Fevarin

I N S T R U C T I O N for medical use of the medicinal product F E V A R I N ® (FEVARIN®)

Composition:

active substance: fluvoxamine;

1 tablet contains fluvoxamine maleate 50 mg or 100 mg;

excipients: mannitol (E 421), maize starch, pregelatinized starch, sodium stearyl fumarate, colloidal anhydrous silicon dioxide, hypromellose, macrogol 6000, talc, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties:

film-coated tablets, 50 mg: round, biconvex, white or almost white, film-coated, with a score line and marking "291" on both sides of it; diameter approximately 9 mm; the tablet can be divided into two equal parts.

film-coated tablets, 100 mg: oval, biconvex, white or almost white, film-coated, with a score line and marking "313" on both sides of it; length approximately 15 mm, width approximately 8 mm; the tablet can be divided into two equal parts.

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06AB08.

Pharmacological properties.

Pharmacodynamics.

Receptor binding studies have shown that fluvoxamine is a potent inhibitor of serotonin reuptake both in vitro and in vivo, and has minimal affinity for subtypes of serotonin receptors. The drug has little ability to bind to α-adrenergic, β-adrenergic, histaminergic, muscarinic, cholinergic, or dopaminergic receptors.

Fluvoxamine has high affinity for sigma-1 receptors, at which it acts as an agonist at therapeutic doses.

Pharmacokinetics.

Absorption.

Fluvoxamine is completely absorbed after oral administration. Maximum plasma concentration is reached within 3–8 hours after intake. Due to the first-pass effect, the average absolute bioavailability is 53%.

Concomitant food intake does not affect the pharmacokinetics of Fevarin®.

Distribution.

In vitro, 80% of fluvoxamine is protein-bound in plasma. The volume of distribution in humans is 25 L/kg.

Metabolism.

Fluvoxamine is extensively metabolized in the liver. Although in vitro studies indicate that CYP2D6 is the main isoenzyme involved in fluvoxamine metabolism, plasma concentrations in individuals with reduced CYP2D6 activity are not substantially higher than in those with normal metabolism.

The mean elimination half-life in plasma is approximately 13–15 hours after a single dose and slightly prolonged (17–22 hours) with repeated administration. Steady-state plasma concentrations are usually achieved within 10–14 days.

Fluvoxamine is extensively transformed in the liver, primarily via oxidative demethylation, resulting in at least nine metabolites, which are excreted renally. Two major metabolites exhibit minimal pharmacological activity. Other metabolites are pharmacologically inactive. Fluvoxamine is a potent inhibitor of CYP1A2 and CYP2C19, and a moderate inhibitor of CYP2C9, CYP2D6, and CYP3A4.

Fluvoxamine exhibits linear pharmacokinetics after single-dose administration. Steady-state plasma concentrations are higher than those predicted from single-dose data, with this disproportionate increase being most pronounced at higher daily doses.

Special patient groups.

The pharmacokinetics of fluvoxamine are similar in healthy adults, elderly individuals, and patients with renal impairment. Metabolism of fluvoxamine is impaired in patients with hepatic disease.

Steady-state plasma concentrations of fluvoxamine are twice as high in children aged 6 to 11 years compared to children aged 12 to 17 years. Plasma concentrations in children aged 12 to 17 years are similar to those in adults.

Clinical characteristics.

Indications.

• Depression
• Obsessive-compulsive disorder (OCD).

Contraindications.

The drug is contraindicated in patients with hypersensitivity to fluvoxamine maleate or to any of the other components of the drug.

Concomitant use with tizanidine or monoamine oxidase inhibitors (MAOIs) is prohibited (see sections "Interaction with other medicinal products and other types of interactions" and "Special precautions for use"). Treatment with Fevarin® should not be initiated earlier than two weeks after discontinuation of irreversible MAOIs or the day after discontinuation of reversible MAOIs (e.g., moclobemide, linezolid).

Treatment with any of the MAOI group drugs should not be initiated earlier than one week after discontinuation of Fevarin®.

Fevarin® must not be co-administered with pimozide or ramelteon (see sections "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Monoamine oxidase inhibitors.

The drug must not be used in combination with monoamine oxidase inhibitors, including linezolid, due to the risk of serotonin syndrome (see section "Contraindications").

Effect of fluvoxamine on oxidative metabolism of other drugs.

Fluvoxamine may inhibit the metabolism of drugs metabolized by certain cytochrome P450 (CYP) isoenzymes. In vitro and in vivo studies demonstrate a potent inhibitory effect of fluvoxamine on CYP1A2 and CYP2C19, while CYP2C9, CYP2D6, and CYP3A4 are less strongly inhibited. Drugs primarily metabolized by these isoenzymes may have higher, and in some cases lower (e.g., clopidogrel, a prodrug) plasma concentrations of active substance/metabolites when co-administered with fluvoxamine. Initiation or adjustment of treatment with fluvoxamine and such drugs should be based on the lowest, rather than the highest, dose within their therapeutic range. Close monitoring of plasma concentrations, efficacy, or adverse effects of concomitant medications is required, and their dosage should be adjusted as necessary. This is particularly important when using drugs with a narrow therapeutic index.

Ramelteon.

When fluvoxamine maleate immediate-release tablets 100 mg twice daily were administered for 3 days, followed by a single 16 mg dose of ramelteon co-administered with fluvoxamine maleate immediate-release tablets, the AUC of ramelteon increased approximately 190-fold and the Cmax increased approximately 70-fold compared to ramelteon administered as monotherapy.

Drugs with a narrow therapeutic index.

Close monitoring is required in patients receiving fluvoxamine concomitantly with drugs with a narrow therapeutic index (such as tacrine, theophylline, methadone, mexiletine, phenytoin, carbamazepine, and cyclosporine) that are metabolized exclusively or partially by CYP isoenzymes inhibited by fluvoxamine. Dose adjustments of these drugs are recommended if necessary.

Due to the narrow therapeutic range of pimozide and its known ability to prolong the QT interval, concomitant administration of pimozide and fluvoxamine is contraindicated (see section "Contraindications").

Tricyclic antidepressants and neuroleptics.

Increased plasma concentrations of tricyclic antidepressants (e.g., clomipramine, imipramine, amitriptyline) and neuroleptics (e.g., clozapine, olanzapine, quetiapine), which are primarily metabolized by cytochrome P450 1A2, have been reported when co-administered with fluvoxamine. Dose reduction of these drugs should be considered when adding fluvoxamine to the treatment regimen.

Benzodiazepines.

Plasma concentrations of benzodiazepines metabolized by oxidation (such as triazolam, midazolam, alprazolam, and diazepam) may increase when co-administered with fluvoxamine. The dose of these benzodiazepines should be reduced when used concomitantly with fluvoxamine.

Increase in plasma concentration.

When ropinirole is administered in combination with fluvoxamine, its plasma concentration may increase, increasing the risk of overdose. Therefore, patient monitoring is required, and dose reduction of ropinirole may be necessary (both during and after discontinuation of fluvoxamine treatment).

Since plasma concentrations of propranolol increase when co-administered with fluvoxamine, dose reduction may be necessary.

When used concomitantly with fluvoxamine, plasma concentrations of warfarin increase significantly and the prothrombin time is prolonged.

Increased risk of adverse reactions.

Isolated cases of cardiovascular disturbances (cardiotoxic effects) have been reported with concomitant use of fluvoxamine and thioridazine.

Plasma levels of caffeine may increase when co-administered with fluvoxamine. Adverse effects of caffeine (tremor, palpitations, nausea, restlessness, insomnia) may occur. Therefore, patients who consume large amounts of caffeine-containing beverages should reduce their intake when prescribed fluvoxamine.

For terfenadine, astemizole, cisapride, and sildenafil, see section "Special precautions for use".

Glucuronidation.

The drug does not affect plasma concentrations of digoxin.

Renal excretion.

The drug does not affect plasma concentrations of atenolol.

Pharmacodynamic interactions.

Serotonergic effects may be enhanced when fluvoxamine is used concomitantly with other serotonergic agents (including triptans, tramadol, buprenorphine, buprenorphine/naloxone, selective serotonin reuptake inhibitors, and St. John's wort), potentially leading to life-threatening conditions (see also section "Special precautions for use").

Fluvoxamine has been used in combination with lithium in the treatment of severely ill, therapy-resistant patients. However, lithium (and possibly also tryptophan) enhances the serotonergic effects of fluvoxamine. This combination should be used with caution in patients with severe, therapy-resistant depression. Close monitoring is required in patients receiving oral anticoagulants and fluvoxamine, as their risk of bleeding may increase.

As with other psychotropic agents, patients should refrain from consuming alcohol during treatment with fluvoxamine.

Special precautions for use.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicide-related events). This risk persists until remission occurs. Since improvement may not occur during the first few weeks of treatment or even over a longer period, patients should be closely monitored by a physician until improvement is observed. Clinical experience suggests that the risk of suicide may increase during the early stages of recovery.

Other psychiatric disorders for which fluvoxamine is used in treatment may also be associated with an increased risk of suicide-related events. In addition, these disorders may be comorbid with major depressive disorder. Therefore, close monitoring is required when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events and those exhibiting high levels of suicidal ideation prior to starting therapy are at greater risk of experiencing suicidal thoughts or suicide attempts and therefore require careful monitoring during treatment.

Close monitoring of patients, especially those at high risk, is necessary during pharmacological treatment, particularly at the beginning of therapy and after dosage adjustments.

Patients (as well as caregivers) should be warned to monitor for any clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior, and to seek immediate medical attention if such symptoms occur.

Akathisia/psychomotor agitation

Fluvoxamine treatment may be associated with the development of akathisia, characterized by a subjective sense of inner restlessness or distress and an urge to move, often accompanied by an inability to sit or stand still. These symptoms are most likely to occur during the first few weeks of treatment. Increasing the dose in patients who develop these symptoms may be harmful.

Hepatic and renal function impairment

In patients with hepatic or renal insufficiency, treatment should be initiated at low doses under close medical supervision.

Rarely, fluvoxamine treatment has been associated with elevated liver enzyme activity, usually accompanied by corresponding clinical symptoms. In such cases, treatment with the drug should be discontinued.

Central nervous system disorders

Although animal studies have not revealed convulsant properties of fluvoxamine, caution is required when prescribing fluvoxamine to patients with a history of seizure disorders. The drug should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored. If seizures occur or their frequency increases, treatment with fluvoxamine should be discontinued.

Isolated cases of serotonin syndrome or serotonin syndrome-like symptoms, resembling neuroleptic malignant syndrome, have been reported in association with fluvoxamine treatment, particularly when used concomitantly with other serotonergic and/or neuroleptic agents or in combination with buprenorphine or buprenorphine/naloxone. Since these syndromes may lead to potentially life-threatening conditions, fluvoxamine treatment should be discontinued if such events occur (characterized by a cluster of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuations in vital signs, and mental status changes including confusion, agitation, irritability progressing to delirium and coma), and supportive symptomatic treatment should be initiated.

Metabolism and nutritional disorders

As with other selective serotonin reuptake inhibitors (SSRIs), hyponatremia has been rarely reported during fluvoxamine treatment, which resolves upon discontinuation of the drug. Some cases may have been related to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Most reports have involved elderly patients.

Glycemic control may be impaired (including hyperglycemia, hypoglycemia, and reduced glucose tolerance), particularly in the early stages of treatment. Patients with a history of diabetes mellitus may require adjustment of their antidiabetic medication during fluvoxamine treatment.

Nausea, sometimes accompanied by vomiting, is the most common adverse effect observed during fluvoxamine treatment. This adverse effect usually diminishes within the first two weeks of treatment.

Ocular disorders

Mydriasis has been reported with the use of selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine. Therefore, fluvoxamine should be prescribed with particular caution in patients with elevated intraocular pressure or at increased risk of acute angle-closure glaucoma.

Hematological disorders

During treatment with SSRIs, cases of skin hemorrhages such as ecchymoses and purpura, as well as other hemorrhagic manifestations (e.g., gastrointestinal bleeding or gynecological/postpartum bleeding), have been reported. Particular caution is recommended when prescribing these drugs to patients, especially elderly patients and those concurrently using medications affecting platelet function (e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, nonsteroidal anti-inflammatory drugs), or drugs that increase bleeding risk, as well as in patients with a history of hemorrhagic conditions or conditions predisposing to bleeding (e.g., thrombocytopenia or coagulation disorders).

Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of postpartum hemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions").

Cardiac disorders

Concomitant use of fluvoxamine may increase plasma concentrations of terfenadine, astemizole, or cisapride, leading to an increased risk of QT interval prolongation and torsade de pointes. Therefore, fluvoxamine should not be co-administered with these drugs. Fluvoxamine may cause a slight decrease in heart rate (by 2–6 beats per minute).

Electroconvulsive therapy (ECT)

Fluvoxamine should be used with particular caution in combination with ECT due to insufficient clinical data.

Withdrawal reactions

Withdrawal symptoms may occur upon discontinuation of fluvoxamine treatment, although preclinical and clinical data do not suggest dependence potential for this drug. The most commonly reported symptoms associated with discontinuation of fluvoxamine include dizziness, sensory disturbances (including paresthesia, visual disturbances, and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation, irritability, confusion, emotional lability, headache, nausea and/or vomiting, diarrhea, sweating, palpitations, tremor, and anxiety (see section "Adverse reactions"). These phenomena are generally mild or moderate and self-limiting, but in some patients they may be severe and/or prolonged. They typically occur within the first few days after stopping treatment. Therefore, it is recommended to gradually reduce the dose of fluvoxamine when discontinuing treatment, according to the patient's needs (see section "Dosage and administration").

Mania/hypomania

Fluvoxamine should be prescribed with particular caution in patients with a history of mania/hypomania. Treatment with fluvoxamine should be discontinued in any patient who develops a manic episode.

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRIs) may cause symptoms of sexual dysfunction (see section "Adverse reactions"). Cases of persistent sexual dysfunction, with symptoms continuing after discontinuation of SSRIs, have been reported.

Elderly patients

Data in elderly patients do not confirm clinically significant differences in normal daily doses compared to younger patients. However, dose titration should be performed more slowly and dosing should always be cautious in elderly patients.

Young adults (18 to 24 years of age)

A meta-analysis of placebo-controlled clinical trials of antidepressants in psychiatric patients under 25 years of age showed an increased risk of suicidal behavior with antidepressant treatment compared to placebo.

Use during pregnancy or breastfeeding

Epidemiological data suggest that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, particularly in the third trimester, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The risk is approximately 5 cases per 1000 pregnancies. In the general population, 1–2 cases of PPHN per 1000 pregnancies are observed.

Fluvoxamine should not be used during pregnancy except when the woman's clinical condition requires treatment with fluvoxamine.

Isolated cases of withdrawal symptoms in newborns have been reported after fluvoxamine use late in pregnancy. After SSRI use during the third trimester of pregnancy, some newborns have exhibited feeding difficulties and/or respiratory problems, seizures, temperature instability, hypoglycemia, tremor, muscle tone disturbances, nervousness, cyanosis, irritability, lethargy, somnolence, vomiting, sleep disturbances, and persistent crying, which may require prolonged hospitalization.

Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage after SSRI use within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").

Breastfeeding

Fluvoxamine is excreted in small amounts in breast milk; therefore, it should not be administered to breastfeeding women.

Fertility

Reproductive toxicity studies in animals have shown that fluvoxamine reduces reproductive function in both male and female animals. The relevance of these findings to humans is unknown. Fluvoxamine should not be used in patients attempting to conceive, except when the patient's clinical condition requires treatment with fluvoxamine.

Ability to affect reaction speed when driving or operating machinery

Fevarin® at a daily dose of 150 mg has no effect or negligible effect on the ability to drive or operate machinery. In healthy volunteers, no effect on psychomotor reactions related to driving or operating mechanical devices was observed. However, cases of somnolence have been reported during fluvoxamine treatment; therefore, the drug should be used with caution until the individual response to the medication is established.

Dosage and Administration.

Fevarin® tablets should be swallowed whole without chewing and taken with sufficient amount of water.

Depression (adults).

The recommended initial dose is 50 or 100 mg once daily in the evening. The dose should be gradually increased until an effective dose is achieved. The effective dose is usually 100 mg per day. This dose should be individually adjusted according to the patient's response to treatment. The daily dose should not exceed 300 mg. When doses exceeding 150 mg are prescribed, they should be divided into several doses throughout the day. According to the World Health Organization guidelines, after recovery from depression, treatment should be continued for at least 6 months. The recommended dose for prevention of depressive relapse is 100 mg of fluvoxamine once daily.

Obsessive-compulsive disorder.

Adults.

The recommended initial dose is 50 mg daily for the first 3–4 days of treatment. The effective dose usually ranges from 100 to 300 mg per day. The dose should be gradually increased until an effective dose is achieved. The maximum daily dose of Fevarin® for adults is 300 mg.

Doses up to 150 mg may be taken once daily, preferably in the evening. If doses exceeding 150 mg are prescribed, they should be divided into 2–3 doses throughout the day. If a therapeutic effect has been achieved, treatment may be continued at the dose adjusted according to clinical response. If no improvement occurs within ten weeks of treatment, the continued use of Fevarin® should be reevaluated. Although systematic studies on the duration of fluvoxamine treatment have not been conducted, considering the chronic nature of obsessive-compulsive disorders, it is advisable to continue treatment beyond 10 weeks in patients who have responded clinically. Dose adjustment should be performed very carefully and individually to maintain the patient on the lowest effective dose. The continued need for treatment should be periodically reassessed. For patients who benefit from pharmacotherapy, some clinicians recommend concomitant behavioral psychotherapy.

Children aged 8 years and older.

The initial dose for children aged 8 years and older is 25 mg daily, preferably taken at bedtime. The dose may be increased by 25 mg every 4–7 days until an effective dose is reached. The effective daily dose usually ranges from 50 to 200 mg. The maximum daily dose for children should not exceed 200 mg. If the total daily dose exceeds 50 mg, it should be divided into two doses. If one of the divided doses is larger than the other, the larger dose should be taken at bedtime.

Abrupt discontinuation of fluvoxamine treatment should be avoided. When discontinuing fluvoxamine therapy, the dose should be gradually reduced over 1–2 weeks to minimize the risk of withdrawal symptoms (see sections "Adverse Reactions" and "Special Warnings and Precautions for Use"). If intolerable symptoms develop after dose reduction or upon discontinuation, the previous dose should be reinstated. The physician may then continue tapering the dose, but more gradually.

Treatment of patients with hepatic or renal impairment should be initiated at a low dose under close medical supervision.

Children.

Fevarin® should not be used for the treatment of children and adolescents (under 18 years of age), except for patients with obsessive-compulsive disorder (OCD). Fluvoxamine cannot be recommended for the treatment of depression in children due to insufficient clinical experience. Suicidality (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behavior, and anger) have been observed more frequently in children and adolescents treated with antidepressants compared to the placebo group in clinical trials. If treatment is clinically warranted, patients should be closely monitored for the emergence of suicidal symptoms.

Furthermore, long-term safety data on the use of the drug in children and adolescents regarding physical, sexual, cognitive, and behavioral development are insufficient.

Overdose.

Symptoms. Symptoms include gastrointestinal complaints (nausea, vomiting, diarrhea), drowsiness, and dizziness. Cardiovascular disorders (tachycardia, bradycardia, hypotension), hepatic dysfunction, seizures, and coma have also been reported.

Fluvoxamine has a wide safety margin in overdose. Since its market introduction, fatal cases due to overdose with fluvoxamine alone have been extremely rare. The highest documented dose of fluvoxamine ingested by a patient was 12 g, with full recovery. More serious complications have occasionally been observed in cases of intentional overdose with fluvoxamine in combination with other medicinal products.

Treatment. There is no specific antidote for fluvoxamine. In case of overdose, gastric lavage should be performed as soon as possible, followed by symptomatic treatment. Repeated administration of activated charcoal and, if necessary, an osmotic laxative are also recommended. Forced diuresis or hemodialysis are of low efficacy.

Adverse Reactions

Adverse events observed during clinical trials, listed below by frequency, were often related to the underlying disease and not necessarily related to treatment.

Adverse effects are classified by frequency as follows:

Very common: ≥ 1/10
Common: ≥ 1/100 to < 1/10
Uncommon: ≥ 1/1000 to < 1/100
Rare: ≥ 1/10,000 to < 1/1000
Very rare: < 1/10,000
Frequency not known: Cannot be estimated based on available data

Endocrine disorders

Frequency not known: Hyperprolactinaemia, inappropriate antidiuretic hormone secretion

Metabolism and nutrition disorders

Common: Anorexia (loss of appetite)
Frequency not known: Hyponatraemia, weight increase or weight decrease

Psychiatric disorders

Uncommon: Hallucinations, confusion, aggression
Rare: Mania
Frequency not known: Suicidal ideation, suicidal behaviour

Nervous system disorders

Common: Agitation, restlessness, anxiety, insomnia, somnolence, tremor, headache, dizziness
Uncommon: Extrapyramidal disorders, ataxia
Rare: Seizures
Frequency not known: Serotonin syndrome; symptoms resembling neuroleptic malignant syndrome; akathisia/psychomotor agitation; paraesthesia; dysgeusia

Eye disorders

Frequency not known: Glaucoma, mydriasis

Cardiac disorders

Common: Palpitations/tachycardia

Vascular disorders

Uncommon: Hypotension (orthostatic)
Frequency not known: Bleeding (including gastrointestinal haemorrhage, gynaecological haemorrhage, ecchymosis, purpura)

Gastrointestinal disorders

Common: Abdominal pain, constipation, diarrhoea, dry mouth, dyspepsia, nausea, vomiting

Hepatobiliary disorders

Rare: Liver function abnormalities

Skin and subcutaneous tissue disorders

Common: Hyperhidrosis
Uncommon: Hypersensitivity skin reactions (including rash, pruritus, angioneurotic oedema)
Rare: Photosensitivity reaction

Musculoskeletal and connective tissue and bone disorders

Uncommon: Arthralgia, myalgia
Frequency not known: Bone fractures*

*Epidemiological studies, mainly conducted in patients aged 50 years and older, have shown an increased risk of bone fractures in patients treated with SSRIs (selective serotonin reuptake inhibitors) and TCAs (tricyclic antidepressants). The mechanism leading to this risk is unknown.

Renal and urinary disorders

Frequency not known: Urinary disorders (including urinary retention, urinary incontinence, polyuria, nocturia, enuresis)

Reproductive system and breast disorders

Uncommon: Impaired (delayed) ejaculation
Rare: Galactorrhoea
Frequency not known: Anorgasmia, menstrual disorders (such as amenorrhoea, hypomenorrhoea, metrorrhagia, menorrhagia), postpartum haemorrhage**

**This event has been reported in association with the SSRI pharmacotherapeutic class (see sections "Special precautions for use" and "Use during pregnancy or breastfeeding").

General disorders

Common: Asthenia, malaise
Frequency not known: Withdrawal syndrome, including in neonates

Withdrawal symptoms observed upon discontinuation of fluvoxamine

Discontinuation of fluvoxamine treatment (especially abrupt) usually leads to withdrawal symptoms. To avoid withdrawal symptoms, gradual discontinuation of fluvoxamine with a stepwise reduction in dose is recommended (see sections "Dosage and administration" and "Special precautions for use").

Shelf life. 3 years

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of the reach of children!

Packaging. Tablets are packaged in PVC/PVDC-aluminium blisters containing 15 tablets per blister, 1 or 2 blisters per cardboard box; or 20 tablets per blister, 3 blisters per cardboard box.

Prescription status. Prescription only

Manufacturer. Mylan Laboratories SAS, France

Manufacturer's address and place of business. Route de Belleville, Lieu dit Maillard, 01400, Chatillon-sur-Chalaronne, France