Donamet

Package leaflet: Information for the patient or user

DONAMET 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 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, consult 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, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

2. What you need to know before using DONAMET

Do not use DONAMET 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 DONAMET.
Inform your doctor if:

• you have previously experienced increased blood ammonia levels after taking oral medications containing ademetionine;
• you have liver or kidney disease;
• 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 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 ADJUSTMENTS ARE NECESSARY.
Contact your doctor if, during treatment with DONAMET:

• 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 DONAMET treatment (false positive);
• you experience dizziness.

Children and adolescents
DONAMET is not intended for use in children and adolescents.
Other medicines and DONAMET
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 called selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (e.g. clomipramine);
• medicines or supplements containing the amino acid (a component of proteins) called tryptophan.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before using this medicine.
During the first three months of pregnancy and during breastfeeding, DONAMET should be used only if clearly necessary and under strict medical supervision.
Driving and using machines
DONAMET may cause dizziness: make sure you do not experience this side effect before driving or operating machinery.
DONAMET powder and solvent for injectable solution contains less than 1 mmol of sodium per dose, i.e. it is practically "sodium-free".

3. How to use DONAMET

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
Initial dose
DONAMET 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 per day for each
kilogram of body weight.
The maximum dose is 800 mg per day.
or
DONAMET tablets: 800 mg daily. Your doctor may determine a different dose based on your
body weight: from 10 to 25 mg per day for each kilogram of body weight.
The maximum dose is 1600 mg per day.
Maintenance therapy dose
DONAMET tablets: 800 – 1600 mg per day.
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 DONAMET with particular caution.
Method of administration
DONAMET tablets: must be taken orally. 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 DONAMET if the tablets appear different from white/yellowish in color (due to the presence of holes in the aluminum wrapper).
DONAMET 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.
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 dislodge 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 has a color different from white/yellowish (due to damage to the ampoule or exposure to heat).
If you take more DONAMET than you should, contact your doctor immediately, as appropriate measures may be necessary.
If you forget to take DONAMET
Do not take a double dose to make up for the missed dose.
If you stop treatment with DONAMET
It is important that you continue taking this

medicine for the full duration of
the treatment prescribed by your doctor.
Do not stop treatment just
because you feel better, as your
symptoms may recur 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 will experience them.
Stop taking DONAMET immediately and contact your doctor if you experience any of the following:

• allergic reactions, even severe ones, which may manifest as sudden or gradual 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 or chest tightness, changes in blood pressure or heart rate (tachycardia, bradycardia);
• breathing difficulties due to throat swelling (laryngeal oedema).

Inform your doctor if, during treatment with DONAMET, 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 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, altered sensation (paraesthesia), 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 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 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.agenziafarmaco.gov.it/it/responsabili”. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store DONAMET

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
DONAMET tablets: no special storage precautions are necessary.
DONAMET powder and solvent for injectable solution: store below 30°C.
Use DONAMET 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 DONAMET Contains
The active substance is: ademetionine.
DONAMET 300 mg/5ml powder and solvent for injectable solution
One vial of powder 300 mg contains: 300 mg of ademetionine.
The other components are:

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

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

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

DONAMET 300 mg tablets
One tablet contains: 300 mg of ademetionine.
The other components are: microcrystalline cellulose, magnesium stearate, polyethylene glycol 6000,
polymethacrylates, polysorbates, colloidal silicon dioxide, glycolic acid sodium starch, emulsified silicone, talc.
DONAMET 500 mg tablets
One tablet contains: 500 mg of ademetionine.
The other components are: microcrystalline cellulose, magnesium stearate, polyethylene glycol 6000,
polymethacrylates, polysorbates, colloidal silicon dioxide, sodium hydroxide, emulsified silicone, glycolic acid sodium starch,
talc.

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

Marketing Authorization Holder
BGP Products S.r.l. - Viale Giorgio Ribotta 11, 00144 Roma (RM)

Manufacturer
DONAMET 300 mg gastro-resistant tablets
Hospira S.p.A. – Via Fosse Ardeatine 2, 20060 Liscate (Milan)
DONAMET 500 mg gastro-resistant tablets
AbbVie S.r.l. - S.R. 148 Pontina km 52 s.n.c Campoverde (LT)
DONAMET 300 mg/5ml powder and solvent for injectable solution
Hospira 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)
DONAMET 500 mg/5ml powder and solvent for injectable solution
Hospira 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)
Famar L’Aigle – Rue de l’Isle Usine de S.Remy -28380 S. Remy sur Avre (France)