Cardosal 10,10 mg 28 pcs

An angiotensin II receptor antagonist (AT1 type). Angiotensin II is the primary vasoactive hormone of the RAAS and plays a significant role in the pathophysiology of arterial hypertension via AT1 receptors. Olmesartan is thought to block all angiotensin II effects mediated by AT1 receptors regardless of the source and pathway of angiotensin II synthesis.

In arterial hypertension, olmesartan causes a dose-dependent prolonged decrease in BP. There is no evidence of arterial hypotension after the first dose, of tachycardia during long-term treatment (for Cardosal® 20 and Cardosal® 40) and of abstinence syndrome (rapid increase of BP after drug withdrawal).

Medoxomil olmesartan once daily effectively and gently reduces BP over 24 hours, and the effect after a single dose is similar to that of twice daily administration at the same daily dose.

The hypotensive effects of olmesartan generally develop as early as 2 weeks, with maximal effect after approximately 8 weeks of therapy.

Pharmacokinetics

Absorption and distribution

Olmesartan medoxomil is a prodrug. It is rapidly converted to the pharmacologically active metabolite olmesartan by enzymes in the intestinal mucosa and in the portal blood during absorption from the GI tract. Olmesartan medoxomil was not detected in unchanged form in plasma. The bioavailability of olmesartan averages 25.6%. Cmax of olmesartan in plasma is reached on average 2 hours after oral administration of olmesartan medoxomil and increases approximately linearly with increasing single dose up to 80 mg.

Eating has no significant effect on the bioavailability of olmesartan, so olmesartan medoxomil can be taken regardless of meals.

There are no clinically significant differences in the pharmacokinetic parameters of olmesartan according to gender.

Olmesartan binds to plasma proteins (99.7%), but the potential for clinically significant shifts in protein binding magnitude when interacting olmesartan with other highly bindable and concomitantly used drugs is low (this is confirmed by the absence of clinically significant interaction between olmesartan and warfarin). Binding of olmesartan to blood cells is insignificant.

Metabolism and excretion

Total plasma clearance is typically 1.3 L/h (coefficient of variation is 19%) and is relatively low compared to hepatic blood flow (approximately 90 L/h). Renal excretion is approximately 40%, with bile about 60%. Intrahepatic circulation of olmesartan is minimal. Since most of olmesartan is excreted through the liver, its use in patients with biliary obstruction is contraindicated.

The T1/2 of olmesartan is 10-15 h after multiple oral administration. Meaningful effect of therapy is achieved after the first few doses of the drug, and no further cumulation is observed after 14 days of repeated use. Renal clearance is approximately 0.5-0.7 l/h and is independent of the drug dose.

Pharmacokinetics in Special Clinical Cases

In patients with impaired renal function, the AUC at steady state (steady state) was increased by approximately 62%, 82% and 179% for mild, moderate and severe renal impairment, respectively, compared to healthy volunteers.

After a single oral dose, AUC values for olmesartan were 6% and 65% higher in patients with mild and moderate hepatic impairment, respectively, compared to healthy volunteers. The unbound fraction of olmesartan 2 hours after a dose of the drug in healthy volunteers and in patients with mild and moderate hepatic impairment was 0.26%, 0.34% and 0.41%, respectively.

Indications

Essential arterial hypertension.

Active ingredient

Composition

Active ingredients:

olmesartan medoxomil 10 mg.

Auxiliary substances:

Microcrystalline cellulose – 10 mg,

Hyprolose low substituted – 20 mg,

Lactose monohydrate – 61.6 mg,

Hyprolose 6-10 mPa×s – 2.5 mg,

Magnesium stearate – 0.9 mg.

The composition of the film coating:

Hypromellose 5 mPa×s – 3.6 mg,

talc – 0.7 mg,

titanium dioxide (E171) – 0.7 mg.

How to take, the dosage

It is recommended that Cardosal® be taken orally every day at the same time, regardless of meals, once daily.

The recommended starting dose for adults is 10 mg (1 tablet of Cardosal® 10) once daily.

If the 10 mg/day dose is insufficient to reduce BP, the dose can be increased to 20 mg/day (possible use of Cardosal® 20).

If additional BP lowering is necessary the drug dose may be increased up to maximum 40 mg/day (possible use of Cardosal® 40) or a diuretic (hydrochlorothiazide) may be used in addition. The maximum daily dose is 40 mg.

Interaction

Co-administration with potassium-saving diuretics, potassium preparations, salt substitutes containing potassium, or other drugs that may increase serum potassium levels (e.g., heparin) is not recommended; this may lead to increased serum potassium levels.

The antihypertensive effect of olmesartan therapy may be enhanced when combined with other hypotensive agents.

The NSAIDs, including acetylsalicylic acid at doses greater than 3 g/day, as well as COX-2 inhibitors, and angiotensin II receptor antagonists may act synergistically to decrease glomerular filtration. When concomitant use of NSAIDs and angiotensin II receptor antagonists, there may be a risk of acute renal failure, so it is recommended to monitor renal function at the beginning of treatment, as well as regular intake of sufficient fluids. At the same time, concomitant treatment may reduce the antihypertensive effect of angiotensin II receptor antagonists, leading to a partial loss of their therapeutic effectiveness.

Concomitant use with antacids (magnesium and aluminum hydroxide) may moderately reduce the bioavailability of olmesartan.

There have been reports of reversible increases in serum lithium concentration and toxicity during concomitant use of lithium with ACE inhibitors and angiotensin II receptor antagonists, so the use of olmesartan medoxomil in combination with lithium preparations is not recommended. If appropriate combination therapy is required, regular monitoring of serum lithium levels is recommended.

Special Instructions

Symptomatic arterial hypotension, especially after the first dose of the drug, may occur in patients with reduced RBC and/or reduced sodium levels due to intensive diuretic therapy, dietary salt restriction, or due to diarrhea or vomiting. These factors should be eliminated before initiating the use of Cardosal®.

In patients in whom vascular tone and renal function are highly dependent on RAAS activity (e.g., in patients with severe chronic heart failure or impaired renal function including renal artery stenosis), treatment with other drugs acting on this system is associated with the possibility of acute arterial hypotension, azotemia, oliguria or, in rare cases, acute renal failure. The possibility of similar action cannot be excluded with angiotensin II receptor antagonists.

There is an increased risk of severe arterial hypotension and renal failure if the patient with bilateral renal artery stenosis or artery stenosis of the only functioning kidney receives therapy with medications that affect the RAAS.

In patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended during use of Cardosal®. There is no experience with the use of Cardosal® in patients with recent kidney transplantation or in patients with end-stage renal impairment (e.g., CKG less than 12 ml/min).

As with other angiotensin II receptor antagonists and ACE inhibitors, treatment with Cardosal® may cause hyperkalemia if the patient has impaired renal function and/or chronic heart failure. In patients of this risk group it is recommended to control serum potassium level.

As with other angiotensin II receptor antagonists, the combination of lithium and Cardosal® is not recommended.

As with other angiotensin II receptor antagonists, therapy with Cardosal® is somewhat less effective in non-Hispanic patients with arterial hypertension than in patients of other races.

As with any antihypertensive drug, excessive BP reduction in patients with CHD or cerebrovascular insufficiency may lead to myocardial infarction or stroke.

Impact on the ability to operate vehicles and other mechanisms requiring increased concentration

Impact on the ability to operate vehicles and other mechanisms requiring increased concentration Influence of the drug Cardosal® on driving and operating machinery has not been studied, that is why during the treatment by the drug Cardosal® one should be careful when driving vehicles and engaging in potentially dangerous activities requiring high concentration and quick psychomotor reactions (dizziness and weakness are possible).

Contraindications

Side effects

Possible side effects are listed below in descending frequency of occurrence:

Hematopoietic system: very rare – thrombocytopenia.

CNS disorders: sometimes – dizziness; very rare – headache.

Respiratory system: often – pharyngitis, rhinitis; very rare – cough, bronchitis.

The digestive system: often – diarrhea, dyspepsia, gastroenteritis; very rare – abdominal pain, nausea, vomiting.

Skin disorders: very rarely – skin itching, rash, angioedema, allergic dermatitis, urticaria.

Musculoskeletal system disorders: often – back pain, bone pain, arthralgia, arthritis; very rarely – muscle cramps, myalgia.

Perior urinary system disorders: frequently – hematuria, urinary tract infection; very rarely – acute renal failure.

Laboratory disorders: very rarely – increased serum creatinine and urea levels, increased liver enzyme activity.

Cardiovascular system disorders: sometimes – angina pectoris, tachycardia; rarely – marked decrease of BP.

Mechanisms: often – increase of CPK level, hypertriglyceridemia, hyperuricemia; rarely – hyperkalemia.

As to the body in general: often – chest pain, flu-like symptoms, peripheral edema; very rarely – asthenia, fatigue, malaise, somnolence.

Overdose

Symptoms: pronounced decrease in BP.

Treatment: if BP is markedly decreased, it is recommended to lie the patient on his back with his legs elevated.

Gastric lavage and/or administration of activated charcoal, therapy aimed at the correction of dehydration and water-salt metabolism disorders, replete blood circulation is recommended.

Pregnancy use

There is no experience with the use of olmesartan medoxomil in pregnant women. However, due to reports of severe teratogenic effects of drugs acting directly on the renin-angiotensin system, like any drug of this class, olmesartan is contraindicated during pregnancy. If pregnancy occurs during therapy with Cardosal® the drug should be discontinued.

There is no data whether olmesartan is excreted with the breast milk, therefore if it is necessary to use Cardosal® during lactation, breastfeeding should be stopped for the period of taking the drug.

Similarities