| Composition |
| Each F.C.Tablet contains valsartan 80 mg + hydrochlorothiazide 12.5 mg. |
| Excipients |
Tablet core: Colloidal Silicon Dioxide (Aerosil) , Cross Povidon, Magnesium Stearate, Microcrystalline Cellulose.
Film Coat: Hypromellose, Iron Oxides, Polyethylene Glycol ,Talc , Titanium dioxide, Iron oxide. |
| Mechanism Of Action |
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. Its action is therefore independent of the pathways for angiotensin II synthesis.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing the 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. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
The mechanism of the antihypertensive effect of thiazides is unknown. |
| Pharmacodynamic properties |
Valsartan:
An oral dose of 80 mg inhibits the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. No information on the effect of larger doses is available.
Hydrochlorothiazide : After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours. |
| PHARMACOKINETIC PROPERTIES |
Valsartan:
peak plasma concentration is reached 2 to 4 hours after dosing.
Absolute bioavailability for the capsule formulation is about 23%. Food decreases the exposure (as measured by AUC) to valsartan by about 48% and peak plasma concentration (Cmax) by about 59%.
Hydrochlorothiazide:
The estimated absolute bioavailability of hydrochlorothiazide after oral administration is about 70%. Peak plasma hydrochlorothiazide concentrations (Cmax) are reached within 2 to 5 hours after oral administration. There is no clinically significant effect of food on the bioavailability of hydrochlorothiazide.
Hydrochlorothiazide binds to albumin (40% to 70%) and distributes into erythrocytes. Following oral administration, plasma hydrochlorothiazide concentrations decline bi-exponentially, with a mean distribution half-life of about 2 hours and an elimination half-life of about 10 hours.
Distribution:
Valsartan is highly bound to serum proteins (95%), mainly serum albumin.
Metabolism:
Valsartan: The primary metabolite, accounting for about 9% of dose, is valeryl 4-hydroxy valsartan.
Hydrochlorothiazide: Is not metabolized.
Excretion :
Valsartan: Valsartan, is primarily eliminated in feces (about 83% of dose) and urine (about 13% of dose).
Hydrochlorothiazide: About 70% of an orally administered dose of hydrochlorothiazide is eliminated in the urine as unchanged drug.
|
| INDICATIONS |
Valican - H is indicated for the treatment of essential hypertension. This fixed-dose combination is indicated in patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy.
|
| CONTRAINDICATIONS |
- is contraindicated in patients who are hypersensitive to any component of this product.
- Because of the presence of hydrochlorothiazide, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
- Do not coadminister aliskiren with valsartan and hydrochlorothiazide in patients with diabetes . |
| Side EFFECTS |
Palpitations and tachycardia, Tinnitus and vertigo, Dyspepsia, diarrhea, flatulence, dry mouth, nausea, abdominal pain, abdominal pain upper, and vomiting, Asthenia, chest pain, fatigue, peripheral edema and pyrexia, Bronchitis, bronchitis acute, influenza, gastroenteritis, sinusitis, upper respiratory tract infection and urinary tract infection, Blood urea increased, Arthralgia, back pain, muscle cramps, myalgia, and pain in extremity, Dizziness postural, paraesthesia, and somnolence ,Anxiety and insomnia, Pollakiuria, Erectile dysfunction, Dyspnea, cough, nasal congestion, pharyngolaryngeal pain and sinus congestion, Hyperhidrosis and rash, Hypotension , Loss of appetite, mild nausea and vomiting, Postural hypotension, Hyponatraemia, hypomagnesaemia, hyperuricaemia, Hypokalaemia, blood lipids increased (mainly at higher doses).
|
| WARNINGS |
Fetal Toxicity: Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death..
Hypotension in Volume – and/or Salt Depleted Patients:
In patients with an activated renin – angiotensin system, such as volume – and/or salt-depleted patients receiving high dose of diuretics, symptomatic hypotension may occur.
This condition should be corrected prior to administration of valsartan /hydrochlorothiazide, or the treatment should start under close medical supervision.
Impaired Renal Function:
Changes in renal function including acute renal failure can be caused by drugs that inhibit the rennin angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on valsartan and hydrochlorothiazide. Monitor renal function periodically in these patients.
Hypersensitivity Reaction:
Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.
Systemic Lupus Erythematous:
Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematous.
Lithium Interaction:
Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of valsartan or thiazide diuretics.
Potassium Abnormalities:
Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. Drugs that inhibit the rennin angiotensin
system can cause hyperkalemia. Monitor serum electrolytes periodically.
Acute Myopia and Secondary Angle-Closure Glaucoma:
Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible.
Metabolic Disturbances:
Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.
Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.
Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium.
Driving and using machines :
This combination may occasionally cause dizziness and affect the ability to concentrate. Patients should be adviced not to drive or use machines.
|
| DRUG INTERACTIONS |
Valsartan:
No clinically significant phatmacolinetic interactions were observerd when valsartan was coadministered with: amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin. The valsartan–atenolol combination was more antihypertensive than either component, but it did not lower the heart rate more than atenolol alone.
Coadministration of valsartan and warfarin change the pharmacokinetics of valsartan or the time-course of the anticoagulant properties of warfarin.
Hydrochlorothiazide:
When administered concurrently the following drugs may interact with thiazide diuretics:
Alcohole, barbiturates, or narcotics – Potentiation of orthostatic hypotention may occure.
Antidiabeticdrugs(oral agents and insulin) – Dosage adjustment of the antidiabetic drug may be required.
Other antihypertensive drugs – Additive effect or potentiation.
Cholestyramine and colestipol resins – Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43% respectively.
Corticosteroids, ACTH-Intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., norepinphtine)- Possible decreased response to pressoramines but not sufficient to preclude their use.
Skeletal muscle relaxents, nondepolarizing (e.g., tubocurarine) – Possible increased responsiveness to the muscle relaxent.
Lithium – should not generally be given with diuretics. Diuretics agents reduce the renal clearance of lithium and add a high risk of lithium toxicity.
Non-steroidal anti-inflammatory Drugs – In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium –sparing and thiazide diuretics. Therefore, when valsartan /hydrochlorothiazide and non-steroidal anti-inflammatory agent are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretics is obtained.
Potassium:
Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If comedication is considered necessary, monitoring of serum potassium is advisable.
Dual Blockade of the Renin-Angiotensin System (RAS):
Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
Do not coadminister aliskiren with valsartan and hydrochlorothiazide in patients with diabetes. Avoid use of aliskiren with valsartan and hydrochlorothiazide in patients with renal impairment (GFR < 60
mL/min). |
| Pregnancy & lactations |
Pregnancy: Teratogenic Effects. Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting
oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.
Nursing Mothers:
It is not known whether valsartan is excreted in women milk, but valsartan was excreted In the milk of lactating rats. Thiazide appear in women milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use:
Safety and effectiveness of valsartan and hydrochlorothiazide in pediatric patients have not been established. |
| Dosage & Administration |
General Considerations:
The usual starting dose of Valican-H tablets is 160 mg/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 320 mg/25 mg tablet once daily as needed to control blood pressure. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.
Add-On Therapy:
A patient whose blood pressure is not adequately controlled with valsartan (or another ARB) alone or hydrochlorothiazide alone may be switched to combination therapy with Valican-H tablets.
The clinical response to Valican-H tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 320 mg/25 mg.
Initial Therapy:
Valican-H tablets are not recommended as initial therapy in patients with intravascular volume depletion.
Valican-H tablets may be administered with other antihypertensive agents.
Renal impairment :
No dose adjustment is required for patients with mild to moderate renal impairment (Glomerular Filtration Rate ≥ 30 ml/min). Due to the presence of hydrochlorothiazide, The combination is contraindicated in patients with severe renal impairment (Glomerular Filtration Rate< 30 ml/min) and anuria. Concomitant use of valsartan with aliskiren is contraindicated in patients with renal impairment (Glomerular Filtration Rate< 60 mL/min/1.73 m2) .
Concomitant use of valsartan with aliskiren is contraindicated in patients with diabetes mellitus .
Hepatic impairment:
In patients with mild to moderate hepatic impairment without cholestasis the dose of valsartan should not exceed 80 mg. No adjustment of the hydrochlorothiazide dose is required for patients with mild to moderate hepatic impairment. Due to the presence of valsartan, The combination is contraindicated in patients with severe hepatic impairment or with biliary cirrhosis and cholestasis .
Elderly :No dose adjustment is required in elderly patients.
Pediatric patients : The combination is not recommended for use in children below the age of 18 years due to a lack of data on safety and efficacy. |
| OVERDOSE |
The most likely manifestations of overdose would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed level of consciousness, circulatory collapse and shock have been reported. If symptomatic hypotention should occur, supportive treatment should be instituted.
Valsartan is not removed from the plasma by dialysis.
The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The most common signs and symptoms observed in patients are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accelerate cardiac arrhythmias.
|
| Storage & Packaging |
Storage conditions:
Store in dry place at temperature between( 15-30 )°C.
Packaging:
Valican – H 80/12.5: Carton box of 20 Film Coated Tablets packed inside blisters with a leaflet. |
