the top of the ampoule to remove any liquid that may have collected at the tip; position the ampoule as shown in Figure 1;
• To open the ampoule, apply pressure with your thumb on the colored spot as shown in Figure 2;
• Draw up the solvent with a syringe and inject it into the vial containing the powder;
• Once the powder has dissolved, draw up the solution.

Use each vial only once and discard any unused solution. Do not mix other medicines into the solution. This is particularly important for alkaline solutions or those containing calcium ions. Do not use the powder if it is not white/yellowish in color (due to damage to the ampoule or exposure to heat).

If you take more SAMYR than you should, contact your doctor immediately, as appropriate measures may be required.

If you forget to use SAMYR
Do not take a double dose to make up for the missed dose.

If you stop treatment with SAMYR
It is important that you continue taking this medicine for the full duration prescribed by your doctor. Do not stop treatment just because you feel better, as your symptoms may return or worsen.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop taking SAMYR immediately and contact your doctor if you experience any of the following:

• allergic reactions, even severe ones, presenting as more or less sudden onset of skin lesions, for example discoloured spots or widespread rash (rash, erythema), itching, hives, swelling (angioedema) of the face, eyes, lips, and breathing difficulties (dyspnoea, bronchospasm), back pain, chest pain or tightness, changes in blood pressure or heart rate (tachycardia, bradycardia);
• breathing difficulties due to throat swelling (laryngeal edema).

Inform your doctor if, during treatment with SAMYR, you notice the following:
Common side effects (may affect up to 1 in 10 people)

• itching;
• headache;
• abdominal pain, diarrhoea, nausea;
• anxiety, sleep disorders (insomnia).

Uncommon side effects (may affect up to 1 in 100 people)

• dry mouth, indigestion (dyspepsia), presence of intestinal gas (flatulence), stomach or intestinal pain or bleeding or other stomach or intestinal disturbances, vomiting;
• fatigue (asthenia), swelling (oedema), fever, chills, injection site reactions;
• urinary tract infection;
• joint pain or muscle spasms, excessive sweating;
• dizziness, disturbances in sensation (paraesthesia) or taste (dysgeusia), restlessness, confusion;
• hot flushes, low blood pressure (hypotension), inflammation of veins (phlebitis).

Rare side effects (may affect up to 1 in 1,000 people)

• abdominal swelling, inflammation of the oesophagus (oesophagitis);
• malaise, suicidal thoughts/behaviour;
• severe pain in the upper abdomen, radiating to the right side and back, occurring suddenly after a fatty meal or during the night (biliary colic).

Side effects with unknown frequency (frequency cannot be determined from available data)

• liver problems due to a disease called cirrhosis;
• heart or blood vessel problems (cardiovascular disorders); influenza-like symptoms.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store SAMYR

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last
day of that month.
SAMYR tablets: no special storage precautions are required.
SAMYR powder and solvent for injectable solution: store at a temperature not exceeding 30°C.
Use SAMYR immediately after preparation of the solution.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What SAMYR contains
The active substance is: ademetionine.

SAMYR 100 mg/5 ml powder and solvent for injectable solution
One vial of powder 100 mg contains: 100 mg of ademetionine.
The other components are:

• Powder vial: mannitol.
• Solvent vial: water for injections, L-lysine, sodium hydroxide.

SAMYR 200 mg/5 ml powder and solvent for injectable solution
One vial of powder 200 mg contains: 200 mg of ademetionine.
The other components are:

• Powder vial: mannitol.
• Solvent vial: water for injections, L-lysine, sodium hydroxide.

SAMYR 200 mg tablets
One tablet contains: 200 mg of ademetionine.
The other components are: colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, methacrylic acid copolymer, polyethylene glycol 6000, simethicone, polysorbate 80, sodium hydroxide, talc, iron oxide.

Description of the appearance of SAMYR and contents of the pack
SAMYR 100 mg/5 ml powder and solvent for injectable solution: available in a pack containing 5 powder vials and 5 solvent vials of 5 ml.
SAMYR 200 mg/5 ml powder and solvent for injectable solution: available in a pack containing 5 powder vials and 5 solvent vials of 5 ml.
SAMYR 200 mg tablets: available in a pack containing 20 tablets.

Marketing Authorization Holder
Mylan Italia S.r.l., Via Vittor Pisani, 20 - 20124 Milano

Manufacturer
SAMYR 100 mg/5 ml powder and solvent for injectable solution
Avara Liscate Pharmaceutical Services S.p.A – Via Fosse Ardeatine 2, 20060 Liscate (Milan)
AbbVie S.r.l. – S.R. 148 Pontina km 52 s.n.c. - Campoverde (LT)

SAMYR 200 mg/5 ml powder and solvent for injectable solution
AbbVie S.r.l. – S.R. 148 Pontina km 52 s.n.c. – Campoverde (LT)
Delpharm Saint Remy - Rue de l'Isle Saint Remy Sur Avre, 28380 (France)
Biologici Italia Laboratories S.r.l. Via F. Serpero 2, 20060 Masate (Milan)

SAMYR 200 mg tablets
AbbVie S.r.l. - S.R. 148 Pontina km 52 s.n.c., Campoverde (LT)