Loris

618 8 minutes read

Active material: Lozartan
When ATH: C09CA01
CCF: Angiotensin II receptor antagonists
ICD-10 codes (testimony): I10, I50.0, I61, N08.3
When CSF: 01.04.02
Manufacturer: Krka-RUS OOO (Russia)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills, Film-coated from light yellow to yellow, Oval, slightly biconcave, chamfered.

	1 tab.
losartan potassium	12.5 mg

Excipients: tsellaktoza (a mixture of lactose monohydrate and cellulose), pre-gelatinized starch, corn starch, microcrystalline cellulose, Colloidal anhydrous silica, magnesium stearate.

The composition of the shell: gipromelloza, talc, propylene glycol, quinoline yellow dye (E104), Titanium dioxide (E171).

7 PC. – packings Valium planimetric (2) – packs cardboard.
10 PC. – packings Valium planimetric (3) – packs cardboard.
10 PC. – packings Valium planimetric (6) – packs cardboard.
10 PC. – packings Valium planimetric (9) – packs cardboard.
14 PC. – packings Valium planimetric (1) – packs cardboard.

Pills, Film-coated yellow color, Oval, slightly biconcave, with Valium on one side and a facet.

	1 tab.
losartan potassium	25 mg

Excipients: tsellaktoza (a mixture of lactose monohydrate and cellulose), pre-gelatinized starch, corn starch, microcrystalline cellulose, Colloidal anhydrous silica, magnesium stearate.

The composition of the shell: gipromelloza, talc, propylene glycol, quinoline yellow dye (E104), Titanium dioxide (E171).

Pills, Film-coated white, round, slightly biconcave, with Valium on one side, chamfered.

	1 tab.
losartan potassium	50 mg

Excipients: tsellaktoza (a mixture of lactose monohydrate and cellulose), pre-gelatinized starch, corn starch, microcrystalline cellulose, Colloidal anhydrous silica, magnesium stearate.

The composition of the shell: gipromelloza, talc, propylene glycol, Titanium dioxide (E171).

Pills, Film-coated white, Oval, slightly biconcave.

	1 tab.
losartan potassium	100 mg

Excipients: tsellaktoza (a mixture of lactose monohydrate and cellulose), pre-gelatinized starch, corn starch, microcrystalline cellulose, Colloidal anhydrous silica, magnesium stearate.

The composition of the shell: gipromelloza, talc, propylene glycol, Titanium dioxide (E171).

Pharmacological action

Selective antagonist of the angiotensin II receptor type AT₁ non-protein nature.

In vivo and in vitro losartan and its biologically active metabolite carboxy (EXP-3174) block all physiologically significant effects on angiotensin II AT₁-receptors regardless of the route of its synthesis: It leads to an increase in plasma renin activity, It reduces the concentration of aldosterone in blood plasma.

Losartan indirectly causes the activation of AT₂-receptors by increasing the level of angiotensin II. Losartan does not inhibit the activity of kininazy II, enzyme, which is involved in the metabolism of bradykinin.

Reduces PR, the pressure in the pulmonary circulation; reduces afterload, It has a diuretic effect.

It prevents the development of myocardial hypertrophy, improves exercise tolerance in patients with chronic heart failure.

Losartan 1 time / day resulted in a statistically significant reduction in systolic and diastolic blood pressure. During the day losartan uniformly control blood pressure, wherein the antihypertensive effect corresponds to the natural circadian rhythm. The decrease in blood pressure at the end of the action dose was approximately 70-80% the effect on the peak of the drug, through 5-6 h after administration. Withdrawal is not observed; Losartan is also no clinically significant effect on heart rate.

Losartan is effective in men and women, and in elderly (≥ 65 years) and younger patients (≤ 65 years).

Pharmacokinetics

Absorption

Losartan is well absorbed from the gastrointestinal tract. Taking the drug with food has no clinically significant impact on its serum concentrations.

Bioavailability is about 33%. C_maxlosartan in plasma achieved through 1 hours after ingestion. C_max EXP-3174 in plasma achieved through 3-4 no.

Distribution

More 99% percent of losartan and EXP-3174 binds to plasma proteins, mostly to albumin.

V_d Losartan is 34 l. It does not penetrate the blood-brain barrier.

Metabolism

Subject to significant metabolism at “first pass” through the liver, forming the active metabolite EXP-3174 (14%) and a number of inactive metabolites, including 2 osnovnыh metabolite, formed by hydroxylation chain butyl group and less significant metabolite, N-2-тетразол глюкуронид.

Deduction

The plasma clearance of losartan and EXP-3174 is approximately 10 ml / sec (600 ml / min) and 0.83 ml / sec (50 ml / min) respectively. Renal clearance of losartan and EXP-3174 is about 1.23 ml / sec (74 ml / min) and 0.43 ml / sec (26 ml / min) respectively. T_1/2 Losartan is 2 no. T_1/2 the active metabolite of 6-9 no. About 58% the drug is excreted in the bile, 35% – urine.

Testimony

- Arterial hypertension;

- Reducing the risk of stroke in patients with hypertension and left ventricular hypertrophy;

- Congestive heart failure (in a combination therapy, in case of intolerance or failure of therapy with ACE inhibitors);

- Protection of the kidney in patients with diabetes mellitus type 2 proteinuria to reduce proteinuria, reduce the progression of kidney damage, reduce the risk of end-stage (prevent the need for dialysis, the probability of increasing the level of serum creatinine) or death.

Dosage regimen

The drug is taken orally, regardless of the meal, the multiplicity of reception – 1 time / day.

At hypertension the average daily dose is 50 mg. The maximum antihypertensive effect is reached within 3-6 weeks of therapy. Possible to achieve a more pronounced effect by increasing the dose to 100 mg / day.

In patients receiving diuretics in high doses is recommended to start therapy Loristoy^® from 25 mg / day.

Elderly patients, with impaired renal function (incl. Patients on hemodialysis) It does not require correction initial dose.

Patients with impaired hepatic function the drug should be administered at a lower dose.

At chronic heart failure the initial dose is 12.5 mg / day. For, to achieve the usual maintenance dose 50 mg / day, the dose should be increased gradually, at intervals of 1 week (eg, 12.5 mg, 25 mg, 50 mg / day). Losartan^® usually given in combination with diuretics and cardiac glycosides.

Increasing dose scheme presented in Table.

1 Sunday (from 1 by 7 day)	by 1 tab. 12.5 mg / day
2 Sunday (from 8 by 14 day)	by 1 tab. 25 mg / day
3 Sunday (from 15 by 21 day)	by 1 tab. 50 mg / day
4 Sunday (from 22 by 28 day)	by 1 tab. 50 mg / day

To reducing the risk of stroke in patients with hypertension and left ventricular hypertrophy the standard starting dose is 50 mg / day. In the future, may be added to hydrochlorothiazide at a low dose and / or increase the dose Loristy^® to 100 mg / day.

To protection of the kidneys in patients with diabetes mellitus type 2 proteinuria the standard starting dose Loristy^® is 50 mg / day. The dose may be increased to 100 mg / day in terms of reduction in blood pressure.

Side effect

From the central and peripheral nervous system: ≥1% – dizziness, asthenia, headache, fatiguability, insomnia; <1 % – anxiety, sleep disturbance, drowsiness, memory disorders, perifericheskaya neuropathy, paresthesia, gipostezii, migraine, tremor, ataxia, depression, syncope.

Cardio-vascular system: orthostatic hypotension (dozozavisimaya), heartbeat, tachycardia, bradycardia, Arrhythmia, angina, vasculitis.

The respiratory system: ≥1% – nasal congestion, cough *, infections of the upper respiratory tract, faringitы, dyspnoea, bronchitis, rhinedema.

From the digestive system: ≥1% – nausea, diarrhea *, dyspepsia *, abdominal pain; <1% – anorexia, dry mouth, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, abnormal liver function; rarely – increase in liver enzymes, giperʙiliruʙinemija.

From the urinary system: <1% – urgent need to urinate, urinary tract infection, impairment of renal function; sometimes – moderate increase in urea and creatinine in the serum.

On the part of the reproductive system: <1% – decreased libido, impotence.

On the part of the musculoskeletal system: ≥1% – convulsions, myalgia *, backache, Chest, legs; <1% – arthralgia, arthritis, shoulder pain, slaughter, fibromyalgia.

From the senses: <1% – tinnitus, taste disturbance, visual impairment, conjunctivitis.

From the hematopoietic system: infrequently – anemia, purpura Shenleyna-Genoa.

Dermatological reactions: <1% – xerosis, эritema, photosensitivity, increased perspiration, alopecia.

Metabolism: hyperkalemia, gout.

Allergic reactions: <1% – hives, skin rash, itch, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, throat). Sometimes angioedema developed earlier when taking other drugs, incl. ACE inhibitors.

*side effects, the frequency of which is comparable to placebo.

In most cases Lorista^® well tolerated, side effects are mild and transient in nature and do not require discontinuation of the drug.

Contraindications

- Hypotension;

- Hyperkalemia;

- Degidratatsiya;

- Lactose intolerance;

- Galactosemia and malabsorption syndrome glucose / galactose;

- Pregnancy;

- Lactation;

- Childhood and adolescence up 18 years (efficacy and safety have not been established);

- Hypersensitivity to losartan and / or other ingredients.

FROM caution use in patients with hepatic and / or renal insufficiency, snizhennom OCK, disruption of water and electrolyte balance, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

Pregnancy and lactation

Data on the use of losartan during pregnancy is not. Fetal renal perfusion, which depends on the development of the renin-angiotensin system, begins to function in the III trimester of pregnancy. The risk to the fetus increases if losartan in II and III trimesters. In establishing pregnancy therapy with losartan should be stopped immediately.

No data on the allocation of losartan in breast milk. Therefore it is necessary to resolve the issue of termination of breastfeeding or cancellation of therapy with losartan in view of its importance for the mother.

Cautions

In patients with reduced BCC (eg, during therapy with high doses of diuretics) may develop symptomatic hypotension. Prior to receiving losartan is necessary to eliminate existing violations, or begin therapy with small doses.

Patients with mild to moderate hepatic cirrhosis the concentration of losartan and its active metabolite in plasma after ingestion above, than in healthy. Therefore, patients with a history of liver disease therapy recommended at lower doses.

In patients with impaired renal function, both diabetic, or without, often developed hyperkalemia, it should be understood, but only in rare cases as a result of this treatment is stopped. During treatment should regularly monitor the concentration of potassium in the blood, especially in elderly patients, renal impairment.

Drugs, acting on the renin-angiotensin system, can increase the content of urea and serum creatinine in patients with bilateral renal artery stenosis or unilateral stenosis of the artery only kidney. Changes in renal function may be reversible upon discontinuation. During treatment should regularly monitor the concentration of serum creatinine at regular intervals.

Use in Pediatrics

The drug is contraindicated for the treatment of children and adolescents under the age of 18 years, because there is no experience with the drug in pediatrics.

Effects on ability to drive vehicles and management mechanisms

Data on the effect of losartan on the ability to drive or other engineering controls are absent.

Overdose

Symptoms: marked reduction in blood pressure, tachycardia; as a result of the parasympathetic (vagal) stimulation may develop bradycardia.

Treatment: diurez, simptomaticheskaya therapy. Hemodialysis nyeeffyektivyen.

Drug Interactions

There was no any clinically significant drug interactions with hydrochlorothiazide, digoksinom, nepryamыmy anticoagulants, cimetidine, fenoʙarʙitalom, ketoconazole and erythromycin.

During simultaneous reception with rifampicin and fluconazole was observed reduction in the active metabolite of losartan potassium. The clinical implications of this phenomenon are unknown.

The simultaneous use of potassium-sparing diuretics (eg, spironolactone, triamterene, amilorid) and potassium supplements increase the risk of hyperkalemia.

Concomitant use of NSAIDs, including selective COX-2 inhibitors, may reduce the effect of diuretics or other antihypertensives.

When losartan administered concurrently with thiazide diuretics, reduction of blood pressure is approximately additive character. Strengthens (mutually) effect of other antihypertensives (diuretics, beta-blockers, simpatolitikov).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, dry place at temperatures no higher than 30 ° C. Shelf life of the drug in tablet form 12.5 mg, 25 mg 100 mg – 2 year; in the form of tablets 50 mg – 5 years.

Vladimir Andreevich Didenko

618 8 minutes read