Lozap

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LOZAP®

Composition:

Active substance: losartan;

1 tablet contains 50 mg or 100 mg of losartan potassium;

Excipients: microcrystalline cellulose, mannitol (E 421), crospovidone, colloidal anhydrous silicon dioxide, magnesium stearate, talc, white coating Sepifilm 752 (containing hypromellose, microcrystalline cellulose, polyglycol stearate, titanium dioxide (E 171)), polyethylene glycol 6000.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

Lozap® (50 mg strength): oval, biconvex, film-coated tablets, white or almost white, with a dividing line, approximately 11.0×5.5 mm in size;

Lozap® (100 mg strength): oval, biconvex, film-coated tablets, white or almost white, with a dividing line, approximately 14.0×7.0 mm in size.

Pharmacotherapeutic group.

Simple preparations of angiotensin II receptor antagonists. ATC code C09C A01.

Pharmacological properties.

Pharmacodynamics.

Losartan is a synthetic angiotensin II receptor antagonist (type AT1) for oral administration. Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin-angiotensin system (RAS) and is one of the most important factors in the pathophysiology of arterial hypertension. Angiotensin II binds to the AT1 receptor, found in many tissues (e.g., vascular smooth muscle, adrenal glands, kidneys, and heart), mediating a range of significant biological effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates smooth muscle cell proliferation.

Losartan selectively blocks the AT1 receptor. In vitro and in vivo, losartan and its pharmacologically active metabolite, carboxylic acid (E-3174), block all physiologically relevant effects of angiotensin II, regardless of its source or pathway of synthesis.

Losartan exhibits neither agonistic nor antagonistic activity on other hormonal receptors or ion channels that play a significant role in cardiovascular regulation. Furthermore, losartan does not inhibit ACE (kininase II), the enzyme responsible for bradykinin degradation. Therefore, there is no potentiation of bradykinin-mediated adverse effects.

During losartan administration, the removal of angiotensin II's negative feedback on renin secretion leads to increased plasma renin activity. This increase results in elevated plasma angiotensin II levels. Despite this rise, antihypertensive activity and suppression of plasma aldosterone concentration are maintained, indicating effective blockade of angiotensin II receptors. After discontinuation of losartan, plasma renin activity and angiotensin II levels return to baseline values within 3 days.

Both losartan and its main metabolite have higher affinity for AT1 receptors than for AT2 receptors. The active metabolite is 10–40 times more potent than losartan (on a mass basis).

Administration of losartan reduces the overall incidence of cardiovascular mortality, stroke, and myocardial infarction in patients with arterial hypertension and left ventricular hypertrophy, and provides renal protection in patients with type 2 diabetes mellitus and proteinuria.

Pharmacokinetics.

Absorption. After oral administration, losartan is well absorbed and undergoes first-pass metabolism, forming the active carboxylic acid metabolite and inactive metabolites. The systemic bioavailability of losartan tablets is approximately 33%. Mean peak concentrations of losartan and its active metabolite are reached at approximately 1 hour and 3–4 hours, respectively.

Distribution. Losartan and its active metabolite are ≥99% bound to plasma proteins, primarily albumin. The volume of distribution of losartan is 34 L.

Biological transformation. Approximately 14% of losartan is converted into the active metabolite after intravenous administration or oral intake. Following intravenous or oral administration of radiolabeled 14C-losartan potassium, circulating plasma radioactivity typically consists of losartan and its metabolites. Minimal conversion of losartan to its active metabolite was observed in approximately 1% of cases. In addition to the active metabolite, several inactive metabolites are formed.

Elimination. Plasma clearance of losartan and its active metabolite is 600 mL/min and 50 mL/min, respectively. Renal clearance of losartan and its active metabolite is approximately 74 mL/min and 26 mL/min, respectively. After oral administration, approximately 4% of the dose is excreted unchanged in urine, and about 6% is excreted in urine as the active metabolite. The pharmacokinetic properties of losartan and its active metabolite are linear at oral doses of losartan potassium up to 200 mg.

After oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially, with terminal half-lives of approximately 2 hours and 6–9 hours, respectively. After oral administration of 14C-labeled losartan, approximately 35% of radioactivity is recovered in urine and 58% in feces.

Pharmacokinetics in specific patient populations

Elderly patients.

Plasma concentrations of losartan and its active metabolite in elderly patients with arterial hypertension do not significantly differ from those in younger hypertensive patients.

Gender.

Plasma concentrations of losartan were twice as high in women with arterial hypertension compared to men. Plasma concentrations of the active metabolite did not differ between men and women.

Hepatic and renal impairment.

Following oral administration to patients with mild to moderate alcoholic cirrhosis, plasma concentrations of losartan and its active metabolite were 1.7–5 times higher, respectively, than in young male volunteers.

Plasma concentrations of losartan in patients with creatinine clearance above 10 mL/min do not differ from those in individuals with normal renal function. When comparing the area under the concentration-time curve (AUC), the AUC of losartan in patients after renal transplantation was approximately twice as high as in patients with normal renal function. Plasma concentrations of the active metabolite remain unchanged in patients with renal impairment or those undergoing hemodialysis. Neither losartan nor its active metabolite can be removed by hemodialysis.

Pharmacokinetics in children.

The pharmacokinetics of losartan were studied in 50 children with arterial hypertension, aged 1 month to 16 years, after once-daily oral administration at doses ranging from 0.54 to 0.77 mg/kg (mean doses). Results showed that the active metabolite of losartan is formed in patients across all age groups. The data indicate approximately similar pharmacokinetic parameters of losartan after oral administration in neonates and children aged 2–3 years, preschool, school-aged children, and adolescents. Pharmacokinetic parameters of the metabolite varied more depending on age group. Statistically significant differences were observed when comparing preschool children and adolescents. Exposure in neonates and children aged 2–3 years was relatively high.

Clinical characteristics.

Indications.

Treatment of essential hypertension in adults, as well as in children and adolescents aged 6–18 years.

Treatment of kidney disease in adult patients with hypertension and type 2 diabetes mellitus with proteinuria ≥ 0.5 g/day – as part of antihypertensive therapy.

Treatment of chronic heart failure in adult patients when angiotensin-converting enzyme (ACE) inhibitors are considered unsuitable due to intolerance, particularly cough, or are contraindicated. Patients with heart failure whose condition has stabilized on an ACE inhibitor should not be switched to losartan therapy. The patient must have a left ventricular ejection fraction ≤ 40%, clinically stable condition, and be receiving established treatment for chronic heart failure.

Reduction of the risk of stroke in adult patients with arterial hypertension and left ventricular hypertrophy confirmed by ECG.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Second and third trimesters of pregnancy.

Severe hepatic impairment.

Concomitant use of losartan with medicinal products containing aliskiren is contraindicated in patients with diabetes mellitus and renal impairment (glomerular filtration rate [GFR] < 60 mL/min/1.73 m²).

Interaction with other medicinal products and other forms of interaction.

Other antihypertensive agents may enhance the hypotensive effect of losartan. Concomitant use with other drugs that may cause hypotension as an adverse reaction (e.g., tricyclic antidepressants, antipsychotics, baclofen, and amifostine) may increase the risk of arterial hypotension.

Losartan is metabolized primarily via the cytochrome P450 (CYP) 2C9 system to its active carboxylic acid metabolite. Fluconazole (a CYP2C9 inhibitor) reduces exposure to the active metabolite by approximately 50%. Concomitant treatment with losartan and rifampicin (an enzyme inducer) has been shown to reduce plasma concentrations of the active metabolite by 40%. The clinical significance of this effect is unknown. No difference in exposure was observed with concomitant administration of losartan and fluvastatin (a weak CYP2C9 inhibitor).

As with other drugs that block angiotensin II or its effects, concomitant use of agents that retain potassium in the body (e.g., potassium-sparing diuretics such as spironolactone, triamterene, amiloride), or that may increase potassium levels (e.g., heparin, trimethoprim-containing preparations), potassium supplements, or potassium-containing salt substitutes may lead to increased serum potassium levels. Concomitant use of such agents is not recommended.

With concomitant use of lithium and ACE inhibitors, there have been reports of reversible increases in serum lithium concentrations and lithium toxicity. Very rare cases of such interaction have also been reported with angiotensin II receptor blockers. Concomitant use of lithium and losartan requires caution. If such combination is considered necessary, monitoring of serum lithium levels during concomitant therapy is recommended.

Concomitant use of angiotensin II antagonists and nonsteroidal anti-inflammatory drugs (e.g., selective cyclooxygenase-2 [COX-2] inhibitors, acetylsalicylic acid at anti-inflammatory doses, nonselective NSAIDs) may attenuate the antihypertensive effect. Concomitant use of angiotensin II antagonists or diuretics with NSAIDs may increase the risk of worsening renal function, including possible development of acute renal failure, as well as increased serum potassium levels, particularly in patients with pre-existing renal impairment. Such combination should be prescribed with caution, especially in elderly patients. Adequate hydration should be ensured, and monitoring of renal function should be considered after initiation of concomitant therapy and periodically thereafter.

Data indicate that dual blockade of the renin-angiotensin-aldosterone system (RAAS) by combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with a higher incidence of adverse events such as arterial hypotension, hyperkalemia, and impaired renal function (including acute renal failure), compared to use of a single RAAS-acting agent.

Special precautions for use.

Hypersensitivity

Angioedema. Patients with a history of angioedema (swelling of the face, lips, throat, and/or tongue) should be monitored frequently.

Arterial hypotension and fluid-electrolyte imbalance

Symptomatic arterial hypotension may occur in patients with hypovolemia and/or hyponatremia resulting from intensive diuretic therapy, dietary salt restriction, diarrhea, or vomiting—particularly after the first dose of the drug or following dose escalation. Such conditions should be corrected prior to initiating losartan therapy or require a lower starting dose (see "Dosage and administration"). These same recommendations apply to children aged 6 years and older.

Electrolyte imbalance

Electrolyte imbalances are commonly observed in patients with impaired renal function (with or without diabetes mellitus) and should be taken into account. In a clinical trial involving patients with type 2 diabetes mellitus and nephropathy, the incidence of hyperkalemia was higher with losartan treatment compared to placebo. Therefore, plasma potassium concentrations and creatinine clearance should be monitored frequently, especially in patients with heart failure and creatinine clearance of 30–50 mL/min.

Concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other medications that may increase serum potassium levels (e.g., trimethoprim-containing drugs) with losartan is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

Evidence shows that concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of arterial hypotension, hyperkalemia, and impaired renal function (including acute kidney injury). Therefore, dual RAAS blockade with combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.

In cases of absolute necessity for dual RAAS blockade, it should be performed under specialist supervision with careful monitoring of renal function, electrolyte balance, and blood pressure.

ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Combination with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR < 60 mL/min/1.73 m²).

Hepatic impairment

Based on pharmacokinetic data indicating significantly increased plasma concentrations of losartan in patients with liver cirrhosis, dose reduction should be considered in patients with a history of hepatic dysfunction. There is no experience with the use of the drug in patients with severe hepatic impairment.

Losartan is not recommended for use in children with hepatic impairment.

Renal impairment

Changes in renal function, including renal failure, have been reported and are associated with suppression of the RAAS (particularly in patients whose renal function depends on the renin-angiotensin-aldosterone system, such as those with severe heart failure or pre-existing renal impairment).

Medicinal products affecting the RAAS may increase blood urea nitrogen and serum creatinine levels in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. These changes in renal function may be reversible upon discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

Use in children with renal impairment

The drug is not recommended for use in children with glomerular filtration rate < 30 mL/min/1.73 m² due to lack of relevant data.

Renal function should be monitored regularly during losartan therapy, as deterioration may occur—particularly in situations where losartan must be used in the presence of other conditions (e.g., fever, dehydration) that may affect renal function.

Concomitant use of losartan and ACE inhibitors worsens renal function; therefore, this combination is not recommended.

Kidney transplantation

There is no experience regarding the safety of using the drug in patients who have recently undergone kidney transplantation.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism generally do not respond to drugs acting via inhibition of the RAAS. Therefore, losartan is not recommended for this patient group.

Coronary artery disease and cerebrovascular disease

As with other antihypertensive agents, excessive reduction in blood pressure in patients with ischemic coronary artery disease or cerebrovascular disease may lead to myocardial infarction or stroke.

Heart failure

As with other drugs affecting the RAAS, patients with heart failure, with or without renal impairment, are at risk of developing severe arterial hypotension and (often acute) renal dysfunction.

There is insufficient therapeutic experience with losartan in patients with heart failure and concomitant severe renal impairment, patients with severe heart failure (NYHA class IV), and patients with heart failure and symptomatic, life-threatening cardiac arrhythmias. Therefore, losartan should be used with caution in these patient groups. Concomitant use of losartan and β-blockers should be approached with caution.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with other vasodilators, the drug should be prescribed with particular caution in patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.

Pregnancy

Initiation of losartan therapy during pregnancy is not recommended. Except when continuation of losartan therapy is deemed urgently necessary, women planning pregnancy should switch to alternative antihypertensive agents with established safety during pregnancy. Upon diagnosis of pregnancy, losartan should be discontinued immediately and alternative therapy initiated if necessary (see sections "Contraindications" and "Use during pregnancy or breastfeeding").

Other warnings

As established for angiotensin-converting enzyme inhibitors, losartan and other angiotensin receptor antagonists are less effective in patients of Black race than in other patients, possibly due to lower renin activity in Black patients with arterial hypertension.

Use during pregnancy or breastfeeding.

Pregnancy

Use of losartan during the first trimester of pregnancy is not recommended (see section "Special precautions for use"). Use of losartan during the second and third trimesters of pregnancy is contraindicated (see sections "Contraindications" and "Special precautions for use").

Epidemiological data on the teratogenic risk of ACE inhibitors used during the first trimester of pregnancy are not conclusive; however, a small increased risk cannot be excluded. Since there are no data from controlled epidemiological studies on the risk associated with angiotensin II receptor antagonists (ARBs), similar risks may apply to this class of drugs. Except when continuation of ARB therapy is deemed urgently necessary, women planning pregnancy should switch to alternative antihypertensive agents with a proven safety profile during pregnancy. Upon diagnosis of pregnancy, losartan should be discontinued immediately and alternative therapy initiated if necessary.

It is known that use of ARBs during the second and third trimesters of pregnancy in humans causes fetal toxicity (impaired renal function, oligohydramnios, delayed skull ossification) and neonatal adverse effects (renal failure, arterial hypotension, hyperkalemia).

If losartan was used from the second trimester of pregnancy, ultrasound evaluation of fetal kidneys and skull is recommended.

Newborns whose mothers took losartan during pregnancy should be closely monitored for arterial hypotension (see also sections "Contraindications" and "Special precautions for use").

Breastfeeding

As there is no information on the use of losartan during breastfeeding, the drug is not recommended. Preferred alternative treatments with better-established safety profiles during breastfeeding are advised, especially during the neonatal period or if the infant is premature.

Ability to influence reaction speed when driving or operating machinery.

No studies have been conducted on the effect of the drug on the ability to drive vehicles or operate machinery. However, the possibility of adverse reactions such as dizziness and somnolence, especially at the beginning of treatment and during dose escalation, should be considered.

Method of Administration and Dosage

Tablets can be taken regardless of food intake, with a glass of water.

Arterial Hypertension

The usual initial and maintenance dose for most patients is 50 mg of the drug once daily. The maximum antihypertensive effect is achieved within 3–6 weeks after initiation of therapy. For some patients, increasing the dose to 100 mg once daily (in the morning) may be beneficial.

The drug can be used in combination with other antihypertensive agents, particularly diuretics (e.g., hydrochlorothiazide).

Patients with Arterial Hypertension and Type 2 Diabetes Mellitus (Proteinuria
≥ 0.5 g/day)

The usual initial dose is 50 mg once daily. The dose may be increased to 100 mg once daily depending on blood pressure levels one month after initiation of treatment. Losartan may be used concomitantly with other antihypertensive agents (e.g., diuretics, calcium channel blockers, α- or β-receptor blockers, centrally acting agents), as well as with insulin and other commonly used hypoglycemic agents (e.g., sulfonylurea derivatives, glitazones, and glucosidase inhibitors).

Heart Failure

The usual initial dose of losartan in patients with heart failure is 12.5 mg once daily. The dose should generally be titrated at weekly intervals (i.e., 12.5 mg daily, 25 mg daily, 50 mg daily, 100 mg daily) up to the maximum dose of 150 mg once daily, depending on patient tolerance.

Reduction of Stroke Risk in Patients with Arterial Hypertension and Electrocardiographically Confirmed Left Ventricular Hypertrophy

The usual initial dose is 50 mg of losartan once daily. Depending on changes in blood pressure levels, addition of low-dose hydrochlorothiazide and/or increasing the losartan dose to 100 mg once daily may be necessary.

Special Patient Groups

Use in Patients with Reduced Blood Volume

In patients with reduced blood volume (e.g., due to high-dose diuretic therapy), consideration should be given to initiating treatment with a 25 mg once-daily dose.

Use in Patients with Renal Impairment and Patients Undergoing Hemodialysis

No initial dose adjustment is required when administering losartan to patients with renal impairment or to those undergoing hemodialysis.

Use in Patients with Hepatic Impairment

For patients with a history of hepatic impairment, a lower initial dose should be considered. There is no experience with losartan in patients with severe hepatic impairment; therefore, losartan is contraindicated in this patient group.

Use in Elderly Patients

Generally, no initial dose adjustment is required for elderly patients, although initiating treatment with a 25 mg dose should be considered for patients aged 75 years and older.

Children

The safety and efficacy of the drug in children aged 6 months to 6 years have not been established. Available data are presented in the section "Pharmacological Properties," but no dosage recommendations can be provided.

For children who can swallow tablets and whose body weight is between 20 kg and 50 kg, the recommended dose is 25 mg once daily. In exceptional cases, the dose may be increased to a maximum of 50 mg once daily. The dose should be adjusted based on the effect on blood pressure.

In patients with body weight above 50 kg, the usual single dose is 50 mg once daily. In exceptional cases, the dose may be increased to a maximum of 100 mg once daily. Doses exceeding 1.4 mg/kg (or more than 100 mg) per day have not been studied in children.

Losartan is not recommended for use in children under 6 years of age due to insufficient data on its use in this patient group.

The drug is not recommended for use in children with a glomerular filtration rate < 30 mL/min/1.73 m² due to lack of relevant data.

Losartan is also not recommended for use in children with hepatic impairment.

Children.

Data on the safety and efficacy of the drug in children aged 6 months to 6 years are not established. Available data are presented in the section "Pharmacological Properties," but no dosage recommendations can be provided for children under 6 years of age.

Overdose.

Symptoms of intoxication. Cases of overdose have not been reported. The most likely symptoms, depending on the amount ingested, would be arterial hypotension and tachycardia. Bradycardia may occur due to stimulation of parasympathetic (vagal) innervation.

Treatment of intoxication.

In the event of symptomatic arterial hypotension, supportive therapy should be administered.

Treatment depends on the time elapsed since drug ingestion and the nature and severity of symptoms.

The primary measure should be stabilization of cardiovascular function. After oral ingestion, activated charcoal in an appropriate dose is indicated. Subsequently, vital signs should be monitored frequently and corrected as necessary. Losartan and its active metabolites are not removed by hemodialysis.

Adverse reactions.

The most commonly reported adverse reaction was dizziness.

The frequency of the adverse reactions listed below is defined as follows: very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1000 to <1/100; rare: ≥1/10000 to <1/1000; very rare: <1/10000; not known (cannot be estimated from the available data).

Table 1.

Frequency of adverse reactions identified in placebo-controlled clinical studies and during post-marketing use of losartan

Adverse reaction	Frequency of adverse reactions in various indications					Other
	Arterial hypertension	Patients with arterial hypertension and left ventricular hypertrophy	Chronic heart failure	Arterial hypertension and type 2 diabetes with kidney disease	Post-marketing experience
Blood and lymphatic system disorders
anemia			common		frequency unknown
thrombocytopenia					frequency unknown
Immune system disorders
hypersensitivity reactions, anaphylactic reactions, angioedema* and vasculitis**					uncommon
Psychiatric disorders
depression					frequency unknown
Nervous system disorders
dizziness	common	common	common	common
drowsiness	uncommon
headache	uncommon		uncommon
sleep disorders	uncommon
paraesthesia			rare
migraine					frequency unknown
dysgeusia					frequency unknown
Ear and labyrinth disorders
vertigo	common	common
tinnitus					frequency unknown
Cardiac disorders
palpitations	uncommon
angina pectoris	uncommon
syncope			rare
atrial fibrillation			rare
cerebrovascular event			rare
Vascular disorders
(orthostatic) arterial hypotension (including dose-dependent orthostatic effects)	uncommon		common	common
Respiratory, thoracic and mediastinal disorders
dyspnea			uncommon
cough			uncommon		frequency unknown
Gastrointestinal disorders
abdominal pain	uncommon
constipation	uncommon
diarrhea			uncommon		frequency unknown
nausea			uncommon
vomiting			uncommon
Hepatobiliary disorders
pancreatitis					frequency unknown
hepatitis					rare
liver function disorders					frequency unknown
Skin and subcutaneous tissue disorders
urticaria			uncommon		frequency unknown
pruritus			uncommon		frequency unknown
rash	uncommon		uncommon		frequency unknown
photosensitivity					frequency unknown
Musculoskeletal and connective tissue disorders
myalgia					frequency unknown
arthralgia					frequency unknown
rhabdomyolysis					frequency unknown
Renal and urinary disorders
renal function disorders			common
renal failure			common
Reproductive system and breast disorders
erectile dysfunction/impotence					frequency unknown
General disorders and administration site conditions
general weakness	uncommon	common	uncommon	common
increased fatigue	uncommon	common	uncommon	common
edema	uncommon
malaise					frequency unknown
Investigations
hyperkalemia	common		uncommon†	common‡
increased levels of alanine aminotransferase (ALT)§	rare
increased blood urea nitrogen, serum creatinine and serum potassium levels			common
hyponatremia					frequency unknown
hypoglycemia				common

* Including angioedema of the larynx, vocal cords, face, lips, pharynx, and/or tongue (causing airway obstruction); some of these patients had a history of angioedema related to other medicinal products, including ACE inhibitors.

** Includes Henoch-Schönlein purpura.

║Particularly in patients with intravascular hypovolemia, e.g., in patients with severe heart failure or those receiving high-dose diuretic therapy.

†This adverse reaction was more frequent among patients receiving 150 mg of losartan than 50 mg.

‡In a clinical trial involving patients with type 2 diabetes and nephropathy, hyperkalemia (> 5.5 mmol/L) was observed in 9.9% of patients receiving losartan tablets and in 3.4% of patients receiving placebo.

§This adverse reaction usually resolved after discontinuation of losartan.

The following additional adverse reactions occurred more frequently in patients receiving losartan than in those receiving placebo (frequency not known): back pain, urinary tract infections, and influenza-like symptoms.

Renal and urinary disorders

In patients at increased risk, changes in renal function due to inhibition of the RAAS, including cases of renal failure, have been reported; these changes in renal function may be reversible upon discontinuation of the drug (see section "Dosage and Administration").

Children.

The adverse reaction profile in children is similar to that in adult patients. Data on adverse reactions in children are limited.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is an important procedure. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions via the national adverse reaction reporting systems.

Shelf life. 2 years.

Storage conditions. Store at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging.

LOZAP®, film-coated tablets, 50 mg

No. 30 (15x2), No. 60 (10x6), No. 60 (15x4), No. 90 (10x9), No. 90 (15x6):

10 tablets in a blister; 6 or 9 blisters in a cardboard box;

15 tablets in a blister; 2, 4, or 6 blisters in a cardboard box.

LOZAP®, film-coated tablets, 100 mg

No. 30 (10x3), No. 30 (15x2), No. 60 (10x6), No. 60 (15x4), No. 90 (10x9), No. 90 (15x6):

10 tablets in a blister; 3, 6, or 9 blisters in a cardboard box;

15 tablets in a blister; 2, 4, or 6 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

1. Saneca Pharmaceuticals Ltd.
2. Zentiva s.r.o.

Manufacturer's address and place of business.

1. Nitrianska 100, 920 27 Glogovec, Slovak Republic.
2. U Kabelovny 130, 102 37 Prague 10, Dolni Měcholupy, Czech Republic.

Marketing Authorization Holder.

Sanofi-Aventis Ukraine LLC.

Address of the Marketing Authorization Holder.

48-50A Zhylianska St., Kyiv, 01033, Ukraine.