Spiridazide

Patient Information Leaflet

Spiridazide 25 mg + 25 mg Hard Capsules

spironolactone + hydrochlorothiazide
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, as it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Spiridazide is and what it is used for
2. What you need to know before taking Spiridazide
3. How to take Spiridazide
4. Possible side effects
5. How to store Spiridazide
6. Contents of the pack and other information

1. What Spiridazide is and what it is used for

Spiridazide contains spironolactone and hydrochlorothiazide, two substances that belong to a group of medicines called "diuretics", which help the body eliminate excess water through urine.
This medicine is prescribed to help remove fluid that tends to accumulate when the body produces excessive amounts of the hormone aldosterone. This condition, called hyperaldosteronism, may occur in the following diseases:

• Congestive heart failure – a disease that may initially present with swelling of the ankles, legs and abdomen, accompanied by fatigue and shortness of breath. This happens when the heart has to pump a larger volume of fluid, causing it to work harder and weaken. By removing excess fluid, the heart will have a reduced workload;
• Nephrotic syndrome – a kidney disease that causes swelling around the eyes, or in the abdomen, hands and legs due to excess fluid in the body;
• Hepatic cirrhosis with ascites – a severe liver disease whose most common complication is the accumulation of fluid in the abdomen. If you have any of these conditions, Spiridazide will help your body eliminate excess fluid.

2. What you should know before taking Spiridazide

Do not take Spiridazide

• if you are allergic to the active substances, to similar substances (other thiazides or sulfonamides), or to any of the other ingredients of this medicine (listed in section 6);
• if you are not producing urine (anuria);
• if you have severe kidney disease (acute renal failure) or conditions that impair the normal filtering function of the kidneys;
• if you have excess potassium in the blood (which may result from the body's inability to excrete potassium through the kidneys, as in Addison's disease);
• if you have severe liver disease (severe hepatic insufficiency);
• if you have excess calcium in the blood;
• if you are undergoing treatment to supplement potassium deficiency, either through medication or a potassium-rich diet.

Warnings and precautions
Talk to your doctor or pharmacist before taking Spiridazide:

• if you have previously had skin cancer or develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from exposure to sunlight and UV rays while taking Spiridazide.
• if you have previously experienced breathing or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe difficulty breathing after taking Spiridazide, consult a doctor immediately. Concomitant administration of Spiridazide with certain medicines, potassium supplements, or potassium-rich foods may cause severe hyperkalemia (increased potassium levels in the blood). Symptoms of severe hyperkalemia may include muscle cramps, irregular heartbeat, diarrhea, nausea, dizziness, or headache.

Consult your doctor and be cautious:

• that your diet is not excessively rich in potassium and does not include potassium salt supplements, as this medicine may increase blood potassium levels;
• if you experience dry mouth, thirst, profound fatigue (asthenia), drowsiness, restlessness, muscle cramps, low blood pressure, reduced urine output (oliguria), rapid heartbeat (tachycardia), or gastrointestinal disturbances. In such cases, consult your doctor, as these may indicate altered levels of certain salts in your blood (potassium, sodium, calcium, nitrogen, phosphate, iodine, ammonia, uric acid), and taking this medicine may further affect the levels of these substances, known as electrolytes, in your blood and urine (see also section “Possible side effects”). Your doctor will regularly monitor your health and may prescribe blood and urine tests during treatment with Spiridazide, especially if you are elderly or experience persistent vomiting during treatment;
• if you have an allergic condition called "systemic lupus erythematosus," as the hydrochlorothiazide contained in this medicine may worsen the symptoms of the disease (see also section “Possible side effects”);
• if you are diabetic, because this medicine may increase blood glucose levels (see also section “Possible side effects”);
• if you are scheduled for surgery or a diagnostic procedure requiring local or general anesthesia. Inform the anesthesiologist that you are taking this medicine;
• if you are allergic to the class of medicines known as "sulfonamides," to which hydrochlorothiazide belongs, or to penicillins (a type of antibiotic), as you may have an increased risk of developing serious eye problems during treatment with Spiridazide (e.g., acute myopia or acute angle-closure glaucoma);
• if you experience decreased vision or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased intraocular pressure and may occur from a few hours to several weeks after taking Spiridazide. If left untreated, this may lead to permanent vision loss. If you have previously had an allergy to penicillin or sulfonamides, your risk of developing these complications may be higher.

Prolonged use of high doses of spironolactone (one of the active substances in Spiridazide) may cause breast gland development in men (gynecomastia). This condition is usually reversible when treatment with Spiridazide is discontinued (see also section “Possible side effects”).
In patients who have undergone sympathectomy (a surgical procedure aimed at interrupting stimuli from the peripheral nervous system in a specific arterial region to improve blood flow), the blood pressure-lowering effects of Spiridazide may be enhanced.

Other medicines and Spiridazide
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Inform your doctor if you are using abiraterone for the treatment of prostate cancer.
In particular, consult your doctor before taking:

• other diuretics or other aldosterone antagonists;
• ACE inhibitors, angiotensin II receptor antagonists: medicines primarily used to treat high blood pressure;
• non-steroidal anti-inflammatory drugs ( NSAIDs ), such as indomethacin;
• medicines used to prevent blood clotting, such as heparin;
• potassium-containing dietary supplements;
• potassium-containing salt substitutes;
• any other medicine that may increase potassium levels in the blood;
• trimethoprim and trimethoprim-sulfamethoxazole.

Taking this medicine together with the above-mentioned potassium-containing medicines or potassium sources may cause a dangerous increase in blood potassium levels.
Other known interactions with Spiridazide are listed below:

• corticosteroids (hormones used mainly as anti-inflammatory agents) and adrenocorticotropic hormone (ACTH): concomitant use with this medicine may cause a decrease in blood potassium levels;
• insulin: this medicine may alter the response to diabetes medications, including insulin. In such cases, your doctor may need to adjust the doses of your medications;
• lithium-containing medicines: this medicine may lead to increased lithium levels in the blood and potentially toxic reactions when taken together with lithium-containing medicines (used to treat mood disorders such as depression);
• anesthetics: this medicine may alter the body's response to anesthetic drugs (used for local or general anesthesia). Concomitant use with anesthetics or sedative medicines (barbiturates) may also increase the risk of sudden drops in blood pressure upon rapid change from a sitting or lying position to an upright position;
• non-steroidal anti-inflammatory drugs (NSAIDs): the effectiveness of this medicine may be reduced by concomitant administration of NSAIDs; therefore, your doctor should verify that the desired therapeutic effect is achieved;
• digoxin: concomitant use with this medicine may lead to increased digoxin levels in the blood and potentially toxic reactions, and may also interfere with radioimmunoassay measurements of digoxin;
• antihypertensive or blood pressure-lowering medicines: this medicine may enhance the effect of drugs used to lower blood pressure. If you are taking such medicines, your doctor may reduce their dosage.

Spiridazide and alcohol
Alcohol consumption during treatment with this medicine should be avoided, as it may increase the risk of sudden drops in blood pressure upon rapid change from a sitting or lying position to an upright position.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Spiridazide is not recommended during pregnancy and MUST NOT be taken if you are more than 3 months pregnant, as it may cause serious harm to the baby if taken after the third month of pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. This medicine is not recommended for women who are breastfeeding, and your doctor may choose an alternative treatment if you wish to breastfeed.

Driving and using machines
Spiridazide may moderately affect the ability to drive or operate machinery, as it may cause drowsiness or dizziness.

For athletes: Using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

3. How to take Spiridazide

Take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
The recommended dose is:
Treatment of congestive heart failure
The recommended dose is 1 capsule 3 - 4 times daily.
Treatment of ascites and edema in patients with hepatic cirrhosis
The recommended dose is 1 capsule 4 times daily.
Your doctor will adjust the dose and duration of treatment according to the progression of your illness.
If you take more Spiridazide than you should
If you take a higher dose than prescribed by your doctor, contact your doctor immediately
or go to the nearest hospital.
In case of overdose, your blood pressure may drop too low.
The most common symptoms caused by an overdose are drowsiness, mental confusion, skin rash,
nausea, vomiting, dizziness, or diarrhea. Changes in the levels of certain electrolytes in your blood may also occur (for example, reduced sodium levels, decreased or increased potassium levels, or increased nitrogen levels), especially in patients with kidney problems.
In cases of severe overdose, hepatic coma has rarely been observed in patients with serious liver disease. Cases of lethargy or coma have also occurred.
If you forget to take Spiridazide
Do not take a double dose to make up for the missed capsule.
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 everybody gets them.
The following side effects are important and require immediate attention if they occur. Stop taking
this medicine and contact your doctor immediately if you experience any of the following symptoms:

• difficulty swallowing or breathing, shortness of breath, swelling of the lips, face, throat or tongue. These may be symptoms of a severe allergic reaction (anaphylactic reactions);
• skin changes such as hives, appearance of red papules or widespread blisters and peeling, particularly on legs, arms, hands and feet, sometimes extending to the face and lips, occasionally accompanied by fever. These may be symptoms of serious diseases such as erythema multiforme, toxic epidermal necrolysis, necrotizing vasculitis and cutaneous lupus erythematosus, which may very rarely occur;
• worsening or reactivation of the autoimmune disease called systemic lupus erythematosus.

Other possible side effects may include:
Very common (may affect more than 1 in 10 people)

• decrease in blood potassium levels (hypokalaemia);
• increase in cholesterol and triglycerides in the blood.

Common (may affect up to 1 in 10 people)

• increased levels of uric acid in the blood (hyperuricaemia), decreased levels of magnesium or sodium in the blood (hypomagnesaemia and hyponatraemia);
• sudden drop in blood pressure upon rapidly changing from a sitting or lying position to standing (orthostatic hypotension);
• loss of appetite, nausea, vomiting;
• difficulty achieving or maintaining an erection suitable for sexual intercourse (impotence).

Rare (may affect up to 1 in 1,000 people)

• decrease in the number of blood cells called platelets (thrombocytopenia), sometimes associated with minor skin bleeding appearing as red-purple spots (purpura);
• increased levels of calcium or glucose in the blood (hypercalcaemia and hyperglycaemia), worsening of disease status in diabetic patients;
• depression, sleep disorders;
• dizziness, headache;
• altered sensation in limbs or other body parts (paraesthesia);
• vision problems;
• changes in heart rhythm (cardiac arrhythmias);
• abdominal discomfort, constipation, diarrhoea;
• obstruction of the liver's bile ducts (intrahepatic cholestasis), yellowing of the skin and whites of the eyes (jaundice);
• abnormal and exaggerated skin reaction, becoming particularly sensitive, upon exposure to sunlight (photosensitivity reactions);
• presence of sugar in the urine (glycosuria).

Very rare (may affect up to 1 in 10,000 people)

• severe reduction in the number of white blood cells in the blood (agranulocytosis), reduction in the number of other blood cell types (haemolytic anaemia, leucopenia and general bone marrow suppression);
• a condition characterized by an increase in blood pH (hypochloraemic alkalosis);
• respiratory failure caused by various types of damage (including pneumonia and pulmonary oedema);
• inflammation of the pancreas (pancreatitis);
• acute respiratory distress (signs include severe shortness of breath, fever, weakness and confusion).

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

• inadequate production by the bone marrow of all types of blood cells (aplastic anaemia);
• reduced vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma);
• eye problems (acute myopia, xanthopsia);
• skin disease characterized by lesions due to infection or allergic reaction (erythema multiforme);
• sudden, involuntary muscle contractions (muscle spasms);
• kidney problems (renal dysfunction, acute renal failure);
• decreased muscle strength (asthenia);
• fever;
• bleeding or inflammation of the stomach lining (ulcer, gastritis), diarrhoea, stomach cramps, nausea and vomiting;
• changes in levels of certain salts in the blood (electrolyte imbalance);
• changes in kidney function;
• development of breast tissue in men (gynaecomastia), erectile dysfunction, menstrual irregularities or absence of menstruation (amenorrhoea), episodes of bleeding during menopause, mild androgenic effects;
• breast cancer (in these cases, a definite link with spironolactone use has not been established);
• skin and lip cancer (non-melanoma skin cancer);
• mental confusion, loss of muscle coordination (ataxia), drowsiness, tendency towards prolonged drowsiness (lethargy);
• liver intoxication (very rare cases);
• bullous pemphigoid (a condition characterized by the appearance of fluid-filled blisters on the skin).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
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.

5. How to store Spiridazide

This medicine does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Expiry".
The expiry date refers to the last day of that month.
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 Spiridazide contains

• The active substances are spironolactone and hydrochlorothiazide. Each hard capsule contains 25 mg of spironolactone and 25 mg of hydrochlorothiazide.
• The other components are: Capsule contents: maize starch, magnesium stearate. Capsule shell: indigo carmine (E132), titanium dioxide (E171) and gelatin.

Description of the appearance of Spiridazide and package contents
Spiridazide 25 mg + 25 mg hard capsules are supplied in a box containing 20 hard capsules in blisters of transparent PVC/aluminum.
Marketing Authorisation Holder and Manufacturer
Laboratorio Farmaceutico SIT S.r.l. - Via Cavour, 70 – 27035 Mede (PV)