Valsartan HCTZ Tablets SMPC Taj Pharmaceuticals

Valsartan and HCT 35 mg Tablet s TajPhar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, Valsartan and
H CT Dosage & Rx Info | Valsartan and H CT Uses , Side Effects - Antihyperte nsive, Valsartan and H CT : Indi cations, Side Effe cts, Warni ngs, Valsartan and H CT - Drug I nformation - TajP harma , Valsartan and HCT dose Taj pharma ceutical s Valsartan and H CT interactions, Taj Phar mace utical Valsartan and H CT contraindi cations , Valsartan and H CT price, Valsartan and HCT TajP harma Antihy pertensive Tablets S mP C - TajP harma Stay conne cted to all updated on Valsartan and H CT Taj Phar mace uticals Taj pharma ceutical s Mumbai. Patient I nforma tion Lea flets, SmPC.
Valsartan and and 3.7mm in thickness, and weighing approx.

156mg. The tablets are coloured light orange
Hydrochlorthiazide Tablets and imprinted with HGH on one side and CG on
USP 80mg/12.5mg, the other side.
160mg/12.5mg, 320mg/12.5mg 4. Clinical particulars

1. Name of the medicinal 4.1 Therapeutic indications
Treatment of essential hypertension in adults.
product
Valsartan HCT TajPharma fixed-dose
Valsartan and Hydrochlorthiazide Tablets USP combination is indicated in patients whose blood
80mg/12.5mg Taj Pharma pressure is not adequately controlled on
Valsartan and Hydrochlorthiazide Tablets USP valsartan or hydrochlorothiazide monotherapy.
160mg/12.5mg Taj Pharma
Valsartan and Hydrochlorthiazide Tablets USP 4.2 Posology and method of administration
320mg/12.5mg Taj Pharma Posology
The recommended dose of Valsartan HCT
2. Qualitative and quantitative TajPharma80mg/12.5 mg is one film-coated
composition tablet once daily. Dose titration with the
individual components is recommended. In each
a) Each film coated tablet contains: case, up-titration of individual components to
Valsartan USP 80mg the next dose should be followed in order to
Hydrochlorthiazide USP 12.5mg reduce the risk of hypotension and other adverse
Excipients q.s. events.
Colour: Red Oxide of Iron & Titanium Dioxide
USP When clinically appropriate direct change from
monotherapy to the fixed combination may be
b) Each film coated tablet contains: considered in patients whose blood pressure is
Valsartan USP 160mg not adequately controlled on valsartan or
Hydrochlorthiazide USP 12.5mg hydrochlorothiazide monotherapy, provided the
Excipients q.s. recommended dose titration sequence for the
Colour: Red Oxide of Iron & Titanium Dioxide individual components is followed.
USP
The clinical response to Valsartan HCT
c) Each film coated tablet contains: TajPharma should be evaluated after initiating
Valsartan USP 320mg therapy and if blood pressure remains
Hydrochlorthiazide USP 12.5mg uncontrolled, the dose may be increased by
Excipients q.s. increasing either one of the components to a
Colour: Red Oxide of Iron & Titanium Dioxide maximum dose of Valsartan HCT TajPharma
USP 320 mg/25 mg.
For the full list of excipients, see section 6.1. The antihypertensive effect is substantially
present within 2 weeks.
3. Pharmaceutical form
In most patients, maximal effects are observed
Valsartan HCT TajPharma80mg/12.5 mg within 4 weeks. However, in some patients, 4-8
Tablets: weeks treatment may be required. This should
Oval, non-divisible, film-coated tablets be taken into account during dose titration.
measuring approx. 10.2 to 5.4mm in diameter Method of administration
Valsartan and HCT 35 mg Tablet s TajPhar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, Valsartan and H CT Dosage & Rx Info | Valsartan and H CT Uses , Side Effects - Antihyperte nsive, Valsartan and H CT : Indi cations, Side Effe cts, Warni ngs, Valsartan and H CT - Drug I nformation - TajP harma , Valsartan and HCT dose Taj pharma ceutical s Valsartan and H CT interactions, Taj Phar mace utical Valsartan and H CT contraindi cations , Valsartan and H CT price, Valsartan and HCT TajP harma Antihy pertensive Tablets S mP C - TajP harma Stay conne cted to all updated on Valsartan and H CT Taj Phar mace uticals Taj pharma ceutical s Mumbai. Patient I nforma tion Lea flets, SmPC.
Valsartan HCT TajPharma can be taken with or - Refractory hypokalaemia, hyponatraemia,

without food and should be administered with hypercalcaemia, and symptomatic
water. hyperuricaemia.
Special populations - Concomitant use of Valsartan HCT TajPharma
with aliskiren containing products in patients
Patients with renal impairment
with diabetes mellitus or renal impairment (GFR
No dose adjustment is required for patients with < 60 mL/min/1.73m2) (see sections 4.5 and 5.1).
mild to moderate renal impairment (Glomerular
4.4 Special warnings and precautions for use
Filtration Rate (GFR) ≥ 30 ml/min). Due to the Serum electrolyte changes
hydrochlorothiazide component, Valsartan HCT
TajPharma is contraindicated in patients with Valsartan
severe renal impairment (GFR < 30 mL/min)
and anuria (see sections 4.3, 4.4 and 5.2). Concomitant use with potassium supplements,
potassium-sparing diuretics, salt substitutes
Patients with hepatic impairment containing potassium, or other agents that may
increase potassium levels (heparin, etc.) is not
In patients with mild to moderate hepatic
recommended. Monitoring of potassium should
impairment without cholestasis the dose of be undertaken as appropriate.
valsartan should not exceed 80 mg (see section
4.4). No adjustment of the hydrochlorothiazide Hydrochlorothiazide
dose is required for patients with mild to
moderate hepatic impairment. Due to the Hypokalaemia has been reported under
valsartan component, Valsartan HCT TajPharma treatment with thiazide diuretics, including
hydrochlorothiazide. Frequent monitoring of
is contraindicated in patients with severe hepatic
serum potassium is recommended.
impairment or with biliary cirrhosis and
cholestasis (see sections 4.3, 4.4 and 5.2). Treatment with thiazide diuretics, including
Older people hydrochlorothiazide, has been associated with
hyponatraemia and hypochloraemic alkalosis.
No dose adjustment is required in elderly Thiazides, including hydrochlorothiazide,
patients. increase the urinary excretion of magnesium,
which may result in hypomagnesaemia. Calcium
Paediatric patients
excretion is decreased by thiazide diuretics. This
Valsartan HCT TajPharma is not recommended may result in hypercalcaemia.
for use in children below the age of 18 years due As for any patient receiving diuretic therapy,
to a lack of data on safety and efficacy. periodic determination of serum electrolytes
4.3 Contraindications should be performed at appropriate intervals.
- Hypersensitivity to active substances, other Sodium and/or volume-depleted patients
sulfonamide-derived medicinal products or to
any of the excipients listed in section 6.1. Patients receiving thiazide diuretics, including
hydrochlorothiazide, should be observed for
- Second and third trimester of pregnancy clinical signs of fluid or electrolyte imbalance.
(section 4.4 and 4.6).
In severely sodium-depleted and/or volume-
- Severe hepatic impairment, biliary cirrhosis
depleted patients, such as those receiving high
and cholestasis. doses of diuretics, symptomatic hypotension
- Severe renal impairment (creatinine clearance may occur in rare cases after initiation of
< 30 ml/min), anuria. therapy with Valsartan HCT TajPharma. Sodium
and/or volume depletion should be corrected
before starting treatment with Valsartan HCT No dosage adjustment is required for patients
TajPharma. with renal impairment with a creatinine
clearance ≥30 ml/min (see section 4.2). Periodic
Patients with severe chronic heart failure or monitoring of serum potassium, creatinine and
other conditions with stimulation of the renin- uric acid levels is recommended when Valsartan
angiotensin-aldosterone-system
HCT TajPharma is used in patients with renal
In patients whose renal function may depend on impairment.
the activity of the renin-angiotensin-aldosterone Kidney transplantation
system (e.g. patients with severe congestive
heart failure), treatment with angiotensin There is currently no experience on the safe use
converting enzyme inhibitors has been of Valsartan HCT TajPharma in patients who
associated with oliguria and/or progressive have recently undergone kidney transplantation.
azotaemia, and in rare cases with acute renal
Hepatic impairment
failure and/or death. Evaluation of patients with
heart failure or post-myocardial infarction In patients with mild to moderate hepatic
should always include assessment of renal impairment without cholestasis, Valsartan HCT
function. The use of Valsartan HCT TajPharma TajPharma should be used with caution (see
in patients with severe chronic heart failure has sections 4.2 and 5.2). Thiazides should be used
not been established. with caution in patients with impaired hepatic
function or progressive liver disease, since
Hence it cannot be excluded that because of the
minor alterations of fluid and electrolyte balance
inhibition of the renin-angiotensin-aldosterone
system the application of Valsartan HCT may precipitate hepatic coma.
TajPharma as well may be associated with History of angioedema
impairment of the renal function. Valsartan HCT
TajPharma should not be used in these patients. Angioedema, including swelling of the larynx
and glottis, causing airway obstruction and/or
Renal artery stenosis swelling of the face, lips, pharynx, and/or tongue
has been reported in patients treated with
Valsartan HCT TajPharma should not be used to
valsartan; some of these patients previously
treat hypertension in patients with unilateral or
bilateral renal artery stenosis or stenosis of the experienced angioedema with other drugs
artery to a solitary kidney, since blood urea and including ACE inhibitors. Valsartan HCT
serum creatinine may increase in such patients. TajPharma should be immediately discontinued
in patients who develop angioedema, and
Primary hyperaldosteronism Valsartan HCT TajPharma should not be re-
administered (see section 4.8).
Patients with primary hyperaldosteronism
should not be treated with Valsartan HCT Systemic lupus erythematosus
TajPharma as their renin-angiotensin system is
not activated. Thiazide diuretics, including
hydrochlorothiazide, have been reported to
Aortic and mitral valve stenosis, hypertrophic exacerbate or activate systemic lupus
obstructive cardiomyopathy erythematosus.
As with all other vasodilators, special caution is Other metabolic disturbances
indicated in patients suffering from aortic or
mitral stenosis, or hypertrophic obstructive Thiazide diuretics, including
cardiomyopathy (HOCM). hydrochlorothiazide, may alter glucose tolerance
and raise serum levels of cholesterol,
Renal impairment triglycerides and uric acid. In diabetic patients
dosage adjustments of insulin or oral pain and typically occur within hours to week of
hypoglycaemic agents may be required. a drug initiation. Untreated acute-angle closure
glaucoma can lead to permanent vision loss.
Thiazides may reduce urinary calcium excretion
and cause an intermittent and slight elevation of The primary treatment is to discontinue
serum calcium in the absence of known hydrochlorothiazide as rapidly as possible.
disorders of calcium metabolism. Marked Prompt medical or surgical treatment may need
hypercalcaemia may be evidence of underlying to be considered if the intraocular pressure
hyperparathyroidism. Thiazides should be remains uncontrolled. Risk factors for
discontinued before carrying out tests for developing acute angle closure glaucoma may
parathyroid function. include a history of sulfonamide or penicillin
allergy.
Photosensitivity
Dual Blockade of the Renin-Angiotensin-
Cases of photosensitivity reactions have been Aldosterone System (RAAS)
reported with thiazide diuretics (see section 4.8).
If photosensitivity reaction occurs during There is evidence that the concomitant use of
treatment, it is recommended to stop the ACE inhibitors, angiotensin II receptor blockers
treatment. If a re-administration of the diuretic is or aliskiren increases the risk of hypotension,
deemed necessary, it is recommended to protect hyperkalaemia, and decreased renal function
exposed areas to the sun or to artificial UVA. (including acute renal failure). Dual blockade of
the RAAS through the combined use of ACE
Pregnancy
inhibitors, angiotensin II receptor blockers or
Angiotensin II Receptor Antagonists (AIIRAs) aliskiren is therefore not recommended (see
should not be initiated during pregnancy. Unless section 4.5 and 5.1).
continued AIIRAs therapy is considered If dual blockade therapy is considered absolutely
essential, patients planning pregnancy should be
necessary, this should only occur under
changed to alternative anti-hypertensive
specialist supervision and subject to frequent
treatments which have an established safety
close monitoring of renal function, electrolytes
profile for use in pregnancy. When pregnancy is and blood pressure. ACE inhibitors and
diagnosed, treatment with AIIRAs should be angiotensin II receptor blockers should not be
stopped immediately, and, if appropriate, used concomitantly in patients with diabetic
alternative therapy should be started (see nephropathy.
sections 4.3 and 4.6).
Non-melanoma skin cancer
General
An increased risk of non-melanoma skin cancer
Caution should be exercised in patients who (NMSC) [basal cell carcinoma (BCC) and
have shown prior hypersensitivity to other squamous cell carcinoma (SCC)] with increasing
angiotensin II receptor antagonists. cumulative dose of hydrochlorothiazide
Hypersensitivity reactions to exposure has been observed in two
hydrochlorothiazide are more likely in patients epidemiological studies based on the Danish
with allergy and asthma.
National Cancer Registry. Photosensitising
Acute Angle-Closure Glaucoma actions of hydrochlorothiazide could act as a
possible mechanism for NMSC.
Hydrochlorothiazide, a sulfonamide, has been
associated with an idiosyncratic reaction Patients taking hydrochlorothiazide should be
resulting in acute transient myopia and acute informed of the risk of NMSC and advised to
angle-closure glaucoma. Symptoms include regularly check their skin for any new lesions
acute onset of decreased visual acuity or ocular and promptly report any suspicious skin lesions.
Possible preventive measures such as limited NSAIDS can attenuate the antihypertensive
exposure to sunlight and UV rays and, in case of effect of both angiotensin II antagonists and
exposure, adequate protection should be advised hydrochlorothiazide when administered
to the patients in order to minimize the risk of simultaneously. Furthermore, concomitant use
skin cancer. Suspicious skin lesions should be of Valsartan HCT TajPharma and NSAIDs may
promptly examined potentially including lead to worsening of renal function and an
histological examinations of biopsies. The use of increase in serum potassium. Therefore,
hydrochlorothiazide may also need to be monitoring of renal function at the beginning of
reconsidered in patients who have experienced the treatment is recommended, as well as
previous NMSC (see also section 4.8). adequate hydration of the patient.
4.5 Interaction with other medicinal products Interactions related to valsartan
and other forms of interaction
Interactions related to both valsartan and Dual blockade of the Renin-Angiotensin-
hydrochlorothiazide Aldosterone System (RAAS) with ARBs, ACEIs,
or aliskiren
Concomitant use not recommended
Clinical trial data has shown that dual blockade
Lithium of the renin-angiotensin-aldosterone-system
(RAAS) through the combined use of ACE
Reversible increases in serum lithium inhibitors, angiotensin II receptor blockers or
concentrations and toxicity have been reported
aliskiren is associated with a higher frequency of
during concomitant administration of lithium
adverse events such as hypotension,
with ACE inhibitors, angiontensin II receptor hyperkalaemia and decreased renal function
antagonist or thiazides, including (including acute renal failure) compared to the
hydrochlorothiazide. Since renal clearance of use of s single RAAS-acting agent (see section
lithium is reduced by thiazides, the risk of 4.3, 4.4 and 5.1).
lithium toxicity may presumably be increased
further with Valsartan HCT TajPharma. If the Concomitant use not recommended
combination proves necessary, a careful
monitoring of serum lithium levels is Potassium-sparing diuretics, potassium
recommended. supplements, salt substitutes containing
potassium and other substances that may
Concomitant use requiring caution increase potassium levels.
Other antihypertensive agents If a medicinal product that affects potassium
levels is considered necessary in combination
Valsartan HCT TajPharma may increase the with valsartan, monitoring of potassium plasma
effects of other agents with antihypertensive levels is advised.
properties (e.g. guanethidine, methyldopa,
vasodilators, ACEI, ARBs, beta-blockers, Transporters
calcium channel blockers and DRIs).
In vitro data indicates that valsartan is a
Pressor amines (e.g. noradrenaline, adrenaline) substrate of the hepatic uptake transporter
OATP1B1/OATP1B3 and the hepatic efflux
Possible decreased response to pressor amines. transporter MRP2. The clinical relevance of this
The clinical significance of this effect is finding is unknown. Co-administration of
uncertain and not sufficient to preclude their use.
inhibitors of the uptake transporter (eg. rifampin,
Non-steroidal anti-inflammatory medicines ciclosporin) or efflux transporter (eg. ritonavir)
(NSAIDs), including selective COX-2 inhibitors, may increase the systemic exposure to valsartan.
acetylsalicylic acid (>3 g/day), and non- Exercise appropriate care when initiating or
selective NSAIDs. ending concomitant treatment with such drugs.
No interaction effects favouring the onset of digitalis-induced

cardiac arrhythmias (see section 4.4).
In drug interaction studies with valsartan, no
interactions of clinical significance have been Calcium salts and vitamin D
found with valsartan or any of the following
substances: cimetidine, warfarin, furosemide, Administration of thiazide diuretics, including
digoxin, atenolol, indomethacin, hydrochlorothiazide, with vitamin D or with
hydrochlorothiazide, amlodipine, glibenclamide. calcium salts may potentiate the rise in serum
Digoxin and indomethacin could interact with calcium. Concomitant use of thiazide type
the hydrochlorothiazide component of Valsartan diuretics with calcium salts may cause
HCT TajPharma (see interactions related to hypercalcaemia in patients pre-disposed for
hydrochlorothiazide). hypercalcaemia (e.g. hyperparathyroidism,
malignancy or vitamin-D-mediated conditions)
Interactions related to hydrochlorothiazide by increasing tubular calcium reabsorption.
Concomitant use requiring caution Antidiabetic agents (oral agents and insulin)
Medicinal products affecting serum potassium Thiazides may alter glucose tolerance. Dose
level adjustment of the antidiabetic medicinal product
may be necessary.
The hypokalaemic effect of hydrochlorothiazide
may be increased by concomitant administration Metformin should be used with caution because
of kaliuretic diuretics, corticosteroids, laxatives, of the risk of lactic acidosis induced by possible
ACTH, amphotericin, carbenoxolone, penicillin functional renal failure linked to
G, salicylic acid and derivatives. hydrochlorothiazide.
If these medicinal products are to be prescribed Beta blockers and diazoxide
with the hydrochlorothiazide-valsartan
Concomitant use of thiazide diuretics, including
combination, monitoring of potassium plasma
levels is advised (see section 4.4). hydrochlorothiazide, with beta blockers may
increase the risk of hyperglycaemia. Thiazide
Medicinal products that could induce torsades diuretics, including hydrochlorothiazide, may
de pointes enhance the hyperglycaemic effect of diazoxide.
Due to the risk of hypokalaemia, Medicinal products used in the treatment of
hydrochlorothiazide should be administered with gout (probenecid, sulfinpyrazone and
caution when associated with medicinal products allopurinol)
that could induce torsades de pointes, in
particular Class Ia and Class III antiarrhythmics Dose adjustment of uricosuric medications may
and some antipsychotics. be necessary as hydrochlorothiazide may raise
the level of serum uric acid. Increase of dosage
Medicinal products affecting serum sodium level of probenecid or sulfinpyrazone may be
necessary. Co-administration of thiazide
The hyponatraemic effect of diuretics may be
diuretics, including hydrochlorothiazide, may
intensified by concomitant administration of
increase the incidence of hypersensitivity
drugs such as antidepressants, antipsychotics, reactions to allopurinol.
antiepileptics, etc. Caution is advised in long-
term administration of these drugs. Anticholinergic agents and other medicinal
products affecting gastric motility
Digitalis glycosides
The bioavailability of thiazide-type diuretics
Thiazide-induced hypokalaemia or may be increased by anticholinergic agents (e.g.
hypomagnesaemia may occur as undesirable atropine, biperiden), apparently due to a
decrease in gastrointestinal motility and the There have been isolated reports of
stomach emptying rate. Conversely, it is haemolyticanaemia in patients receiving
anticipated that prokinetic drugs such as concomitant treatment with methyldopa and
cisapride may decrease the bioavailability of hydrochlorothiazide.
thiazide-type diuretics.
Iodine contrast media
Amantadine
In case of diuretic-induced dehydration, there is
Thiazides, including hydrochlorothiazide, may an increased risk of acute renal failure,
increase the risk of adverse effects caused by especially with high doses of the iodine product.
amantadine. Patients should be rehydrated before the
administration.
Ion exchange resins
4.6 Fertility, pregnancy and lactation
Absorption of thiazide diuretics, including Pregnancy
hydrochlorothiazide, is decreased by
cholestyramine or colestipol. This could result in Valsartan
sub-therapeutic effects of thiazide diuretics.
However, staggering the dosage of The use of Angiotensin II Receptor Antagonists
hydrochlorothiazide and resin such that (AIIRAs) is not recommended during first
hydrochlorothiazide is administered at least 4 h trimester of pregnancy (see section 4.4). The use
before or 4-6 h after the administration of resins of AIIRAs is contra-indicated during the second
would potentially minimise the interaction. and third trimester of pregnancy (see sections
4.3 and 4.4).
Cytotoxic agents Epidemiological evidence regarding the risk of
Thiazides, including hydrochlorothiazide, may teratogenicity following exposure to ACE
reduce renal excretion of cytotoxic agents (e.g. inhibitors during the first trimester of pregnancy
cyclophosamide, methotrexate) and potentiate has not been conclusive; however a small
their myelosuppressive effects. increase in risk cannot be excluded. Whilst there
is no controlled epidemiological data on the risk
Non-depolarising skeletal muscle relaxants (e.g. with Angiotensin II Receptor Inhibitors
tubocurarine) (AIIRAs), similar risks may exist for this class
Thiazides, including hydrochlorothiazide, of drugs. Unless continued AIIRAs therapy is
potentiate the action of skeletal muscle relaxants considered essential, patients planning
such as curare derivatives. pregnancy should be changed to alternative anti-
hypertensive treatments which have an
Ciclosporin established safety profile for use in pregnancy.
When pregnancy is diagnosed, treatment with
Concomitant treatment with ciclosporin may
AIIRAs should be stopped immediately and, if
increase the risk of hyperuricaemia and gout-
appropriate, alternative therapy should be
type complications.
started.
Alcohol, barbiturates or narcotics
AIIRAs therapy exposure during the second and
Concomitant administration of thiazide diuretics third trimesters is known to induce human
with substances that also have a blood pressure fetotoxicity (decreased renal function,
lowering effect (e.g. by reducing sympathetic oligohydramnios, skull ossification retardation)
central nervous system activity or direct and neonatal toxicity (renal failure, hypotension,
vasodilatation activity) may potentiate hyperkalaemia) (see also section 5.3).
orthostatic hypotension.
Should exposure to AIIRAs have occurred from
Methyldopa the second trimester of pregnancy, ultrasound
check of renal function and skull is not been seen in clinical trials may occur during
recommended. treatment with valsartan/ hydrochlorothiazide.
Infants whose mothers have taken AIIRAs Adverse Drug Reactions
should be closely observed for hypotension (see
also section 4.3 and 4.4). Adverse drug reactions are ranked by frequency,
the most frequent first, using the following
Hydrochlorothiazide convention: very common (≥ 1/10); common (≥
1/100 to < 1/10); uncommon (≥ 1/1,000 to <
There is limited experience with 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare
hydrochlorothiazide during pregnancy, (< 1/10,000); not known (frequency cannot be
especially during the first trimester. Animal estimated from the available data).
studies are insufficient. Hydrochlorothiazide
crosses the placenta. Based on the Within each frequency grouping, adverse drug
pharmacological mechanism of action of reactions are ranked in order of decreasing
hydrochlorothiazide its use during the second seriousness.
and third trimester may compromise foeto-
Table 1. Frequency of adverse reactions with
placental perfusion and may cause foetal and
valsartan/hydrochlorothiazide
neonatal effects like icterus, disturbance of
electrolyte balance and thrombocytopenia. Metabolism and nutrition disorders
Breast-feeding Uncommon Dehydration
No information is available regarding the use of Nervous system disorders
valsartan during breastfeeding. Very rare Dizziness
Hydrochlorothiazide is excreted in human milk.. Uncommon Paraesthesia
Therefore the use of Valsartan HCT TajPharma Not known Syncope
during breast feeding is not recommended.
Alternative treatments with better established Eye disorders
safety profiles during breast-feeding are Uncommon Vision blurred
preferable, especially while nursing a newborn Ear and
or preterm infant. labyrinth
disorders
4.7 Effects on ability to drive and use
machines Uncommon Tinnitus
No studies on the effect of Valsartan HCT Vascular disorders
TajPharma, on the ability to drive and use Uncommon Hypotension
machines have been performed. When driving Respiratory, thoracic and mediastinal
vehicles or operating machines it should be disorders
taken into account that occasionally dizziness or
weariness may occur. Uncommon Cough
Not known Non cardiogenic pulmonary
4.8 Undesirable effects oedema
Adverse drug reactions reported in clinical trials
and laboratory findings occurring more Gastrointestinal disorders
frequently with valsartan plus Very rare Diarrhoea
hydrochlorothiazide versus placebo and Musculoskeletal and connective tissue
individual postmarketing reports are presented disorders
below according to system organ class. Adverse Uncommon Myalgia
drug reactions known to occur with each
Very rare Arthralgia
component given individually but which have
Renal and urinary disorders Not known Angioedema, dermatitis bullous,

Not known Impaired renal function rash, pruritus
General disorders and administration site Renal and urinary disorders
conditions Not known Renal failure
Uncommon Fatigue Table 3. Frequency of adverse reactions with
Investigations hydrochorothiazide
Not known Serum uric acid increased, Serum Hydrochlorothiazide has been extensively
bilirubin and Serum creatinine prescribed for many years, frequently in higher
increased, Hypokalaemia, doses than those administered with Valsartan
Hyponatraemia, Elevation of HCT TajPharma. The following adverse
Blood Urea Nitrogen, reactions have been reported in patients treated
Neutropenia with monotherapy of thiazide diuretics,
Additional information on the individual including hydrochlorothiazide:
components
Neoplasms benign, malignant and unspecified
Adverse reactions previously reported with one (incl. cysts and polyps)
of the individual components may be potential Not known Non-melanoma skin cancer
undesirable effects with Valsartan HCT (Basal cell carcinoma and
TajPharma as well, even if not observed in Squamous cell carcinoma)
clinical trials or during postmarketing period.
Blood and lymphatic system disorders
Table 2. Frequency of adverse reactions with Rare Thrombocytopenia sometimes
valsartan with purpura
Blood and lymphatic system disorders Very rare Agranulocytosis, leucopenia,
haemolyticanaemia, bone marrow
Not known Decrease in haemoglobin, failure
decrease in haematocrit,
thrombocytopenia Not known Aplastic anemia
Immune system disorders Immune system disorders
Not known Other hypersensitivity/allergic Very rare Hypersensitivity reactions
reactions including serum Metabolism and nutrition disorders
sickness Very Hypokalaemia, blood lipids
Metabolism and nutrition disorders common increased (mainly at higher
Not known Increase of serum potassium, doses)
hyponatraemia Common Hyponatraemia,
Ear and labyrinth disorders hypomagnesaemia,
hyperuricaemia
Uncommon Vertigo
Rare Hypercalcaemia, hyperglycaemia,
Vascular disorders glycosuria and worsening of
Not known Vasculitis diabetic metabolic state
Gastrointestinal disorders Very rare Hypochloraemic alkalosis
Uncommon Abdominal pain Psychiatric disorders
Hepatobiliary disorders Rare Depression, sleep disturbances
Not known Elevation of liver function values Nervous system disorders
Skin and subcutaneous tissue disorders Rare Headache, dizziness, paraesthesia
Eye disorders Non-melanoma skin cancer: based on available

Rare Visual impairment data from epidemiological studies, cumulative
dose dependent association between
Not known Acute angle-closure glaucoma hydrochlorothiazide and NMSC has been
Cardiac disorders observed (see also sections 4.4 and 5.1).
Rare Cardiac arrhythmias
Reporting of suspected adverse reactions
Vascular disorders
Common Postural hypotension Reporting suspected adverse reactions after
authorisation of the medicinal product is
Respiratory, thoracic and mediastinal important. It allows continued monitoring of the
disorders benefit/risk balance of the medicinal product.
Very rare Respiratory distress including
pneumonitis and pulmonary 4.9 Overdose
oedema Symptoms
Gastrointestinal disorders Overdose with valsartan may result in marked
Common Loss of appetite, mild nausea and hypotension, which could lead to depressed level
vomiting of consciousness, circulatory collapse and/or
shock. In addition, the following signs and
Rare Constipation, gastrointestinal
symptoms may occur due to an overdose of the
discomfort, diarrhoea
hydrochlorothiazide component: nausea,
Very rare Pancreatitis somnolence, hypovolaemia, and electrolyte
Hepatobiliary disorders disturbances associated with cardiac arrhythmias
Rare Intrahepatic cholestasis or and muscle spasms.
jaundice Treatment
Renal and urinary disorders
The therapeutic measures depend on the time of
Not known Renal dysfunction, acute renal
ingestion and the type and severity of the
failure
symptoms, stabilisation of the circulatory
Skin and subcutaneous tissue disorders condition being of prime importance.
Common Urticaria and other forms of rash
If hypotension occurs, the patient should be
Rare Photosensitisation placed in the supine position and salt and
Very rare Necrotisingvasculitis and toxic volume supplementation should be given
epidermal necrolysis, cutaneous rapidly.
lupus erythematosus-like
reactions, reactivation of Valsartan cannot be eliminated by means of
cutaneous lupus erythematosus haemodialysis because of its strong plasma
binding behaviour whereas clearance of
Not known Erythema multiforme hydrochlorothiazide will be achieved by
General disorders and administration site dialysis.
conditions
Not known Pyrexia, asthenia
Musculoskeletal and connective tissue 5. Pharmacological properties
disorders
Not known Muscle spasm 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Angiotensin II
Reproductive system and breast disorders antagonists and diuretics, valsartan and diuretics
Common Impotence
Description of selected adverse reactions Valsartan/hydrochlorothiazide
Valsartan HCT TajPharma80mg/12.5 mg (64%) compared to placebo (29%) and

Tablets only: hydrochlorothiazide (41%).
In a double-blind, randomised, active-controlled Valsartan HCT TajPharma 160/12.5 mg and
trial in patients not adequately controlled on 160/25mg Tablets only:
hydrochlorothiazide 12.5 mg, significantly
greater mean systolic/diastolic BP reductions In a double-blind, randomised, active-controlled
were observed with the combination of trial in patients not adequately controlled on
valsartan/hydrochlorothiazide 80mg/12.5 mg hydrochlorothiazide 12.5 mg, significantly
(14.9/11.3 mmHg) compared to greater mean systolic/diastolic BP reductions
hydrochlorothiazide 12.5 mg (5.2/2.9 mmHg) were observed with the combination of
and hydrochlorothiazide 25 mg (6.8/5.7 mmHg). valsartan/ hydrochlorothiazide 160/12.5 mg
(12.4/7.5 mmHg) compared to
In addition, a significantly greater percentage of
patients responded (diastolic BP <90 mmHg or hydrochlorothiazide 25 mg (5.6/2.1 mmHg). In
reduction ≥10 mmHg) with addition, a significantly greater percentage of
valsartan/hydrochlorothiazide 80mg/12.5 mg patients responded (BP <140/90 mmHg or SBP
(60%) compared to hydrochlorothiazide 12.5 mg reduction ≥20 mmHg or DBP reduction ≥10
(25%) and hydrochlorothiazide 25 mg (27%). mmHg) with valsartan/hydrochlorothiazide
160/12.5 mg (50%) compared to
In a double-blind, randomised, active-controlled hydrochlorothiazide 25 mg (25%).
trial in patients not adequately controlled on
valsartan 80 mg, significantly greater mean In a double-blind, randomised, active-controlled
systolic/diastolic BP reductions were observed trial in patients not adequately controlled on
with the combination of valsartan 160 mg, significantly greater mean
valsartan/hydrochlorothiazide 80mg/12.5 mg systolic/diastolic BP reductions were observed
(9.8/8.2 mmHg) compared to valsartan 80 mg with both the combination of
valsartan/hydrochlorothiazide 160/25 mg
(3.9/5.1 mmHg) and valsartan 160 mg (6.5/6.2
mmHg). In addition, a significantly greater (14.6/11.9 mmHg) and
percentage of patients responded (diastolic BP valsartan/hydrochlorothiazide 160/12.5 mg
<90 mmHg or reduction ≥10 mmHg) with (12.4/10.4 mmHg) compared to valsartan 160
mg (8.7/8.8 mmHg). The difference in BP
valsartan/hydrochlorothiazide 80mg/12.5 mg
(51%) compared to valsartan 80 mg (36%) and reductions between the 160/25 mg and 160/12.5
valsartan 160 mg (37%). mg doses also reached statistical significance. In
addition, a significantly greater percentage of
In a double-blind, randomised, placebo- patients responded (diastolic BP <90 mmHg or
controlled, factorial design trial comparing reduction ≥10 mmHg) with
various dose combinations of valsartan/hydrochlorothiazide 160/25 mg (68%)
valsartan/hydrochlorothiazide to their respective and 160/12.5 mg (62%) compared to valsartan
components, significantly greater mean 160 mg (49%).
systolic/diastolic BP reductions were observed
with the combination of In a double-blind, randomised, placebo-
valsartan/hydrochlorothiazide 80mg/12.5 mg controlled, factorial design trial comparing
(16.5/11.8 mmHg) compared to placebo (1.9/4.1 various dose combinations of
mmHg) and both hydrochlorothiazide 12.5 mg valsartan/hydrochlorothiazide to their respective
components, significantly greater mean
(7.3/7.2 mmHg) and valsartan 80 mg (8.8/8.6
mmHg). In addition, a significantly greater systolic/diastolic BP reductions were observed
percentage of patients responded (diastolic BP with the combination of
<90 mmHg or reduction ≥10 mmHg) with valsartan/hydrochlorothiazide 160/12.5 mg
valsartan/hydrochlorothiazide 80mg/12.5 mg (17.8/13.5 mmHg) and 160/25 mg (22.5/15.3
mmHg) compared to placebo (1.9/4.1 mmHg)
and the respective monotherapies, i.e., AT1 receptor and has much (about 20,000 fold)
hydrochlorothiazide 12.5 mg (7.3/7.2 mmHg), greater affinity for the AT1 receptor than for the
hydrochlorothiazide 25 mg (12.7/9.3 mmHg) AT2 receptor. Valsartan is not known to bind to
and valsartan 160 mg (12.1/9.4 mmHg). In or block other hormone receptors or ion
addition, a significantly greater percentage of channels known to be important in
patients responded (diastolic BP <90 mmHg or cardiovascular regulation.
reduction ≥10 mmHg) with
valsartan/hydrochlorothiazide 160/25 mg (81%) Valsartan does not inhibit ACE, also known as
and valsartan/hydrochlorothiazide 160/12.5 mg kininase II, which converts Ang I to Ang II and
(76%) compared to placebo (29%) and the degrades bradykinin. Since there is no effect on
ACE and no potentiation of bradykinin or
respective monotherapies, i.e.,
substance P, angiotensin II antagonists are
hydrochlorothiazide 12.5 mg (41%),
hydrochlorothiazide 25 mg (54%), and valsartan unlikely to be associated with coughing. In
160 mg (59%). clinical trials where valsartan was compared
with an ACE inhibitor, the incidence of dry
Valsartan HCT TajPharma 80/12.5mg, 160/12.5 cough was significantly (P <0.05) lower in
mg and 160/25mg Tablets: patients treated with valsartan than in those
treated with an ACE inhibitor (2.6% versus
Dose-dependent decreases in serum potassium
7.9% respectively). In a clinical trial of patients
occurred in controlled clinical studies with with a history of dry cough during ACE
valsartan + hydrochlorothiazide. Reduction in inhibitor therapy, 19.5% of trial subjects
serum potassium occurred more frequently in receiving valsartan and 19.0% of those receiving
patients given 25 mg hydrochlorothiazide than a thiazide diuretic experienced cough compared
in those given 12.5 mg hydrochlorothiazide. In to 68.5% of those treated with an ACE inhibitor
controlled clinical trials with (P <0.05).
valsartan/hydrochlorothiazide the potassium
lowering effect of hydrochlorothiazide was Administration of valsartan to patients with
attenuated by the potassium-sparing effect of hypertension results in reduction of blood
valsartan. pressure without affecting pulse rate. In most
patients, after administration of a single oral
Beneficial effects of valsartan in combination
dose, onset of antihypertensive activity occurs
with hydrochlorothiazide on cardiovascular within 2 hours, and the peak reduction of blood
mortality and morbidity are currently unknown.
pressure is achieved within 4-6 hours. The
Epidemiological studies have shown that long- antihypertensive effect persists over 24 hours
term treatment with hydrochlorothiazide reduces after dosing. During repeated dosing, the
the risk of cardiovascular mortality and maximum reduction in blood pressure with any
morbidity. dose is generally attained within 2-4 weeks and
is sustained during long-term therapy. Combined
Valsartan with hydrochlorothiazide, a significant
Valsartan is an orally active and specific additional reduction in blood pressure is
angiotensin II (Ang II) receptor antagonist. It achieved.
acts selectively on the AT1 receptor subtype, Abrupt withdrawal of valsartan has not been
which is responsible for the known actions of associated with rebound hypertension or other
angiotensin II. The increased plasma levels of adverse clinical events.
Ang II following AT1 receptor blockade with
valsartan may stimulate the unblocked In hypertensive patients with type 2 diabetes and
AT2 receptor, which appears to counterbalance microalbuminuria, valsartan has been shown to
the effect of the AT1 receptor. Valsartan does not reduce the urinary excretion of albumin. The
exhibit any partial agonist activity at the MARVAL (Micro Albuminuria Reduction with
Valsartan) study assessed the reduction in damage. VA NEPHRON-D was a study in

urinary albumin excretion (UAE) with valsartan patients with type 2 diabetes mellitus and
(80-160 mg/od) versus amlodipine (5-10 diabetic nephropathy.
mg/od), in 332 type 2 diabetic patients (mean
age: 58 years; 265 men) with microalbuminuria These studies have shown no significant
(valsartan: 58 µg/min; amlodipine: 55.4 beneficial effect on renal and/or cardiovascular
µg/min), normal or high blood pressure and with outcomes and mortality, while an increased risk
preserved renal function (blood creatinine<120 of hyperkalaemia, acute kidney injury and/or
µmol/l). At 24 weeks, UAE was reduced (p hypotension as compared to monotherapy was
<0.001) by 42% (–24.2 µg/min; 95% CI: –40.4 observed. Given their similar pharmacodynamic
properties, these results are also relevant for
to –19.1) with valsartan and approximately 3%
other ACE inhibitors and angiotensin II receptor
(–1.7 µg/min; 95% CI: –5.6 to 14.9) with
amlodipine despite similar rates of blood blockers.
pressure reduction in both groups. The Diovan ACE inhibitors and angiotensin II receptor
Reduction of Proteinuria (DROP) study further blockers should therefore not be used
examined the efficacy of valsartan in reducing concomitantly in patients with diabetic
UAE in 391 hypertensive patients (BP=150/88 nephropathy.
mmHg) with type 2 diabetes, albuminuria
(mean=102 µg/min; 20–700 µg/min) and ALTITUDE (Aliskiren Trial in Type 2 Diabetes
preserved renal function (mean serum creatinine Using Cardiovascular and Renal Disease
= 80 µmol/l). Patients were randomised to one Endpoints) was a study designed to test the
of 3 doses of valsartan (160, 320 and 640 benefit of adding aliskiren to a standard therapy
mg/od) and treated for 30 weeks. The purpose of of an ACE inhibitor or an angiotensin II receptor
the study was to determine the optimal dose of blocker in patients with type 2 diabetes mellitus
valsartan for reducing UAE in hypertensive and chronic kidney disease, cardiovascular
patients with type 2 diabetes. At 30 weeks, the disease, or both. The study was terminated early
percentage change in UAE was significantly because of an increased risk of adverse
reduced by 36% from baseline with valsartan outcomes. Cardiovascular death and stroke were
160 mg (95%CI: 22 to 47%), and by 44% with both numerically more frequent in the aliskiren
valsartan 320 mg (95%CI: 31 to 54%). It was group than in the placebo group and adverse
concluded that 160-320 mg of valsartan events and serious adverse events of interest
produced clinically relevant reductions in UAE (hyperkalaemia, hypotension and renal
in hypertensive patients with type 2 diabetes. dysfunction) were more frequently reported in
the aliskiren group than in the placebo group.
Other: dual blockade of the renin-angiotensin-
aldosterone system (RAAS) Hydrochlorothiazide
Two large randomised, controlled trials The site of action of thiazide diuretics is
(ONTARGET (ONgoingTelmisartan Alone and primarily in the renal distal convoluted tubule. It
in combination with Ramipril Global Endpoint has been shown that there is a high-affinity
Trial) and VA NEPHRON-D (The Veterans receptor in the renal cortex as the primary
Affairs Nephropathy in Diabetes)) have binding site for the thiazide diuretic action and
examined the use of the combination of an ACE- inhibition of NaCl transport in the distal
inhibitor with an angiotensin II receptor blocker. convoluted tubule. The mode of action of
thiazides is through inhibition of the Na+Cl-
ONTARGET was a study conducted in patients symporter perhaps by competing for the Cl- site,
with a history of cardiovascular or thereby affecting electrolyte reabsorption
cerebrovascular disease, or type 2 diabetes mechanisms:directly increasing sodium and
mellitus accompanied by evidence of end-organ chloride excretion to an approximately equal
extent, and indirectly by this diuretic action with either active substance given alone, or
reducing plasma volume, with consequent placebo.
increases in plasma renin activity, aldosterone
Valsartan
secretion and urinary potassium loss, and a
decrease in serum potassium. The renin- Absorption
aldosterone link is mediated by angiotensin II,
so with co-administration of valsartan the Following oral administration of valsartan alone,
reduction in serum potassium is less pronounced peak plasma concentrations of valsartan are
as observed under monotherapy with reached in 2–4 hours. Mean absolute
hydrochlorothiazide. bioavailability is 23%. Food decreases exposure
(as measured by AUC) to valsartan by about
Non-melanoma skin cancer: 40% and peak plasma concentration (Cmax) by
about 50%, although from about 8 h post dosing
Based on available data from epidemiological
studies, cumulative dose-dependent association plasma valsartan concentrations are similar for
the fed and fasted groups. This reduction in
between hydrochlorothiazide and NMSC has
been observed. One study included a population AUC is not, however, accompanied by a
comprised of 71,533 cases of BCC and of 8,629 clinically significant reduction in the therapeutic
cases of SCC matched to 1,430,833 and 172,462 effect, and valsartan can therefore be given
either with or without food.
population controls, respectively. High
hydrochlorothiazide use (≥50,000 mg Distribution
cumulative) was associated with an adjusted
Odds Ratio (OR) of 1.29 (95% CI: 1.23-1.35) The steady-state volume of distribution of
for BCC and 3.98 (95% CI: 3.68-4.31) for SCC. valsartan after intravenous administration is
A clear cumulative dose response relationship about 17 litres, indicating that valsartan does not
was observed for both BCC and SCC. Another distribute into tissues extensively. Valsartan is
study showed a possible association between lip highly bound to serum proteins (94 – 97%),
cancer (SCC) and exposure to mainly serum albumin.
hydrochlorothiazide: 633 cases of lip-cancer Biotransformation
were matched with 63,067 population controls,
using a risk-set sampling strategy. A cumulative Valsartan is not biotransformed to a high extent
dose- response relationship was demonstrated as only about 20% of dose is recovered as
with an adjusted OR 2.1 (95% CI: 1.7-2.6) metabolites. A hydroxy metabolite has been
increasing to OR 3.9 (3.0-4.9) for high use identified in plasma at low concentrations (less
(~25,000 mg) and OR 7.7 (5.7-10.5) for the than 10% of the valsartan AUC). This
highest cumulative dose (~100,000 mg) (see also metabolite is pharmacologically inactive.
section 4.4). Elimination
5.2 Pharmacokinetic properties Valsartan shows multiexponential decay kinetics
Valsartan/hydrochlorothiazide (t½α <1 h and t½ß about 9 h). Valsartan is
The systemic availability of hydrochlorothiazide primarily eliminated in faeces (about 83% of
is reduced by about 30% when co-administered dose) and urine (about 13% of dose), mainly as
with valsartan. The kinetics of valsartan are not unchanged drug. Following intravenous
markedly affected by the co-administration of administration, plasma clearance of valsartan is
hydrochlorothiazide. This observed interaction about 2 l/h and its renal clearance is 0.62 l/h
has no impact on the combined use of valsartan (about 30% of total clearance). The half-life of
and hydrochlorothiazide, since controlled valsartan is 6 hours.
clinical trials have shown a clear anti- Hydrochlorothiazide
hypertensive effect, greater than that obtained
Absorption At the recommended dose of Valsartan HCT

TajPharma no dose adjustment is required for
The absorption of hydrochlorothiazide, after an patients with a Glomerular Filtration Rate (GFR)
oral dose, is rapid (tmax about 2 h). The increase of 30–70 ml/min.
in mean AUC is linear and dose proportional in
the therapeutic range. In patients with severe renal impairment (GFR
<30 ml/min) and patients undergoing dialysis no
The effect of food on hydrochlorothiazide data are available for Valsartan HCT TajPharma.
absorption, if any, has little clinical significance. Valsartan is highly bound to plasma protein and
Absolute bioavailability of hydrochlorothiazide is not to be removed by dialysis, whereas
is 70% after oral administration.
clearance of hydrochlorothiazide will be
Distribution achieved by dialysis.
The apparent volume of distribution is 4–8 l/kg. In the presence of renal impairment, mean peak
plasma levels and AUC values of
Circulating hydrochlorothiazide is bound to hydrochlorothiazide are increased and the
serum proteins (40–70%), mainly serum urinary excretion rate is reduced. In patients
albumin. Hydrochlorothiazide also accumulates with mild to moderate renal impairment, a 3-fold
in erythrocytes at approximately 3 times the increase in hydrochlorothiazide AUC has been
level in plasma. observed. In patients with severe renal
Elimination impairment an 8-fold increase in AUC has been
observed. Hydrochlorothiazide is
Hydrochlorothiazide is eliminated contraindicated in patients with severe renal
predominantly as unchanged drug. impairment (see section 4.3).
Hydrochlorothiazide is eliminated from plasma
with a half-life averaging 6 to 15 hours in the Hepatic impairment
terminal elimination phase. There is no change In a pharmacokinetics trial in patients with mild
in the kinetics of hydrochlorothiazide on (n=6) to moderate (n=5) hepatic dysfunction,
repeated dosing, and accumulation is minimal exposure to valsartan was increased
when dosed once daily. There is more than 95% approximately 2-fold compared with healthy
of the absorbed dose being excreted as volunteers (see sections 4.2 and 4.4).
unchanged compound in the urine. The renal
clearance is composed of passive filtration and There is no data available on the use of valsartan
active secretion into the renal tubule. in patients with severe hepatic dysfunction (see
section 4.3). Hepatic disease does not
Special populations significantly affect the pharmacokinetics of
Older people hydrochlorothiazide.
A somewhat higher systemic exposure to 5.3 Preclinical safety data

valsartan was observed in some elderly subjects The potential toxicity of the valsartan -
than in young subjects; however, this has not hydrochlorothiazide combination after oral
been shown to have any clinical significance. administration was investigated in rats and
marmosets in studies lasting up to six months.
Limited data suggest that the systemic clearance No findings emerged that would exclude the use
of hydrochlorothiazide is reduced in both of therapeutic doses in man.
healthy and hypertensive elderly subjects
compared to young healthy volunteers. The changes produced by the combination in the
chronic toxicity studies are most likely to have
Renal impairment been caused by the valsartan component. The
toxicological target organ was the kidney, the
reaction being more marked in the marmoset represent 18 and 73 times the maximum
than the rat. The combination led to kidney recommended human dose (MRHD) of valsartan
damage (nephropathy with tubular basophilia, and hydrochlorothiazide on a mg/m2 basis.
rises in plasma urea, plasma creatinine and (Calculations assume an oral dose of 320
serum potassium, increases in urine volume and mg/day valsartan in combination with 25
urinary electrolytes from 30 mg/kg/day valsartan mg/day hydrochlorothiazide and a 60-kg
+ 9 mg/kg/day hydrochlorothiazide in rats and patient).
10 + 3 mg/kg/d in marmosets), probably by way
of altered renal haemodynamics. These doses in The above mentioned effects appear to be due to
rat, respectively, represent 0.9 and 3.5–times the the pharmacological effects of high valsartan
doses (blockade of angiotensin II-induced
maximum recommended human dose (MRHD)
inhibition of renin release, with stimulation of
of valsartan and hydrochlorothiazide on a
mg/m2 basis. These doses in marmoset, the renin-producing cells) and also occur with
respectively, represent 0.3 and 1.2–times the ACE inhibitors. These findings appear to have
maximum recommended human dose (MRHD) no relevance to the use of therapeutic doses of
valsartan in humans.
of valsartan and hydrochlorothiazide on a
mg/m2 basis. (Calculations assume an oral dose The valsartan - hydrochlorothiazide combination
of 320 mg/day valsartan in combination with 25 was not tested for mutagenicity, chromosomal
mg/day hydrochlorothiazide and a 60-kg breakage or carcinogenicity, since there is no
patient.) evidence of interaction between the two
High doses of the valsartan - substances. However, these tests were performed
hydrochlorothiazide combination caused falls in separately with valsartan and
red blood cell indices (red cell count, hydrochlorothiazide, and produced no evidence
of mutagenicity, chromosomal breakage or
haemoglobin, haematocrit, from 100 + 31
carcinogenicity.
mg/kg/d in rats and 30 + 9 mg/kg/d in
marmosets). These doses in rat, respectively, In rats, maternally toxic doses of valsartan (600
represent 3.0 and 12 times the maximum mg/kg/day) during the last days of gestation and
recommended human dose (MRHD) of valsartan lactation led to lower survival, lower weight
and hydrochlorothiazide on a mg/m2 basis. gain and delayed development (pinna
These doses in marmoset, respectively, represent detachment and ear-canal opening) in the
0.9 and 3.5 times the maximum recommended offspring (see section 4.6). These doses in rats
human dose (MRHD) of valsartan and (600 mg/kg/day) are approximately 18 times the
hydrochlorothiazide on a mg/m2 basis. maximum recommended human dose on a
(Calculations assume an oral dose of 320 mg/m2 basis (calculations assume an oral dose of
mg/day valsartan in combination with 25 320 mg/day and a 60-kg patient). Similar
mg/day hydrochlorothiazide and a 60-kg findings were seen with
patient). valsartan/hydrochlorothiazide in rats and rabbits.
In embryo-fetal development (Segment II)
In marmosets, damage was observed in the
studies with valsartan/hydrochlorothiazide in rat
gastric mucosa (from 30 + 9 mg/kg/d). The
and rabbit, there was no evidence of
combination also led in the kidney to
hyperplasia of the afferent aterioles (at 600 + teratogenicity; however, fetotoxicity associated
188 mg/kg/d in rats and from 30 + 9 mg/kg/d in with maternal toxicity was observed.
marmosets). These doses in marmoset,
respectively, represent 0.9 and 3.5 times the
6. Pharmaceutical particulars
maximum recommended human dose (MRHD) 6.1 List of excipients
of valsartan and hydrochlorothiazide on a Microcrystalline cellulose,Silica, colloidal
mg/m2 basis. These doses in rat, respectively, anhydrous, Crospovidone, Magnesium stearate,
Hypromellose, Macrogol ,Talc, Red iron oxide,

Yellow iron oxide,Titanium dioxide.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 30°C.
Store in the original package in order to protect
from moisture.
6.5 Nature and contents of container
PVC/aluminium blister packs containing 7,28,
30, 50, 100 and 500 tablets per pack.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other
handling
No specific instructions for use/handling.
7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai - 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-
222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m.
EST
E-mail: tajgroup@tajpharma.com

Valsartan HCTZ Tablets SMPC Taj Pharmaceuticals

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Valsartan HCTZ Tablets SMPC Taj Pharmaceuticals

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Valsartan and HCT 35 mg Tablet s TajPhar ma : Use s, Side Effe cts, Interacti ons, Pi ctures, Warning s, Valsartan and

Valsartan and and 3.7mm in thickness, and weighing approx.

160mg/12.5mg, 320mg/12.5mg 4. Clinical particulars

Valsartan HCT TajPharma can be taken with or - Refractory hypokalaemia, hyponatraemia,

No interaction effects favouring the onset of digitalis-induced

Renal and urinary disorders Not known Angioedema, dermatitis bullous,

Eye disorders Non-melanoma skin cancer: based on available

Valsartan HCT TajPharma80mg/12.5 mg (64%) compared to placebo (29%) and

Valsartan) study assessed the reduction in damage. VA NEPHRON-D was a study in

Absorption At the recommended dose of Valsartan HCT

A somewhat higher systemic exposure to 5.3 Preclinical safety data

Hypromellose, Macrogol ,Talc, Red iron oxide,

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