Transmetil

Package leaflet: Information for the patient or user

TRANSMETIL 300 mg/5ml powder and solvent for injectable solution, 500 mg/5ml powder and solvent for injectable solution, 300 mg gastro-resistant tablets, 500 mg gastro-resistant tablets

Ademetionine
Please read all of 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 effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What TRANSMETIL 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.
TRANSMETIL is used in the treatment of cholestasis, a condition caused by impaired bile flow within the
liver due to liver disorders (pre-cirrhotic and cirrhotic states) or pregnancy.
It manifests with itching, yellowish discoloration of the skin and eyes, dark urine, and pale stools.

2. What you should know before using TRANSMETIL

Do not use TRANSMETIL 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 defects).

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

• you have previously experienced elevated blood ammonia levels after taking oral medications containing ademetionine;
• you have liver or kidney diseases;
• you suffer from bipolar disorder, depression, or other psychiatric disorders;
• you have a reduced number of red blood cells (anemia);
• you have vitamin deficiency due to diseases 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 EVALUATE WHETHER CONTROL TESTS OR THERAPY ADJUSTMENTS ARE NECESSARY.
Contact your doctor if, during treatment with TRANSMETIL:

• you develop anxiety or your existing anxiety worsens, as your therapy may need to be reassessed;
• you experience elevated levels of homocysteine in the blood, which could be caused by treatment with TRANSMETIL (false positive);
• you experience dizziness.

Children and adolescents
TRANSMETIL is not intended for use in children and adolescents.
Other medicines and TRANSMETIL
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:

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

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning pregnancy, or are breastfeeding, consult your doctor before using this medicine.
During the first three months of pregnancy and during breastfeeding, TRANSMETIL should only be used when clearly necessary and under strict medical supervision.
Driving and using machines
TRANSMETIL may cause dizziness: ensure you do not experience this adverse effect before driving or operating machinery.
TRANSMETIL 300 mg/5ml powder and solvent for injectable solution powder and solvent for injectable solution contains less than 1 mmol of sodium (23 mg) per dose, i.e. practically "sodium-free".
TRANSMETIL 500 mg/5ml powder and solvent for injectable solution powder and solvent for injectable solution contains less than 1 mmol of sodium (23 mg) per dose, i.e. practically "sodium-free".
TRANSMETIL 300 mg gastro-resistant tablets contain less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".
TRANSMETIL 500 mg gastro-resistant tablets contain less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".

3. How to use TRANSMETIL

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
Initial dose
TRANSMETIL powder and solvent for injectable solution: 500 mg daily for 2 weeks. Your doctor
may determine a different dose based on your body weight: from 5 to 12 mg daily per kilogram
of body weight.
The maximum dose is 800 mg daily.
or
TRANSMETIL tablets: 800 mg daily. Your doctor may determine a different dose based on
your body weight: from 10 to 25 mg daily per kilogram of body weight.
The maximum dose is 1600 mg daily.
Maintenance therapy dose
TRANSMETIL tablets: 800 – 1600 mg daily.
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 TRANSMETIL with particular caution.
Method of administration
TRANSMETIL 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 TRANSMETIL if the tablets appear different from white/yellowish in color (due to damage to the aluminum wrapper).
TRANSMETIL powder and solvent for injectable solution: must be administered via injection into a vein (intravenous route) or into a muscle (intramuscular route). Intravenous administration 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 injection solution:

• on the neck of the ampoule, there is a small colored dot. Gently tap the top of the ampoule to dislodge any liquid droplets that may be present at the tip; position the ampoule as shown in figure 1;
• to open the ampoule, apply pressure with your thumb on the colored dot as shown in figure 2;
• withdraw the solvent using a syringe and inject it into the vial containing the powder;
• once the powder has dissolved, withdraw 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 differs in color from white/yellowish (due to damage to the
vial or exposure to heat).
If you take more TRANSMETIL than you should, contact your doctor immediately, as appropriate measures may be required.
If you forget to use TRANSMETIL
Do not take a double dose to make up for the missed dose.
If you stop using TRANSMETIL
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 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 gets them.
Stop taking TRANSMETIL immediately and contact your doctor if you experience any of the following:

• allergic reactions, even severe ones, which may manifest as sudden onset of skin lesions, such as discolored 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 or heart rate (tachycardia, bradycardia);
• difficulty breathing due to swelling of the throat (laryngeal edema).

Inform your doctor if, during treatment with TRANSMETIL, you notice the following:

Common side effects (may affect up to 1 in 10 people)

• itching;
• headache;
• abdominal pain, diarrhea, 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 intestine, vomiting;
• fatigue (asthenia), swelling (edema), fever, chills, injection site reactions;
• urinary tract infection;
• joint pain or muscle spasms, excessive sweating;
• dizziness, disturbances in sensation (paresthesia) or taste (dysgeusia), restlessness, 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 swelling, inflammation of the esophagus (esophagitis);
• malaise, suicidal thoughts or behavior;
• 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 estimated from the available data)

• liver problems due to a condition called cirrhosis;
• heart or blood vessel problems (cardiovascular disorders);
• flu-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 TRANSMETIL

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.
TRANSMETIL tablets: no special storage precautions are required.
TRANSMETIL powder and solvent for injectable solution: store at a temperature not exceeding 30°C. Use TRANSMETIL immediately after reconstitution of 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 TRANSMETIL Contains
The active substance is: ademetionine.

TRANSMETIL 300 mg/5 ml powder and solvent for injectable solution
One vial of 300 mg powder contains: 300 mg of ademetionine.
Other components are:

• Solvent vial: water for injectable preparations, L-lysine, sodium hydroxide.

TRANSMETIL 500 mg/5 ml powder and solvent for injectable solution
One vial of 500 mg powder contains: 500 mg of ademetionine.
Other components are:

• Solvent vial: water for injectable preparations, L-lysine, sodium hydroxide.

TRANSMETIL 300 mg tablets
One tablet contains: 300 mg of ademetionine.
Other components are: microcrystalline cellulose, magnesium stearate, polyethylene glycol 6000, polymethacrylates, polysorbates, colloidal anhydrous silica, emulsified silicone, sodium starch glycolate, talc.

TRANSMETIL 500 mg tablets
One tablet contains: 500 mg of ademetionine.
Other components are: microcrystalline cellulose, magnesium stearate, polyethylene glycol 6000, polymethacrylates, polysorbates, colloidal anhydrous silica, sodium hydroxide, emulsified silicone, sodium starch glycolate, talc.

Description of the Appearance of TRANSMETIL and Contents of the Package
TRANSMETIL 300 mg/5 ml powder and solvent for injectable solution: available in a pack containing 5 powder vials and 5 solvent vials of 5 ml.
TRANSMETIL 500 mg/5 ml powder and solvent for injectable solution: available in a pack containing 5 powder vials and 5 solvent vials of 5 ml.
TRANSMETIL 300 mg tablets: available in a pack of 20 tablets.
TRANSMETIL 500 mg tablets: available in a pack of 10 tablets.

Marketing Authorization Holder
Mylan Italia S.r.l., Via Vittor Pisani 20, 20124 Milan, Italy

Manufacturer
TRANSMETIL 300 mg gastro-resistant tablets
Avara Liscate Pharmaceutical Services S.p.A. – Via Fosse Ardeatine 2, 20060 Liscate (Milan), Italy
TRANSMETIL 500 mg gastro-resistant tablets
AbbVie S.r.l. – S.R. 148 Pontina km 52 s.n.c., Campoverde (LT), Italy
TRANSMETIL 300 mg/5 ml powder and solvent for injectable solution
Avara Liscate Pharmaceutical Services S.p.A. – Via Fosse Ardeatine 2, 20060 Liscate (Milan), Italy
AbbVie S.r.l. – S.R. 148 Pontina km 52 s.n.c., Campoverde (LT), Italy
TRANSMETIL 500 mg/5 ml powder and solvent for injectable solution
AbbVie S.r.l. – S.R. 148 Pontina km 52 s.n.c., Campoverde (LT), Italy
Delpharm Saint Remy – Rue de l’Isle Saint Remy, 28380 Saint Remy Sur Avre, France
Biologici Italia Laboratories S.r.l., Via F. Serpero 2, 20060 Masate (Milan), Italy