Active ingredients: Flunarizine
FLUGERAL 5 mg hard capsules 20 capsules
FLUGERAL 5 mg hard capsules 30 capsules
FLUGERAL 5 mg hard capsules 50 capsules
FLUGERAL 10 mg hard capsules 20 capsules
FLUGERAL 10 mg hard capsules 30 capsules
FLUGERAL 10 mg hard capsules 50 capsules
Why is Flugeral used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antivertigo preparation.
THERAPEUTIC INDICATIONS
Prophylactic treatment of migraine with frequent and severe attacks limited to patients who have not responded to other therapies or in whom these therapies have caused serious side effects.
Contraindications When Flugeral should not be used
Flunarizine is contraindicated in patients with:
- Current depressive illness or history of relapsing depression (see "Precautions for use" and "Undesirable effects")
- pre-existing symptoms of Parkinson's disease or other extrapyramidal disorders (see "Precautions for use" and "Undesirable effects")
- known hypersensitivity to flunarizine or to any of the excipients contained in the formulation.
Precautions for use What you need to know before taking Flugeral
Flunarizine can cause extrapyramidal and depressive symptoms and highlight parkinsonism, especially in elderly patients. Therefore it should be used with caution in such patients.
The recommended doses should not be exceeded. Patients should be evaluated at regular intervals, especially during maintenance therapy, so that extrapyramidal or depressive symptoms can be detected early and, if present, treatment can be stopped. This control must be particularly careful in elderly patients.
In rare cases, asthenia may progressively increase during flunarizine therapy. In these cases, therapy should be discontinued. Any loss of drug efficacy during the maintenance phase requires discontinuation of therapy (for the duration of treatment see "Dose, method and time of administration").
Lactose
Flunarizine capsules contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Interactions Which drugs or foods can modify the effect of Flugeral
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The concomitant intake of flunarizine with alcohol, hypnotics, tranquilizers or other psychotropic drugs can cause excessive sedation. It is not recommended to drink alcoholic beverages during therapy.
The pharmacokinetics of flunarizine are not affected by topiramate. Following repeated dosing in migraine patients, the systemic exposure to flunarizine was increased by 14%. When flunarizine was administered concomitantly with topiramate 50 mg every 12 hours, administration of repeated doses resulted in a 16% increase. in systemic exposure to flunarizine. Steady state pharmacokinetics of topiramate are not affected by flunarizine.
Chronic administration of flunarizine does not alter the bioavailability of phenytoin, carbamazepine, valproate or phenobarbital. Plasma concentrations of flunarizine were generally lower in patients with epilepsy taking these anti-epileptic drugs compared to healthy subjects given similar doses. The plasma protein binding of carbamazepine, valproate and phenytoin is not affected by concomitant administration of flunarizine.
Warnings It is important to know that:
Ask your doctor for advice before taking any medicine.
Use during pregnancy and lactation
Pregnancy
There are no data on the use of flunarizine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid using flunarizine during pregnancy.
Feeding time
It is unknown whether flunarizine is excreted in human milk. Animal studies have documented the excretion of flunarizine in breast milk. A decision to discontinue breast-feeding or to continue / discontinue flunarizine therapy must be made taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Effects on ability to drive and use machines.
As somnolence may occur, especially at the initiation of treatment, caution should be exercised during activities such as driving vehicles or operating hazardous machinery.
Dosage and method of use How to use Flugeral: Dosage
Migraine prophylaxis
Attack therapy:
In patients less than 65 years of age, treatment should be started at a dose of 10 mg per day to be taken at bedtime; in patients over the age of 65 this dosage should be reduced to 5 mg.
If depression, extrapyramidal signs or other serious side effects appear during this phase of treatment, the treatment should be discontinued.
If no significant improvement is observed after two months, patients should be considered refractory to therapy and drug administration discontinued.
Maintenance therapy:
If the patient responds satisfactorily, and if maintenance therapy is deemed necessary, the daily dose should be reduced and administered on alternate days or for 5 consecutive days with a two-day interruption each week. Even if the prophylactic treatment is effective and well tolerated, it must be stopped after six months and can only be resumed in case of relapse.
Overdose What to do if you have taken an overdose of Flugeral
In case of accidental ingestion / intake of an excessive dose of Fluferal, notify your doctor immediately or go to the nearest hospital.
Based on the pharmacological characteristics of the drug, sedation and asthenia are likely in case of overdose. Acute overdose (up to 600 mg in one intake) has been reported and symptoms observed were sedation, agitation and tachycardia. Treatment of acute overdose consists of administration of activated charcoal, induction of vomiting or gastric lavage, and supportive measures. No specific antidote is known.
If you have any further questions on the use of Flugeral, ask your doctor or pharmacist.
Side Effects What are the side effects of Flugeral
Like all medicines, Flugeral can cause side effects, although not everybody gets them.
The safety of flunarizine was evaluated in 247 flunarizine-treated subjects who participated in two placebo-controlled clinical trials in the treatment of dizziness and migraine, respectively, and in 476 flunarizine-treated subjects who participated in two controlled clinical trials with comparator in the treatment of dizziness and / or migraine. Based on the pooled safety data from these clinical trials, the most commonly reported undesirable effects (incidence ≥ 4%) were (% incidence): weight gain (11% ), sleepiness (9%), depression (5%), increased appetite (4%) and rhinitis (4%).
The following undesirable effects, including those mentioned above, have been reported with the use of flunarizine in both clinical trials and post-marketing. Undesirable effects are listed by frequency using the following convention:
Very common ≥ 1/10
Common ≥ 1/100 to
Uncommon ≥ 1/1000 to
Rare ≥ 1/10000 y
Very rare
Not known (frequency cannot be estimated from the available data)
Very common:
- Weight gain.
Common:
- Rhinitis
- Increased appetite
- Depression, insomnia
- Drowsiness
- Constipation
- Upset stomach
- Nausea
- Myalgia
- Menstrual irregularities
- Breast pain
- Fatigue.
Uncommon:
- Depressive symptoms
- Sleep disorders
- Apathy
- Anxiety
- Coordination anomalies
- Disorientation
- Lethargy
- Paresthesia
- Restlessness
- Lack of energy
- Tinnitus
- Stiff neck
- Palpitations
- hypotension
- Intestinal obstruction
- Dry mouth
- Gastrointestinal disorders
- Hyperhidrosis
- Muscle spasms
- Muscle contractions
- Menorrhagia
- Menstrual disturbances
- Oligomenorrhea
- Breast hypertrophy
- Decreased libido
- Generalized edema
- Peripheral edema
- Asthenia.
Frequency not known:
- Akathisia
- Increased blood levels of hepatic transaminases
- Bradykinesia
- toothed wheel stiffness
- Dyskinesia
- Essential tremor
- Extrapyramidal disorders
- Parkinsonism
- Sedation
- Tremor
- Erythema
- Muscle stiffness
- Galactorrhea.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can 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.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The validity period is intended for the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package.
Keep this medicine out of the reach of children.
COMPOSITION
Each 5 mg hard capsule contains.
Active principle
flunarizine dihydrochloride 5.9 mg (corresponding to flunarizine 5 mg)
Excipients
Lactose, talc
Constituents of the capsule:
gelatin, titanium dioxide (E 171), iron oxide (E 172)
Each 10 mg hard capsule contains.
Active principle
11.8 mg flunarizine dihydrochloride (corresponding to 10 mg flunarizine)
Excipients
Lactose, talc
Capsule constituents: gelatin, titanium dioxide (E 171), iron oxide (E 172)
PHARMACEUTICAL FORM AND CONTENT
Stiff caps
Pack size of 20 - 30 - 50 hard capsules of 5 mg in blister packs
Pack size of 20 - 30 - 50 hard capsules of 10 mg in blister packs
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
FLUGERAL HARD CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
FLUGERAL - 10 mg hard capsules
Each hard capsule contains:
Flunarizine dihydrochloride 11.8 mg
(Equal to 10 mg of flunarizine base).
FLUGERAL - 5 mg hard capsules
Each hard capsule contains:
flunarizine dihydrochloride 5.9 mg
(equal to 5 mg of flunarizine base).
For excipients see 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsules.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
- Prophylactic treatment of migraine with frequent and severe attacks limited to patients who have not responded to other therapies or in whom these therapies have caused serious side effects.
04.2 Posology and method of administration
Migraine prophylaxis:
Attack therapy: in patients under the age of 65, treatment should be started at a dose of 10 mg per day to be taken at bedtime; in patients over 65 years of age this dose should be reduced to 5 mg.
If depression, extrapyramidal signs or other serious side effects appear during this phase of treatment, treatment should be discontinued.
If no significant improvement is observed after two months, patients should be considered refractory to therapy and drug administration discontinued.
Maintenance therapy: If the patient responds satisfactorily and if maintenance therapy is deemed necessary, the daily dose should be reduced and administered on alternate days or for 5 consecutive days with a two-day interruption each week.
Even if the prophylactic treatment is effective and well tolerated, it must be stopped after six months and can only be resumed in case of relapse.
04.3 Contraindications
Flunarizine is contraindicated in patients with:
- current depressive illness or a history of relapsing depression (see sections 4.4 and 4.8)
- pre-existing symptoms of Parkinson's disease or other extrapyramidal disorders (see sections 4.4 and 4.8)
- known hypersensitivity to flunarizine or to any of the excipients contained in the formulation.
04.4 Special warnings and appropriate precautions for use
Flunarizine can cause extrapyramidal and depressive symptoms and highlight parkinsonism, especially in elderly patients. Therefore it should be used with caution in such patients.
The recommended doses should not be exceeded. Patients should be evaluated at regular intervals, especially during maintenance therapy, so that extrapyramidal or depressive symptoms can be detected early and, if present, treatment can be stopped. This control must be particularly careful in elderly patients.
In rare cases, asthenia may progressively increase during flunarizine therapy. In these cases, therapy should be discontinued.
The possible loss of efficacy of the drug during the maintenance phase requires the suspension of the therapy (for the duration of the treatment see the item posology).
Keep out of reach of children.
Lactose
Flunarizine capsules contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
The concomitant intake of flunarizine with alcohol, hypnotics, tranquilizers or other psychotropic drugs can cause excessive sedation.
It is not recommended to drink alcoholic beverages during therapy.
The pharmacokinetics of flunarizine are not affected by topiramate.Following repeated dosing in migraine patients, the systemic exposure to flunarizine was increased by 14%. When flunarizine was administered concomitantly with topiramate 50 mg every 12 hours, administration of repeated doses resulted in a 16% increase. in systemic exposure to flunarizine. Steady state pharmacokinetics of topiramate are not affected by flunarizine.
Chronic administration of flunarizine does not alter the bioavailability of phenytoin, carbamazepine, valproate or phenobarbital. Plasma concentrations of flunarizine were generally lower in patients with epilepsy taking these anti-epileptic drugs compared to healthy subjects given similar doses. The plasma protein binding of carbamazepine, valproate and phenytoin is not affected by concomitant administration of flunarizine.
04.6 Pregnancy and lactation
Pregnancy
There are no data on the use of flunarizine in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid using flunarizine during pregnancy.
Feeding time
It is unknown whether flunarizine is excreted in human milk. Animal studies have documented the excretion of flunarizine in breast milk. A decision to discontinue breast-feeding or to continue / discontinue flunarizine therapy must be made taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
04.7 Effects on ability to drive and use machines
As somnolence may occur, especially at the initiation of treatment, caution should be exercised during activities such as driving vehicles or operating hazardous machinery.
04.8 Undesirable effects
The safety of flunarizine was evaluated in 247 flunarizine-treated subjects who participated in two placebo-controlled clinical trials in the treatment of dizziness and migraine, respectively, and in 476 flunarizine-treated subjects who participated in two controlled clinical trials with comparator in the treatment of dizziness and / or migraine. Based on the pooled safety data from these clinical trials, the most commonly reported undesirable effects (incidence ≥ 4%) were (% incidence): weight gain (11% ), sleepiness (9%), depression (5%), increased appetite (4%) and rhinitis (4%).
The following undesirable effects, including those mentioned above, have been reported with the use of flunarizine in both clinical trials and post-marketing. Undesirable effects are listed by frequency using the following convention:
Very common ≥ 1/10
Common ≥ 1/100 to
Uncommon ≥ 1/1000 to
Rare ≥ 1/10000 y
Very rare
Not known (frequency cannot be estimated from the available data)
* the elderly are particularly at risk.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. at the address: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Based on the pharmacological characteristics of the drug, sedation and asthenia are likely in case of overdose.
Acute overdose (up to 600 mg in one intake) has been reported and symptoms observed were sedation, agitation and tachycardia. Treatment of acute overdose consists of administration of activated charcoal, induction of vomiting or gastric lavage, and supportive measures. No specific antidote is known.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antivertigo preparation.
ATC code N07CA03.
Flunarizine is a bifluorinated derivative of cinnarizine with antihistamine and CNS depressant properties.
Flunarizine is a WHO class IV calcium antagonist; it has no effect on contractility and cardiac conduction.
Flunarizine also possesses a "neuroleptic type action which could be the cause of certain side effects on the central nervous system.
05.2 "Pharmacokinetic properties
In healthy volunteers, peak plasma is reached after 2-4 hours following oral administration of a single dose of Flunarizine. During chronic treatment, for administration of a daily dose of 10 mg, plasma concentrations gradually increase, until the steady state concentration is reached around the 5th-6th week of drug intake: at steady-state, plasma levels remain almost constant over a range between 39 and 115 ng / ml.
The pharmacokinetic parameters of Flunarizine are characterized by a large volume of distribution (apparent volume of distribution = 43.2 l / kg in healthy volunteers) and high tissue distribution.
In fact, from the results of animal experiments, it emerged that drug concentrations in various tissues are much higher than the corresponding plasma levels, especially in adipose tissue and skeletal muscles.
About 0.8% of Flunarizine is present in free plasma, as it binds 90% to plasma proteins and 9% to erythrocytes.
Only a negligible portion of the drug is excreted unchanged in the urine. After extensive hepatic metabolism (dealkylation - N-oxidative, aromatic hydroxylation and glucuronidation), flunarizine and its metabolites are excreted with the faeces via the bile.
In "humans" the mean terminal elimination half-life is about 18 days.
05.3 Preclinical safety data
Non-clinical data reveal no risk for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose, talc
Capsule constituents: pure gelatin containing E171 titanium dioxide and E 172 iron oxide.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
No special storage precautions.
06.5 Nature of the immediate packaging and contents of the package
Lithographed cardboard box containing 20 hard capsules of 5 mg in Al / PVC blisters
Lithographed cardboard box containing 30 hard capsules of 5 mg in Al / PVC blister
Lithographed cardboard box containing 50 hard capsules of 5 mg in Al / PVC blisters
Lithographed cardboard box containing 20 hard capsules of 10 mg in Al / PVC blisters
Lithographed cardboard box containing 30 hard capsules of 10 mg in Al / PVC blister
Lithographed cardboard box containing 50 hard capsules 10 mg in Al / PVC blister
06.6 Instructions for use and handling
07.0 MARKETING AUTHORIZATION HOLDER
FLUGERAL 5 mg hard capsules 20 capsules - cod. AIC 024414017
FLUGERAL 5 mg hard capsules 30 capsules - cod. AIC 024414029
FLUGERAL 5 mg hard capsules 50 capsules - cod. AIC 024414031
FLUGERAL 10 mg hard capsules 20 capsules - cod. AIC 024414043
FLUGERAL 10 mg hard capsules 30 capsules - cod. AIC 024414056
FLUGERAL 10 mg hard capsules 50 capsules - cod. AIC 024414068
08.0 MARKETING AUTHORIZATION NUMBER
FLUGERAL 5 mg hard capsules 20 capsules - cod. AIC 024414017
FLUGERAL 5 mg hard capsules 30 capsules - cod. AIC 024414029
FLUGERAL 5 mg hard capsules 50 capsules - cod. AIC 024414031
FLUGERAL 10 mg hard capsules 20 capsules - cod. AIC 024414043
FLUGERAL 10 mg hard capsules 30 capsules - cod. AIC 024414056
FLUGERAL 10 mg hard capsules 50 capsules - cod. AIC 024414068
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Authorization: 28/05/1981
Renewal: 01/06/2010
10.0 DATE OF REVISION OF THE TEXT
June 2015
