CHIARIDOXINA 2 mg Coated Tablet

Зміст інструкції

1. Chiaridoxina 2 mg tablets

Chiaridoxina 2 mg tablets

Chiaridoxina 4 mg tablets
(doxazosina)

PHARMACOTHERAPEUTIC CATEGORY
Cardiovascular, antihypertensive.
Urological: drug for the treatment of benign prostatic hyperplasia.

THERAPEUTIC INDICATIONS
CHIARIDOXINA (doxazosina) is indicated in the treatment of essential hypertension.
CHIARIDOXINA is indicated in the treatment of clinical symptoms associated with benign prostatic hyperplasia
(BPH).

CONTRAINDICATIONS
CHIARIDOXINA is contraindicated in the following cases:

• 1. in patients with known hypersensitivity to quinazolines (e.g. prazosin, terazosin, doxazosin), or to any of the excipients.
• 2. in patients with a history of orthostatic hypotension
• 3. in patients with benign prostatic hyperplasia (BPH) and concomitant upper urinary tract obstruction, chronic urinary tract infection or bladder stones
• 4. during breastfeeding (see “pregnancy and breastfeeding”)
• 5. in patients with hypotension Doxazosina in monotherapy is contraindicated in patients with overflow incontinence, or anuria with or without progressive renal insufficiency.

PRECAUTIONS FOR USE
Use in patients presenting with acute cardiac disorders: as with all vasodilating antihypertensive agents, it is
good medical practice to exercise particular caution when administering doxazosina to patients who
present with the following acute cardiac disorders:

• pulmonary edema resulting from aortic or mitral stenosis
• high-output heart failure
• right heart failure due to pulmonary embolism or pericardial effusion
• left ventricular heart failure with low filling pressure In patients with severe ischemic heart disease, a too rapid or pronounced decrease in blood pressure can lead to worsening of angina. Use in patients with hepatic impairment: as with all other drugs entirely metabolized by the liver, CHIARIDOXINA should be administered with particular caution to patients who present evidence of impaired liver function. Since clinical data are not available in patients with severe hepatic insufficiency, use in these patients is not recommended. Caution is also required when doxazosina is administered in conjunction with drugs that affect hepatic metabolism (e.g. cimetidine). Doxazosina should be used with caution in patients with diabetic autonomic neuropathy. Children The use of doxazosina is not recommended in children under 12 years of age due to a lack of safety and efficacy data.

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INTERACTIONS
The concomitant administration of doxazosina and a PDE-5 inhibitor may result in symptomatic hypotension
in some patients (see sections “special warnings” and “precautions for use”). No
studies have been conducted with the prolonged-release formulations of doxazosina.
Doxazosina is largely (98%) bound to plasma proteins. In vitrodata on human plasma indicate
that doxazosina does not interfere with the protein binding of digoxin, warfarin, phenytoin or indometacin.
Clinical experience has shown that the administration of doxazosina in standard formulations does not
involve any interaction with thiazide diuretics, furosemide, beta-blockers, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycemic agents, uricosuric agents and anticoagulants. However, data derived from formal drug-drug interaction studies are not
available.
Doxazosina potentiates the blood pressure lowering activity of other alpha-blockers and other
antihypertensives. The hypotensive effect may be more intense if doxazosina is used in conjunction with vasodilating drugs and nitrates.
Sympathomimetics reduce the hypotensive effect of doxazosina; doxazosina inhibits the action of dopamine,
ephedrine, adrenaline, metaraminol and phenylephrine on blood pressure and blood vessels.
In an open-label, randomized, placebo-controlled study, in 22 healthy male volunteers, the
administration of a single dose of 1 mg of doxazosina on day 1 in a dosing regimen
lasting 4 days with oral cimetidine (400 mg twice a day), led to a 10% increase in
the average AUC of doxazosina and non-statistically significant changes in the average Cmax and
the average half-life of doxazosina. The 10% increase in the average AUC of doxazosina with cimetidine is
within the inter-subject variability (27%) of the average AUC of doxazosina compared to placebo.
Doxazosina may affect the activity of plasma renin and the secretion of vanilmandelic acid
through urine. This must be taken into account when interpreting laboratory results.
Inform your doctor (or pharmacist) if you have recently taken any other medicines, even those
available without a prescription.

SPECIAL WARNINGS
Start of therapy: in relation to the alpha-blocking properties of doxazosina, patients may experience
postural hypotension characterized by dizziness and weakness or, more rarely, loss of consciousness
(syncope), especially at the beginning of treatment. Therefore, it is good medical practice to check blood
pressure at the beginning of treatment to minimize possible postural effects. The patient should be
advised to avoid situations that may result in injury due to dizziness or weakness in the early
stages of doxazosina therapy.
Use with PDE-5 inhibitors: the concomitant administration of doxazosina with phosphodiesterase-5 (PDE-5) inhibitors (e.g. sildenafil, tadalafil and vardenafil) should be carried out with caution as both
medicines have vasodilating effects and may cause symptomatic hypotension in some patients. To
reduce the risk of orthostatic hypotension, it is recommended to start treatment with the PDE-5
inhibitor only if the patient is hemodynamically stabilized with alpha-blocker therapy. It is also
recommended to start treatment with PDE-5 inhibitors with the lowest possible dose and to
respect the interval of 6 hours from taking doxazosina. No studies have been conducted with
the prolonged-release formulations of doxazosina.
Use in patients undergoing cataract surgery: during cataract surgery, some patients, previously treated or undergoing treatment with tamsulosin, have developed
iris floppy syndrome (IFIS - Intraoperative Floppy Iris Syndrome, a variant of the small pupil syndrome). Isolated cases have occurred with other alpha-1 adrenergic antagonists and the possibility of a class effect cannot be excluded. Since IFIS may increase surgical complications during
surgery, the surgeon should be aware of ongoing or previous treatment with alpha-1-adrenergic antagonists.
It is recommended to inform your ophthalmologist of ongoing or previous treatment with doxazosina before
undergoing cataract surgery (clouding of the lens).
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Pregnancy and breastfeeding

Pregnancy
For the indication of hypertension:
the safety of doxazosina during pregnancy has not been established as adequate or well-controlled studies on pregnant women have not been conducted. Therefore, this medicine should be used only if,
in the opinion of the doctor, the potential benefits outweigh the possible risks. Although teratogenic effects have not been observed in animal studies, reduced
fetal survival has been observed in animals at very high doses.

Breastfeeding
Doxazosina is contraindicated during breastfeeding as the drug accumulates in the milk of lactating rats
and there is no information on the excretion of the drug in the milk of breastfeeding women. Alternatively, mothers should discontinue breastfeeding if treatment with doxazosina is
necessary.
For the indication of benign prostatic hyperplasia: this section is not applicable.
Ask your doctor (or pharmacist) for advice before taking any medicine.
Driving and using machines
The ability to engage in activities such as using machinery and driving vehicles may be reduced,
especially in the early stages of treatment.
Important information about some excipients of CHIARIDOXINA
This medicine contains lactose: if the patient is aware of suffering from intolerance to any
sugar, they should consult a doctor before taking this medicine.

DOSAGE, METHOD AND TIME OF ADMINISTRATION
The tablets should be taken in a single daily dose (with sufficient
water). The duration of treatment must be established by the doctor.

Arterial hypertension
The usual dose of CHIARIDOXINA is from 1 to 8 mg per day. The maximum recommended dose is 16
mg per day.
The initial dose is 1 mg before bedtime (1/2 2 mg tablet) and this dose should be maintained
for one to two weeks of treatment. After this period the dosage may be increased to 2 mg once
a day and maintained for another one to two weeks. If necessary, the daily dosage may be
further gradually increased, always after the same time interval, to 4, 8 and 16 mg once
a day, according to the patient's response as directed by the treating physician.

Benign prostatic hyperplasia
At the beginning of treatment with CHIARIDOXINA, the following dosing regimen is recommended:

• days 1 to 8:1 mg per day (1/2 CHIARIDOXINA 2 mg tablet)
• days 9 to 14:2 mg per day (1 CHIARIDOXINA 2 mg tablet) Based on urodynamic parameters and symptoms, as directed by the treating physician, this dose may be increased to 4 mg (1 CHIARIDOXINA 4 mg tablet) and subsequently to the maximum recommended dose of 8 mg (2 CHIARIDOXINA 4 mg tablets). The recommended time interval between successive dose increases is 1 to 2 weeks. The usual recommended daily dose is 2 - 4 mg. CHIARIDOXINA should be used in a single daily dose.

Elderly patients and patients with renal impairment:
the pharmacokinetics of doxazosina remain unchanged in elderly patients and those with renal impairment.
Furthermore, there is no evidence that doxazosina exacerbates pre-existing renal insufficiency. Therefore, the usual dose is generally recommended. However, due to the possible occurrence of hypersensitivity in
some of these patients, particular caution is necessary at the beginning of treatment.
Doxazosina is not dialyzable.
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Patients with hepatic impairment:
the dosage should be increased with particular caution in patients with hepatic impairment. No
clinical experience is available in patients with severe hepatic insufficiency (see precautions for
use).
Children:
the use of doxazosina is not recommended in children under 12 years of age due to a lack of efficacy data.

OVERDOSAGE
If overdose leads to hypotension, the patient should be immediately placed supine with the
head in a downward position. Other supportive measures should be taken in relation to the individual case.
Since doxazosina is highly bound to plasma proteins, dialysis is not indicated.
If the measure taken is not sufficient, shock should initially be treated with a volume expander.
If necessary, a vasopressor drug should then be used. Renal function should
be monitored and supported as needed.
In case of accidental ingestion/intake of an excessive dose of CHIARIDOXINA, immediately warn
your doctor or go to the nearest hospital.

WHAT TO DO IF YOU FORGET TO TAKE ONE OR MORE DOSES
If you stop taking doxazosina for a few days, resuming treatment should be done
starting from the initial dose of 1 mg.

EFFECTS DUE TO DISCONTINUATION OF TREATMENT
If you have any doubts about the use of CHIARIDOXINA, consult your doctor (or pharmacist).

UNDESIRABLE EFFECTS
Like all medicines, CHIARIDOXINA can cause side effects, although not everyone will
experience them.
The following undesirable effects have been observed and reported during treatment with doxazosina with the
following frequencies:
very common (≥1/10);
common (≥1/100 to <1/10);
uncommon (≥1/1.000 to <1/100);
rare (≥1/10.000 to <1/1.000);
very rare (<1/10.000).

Classification by Systems and Organs
Infections and infestations

commonRespiratory tract infections, urinary tract infections

Blood and lymphatic system disorders

very rareLeukopenia, thrombocytopenia

Immune system disorders

uncommonDrug allergic reaction

Metabolism and nutrition disorders

uncommonGout, increased appetite, anorexia, hypokalemia, heartburn

rareHypoglycemia
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Psychiatric disorders

commonDelayed ejaculation

uncommonAgitation, depression, anxiety, insomnia, nervousness, restless dreams, amnesia, emotional lability

Nervous system disorders

commonDrowsiness, dizziness, headache

uncommonCerebrovascular stroke, hypoesthesia, syncope, tremor

very rarePostural dizziness, paresthesia

Eye disorders

commonVisual accommodation disorders

uncommonAbnormal lacrimation, photophobia

rareConjunctivitis

very rareBlurred vision

not knownIris flag syndrome

Ear and labyrinth disorders

CommonVertigo

uncommonTinnitus

Cardiac disorders

commonPalpitations, tachycardia, edema

uncommonAngina pectoris, myocardial infarction

very rareBradycardia, cardiac arrhythmia

Vascular disorders

commonHypotension, postural hypotension

uncommonPeripheral ischemia

very rareHot flashes

Respiratory, thoracic and mediastinal disorders

commonBronchitis, cough, dyspnea, rhinitis

uncommonEpistaxis, sore throat

rareLaryngeal edema

very rareBronchospasm

Gastrointestinal disorders

CommonAbdominal pain, dyspepsia, dry mouth, nausea

uncommonConstipation, flatulence, vomiting, gastroenteritis, diarrhea

Hepatobiliary disorders

uncommonAbnormal liver function test results

very rareCholestasis, hepatitis, jaundice

Skin and subcutaneous tissue disorders

commonPruritus

uncommonSkin rash

rareSweating

very rareUrticaria, alopecia, purpura

Musculoskeletal and connective tissue disorders

commonBack pain, myalgia

uncommonArthralgia, muscle rigidity

rareMuscle cramps, muscle weakness
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Renal and urinary disorders

commonCystitis, urinary incontinence

uncommonDysuria, frequent urination, hematuria

rarePolyuria

very rareIncreased diuresis, urination disorders, nocturia

Reproductive system and breast disorders

uncommonImpotence

very rareGynecomastia, priapism

not knownRetrograde ejaculation

Systemic disorders and conditions related to the site of administration

commonAsthenia, chest pain, flu-like symptoms, peripheral edema

uncommonPain, facial edema, flushing, chills, fever, pallor, taste alteration

rareReduction of body temperature in the elderly

very rareFatigue, malaise

Laboratory tests

uncommonWeight gain
If any of these side effects become severe, or if you notice any side effect not listed in this leaflet

EXPIRY DATE AND STORAGE
Do not use CHIARIDOXINA after the expiry date which is stated on the packaging.
The expiry date refers to the last day of the month.
The medicine does not require any special storage precautions.

Keep CHIARIDOXINA out of the reach and sight of children
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

COMPOSITION
CHIARIDOXINA 2 mg tablets
Each tablet contains: doxazosine mesylate 2.43 mg (equivalent to doxazosine base 2 mg).

Excipients:Microcrystalline cellulose, lactose monohydrate, sodium glycolate starch, magnesium stearate, sodium
lauryl sulfate.
CHIARIDOXINA 4 mg tablets
Each tablet contains: doxazosine mesylate 4.85 mg (equivalent to doxazosine base 4 mg).

Excipients:Microcrystalline cellulose, lactose monohydrate, sodium glycolate starch, magnesium stearate, sodium
lauryl sulfate.

PHARMACEUTICAL FORM AND CONTENT
Divisible tablets.
Pack containing 30 divisible tablets of 2 mg in blisters.
Pack containing 20 divisible tablets of 4 mg in blisters.

MARKETING AUTHORISATION HOLDER
DYMALIFE PHARMACEUTICAL S.R.L.- VIA BAGNULO 95, 80063 - PIANO DI SORRENTO -
NAPLES (NA).

MANUFACTURER AND FINAL CONTROL
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Doppel Farmaceutici S.r.l.
Via Volturno, 48
20089 Quinto de’ Stampi - Rozzano (Milan)

REVISION OF THE PACKAGE LEAFLET BY THE ITALIAN MEDICINES AGENCY
March 2012
only for the hypertension indication
for the benign prostatic hyperplasia indication
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