Package Leaflet

Chiaridoxina 2 mg tablets, 4 mg tablets

(doxazosin)
THERAPEUTIC PHARMACOLOGICAL CATEGORY
Cardiovascular, antihypertensive.
Urologicals: drug for the treatment of benign prostatic hyperplasia.
THERAPEUTIC INDICATIONS
CHIARIDOXINA (doxazosin) is indicated in the treatment of essential arterial hypertension.
CHIARIDOXINA is indicated in the treatment of clinical symptoms associated with benign prostatic hyperplasia (BPH).
CONTRAINDICATIONS
CHIARIDOXINA is contraindicated in the following cases:

in patients with known hypersensitivity to quinazolines (e.g. prazosin, terazosin, doxazosin), or to any of the excipients.
in patients with a history of orthostatic hypotension
in patients with benign prostatic hyperplasia (BPH) and concomitant upper urinary tract obstruction, chronic urinary tract infection, or bladder stones
during breastfeeding (see "Pregnancy and breastfeeding")
in patients with hypotension. Doxazosin as monotherapy is contraindicated in patients with overflow incontinence, or anuria with or without progressive renal failure.

PRECAUTIONS FOR USE
Use in patients with acute cardiac disorders: as with all vasodilating antihypertensive agents, it is good medical practice to pay particular attention when administering doxazosin to patients with the following acute cardiac disorders:

pulmonary edema due to aortic or mitral stenosis
high-output heart failure
right-sided 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 reduction in blood pressure may worsen angina.
Use in patients with hepatic impairment: as with all other drugs entirely metabolized by the liver, CHIARIDOXINA must be administered with particular caution to patients showing 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 doxazosin is administered concomitantly with drugs affecting hepatic metabolism (e.g. cimetidine). Doxazosin must be used with caution in patients with diabetic autonomic neuropathy.
Children
The use of doxazosin is not recommended in children under 12 years of age due to lack of safety and efficacy data.

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INTERACTIONS
Concomitant administration of doxazosin and a PDE-5 inhibitor may lead to symptomatic hypotension in some patients (see sections "Special Warnings" and "Precautions for Use"). No studies have been conducted with prolonged-release formulations of doxazosin.
Doxazosin is highly (98%) bound to plasma proteins. In vitro data from human plasma indicate that doxazosin does not interfere with the protein binding of digoxin, warfarin, phenytoin, or indomethacin.
Clinical experience has shown that administration of doxazosin in standard formulations does not result in any interaction with thiazide diuretics, furosemide, beta-blockers, non-steroidal anti-inflammatory drugs, antibiotics, oral hypoglycemics, uricosuric agents, or anticoagulants. However, data from formal drug-drug interaction studies are not available.
Doxazosin potentiates the blood pressure-lowering activity of other alpha-blockers and other antihypertensives. The hypotensive effect may be more pronounced when doxazosin is used concomitantly with vasodilators and nitrates.
Sympathomimetics reduce the hypotensive effect of doxazosin; doxazosin inhibits the action of dopamine, ephedrine, adrenaline, metaraminol, and phenylephrine on blood pressure and blood vessels.
In an open, randomized, placebo-controlled study in 22 healthy male volunteers, administration of a single 1 mg dose of doxazosin on day 1 in a 4-day dosing regimen with oral cimetidine (400 mg twice daily) resulted in a 10% increase in mean AUC of doxazosin and non-statistically significant changes in mean Cmax and half-life of doxazosin. The 10% increase in mean AUC of doxazosin with cimetidine falls within the inter-subject variability (27%) of mean AUC of doxazosin compared to placebo.
Doxazosin may affect plasma renin activity and urinary vanillylmandelic acid excretion. This should be taken into account when interpreting laboratory results.
Inform your doctor (or pharmacist) if you have recently taken any other medicine, including those without a prescription.
SPECIAL WARNINGS
Initiation of therapy: due to the alpha-blocking properties of doxazosin, patients may experience postural hypotension characterized by dizziness and weakness, or more rarely by loss of consciousness (syncope), especially at the beginning of treatment. Therefore, it is good medical practice to monitor blood pressure at the start of treatment to minimize possible postural effects. Patients should be advised to avoid situations that could lead to injury due to dizziness or weakness in the early stages of therapy with doxazosin.
Use with PDE-5 inhibitors: concomitant administration of doxazosin with phosphodiesterase-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) should be performed with caution, as both drugs have vasodilatory effects and may cause symptomatic hypotension in some patients. To reduce the risk of orthostatic hypotension, it is recommended to initiate treatment with the PDE-5 inhibitor only after the patient has been hemodynamically stabilized on alpha-blocker therapy. Furthermore, it is recommended to start treatment with PDE-5 inhibitors at the lowest possible dose and to maintain a 6-hour interval from doxazosin intake. No studies have been conducted with prolonged-release formulations of doxazosin.
Use in patients undergoing cataract surgery: during cataract surgery, some patients previously or currently treated with tamsulosin have experienced intraoperative floppy iris syndrome (IFIS – a variant of the small pupil syndrome). Isolated cases have been reported with other alpha-1 adrenergic antagonists, and a class effect cannot be excluded. Since IFIS may increase surgical complications during the procedure, the surgeon should be informed of current or previous treatment with alpha-1 adrenergic antagonists before surgery.
Patients are advised to inform their ophthalmologist about current or previous treatment with doxazosin before undergoing cataract surgery (lens opacity).
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Pregnancy and breastfeeding
Pregnancy
For the indication of hypertension:
the safety of doxazosin during pregnancy has not been established, as adequate and well-controlled studies in pregnant women have not been conducted. Therefore, this medicinal product should be used only if, in the physician's judgment, 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
Doxazosin is contraindicated during breastfeeding, as the drug accumulates in the milk of lactating rats and there is no information regarding excretion of the drug in human breast milk. Alternatively, mothers must discontinue breastfeeding if treatment with doxazosin is necessary.
For the indication of benign prostatic hyperplasia: this section does not apply.
Consult your doctor (or pharmacist) before taking any medicine.
Driving and use of machines
The ability to perform activities such as operating machinery and driving vehicles may be reduced, especially in the initial stages of treatment.
Important information about some excipients of CHIARIDOXINA
This medicine contains lactose: if you know you have an intolerance to certain sugars, consult your doctor before taking this medicine.
DOSAGE, METHOD AND TIME OF ADMINISTRATION
The tablets should be taken once daily (with sufficient water). The duration of treatment should be determined by the physician.
Arterial hypertension
The usual dose of CHIARIDOXINA is 1 to 8 mg per day. The maximum recommended dose is 16 mg per day.
The initial dose is 1 mg taken at bedtime (1/2 of a 2 mg tablet), and this dose should be maintained for one to two weeks. After this period, the dosage may be increased to 2 mg once daily and maintained for another one to two weeks. If necessary, the daily dosage may be gradually increased further, always after the same time interval, to 4, 8, and 16 mg once daily, according to the patient's response and under physician's guidance.
Benign prostatic hyperplasia
At the beginning of treatment with CHIARIDOXINA, the following dosing schedule is recommended:

Days 1 to 8: 1 mg daily (1/2 tablet of CHIARIDOXINA 2 mg)
Days 9 to 14: 2 mg daily (1 tablet of CHIARIDOXINA 2 mg)
Depending on urodynamic parameters and symptoms, under physician's guidance, this dose may be increased to 4 mg (1 tablet of CHIARIDOXINA 4 mg) and subsequently to the maximum recommended dose of 8 mg (2 tablets of CHIARIDOXINA 4 mg). The recommended interval between dose increases is 1 to 2 weeks. The usual recommended daily dose is 2–4 mg. CHIARIDOXINA should be taken as a single daily dose.

Elderly patients and patients with renal impairment:
the pharmacokinetics of doxazosin remain unchanged in elderly patients and in those with renal impairment. Furthermore, there is no evidence that doxazosin worsens pre-existing renal failure. Therefore, the usual dose is generally recommended. However, due to the possible occurrence of hypersensitivity in some of these patients, particular attention should be paid at the beginning of treatment.
Doxazosin 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 impairment (see Precautions for Use).
Children:
the use of doxazosin is not recommended in children under 12 years of age due to lack of efficacy data.
OVERDOSE
If overdose leads to hypotension, the patient should be immediately placed in a supine position with the head in a downward position. Other supportive measures should be taken according to the individual case.
Since doxazosin is highly bound to plasma proteins, dialysis is not indicated.
If the measures taken are insufficient, shock should initially be treated with a volume expander. Subsequently, if necessary, a vasopressor drug should be used. Renal function should be monitored and supported as needed.
In case of accidental ingestion/overdose of CHIARIDOXINA, contact your doctor immediately or go to the nearest hospital.
WHAT TO DO IF YOU FORGET TO TAKE ONE OR MORE DOSES
If administration of doxazosin is interrupted for several days, treatment should be resumed starting from the initial dose of 1 mg.
EFFECTS DUE TO TREATMENT DISCONTINUATION
If you have any doubts about the use of CHIARIDOXINA, consult your doctor (or pharmacist).
UNDESIRABLE EFFECTS
Like all medicines, CHIARIDOXINA can cause undesirable effects, although not everyone experiences them.
The following undesirable effects have been observed and reported during treatment with doxazosin 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 System and Organ
Infections and infestations
common Respiratory tract infections, urinary tract infections
Hematopoietic and lymphatic system disorders
very rare Leukopenia, thrombocytopenia
Immune system disorders
uncommon Drug allergy reaction
Metabolism and nutrition disorders
uncommon Gout, increased appetite, anorexia, hypokalemia, thirst
rare Hypoglycemia
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Psychiatric disorders
common Delayed ejaculation
uncommon Agitation, depression, anxiety, insomnia, nervousness, restless dreams, amnesia, emotional lability
Nervous system disorders
common Somnolence, dizziness, headache
uncommon Cerebrovascular stroke, hypoesthesia, syncope, tremor
very rare Postural-type dizziness, paresthesia
Eye disorders
common Visual accommodation disorders
uncommon Abnormal lacrimation, photophobia
rare Conjunctivitis
very rare Blurred vision
not known Intraoperative Floppy Iris Syndrome
Ear and labyrinth disorders
common Vertigo
uncommon Tinnitus
Cardiac disorders
common Palpitations, tachycardia, edema
uncommon Angina pectoris, myocardial infarction
very rare Bradycardia, cardiac arrhythmia
Vascular disorders
common Hypotension, postural hypotension
uncommon Peripheral ischemia
very rare Hot flushes
Respiratory, thoracic and mediastinal disorders
common Bronchitis, cough, dyspnea, rhinitis
uncommon Epistaxis, sore throat
rare Laryngeal edema
very rare Bronchospasm
Gastrointestinal disorders
common Abdominal pain, dyspepsia, dry mouth, nausea
uncommon Constipation, flatulence, vomiting, gastroenteritis, diarrhea
Hepatobiliary disorders
uncommon Abnormal liver function tests
very rare Cholestasis, hepatitis, jaundice
Skin and subcutaneous tissue disorders
common Pruritus
uncommon Skin rash
rare Sweating
very rare Urticaria, alopecia, purpura
Musculoskeletal and connective tissue disorders
common Back pain, myalgia
uncommon Arthralgia, muscle stiffness
rare Muscle cramps, muscle weakness
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Renal and urinary disorders
common Cystitis, urinary incontinence
uncommon Dysuria, frequent need to urinate, hematuria
rare Polyuria
very rare Increased diuresis, micturition disorders, nocturia
Reproductive system and breast disorders
uncommon Impotence
very rare Gynecomastia, priapism
not known Retrograde ejaculation
General disorders and administration site conditions
common Asthenia, chest pain, influenza-like symptoms, peripheral edema
uncommon Pain, facial edema, facial flushing, chills, fever, pallor, taste alteration
rare Decreased body temperature in the elderly
very rare Fatigue, malaise
Investigations
uncommon Weight gain
If any of the undesirable effects worsens, or if you notice any undesirable effect not listed in this leaflet, inform your doctor (or pharmacist).
EXPIRY DATE AND STORAGE
Do not use CHIARIDOXINA after the expiry date 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 must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.
COMPOSITION
CHIARIDOXINA 2 mg tablets
One tablet contains: doxazosin mesylate 2.43 mg (equivalent to 2 mg doxazosin base).
Excipients: Microcrystalline cellulose, lactose monohydrate, sodium glycolate starch, magnesium stearate, sodium lauryl sulfate.
CHIARIDOXINA 4 mg tablets
One tablet contains: doxazosin mesylate 4.85 mg (equivalent to 4 mg doxazosin base).
Excipients: Microcrystalline cellulose, lactose monohydrate, sodium glycolate starch, magnesium stearate, sodium lauryl sulfate.
PHARMACEUTICAL FORM AND CONTENT
Scored tablets.
Box containing 30 scored 2 mg tablets in blister.
Box containing 20 scored 4 mg tablets in blister.
MARKETING AUTHORIZATION HOLDER
DYMALIFE PHARMACEUTICAL S.R.L. - VIA BAGNULO 95, 80063 - PIANO DI SORRENTO - NAPOLI (NA).
MANUFACTURER AND FINAL CONTROLLER
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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 indication of hypertension
for the indication of benign prostatic hyperplasia
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