Diovan

Diovan is the active specific antagonist of receptors of angiotensin II for oral administration.

Form of release and structure

Diovan release in the form of tablets, coated:

• Yellow, oval, with slanted edges, on one of the parties of risk and a text of "DO", on another – "NVR" (on 14 pieces in blisters, on 1, 2, 4 or 7 blisters in a cardboard pack);
• Light pink, round, with slanted edges, on one of the parties of risk and a text of "D/V", on another – "NVR" (on 14 pieces in blisters, on 1, 2, 4 or 7 blisters in a cardboard pack);
• Gray-orange, oval, on one of the parties of risk and a text of "DX/DX", on another – "NVR" (on 14 pieces in blisters, 1, 2, 4 or 7 blisters in a cardboard pack);
• Dark gray-violet, oval, with slanted edges, on one of the parties of risk and a text of "DXL", on another – "NVR" (on 7 pieces in blisters, on 1, 2, 4, 7 or 20 blisters in a cardboard pack; on 14 pieces in blisters, on 1, 2, 4, 7 or 20 blisters in a cardboard pack; on 56, 98 or 280 pieces in bottles from polyethylene of high density).

Is a part of 1 tablet:

• Active ingredient: валсартан – 40, 80, 160 or 320 mg;
• Auxiliary components: кросповидон, microcrystallic cellulose, anhydrous colloid silicon dioxide, gidroksipropilmetiltsellyuloz (gipromelloz), magnesium stearate, titanium dioxide (E171), macrogoal 8000, iron oxide.

Indications to use

• CHF (chronic heart failure) of the II-IV functional class on classification of NYHA at the patients receiving standard therapy, including diuretics, foxglove drugs, and also APF inhibitors or β-adrenoblockers ((((((((((not at the same time) (use of the listed drugs is not obligatory);
• Arterial hypertension;
• The acute myocardial infarction complicated by a left ventricular failure and/or systolic dysfunction of a left ventricle (at stability of indicators of a hemodynamics) – for increase in survival of patients.

Contraindications

Absolute:

• Pregnancy;
• Period of breastfeeding (lactation);
• Hypersensitivity to drug components.

Relative (Diovan it is necessary to take with caution):

• Bilateral stenosis of renal arteries;
• Stenosis of an artery of the only kidney;
• Observance of a diet with sodium restriction;
• The states which are followed by decrease in the volume of the circulating blood (VCB) including diarrhea, vomiting;
• Liver failure against the background of obstruction of biliary tract;
• Renal failure with the clearance of creatinine (CC) ≤ 10 ml/min., including patients on a hemodialysis.

Specific recommendations about Diovan's use at children's age cannot be formulated as controlled researches of safety and efficiency of therapy valsartany at children and teenagers up to 18 years were not conducted.

Route of administration and dosage

Pill should be taken orally, without chewing.

The recommended dosing mode depending on a disease/state:

• Arterial hypertension: 80 mg of 1 times a day, daily (irrespective of a sex, age and race). The anti-hypertensive effect is reached in the first 2 weeks of a course, the maximum effect is observed in 4 weeks. If it is not possible to reduce adequately the arterial pressure (AP), about 320 mg are allowed to increase a daily dose, or in addition to appoint diuretics;
• Chronic heart failure: an initial dose – 40 mg 2 times a day, daily. A dose it is necessary to increase gradually to 80 mg 2 times a day, and in case of good tolerance – do160 mg 2 times a day. At the same time perhaps it will be required to lower a dose of the diuretics accepted along with Diovan. The maximum daily dose – 320 mg divided into 2 receptions. At assessment of a condition of patients with chronic heart failure it is necessary to carry out assessment of a functional condition of kidneys also;
• State after the postponed myocardial infarction (therapy valsartany needs to be begun during 12 h after the postponed myocardial infarction): an initial dose – 20 mg (^1/2 tablets of 40 mg) 2 times a day. Increase in a dose it is necessary to carry out by a titration method (40, 80, 160 mg 2 times a day), gradually, for several weeks, to achievement of a target dose to 160 mg 2 times a day. The maximum daily dose – 320 mg divided into 2 receptions. As a rule, achievement of a dose of 80 mg 2 times a day is recommended by the end of the second week of therapy; the maximum target dose (160 mg 2 times a day) is usually reached by the end of the third month. Achievement of a target dose depends on portability of a valsartan during titration. At assessment of a condition of patients after the postponed myocardial infarction it is necessary to carry out assessment of a functional condition of kidneys also.

If at Diovan's reception hypotension which is followed by clinical manifestations or disturbances of work of kidneys develops, it is recommended to consider the possibility of a dose decline.

Correction of the mode of dosing is not required to patients with a liver failure of not biliary origin without the phenomena of a cholestasia and to patients with a renal failure.

Side effects

The side effects from reception of a valsartan observed with a frequency of 1% regardless of duration of therapy, a dose of drug, age, sex or race of patients, including data of post-market researches in group of patients with arterial hypertension:

• System of a hemopoiesis: very seldom – thrombocytopenia; often – a neutropenia;
• Immune system: very seldom – hypersensitivity reactions, including a serum disease;
• Central Nervous System (CNS): very seldom – head ^bol4; seldom – ^{golovokruzheniye4}; sometimes – ^obmorok1, вертиго, decrease in a libido, sleeplessness; often – postural ^{golovokruzheniye2};
• Cardiovascular system (CCC): very seldom – a vasculitis; sometimes – cordial ^{nedostatochnost1}, arterial ^{gipotenziya1,4}; often – orthostatic ^gipotenziya2;
• Alimentary system: very seldom – ^toshnota4; sometimes – abdominal pains, diarrhea;
• Respiratory system: sometimes – cough;
• Dermatological answers: very seldom – an itch, rash, angioneurotic ^otek3;
• Musculoskeletal system: very seldom – a mialgiya, an arthralgia; sometimes – a dorsodynia;
• Urinary system: very seldom – dysfunctions ^pochek3,4, renal ^{nedostatochnost3}, acute renal ^{nedostatochnost3};
• Infections and invasions: very seldom – rhinitis; sometimes – infections of upper parts of respiratory tracts, sinusitis, pharyngitis; often – viral infections;
• Another: sometimes – feeling of fatigue, hypostases, an adynamy, ^{giperkaliyemiya1,2}.

Criteria for evaluation of frequency of the undesirable phenomena: very seldom – <1/10 000; seldom – <1/1000 –> 1/10 000; sometimes – <1/100 –> 1/1000; often – <1/10 –> 1/100; very often –> 1/10.

Footnotes

1 – at the patients receiving Diovan after the postponed myocardial infarction.

2 – at the patients receiving drug at therapy of HSN.

3 – with a frequency "sometimes" (<1/100 –> 1/1000) at the patients receiving Diovan after the postponed myocardial infarction.

4 – more often at the sick HSN receiving Diovan (it is frequent – dizziness, hypotension, a renal failure; sometimes – nausea, a headache).

All patients with HSN accepted traditional medicinal therapy, including foxglove drugs, diuretics, APF inhibitors or β-adrenoblockers.......... In case of long reception of a valsartan at sick HSN additional side effects were not noted.

Data of changes of laboratory indicators:

• Concentration of hemoglobin and hematocrit: in controlled clinical trials reception of a valsartan showed essential (more than 20%) decrease in a hematocrit at 0,8% of patients, hemoglobin – at 0,4%. For comparison – the patients receiving placebo showed decrease, both hemoglobin, and a hematocrit in 0,1% of cases;
• Neutropenia: at receiving Diovan was revealed in 1,9% of cases; at receiving APF inhibitors – in 1,6%;
• Concentration of the general bilirubin of creatinine and potassium in blood serum: significant increase in values was noted, respectively, at 0,8%, 4,4%, 6% of the patients accepting Diovan, and at 1,6%, 6,4%, 12,9% – accepting APF inhibitors. At patients with HSN increase in concentration of creatinine more than for 50% was noted in 3,9% of cases at therapy by Diovan, in comparison with 0,9% in group of placebo. At the same time potassium level in blood serum increased more than by 20% at 10,0% of the patients receiving Diovan, and at 5,1% – the receiving placebos. At therapy after the postponed myocardial infarction increase in concentration of creatinine in serum twice at 4,2% accepting валсартан at 3,4% accepting captopril and at 4,8% of the patients accepting валсартан + captopril was noted;
• Increases in activity of hepatic transaminases: the patients receiving валсартан have messages on cases;
• Increase in concentration in urea nitrogen blood serum (more than for 50%): at therapy valsartany – 16,6%, at patients from group are placebo – 6,3%.

The overdose by Diovan first of all is shown by the expressed decrease in the ABP which effects can be a collapse and/or shock. It is necessary to cause vomiting if drug was accepted recently. The expressed decrease in the ABP usually is removed intravenous administration of 0,9% of solution of sodium of chloride. By means of a hemodialysis it is improbable to bring валсартан out of an organism.

Special instructions

At therapy by Diovan regular control of laboratory indicators at patients with essential arterial hypertension is not necessary.

In case of the expressed deficit of sodium and/or volume of the circulating blood in an organism, for example, when receiving high doses of diuretics, occasionally, at the beginning of therapy by Diovan, there can be arterial hypotonia with typical clinical manifestations. Therefore prior to treatment it is recommended to carry out correction of content of sodium and OTsK, for example, reducing diuretic doses. At development of hypotonia of the patient it is necessary to lay horizontally, to raise his legs, further, if it is necessary, to make intravenous infusion of 0,9% chloride sodium solution. After stabilization by the ABP therapy by Diovan can be continued.

As a result of Diovan's reception by a short course by group of 12 patients with the renovascular hypertensia which developed for the second time as a result of a unilateral renal artery stenosis, some essential changes of a renal hemodynamics, concentration of the blood urea nitrogen (BUN) or creatinine in blood serum were not noted. However, considering that reception of other medicines influencing the renin-angiotensin-aldosteronovuyu system (RAAS) can become the reason of increase in concentration of creatinine in blood serum and urea at patients with a unilateral or bilateral renal artery stenosis, it is recommended to control these indicators from precaution.

After the postponed myocardial infarction or at patients with HSN at the beginning of therapy by Diovan some decrease in the ABP is often observed, during this period it is recommended to control its indicators. At observance of recommendations about the dosing mode usually there is no need of cancellation of Diovan because of hypotension. Sensitive patients as a result of inhibition of RAAS have a probability of change of work of kidneys. At a severe form of HSN treatment by APF inhibitors and antagonists of receptors of angiotensin can be followed by increase of an azotemia and/or an oliguria, in isolated cases – an acute renal failure and/or death (for this reason it is necessary to carry out assessment of function of kidneys at the patients who had an acute myocardial infarction and at patients with heart failure). Diovan's reception at therapy of a state after the postponed myocardial infarction in a complex with acetylsalicylic acid, trombolitika, statines and β-adrenoblockers is allowed..........

Accepting Diovan, it is recommended to be careful at control of motor transport or work with other difficult mechanisms.

Medicinal interaction

Simultaneous use of a valsartan with kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), the drugs of potassium or salts containing potassium can lead to increase in potassium concentration in blood serum. In case of need such combined treatment, it is necessary to observe extra care.

By results of drug use study Diovan with the following medicinal substances / means: warfarin, furosemide, Cimetidinum, digoxin, a hydrochlorothiazide, атенолол, indometacin, glibenclamide and амлодипин – clinically significant interaction was not noted.

As Diovan is not exposed to essential metabolism, for it clinically significant interactions with other medicines – inhibitors or inductors of system of P450 cytochrome are also improbable. In spite of the fact that substantially валсартан contacts proteins of a blood plasma, any interaction (in vitro) at this level with a number of the molecules having the same high linkng with proteins of plasma, for example, furosemide, diclofenac and warfarin was not revealed.

Terms and storage conditions

To store in the dry, dark place unavailable to children, at a temperature up to 30 °C.

Period of validity – 3 years.