Package leaflet: Information for the patient

Gradient Polifarma 5 mg hard capsules, 10 mg hard capsules

Flunarizine dihydrochloride
Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Gradient Polifarma is and what it is used for
What you need to know before taking Gradient Polifarma
How to take Gradient Polifarma
Possible side effects
How to store Gradient Polifarma
Contents of the pack and other information

1. What Gradient Polifarma is and what it is used for

Gradient Polifarma contains flunarizine dihydrochloride, which belongs to a group of medicines that
relax blood vessels, allowing blood to flow more easily to the brain.
Gradient Polifarma is indicated in adults for the prevention of migraine (headache) occurring
with frequent and severe attacks.
Gradient Polifarma is used when other therapies have not been effective or have caused severe
adverse effects.
Contact your doctor if you do not feel better or if you feel worse.

2. What you need to know before taking Gradient Polifarma

Do not take Gradient Polifarma

if you are allergic to flunarizine dihydrochloride or to any of the other ingredients of this medicine (listed in section 6)
if you currently have or have previously had depression
if you suffer from symptoms of Parkinson's disease (a disease that impairs movement control, manifesting, for example, with tremors, muscle stiffness, and slowed movements)
if you suffer from extrapyramidal disorders (movement control disorders).

Warnings and precautions
Talk to your doctor or pharmacist before taking Gradient Polifarma.
During treatment, and especially during maintenance therapy:

you may experience serious adverse effects such as excessive tiredness, movement disorders, or depression. At the first signs of these symptoms, inform your doctor immediately (see section “Possible side effects”);
your doctor will regularly monitor you for the occurrence of serious adverse effects so that treatment can be promptly discontinued, especially if you are elderly (see section “Possible side effects”);
if your doctor observes no improvement or a loss of effect of this medicine, treatment interruption will be considered (see section “How to take Gradient Polifarma”).

Other medicines and Gradient Polifarma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Inform your doctor if you are taking the following medicines, as their concomitant administration with Gradient Polifarma may cause excessive sedation (physical and mental relaxation):

hypnotics (sleeping pills, substances that help sleep)
tranquillisers (medicines used to treat anxiety)
Inform your doctor if you are taking the following medicines, as their concomitant administration may affect Gradient Polifarma:
topiramate, phenytoin, carbamazepine, valproate, and phenobarbital (used to treat epilepsy)

Gradient Polifarma and alcohol
Avoid drinking alcoholic beverages during treatment with Gradient Polifarma, as concomitant administration of Gradient Polifarma with alcohol may cause excessive sedation (physical and mental relaxation).
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take this medicine during pregnancy or while breastfeeding, as safety of use has not been established during pregnancy and breastfeeding.
Driving and using machines
Exercise particular caution if you intend to drive or operate machinery or perform tasks requiring full alertness, as Gradient Polifarma, especially during the initial phase of treatment, may cause drowsiness.
Gradient Polifarma contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

3. How to take Gradient Polifarma

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Adults
Initial attack therapy
If you are under 65 years of age, the recommended starting dose is 10 mg daily (1 capsule of 10 mg or
2 capsules of 5 mg, according to your doctor's prescription), to be taken in the evening at bedtime.
Do not exceed the dose prescribed by your doctor.
Maintenance therapy
If your doctor considers that you have responded positively to the initial attack therapy, he/she will
prescribe maintenance therapy.
During maintenance therapy, your doctor will reduce the dose and instruct you to take this medicine
on alternate days for 5 consecutive days, with a break of two days each week; for example, on Monday,
Wednesday and Friday, with interruption on Saturday and Sunday.
Do not exceed the dose prescribed by your doctor.
Elderly patients
If you are over 65 years of age, the recommended starting dose is 5 mg daily (1 capsule of 5 mg). Do not exceed
the dose prescribed by your doctor.
Duration of treatment

The duration of the initial attack therapy is 2 months.
If, after 2 months from the start of treatment, your doctor considers that you have responded positively to the initial attack therapy, he/she will prescribe a 6-month maintenance therapy.
After 6 months of maintenance therapy, your doctor will discontinue treatment with Gradient Polifarma, even if you have responded positively to the treatment.
If during the 6-month maintenance therapy your doctor observes a loss of effect of this medicine or the occurrence of adverse reactions, he/she will evaluate whether to discontinue treatment with Gradient Polifarma.
Your doctor may restart treatment with Gradient Polifarma only in case of relapse.

If you take more Gradient Polifarma than you should
If you take an excessive dose of this medicine, inform your doctor immediately or go to the nearest
hospital, where appropriate medical care will be provided.
If you take an excessive dose of this medicine, you may experience the following symptoms:

sedation (physical and mental relaxation)
asthenia (weakness)
agitation
tachycardia (increased heart rate per minute).

Treatment
Your doctor will provide appropriate supportive therapy, including induction of vomiting, activated charcoal, gastric lavage, and other supportive measures to reduce symptoms.
There is no known specific antidote.
If you forget to take Gradient Polifarma
Do not take a double dose to make up for the missed capsule.
If you stop taking Gradient Polifarma
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
If you experience any of the following serious side effects while being treated with Gradient Polifarma, inform your doctor immediately, who will DISCONTINUE treatment with Gradient Polifarma:

progressive asthenia (excessive weakness)
depression, particularly in women who have previously suffered from depression (see "Do not take Gradient Polifarma")
extrapyramidal symptoms (movement control disorders; see "Do not take Gradient Polifarma"), such as:
- difficulty initiating a new body movement, resulting in slowed movement
- rigidity
- inability to remain still and/or sit still, with a constant urge to move
- uncontrollable movements of the mouth, tongue, and facial muscles
- tremors. These effects occur especially after prolonged treatment, particularly in elderly patients.

The side effects listed below are categorized according to their frequency of occurrence.
Very common (occurring in 1 out of 10 users):

weight gain

Common (occurring in 1 to 10 out of 100 users):

rhinitis (inflammation of the nasal cavities)
increased appetite
depression
insomnia
drowsiness
constipation
stomach discomfort
nausea
muscle pain
menstrual irregularities
breast pain
fatigue

Uncommon (occurring in 1 to 10 out of 1,000 users):

depressive symptoms
sleep disturbances
anxiety
apathy
movement coordination abnormalities
disorientation
lethargy (deep drowsiness)
tingling in arms, legs, or other body parts, numbness, sensations of heat or cold
restlessness
inertia (lack of energy)
tinnitus (ringing in the ears)
torticollis (stiff neck)
palpitations (awareness of increased heartbeat)
hypotension (low blood pressure)
intestinal obstruction
dry mouth
gastrointestinal disturbances (stomach ache or other digestive problems)
excessive sweating
muscle spasms and/or contractions
menorrhagia (abnormally heavy menstrual bleeding)
menstrual disorders (excessive increase in menstrual flow)
oligomenorrhea (infrequent or reduced menstrual flow)
excessive breast development (large breasts)
decreased sexual desire
swelling affecting hands and feet (peripheral edema) or multiple body parts (generalized edema)
asthenia (weakness, fatigue)

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

inability to sit still
pathological slowness of movement
cogwheel rigidity (when moving an arm, the elbow seems to move in jerks as if driven by a cogwheel)
abnormal, involuntary muscle movements
extrapyramidal disorders (rigidity, tremor) and parkinsonism
sedation
tremor
increased liver enzymes (transaminases), which may lead to abnormalities in certain clinical tests
erythema (skin irritation)
muscle rigidity
galactorrhea (abnormal milk secretion in women not breastfeeding)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You may also report side effects directly via the national reporting system at the following website: http://www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Gradient Polifarma

Keep this medicine out of the sight and reach of children.
5 mg capsule: store below 25°C.
10 mg capsule: this medicine requires no special storage conditions.
Do not use this medicine after the expiry date stated on the packaging after "Exp".
The expiry date refers to the last day of that month.
Do not use this medicine if you notice any changes in the colour of the capsule.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Gradient Polifarma contains
5 mg capsule

The active substance is: flunarizine dihydrochloride (1 capsule contains 5.9 mg of flunarizine dihydrochloride equivalent to 5 mg of flunarizine base)
The other components are: lactose (see section “Gradient Polifarma contains lactose”), maize starch, magnesium stearate, titanium dioxide, gelatin.

10 mg capsule

The active substance is: flunarizine dihydrochloride (1 capsule contains 11.8 mg of flunarizine dihydrochloride equivalent to 10 mg of flunarizine base)
The other components are: lactose (see section “Gradient Polifarma contains lactose”), maize starch, magnesium stearate, titanium dioxide, gelatin.

Description of the appearance of Gradient Polifarma and contents of the pack
Hard capsules
Gradient Polifarma 5 mg: carton containing 50 hard capsules packed in five blisters of 10
white, opaque capsules
Gradient Polifarma 10 mg: carton containing 50 hard capsules packed in five blisters of 10
white, opaque capsules.

Marketing Authorization Holder
POLIFARMA S.p.A.
Viale dell’Arte, 69
00144 Rome
Italy

Manufacturer
ISTITUTO DE ANGELI S.r.l.
Località Prulli n. 103/C
50066 Reggello (FI)
Italy