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ARB + thiazide Pregnancy: §4.6, verbatim. 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.' '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.' Second- and third-trimester exposure 'is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia)'; if exposure has occurred from the second trimester, ultrasound check of renal function and skull is recommended and infants should be closely observed for hypotension. Hydrochlorothiazide: crosses the placenta; 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'. Breast-feeding: '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.'

Valsartan with hydrochlorothiazide

Brand names: Co-Diovan

A fixed-dose combination of valsartan (an angiotensin-II receptor blocker) with hydrochlorothiazide (a thiazide diuretic), used to treat hypertension inadequately controlled by either agent alone.

Adult dose

Dose: Co-Diovan 80/12.5 mg — one film-coated tablet (valsartan 80 mg with hydrochlorothiazide 12.5 mg) once daily
Route: Oral — §4.2: 'Co-Diovan can be taken with or without food and should be administered with water.'
Frequency: Once daily
Max: Maximum dose of Co-Diovan 320 mg/25 mg once daily (valsartan 320 mg with hydrochlorothiazide 25 mg) — §4.2, verbatim: 'if blood pressure remains uncontrolled, the dose may be increased by increasing either one of the components to a maximum dose of Co-Diovan 320 mg/25 mg.'
INDICATION SCOPE: the fetched §4.2 addresses blood-pressure control only ('The antihypertensive effect is substantially present within 2 weeks'; patients 'whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy'), which is this page's primary indication. VERBATIM: 'The recommended dose of Co-Diovan 80/12.5mg is one film-coated tablet once daily.' STRENGTH DISCREPANCY: the fetched SPC page is Co-Diovan 160/12.5 mg but the sentence above names Co-Diovan 80/12.5 mg; the two cannot be reconciled from this bundle (no composition section, no openFDA or WHO source), so the mg figures above are taken from the source sentence itself and both components are stated explicitly rather than as 'one tablet'. TITRATION (verbatim): 'Dose titration with the individual components is recommended. In each case, up-titration of individual components to the next dose should be followed in order to reduce the risk of hypotension and other adverse events. When clinically appropriate direct change from monotherapy to the fixed combination may be considered in patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy, provided the recommended dose titration sequence for the individual components is followed.' RESPONSE ASSESSMENT (verbatim): 'The clinical response to Co-Diovan should be evaluated after initiating therapy... The antihypertensive effect is substantially present within 2 weeks. In most patients, maximal effects are observed within 4 weeks. However, in some patients, 4-8 weeks treatment may be required. This should be taken into account during dose titration.' OLDER PEOPLE: 'No dose adjustment is required in elderly patients.' PAEDIATRIC: 'Co-Diovan is not recommended for use in children below the age of 18 years due to a lack of data on safety and efficacy' — hence paedDose is null. VOLUME STATUS (§4.4): 'Sodium and/or volume depletion should be corrected before starting treatment with Co-Diovan.' Some sections of the product information we used were incomplete — check the full SPC.

Dose adjustments

Renal

§4.2, verbatim: 'No dose 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 severe renal impairment (GFR < 30 mL/min) and anuria.' §4.3 states the same bar as 'Severe renal impairment (creatinine clearance < 30 ml/min), anuria', and §4.4 adds that 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.'

Hepatic

§4.2, verbatim: '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 valsartan component, Co-Diovan is contraindicated in patients with severe hepatic impairment or with biliary cirrhosis and cholestasis.'

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Hypersensitivity to the active substances, other sulfonamide-derived medicinal products, or to any of the excipients listed in section 6.1
  • Second and third trimester of pregnancy
  • Severe hepatic impairment, biliary cirrhosis and cholestasis
  • Severe renal impairment (creatinine clearance < 30 ml/min), anuria
  • Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia
  • Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73m2)
  • Not a contraindication but a §4.4 exclusion: patients with severe chronic heart failure ('Co-Diovan should not be used in these patients'), patients with primary hyperaldosteronism, and patients with renal artery stenosis

Side effects

  • Uncommon (§4.8, valsartan/hydrochlorothiazide combination): dehydration, paraesthesia, vision blurred, tinnitus, hypotension, cough, myalgia, fatigue
  • Very rare (§4.8, combination): dizziness, diarrhoea, arthralgia
  • Not known (§4.8, combination): syncope, non-cardiogenic pulmonary oedema, impaired renal function
  • Laboratory (§4.8, frequency not known): serum uric acid increased, serum bilirubin and serum creatinine increased, hypokalaemia, hyponatraemia, elevation of blood urea nitrogen, neutropenia
  • With valsartan alone (§4.8): decrease in haemoglobin, decrease in haematocrit, thrombocytopenia, hypersensitivity reactions including serum sickness, increase of serum potassium, hyponatraemia, vertigo, vasculitis, abdominal pain, intestinal angioedema, elevation of liver function values, angioedema, dermatitis bullous, rash, pruritus, renal failure
  • Electrolyte disturbance with the thiazide component (§4.4): hypokalaemia, hyponatraemia and hypochloraemic alkalosis, hypomagnesaemia, and hypercalcaemia (calcium excretion is decreased by thiazide diuretics)
  • Symptomatic hypotension may occur after initiation in severely sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics (§4.4)
  • NOTE: the fetched §4.8 was truncated at the source-fetch limit before the hydrochlorothiazide-alone table (Table 3), so that component's own reaction list is not included here

Monitoring

  • Serum potassium (§4.4, valsartan): 'Monitoring of potassium should be undertaken as appropriate' where potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes or other agents that may increase potassium (e.g. heparin) are used — concomitant use is not recommended
  • Serum potassium (§4.4, hydrochlorothiazide): 'Frequent monitoring of serum potassium is recommended'
  • Serum electrolytes (§4.4): 'As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals'; observe for clinical signs of fluid or electrolyte imbalance
  • Blood pressure response (§4.2): 'The clinical response to Co-Diovan should be evaluated after initiating therapy' — effect substantially present within 2 weeks, maximal in most patients within 4 weeks, sometimes 4-8 weeks
  • Renal function (§4.4): 'Evaluation of patients with heart failure or post-myocardial infarction should always include assessment of renal function'; blood urea and serum creatinine may rise in renal artery stenosis

Clinical monograph

How it works

Valsartan blocks the angiotensin-II type-1 receptor to produce vasodilatation and reduce sodium-retaining aldosterone effects, while hydrochlorothiazide inhibits the distal tubular sodium-chloride co-transporter to promote natriuresis, giving additive blood-pressure reduction.

Prescribing in practice

  • The combination is contraindicated in pregnancy because ARBs can cause serious foetal harm, so it must be stopped if pregnancy is planned or confirmed.
  • Thiazide can lower potassium and sodium and raise urate and glucose, while valsartan tends to raise potassium, and concurrent NSAIDs increase the risk of acute kidney injury.
  • Avoid combining with another renin-angiotensin blocker, and use caution in renal artery stenosis, volume depletion and significant renal impairment.

Monitoring

Check renal function and serum electrolytes before starting and periodically during treatment, particularly after dose changes or intercurrent illness.

Counselling the patient

  • Stop the tablet and seek advice if you become pregnant or are planning pregnancy.
  • Report dizziness, cramps or weakness suggesting an electrolyte problem.
  • Avoid regular over-the-counter anti-inflammatory painkillers unless advised.

Evidence & guidelines

ARB plus thiazide combinations are well-established antihypertensive therapy, and NICE guidance supports stepwise combination treatment to achieve blood-pressure targets.

Reference: NICE NG136; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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