Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue valsartan as soon as possible.
Hypertension:
Note: Oral dosage forms (tablets, solution [commercially available], and extemporaneously compounded suspension) are not bioequivalent on a mg:mg basis. Due to increased bioavailability of the oral solution (commercially available) and oral suspension (extemporaneously compounded), patients may require a higher dose when converting from oral suspension or solution to tablet dosage form.
Infants ≥6 months and weighing ≥6 kg: Limited data available; optimal dosage not defined: Oral: Suspension (extemporaneously compounded): Initial: 1 mg/kg/dose once daily; titrate every 2 weeks to effect up to a maximum daily dose: 4 mg/kg/day; reported dosage range: 0.25 to 4 mg/kg/dose once daily(Ref).
Children <6 years: Tablet, suspension (extemporaneously compounded): Oral: Initial: 1 mg/kg/dose once daily; maximum initial daily dose: 40 mg/day; some patients may require a higher initial dose of 2 mg/kg/dose once daily. May titrate to effect up to a maximum daily dose: 4 mg/kg/day not to exceed 160 mg/day.
Children ≥6 years and Adolescents <17 years:
Solution (commercially available): Oral: Initial: 0.65 mg/kg/dose twice daily; maximum initial daily dose: 40 mg/day. May titrate to effect up to a maximum dose of 1.35 mg/kg/dose twice daily not to exceed 160 mg/day.
Tablet, suspension (extemporaneously compounded): Oral: Initial: 1 to 1.3 mg/kg/dose once daily; maximum initial daily dose: 40 mg/day; some patients may require a higher initial dose of 2 mg/kg/dose once daily. May titrate to effect up to a maximum daily dose: 4 mg/kg/day not to exceed 160 mg/day (Ref). Note: Pediatric patients 6 to 16 years of age with obesity were observed to respond at similar doses as patients without obesity (Ref).
Adolescents ≥17 years: Oral: Initial: 80 mg or 160 mg once daily; some patients may require the higher initial dose. May titrate to effect up to a maximum daily dose: 320 mg/day. Note: If the commercially available oral solution is used, the manufacturer labeling recommends administering the dose in 2 divided doses.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents:
CrCl ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
CrCl <30 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; has not been studied; use with caution; valsartan use in chronic kidney disease undefined (Ref).
Dialysis: Not significantly removed.
Children and Adolescents:
Mild to moderate impairment: No initial dosage adjustment necessary; use caution in patients with liver disease. Patients with mild to moderate chronic disease have twice the exposure as healthy volunteers.
Severe impairment: There are no dosage adjustments provided in manufacturer's labeling; has not been studied; use with caution.
(For additional information see "Valsartan: Drug information")
Dosage guidance:
Dosage form information: The commercially available oral solution and extemporaneously compounded oral suspension have greater bioavailability than tablets. All doses shown in this monograph are for the oral tablets. When converting to an oral liquid preparation, reassess dose.
Acute coronary syndrome:
Note: Alternative in patients who cannot tolerate an angiotensin-converting enzyme (ACE) inhibitor (eg, due to cough) (Ref). In patients with prior ACE inhibitor–associated angioedema (ie, without urticaria or other signs of hypersensitivity), an angiotensin II receptor blocker (ARB) may still be an alternative. ARBs do not appear to elevate the risk of angioedema (Ref); however, patients must be educated that angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Ref); referral to an allergist may be appropriate.
Non–ST-elevation acute coronary syndrome (alternative agent):
Note: Initiate in stable patients prior to hospital discharge as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40%, hypertension, or stable chronic kidney disease (Ref).
Oral: Initial: 20 mg twice daily; may increase dose as tolerated up to 160 mg twice daily under close monitoring to avoid hypotension.
ST-elevation myocardial infarction (alternative agent):
Note: In hemodynamically stable patients with large anterior ST-elevation myocardial infarction, consider starting within 24 hours of presentation as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue therapy indefinitely (Ref).
Oral: Initial: 20 mg twice daily; may increase dose as tolerated up to 160 mg twice daily under close monitoring to avoid hypotension.
Heart failure with reduced ejection fraction (alternative agent):
Note: Alternative therapy in patients who cannot tolerate an angiotensin II receptor-neprilysin inhibitor (ARNI) or an ACE inhibitor (eg, due to cough or angioedema); consultation with a heart failure specialist and/or an allergist may be appropriate (Ref). ARBs do not appear to elevate the risk of angioedema (Ref); however, angioedema due to an ACE inhibitor can sometimes reoccur within months following discontinuation (Ref).
Oral: Initial: 20 to 40 mg twice daily; increase dose (eg, double) every ≥1 to 2 weeks based on response and tolerability to a target dose of 160 mg twice daily (Ref). In hospitalized patients, may titrate more rapidly as tolerated (Ref).
Hypertension, chronic:
Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (Ref).
Oral: Initial: 80 to 160 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling) as needed up to a maximum of 320 mg once daily; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref). If the commercially available oral solution is used, the manufacturer labeling recommends administering the dose in 2 divided doses.
Proteinuric chronic kidney disease, diabetic or nondiabetic (off-label use):
Oral: Initial: 80 to 160 mg once daily or in two divided doses depending on baseline BP; titrate gradually (eg, by doubling the dose every 2 to 4 weeks) up to the maximally tolerated dose, not to exceed 320 mg/day. If proteinuria target is not met despite optimized dosage, consider additional therapies (eg, sodium-glucose cotransporter-2 inhibitor) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref). Note: Use with caution in patients with kidney impairment (especially CrCl <30 mL/minute); monitor kidney function and potassium more closely (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Ref): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Note: Should be used with caution in patients with ascites due to cirrhosis (Ref).
Mild to moderate impairment: No initial dosage adjustment necessary; use with caution.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Valsartan may be associated with increased serum creatinine and/or acute kidney injury. Increases in serum creatinine secondary to angiotensin receptor blockers usually stabilize within 20% to 30% from baseline and are expected; additional increases may indicate renal artery stenosis or volume depletion (Ref).
Mechanism: Related to pharmacologic action; inhibits efferent renal arteriolar vasoconstriction, lowering glomerular filtration pressure which can lead to a modest reduction in glomerular filtration rate (GFR) (Ref).
Onset: Expected to be similar to angiotensin-converting enzyme inhibitors: Intermediate; transient increases in serum creatinine generally occur within 2 weeks initiation and stabilize within 2 to 4 weeks (Ref).
Risk factors:
• Sodium or volume depletion (Ref)
• Heart failure (Ref)
• Concurrent diuretic and/or nonsteroidal anti-inflammatory use (Ref)
• Older patients
• Hypotension (Ref)
• Preexisting kidney impairment (Ref)
• Patients with low renal blood flow (eg, renal artery stenosis) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II (Ref)
Hyperkalemia may occur in adult and pediatric patients (Ref).
Mechanism: Related to the pharmacologic action; blocks angiotensin II from binding to the adrenal receptor and interferes with generation of angiotensin II within the adrenal cortex, decreasing aldosterone release and impairing renal potassium excretion (Ref).
Onset: Generally occurs within 1 week of treatment initiation (Ref).
Risk factors:
• High dietary intake of potassium (Ref)
• Baseline elevated potassium (≥5 mmol/L) (Ref)
• Older patients (Ref)
• Kidney dysfunction (Ref)
• Diabetes mellitus (Ref)
• Concurrent use of medications known to decrease renin and aldosterone (eg, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, cyclosporine, tacrolimus, beta-blockers, sulfamethoxazole/trimethoprim, azole antifungals) (Ref)
• Concurrent use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. Adverse reactions occurred with heart failure or post-MI unless otherwise indicated.
>10%:
Nervous system: Dizziness (17%; hypertension: 2% to 8%)
Renal: Increased blood urea nitrogen (>50% increase: 17%)
1% to 10%:
Cardiovascular: Hypotension (6% to 7%; hypertension: <1%), orthostatic dizziness (2%), orthostatic hypotension (2%), syncope (>1%; hypertension: <1%)
Endocrine & metabolic: Hyperkalemia (2%) (table 1)
Drug (Valsartan) |
Placebo |
Indication |
Number of Patients (Valsartan) |
Number of Patients (Placebo) |
---|---|---|---|---|
2% |
1% |
Heart failure |
3,282 |
2,740 |
Gastrointestinal: Abdominal pain (hypertension: 2%), diarrhea (5%), nausea (>1%), upper abdominal pain (>1%)
Hematologic & oncologic: Neutropenia (2%)
Nervous system: Fatigue (3%; hypertension: 2%), headache (>1%), vertigo (>1%)
Neuromuscular & skeletal: Arthralgia (3%), back pain (3%)
Ophthalmic: Blurred vision (>1%)
Renal: Increased serum creatinine (4%) (table 2) , renal insufficiency (>1%)
Drug (Valsartan) |
Comparator (Captopril) |
Placebo |
Indication |
Number of Patients (Valsartan) |
Number of Patients (Captopril) |
Number of Patients (Placebo) |
Comments |
---|---|---|---|---|---|---|---|
4% |
N/A |
0.9% |
Heart failure |
3,282 |
N/A |
2,740 |
>50% Increase in creatinine |
4% |
3% |
N/A |
Post-myocardial infarction |
4,885 |
4,879 |
N/A |
Doubling of creatinine |
Respiratory: Dry cough (hypertension: 3%)
Postmarketing:
Cardiovascular: Vasculitis
Dermatologic: Alopecia, bullous dermatitis (Gao 2021), lichenoid eruption (Gencoglan 2009), skin rash (Ozturk 2012)
Hematologic & oncologic: Thrombocytopenia
Hepatic: Hepatitis, increased liver enzymes
Hypersensitivity: Angioedema (Alhowary 2018, Kalra 2012)
Neuromuscular & skeletal: Rhabdomyolysis
Renal: Acute kidney injury
Hypersensitivity to valsartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with aliskiren in patients with moderate to severe kidney impairment (GFR <60 mL/minute/1.73 m2); pregnancy; breastfeeding.
Concerns related to adverse effects:
• Angioedema: Angiotensin II receptor antagonists (ARBs) do not appear to elevate the risk of angioedema (Rasmussen 2019; Toh 2012). Patients with a history of angioedema due to an angiotensin-converting enzyme inhibitor must be educated that sometimes there can be recurrence within months following discontinuation (Beltrami 2011). No matter the cause of angioedema, prolonged frequent monitoring is required, especially if tongue, glottis, or larynx are involved, as they are associated with airway obstruction. Discontinue therapy immediately if angioedema occurs. Aggressive early management is critical. IM administration of epinephrine may be necessary. Do not readminister the ARB to patients who experience angioedema from this medication.
• Hypotension: Symptomatic hypotension may occur upon initiation in patients who are salt- or volume-depleted (eg, those treated with high-dose diuretics); correct volume depletion prior to administration. This transient hypotensive response is not a contraindication to further treatment with valsartan.
Disease-related concerns:
• Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis.
• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and kidney function carefully to avoid rapid development of kidney failure (AASLD [Runyon 2013]).
• Hepatic impairment: Use with caution in patients with hepatic impairment (exposure to valsartan is increased).
• Kidney impairment: Use with caution in patients with kidney impairment.
Special populations:
• Race/Ethnicity: In Black patients, the BP-lowering effects of ARBs may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2018; manufacturer's labeling).
• Surgical patients: In patients on chronic ARB therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (ACCF/AHA [Hillis 2011]). Based on current research and clinical guidelines in patients undergoing noncardiac surgery, continuing ARBs is reasonable in the perioperative period. If ARBs are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).
Dosage form specific issues:
• Product interchangeability: The commercially available oral solution, extemporaneously compounded oral suspension, and tablets are not interchangeable with each other due to differences in pharmacokinetics; do not combine the 2 dosage forms to achieve the total dose.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Generic: 4 mg/mL (120 mL)
Tablet, Oral:
Diovan: 40 mg [scored]
Diovan: 80 mg, 160 mg, 320 mg
Generic: 40 mg, 80 mg, 160 mg, 320 mg
Yes
Solution (Valsartan Oral)
4 mg/mL (per mL): $2.75 - $9.27
Tablets (Diovan Oral)
40 mg (per each): $9.28
80 mg (per each): $11.09
160 mg (per each): $11.93
320 mg (per each): $15.09
Tablets (Valsartan Oral)
40 mg (per each): $0.25 - $5.12
80 mg (per each): $0.29 - $6.12
160 mg (per each): $0.31 - $6.58
320 mg (per each): $0.37 - $8.32
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Diovan: 40 mg, 80 mg, 160 mg, 320 mg
Generic: 40 mg, 80 mg, 160 mg, 320 mg
Note: A valsartan oral solution (4 mg/mL) is commercially available.
4 mg/mL Oral Suspension
A 4 mg/mL oral suspension may be made from tablets, Ora-Plus, and Ora-Sweet SF. Add 80 mL of Ora-Plus to an 8-ounce amber glass bottle containing eight valsartan 80 mg tablets. Shake well for ≥2 minutes. Allow the suspension to stand for a minimum of 1 hour, then shake for ≥1 minute. Add 80 mL of Ora-Sweet SF to the bottle and shake for ≥10 seconds. Store in amber glass prescription bottles; label "shake well". Stable for 30 days at room temperature (below 30°C [86°F]), or 75 days refrigerated (2°C to 8°C [35°F to 46°F]).
Oral: May be administered without regard to food; shake oral suspension well before use.
Missed dose: Take missed dose as soon as possible unless almost time for the next dose; do not double a dose to make up for a missed dose.
Oral:
Oral solution: Administer consistently with regard to food because high-fat meals decrease AUC ~8% and Cmax ~44%.
Oral suspension: Shake well before use.
Tablets: Administer with or without food.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect tablets from moisture.
Treatment of hypertension alone or in combination with other antihypertensive agents (Tablet: FDA approved in ages ≥1 year and adults; solution: FDA approved in ages ≥6 years and adults); reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (FDA approved in adults); reduction of risk of hospitalization in patients with heart failure (NYHA Class II-IV) (FDA approved in adults).
Valsartan may be confused with losartan, Valstar, Valturna
Diovan may be confused with Zyban
Diovan [US, Canada, and multiple international markets] may be confused with Darvon brand name for betahistine [Indonesia] and Dianben brand name for metformin [Spain]
Substrate of MRP2, OATP1B1/1B3 (SLCO1B1/1B3)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Angiotensin II: Receptor Blockers may diminish the therapeutic effect of Angiotensin II. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider therapy modification
Antihepaciviral Combination Products: May increase the serum concentration of Valsartan. Management: Consider decreasing the valsartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination. Risk D: Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Belumosudil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of OATP1B1/1B3 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the OATP1B1/1B3 substrate may be required. Risk D: Consider therapy modification
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Bulevirtide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider therapy modification
Ceftobiprole Medocaril: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Finerenone: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Heparin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Isocarboxazid: May enhance the antihypertensive effect of Antihypertensive Agents. Risk X: Avoid combination
Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Leniolisib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Initiate lithium at lower doses in patients receiving an angiotensin II receptor blocker (ARB). Consider lithium dose reductions in patients stable on lithium therapy who are initiating an ARB. Monitor lithium concentrations closely when combined. Risk D: Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of Angiotensin II Receptor Blockers. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ranolazine: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sodium Phosphates: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy
Sparsentan: May enhance the adverse/toxic effect of Angiotensin II Receptor Blockers. Risk X: Avoid combination
Tacrolimus (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider therapy modification
Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Food decreases tablet Cmax and AUC by 50% and 40%, respectively. Oral solution Cmax and AUC are decreased by ~44% and 8%, respectively, with a high-fat, high-calorie meal. Management: Administer consistently with regard to food.
Avoid salt substitutes which contain potassium.
Avoid use of an angiotensin II receptor blocker (ARB) in patients who may become pregnant and who are not using effective contraception (ADA 2021).
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. ARBs are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
When an ARB is used for the treatment of proteinuric chronic kidney disease in patients who could become pregnant, discontinue use at the first positive pregnancy test (ADA 2021; Fakhouri 2022).
ARBs are not recommended for the treatment of heart failure in patients planning to become pregnant (AHA/ACC/HFSA [Heidenreich 2022]).
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Exposure to an angiotensin II receptor blocker (ARB) during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 2019; ESC [Regitz-Zagrosek 2018]). Following exposure during the second or third trimesters, drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal kidney function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ARB use during pregnancy is also associated with anuria, hypotension, kidney failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ARB in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function.
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated hypertension may also increase the risk of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 2019).
Discontinue ARBs as soon as possible once pregnancy is detected. Agents other than an ARB are recommended for the treatment of chronic hypertension during pregnancy (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]). Closely monitor patients exposed to an ARB during pregnancy with serial ultrasounds.
ARBs are not recommended for the treatment of heart failure or proteinuric chronic kidney disease during pregnancy (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Regitz-Zagrosek 2018]; Fakhouri 2022).
Baseline and periodically with therapy: Blood pressure, BUN, serum creatinine, renal function, serum electrolytes (particularly potassium; monitor more frequently in patients with kidney impairment).
Valsartan produces direct antagonism of the angiotensin II (AT2) receptors, unlike the ACE inhibitors. It displaces angiotensin II from the AT1 receptor and produces its blood pressure-lowering effects by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. This action results in more efficient blockade of the cardiovascular effects of angiotensin II and fewer side effects than the ACE inhibitors.
Note: Commercially available oral solution and extemporaneously compounded oral suspension are not therapeutically equivalent to the tablet formulation. For an equivalent dose, valsartan oral solution has 86% higher Cmax and 25% higher AUC compared to tablet formulation.
Onset of action: ~2 hours.
Duration: 24 hours.
Distribution: Vd: 17 L.
Protein binding: 95%, primarily albumin.
Metabolism: To inactive metabolite (valeryl 4-hydroxy valsartan).
Bioavailability: Tablet: 25% (range: 10% to 35%); Suspension (extemporaneously prepared): ~40% (~1.6 times more than tablet).
Half-life elimination:
Children 1 to 5 years: ~4 hours (Blumer 2009).
Children and Adolescents 6 to 16 years: ~5 hours (Blumer 2009).
Adults: ~6 hours; ~35% longer in elderly patients.
Time to peak, serum:
Children and Adolescents 1 to 16 years: Oral suspension: 2 hours (Blumer 2009).
Adults: Oral solution: 0.7 to 3.7 hours (high-fat, high-calorie meal decreased Cmax ~44%); Tablet: 2 to 4 hours.
Excretion: Feces (83%) and urine (~13%) as unchanged drug.
Clearance: Found to be similar per kg bodyweight in children vs adults receiving a single dose of the suspension (Blumer 2009).
Hepatic function impairment: Patients with mild-to-moderate chronic liver disease have about twice the AUC value.
Older adult: AUC is about 70% higher and the half-life is 35% longer in elderly patients.
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