Dafiro (Amlodipine/Valsartan)
Combination antihypertensive for the treatment of high blood pressure
Dafiro is a prescription combination medication containing two active ingredients — amlodipine (a calcium channel blocker) and valsartan (an angiotensin II receptor blocker) — used to treat high blood pressure (hypertension) in adults. By combining two complementary mechanisms of action in a single tablet, Dafiro provides more effective blood pressure control than either component alone, helping to reduce the risk of heart attack, stroke, and kidney disease.
Quick Facts
Key Takeaways
- Dual-action therapy: Dafiro combines amlodipine (calcium channel blocker) and valsartan (ARB) in one tablet for more effective blood pressure control than monotherapy.
- Once-daily dosing: Take one tablet per day, with or without food, ideally at the same time each day to maintain consistent blood levels.
- Contraindicated in pregnancy: Dafiro must not be used during pregnancy as valsartan can cause serious harm to the developing fetus, especially in the second and third trimesters.
- Monitor kidney function: Regular blood tests for kidney function and potassium levels are recommended, particularly when starting treatment or adjusting doses.
- Proven cardiovascular benefit: The amlodipine-valsartan combination has been shown in major clinical trials (ACCOMPLISH, VALUE) to effectively reduce cardiovascular events in hypertensive patients.
What Is Dafiro and What Is It Used For?
Dafiro belongs to a class of medications known as fixed-dose combination antihypertensives. It contains two well-established active ingredients that work through complementary mechanisms to lower blood pressure. Amlodipine is a dihydropyridine calcium channel blocker (CCB) that relaxes blood vessels by blocking the influx of calcium ions into vascular smooth muscle cells. Valsartan is an angiotensin II receptor blocker (ARB) that prevents the hormone angiotensin II from binding to its receptors, thereby reducing vasoconstriction, aldosterone release, and sodium retention.
The rationale for combining these two agents is well-supported by clinical evidence. International guidelines from the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH), as well as the American Heart Association (AHA) and the American College of Cardiology (ACC), recommend initiating combination therapy for most patients with hypertension, particularly those with blood pressure significantly above target or those who have not achieved adequate control with monotherapy. The 2023 ESC/ESH guidelines specifically endorse the combination of a calcium channel blocker with a renin-angiotensin system inhibitor as a preferred first-line combination.
Hypertension is a leading modifiable risk factor for cardiovascular disease worldwide. According to the World Health Organization (WHO), an estimated 1.28 billion adults aged 30–79 years have hypertension globally, with approximately two-thirds living in low- and middle-income countries. Uncontrolled hypertension dramatically increases the risk of heart attack, stroke, heart failure, kidney disease, and premature death. Effective blood pressure management with medications like Dafiro has been shown to significantly reduce these risks.
Dafiro is marketed by Novartis and is also available under the brand name Exforge in many markets. The medication was first approved by the European Medicines Agency (EMA) and has subsequently been authorized in numerous countries worldwide. It is available in various strength combinations, though the 5 mg/80 mg formulation discussed here is the most commonly prescribed starting dose.
How Does Dafiro Work?
The two components of Dafiro work through distinct but complementary pathways to reduce blood pressure:
- Amlodipine (Calcium Channel Blocker): Selectively blocks L-type calcium channels in vascular smooth muscle, reducing calcium influx and causing arterial vasodilation. This decreases peripheral vascular resistance and directly lowers blood pressure. Amlodipine has a gradual onset and long duration of action (plasma half-life of 35–50 hours), providing smooth, sustained blood pressure reduction over 24 hours.
- Valsartan (Angiotensin II Receptor Blocker): Competitively blocks the angiotensin II type 1 (AT1) receptor, preventing the vasoconstrictive and aldosterone-secreting effects of angiotensin II. This leads to vasodilation, reduced sodium and water retention, and decreased sympathetic nervous system activity. Valsartan has a half-life of approximately 6 hours but provides effective 24-hour blood pressure control.
The combination is particularly effective because the calcium channel blocker component triggers compensatory activation of the renin-angiotensin-aldosterone system (RAAS) — specifically, the peripheral edema caused by amlodipine is partially offset by the venodilatory effect of valsartan. This means that the combination not only provides greater blood pressure reduction but may also reduce the incidence of ankle edema compared to higher doses of amlodipine alone.
What Should You Know Before Taking Dafiro?
Understanding the contraindications, warnings, and precautions associated with Dafiro is essential for safe and effective treatment. While Dafiro is generally well-tolerated, certain conditions and drug interactions require careful evaluation before starting therapy. Always provide your prescribing physician with a complete medical history and a list of all current medications, including over-the-counter products and herbal supplements.
Contraindications
Dafiro must not be used in the following situations:
- Pregnancy: Dafiro is absolutely contraindicated during pregnancy, particularly during the second and third trimesters. Drugs that act on the renin-angiotensin system (such as valsartan) can cause fetal renal dysfunction, oligohydramnios (reduced amniotic fluid), skeletal deformities, and neonatal death. If pregnancy is detected, Dafiro must be discontinued immediately.
- Hypersensitivity: Known allergy to amlodipine, valsartan, other dihydropyridine derivatives, or any of the excipients in the formulation.
- Severe hepatic impairment: Patients with severe liver disease, biliary cirrhosis, or cholestasis should not take Dafiro, as both components are hepatically metabolized.
- Severe aortic stenosis: Amlodipine should be used with extreme caution (or avoided) in patients with hemodynamically significant aortic stenosis, as vasodilation may compromise coronary perfusion.
- Concomitant use with aliskiren: Co-administration with aliskiren is contraindicated in patients with diabetes mellitus or moderate-to-severe renal impairment (GFR <60 mL/min/1.73 m²) due to increased risk of hypotension, hyperkalemia, and renal failure.
Warnings and Precautions
Dafiro can cause symptomatic hypotension, particularly in patients who are volume-depleted (e.g., those on high-dose diuretics, on a salt-restricted diet, or experiencing diarrhea or vomiting). Correct volume and/or salt depletion before starting treatment. If significant hypotension occurs, place the patient in a supine position and administer intravenous normal saline if necessary.
The following conditions require special caution and close monitoring when using Dafiro:
- Renal impairment: Regular monitoring of serum creatinine and potassium is recommended. In patients with severe renal impairment (creatinine clearance <10 mL/min), there is no clinical experience, and Dafiro should be used with caution.
- Renal artery stenosis: There is an increased risk of severe hypotension and renal insufficiency in patients with bilateral renal artery stenosis or stenosis in a solitary kidney. Monitor renal function closely.
- Heart failure: In patients with congestive heart failure, amlodipine has been shown to be safe (PRAISE trial), but caution is warranted as calcium channel blockers may worsen heart failure in some patients.
- Hepatic impairment: Both amlodipine and valsartan are extensively metabolized by the liver. Use lower doses and monitor liver function in patients with mild to moderate hepatic impairment.
- Hyperkalemia: Valsartan may increase serum potassium levels. Monitor potassium regularly, especially in patients with renal impairment, diabetes, or those taking potassium-sparing diuretics or potassium supplements.
- Elderly patients: Start with caution. Elderly patients may have reduced renal and hepatic function and are more susceptible to hypotension. Dose adjustment may be necessary.
Pregnancy and Breastfeeding
Dafiro must not be used during pregnancy. Use of drugs affecting the renin-angiotensin system during the second and third trimesters has been associated with fetal and neonatal injury including hypotension, renal failure, hyperkalemia, skull hypoplasia, and death. Women of childbearing potential should use effective contraception during treatment. If pregnancy occurs, discontinue Dafiro immediately and consult your physician for alternative antihypertensive options.
There is limited data on the use of amlodipine during pregnancy. Animal studies have shown reproductive toxicity at high doses. As a precautionary measure, Dafiro should not be initiated during pregnancy, and women who become pregnant during therapy should be switched to an alternative treatment immediately.
Breastfeeding: Amlodipine is excreted in human breast milk. There is no information regarding the excretion of valsartan in human milk, though it is excreted in animal milk. Due to the potential for serious adverse effects in nursing infants, a decision should be made to either discontinue breastfeeding or discontinue Dafiro, taking into account the importance of the drug to the mother. Alternative antihypertensive medications with better-established safety profiles during breastfeeding should be considered.
How Does Dafiro Interact with Other Drugs?
Drug interactions with Dafiro can occur through both pharmacokinetic mechanisms (affecting how the drug is absorbed, distributed, metabolized, or eliminated) and pharmacodynamic mechanisms (affecting the drug's therapeutic or adverse effects). Understanding these interactions is critical to ensuring both safety and efficacy of treatment.
Amlodipine is primarily metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme system in the liver. Medications that inhibit or induce this enzyme can alter amlodipine plasma concentrations. Valsartan, on the other hand, does not rely significantly on CYP450 metabolism but is a substrate of hepatic uptake transporters (OATP1B1/OATP1B3) and efflux transporters (MRP2).
Major Interactions
| Interacting Drug | Mechanism | Clinical Effect | Recommendation |
|---|---|---|---|
| ACE inhibitors (e.g., enalapril, ramipril) | Dual RAAS blockade | Increased risk of hypotension, hyperkalemia, and renal impairment | Avoid combination; monitor closely if unavoidable |
| Aliskiren | Triple RAAS blockade | Severe hypotension, hyperkalemia, renal failure | Contraindicated in diabetes or renal impairment |
| Potassium-sparing diuretics (e.g., spironolactone, eplerenone) | Reduced potassium excretion | Hyperkalemia | Monitor serum potassium frequently |
| Lithium | Reduced renal lithium clearance | Lithium toxicity (tremor, confusion, seizures) | Monitor lithium levels; consider dose reduction |
| NSAIDs (e.g., ibuprofen, naproxen) | Prostaglandin inhibition, sodium retention | Reduced antihypertensive effect; increased renal impairment risk | Use with caution; monitor blood pressure and renal function |
Minor Interactions
| Interacting Drug | Mechanism | Clinical Effect | Recommendation |
|---|---|---|---|
| CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) | Inhibition of amlodipine metabolism | Increased amlodipine plasma levels; enhanced hypotensive effect | Monitor blood pressure; consider amlodipine dose reduction |
| CYP3A4 inducers (e.g., rifampicin, St. John's wort) | Increased amlodipine metabolism | Reduced amlodipine efficacy | Monitor blood pressure; may need dose adjustment |
| Simvastatin | CYP3A4 competition | Increased simvastatin exposure (up to 77%) | Limit simvastatin to 20 mg/day |
| Cyclosporine | CYP3A4 inhibition; altered valsartan transport | Increased amlodipine and valsartan levels | Monitor drug levels and blood pressure |
| Grapefruit juice | CYP3A4 inhibition in gut wall | Slightly increased amlodipine absorption | Moderate intake acceptable; avoid large quantities |
The ONTARGET trial demonstrated that combining an ACE inhibitor with an ARB (dual RAAS blockade) increases the risk of adverse renal outcomes without additional cardiovascular benefit. For this reason, the combination of Dafiro (which contains the ARB valsartan) with an ACE inhibitor is generally not recommended. If dual RAAS blockade is considered absolutely necessary under specialist supervision, close monitoring of blood pressure, renal function, and electrolytes is essential.
What Is the Correct Dosage of Dafiro?
Dafiro should be taken exactly as prescribed by your healthcare provider. The dosage is individualized based on the patient's blood pressure response, tolerability, and previous antihypertensive therapy. The fixed-dose combination is typically prescribed after initial dose titration with the individual components, or when switching from a free combination of the same components at equivalent doses.
Adults
Standard Adult Dosage
Starting dose: One tablet of Dafiro 5 mg/80 mg once daily. This is the recommended starting dose for patients whose blood pressure is not adequately controlled with amlodipine 5 mg or valsartan 80 mg alone.
Dose titration: If blood pressure remains uncontrolled after 2–4 weeks, the dose may be increased. Higher-strength combinations (5 mg/160 mg, 10 mg/160 mg, or 10 mg/320 mg) are available depending on the brand and market.
Maximum dose: Amlodipine 10 mg/valsartan 320 mg per day.
Administration: Swallow the tablet whole with water. Can be taken with or without food. Take at the same time each day, preferably in the morning.
| Patient Group | Recommended Dose | Special Considerations |
|---|---|---|
| Adults (standard) | 5 mg/80 mg once daily | May increase after 2-4 weeks if needed |
| Adults (higher dose) | Up to 10 mg/320 mg once daily | Titrate based on blood pressure response |
| Elderly (≥65 years) | 5 mg/80 mg once daily (start low) | Increased sensitivity to hypotension; monitor closely |
| Mild-moderate renal impairment | 5 mg/80 mg once daily | No dose adjustment needed; monitor kidney function |
| Mild-moderate hepatic impairment | Max amlodipine 5 mg component | Amlodipine clearance reduced; valsartan max 80 mg |
Children
Dafiro is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of the fixed-dose combination of amlodipine and valsartan have not been established in the pediatric population. While the individual components (amlodipine and valsartan) may be used separately in children with hypertension under specialist supervision, the combination product requires adult dosing that is inappropriate for pediatric patients. Treatment of hypertension in children should be managed by a pediatric cardiologist or nephrologist.
Elderly
Elderly patients (aged 65 years and older) may be more susceptible to the blood pressure-lowering effects of Dafiro and are at increased risk of symptomatic hypotension. The starting dose of 5 mg/80 mg is generally appropriate, but initiation of treatment should be done with caution. Blood pressure should be monitored regularly, particularly during the first few weeks of treatment and after any dose adjustment. Renal function and serum electrolytes (particularly potassium) should also be checked periodically, as age-related decline in kidney function can increase the risk of adverse effects.
In the VALUE trial, which included a significant proportion of elderly patients, valsartan-based therapy demonstrated comparable cardiovascular protection to amlodipine-based therapy, with a lower incidence of new-onset diabetes. This suggests that the combination is both effective and safe in older adults when appropriately monitored.
Missed Dose
If you miss a dose of Dafiro, take it as soon as you remember on the same day. If it is already close to the time for your next dose (i.e., less than 12 hours before the next scheduled dose), skip the missed dose and take your next dose at the regular time. Do not take a double dose to make up for a missed one. Missing a single dose is unlikely to cause a significant rise in blood pressure, but consistent daily dosing is important for optimal blood pressure control.
Overdose
An overdose of Dafiro may cause excessive blood pressure lowering (hypotension), which can lead to dizziness, fainting, or in severe cases, cardiovascular collapse. If overdose is suspected, seek emergency medical attention immediately. Treatment is supportive and symptomatic: place the patient in a supine position with legs elevated, administer intravenous fluids, and use vasopressors if needed. Valsartan is unlikely to be removed by hemodialysis. Activated charcoal may be considered if given within 1–2 hours of ingestion.
What Are the Side Effects of Dafiro?
Like all medications, Dafiro can cause side effects, although not everyone experiences them. The side effect profile of Dafiro reflects the combined adverse effects of its two active components. In clinical trials involving over 5,000 patients treated with the amlodipine/valsartan combination, the overall incidence of adverse events was comparable to placebo. The majority of side effects are mild to moderate in severity and transient in nature.
Understanding the frequency of side effects helps patients and healthcare providers weigh the benefits of treatment against potential risks. The following classification uses the standard frequency categories defined by the Council for International Organizations of Medical Sciences (CIOMS):
Very Common (>1 in 10)
Affects more than 10% of patients
- Peripheral edema (swelling of ankles and feet) — primarily due to the amlodipine component
Common (1 in 10 to 1 in 100)
Affects 1–10% of patients
- Headache
- Nasopharyngitis (cold-like symptoms)
- Influenza-like illness
- Dizziness
- Fatigue
- Flushing (hot flushes)
- Upper abdominal pain
- Nausea
Uncommon (1 in 100 to 1 in 1,000)
Affects 0.1–1% of patients
- Palpitations
- Orthostatic hypotension (dizziness on standing)
- Cough
- Diarrhea
- Constipation
- Dry mouth
- Muscle cramps
- Joint pain
- Back pain
- Vertigo
- Somnolence (drowsiness)
- Visual disturbances
- Tinnitus
- Erectile dysfunction
- Skin rash
- Hyperkalemia (elevated potassium)
Rare (<1 in 1,000)
Affects fewer than 0.1% of patients
- Angioedema (swelling of face, lips, tongue, or throat)
- Hepatitis or elevated liver enzymes
- Severe hypotension with syncope
- Thrombocytopenia (low platelet count)
- Leukopenia (low white blood cell count)
- Gingival hyperplasia (gum overgrowth) — associated with amlodipine
- Pancreatitis
- Interstitial nephritis
- Stevens-Johnson syndrome (very rare skin reaction)
Contact your doctor or seek emergency medical attention immediately if you experience: swelling of the face, lips, tongue, or throat (angioedema); difficulty breathing; severe dizziness or fainting; chest pain; irregular heartbeat; yellowing of the skin or eyes (jaundice); unexplained muscle pain with dark-colored urine; or any severe allergic reaction. These symptoms are rare but may require urgent treatment.
It is worth noting that peripheral edema, the most commonly reported side effect, tends to be dose-dependent and is primarily related to the amlodipine component. In clinical studies, the incidence of edema was lower with the amlodipine/valsartan combination compared to the same dose of amlodipine alone. This is because valsartan promotes venous dilation, which counteracts the arterial-predominant vasodilation of amlodipine. For patients who experience troublesome edema, switching to a lower amlodipine dose within the combination or adding a low-dose diuretic may be helpful.
How Should You Store Dafiro?
Proper storage of Dafiro is essential to maintain its effectiveness and safety throughout the treatment period. Incorrect storage conditions can degrade the active ingredients and compromise the medication's therapeutic effect.
- Temperature: Store at or below 30°C (86°F). Do not refrigerate or freeze.
- Moisture: Store in the original blister packaging or container to protect from moisture and humidity. Avoid storing in bathrooms or near sinks.
- Light: Protect from excessive light. Keep in the original carton when not in use.
- Children: Store securely out of reach and sight of children. Consider using child-resistant storage if available.
- Expiry date: Check the expiry date on the package before use. Do not take Dafiro after the stated expiry date (month/year). The expiry date refers to the last day of that month.
- Disposal: Do not dispose of unused medications via household waste or wastewater. Return unused or expired tablets to your pharmacy for safe disposal in accordance with local regulations.
If tablets appear discolored, crumbled, or otherwise damaged, do not take them. Contact your pharmacist for replacement. When traveling, keep Dafiro in your carry-on luggage in its original packaging, and avoid exposing it to extreme temperatures (such as in a hot car or in direct sunlight).
What Does Dafiro Contain?
Each Dafiro 5 mg/80 mg film-coated tablet contains the following:
Active Ingredients
- Amlodipine 5 mg (as amlodipine besylate) — a third-generation dihydropyridine calcium channel blocker
- Valsartan 80 mg — a selective angiotensin II type 1 (AT1) receptor antagonist
Inactive Ingredients (Excipients)
The inactive ingredients in Dafiro may include:
- Tablet core: Microcrystalline cellulose, crospovidone, colloidal silicon dioxide (colloidal anhydrous silica), magnesium stearate
- Film coating: Hypromellose (hydroxypropyl methylcellulose), titanium dioxide (E171), macrogol (polyethylene glycol), talc, iron oxide yellow (E172)
The 5 mg/80 mg tablets are typically dark yellow, oval-shaped, film-coated tablets with beveled edges. The appearance may vary slightly depending on the manufacturing site. Patients with known hypersensitivity to any of the excipients listed above should inform their prescribing physician before starting Dafiro.
Dafiro tablets do not contain lactose or gluten. However, formulations may vary by market. Always check the patient information leaflet supplied with your specific product, or consult your pharmacist if you have food allergies or intolerances.
Frequently Asked Questions About Dafiro
References
All medical information in this article is based on peer-reviewed clinical evidence and international guidelines from recognized medical authorities. No pharmaceutical company funding or influence was involved in the creation of this content.
- European Medicines Agency (EMA). Dafiro – Summary of Product Characteristics. EMA/EPAR. Available at: www.ema.europa.eu.
- Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39(33):3021-3104. doi:10.1093/eurheartj/ehy339.
- Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension. Journal of Hypertension. 2023;41(12):1874-2071. doi:10.1097/HJH.0000000000003480.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2018;71(6):e13-e115.
- Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients (ACCOMPLISH). New England Journal of Medicine. 2008;359(23):2417-2428. doi:10.1056/NEJMoa0806182.
- Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022-2031.
- ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. New England Journal of Medicine. 2008;358(15):1547-1559.
- World Health Organization. WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: World Health Organization; 2023.
- National Institute for Health and Care Excellence (NICE). Hypertension in adults: diagnosis and management. NICE guideline [NG136]. Updated 2022.
- Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure (PRAISE). New England Journal of Medicine. 1996;335(15):1107-1114.
About the Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising board-certified specialists in cardiology, internal medicine, and clinical pharmacology. Our editorial process follows the GRADE evidence framework and adheres to international standards for medical content accuracy and transparency.
All drug information is cross-referenced with the European Medicines Agency (EMA) Summary of Product Characteristics, the FDA prescribing information, and current international clinical guidelines. Content is reviewed at least annually or when new significant clinical data becomes available.
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