Package Insert: Information for the Patient

Plenur 400 mg Modified Release Tablets

Lithium Carbonate

Read this package insert carefully before taking this medication, as it contains important information for you.

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

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

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

Do not take Plenur

• if you are allergic to lithium carbonate or any of the other ingredients of this medication (listed in section 6)
• if you are pregnant or breastfeeding
• if you have severe kidney disease
• if you have a serious heart disease
• if you have any heart disease associated with arrhythmia
• if you are very weak, dehydrated, have severe sodium deficiency, follow 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 unresponsive 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 a high fever
• if you are taking diuretics
• if you follow a low-sodium diet
• if you have hypothyroidism or psoriasis
• if you are receiving lithium from another source
• if you are epileptic
• if you have an acute infectious disease (flu, urinary tract infection, etc.)
• if you have kidney disease
• if you have a condition called Brugada syndrome (a hereditary heart condition), 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 at any time.

Plenur should be used under medical supervision. Visit your doctor regularly. Your doctor may request blood tests periodically to control the treatment correctly.

Patients with severe kidney disease, severe heart 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 may cause hypothyroidism.

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

Electrolyte/fluid balance

Care should be taken to ensure that the diet and fluid intake are adequate to maintain a stable electrolyte balance (sodium/water). Infectious diseases such as the common cold, 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 sectionOther medications and Plenur).

Renal tumors

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

Serotonin syndrome

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

Care should be taken to monitor the appearance of signs and symptoms of serotonin syndrome, especially at the beginning of treatment. If this syndrome occurs, the doctor should consider interrupting lithium treatment or its concomitant use with other serotoninergic medications.

Patients treated with typical and atypical antipsychotics

The use of typical and atypical antipsychotics is not recommended while taking Plenur due to the possible occurrence of neurologic adverse 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 may exacerbate or mask Brugada syndrome (a hereditary heart condition). 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.

Benign intracranial 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, patients taking other medications that prolong the QT interval, and patients with risk factors for QT interval prolongation (heart disease, bradycardia, thyroid disease, hypopotasemia, 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 taking this medication and are about to undergo any laboratory test such as blood glucose test, iodine-bound proteins, or uric acid.

Children

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

Older adults

Older adults 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 taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

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

Interactions that increase lithium levels:

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

• antibiotics (such asmetronidazole,tetracyclines, cotrimoxazoleortrimethoprim)
• nonsteroidal anti-inflammatory drugs (such asindomethacin,mefenamic acid,phenylbutazone,piroxicam,ibuprofen, celecoxib, or etoricoxib)
• medications to treat high blood pressure (such ascaptoprilorenalapril)
• diuretics used to increase urine production (such asthiazides,furosemideorbumetanide), including herbal preparations
• medications that alter the hydroelectrolyte balance (such ascorticosteroids: hydrocortisoneorprednisone)

Interactions that decrease lithium levels:

The administration of lithium with the following medications may lead to a decrease in lithium levels and produce, therefore, a risk of lithium deficiency.

• antidiabetic medications used to treat type 2 diabetes (such asempagliflozinanddapagliflozin)
• xanthines (such ascaffeineandtheophylline) used to treat asthma
• diuretics that inhibit carbonic anhydrase (such asacetazolamide, also used to treat glaucoma)
• urea
• sodium-rich products such assodium bicarbonate

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

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

• typical and atypical antipsychotics (such asrisperidone,haloperidol,thioridazine,fluphenazine,chlorpromazine,perphenazine,olanzapine,clozapine…)
• antiepileptic medications (such ascarbamazepine,phenytoinorclonazepam)
• serotoninergic medications (such asfluoxetine) and tricyclic and tetracyclic antidepressants, used to treat depression
• antihypertensive medications (such asmethyldopa) and calcium channel blockers (such asdiltiazem,nifedipine,verapamil), used to treat high blood pressure
• muscle relaxants, used to relax muscles during surgery (such assuccinylcholineorpancuronium):
• iodides (such aspotassium iodide)
• sodium
• medications that may prolong the QT interval of the electrocardiogram, such as:
• antiarrhythmic medications (such asajmaline,disopyramide,hydroquinidine,procainamide,quinidine,amiodarone,azimilide,cibenzoline,dofetilide,ibutilide,sotalol…)
• antipsychotics (such asamisulpride,haloperidol,droperidol,mesoridazine,pimozide,sertindole,thioridazine,clozapine),antibiotics (such asintravenouseritromycinoresparfloxacina),serotonin antagonists (such asketanserinaormesilato de dolasetrón),antihistamines (astemizol,terfenadine),antimalarials (derivatives of artemisinin,mefloquine,halofantrine),and other medications such asarsenic trioxide,cisapride,ranolazine.

Plenur with food and beverages

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

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

If you follow a low-sodium diet, inform your doctor.

Pregnancy, lactation, and fertility

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

Pregnancy

Plenur is contraindicated during pregnancy, especially during the first trimester due to its possible teratogenicity. Women under lithium treatment should use appropriate contraceptive methods. In the case of women of childbearing age who wish to become pregnant, it is recommended to suspend lithium treatment due to the possible damage it may cause to the fetus.

In the case of women who need to continue lithium treatment during pregnancy, it is likely that your doctor will closely monitor your lithium serum levels, and it may be necessary to adjust the dose.

Newborns may experience lithium intoxication (e.g., muscle weakness or hypotonia).

Lactation

Plenur is contraindicated during lactation due to the fact that lithium is excreted in breast milk.

In the case of necessary treatment, your doctor will evaluate the interruption of Plenur treatment or the interruption of breastfeeding, depending on the importance of the medication for the mother and the importance of breastfeeding for the baby.

Fertility

Based on studies conducted in animals, fertility may be affected, leading to a decrease in fertility.

Driving and operating machinery

Plenur may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may impair your ability to react. These effects, as well as the underlying disease, may make it difficult for you to drive vehicles or operate machinery. Therefore, do not drive or operate machinery or engage in other activities that require special attention until your doctor evaluates your response to this medication.

Plenur contains sodium (from croscarmellose sodium)

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The recommended dose varies from one patient to another. Your doctor will adjust the dose based on your response and your levels of lithium (amount or levels of lithium in the blood).

The normal doses are between 1 and 4 tablets per day.

Lithium blood levels

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

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

You may need to have other blood tests to determine the possible harmful effects of lithium on the kidneys or thyroid.

Mode of use

Plenur is administered orally. For proper use of Plenur, note that the tablets are made with special excipients that make the main component (lithium carbonate) release slowly in the digestive tract. Therefore, the tablets must be swallowed whole, without chewing or crushing them, and with a glass of water or other non-alcoholic beverage, to maintain its effectiveness. It is recommended to take the medication with meals.

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

If you consider that the action of Plenur is too strong or too weak, inform your doctor or pharmacist.

Use in children

Plenur is not recommended for use in children.

Use in elderly patients

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

Use in patients on low-sodium diets

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

Use in patients with mild or moderate renal 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 must be closely monitored and thyroid hormone supplementation 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. The 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 forgot to take Plenur

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Plenur

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

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

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

Like all medicines, this medicine can cause side effects, although not everyone will experience 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 common side effects(may affect more than 1 in 10 patients)

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

Common side 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 activity), euthyroid goiter (enlargement of the thyroid gland not associated with hyper or hypothyroidism)
• Loss 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 within a few weeks. If they persist or become problematic, contact your doctor.

Rare side 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 near the thyroid gland).
• Weight loss or gain.
• Transient hyperglycemia (high blood sugar)
• Dizziness, vertigo, seizures, 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.
• Pseudotumor cerebri (increased intracranial pressure and papilledema) has been reported in patients treated with lithium, which, if not detected, can result in optic disc enlargement, optic nerve constriction, 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 insufficiency, fluid retention, and inflammation (edema), syncope (fainting).
• Dry mouth, altered taste.
• Acne, skin rash, reversible in a spontaneous or upon discontinuation of the medication.
• Renal problems such as presence of sugar or albumin in the urine, decreased urine production.
• Impotence, sexual dysfunction.

Very rare side effects(may affect up to 1 in 10,000 patients)

• Psoriasis (a skin disease in which red plaques covered with scales appear, especially on the knees, elbows, or head), or worsening of psoriasis in patients who already have it, hair loss, dry and brittle hair, itching with or without skin rash, skin ulcers or desquamation, dry skin, decreased skin sensitivity.

Very rare side effects(may affect fewer than 1 in 10,000 patients)

• A single case of painful discoloration of the fingers and soles when cold has been reported. It disappears when treatment is suspended.

Unknown frequency (cannot be estimated from available data)

• Increased antinuclear antibodies
• Hyperthyroidism (increased thyroid activity) and parathyroid adenoma
• Increased magnesium or sugar in the blood
• Encephalopathy, neuroleptic malignant syndrome, cerebellar syndrome, serotonin syndrome, delirium, irreversible neurotoxicity caused by lithium (permanent nerve damage), parkinsonism, myasthenia gravis (muscle weakness and fatigue)
• Memory loss, lack of coordination, mild cognitive impairment, feeling of drowsiness
• 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 disturbances such as increased salivation and gastritis
• Skin rash or mucosal lesions (drug-induced lichenoid reaction), acne, skin lesions
• Muscle weakness and rhabdomyolysis (muscle breakdown that causes pain, weakness, and discoloration of the urine)
• Tubulointerstitial nephritis, renal function deterioration
• Benign or malignant renal tumors (microquists, oncocitomas, or renal tubular carcinoma) in long-term treatments
• General disorders such as: edema, fatigue, drowsiness, thirst, fatigue, general malaise, and sudden unexplained death
• Unmasking or worsening of Brugada syndrome (a hereditary condition that affects the heart).

Reporting side effects

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

Keep this medication out of the sight and reach of children.

This medication does not require special storage conditions. Store in the original packaging.

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

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Plenur

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

Appearance of the product and content of the packaging

Plenur are modified-release coated tablets, white in color, biconvex, round, and with a notch on one of their faces. Each bottle contains 100 tablets.

Holder of the marketing authorization

Faes Farma, S.A.

Autoridad Etorbidea, 10

48940 Leioa (Bizkaia)

Spain

Responsible for manufacturing

Faes Farma, S.A.

M á ximo Agirre, 14

48940 Leioa (Bizkaia)

Spain

Last review date of this leaflet: July 2024

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS): https://www.aemps.gob.es/ .