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Amlodipine with valsartan oral


All formulations of amlodipine with valsartan.

Drugs List

  • amlodipine 10mg and valsartan 160mg tablets
  • amlodipine 5mg and valsartan 160mg tablets
  • amlodipine 5mg and valsartan 80mg tablets
  • EXFORGE 10mg+160mg tablets
  • EXFORGE 5mg+160mg tablets
  • EXFORGE 5mg+80mg tablets
  • Therapeutic Indications


    Hypertension-not adequately controlled by individual components


    Individual dose titration with the components is recommended prior to administering the fixed combination dose formulation


    5 mg amlodipine with 80 mg valsartan once daily in patients whose blood pressure is not adequately controlled with amlodipine 5 mg or valsartan 80 mg alone.
    5 mg amlodipine with 160 mg valsartan once daily in patients whose blood pressure is not adequately controlled with amlodipine 5 mg or valsartan 160 mg alone.
    10mg amlodipine with 160mg valsartan once daily in patients whose blood pressure is not adequately controlled with amlodipine 10 mg or valsartan 160 mg alone.


    (See Dosage; Adult).

    Patients with Hepatic Impairment

    Mild to moderate hepatic impairment (without cholestasis)
    The maximum recommended dose of valsartan is 80mg in these patients.


    Children under 18 years
    Biliary cirrhosis
    Cardiac failure within 1 month of a myocardial infarction
    Cardiogenic shock
    Left ventricular outflow obstruction
    Renal dialysis
    Renal impairment - glomerular filtration rate below 30ml/minute/1.73m sq
    Severe aortic stenosis
    Severe bilateral renal artery stenosis
    Severe hepatic impairment
    Severe hypotension
    Severe unilateral stenosis of solitary functioning kidney
    Unstable angina

    Precautions and Warnings

    Females of childbearing potential
    Acute porphyria
    Aortic stenosis
    Bilateral renal artery stenosis
    Electrolyte depletion
    Hepatic impairment
    Hypertrophic obstructive cardiomyopathy
    Mitral stenosis
    Peripheral vascular disease
    Renal impairment - creatinine clearance 30-60ml/minute
    Renovascular disorder
    Severe congestive cardiac failure
    Severe generalised atherosclerosis
    Unilateral stenosis of solitary functioning kidney

    Patients with primary aldosteronism may not benefit from this treatment
    Reduce dose in patients with hepatic impairment
    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
    Place patient in supine position if severe hypotension occurs
    Evaluate renal function before and during treatment
    Monitor serum electrolytes before and during treatment
    Monitor serum potassium regularly
    Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
    Advise patient to seek advice at first indications of pregnancy
    Discontinue if angioedema occurs
    Advise patient not to take NSAIDs unless advised by clinician
    Advise on problems of salt substitutes/high intake of potassium-rich food
    Grapefruit prod increase dihydropyridine Ca channel blocker bioavailability
    Female: Ensure adequate contraception during treatment

    Renal function and electrolytes should be checked before starting treatment and monitored during therapy, especially in patients post myocardial infarction, those with heart failure and when treating hypertension in children or adolescents. Side effects (such as hyperkalaemia) are more common in patients with renal impairment- the dose may need to be reduced. A specialist should be involved if renal function is significantly reduced.

    Monitor plasma potassium, particularly in the elderly, patients with renal impairment, in the presence of other conditions (fever, dehydration) which affect renal function and patients in whom potassium supplements / retaining medication is essential.

    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.

    Avoid use in patients with known or suspected renovascular disease, unless the blood pressure cannot be controlled with other drugs. Use with particular precaution in patients who have undiagnosed and clinically silent renovascular disease.

    Co-administration of NSAIDS may reduce the antihypertensive effect of angiotensin II receptor antagonists, increase serum potassium and exacerbate renal impairment.

    Pregnancy and Lactation


    Contraindicated in pregnancy. Adequate contraception is recommended for women of childbearing potential. When pregnancy is diagnosed, treatment should be immediately discontinued and if possible an alternative treatment started.

    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.

    Some dihydropyridine compounds have been found to be teratogenic in animals. However, amlodipine was found not to be teratogenic or embryotoxic in rats and rabbits up to 8 and 23 times, respectively, the maximum human dose based on BSA (MRHD) during their respective periods of major organogenesis. Effects on reproduction in animals were found at high dosages (including delayed parturition, difficult labour and impaired foetal and pup survival) (Briggs, 2011). There is no adequate data for the use of amlodipine in pregnant women. The molecular weight of amlodipine is low enough that passage to the foetus should be expected. Calcium channel blockers may inhibit labour (Schaefer,2007). In the first trimester, calcium antagonists are considered to be second-line therapy. Manufacturers advise amlodipine should not be administered during pregnancy or to women of childbearing potential unless effective contraception is used unless clearly needed. Schaefer (2007) suggests that if exposure to amlodipine has occurred during the first trimester, a detailed ultrasound diagnosis is advisable. Overall exposure to a calcium antagonist during pregnancy is not an indication for either invasive diagnostic procedures or termination of pregnancy.

    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 14-17 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 ( ) or if this is unavailable at the backup site ( ).

    Licensed in pregnancy? - Contraindicated

    Recommended for use in pregnancy? - No

    Known human teratogen? - Yes, angiotensin II receptor antagonists

    Other information - Methyldopa, labetalol, hydralazine, modified-release preparations of nifedipine are the drugs with most safety data during pregnancy.


    Contraindicated during breastfeeding.

    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.

    There is no adequate data for the use of amlodipine in breastfeeding. Hale (2010) comments that because most calcium channel blockers readily transfer into milk, that the same should be assumed for this drug. The molecular weight of amlodipine is low enough that excretion into breast milk should be expected. No paediatric concerns have been reported but the infant should be observed for bradycardia or hypotension upon prolonged use. Guidelines from NICE recommend that women who still need antihypertensive treatment in the postnatal period are told that there is insufficient evidence on the safety in babies receiving breast milk of amlodipine. Some manufacturers advise patients to stop breast feeding during treatment with amlodipine as it is not known whether amlodipine is excreted in breast milk. Schaefer (2007) comments that individual doses of amlodipine do not require limitation of breastfeeding, but therapy should be changed. An alternative drug may be preferred.

    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

    Considered suitable or recommended by manufacturer? - No

    Drug substances licensed in infants? - No

    Side Effects

    Abdominal pain
    Altered bowel habit
    Atrial fibrillation
    Back pain
    Chest pain
    Cholestatic jaundice
    Decrease in haemoglobin and haematocrit
    Dry mouth
    Electrolyte disturbances
    Erectile dysfunction
    Erythema multiforme
    Exfoliative dermatitis
    Extrapyramidal effects
    Facial oedema
    Gingival hyperplasia
    Hypersensitivity reactions
    Impaired co-ordination
    Increases in hepatic enzymes
    Joint swelling
    Mood changes
    Muscle spasm
    Myocardial infarction
    Orthostatic hypotension
    Peripheral neuropathy
    Peripheral oedema
    Pharyngolaryngeal pain
    Pitting Oedema
    Renal failure
    Renal impairment
    Sensation of heaviness
    Serum bilirubin increased
    Serum creatinine increased
    Skin discolouration
    Sleep disturbances
    Stevens-Johnson syndrome
    Taste disturbances
    Urinary abnormalities
    Ventricular tachycardia
    Visual disturbances
    Weight changes


    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 ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: April 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.

    Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

    Summary of Product Characteristics: Exforge 5mg/80mg, 5mg/160mg, 10mg/160mg film coated tablets. Novartis Pharmaceutical UK Ltd. Revised October 2012.

    MHRA Drug Safety Update: Volume 1, Issue 5 December 2007.
    Available at:
    Last accessed: April 12, 2013.

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Amlodipine Last revised: October 2, 2012
    Last accessed: April 12, 2013

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Valsartan Last revised: September 29, 2009
    Last accessed: April 12, 2013

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