Valsartan Oral
FDA Drug Information • Also known as: Valsartan
- Brand Names
- Valsartan
- Drug Class
- Angiotensin 2 Receptor Blocker [EPC]
- Route
- ORAL
- Dosage Form
- SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue valsartan oral solution as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 ) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue valsartan oral solution as soon as possible. ( 5.1 ) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 )
Description
11 DESCRIPTION Valsartan is a nonpeptide, orally active, and specific angiotensin II receptor blocker acting on the AT 1 receptor subtype. Valsartan is chemically described as N -(1-oxopentyl)- N -[[2′-(1 H -tetrazol-5-yl) [1,1′-biphenyl]-4-yl]methyl]-L-valine. Its empirical formula is C 24 H 29 N 5 O 3 , its molecular weight is 435.5, and its structural formula is: Valsartan is an off white to white powder. It is soluble in methanol, freely soluble in anhydrous ethanol, sparingly soluble in methylene chloride, practically insoluble in water. Valsartan oral solution is formulated at a concentration of 4 mg/mL valsartan, as a clear, colorless solution with grape flavor, free from any visible foreign and particulate matter, free of precipitation and hazy mass. The inactive ingredients are: grape flavor, methylparaben, poloxamer, potassium sorbate, propylene glycol, sodium hydroxide, purified water, trisodium citrate dihydrate, and sucralose. Each 5 mL of Valsartan oral solution contains 18.46 mg of sodium. Valsartan Oral Solution Structure
What Is Valsartan Oral Used For?
1 INDICATIONS AND USAGE Valsartan is an angiotensin II receptor blocker (ARB) indicated for: Hypertension in adults and children six years and older, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions ( 1.1 ) Heart failure (NYHA class II-IV); Valsartan oral solution significantly reduces hospitalization for heart failure in patients who are unable to swallow valsartan tablets ( 1.2 ) Stable left ventricular failure or left ventricular dysfunction following myocardial infarction; Valsartan oral solution reduces cardiovascular mortality in patients who are unable to swallow valsartan tablets ( 1.3 ) 1.1 Hypertension Valsartan is indicated for the treatment of hypertension in adults and children six years and older, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which valsartan principally belongs. There are no controlled trials in hypertensive patients demonstrating risk reduction with valsartan. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive...
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Indication Starting Dose Dose Range Target Maintenance Dose as tolerated by patient Hypertension - adults ( 2.1 ) 40 or 80 mg twice daily 40 -160 mg twice daily --- Hypertension—age 6 to16 years ( 2.2 ) 0.65 mg/kg twice daily (up to 40 mg total) 0.65-1.35 mg/kg twice daily (up to 40 mg-160 mg total) --- He art Failure ( 2.3 ) 40 mg twice daily 40 mg-160 mg twice daily 160 mg twice daily Post-Myocardial Infarction ( 2.4 ) 20 mg twice daily 20 mg - 160 mg twice daily 160 mg twice daily 2.1 General Considerations Valsartan oral solution is not therapeutically equivalent to the tablet formulation of Diovan. The peak concentration of valsartan with valsartan oral solution is higher than with Diovan [see Warnings and Precautions (5.2) , Clinical Pharmacology (12.3) ]. Follow dosing instructions given here. 2.2 Adult Hypertension The recommended starting dose of valsartan oral solution is 40 mg or 80 mg twice daily when used as monotherapy in patients who are not volume-depleted. Patients requiring greater reductions in blood pressure may be started at 80 mg administered twice a day. Valsartan oral solution may be used over a total daily dose range of 80 mg to 320 mg. The antihypertensive effect is substantially present within 2 weeks and maximal reduction is generally attained after 4 weeks. If additional antihypertensive effect is required over the starting dose range, the total daily dose may be increased to a maximum of 320 mg or a diuretic may be added. Addition of a diuretic has a greater effect than dose increases beyond 80 mg. No initial dosage adjustment is required for elderly patients, for patients with mild or moderate renal impairment, or for patients with mild or moderate liver insufficiency. Monitor closely patients with severe hepatic or renal impairment. Valsartan oral solution may be administered with other antihypertensive agents. 2.3 Pediatric Hypertension 6 to 16 Years of Age The recommended starting dose is 0.65 mg/kg twice daily (up to 40 mg total daily dose). The dosage should be adjusted according to blood pressure response. Doses higher than 1.35 mg/kg twice daily (or >160 mg total daily dose) have not been studied in pediatric patients 6 to 16 years old. No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate <30 mL/min/1.73 m 2 [see Use in Specific Populations (8.4) ]. Valsartan oral solution is not recommended for patients under 6 years of age [see Adverse Reactions (6.1) , Use in Specific Populations (8.4) , Clinical Studies (14.1) ]. 2.4 Heart Failure The recommended starting dose of valsartan oral solution is 40 mg twice daily. Titrate to 80 mg and 160 mg twice daily, as tolerated by the patient. Consider reducing the dose of concomitant diuretics. The maximum daily dose administered in clinical trials is 320 mg in divided doses. 2.5 Post-Myocardial Infarction Valsartan oral solution may be initiated as early as 12 hours after a myocardial...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS Hypertension: Most common adverse reactions are headache, dizziness, fatigue and abdominal pain ( 6.1 ) Heart Failure: Most common adverse reactions are dizziness, hypotension, diarrhea, arthralgia, back pain, fatigue and hyperkalemia ( 6.1 ) Post-Myocardial Infarction: Most common adverse reactions which caused patients to discontinue therapy are hypotension, cough and increased blood creatinine ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Advagen Pharma Ltd, at 866-488-0312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Adult Hypertension Valsartan has been evaluated for safety in more than 4,000 patients, including over 400 treated for over 6 months, and more than 160 for over 1 year. Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse reactions with valsartan was similar to placebo. The overall frequency of adverse reactions was neither dose-related nor related to gender, age, race, or regimen. Discontinuation of therapy due to side effects was required in 2.3% of valsartan patients and 2.0% of placebo patients. The most common reasons for discontinuation of therapy with valsartan were headache and dizziness. The adverse reactions that occurred in placebo-controlled clinical trials in at least 1% of patients treated with valsartan and at a higher incidence in valsartan (n=2,316) than placebo (n=888) patients included fatigue (2% vs. 1%) and abdominal pain (2% vs. 1%). Headache, dizziness, upper respiratory infection, cough, diarrhea, rhinitis, sinusitis, nausea, pharyngitis, edema, and arthralgia occurred at a more than 1% rate, but at about the same incidence in placebo and valsartan patients. In trials in which valsartan was compared to an ACE inhibitor with or without placebo, the incidence of dry cough was significantly greater in the ACE-inhibitor group (7.9%) than in the groups who received valsartan (2.6%) or placebo (1.5%). In a 129-patient trial limited to patients who had dry cough when they had previously received ACE inhibitors, the incidences of cough in patients who received valsartan, HCTZ, or lisinopril were 20%, 19%, and 69% respectively (p <0.001). Dose-related orthostatic effects were seen in less than 1% of patients. An increase in the incidence of dizziness was observed in patients treated with valsartan 320 mg (8%) compared to 10 to 160 mg (2% to 4%). Valsartan has been used concomitantly with hydrochlorothiazide without evidence of clinically important adverse interactions. Other adverse reactions that occurred in controlled clinical trials of patients treated with valsartan (>0.2% of valsartan patients) are listed below. It cannot be determined whether these events were causally related to valsartan. Body as a Whole: Allergic reaction and asthenia Cardiovascular: Palpitations Dermatologic: Pruritus and rash Digestive: Constipation, dry mouth, dyspepsia, and flatulence Musculoskeletal: Back pain, muscle cramps, and myalgia Neurologic and Psychiatric: Anxiety, insomnia, paresthesia, and somnolence Respiratory: Dyspnea Special Senses: Vertigo Urogenital: Impotence Other reported events seen less frequently in clinical trials included chest pain, syncope, anorexia, vomiting, and angioedema. Pediatric Hypertension Valsartan has been evaluated for safety in over 400 pediatric patients aged 6 to 17 years and more than 160 pediatric patients aged 6 months to 5 years. No relevant differences were identified between the adverse experience profile for pediatric patients aged 6 to 16 years and that previously reported for adult patients. Headache and hyperkalemia were the...
Drug Interactions
7 DRUG INTERACTIONS Potassium-sparing diuretics, potassium supplements or salt substitutes may lead to increases in serum potassium, and in heart failure patients, increases in serum creatinine ( 7 ) NSAIDs increase risk of renal impairment and loss of antihypertensive effect ( 7 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7 ) Lithium: Increases in serum lithium concentrations and lithium toxicity ( 7 ) 7.1 Agents Increasing Serum Potassium Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium- sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If co- medication is considered necessary, monitor serum potassium. 7.2 Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including valsartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving valsartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including valsartan, may be attenuated by NSAIDs including selective COX-2 inhibitors. 7.3 Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on valsartan oral solution and other agents that affect the RAS. Do not coadminister aliskiren with valsartan oral solution in patients with diabetes. Avoid use of aliskiren with valsartan oral solution in patients with renal impairment (GFR < 60 mL/min). 7.4 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists, including valsartan. Monitor serum lithium levels during concomitant use.
Contraindications
4 CONTRAINDICATIONS Do not use in patients with known hypersensitivity to any component. Do not coadminister aliskiren with valsartan oral solution in patients with diabetes [see Drug Interactions (7) ]. Known hypersensitivity ( 4 ) Patients with diabetes on aliskiren ( 4 )
Overdosage
10 OVERDOSAGE Limited data are available related to overdosage in humans. The most likely manifestations of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed level of consciousness, circulatory collapse and shock have been reported. If symptomatic hypotension should occur, supportive treatment should be instituted. Valsartan is not removed from the plasma by hemodialysis. Valsartan was without grossly observable adverse effects at single oral doses up to 2000 mg/kg in rats and up to 1000 mg/kg in marmosets, except for salivation and diarrhea in the rat and vomiting in the marmoset at the highest dose (60 and 31 times, respectively, the maximum recommended human dose on a mg/m 2 basis). (Calculations assume an oral dose of 320 mg/day and a 60-kg patient.)
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Valsartan Oral Solution containing 4 mg/mL valsartan, USP for oral administration. Each mL contains 4 mg valsartan. It is a clear, colorless solution and is supplied as: White HDPE bottles of 120 mL: NDC 72888-184-48 White HDPE bottles of 473 mL: NDC 72888-184-13 Store at 20 °C-25 °C (68 °F-77 °F); excursions permitted to 15 °C -30 °C (59 °F -86 °F) [see USP Controlled Room Temperature]. Dispense in tight container (USP).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.