RESILIENT 83 mg Extended-Release Tablet

Зміст інструкції

1. RESILIENT 83 mg prolonged-release tablets
   1. What is Resilient and what is it used for
   2. What you need to know before taking Resilient
   3. How to take Resilient
   4. Possible side effects
   5. How to store Resilient
   6. Contents of the pack and other information

RESILIENT 83 mg prolonged-release tablets

Lithium

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 pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Resilient and what is it used for

Resilient contains an active substance called lithium.
Resilient is a medicine used for the treatment of mental disorders.
Resilient is used for

• the preventionof recurrences of bipolar disorder (strong mood swings with transitions from an abnormal state of euphoria and hyperactivity (hypomania or mania) and profound depression characterized by a decrease in vigor and activity (depression))
• preventionof recurrences of depressive episodes (major depressive episodes)
• treatmentof abnormal states of euphoria characterized by excessive activity (manic episodes), if necessary in combination with other medicines called antipsychotics.

2. What you need to know before taking Resilient

Do not take Resilient:

• if you are allergic to lithium or any of the other ingredients of this medicine (listed in section 6)
• if you have acute kidney failure or severe impairment of kidney function
• if you have an acute myocardial infarction (heart attack)
• if you have a congenital syndrome affecting the heart (Brugada syndrome) or if a close family member is affected by it
• if you suffer from severe sodium deficiency (hyponatremia).

Warnings and precautions
Talk to your doctor before taking Resilient:
If you have a condition called Brugada syndrome (a hereditary syndrome affecting the heart) or if one of
your family members has had Brugada syndrome, cardiac arrest or died of sudden death
(see section 2 Do not take Resilient)
Resilient should not be taken in the following cases, unless you have a psychiatric disorder
that is potentially life-threatening and other treatment options have failed. In such cases, treatment should take place
in hospital with daily monitoring of blood lithium levels:

• mild or moderate kidney problems (renal insufficiency)
• heart problems (heart failure)
• poor thyroid function
• a rare, potentially life-threatening disease of the adrenal gland (Addison's disease)
• severe muscle weakness (myasthenia gravis)
• certain blood cell diseases (myeloid leukemia)
• psoriasis
• all conditions that require a low-salt diet (low sodium), disorders of sodium and water balance in the body, or weight-loss diets with reduced sodium chloride intake
• excessive loss of body fluids (dehydration)
• heart rhythm disorders
• untreated potassium deficiency (uncorrected hypokalemia), slow heartbeat (bradycardia) and concomitant treatment with medicines that alter the QT interval on the ECG. Patients who present with certain changes in the ECG (congenital long QT syndrome or acquired QT prolongation) should avoid taking this medicine
• low seizure threshold (epilepsy)
• patients scheduled for anesthesia or surgery should stop taking Resilient 48 hours before the procedure. Resilient administration can be reintroduced immediately afterwards, provided that kidney function and electrolyte balance are normal
• stop taking Resilient 48 hours before starting electroconvulsive therapy to reduce the risk of acute confusional state (delirium). Delirium may occur when the two therapies are used together

During treatment with Resilient, the intake of diuretics, some medicines for the treatment of
mental disorders (antipsychotics), painkillers and anti-inflammatory drugs (NSAIDs) and some medicines for
hypertension, must be done with particular caution.
Are you planning or have you already undergone weight loss surgery, as a lower dose of lithium may be needed. The doctor will monitor the lithium level in the blood and adjust
the dose accordingly.

Elderly patients
Since kidney function is often impaired in elderly patients, even doses well tolerated by
younger patients can produce higher concentrations of lithium in the blood and signs of
lithium intoxication in the elderly (see section 3 “How to take Resilient”).

Precautions for use
The amount of Resilient to be taken must be established based on the specific needs of the patient, depending on
the concentration of lithium in the blood. Consequently, it is advisable to consult your
doctor regularly and undergo check-ups that will be weekly during the first month of treatment, then
monthly during the first six months of treatment and, subsequently, usually every three months. Longer intervals
are acceptable only in exceptional cases.
The doctor will check the concentration of lithium in the blood as far as possible exactly 12 hours
after the last administration. The sample can be taken in the morning before taking the next dose.

Monitoring tests
After a thorough medical examination at the beginning of treatment, lithium therapy must be carried out under close
monitoring.
In addition to checking the lithium concentration in the blood, the following tests must be performed:

• Measurement of kidney function (serum creatinine) simultaneously with the determination of lithium concentration
• Thyroid function: once a year
• Determination of sodium, potassium and calcium: once a year
• Complete blood count: once a year
• Body weight and neck circumference: once every three months
• Blood pressure measurement
• Heart function measurement (ECG): once a year
• Measurement of brain electrical activity (EEG): if necessary
• 24-hour urine collection, kidney filtration capacity (creatinine clearance): once a year
• Urine examination
• If necessary, a further examination of the kidney's ability to concentrate (desmopressin test on the 28th day)
• Renal ultrasound after prolonged treatment (over 10 years): once a year.

Concomitant diseases associated with severe vomiting or diarrhea or high fever can lead to an alteration
of the concentration of lithium in the blood; in these cases it is advisable to consult your doctor. Contact
your doctor also in case of excessive amount of urine produced and excessive thirst.
If you suspect lithium intoxication, stop therapy immediately and consult a doctor urgently (to know the signs of lithium intoxication, see section 3 "If you take more Resilient than
you should").
Make sure you take an adequate amount of sodium chloride and fluids. This is especially true if you are
following a weight-loss diet or another specific diet.

Kidney tumors:
Patients suffering from severe kidney impairment (renal insufficiency) treated with
lithium for over 10 years may be at risk of developing benign and/or malignant kidney tumors (microcysts,
oncocytoma or collecting duct carcinoma).

Children and adolescents
Resilient must notbe administered to children under 12 years of age, as safety and efficacy data are not available for this age group.

Other medicines and Resilient
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicine.
Other medicines must be administered together with Resilient only with particular caution, because many
medicines can interact with Resilient.
The doctor will need to check the lithium concentration in the blood more frequently and adjust the dose of
Resilient, especially in case of co-administrationof the following medicines:

• diuretics
• metronidazole, a medicine used in the treatment of infections (antibiotic)
• some painkillers and anti-inflammatory drugs (NSAIDs, e.g. diclofenac, indometacin, celecoxib)
• some medicines that lower high blood pressure (sartans, beta-blockers, ACE inhibitors such as captopril, enalapril)
• urea
• medicines containing theophylline, used in the treatment of asthma
• medicines that improve circulation (such as pentoxifylline, xantinol nicotinate)
• substances that increase the pH (such as sodium bicarbonate)
• calcitonin, a medicine used to treat osteoporosis
• medicines used to treat glaucoma and other conditions (such as acetazolamide, dorzolamide, brinzolamide)
• dapagliflozin (used to treat diabetes or heart failure or chronic kidney disease)
• medicines used to control seizures (such as phenytoin)
• methyldopa, a medicine used to lower blood pressure
• certain medicines used to treat depression (tricyclic antidepressants, such as imipramine)
• other medicines used to treat mental disorders (antipsychotics, such as haloperidol, thioridazine, clozapine). Especially if you are taking higher doses of these medicines, pay attention to the onset of side effects such as weakness, fever, tremors, confusion, convulsions, uncoordinated movements, decreased attention, increased muscle tone and changes in blood counts and serum. These phenomena may represent signs of a serious neurological disorder (called neuroleptic malignant syndrome)
• medicines that interfere with serotonin metabolism (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, 5-HT agonists [some medicines used to treat migraine headaches such as sumatriptan]). Note: consult a doctor as soon as possible if you experience some of the following signs: impaired consciousness, restlessness, muscle contractions, increased reflexes, sweating, chills and tremors
• certain medicines used to treat cardiovascular diseases (calcium antagonists such as diltiazem, verapamil)
• medicines used for muscle relaxation during surgery (neuromuscular blocking agents)
• potassium iodide
• tetracyclines, medicines used in the treatment of infections (antibiotics)
• topiramate (used to treat epilepsy or migraine)

Exercise particular caution during concomitant treatment with medicines that prolong the QT interval
on the ECG, such as:

• medicines used to treat heart rhythm disorders (antiarrhythmics, e.g. quinidine, disopyramide, amiodarone, sotalol)
• cisapride (a medicine used to increase the motility of food through the gastrointestinal tract)
• medicines used to treat infections (antibiotics such as erythromycin)
• medicines used to treat mental disorders (antipsychotics, such as thioridazine, amisulpride).

Resilient with food, drinks and alcohol
Avoid all foods, drinks and other products that contain alcohol.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy
Resilient should not be taken during pregnancy, especially during the first trimester. An increased risk of
malformations and complications due to lithium intake cannot be excluded. Pregnancy should be ruled out
before starting therapy with Resilient and effective birth control should be used during treatment. If you are
pregnant, contact your doctor immediately to assess whether to continue and adjust the therapy with Resilient.

Breastfeeding
Because lithium is excreted in breast milk, you should not take Resilient during breastfeeding, unless
your doctor considers it essential. If you take Resilient after birth, for the first
two weeks of the newborn's life, breast milk must be expressed and discarded. During this time, the
newborn must be artificially fed. Contact your doctor immediately if your newborn
shows signs of intoxication, such as discoloration of the skin and lips or apathy.

Driving and using machines
Even when taken as directed, this medicine can alter alertness to the point of
impairing the ability to drive vehicles or use machines. Taking alcohol at the same time
accentuates these effects.

3. How to take Resilient

Take this medicine following exactly the instructions of your doctor. If you have any doubts, consult your
doctor or pharmacist.
The dose of lithium must be adjusted to the specific needs of the patient, always starting therapy with
low doses of medicine and gradually increasing the dose.
The following information is valid, unless otherwise prescribed by your doctor for Resilient. To
obtain the best possible efficacy, follow the dosage instructions.

Unless otherwise prescribed by your doctor, the following treatment schedule is recommended:
Days 1 and 2: half a Resilient tablet per day (equivalent to 6 mmol of lithium).
Days 3 and 4: half a Resilient tablet twice a day (equivalent to 12 mmol of lithium).
Days 5 and 6: half a Resilient tablet in the morning and 1 in the evening (equivalent to 18 mmol of lithium).
Subsequently, 1 lithium tablet twice a day (equivalent to 24 mmol of lithium).
The effective lithium concentration in the blood is between 0.5 and 1.2 mmol/l. For preventive treatments
a lithium concentration between 0.5 and 0.8 mmol/l is recommended. In some patients in an acute phase,
a lithium concentration between 1.0 and 1.2 mmol/l may be necessary. Any undesirable effects
must be carefully monitored.
Taking Resilient should occur daily at a set time(e.g. morning and
evening with an interval of 10-12 hours between the two doses).
Alternatively, the daily dose can be taken as a single dose in the evening before bedtime, if your
doctor, after checking the lithium concentration in the blood, considers it a valid alternative in your
specific case. If switching from a multiple-dose regimen to a single-dose regimen, monitoring tests should be
performed more frequently.
Patients who have previously followed lithium therapy can generally start with a
dose of 1 tablet twice a day. The lithium concentration in the blood should be checked for the
first time 1 week after starting treatment.
Experience has shown that a lower dose is sufficient for elderly patients. In the elderly, if
possible, a lithium concentration in the blood greater than 0.6 mmol/l should be avoided. Furthermore, the
lithium concentration in the blood must therefore be checked more frequently (see
paragraph 2 “Elderly patients - Warnings and precautions”).

How to take Resilient
Resilient is for oral use.
The tablets must be swallowed whole with plenty of water. The tablet can be divided into two
equal doses.

How long should you take Resilient
Occasionally, the therapeutic response may only manifest when treatment has been prolonged for some
time. In any case, the doctor will determine the duration of treatment, based on the course of the
disease. If you stop taking the medicine, you must gradually reduce the dose
to limit the risk of relapses.
Contact your doctor or pharmacist if you feel that the effect of Resilient is too strong or too weak.

If you take more Resilient than you should
The signs of lithium intoxication may include:

• increased urine production,
• increased thirst,
• diarrhea,
• malaise,
• excessive loss of body fluids (dehydration),
• muscle weakness,
• increased muscle tone,
• involuntary muscle contractions (fasciculations),
• fatigue,
• coordination disorders and difficulty concentrating,
• slurred speech,
• confusion,
• abnormal drowsiness,
• rapid and involuntary eye movements (nystagmus),
• agitation,
• increased reflexes (hyperreflexia),
• ringing in the ears,
• blurred vision,
• unsteady gait (ataxia),
• state of indifference (apathy),
• heart rhythm disturbances,
• circulatory collapse,
• impaired kidney function (rarely even acute renal failure).

The resulting increase in lithium concentration in the blood can be potentially fatal. In severe cases,
seizures, coma and fatal outcome may occur. If you suspect lithium intoxication, contact your
doctor immediately.

If you forget to take Resilient
Donot take a double dose to make up for a missed dose.
If you should forget to take a dose, exceptionally, you can skip it. Make sure to take the dose
recommended by your doctor for the next dose and so on.

If you stop treatment with Resilient
You should not stop or interrupt treatment with Resilient without first consulting your doctor. To
avoid relapses, treatment should not be stopped abruptly.
If you have any doubts about the use of this medicine, contact your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The frequency and intensity of side effects usually depend on the
lithium concentration in the blood and individual sensitivity to lithium.
Especially at the beginning of therapy
At the beginning of therapy, the reabsorption of sodium and potassium at the renal level may be impaired. However, the
situation should normalise within 1 week.
The following side effects usually resolve during treatment or after a dose reduction.

Very common(may affect more than 1 in 10 people)

• fine tremors of the hands.

Common(may affect up to 1 in 10 people)

• increased urine production
• increased thirst
• feeling unwell
• weight gain, sometimes dose-related, especially during the first 2 years of treatment. Therefore, you should avoid high-calorie foods and beverages.

During treatment

Very common(may affect more than 1 in 10 people)

• shivering chills
• disturbances of cardiac impulse conduction (ECG changes)
• metallic taste
• dry mouth
• weight gain.
• Excessive levels of calcium in the blood.

Common(may affect up to 1 in 10 people)

• increased urine production
• increased thirst
• burning, itching and watery eyes
• loss of appetite
• feeling unwell
• malaise
• diarrhoea
• abdominal pain
• enlarged thyroid (goitre)
• decreased thyroid function
• increased magnesium concentration in the blood.

Uncommon(may affect up to 1 in 100 people)

• development of antibodies against the thyroid (autoimmune thyroiditis).

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

• heart rhythm disturbances (usually with a low pulse rate)
• disorders of hyperthyroidism
• hair loss
• acne-like rash
• inflammation of the hair follicles (folliculitis)
• itching
• recurrence or worsening of psoriasis
• swelling of the face (angioedema)
• rashes and other signs of hypersensitivity.

Very rare(may affect up to 1 in 10,000 people)

• abnormal ECG result called "prolongation of the QT interval"
• kidney disorders characterised by protein loss and water retention (nephrotic syndrome)
• impaired kidney function
• changes in the kidneys (e.g. interstitial fibrosis) after many years of treatment
• hyperparathyroidism (a condition in which the parathyroid glands produce an excessive amount of parathyroid hormone, which increases calcium levels in the blood)

Not known(frequency cannot be estimated from available data)

• hallucinations
• abnormal drowsiness
• difficulty concentrating and impaired memory
• muscle weakness
• involuntary muscle contractions (fasciculations)
• involuntary movements of the limbs
• unstable gait (ataxia)
• uncoordinated movements
• exaggerated tendon reflexes
• movement disorders originating from the central nervous system (extrapyramidal motor symptoms)
• brief loss of consciousness that can lead to coma
• convulsions
• slurred speech
• abnormal coordination
• headache
• dizziness
• mental confusion
• generalised rigidity in a conscious state (stupor)
• taste disorders
• increased intracranial pressure (pseudotumour cerebri)
• severe muscle weakness (myasthenia gravis)
• muscle and joint pain
• sensitivity to light (photophobia)
• eyelid spasm (blepharospasm)
• inability to perform specific movements (apraxia)
• visual field defects
• rapid involuntary eye movements
• blurred vision
• circulatory failure
• low blood pressure
• fluid accumulation (oedema)
• circulatory disorders in the hands and feet (Raynaud's syndrome)
• latentisation and/or worsening of Brugada syndrome (an inherited condition affecting the heart).
• inflammation of the stomach lining (gastritis)
• excessive saliva production
• uncontrolled urine leakage (urinary incontinence)
• benign or malignant kidney tumours (microcysts, oncocytoma or renal collecting duct carcinoma) during long-term treatment
• high blood sugar (hyperglycaemia)
• impotence
• sexual disorders
• skin or mucous membrane rash (drug-induced lichenoid reaction)
• increased size of the parathyroid glands
• parathyroid adenoma (a non-cancerous tumour)
• extensive rash, high body temperature, increased liver enzymes, blood abnormalities (eosinophilia), enlarged lymph nodes and involvement of other organs of the body (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome). Stop using Resilient if you develop these symptoms and contact your doctor or seek immediate medical attention.

What to do if you experience side effects
The doctor may consider reducing the dose. Other measures depend on the
nature of the side effect. If you notice the onset of side effects, it is therefore essential that you
consult your doctor who will decide how to proceed.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the national
reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . Reporting
side effects can help provide more information on the safety of this medicine.

5. How to store Resilient

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the packaging and blister. The expiry date refers to the last day of that month.
Do not store at a temperature above 30  C. Store in the original packaging to protect the
medicine from humidity.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Resilient contains
The active ingredient is lithium.
Each prolonged-release tablet contains 83 mg of lithium as 660 mg of lithium sulfate,
equivalent to 12 mmol of Li+.
The other ingredients are:
ammonium methacrylate copolymer (type B), hypromellose, magnesium stearate.

Description of the appearance of Resilient and contents of the pack
Prolonged-release tablet.
White, oblong tablet (16.2 x 8.7 mm) with an inscription on both sides.
50 prolonged-release tablets.
100 prolonged-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Aziende Chimiche Riunite Angelini Francesco – A.C.R.A.F. S.p.A
Viale Amelia 70
00181 Roma
A.C.R.A.F. S.p.A.
Via Vecchia del Pinocchio, 22
60131 Ancona (Italy)

This medicinal product is authorised in the Member States of the European Economic Area with the following
names:
Italy: Resilient 83 mg prolonged-release tablets