Presentation and Status in Health Basket
Film Coated Tablets
28 X 80/12.5 mg
Film Coated Tablets
28 X 160/12.5 mg
Film Coated Tablets
28 X 160/25 mg
The recommended dose of Co-Diovan is 1 coated tablet per day. When clinically appropriate either 80 mg valsartan and 12.5 mg hydrochlorothiazide or 160 mg valsartan and 12.5 mg hydrochlorothiazide may be used. When necessary 160 mg valsartan and 25 mg may be used. The maximum daily dose is 320 mg/25 mg. The maximum antihypertensive effect is seen within 2 to 4 weeks. Co-Diovan must not be used in combination with aliskiren in patients with diabetes mellitus.
Renal impairment: No dosage adjustment is required for patients with mild to moderate renal impairment (Glomerular Filtration Rate (GFR) ≥ 30 mL/min). Due to the hydrochlorothiazide component, Co-Diovan is contraindicated in patients with anuria and should be used with caution in patients with severe renal impairment (GFR < 30 mL/min). Thiazide diuretics are ineffective as monotherapy in severe renal impairment (GFR < 30 mL/min) but may be useful in these patients, when used with due caution in combination with a loop diuretic even in patients with GFR < 30 mL/min. Concomitant use of Co-Diovan with aliskiren is contraindicated in patients with renal impairment (GFR < 60 ml/min/1.73 m²).
Hepatic impairment: No dosage adjustment is required in patients with mild to moderate hepatic impairment. Due to the hydrochlorothiazide component, Co-Diovan should be used with particular caution in patients with severe hepatic impairment. Due to the valsartan component, Co-Diovan should be used with particular caution in patients with biliary obstructive disorders.
Pediatrics (below 18 years): The safety and efficacy of Co-Diovan have not been established in children below the age of 18 years.
80/12.5 mg: Treatment of hypertension. Co-Diovan is indicated for the treatment of hypertension in patients whom combination therapy is appropriate.
160/12.5 mg, 160/25 mg: Treatment of hypertension. Co-Diovan is indicated for the treatment of hypertension in patients whose blood pressure is not adequately controlled by monotherapy. These fixed dose combinations should be used as second-line therapy.
Hypersensitivity to the active substance(s), other sulfonamide-derived medicinal products or to any of the excipients.
Second and third trimester of pregnancy.
Biliary cirrhosis and cholestasis.
Patients with anuria.
Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia.
Concomitant use of Co-Diovan with aliskiren-containing products in patients
with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73m²).
Serum electrolyte changes
Valsartan:Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other agents that may increase potassium levels (heparin, etc.) is not recommended. Monitoring of potassium should be undertaken as appropriate.
Hydrochlorothiazide: Hypokalaemia has been reported under treatment with thiazide diuretics, including hydrochlorothiazide. Frequent monitoring of serum potassium is recommended.
Treatment with thiazide diuretics, including hydrochlorothiazide, has been associated with hyponatraemia and hypochloraemic alkalosis. Thiazides, including hydrochlorothiazide, increase the urinary excretion of magnesium, which may result in hypomagnesaemia. Calcium excretion is decreased by thiazide diuretics. This may result in hypercalcaemia.
As for any patient receiving diuretic therapy, periodic determination of serum
electrolytes should be performed at appropriate intervals.
Sodium and/or volume-depleted patients: Patients receiving thiazide diuretics, including hydrochlorothiazide, should be observed for clinical signs of fluid or electrolyte imbalance.
In severely sodium-depleted and/or volume-depleted patients, such as those
receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with Co-Diovan. Sodium and/or volume depletion should be corrected before starting treatment with Co-Diovan.
Patients with severe chronic heart failure or other conditions with stimulation of the renin-angiotensin-aldosterone-system: In patients whose renal function may depend on the activity of the renin-angiotensinaldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotaemia, and in rare cases with acute renal failure and/or death. Evaluation of patients with heart failure or post-myocardial infarction should always include assessment of renal function. The use of Co-Diovan in patients with severe chronic heart failure has not been established.
Hence it cannot be excluded that because of the inhibition of the renin-angiotensinaldosterone system the application of Co-Diovan as well may be associated with impairment of the renal function. Co-Diovan should not be used in these patients.
Renal artery stenosis: Co-Diovan should not be used to treat hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, since blood urea and serum creatinine may increase in such patients.
Primary hyperaldosteronism: Patients with primary hyperaldosteronism should not be treated with Co-Diovan.
Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy: As with all other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).
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 when Co-Diovan is used in patients with renal impairment.
Kidney transplantation: There is currently no experience on the safe use of Co-Diovan in patients who have recently undergone kidney transplantation.
Hepatic impairment: In patients with mild to moderate hepatic impairment without cholestasis, Co-Diovan 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.
History of angioedema: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported in patients treated with valsartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Co-Diovan should be immediately discontinued in patients who develop angioedema, and Co-Diovan should not be readministered.
Systemic lupus erythematosus: Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate systemic lupus erythematosus.
Other metabolic disturbances: Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels of cholesterol, triglycerides and uric acid. In diabetic patients dosage adjustments of insulin or oral hypoglycaemic agents may be required.
Thiazides may reduce urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism.
Marked hypercalcaemia may be evidence of underlying hyperparathyroidism.
Thiazides should be discontinued before carrying out tests for parathyroid function.
Photosensitivity: Cases of photosensitivity reactions have been reported with thiazide diuretics. If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.
Pregnancy: Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
General: Caution should be exercised in patients who have shown prior hypersensitivity to other angiotensin II receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients with allergy and asthma.
Acute Angle-Closure Glaucoma: Hydrochlorothiazide, a sulfonamide, has been associated with 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 week of a drug initiation. Untreated acute-angle closure glaucoma can lead to permanent vision loss.
The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible.
Prompt medical or surgical treatment may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle closure glaucoma may include a history of sulfonamide or penicillin allergy.
Dual Blockade of the Renin-Angiotensin-Aldosterone System (RAAS): There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor
blockers or aliskiren increases the risk of hypotension, hyperkalaemia, and
decreased renal function (including acute renal failure). Dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended. If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Non-melanoma skin cancer: An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitising actions of hydrochlorothiazide could act as a possible mechanism for NMSC.
Patients taking hydrochlorothiazide should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of hydrochlorothiazide may also need to be reconsidered in patients who have experienced previous NMSC.
See prescribing information for full details.
Interactions related to both valsartan and hydrochlorothiazide
Concomitant use not recommended
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors, angiotensin II receptor antagonists or thiazides, including hydrochlorothiazide. Since renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity may presumably be increased further with Co-Diovan. If the combination proves necessary, a careful monitoring of serum lithium levels is recommended.
Concomitant use requiring caution
Other antihypertensive agents: Co-Diovan may increase the effects of other agents with antihypertensive properties (e.g. guanethidine, methyldopa, vasodilators, ACEI, ARBs, beta blockers, calcium channel blockers and DRIs).
Pressor amines (e.g. noradrenaline, adrenaline): Possible decreased response to pressor amines. The clinical significance of this effect is uncertain and not sufficient to preclude their use.
Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day), and non-selective NSAIDs:
NSAIDS can attenuate the antihypertensive effect of both angiotensin II antagonists and hydrochlorothiazide when administered simultaneously. Furthermore, concomitant use of Co-Diovan and NSAIDs may lead to worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, as well as adequate hydration of the patient.
See prescribing information for full details.
Pregnancy and Lactation
Pregnancy: Valsartan: The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during first trimester of pregnancy.The use of AIIRAs is contra-indicated during the second and third trimester of pregnancy.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Inhibitors (AIIRAs), similar risks may exist for this class of drugs. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately and, if appropriate, alternative therapy should be started.
AIIRAs therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for
Hydrochlorothiazide: There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.
Lactation: No information is available regarding the use of valsartan during breastfeeding. Hydrochlorothiazide is excreted in human milk. Therefore the use of Co-Diovan during breast feeding is not recommended. Alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
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.
Storage: Store below 30°C, protect from moisture.