RESILIENT

Package leaflet: Information for the patient

RESILIENT 83 mg prolonged-release tablets

Lithium
Please read this leaflet carefully before taking 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 they have the same symptoms 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 Resilient is and what it is 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

1. What Resilient is and what it is 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 prevention of recurrences in bipolar disorder (marked mood swings alternating between a state of abnormal euphoria and hyperactivity (hypomania or mania) and deep depression characterized by reduced energy and activity (depression))
• prevention of recurrences of depressive episodes (episodes of major depression)
• treatment of abnormally euphoric states characterized by excessive activity (manic episodes), when necessary in combination with other medicines known as antipsychotics.

2. What you should know before taking Resilient

Do not take Resilient:

• if you are allergic to lithium or to any of the other ingredients of this medicine (listed in section 6)
• if you suffer from acute renal failure or severe impairment of kidney function
• if you have acute myocardial infarction
• if you have a congenital heart syndrome (Brugada syndrome) or if a close family member has Brugada syndrome
• 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 (an inherited heart disorder) or if any of your close relatives
has had Brugada syndrome, cardiac arrest, or sudden death (see section 2 Do not take Resilient)
Resilient must not be taken in the following cases unless you have a potentially life-threatening psychiatric
disorder and other treatment options have failed. In such cases, treatment must be carried out in a hospital
setting with daily monitoring of blood lithium levels:

• mild or moderate kidney function problems (renal insufficiency)
• heart function problems (heart failure)
• poor thyroid function
• a rare potentially fatal adrenal gland disorder (Addison's disease)
• severe muscle weakness (myasthenia gravis)
• certain white blood cell disorders (myeloid leukemia)
• psoriasis
• any condition requiring a low-salt diet (low sodium), disturbances in the body's sodium and water balance, or weight-loss diets with reduced sodium chloride intake
• excessive loss of body fluids (dehydration)
• heart rhythm disorders
• untreated potassium deficiency (uncorrected hypokalemia), slow heart rate (bradycardia), and concomitant treatment with medicines that affect the QT interval on ECG. Patients with certain ECG abnormalities (congenital long QT syndrome or acquired QT prolongation) should avoid taking this medicine
• low seizure threshold (epilepsy)
• if you are scheduled for or have already undergone anesthesia or surgery, you must stop taking Resilient 48 hours before the procedure. Resilient administration may be resumed immediately afterwards, provided renal function and electrolyte balance are normal
• stop taking Resilient 48 hours before starting electroconvulsive therapy to reduce the risk of acute confusion (delirium). Delirium may occur when both treatments are used together

During treatment with Resilient, concomitant use of diuretics, certain medicines for mental disorders
(antipsychotics), painkillers and anti-inflammatory drugs (NSAIDs), and certain antihypertensive medicines
should be done with particular caution.
If you are planning or have already undergone bariatric surgery, a lower dose of lithium may be required.
Your doctor will monitor your blood lithium levels and adjust the dose accordingly.
Elderly patients
Since kidney function is often impaired in elderly patients, even doses well tolerated by younger patients may
lead to higher blood lithium levels and signs of lithium toxicity in the elderly (see section 3 "How to take Resilient").
Precautions for use
The dose of Resilient must be individualized according to the patient's specific needs and blood lithium
concentrations. Therefore, regular medical check-ups are essential: weekly during the first month of
treatment, monthly during the first six months, and thereafter usually every three months. Longer intervals
are acceptable only in exceptional cases.
Your doctor will measure blood lithium levels as close as possible to 12 hours after the last dose. Blood
samples may be taken in the morning before the next dose is administered.
Monitoring tests
After a thorough medical examination at the start of treatment, lithium therapy must be closely monitored.
In addition to measuring blood lithium levels, the following tests should be performed:

• Kidney function test (serum creatinine) measured simultaneously with 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: every three months
• Blood pressure measurement
• Heart function assessment (ECG): once a year
• Brain electrical activity measurement (EEG): if necessary
• 24-hour urine collection, kidney filtration capacity (creatinine clearance): once a year
• Urine analysis
• If necessary, an additional test of kidney concentrating ability (desmopressin test on day 28)
• Renal ultrasound after long-term treatment (beyond 10 years): once a year.

Concomitant illnesses associated with severe vomiting, diarrhea, or high fever may alter blood lithium
concentrations; in such cases, consult your doctor. Also consult your doctor if you experience excessive
urine output and excessive thirst.
If you suspect lithium poisoning, stop treatment immediately and urgently consult a doctor (for symptoms of
lithium toxicity, see section 3 "If you take more Resilient than you should").
Ensure you consume an adequate amount of sodium chloride and fluids. This is especially important if you
are on a weight-loss diet or any other specific diet.
Careful medical monitoring is required during long-term lithium therapy, particularly if you notice increased
urine production and increased thirst, to prevent excessive fluid loss associated with high blood lithium levels.
Renal tumors:
Patients with severe kidney function impairment (renal insufficiency) treated with lithium for over 10 years may
be at risk of developing benign and/or malignant renal tumors (microcysts, oncocytoma, or collecting duct
carcinoma).
Children and adolescents
Resilient must not be administered to children under 12 years of age, as safety and efficacy data are not
available for this age group.
Other medicines and Resilient
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Other medicines should be used together with Resilient only with particular caution, as many drugs may
interact with Resilient.
Your doctor should monitor blood lithium levels more frequently and adjust the Resilient dose, especially when
co-administering the following medicines:

• diuretics
• metronidazole, a medicine used to treat infections (antibiotic)
• certain painkillers and anti-inflammatory drugs (NSAIDs, e.g., diclofenac, indomethacin, celecoxib)
• certain antihypertensive medicines (sartans, beta-blockers, ACE inhibitors such as captopril, enalapril)
• urea
• medicines containing theophylline, used in asthma treatment
• medicines that improve circulation (such as pentoxifylline, xanthinol nicotinate)
• substances that increase 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, heart failure, or chronic kidney disease)
• medicines used to control seizures (such as phenytoin)
• methyldopa, a medicine used to lower blood pressure
• certain antidepressants (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, be alert for side effects such as weakness, fever, tremors, confusion, seizures, uncoordinated movements, reduced attention, increased muscle tone, and changes in blood count and serum. These symptoms may indicate a serious neurological disorder (known as 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 any of the following signs: altered mental status, 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, antibiotics used to treat infections
• topiramate (used to treat epilepsy or migraine)

Exercise particular caution when using medicines that prolong the QT interval on ECG, such as:

• medicines used to treat heart rhythm disorders (antiarrhythmics, e.g., quinidine, disopyramide, amiodarone, sotalol)
• cisapride (a medicine used to increase gastrointestinal motility)
• 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 containing alcohol.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding,
consult your doctor or pharmacist before taking this medicine.
Pregnancy
Resilient must not be taken during pregnancy, especially during the first trimester. An increased risk of
birth defects and complications due to lithium intake cannot be ruled out. Before starting Resilient therapy,
pregnancy should be excluded, and an effective method of birth control must be used during treatment.
If you become pregnant, contact your doctor immediately to evaluate whether to continue and adjust
Resilient therapy.
Breastfeeding
Since lithium is excreted in breast milk, you must not take Resilient during breastfeeding unless your doctor
considers it essential. If Resilient is taken after delivery, breast milk should be expressed and discarded for
the first two weeks of the newborn's life. During this period, the infant must be fed artificially. Contact your
doctor immediately if your newborn shows signs of lithium toxicity, such as skin or lip discoloration or lethargy.
Driving and using machines
Even when taken as directed, this medicine may affect alertness to the extent that your ability to drive or
operate machinery may be impaired. The concomitant intake of alcohol intensifies these effects.

3. How to take Resilient

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
The lithium dose must be adjusted according to the individual needs of the patient, always starting therapy with
low doses of the medicine and gradually increasing the dose.
The following information applies unless otherwise prescribed by your doctor for Resilient. To achieve the best possible
efficacy, follow the dosing instructions carefully.
Unless otherwise prescribed by your doctor, the following treatment schedule is recommended:
Days 1 and 2: half a tablet of Resilient per day (equivalent to 6 mmol of lithium).
Days 3 and 4: half a tablet of Resilient twice daily (equivalent to 12 mmol of lithium).
Days 5 and 6: half a tablet of Resilient in the morning and 1 tablet in the evening (equivalent to 18 mmol of lithium).
Thereafter, 1 tablet of lithium twice daily (equivalent to 24 mmol of lithium).
The effective blood concentration of lithium ranges between 0.5 and 1.2 mmol/l. For prophylactic treatment,
a lithium concentration between 0.5 and 0.8 mmol/l is recommended. In some patients during acute phases,
a lithium concentration between 1.0 and 1.2 mmol/l may be required. Any adverse effects must be carefully monitored.
Resilient should be taken daily at a fixed time (e.g., morning and evening, with an interval of 10–12 hours between doses).
Alternatively, the daily dose may be taken as a single evening dose before bedtime, if your
doctor, after checking your blood lithium concentration, considers this a suitable 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 been treated with lithium usually can start with a dose of 1 tablet twice daily. Blood lithium concentration should be checked for the first time one week after starting treatment.
Experience has shown that lower doses are sufficient for elderly patients. In elderly patients, a blood lithium concentration exceeding 0.6 mmol/l should be avoided whenever possible. Furthermore, blood lithium concentration should be monitored more frequently in the elderly (see section 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 may be divided into two equal doses.

How long to take Resilient
Occasionally, the therapeutic response may only become evident after prolonged treatment. In any case, your doctor will determine the duration of treatment based on the course of the disease. If you discontinue taking the medicine, the dose must be gradually reduced to minimize the risk of relapse.
If you think that the effect of Resilient is too strong or too weak, consult your doctor or pharmacist.

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

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

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

If you forget to take Resilient
Do not take a double dose to make up for a missed dose.
If you forget to take a dose, you may exceptionally skip it. Make sure to take the dose prescribed by your doctor at the next scheduled time, and continue accordingly.

If you stop taking Resilient
Do not stop or interrupt treatment with Resilient without first consulting your doctor. To avoid relapses, treatment must not be stopped abruptly.
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.
The frequency and severity of side effects usually depend on the lithium concentration in the blood and on individual sensitivity to lithium.

At the beginning of therapy
At the start of treatment, the renal reabsorption of sodium and potassium may be impaired. However, this condition should normalize 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 hand tremors

Common (may affect up to 1 in 10 people)

• increased urine production
• increased thirst
• feeling unwell
• weight gain, sometimes dose-related, particularly during the first 2 years of treatment. You should therefore avoid high-calorie foods and drinks.

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

• shaking chills
• disturbances in cardiac impulse conduction (ECG abnormalities)
• 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 gland (goitre)
• reduced 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 disorders (usually with a low pulse rate)
• disorders due to overactive thyroid
• hair loss
• acne-like skin eruption
• inflammation of hair follicles (folliculitis)
• itching
• recurrence or worsening of psoriasis
• facial swelling (angioedema)
• skin rashes and other signs of hypersensitivity

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

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

Not known (frequency cannot be estimated from the available data)

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

What to do if you experience side effects
Your doctor may consider reducing the dose. Other measures depend on the nature of the side effect. If you notice any side effects, it is essential to consult your doctor, who will decide on the appropriate course of action.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://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 Resilient

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack and the blister. The expiry date refers to the last day of that month.
Do not store above 30 °C. Keep in the original packaging to protect the medicine from moisture.
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 Resilient contains
The active substance is lithium.
Each prolonged-release tablet contains 83 mg of lithium in the form of 660 mg lithium sulfate,
equivalent to 12 mmol of Li+.
The other components are:
ammonio methacrylate copolymer (type B), hypromellose, magnesium stearate.
Description of the appearance of Resilient and contents of the pack
Prolonged-release tablet.
White, oval-shaped tablet (16.2 x 8.7 mm) engraved 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
Manufacturer
A.C.R.A.F. S.p.A.
Via Vecchia del Pinocchio, 22
60131 Ancona (Italy)
This medicinal product is authorised in the European Economic Area countries under the following
names:
Italy: Resilient 83 mg prolonged-release tablets