Zaroxolyn - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Metolazone

ZAROXOLYN 5 mg tablets
ZAROXOLYN 10 mg tablets

Why is Zaroxolyn used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Diuretics with minor diuretic action, not associated.

THERAPEUTIC INDICATIONS

Zaroxolyn is indicated in the treatment of hypertension alone or, in more severe forms, in combination with other antihypertensive drugs.

Zaroxolyn is also indicated as a diuretic, in all cases of water-saline retention.

Contraindications When Zaroxolyn should not be used

Hypersensitivity to the active substance or to any of the excipients. Severe hepatic and renal insufficiency. Refractory hypokalaemia, symptomatic hyperuricemia, Addison's disease.

Precautions for use What you need to know before taking Zaroxolyn

Electrolyte imbalances

The product should be administered with caution in case of hypokalaemia, hyponatremia, hypercalcemia and hypochloraemic alkalosis.

Determinations of serum electrolytes (sodium, potassium, chlorine, calcium), in order to detect possible imbalances, must be carried out at regular intervals. These checks are particularly important if the patient vomits excessively or is treated with fluids by parenteral route. BUN, blood sugar and blood glucose should also be periodically monitored during diuretic therapy.

All patients treated with Zaroxolyn should be observed in order to detect clinical signs of water-saline balance imbalances (hypokalemia, hyponatremia, hypochloraemic alkalosis). Some therapies, such as digitalis, can also be influenced by the effects of the diuretic on serum electrolytes.

The first signs of electrolyte imbalance, regardless of the cause, are: dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle aches or cramps, muscle fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances (nausea, vomiting, etc. ).

In case of hypokalaemia, a supplementary intake of potassium or the administration of a potassium-sparing drug is indicated. Hypokalaemia may occur more often when diuretic therapy has been intense and prolonged, with concomitant steroid or ACTH therapy, and with inadequate salt intake.

Patients with hyperuricemia and hyperglycemia

Caution should be exercised in these patients. Hyperglycemia and glycosuria may occur in subjects with latent diabetes. In diabetic patients Zaroxolyn can interfere with antidiabetic therapy.

Hepatic or renal insufficiency

In liver failure, diuretic-induced hypokalemia can precipitate encephalopathy.

Caution should be exercised when administering Zaroxolyn to patients with impaired renal function. Since most of the drug is excreted through the kidneys, the plasma levels of this drug may increase under such conditions.

Other situations

A chloride deficiency and hypochloraemic alkalosis may occur. Hyposaline syndrome may occur in patients with conspicuous edema associated with heart failure or renal insufficiency; a warm climate and a hyposaline diet can contribute to this.

Marked diuresis can lead to acute hypotension.

Interactions Which drugs or foods can modify the effect of Zaroxolyn

Combining Zaroxolyn with the following drugs requires special precautions or dosage adjustment:

  • Diuretics: increased risk of hypokalemia; the administration of metolazone with furosemide causes profuse diuresis which must be carefully followed.
  • Other Antihypertensives: increased hypotensive effect; adequate monitoring of blood pressure is required, especially in the initial phase, in order to promptly modify doses, if indicated.
  • Barbiturates and opioid analgesics: increased hypotensive effect.
  • Ciclosporin: increase in serum creatinine, when combined with metolazone
  • Captopril: deterioration of kidney function, which improves with discontinuation of metolazone.
  • Digitalis: increased toxicity with risk of serious arrhythmias, particularly in case of hypokalaemia
  • Corticosteroids and ACTH: increased risk of hypokalaemia and water-saline retention.
  • Lithium: the elimination of lithium is reduced with an increase in its plasma concentrations and a risk of toxicity.
  • Neuromuscular blockers: increased neuromuscular blocking effect with respiratory depression up to apnea; therefore Zaroxolyn must be discontinued at least 3 days before surgery.
  • Non-steroidal anti-inflammatory drugs (NSAIDs): increased risk of NSAID nephrotoxicity. NSAIDs may attenuate the antihypertensive effect of Zaroxolyn.
  • Sympathomimetics: metolazone may decrease the response to norepinephrine, without however preventing its efficacy as a pressure agent
  • Antidiabetics: reduction of the hypoglycemic effect. The need for an increase in the dose of hypoglycemic agents should be considered.
  • Anticoagulants: increased bleeding time has been observed with warfarin.Zaroxolyn, like thiazide diuretics, can modify the hypoprothrombinemic response, hence the need to adjust the dose. Alcohol may increase the hypotensive effect of metolazone.

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those without a prescription.

Warnings It is important to know that:

As with other diuretics, higher doses can produce marked changes in plasma potassium, uric acid, glucose and lipids.

Hypokalemia may occur, with consequent phenomena of asthenia, cramps and cardiac arrhythmias. Hypokalaemia is particularly dangerous in patients treated with digitalis, as it can cause life-threatening or life-threatening arrhythmias.

"Azotemia and" hyperuricaemia may be induced or aggravated by administration of Zaroxolyn (rare cases of gouty attacks have been reported in subjects with a history of gout). If azotemia and oliguria worsen during treatment of patients with renal insufficiency, Zaroxolyn should be discontinued. When Zaroxolyn and furosemide are administered simultaneously, remarkable and protracted results can be had in urinary hydroelectrolytic excretion; it is therefore recommended that the concomitant administration of these diuretics for the treatment of resistant edema is initiated in a hospital setting in order to provide adequate monitoring. In the event that Zaroxolyn is used together with other antihypertensive drugs, particular attention should be paid especially in the early stages of therapy. The posology of other antihypertensive agents should be suitably reduced. Zaroxolyn can be administered, when indicated, together with a potassium-sparing diuretic. In this case the diuresis could be enhanced and the dosage should be reduced.

Potassium retention and hyperkalaemia could occur: kalaemia should be determined frequently.

An additional potassium intake is contraindicated when a potassium sparing diuretic is administered.

For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.

PREGNANCY AND BREASTFEEDING

Metolazone crosses the placental barrier and is therefore not recommended for use in pregnancy; there have been reports of jaundice and neonatal thrombocytopenia in births to mothers who took the drug.

Metolazone passes into breast milk, so breastfeeding must be stopped.

Ask your doctor for advice before taking any medicine.

EFFECTS ON THE ABILITY "TO DRIVE VEHICLES AND ON THE" USE OF MACHINERY

There are no known effects of metolazone on the ability to drive and use machines.

Dosage and method of use How to use Zaroxolyn: Dosage

Hypertension: The recommended starting dose is 2.5 mg (equivalent to half a tablet) or 5 mg per day, in the morning.

Heart failure edema: 5-10 mg once a day, in the morning.

Edema due to renal insufficiency: 5-20 mg once a day, in the morning.

After obtaining the desired therapeutic effect, it is usually advisable to reduce the dose of Zaroxolyn to the lowest levels of the maintenance treatment (2.5 or 5 mg every other day). The duration of the attack treatment with the highest posology it can vary from a few days in oedematous states, to 3-4 weeks in the treatment of hypertensive states.

Elderly: Lower starting doses should be used as they are more susceptible to side effects.

Patients with renal insufficiency: the dosage should be adjusted according to renal function.

Pediatric age: the use of the product is not recommended.

Overdose What to do if you have taken too much Zaroxolyn

In case of overdose there is a risk of dehydration and electrolyte depletion. Treatment of overdose should be directed at water replenishment and correction of electrolyte imbalances. In case of accidental intake of an excessive dose of the medicine, notify your doctor immediately or go to the nearest hospital.

Side Effects What are the side effects of Zaroxolyn

Like all medicines, this can cause side effects, although not everybody gets them.

Headache, anorexia, vomiting, abdominal discomfort, muscle cramps and dizziness have occasionally been reported during treatment with Zaroxolyn. Hyperuricaemia and azotemia have been reported mainly in patients with impaired renal function.

Side effects reported with metazolone are listed below are considered rare (

  • Disorders of the blood and lymphatic system

leukopenia, aplastic anemia, thrombocytopenia.

  • Metabolism and nutrition disorders

gout attacks.

  • Disorders of the nervous system

dizziness, somnolence, headache, paraesthesia, restlessness, insomnia, syncope.

  • Eye disorders

blurring of vision.

  • Heart ailments

palpitations, chest pains.

  • Vascular disorders

orthostatic hypotension, hypovolemia, venous thrombosis, haemoconcentration.

  • Disorders of the gastrointestinal system

constipation, dry mouth, nausea, vomiting, anorexia, diarrhea, flatulence, epigastric weight, pancreatitis.

  • Disorders of the hepatobiliary system

intrahepatic cholestasis, hepatitis

  • Alterations of the skin and subcutaneous tissue

Rashes, severe skin reactions

  • Disorders of the musculoskeletal and connective tissue

cramps, muscle spasms

  • Diagnostic investigations

hypokalaemia, hyponatremia, hypochloraemia, hypochloraemic alkalosis, hypophosphataemia, glycosuria, increased azotemia and creatinine, hyperuricaemia, hyperglycemia.

  • General disorders and changes in the administration site

hypersensitivity reactions: urticaria, purpura, necrotizing angiopathy. Chills, asthenia.

When moderate or severe side effects occur, the dose of Zaroxolyn should be reduced or treatment discontinued.

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. It is important to inform your doctor or pharmacist of any undesirable effect, even if not described in the package leaflet, please inform your pharmacist.

Expiry and Retention

Expiry: see the expiry date indicated on the package.

Composition: - Keep away from light.

Do not use the medicine after the expiry date which is stated on the package.

The expiry date refers to the product in intergo packaging, properly stored.

Keep this medicine out of the reach and sight of children.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

COMPOSITION

One 5 mg tablet contains:

Active ingredient: metolazone 5 mg

Excipients: microcrystalline cellulose, magnesium stearate

One 10 mg tablet contains:

Active ingredient: metolazone 10 mg

Excipients: microcrystalline cellulose; magnesium stearate, E 127 (in the form of 15% aluminum lake

PHARMACEUTICAL FORM AND CONTENT

50 tablets of 5 mg 50 tablets of 10 mg

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.

Further information on Zaroxolyn can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on the ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical data of 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 HOLDER OF THE ALL AUTHORIZATION "PLACING ON MARKETING 08.0 MARKETING AUTHORIZATION NUMBER 09.0 DATE OF PR IMA AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

ZAROXOLYN

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Zaroxolyn 5 mg tablets

One tablet contains:

Active ingredient: metolazone 5 mg.

Zaroxolyn 10 mg tablets

One tablet contains:

Active ingredient: metolazone 10 mg.

03.0 PHARMACEUTICAL FORM

Tablets.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Zaroxolyn is indicated in the treatment of hypertension alone or, in more severe forms, in combination with other antihypertensive drugs.

Zaroxolyn is also indicated as a diuretic in all cases of water-saline retention.


04.2 Posology and method of administration

Hypertension: The recommended starting dose is 2.5 mg (equivalent to half a tablet) or 5 mg per day, in the morning.

Heart failure edema: 5-10 mg once a day, in the morning;

Edema due to renal insufficiency: 5-20 mg once a day, in the morning.

After obtaining the desired therapeutic effect, it is usually advisable to reduce the dose of Zaroxolyn to the lowest levels of the maintenance treatment (2.5 or 5 mg every other day). The duration of the attack treatment with the highest posology it can vary from a few days in the oedematous states, to 3-4 weeks in the treatment of hypertensive states.

Senior citizens: Lower starting doses should be used as they are more susceptible to side effects.

Patients with renal insufficiency: the posology should be modified according to renal function.

Pediatric age: the use of the product is not recommended.


04.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients. Severe hepatic and renal insufficiency. Refractory hypokalaemia, symptomatic hyperuricemia, Addison's disease.


04.4 Special warnings and appropriate precautions for use

As with other diuretics, higher doses can produce marked changes in plasma potassium, uric acid, glucose and lipids.

Electrolyte imbalances

The product should be administered with caution in case of hypokalemia, hypokalemia, hypercalcemia and hypochloraemic alkalosis.

Determinations of serum electrolytes (sodium, potassium, chlorine, calcium), in order to detect possible imbalances, must be carried out at regular intervals. These checks are particularly important if the patient vomits excessively or is treated with fluids by parenteral route. BUN, blood sugar and blood glucose should also be periodically monitored during diuretic therapy.

All patients treated with Zaroxolyn should be observed in order to detect clinical signs of water-saline balance imbalances (hypokalemia, hyponatremia, hypochloraemic alkalosis). Some therapies, such as digitalis, may also be affected by the effects of the diuretic on serum electrolytes (see 4.5).

The first signs of electrolyte imbalance, regardless of the cause, are: dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle aches or cramps, muscle fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances (nausea, vomiting, etc. ).

In case of hypokalaemia, a supplementary intake of potassium or the administration of a potassium-sparing drug is indicated. Hypokalaemia may occur more often when diuretic therapy has been intense and prolonged, with concomitant steroid or ACTH therapy, and with inadequate salt intake.

Patients with hyperuricemia and hyperglycemia

Caution should be exercised in these patients. Hyperglycemia and glycosuria may occur in subjects with latent diabetes. In diabetic patients Zaroxolyn may interfere with antidiabetic therapy (see 4.5).

Hepatic or renal insufficiency

In liver failure, diuretic-induced hypokalemia can precipitate encephalopathy.

Caution should be exercised when administering Zaroxolyn to patients with impaired renal function. Since most of the drug is excreted through the kidneys, the plasma levels of this drug may increase under such conditions.

Other situations

A chloride deficiency and hypochloraemic alkalosis may occur. Hyposaline syndrome may occur in patients with conspicuous edema associated with heart failure or renal insufficiency; a warm climate and a hyposaline diet can contribute to this. Marked diuresis can lead to acute hypotension.


04.5 Interactions with other medicinal products and other forms of interaction

Combining Zaroxolyn with the following drugs requires special precautions or dosage adjustment:

- Diuretics: increased risk of hypokalemia; the administration of metolazone with furosemide causes profuse diuresis which must be carefully followed.

- Other Antihypertensives: increased hypotensive effect; adequate monitoring of blood pressure is required, especially in the initial phase, in order to promptly modify doses, if indicated.

- Barbiturates and opioid analgesics: increased hypotensive effect.

- Ciclosporin: increase in serum creatinine, when combined with metolazone.

Captopril: deterioration of kidney function, which improves with discontinuation of metolazone.

- Digitalis: increased toxicity with risk of serious arrhythmias, especially in case of hypokalaemia

- Corticosteroids and ACTH: increased risk of hypokalaemia and water and salt retention.

- Lithium: the elimination of lithium is reduced with an increase in its plasma concentrations and a risk of toxicity.

- Neuromuscular blockers: increased neuromuscular blocking effect with respiratory depression up to apnea; therefore Zaroxolyn must be discontinued at least 3 days before surgery.

- Non-steroidal anti-inflammatory drugs (NSAIDs): increased risk of NSAID nephrotoxicity. NSAIDs may attenuate the antihypertensive effect of Zaroxolyn.

- Sympathomimetics: metolazone can decrease the response to norepinephrine, without however preventing its efficacy as a pressure agent.

- Antidiabetics: reduction of the hypoglycemic effect. The need for an increase in the dose of hypoglycemic agents should be considered.

- Anticoagulants: increased bleeding time has been observed with warfarin.

Zaroxolyn, like thiazide diuretics, can modify their hypoprothrombinemic response, hence the need to adjust the dose.

Alcohol may increase the hypotensive effect of metolazone.


04.6 Pregnancy and breastfeeding

Pregnancy

Metolazone crosses the placental barrier and therefore its use in pregnancy is not recommended; There have been reports of jaundice and neonatal thrombocytopenia in births of mothers who had taken the drug.

Feeding time

Metolazone passes into breast milk, so breastfeeding must be stopped.


04.7 Effects on ability to drive and use machines

There are no known effects of metolazone on the ability to drive and use machines.


04.8 Undesirable effects

Headache, anorexia, vomiting, abdominal discomfort, muscle cramps and dizziness have occasionally been reported during treatment with Zaroxolyn. Hyperuricaemia and azotemia have been reported mainly in patients with impaired renal function.

The undesirable effects reported with metazolone and listed below by organ system class, are to be considered rare (

- Disorders of the blood and lymphatic system. leukopenia, aplastic anemia, thrombocytopenia

- Metabolism and nutrition disorders gout attacks

- Nervous system disorders dizziness, somnolence, headache, paraesthesia, restlessness, insomnia, syncope

- Eye disorders, blurred vision

- Heart problems palpitations, chest pains

- Vascular disorders orthostatic hypotension, hypovolaemia, venous thrombosis

- Gastrointestinal disorders constipation, dry mouth, nausea, vomiting, anorexia, diarrhea, flatulence, epigastric weight, pancreatitis

- Disorders of the hepatobiliary system, intrahepatic cholestasis, hepatitis

- Alterations of the skin and subcutaneous tissue

Rashes, severe skin reactions

- Disorders of the musculoskeletal and connective tissue cramps, muscle spasms

-Diagnostic investigations hypokalaemia, hyponatremia, hypochloraemia, hypochloraemic alkalosis, hypophosphataemia, glycosuria, increased azotemia and creatinine, hyperuricaemia, hyperglycemia.

- General disorders and changes in the administration site hypersensitivity reactions: urticaria, purpura, necrotizing angiopathy. Chills, asthenia.

When moderate or severe side effects occur, the dose of Zaroxolyn should be reduced or the treatment discontinued.


04.9 Overdose

In case of overdose there is a risk of dehydration and electrolyte depletion.

Treatment of overdose should be directed at water replenishment and correction of electrolyte imbalances.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: diuretic.

ATC code: C03BA08.

Metolazone is a quinazoline diuretic with general characteristics similar to those of thiazide diuretics.Its action consists in an "interference with the renal tubular mechanism of reabsorption of electrolytes. Zaroxolyn inhibits the reabsorption of sodium at the level of the cortical diluent segment and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in an almost equivalent quantity. The increased sodium load in the distal tubule leads to an increase in potassium elimination. Zaroxolyn does not inhibit carbonic anhydrase.

An increase in excretions of phosphate ions and magnesium ions has also been shown.

The diuretic effect usually begins within one "hour of" intake, peaks in activity in about 2 hours and lasts for about 24 hours or more, also depending on the dosage.

Zaroxolyn has a thiazide-like activity, but can produce diuresis even in patients with glomerular filtrate less than 20 ml / min.


05.2 "Pharmacokinetic properties

Absorption and distribution

Metolazone is slowly and incompletely absorbed from the gastrointestinal tract. In normal subjects, the average amount absorbed is 65%; the share drops to 40% in heart patients. About 95% of the drug is bound to erythrocytes and to a lesser extent to plasma proteins. The half-life is 8-10 hours in the whole blood and 4-5 hours in the plasma.

Metabolism and excretion

Approximately 70-80% of the absorbed amount is eliminated in the urine, mainly in unmodified form; the remainder is excreted via the biliary route.


05.3 Preclinical safety data

Preclinical data have little clinical relevance in light of the extensive experience acquired with the use of the drug in humans.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

5 mg tablets: microcrystalline cellulose, magnesium stearate.

10 mg tablets: microcrystalline cellulose, magnesium stearate, color E 127 (in the form of 15% aluminum lake).


06.2 Incompatibility

Not known.


06.3 Period of validity

48 months, as the product is properly stored and in intact packaging conditions.

Do not use the product after the expiry date shown on the package.


06.4 Special precautions for storage

Keep away from light.


06.5 Nature of the immediate packaging and contents of the package

5 mg tablets. Box of 50 tablets in PVC / PVDC blister heat-sealed with aluminum / PVDC foil.

10 mg tablets. Box of 50 tablets in PVC / PVDC blister heat-sealed with aluminum / PVDC foil.


06.6 Instructions for use and handling

07.0 MARKETING AUTHORIZATION HOLDER

TEOFARMA S.r.l.

via F.lli Cervi, 8

27010 Salimbene Valley (PV)

08.0 MARKETING AUTHORIZATION NUMBER

5 mg tablets. AIC 024488064

10 mg tablets. AIC 024488090

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

1981 - June 2010.

10.0 DATE OF REVISION OF THE TEXT

June 2010.

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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