Valsartan with hydrochlorothiazide oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of valsartan with hydrochlorothiazide
Drugs List
Therapeutic Indications
Uses
Hypertension-not adequately controlled by individual components
Dosage
Adults
Doses between 80 mg valsartan with 12.5 mg hydrochlorothiazide once daily and 160 mg valsartan with 25 mg hydrochlorothiazide once daily are recommended.
The response to this medication should be evaluated after initiating therapy and if blood pressure remains uncontrolled, the dose may be increased by increasing either one of the components to a maximum dose of 320 mg valsartan with 25 mg hydrochlorothiazide.
The peak anti-hypertensive effect is seen within 2 to 4 weeks from the initiation of therapy. However, in some patients 4 to 8 weeks of treatment may be necessary. This should be taken into account during dose titration.
Elderly
(See Dosage; Adult)
Patients with Hepatic Impairment
Mild to moderate hepatic impairment without cholestasis
The dose of valsartan should not exceed 80 mg - use with caution in this population.
Additional Dosage Information
When clinically appropriate direct change from monotherapy to the fixed combination therapy 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.
Contraindications
Children under 18 years
Addison's disease
Anuria
Biliary cirrhosis
Breastfeeding
Cholestasis
Galactosaemia
Hepatic encephalopathy
Hypercalcaemia
Hyperuricaemia
Hyponatraemia
Pregnancy
Refractory hypokalaemia
Renal impairment - creatinine clearance below 30 ml/minute
Severe bilateral renal artery stenosis
Severe hepatic impairment
Severe unilateral stenosis of solitary functioning kidney
Precautions and Warnings
Elderly
Aortic stenosis
Asthma
Bilateral renal artery stenosis
Diabetes mellitus
Electrolyte depletion
Glucose-galactose malabsorption syndrome
Gout
Hepatic cirrhosis
History of skin cancer
Hyperaldosteronism
Hypertrophic obstructive cardiomyopathy
Hypovolaemia
Lactose intolerance
Malnutrition
Mild hepatic impairment
Mitral stenosis
Nephrotic syndrome
Peripheral vascular disease
Renal impairment
Renovascular disorder
Severe congestive cardiac failure
Severe generalised atherosclerosis
Systemic lupus erythematosus
Unilateral stenosis of solitary functioning kidney
Advise patient to protect skin if restarting following photosensitivity
Patients with primary aldosteronism may not benefit from this treatment
Advise ability to drive/operate machinery may be affected by side effects
Afro-Caribbean or black patients may show reduced response
Correct volume and/or salt depletion before initiating therapy
Some formulations contain lactose
Some products may contain soya or soya derivative
Evaluate renal function before and during treatment
Diabetic control may need adjustment
Monitor periodically for signs of fluid or electrolyte imbalance
Monitor serum potassium regularly
Advise patient of increased risk of non-melanoma skin cancer
Advise patient to monitor for and report any skin changes
Excess consumption of liquorice may increase the risk of hypokalaemia
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Increases in cholesterol and triglyceride levels may be seen
May precipitate diabetes mellitus
May precipitate gout
Patient to report nausea, vomiting or situations leading to salt/water loss
Withdraw and consider hyperparathyroidism if frank hypercalcaemia develops
Discontinue before parathyroid function tests
Advise patient to seek advice at first indications of pregnancy
Discontinue if angioedema occurs
Discontinue if patient develops decreased visual acuity +/or ocular pain
Discontinue if photosensitivity occurs
Discontinue if symptoms of acute angle closure glaucoma occur
Additional calcium/vitamin D under strict medical supervision only
Advise patient not to take NSAIDs unless advised by clinician
Hypotensive effects may be potentiated by alcohol
Advise on problems of salt substitutes/high intake of potassium-rich food
Female: Ensure adequate contraception during treatment
Advise pt. to minimise exposure to sunlight & avoid sunlamps during therapy
In patients whose renal function may depend on the activity of the renin-angiotensin system (e.g. patients with severe congestive heart failure), treatment with ACE inhibitors has been associated with oliguria and/ or progressive azotaemia and in rare cases with acute renal failure and/ or death. As valsartan is an angiotensin II antagonist, it cannot be excluded that the use of this medication may be associated with impairment of the renal function.
Hydrochlorothiazide has been associated with an idiosyncratic reaction resulting in choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma. Symptoms can occur within hours to weeks of the drug initiation, these include acute onset of decreased visual activity or ocular pain.
If intraocular pressure remains uncontrolled, consider prompt medical or surgical treatment. Risk factors for developing acute closure glaucoma may include a history of sulfonamide or penicillin allergy.
Pregnancy and Lactation
Pregnancy
Valsartan with hydrochlorothiazide is contraindicated in pregnancy.
Valsartan
Angiotensin II receptor antagonists may be associated with similar risks as ACE inhibitors. Angiotensin II receptor antagonist exposure during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).
The MHRA states that the use of angiotensin II receptor antagonists in late pregnancy has been associated with adverse effects on the foetal kidney and other congenital anomalies, therefore angiotensin II receptor antagonists should not be used at any stage during of pregnancy unless absolutely necessary and only then after the potential risks and benefits have been discussed with the patient.
Exposure to angiotensin II receptor antagonists during the first trimester has been inconclusive, however, a small increase in risk cannot be excluded and a detailed ultrasound is recommended.
If pregnancy is detected during therapy, valsartan should be discontinued as soon as possible and alternative treatment should be offered. Guidelines advise that women who are taking angiotensin II receptor blockers are told that there is an increased risk of congenital abnormalities if these drugs are taken during pregnancy and other antihypertensive treatments should be discussed and offered.
Hydrochlorothiazide
Diuretics can reduce plasma volume and lead to a reduced perfusion of the placenta. Schaefer (2007) comments that diuretics are no longer part of the standard therapy for hypertension and oedema during pregnancy; they should only be used for particular indications. In such cases hydrochlorothiazide is the diuretic of choice. Use of hydrochlorothiazide is not an indication for interrupting pregnancy. Briggs (2011) comments that in general, diuretics are not recommended in the treatment of gestational hypertension because of the maternal hypovolaemia characteristic of the disease.
Thiazides and related diuretics may cause neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbance and hypoglycaemia. Stimulation of labour, uterine inertia and meconium staining have also been reported.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Valsartan with hydrochlorothiazide is contraindicated in breastfeeding.
Valsartan
Schaefer (2007) suggests that accidental administration of a single dose does not require weaning, however, therapy should be changed to an antihypertensive which has been better studied in breastfeeding. The MHRA concludes that the use of angiotensin II receptor antagonists in breastfeeding mothers is not recommended. Alternative agents with more established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm baby.
Hydrochlorothiazide
Hydrochlorothiazide is excreted in small quantities into breast milk. There have been reports of thrombocytopenia in the nursing infants of mothers receiving a thiazide diuretic, however, the risk is considered low by, Hale (2010) and Briggs (2011). Thiazide diuretics have been used in large quantities to suppress lactation. Overall, hydrochlorothiazide is considered safe while breastfeeding (Briggs, 2011, Schaefer, 2007 and Hale, 2010).
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal discomfort
Abdominal pain
Acute respiratory distress
Agranulocytosis
Altered glucose tolerance
Angioedema
Arthralgia
Blurred vision
Bone marrow depression
Cardiac arrhythmias
Choroidal effusion
Constipation
Cough
Decrease in haematocrit
Decreased appetite
Dehydration
Depression
Diarrhoea
Dizziness
Electrolyte disturbances
Elevated triglyceride levels
Elevation of liver enzymes
Exacerbation of systemic lupus erythematosus
Fatigue
Glaucoma (closed angle)
Gout
Haemoglobin decrease
Haemolytic anaemia
Headache
Hypercalcaemia
Hyperkalaemia
Hypersensitivity reactions
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypotension
Impaired renal function
Impotence
Increase in blood urea nitrogen
Increase in creatinine
Increase in plasma cholesterol
Increased uric acid level
Intrahepatic cholestasis
Jaundice
Leucopenia
Lupus erythematosus-like syndrome
Myalgia
Nausea
Necrotising vasculitis
Neutropenia
Pancreatitis
Paraesthesia
Photosensitivity
Pneumonitis
Postural hypotension
Pruritus
Pulmonary oedema
Rash
Renal failure
Serum bilirubin increased
Serum sickness
Sleep disturbances
Syncope
Thrombocytopenia
Thrombocytopenic purpura
Tinnitus
Toxic epidermal necrolysis
Urticaria
Vasculitis
Vertigo
Visual disturbances
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: August 2013
Reference Sources
British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Co-Diovan 80/12.5mg, 160/12.5mg, 160/25mg tablets. Novartis Pharmaceuticals UK Ltd. Revised August 2020.
Summary of Product Characteristics: Valsartan/hydrochlorothiazide 80/12.5mg film-coated tablets. Actavis UK Ltd. Revised July 2012.
Summary of Product Characteristics: Valsartan/hydrochlorothiazide 160/12.5mg film-coated tablets. Actavis UK Ltd. Revised July 2012.
Summary of Product Characteristics: Valsartan/hydrochlorothiazide 160/25mg film-coated tablets. Actavis UK Ltd. Revised July 2012.
MHRA Drug Safety Update: Volume 1, Issue 5 December 2007.
Available at: https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/index.htm
Last accessed: August 6, 2013
MHRA Drug Safety Update: Volume 2. Issue 10. May 2009.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON046451
Last accessed: August 6, 2013
MHRA Drug Safety Update November 2018
Available at: https://www.mhra.gov.uk
Last accessed: 08 January 2019
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Hydrochlorothiazide, Last revised: January 24, 2013.
Last accessed: August 6, 2013.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Valsartan, Last revised: September 29, 2009.
Last accessed: August 6, 2013.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.