VALSAMAK PLUS          Film Coated Tablets

VLSARTAN  & HYDROCHLOROTHIAZIDE               

COMPOSITION:

VALSAMAK PLUS-80 F.C.Tablets: Each film coated tablet contains valsartan 80mg + hydrochlorothiazide 12.5mg.

 VALSAMAK PLUS-160 F.C.Tablets: Each film coated tablet contains valsartan 160mg +hydrochlorothiazide 12.5mg.

Excipient

Microcrystalline cellulose -Crospovidone -Colloidal Silicon Dioxide-Magnesium stearate- Hydroxy propyl Methylcellulose-Poly Ethylene Glycol -Titanium dioxide –Talc-Yellow iron oxide-Red iron oxide

PHARMACOLOGY:

Valsartan blocks the vasoconstrictor and aldosterone secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues , such as vascular smooth muscle and the adrenal gland.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium.

PHARMACOKINETIC PROPERTIES
Valsartan/hydrochlorothiazide
The systemic availability of hydrochlorothiazide is reduced by about 30% when co-administered with valsartan. The kinetics of valsartan are not markedly affected by the co-administration of hydrochlorothiazide. This observed interaction has no impact on the combined use of valsartan and hydrochlorothiazide, since controlled clinical trials have shown a clear anti-hypertensive effect, greater than that obtained with either active substance given alone, or placebo.

Valsartan

Onset of action: ~2 hours

Duration: 24 hours

Distribution: Vd: 17 L (adults)

Protein binding: 95%, primarily albumin

Metabolism: Only about 20% of dose is recovered as metabolites, This metabolite is inactive.

Time to peak, serum: 2-4 hours

Bioavailability: 25% (range: 10% to 35%), Food decreases exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%. This reduction in AUC is not, however, accompanied by a clinically significant reduction in the therapeutic effect, and valsartan can therefore be given either with or without food.

Half-life elimination: ~6 hours

Excretion: Feces (83%) and urine (13%) as unchanged drug

Hydrochlorothiazide

Onset of action: Diuresis: ~2 hours

Duration: 6-12 hours

Absorption: ~50% to 80%

Distribution: 3.6-7.8 L/kg

Protein binding: 68%, mainly serum albumin

Metabolism: Not metabolized

Bioavailability: 50% to 80%, The effect of food on hydrochlorothiazide absorption has little clinical significance

Half-life elimination: 5.6-14.8 hours

Time to peak: 1-2.5 hours

Excretion: Urine (as unchanged drug)

INDICATIONS:

Hypertension :VALSAMAK PLUS is indicated for the treatment of hypertension.

CONTRAINDICATIONS:

- Known hypersensitivity to the components of this product or to sulfonamide derivative.

- pregnancy and lactation.

- biliary cirrhosis and cholestasis

- anuria

PRECAUTIONS:

-  hypotension may occur .

-  Caution is advised when administering VALSAMAK PLUS to patients with renal artery stenosis, renal and liver disease or systemic lupus erythematosus.

- Like other thiazide diuretics, hydrochlorothiazide can cause hypokalemia, Caution in patients with hypokalemia, hyponatremia , hypercalcemia or symptomatic hyperuricemia.

- Disturbance of serum electrolyte balance,glucose tolerance and serum levels of cholesterol, tryglicerides and uric acid.

- Caution in driving or operating machinery.

-  Acute angle-closure glaucoma.

- Caution in patients with allergy or asthma.

SIDE EFFECTS:

- Most common adverse reactions are headache, dizziness, fatigue and syncope.

- For the hydrochlorothiazide component: Most common adverse reactions: Hypokalemia and rise in blood lipids, hypomagnesemia, hyperuricemia,hyponatremia, urticaria and other forms of rash ,decreased appetite, mild nausea and vomiting ,orthostatic hypotenstion .

DRUG INTERACTIONS:

- Concomitant treatment with potassium-sparing diuretics or potassium supplements may increase

potassium levels.

- Caution if combined with other antihypertensive.

- Caution with drugs causing hypokalemia (e.g. corticosteroids, amphotericin, penicillin G, carbenoxolone).

- Monitoring of serum electrolyte balance with drugs causing hyponatremia (e.g. antidepressants, antipsychotics, antiepileptics).

- Concomitant treatment with NSAIDs including Cox-2 Inhibitors may decrease antihypertensive effects. Monitoring of renal function with NSAIDs and Cox-2 selective inhibitors.

- Caution with insulin and oral antidiabetic agents.

- Caution with anionic exchange resins, allopurinol, amantadine, diazoxide, cytotoxic drugs, anticholinergic agents, vitamin D, calcium salts, ciclosporin, methyldopa, pressor amines (e.g. noradrenaline),barbiturates, narcotics and alcohol.

DOSAGE & ADMINISTRATION:

The recommended dose of VALSAMAK PLUS-80 or VALSAMAK PLUS-160 is one tablet once daily.

Renal impairment
No dosage adjustment is required for patients with renal impairment with a creatinine clearance > 30 ml/min. Periodic monitoring of serum potassium, creatinine and uric acid levels is recommended in patients with renal impairment.

Hepatic impairment
In patients with mild to moderate hepatic impairment without cholestasis, The product should be used with caution. Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Overdose
Symptoms
Overdose with valsartan may result in marked hypotension, which could lead to depressed level of consciousness, circulatory collapse and/or shock. In addition, the following signs and symptoms may occur due to an overdose of the hydrochlorothiazide component: nausea, somnolence, hypovolaemia, and electrolyte disturbances associated with cardiac arrhythmias and muscle spasms.

Treatment
The therapeutic measures depend on the time of ingestion and the type and severity of the symptoms, stabilisation of the circulatory condition being of prime importance.
If hypotension occurs, the patient should be placed in the supine position and salt and volume supplementation should be given rapidly.
Valsartan cannot be eliminated by means of haemodialysis because of its strong plasma binding behaviour whereas clearance of hydrochlorothiazide will be achieved by dialysis.

PACKAGING:

VALSAMAK PLUS-80 F.C.Tablets: A pack of 30 F.C.Tablets.

VALSAMAK PLUS-160 F.C.Tablets: A pack of 30 F.C.Tablets.

STORAGE CONDITIONS:

Store VALSAMAK PLUS at temperature between  (15-30)°C, Protect from moisture.