PLENUR 400 MG MODIFIED-RELEASE TABLETS

Introduction

Package Leaflet: Information for the Patient

Plenur 400 mg Modified Release Tablets

lithium, carbonate

Read the package leaflet carefully before starting to take this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are side effects not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Plenur and what is it used for

Plenur contains the active ingredient lithium carbonate, an antipsychotic used as a mood stabilizer.

It is indicated for the prevention and treatment of bipolar disorder (mood disorders in which periods of depression alternate with periods of great euphoria) and as an additional treatment in major depressive disorder (repeated episodes of severe depression) in patients who have not had an optimal response to antidepressant treatment.

2. What you need to know before taking Plenur

Do not take Plenur

• if you are allergic to lithium carbonate or any of the other components of this medication (listed in section 6)
• if you are pregnant or breastfeeding
• if you have severe kidney failure
• if you have severe heart disease
• if you have any heart disease associated with arrhythmia
• if you are very weak, dehydrated, have severe sodium deficiency, are on a low-sodium diet, or have Addison's disease
• if you have Brugada syndrome or a family history of Brugada syndrome
• if you have untreated or intractable hypothyroidism

Warnings and precautions

Consult your doctor or pharmacist before starting to take Plenur

• if you have excessive sweating
• if you have diarrhea
• if you have nausea
• if you have vomiting
• if you have high fever
• if you are taking diuretics
• if you are on a low-salt diet (hyposodic)
• if you have hypothyroidism or psoriasis
• if you are receiving lithium in any other form
• if you are epileptic
• if you have an acute infectious condition (flu, urinary tract infection...)
• if you have kidney failure
• if you have a condition called Brugada syndrome (a hereditary condition that affects the heart), or if someone in your family has had Brugada syndrome, cardiac arrest, or sudden death.

Consult your doctor even if any of the above circumstances have occurred to you in the past.

Plenurshould always be used under medical supervision. Go to your doctor regularly. To monitor the treatment correctly, your doctor may ask you to have blood tests done periodically.

Patients with severe kidney disease, severe cardiovascular disease, severe dehydration, and patients treated with diuretics

In these patient groups, lithium will be used under extreme vigilance and caution, and only if the risk-benefit balance is favorable and there are no other therapeutic alternatives.

Patients with thyroid diseases

Lithium can cause hypothyroidism.

Some cases of hypothyroidism have been reported, including Graves' disease, multinodular toxic goiter, and silent thyroiditis.

Electrolyte/fluid balance

Caution should be taken to ensure that the diet and fluid intake are adequate to maintain a stable electrolyte balance (salt/water). Infectious diseases such as colds, flu, gastroenteritis, and urinary tract infections can alter the electrolyte balance and, consequently, lithium serum levels. In the case of intercurrent infections, treatment interruption should be considered.

Risk of seizures

The risk of seizures may increase if lithium is used with other medications (see section Other medications and Plenur).

Kidney tumors

Cases of microcysts, oncocytomas, and collecting duct renal cell carcinomas have been reported in patients with severe kidney failure who received lithium for more than 10 years.

Serotonin syndrome

Lithium can precipitate the onset of serotonin syndrome, increasing the risk when used with other serotonergic medications or those that alter serotonin metabolism (see section “Other medications and Plenur”).

Signs and symptoms of serotonin syndrome should be monitored, especially at the start of treatment. If this syndrome occurs, the doctor should consider interrupting treatment with lithium or its concomitant use with other serotonergic medications.

Patients treated with typical and atypical antipsychotics

The use of typical and atypical antipsychotics is not recommended while using Plenur due to the possible occurrence of adverse neurological reactions (see section “Other medications and Plenur”).

Patients undergoing bariatric surgery

In patients undergoing bariatric surgery (a surgical procedure used to treat obesity), a reduction in the maintenance dose of lithium should be considered due to the risk of lithium toxicity after significant weight loss.

Brugada syndrome

Lithium can worsen or mask Brugada syndrome (a hereditary condition that affects the heart). This medication should not be administered to patients with Brugada syndrome or a family history of Brugada syndrome. Caution should be exercised in patients with a family history of cardiac arrest or sudden death.

Hypertension

Cases of benign intracranial hypertension have been reported. Inform your doctor if you experience persistent headache and/or visual disturbances.

Patients with long QT syndrome

The use of lithium is not recommended in patients with congenital long QT interval syndrome, in patients taking other medications that prolong the QT interval, and in patients with risk factors for QT interval prolongation (heart disease, bradycardia, thyroid disease, hypokalemia, hypomagnesemia, hypocalcemia, advanced age, female sex).

Interference with laboratory tests: taking this medication may alter the values of some laboratory tests. Consult your doctor if you are using this medication and are going to undergo any laboratory tests, such as blood glucose analysis, protein-bound iodine, or uric acid.

Children

The use of lithium is not recommended in children due to the lack of studies on its safety and efficacy in this population.

Elderly population

Elderly patients have a higher risk of lithium toxicity, so the use of this medication should be done with caution.

Other medications and Plenur

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication, including those purchased without a prescription.

Inform your doctor if you are using any of the following medications, as they may interact with Plenur and increase or decrease lithium levels.

Interactions that increase lithium levels:

Administration of lithium with the following medications may lead to an increase in lithium levels and produce a risk of lithium toxicity. In these cases, continuous monitoring of lithium levels will be carried out, and the dose will be adjusted if necessary.

• antibiotics (such as metronidazole, tetracyclines, cotrimoxazole, or trimethoprim)
• non-steroidal anti-inflammatory drugs (such as indomethacin, acid mefenamic, phenylbutazone, piroxicam, ibuprofen, celecoxib, or eterocoxib)
• medications for treating high blood pressure (such as captoprilor enalapril)
• diuretics used to increase urine production (such as thiazides, furosemide, or bumetanide), including herbal preparations
• drugs that alter the hydroelectrolytic balance (such as corticosteroids: hydrocortisoneor prednisone)

Interactions that decrease lithium levels:

Administration of lithium with the following medications may lead to a decrease in lithium levels and produce a risk of lack of efficacy.

• antidiabetic medications used to treat type 2 diabetes mellitus (such as empagliflozinand dapagliflozin)
• xanthines (such as caffeineand theophylline) used to treat asthma
• diuretics that inhibit carbonic anhydrase (such as acetazolamide, also used in the treatment of glaucoma)
• urea
• sodium-rich products such as sodium bicarbonate

Interactions that may not be associated with elevated or decreased lithium levels:

Administration of lithium with the following medications may cause symptoms of intoxication in the presence of normal lithium levels.

• typical and atypical antipsychotics (such as risperidone, haloperidol, thioridazine, flufenazine, chlorpromazine, perphenazine, olanzapine, clozapine…)
• antiepileptics (such as carbamazepine, phenytoin, or clonazepam)
• serotonergic medications (such as fluoxetine) and tricyclic and tetracyclic antidepressants used in the treatment of depression
• antihypertensives (such as methyldopa) and calcium channel blockers (such as diltiazem, nifedipine, verapamil), used in the treatment of arterial hypertension
• neuromuscular blockers/relaxants, used to relax muscles during surgery (such as succinylcholineor pancuronium):
• iodides (such as potassium iodide)
• sodium
• medications that can prolong the QT interval on the electrocardiogram, such as: antiarrhythmics (ajmaline, disopyramide, hydroquinidine, procainamide, quinidine, amiodarone, azimilide, cibenzoline, dofetilide, ibutilide, sotalol…), antipsychotics (such as amisulpride, haloperidol, droperidol, mesoridazine, pimozide, sertindole, thioridazine, and clozaril), antibiotics (such as intravenous erythromycinor esparfloxacina), serotonin antagonists (such as ketanserineor dolasetron mesylate), antihistamines (astemizole, terfenadine), antimalarials (artemisinin derivatives, mefloquine, halofantrine), and other medications such as arsenic trioxide, cisapride, and ranolazine.

Taking Plenur with food and drinks

This medication can be taken with any food or non-alcoholic beverage.

During treatment, it is recommended that you drink plenty of water or other fluids each day, avoiding situations that may lead to dehydration.

If you are on a low-salt diet, inform your doctor.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Plenur is contraindicated during pregnancy, especially during the first trimester, due to its potential teratogenicity. Women under treatment with lithium should use appropriate contraceptive methods. In the case of women of childbearing age who wish to become pregnant, it is recommended to suspend treatment with lithium due to the possible harm that can be caused to the fetus.

If it is considered necessary to maintain treatment with lithium during pregnancy, it is likely that your doctor will closely monitor lithium levels in your serum, and a dose adjustment may be necessary.

Newborns may experience lithium intoxication (e.g., flaccid muscles or hypotonia).

Breastfeeding

Plenur is contraindicated during breastfeeding because lithium is eliminated in breast milk.

If necessary, the doctor will assess whether to interrupt treatment with Plenur or breastfeeding, depending on the importance of the medication for the mother and the importance of breastfeeding for the baby.

Fertility

Based on animal studies, spermatogenesis (formation of sperm) may be affected, leading to decreased fertility.

Driving and using machines

Plenur may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may decrease reaction capacity. These effects, as well as the underlying disease, may impair your ability to drive vehicles or operate machines. Therefore, do not drive or operate machines or engage in other activities that require special attention until your doctor assesses your response to this medication.

Plenur contains sodium (from sodium croscarmellose)

This medication contains less than 1 mmol (23 mg) of sodium per tablet; this is essentially "sodium-free".

3. How to take Plenur

Follow your doctor's instructions for taking this medication exactly. If you have any doubts, consult your doctor or pharmacist again.

The recommended dose varies from patient to patient. Your doctor will adjust the dose based on your response and lithium levels in your blood.

Normal doses are between 1 and 4 tablets per day.

Lithium levels in blood

For lithium to be effective, there must be certain levels of lithium in the blood. Your doctor may request blood tests to ensure you have an adequate and not excessive amount of lithium in your blood. At the beginning of treatment, it may be necessary to perform tests 1 or 2 times a week, and later every 1-2 months. Tests should be done immediately before taking the medication; if you need to take a Plenur tablet in the morning, take it after having the blood test.

If you change from one lithium formulation to another, lithium serum levels should be monitored, and treatment with lithium should only be started at a daily dose as close as possible to the initial formulation dose. The product change should be considered as the start of a new treatment.

Other blood tests may be necessary to determine the potential adverse effects of lithium on the kidneys or thyroid.

Mode of administration

Plenur is administered orally. For proper use of Plenur, note that the tablets are made with special excipients that allow the active ingredient (lithium carbonate) to be released slowly in the digestive tract. Therefore, the tablets should be swallowed whole, without chewing or crushing, and with a glass of water or another non-alcoholic beverage, to maintain their efficacy. It is recommended to take the medication with meals.

If treatment with this medication needs to be discontinued, the dose should be gradually reduced, as indicated by your doctor, over a reasonable period to avoid the risk of relapse.

If you think the effect of Plenur is too strong or too weak, inform your doctor or pharmacist.

Use in children

The use of Plenur is not recommended in children.

Use in elderly patients

Elderly patients generally require lower doses of lithium and more frequent monitoring of lithium levels in the blood.

Use in patients on low-salt diets

These patients require more frequent visits and monitoring of lithium levels in the blood.

Use in patients with mild or moderate kidney disease, severe cardiovascular disease, patients treated with diuretics, and in situations of significant fluid loss (excessive sweating, diarrhea, high fever)

In these cases, lithium will be used under extreme vigilance and caution.

Use in patients with hypothyroidism

Thyroid function should be closely monitored, and supplemental thyroid treatment may be necessary.

If you take more Plenur than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount taken. Symptoms of a possible overdose may include diarrhea, vomiting, fatigue, muscle weakness, lack of coordination, and dysarthria. Finally, coma, generalized tonic-clonic seizures, circulatory collapse, etc. may occur.

If you forget to take Plenur

Do not take a double dose to make up for forgotten doses.

If you interrupt treatment with Plenur

Your doctor will indicate the duration of your treatment with Plenur.

Do not stop treatment without consulting your doctor, as your problem may reappear or you may experience other symptoms.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Contact your doctor immediately if the following symptoms appear or worsen suddenly:

• Diarrhea, vomiting, fatigue, muscle weakness, lack of coordination or difficulty speaking.

Very frequent adverse effects (may affect more than 1 in 10 patients)

• Excessive thirst or increased amount or frequency of urine (diabetes insipidus): usually appears at the start of treatment and disappears with continued use of lithium.
• Increased calcium levels in the blood.
• Fatigue, tremors, muscle weakness, headache, difficulty speaking, confusion, mild difficulty concentrating. Appears at the start of treatment and usually disappears with continued use of lithium. Stress and caffeine can exacerbate tremors.
• Somnolence: usually disappears over time. If it appears, be cautious when driving or operating hazardous machinery.
• Muscle hyperirritability (involuntary muscle contractions and movements)
• Mild alterations in the electrocardiogram: disappear when treatment is interrupted.

Frequent adverse effects (may affect up to 1 in 100 patients)

• Increased white blood cells in the blood, which disappears when the medication is stopped.
• Hypothyroidism (low thyroid gland activity), euthyroid goiter (enlargement of the thyroid gland not associated with hyper or hypothyroidism)
• Lack of appetite that can cause weight loss.
• Muscle stiffness, excessive reaction to stimuli, increased muscle tone.
• Nausea, vomiting, diarrhea or constipation, abdominal pain, abdominal distension: usually disappear with continued use over a few weeks. If they persist or become problematic, contact your doctor.

Infrequent adverse effects (may affect up to 1 in 1,000 patients)

• Mild primary hyperparathyroidism (enlargement and increased activity of the parathyroid glands located in the neck next to the thyroid gland).
• Weight loss or gain.
• Transient excess sugar in the blood
• Dizziness, vertigo, convulsions, transient loss of consciousness, stupor, coma. Rapid, uncontrolled eye movements, blurred vision, transient loss of vision, bulging eyes. Visual disturbances, abnormal involuntary movements, involuntary muscle contractions, restlessness.
• Isolated cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been described in patients treated with lithium, which, if not detected, can result in an enlargement of the blind spot, constriction of the optic fibers, and eventual blindness due to optic nerve atrophy. In such cases, lithium treatment will be discontinued.
• Changes in heart rhythm, decreased heart rate, decreased blood pressure, peripheral circulatory failure, fluid retention, and inflammation (edema), syncope (fainting).
• Dry mouth, altered taste.
• Acne, skin rash, reversible spontaneously or when the medication is stopped.
• Kidney problems such as sugar or albumin in the urine, decreased urine production.
• Impotence, sexual dysfunction.

Rare adverse effects (may affect up to 1 in 10,000 patients)

• Psoriasis (skin disease characterized by red plaques covered with scales, especially on the knees, elbows, or head), or worsening of psoriasis in patients who already have it, hair loss, dryness, and fragility of hair, itching with or without skin rash, ulcers, or skin peeling, dry skin, lack of sensitivity in the skin.

Very rare adverse effects (may affect less than 1 in 10,000 patients)

• A single case of painful loss of color in the fingers and heels when they are cold has been reported. It disappears when treatment is suspended.

Frequency not known (cannot be estimated from available data)

• Increased antinuclear antibodies
• Hyperthyroidism (increased thyroid gland activity) and parathyroid adenoma
• Increased magnesium or sugar in the blood
• Encephalopathy, malignant neuroleptic syndrome, cerebellar syndrome, serotonergic syndrome, delirium, irreversible neurotoxicity syndrome caused by lithium (permanent nerve damage), parkinsonism, myasthenia gravis (muscle weakness and fatigue).
• Memory loss, lack of coordination, mild cognitive impairment, feeling of dizziness
• Ocular irritation, optic nerve edema, eyelid edema (swelling of the eyelid)
• Cardiomyopathy, changes in the electrocardiogram, arrhythmia, prolonged QT interval (Torsade de Pointes), cardiac arrest
• Gastrointestinal disorders such as increased salivation and gastritis
• Skin or mucous membrane rash (lichenoid drug reaction), acne, skin lesions
• Weakness and rhabdomyolysis (breakdown of damaged muscles that occurs with pain, weakness, and discoloration of the urine)
• Tubulointerstitial nephritis, deterioration of renal function
• Benign or malignant kidney tumors (renal microcysts, oncocytomas, or collecting duct carcinomas) in long-term treatments
• General disorders such as edema, fatigue, somnolence, thirst, fatigue, malaise, and sudden unexplained death
• Unmasking or worsening of Brugada syndrome (a hereditary syndrome that affects the heart).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Plenur

Keep this medicine out of sight and reach of children.

This medicine does not require special storage conditions. Store in the original package.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Plenur

• The active ingredient is lithium carbonate. Each tablet contains 400 mg of lithium carbonate.
• The other components (excipients) are: carbomer, sodium carmellose, magnesium carbonate, microcrystalline cellulose, glycerol (E-422), magnesium stearate, macrogol 6000, titanium dioxide (E-171), basic butyl methacrylate copolymer, talc.

Appearance of the Product and Package Contents

Plenur is a modified-release, coated tablet, white, biconvex, round, and with a notch on one of its faces. Each bottle contains 100 tablets.

Marketing Authorization Holder

Faes Farma, S.A.

Autonomia Etorbidea, 10

48940 Leioa (Bizkaia)

Spain

Manufacturer

Faes Farma, S.A.

Maximo Agirre Kalea, 14

48940 Leioa (Bizkaia)

Spain

O

Faes Farma, S.A.

Parque Científico y Tecnológico de Bizkaia

Ibaizabal Bidea, Edificio 901

48160 Derio (Bizkaia)

Spain

Date of the Last Revision of this Prospectus: July 2024

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS):https://www.aemps.gob.es/.