Candesartan 4 mg Tablet, 30-count — NDC 33342-114-07 (Billing 33342-0114-07)
This is a package of 30 tablets of Candesartan 4 mg Tablet from Macleods Pharmaceuticals Limited, marketed since Dec 2016 and currently FDA-listed; retail pharmacies pay about $0.5686 per tablet (NADAC). It is the main listing for this product, which comes in 4 package sizes.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 037015
- GCN: 73542
- GPI-14 (Medi-Span): 36150020100310
- HICL (First Databank): 016913
- AHFS class code: 24:32.08.00
- RxCUI (RxNorm): 153822
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Angiotensin 2 Receptor Blocker class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It treats high blood pressure in adults and in children 1 to under 17 years. It also treats heart failure in adults, where it helps reduce hospital stays and cardiovascular death....
- Take it by mouth, usually once a day, with or without food. Your prescriber may split the daily amount into two doses. For heart failure, the dose is often raised gradually, so fol...
- The most common ones are dizziness, headache, back pain, and cold-like symptoms such as a sore throat or runny nose. Call your doctor if you feel faint, notice swelling of the face...
- Check with me first. NSAIDs like ibuprofen can weaken candesartan's effect and strain the kidneys. Potassium-based salt substitutes and potassium supplements can push your potassiu...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Candesartan Cilexetil — tap one for details:
Candesartan Cilexetil may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.569 | $17.06 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.7137 | $21.41 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.8574 | $25.72 / 30 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 33342-0114-07 You're viewing this Main listing | 30 TABLET in 1 CONTAINER | $0.5686 / ea | $17.06 | 2016-12-06 | — | Active |
| 33342-0114-10 33342-114-10 | 90 TABLET in 1 CONTAINER | $0.5686 / ea | $51.17 | 2016-12-06 | — | Active |
| 33342-0114-12 33342-114-12 | 10 BLISTER PACK in 1 CARTON / 10 TABLET in 1 BLISTER PACK | — | — | 2016-12-06 | — | Active |
| 33342-0114-51 33342-114-51 | 300 TABLET in 1 CONTAINER | — | — | 2016-12-06 | — | Active |
This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.5686 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 33342-0114-10?
What NDC number is used to bill for this package of Candesartan 4 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| candesartan cilexetil 4 mg 00378-3224-77 | Mylan | 90 tablets | $0.569 | AB | Availability likely | — |
| Candesartan 4 mgthis 33342-0114-07 | Macleods | 30 tablets | $0.569 | AB | Availability likely | — |
| Candesartan Cilexetil 4 mg 62332-0341-30 | Alembic | 30 tablets | $0.569 | AB | Availability likely | — |
| Candesartan Cilexetil 4 mg 46708-0341-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
| Candesartan cilexetil 4 mg 51407-0882-90 | Golden | 90 tablets | — | AB | FDA listed | — |
| Atacand 4 mg 62559-0640-30 | ANI | 30 tablets | — | AB | FDA listed | — |
| Candesartan cilexetil 4 mg 62559-0686-99 | ANI | 50000 tablets | — | AB | FDA listed | — |
| Candesartan cilexetil 4 mg 70771-1204-03 | Zydus | 30 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue candesartan cilexetil tablets as soon as possible. [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )] Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )]. WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. · When pregnancy is detected, discontinue candesartan cilexetil tablets as soon as possible.
( 5.1 , 8.1 ) · Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. ( 5.1 , 8.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Candesartan cilexetil tablets are an angiotensin II receptor blocker (ARB) indicated for: · Treatment of hypertension in adults and children 1 to < 17 years of age, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions ( 1.1 ). · Treatment of heart failure (NYHA class II-IV); candesartan reduces cardiovascular death and heart failure hospitalization ( 1.2 ).
1.1Hypertension Candesartan cilexetil tablets are indicated for the treatment of hypertension in adults and in children 1 to <17 years of age, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal 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 this drug principally belongs.
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 (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Candesartan cilexetil tablets may be used alone or in combination with other antihypertensive agents.
1.2Heart Failure Candesartan cilexetil tablets are indicated for the treatment of heart failure (NYHA class II-IV) in adults with left ventricular systolic dysfunction (ejection fraction ≤ 40%) to reduce cardiovascular death and to reduce heart failure hospitalizations [see Clinical Studies ( 14.2 )] . Candesartan cilexetil tablets also has an added effect on these outcomes when used with an ACE inhibitor [see Drug Interactions ( 7.4 )] .
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Starting Dose Target Dose Adult Hypertension ( 2.1 ) 16 mg tablet once daily 8 - 32 mg tablet total daily dose Pediatric Hypertension (1 to < 6 years) ( 2.2 ) 0.20 mg/kg oral suspension once daily 0.05 - 0.4 mg/kg oral suspension once daily or consider divided dose Pediatric Hypertension (6 to < 17 years) ( 2.2 ) < 50 kg 4 – 8 mg tablet once daily > 50 kg 8 – 16 mg tablet once daily < 50 kg 4 – 16 mg tablet once daily or consider divided dose > 50 kg 4 – 32 mg tablet once daily or consider divided dose Adult Heart Failure ( 2.3 ) 4 mg tablet once daily 32 mg tablet once daily 1 1 The target dose is 32 mg once daily, which is achieved by doubling the dose at approximately 2-week intervals, as tolerated by patient.
2.1Adult Hypertension Dosage must be individualized. Blood pressure response is dose related over the range of 2 to 32 mg. The usual recommended starting dose of candesartan cilexetil tablets are 16 mg once daily when it is used as monotherapy in patients who are not volume depleted.
Candesartan cilexetil tablets can be administered once or twice daily with total daily doses ranging from 8 mg to 32 mg. Larger doses do not appear to have a greater effect, and there is relatively little experience with such doses. Most of the antihypertensive effect is present within 2 weeks, and maximal blood pressure reduction is generally obtained within 4 to 6 weeks of treatment with candesartan cilexetil tablets.
Use in Hepatic Impairment: Initiate with 8 mg candesartan cilexetil tablets in patients with moderate hepatic insufficiency. Dosing recommendations cannot be provided for patients with severe hepatic insufficiency [see Clinical Pharmacology ( 12.3 )] Candesartan cilexetil tablets may be administered with or without food. If blood pressure is not controlled by candesartan cilexetil tablets alone, a diuretic may be added.
Candesartan cilexetil tablets may be administered with other antihypertensive agents.
2.2Pediatric Hypertension 1 to < 17 Years of Age Candesartan cilexetil tablets may be administered once daily or divided into two equal doses. Adjust the dosage according to blood pressure response. For patients with possible depletion of intravascular volume (e.g., patients treated with diuretics, particularly those with impaired renal function), initiate candesartan cilexetil tablets under close medical supervision and consider administration of a lower dose [see Warnings and Precautions ( 5.3 )].
Children 1 to < 6 years of age: The dose range is 0.05 to 0.4 mg/kg per day. The recommended starting dose is 0.20 mg/kg (oral suspension). Children 6 to < 17 years of age: For those less than 50 kg, the dose range is 2 to 16 mg per day.
The recommended starting dose is 4 to 8 mg. For those greater than 50 kg, the dose range is 4 to 32 mg per day. The recommended starting dose is 8 to 16 mg.
Doses above 0.4 mg/kg (1 to < 6 year olds) or 32 mg (6 to < 17 year olds) have not been studied in pediatric patients [see Clinical Studies ( 14.1 )]. An antihypertensive effect is usually present within 2 weeks, with full effect generally obtained within 4 weeks of treatment with candesartan cilexetil tablets Children < 1 year of age must not receive candesartan cilexetil tablets for hypertension. All pediatric patients with a glomerular filtration rate less than 30 mL/min/1.73m 2 should not receive candesartan cilexetil tablets since candesartan cilexetil tablets has not been studied in this population [see Use in Specific Populations ( 8.4 )].
For children who cannot swallow tablets, an oral suspension may be substituted as described below: Preparation of Oral Suspension: Candesartan cilexetil oral suspension can be prepared in concentrations within the range of 0.1 to 2.0 mg/mL. Typically, a concentration of 1 mg/mL will be suitable for the prescribed dose. Any strength of candesartan cilexetil tablets can be used in the preparation of the suspension.
Follow the steps below for preparation of the suspension… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 4 mg are white to off-white, circular, biconvex, uncoated tablets, debossed with “ML 52” on one side and breakline on other side. 8 mg are light pink, circular, biconvex, uncoated tablets, debossed with “ML 53” on one side and breakline on other side. 16 mg are pink, circular, biconvex, uncoated tablets, debossed with “ML 54” on one side and breakline on other side.
32 mg are pink, circular, biconvex, uncoated tablets, debossed with “ML 55” on one side and breakline on other side. Tablets 4 mg, 8 mg, 16 mg, 32 mg ( 3 ).
⛔ Contraindications ▾
4 CONTRAINDICATIONS Candesartan cilexetil tablets are contraindicated in patients who are hypersensitive to candesartan. Do not co-administer aliskiren with candesartan cilexetil tablets in patients with diabetes [see Drug Interactions (7.4)]. Known hypersensitivity to product components ( 4 ). Do not co-administer aliskiren with candesartan cilexetil in patients with diabetes ( 4 ).
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Observe for signs and symptoms of hypotension ( 5.3 ). • Monitor renal function ( 5.4 ) and potassium levels ( 5.5 ).
5.1Fetal Toxicity Candesartan cilexetil tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.
Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure and death. When pregnancy is detected, discontinue candesartan cilexetil as soon as possible [see Use in Specific Populations ( 8.1 )].
5.2Morbidity in Infants Children < 1 year of age must not receive candesartan cilexetil for hypertension. Drugs that act directly on the renin-angiotensin system (RAS) can have effects on the development of immature kidneys.
5.3Hypotension Candesartan cilexetil can cause symptomatic hypotension. Symptomatic hypotension is most likely to occur in patients who have been volume and/or salt depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Patients with symptomatic hypotension may require temporarily reducing the dose of candesartan cilexetil, diuretic or both, and volume repletion.
Volume and/or salt depletion should be corrected before initiating therapy with candesartan cilexetil. In the CHARM program (heart failure patients), hypotension was reported in 18.8% of patients on candesartan cilexetil versus 9.8% of patients on placebo. The incidence of hypotension leading to drug discontinuation in candesartan cilexetil-treated patients was 4.1% compared with 2.0% in placebo-treated patients.
In the CHARM-Added program, where candesartan or placebo was given in addition to ACE inhibitors, hypotension was reported in 22.6% of patients treated with candesartan cilexetil versus 13.8% treated with placebo [see Drug Interactions ( 7.3 )] .Monitoring of blood pressure is recommended during dose escalation and periodically thereafter. Major Surgery/Anesthesia Hypotension may occur during major surgery and anesthesia in patients treated with angiotensin II receptor antagonists, including candesartan cilexetil, due to blockade of the renin-angiotensin system.
Very rarely, hypotension may be severe such that it may warrant the use of intravenous fluids and/or vasopressors.
5.4Impaired Renal Function Monitor renal function periodically in patients treated with candesartan cilexetil. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend, in part, on the activity of the renin-angiotensin system (e.g., patient with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion) may be at particular risk of developing oliguria, progressive azotemia or acute renal failure when treated with candesartan cilexetil.
Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on candesartan cilexetil.In the CHARM program (heart failure patients), the incidence of abnormal renal function (e.g., creatinine increase) was 12.5% in patients treated with candesartan cilexetil versus 6.3% in patients treated with placebo. The incidence of abnormal renal function (e.g., creatinine increase) leading to drug discontinuation in candesartan cilexetil -treated patients was 6.3% compared with 2.9% in placebo-treated patients.
In the CHARM-Added program, where candesartan or placebo was given in addition to ACE inhibitors, the incidence of abnormal renal function (e.g., creatinine increase) was 15% in patients treated with candesartan cilexetil versus 9% in patients treated with placebo [see Drug Interactions ( 7.3 )].
5.5Hyperkalemia Drugs that inhi… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS • Most common adverse reactions which caused adult patients to discontinue therapy for: ○ Hypertension were headache (0.6%) and dizziness (0.3%) ( 6.1 ). ○ Heart Failure were hypotension (4.1%) ( 5.3 ), abnormal renal function (6.3%) ( 5.4 ), and hyperkalemia (2.4%) ( 5.5 ). To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 Candesartan cilexetil has been evaluated for safety in more than 3600 patients/subjects, including more than 3200 patients treated for hypertension. About 600 of these patients were studied for at least 6 months and about 200 for at least 1 year.
In general, treatment with candesartan cilexetil was well tolerated. The overall incidence of adverse events reported with candesartan cilexetil was similar to placebo. The rate of withdrawals due to adverse events in all trials in patients (7510 total) was 3.3% (i.e., 108 of 3260) of patients treated with candesartan cilexetil as monotherapy and 3.5% (i.e., 39 of 1106) of patients treated with placebo.
In placebo-controlled trials, discontinuation of therapy due to clinical adverse events occurred in 2.4% (i.e., 57 of 2350) of patients treated with candesartan cilexetil and 3.4% (i.e., 35 of 1027) of patients treated with placebo. The most common reasons for discontinuation of therapy with candesartan cilexetil were headache (0.6%) and dizziness (0.3%). The adverse events that occurred in placebo-controlled clinical trials in at least 1% of patients treated with candesartan cilexetil and at a higher incidence in candesartan cilexetil (n = 2350) than placebo (n = 1027) patients included back pain (3% vs.
2%), dizziness (4% vs. 3%), upper respiratory tract infection (6% vs. 4%), pharyngitis (2% vs.
1%), and rhinitis (2% vs. 1%). Pediatric Hypertension Among children in clinical studies, 1 in 93 children age 1 to < 6 and 3 in 240 age 6 to < 17 experienced worsening renal disease.
The association between candesartan and exacerbation of the underlying condition could not be excluded. Heart Failure The adverse event profile of candesartan cilexetil in adult heart failure patients was consistent with the pharmacology of the drug and the health status of the patients. In the CHARM program, comparing candesartan cilexetil in total daily doses up to 32 mg once daily (n=3803) with placebo (n=3796), 21.0% of patients discontinued candesartan cilexetil for adverse events vs.
16.1% of placebo patients.
6.2Postmarketing Experience The following adverse reactions were identified during post-approval use of candesartan cilexetil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following have been very rarely reported in post-marketing experience: Digestive: Abnormal hepatic function and hepatitis.
Hematologic: Neutropenia, leukopenia, and agranulocytosis. Immunologic: Angioedema. Metabolic and Nutritional Disorders: Hyperkalemia, hyponatremia.
Respiratory System Disorders: Cough. Skin and Appendages Disorders : Pruritus, rash and urticaria.Rare reports of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Lithium: Increases in serum lithium concentrations and toxicity ( 7 ). • NSAIDs use may lead to increased risk of renal impairment and loss of antihypertensive effect ( 7 ) • Combined inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7 )
7.1Agents Increasing Serum Potassium Co-administration of candesartan cilexetil with potassium sparing diuretics, potassium supplements, potassium-containing salt substitutes or other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.
7.2Lithium Increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists, including candesartan cilexetil. Monitor serum lithium levels.
7.3Non-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, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including candesartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving candesartan and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including candesartan may be attenuated by NSAIDs including selective COX-2 inhibitors.
7.4Combination 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. Triple combination of candesartan cilexetil with an ACE-inhibitor and a mineralocorticoid receptor antagonist is generally not recommended. Closely monitor blood pressure, renal function and electrolytes in patients on candesartan cilexetil and other agents that affect the RAS.
Do not co-administer aliskiren with candesartan cilexetil in patients with diabetes. Avoid use of aliskiren with candesartan cilexetil in patients with renal impairment (GFR <60 mL/min) [see Contraindications ( 4 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS · Nursing Mothers : Either nursing or drug should be discontinued ( 8.2 ). · Pediatrics : Children < 1 year of age must not receive candesartan cilexetil for hypertension ( 5.2 ). Inhibitors of the renin-angiotensin system can cause renal abnormalities in neonatal animals ( 12.3 ).
8.1Pregnancy Risk Summary Candesartan cilexetil can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
When pregnancy is detected, discontinue candesartan cilexetil as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Pregnant women with chronic heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester.
Heart failure may worsen with pregnancy and may lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of pregnancy.
Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe infants with histories of in utero exposure to candesartan cilexetil for hypotension, oliguria, hyperkalemia or other symptoms of renal impairment [see Use in Specific Populations ( 8.4 )].
In neonates with a history of in utero exposure to candesartan cilexetil, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Animal Data Oral doses ≥10 mg of candesartan cilexetil/kg/day administered to pregnant rats during late gestation and continued through lactation were associated with reduced survival and an increased incidence of hydronephrosis in the offspring.
The 10-mg/kg/day dose in rats is approximately 2.8 times the maximum recommended daily human dose (MRHD) of 32 mg on a mg/m2 basis (comparison assumes human body weight of 50 kg). Candesartan cilexetil is toxic to rabbits. When given to p… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Candesartan cilexetil can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
When pregnancy is detected, discontinue candesartan cilexetil as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Pregnant women with chronic heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester.
Heart failure may worsen with pregnancy and may lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of pregnancy.
Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe infants with histories of in utero exposure to candesartan cilexetil for hypotension, oliguria, hyperkalemia or other symptoms of renal impairment [see Use in Specific Populations ( 8.4 )].
In neonates with a history of in utero exposure to candesartan cilexetil, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Animal Data Oral doses ≥10 mg of candesartan cilexetil/kg/day administered to pregnant rats during late gestation and continued through lactation were associated with reduced survival and an increased incidence of hydronephrosis in the offspring.
The 10-mg/kg/day dose in rats is approximately 2.8 times the maximum recommended daily human dose (MRHD) of 32 mg on a mg/m2 basis (comparison assumes human body weight of 50 kg). Candesartan cilexetil is toxic to rabbits. When given to pregnant rabbits at an oral dose of 3 mg/kg/day (approximately 1.7 times the MRHD on a mg/m 2 basis), candesartan cilexetil caused maternal toxicity (decreased body weight and death) but, in surviving dams, had no adverse effects on fetal survival, fetal weight, or external, visceral, or skeletal development.
No… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use The antihypertensive effects of candesartan cilexetil were evaluated in hypertensive children 1 to < 17 years of age in randomized, double-blind clinical studies [see Clinical Studies ( 14.1 )]. The pharmacokinetics of candesartan cilexetil have been evaluated in pediatric patients 1 to < 17 years of age [see Clinical Pharmacology ( 12.3 )]. Children < 1 year of age must not receive candesartan cilexetil for hypertension [see see Warnings and Precautions ( 5.2 )]
🆘 Overdosage ▾
10 OVERDOSAGE No lethality was observed in acute toxicity studies in mice, rats, and dogs given single oral doses of up to 2000 mg/kg of candesartan cilexetil. In mice given single oral doses of the primary metabolite, candesartan, the minimum lethal dose was greater than 1000 mg/kg but less than 2000 mg/kg. The most likely manifestation of overdosage with candesartan cilexetil would be hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.
If symptomatic hypotension should occur, supportive treatment should be instituted. Candesartan cannot be removed by hemodialysis. Treatment: To obtain up-to-date information about the treatment of overdose, consult your Regional Poison Control Center.
Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and altered pharmacokinetics in your patient
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland.
Its action is, therefore, independent of the pathways for angiotensin II synthesis. There is also an AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity (>10,000-fold) for the AT 1 receptor than for the AT 2 receptor.Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension.
ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known.
Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of candesartan on blood pressure.
12.2Pharmacodynamics Candesartan inhibits the pressor effects of angiotensin II infusion in a dose-dependent manner. After 1 week of once daily dosing with 8 mg of candesartan cilexetil, the pressor effect was inhibited by approximately 90% at peak with approximately 50% inhibition persisting for 24 hours. Plasma concentrations of angiotensin I and angiotensin II, and plasma renin activity (PRA), increased in a dose-dependent manner after single and repeated administration of candesartan cilexetil to healthy subjects, hypertensive, and heart failure patients.
ACE activity was not altered in healthy subjects after repeated candesartan cilexetil administration. The once-daily administration of up to 16 mg of candesartan cilexetil to healthy subjects did not influence plasma aldosterone concentrations, but a decrease in the plasma concentration of aldosterone was observed when 32 mg of candesartan cilexetil was administered to hypertensive patients. In spite of the effect of candesartan cilexetil on aldosterone secretion, very little effect on serum potassium was observed.
Hypertension Adults In multiple-dose studies with hypertensive patients, there were no clinically significant changes in metabolic function, including serum levels of total cholesterol, triglycerides, glucose, or uric acid. In a 12-week study of 161 patients with non-insulin-dependent (type 2) diabetes mellitus and hypertension, there was no change in the level of HbA 1c . Heart Failure In heart failure patients, candesartan ≥ 8 mg resulted in decreases in systemic vascular resistance and pulmonary capillary wedge pressure.
12.3 Pharmacokinetics Distribution The volume of distribution of candesartan is
0.13L/kg. Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells. The protein binding is constant at candesartan plasma concentrations well above the range achieved with recommended doses.
In rats, it has been demonstrated that candesartan crosses the blood-brain barrier poorly, if at all. It has also been demonstrated in rats that candesartan passes across the placental barrier and is distributed in the fetus. Metabolism and Excretion Because candesartan is not signif… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland.
Its action is, therefore, independent of the pathways for angiotensin II synthesis. There is also an AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity (>10,000-fold) for the AT 1 receptor than for the AT 2 receptor.Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension.
ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known.
Candesartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of candesartan on blood pressure.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Candesartan cilexetil tablets, USP 4 mg, are white to off-white, circular, biconvex, uncoated tablets, debossed with "ML 52" on one side and breakline on other side. They are supplied as follows: NDC 33342-114-07 unit of use bottles of 30 NDC 33342-114-10 unit of use bottles of 90 NDC 33342-114-51 unit of use bottles of 300 NDC 33342-114-12 unit dose blister packages of 100. Candesartan cilexetil tablets, USP 8 mg, are light pink, circular, biconvex, uncoated tablets, debossed with "ML 53" on one side and breakline on other side.
They are supplied as follows: NDC 33342-115-07 unit of use bottles of 30 NDC 33342-115-10 unit of use bottles of 90 NDC-33342-115-51 unit of use bottles of 300 NDC 33342-115-12 unit dose blister packages of 100. Candesartan cilexetil tablets, USP 16 mg, are pink, circular, biconvex, uncoated tablets, debossed with "ML 54" on one side and breakline on other side.They are supplied as follows: NDC 33342-116-07 unit of use bottles of 30 NDC 33342-116-10 unit of use bottles of 90 NDC 33342-116-51 unit of use bottles of 300 NDC 33342-116-12 unit dose blister packages of 100.
Candesartan cilexetil tablets, USP 32 mg, are pink, circular, biconvex, uncoated tablets, debossed with "ML 55" on one side and breakline on other side. They are supplied as follows: NDC 33342-117-07 unit of use bottles of 30 NDC 33342-117-10 unit of use bottles of 90 NDC 33342-117-51 unit of use bottles of 300 NDC 33342-117-12 unit dose blister packages of 100. Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Keep container tightly closed.
📋 Description ▾
11 DESCRIPTION Candesartan cilexetil, USP a prodrug, is hydrolyzed to candesartan during absorption from the gastrointestinal tract. Candesartan is a selective AT 1 subtype angiotensin II receptor antagonist. Candesartan cilexetil, USP a nonpeptide, is chemically described as (±)-1-Hydroxyethyl 2-ethoxy-1-[ p -( o -1 H- tetrazol-5-ylphenyl)benzyl]-7-benzimidazolecarboxylate, cyclohexyl carbonate (ester).
Its molecular formula is C 33 H 34 N 6 O 6 , and its structural formula is Candesartan cilexetil, USP is a white to off-white powder with a molecular weight of 610.67. It is practically insoluble in water and sparingly soluble in methanol. Candesartan cilexetil USP is a racemic mixture containing one chiral center at the cyclohexyloxycarbonyloxy ethyl ester group.
Following oral administration, candesartan cilexetil undergoes hydrolysis at the ester link to form the active drug, candesartan, which is achiral. Candesartan cilexetil, USP is available for oral use as tablets containing either 4 mg, 8 mg, 16 mg, or 32 mg of candesartan cilexetil and the following inactive ingredients: hydroxypropyl cellulose, lactose monohydrate, corn starch, glycerin, carboxymethylcellulose calcium, and magnesium stearate. Ferric oxide is added to the 8-mg, 16-mg, and 32-mg tablets as a colorant.
1
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patient to read FDA-approved patient labeling (Patient Information). Pregnancy Advise female patients of childbearing age about the consequences of exposure to candesartan cilexetil during pregnancy. Discuss treatment options with women planning to become pregnant.
Tell patients to report pregnancies to their physicians as soon as possible. Manufactured by: Macleods Pharmaceuticals Limited, INDIA Manufactured for: Macleods Pharma USA, Inc. Princeton, NJ 08540 All brand names listed are the registered trademarks of their respective owners.
All brand names listed are the registered trademarks of their respective owners. Revised: 12/2022
🧬 Pharmacokinetics ▾
12.3 Pharmacokinetics Distribution The volume of distribution of candesartan is
0.13L/kg. Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells. The protein binding is constant at candesartan plasma concentrations well above the range achieved with recommended doses.
In rats, it has been demonstrated that candesartan crosses the blood-brain barrier poorly, if at all. It has also been demonstrated in rats that candesartan passes across the placental barrier and is distributed in the fetus. Metabolism and Excretion Because candesartan is not significantly metabolized by the cytochrome P450 system and at therapeutic concentrations has no effects on P450 enzymes, interactions with drugs that inhibit or are metabolized by those enzymes would not be expected.
Total plasma clearance of candesartan is 0.37 mL/min/kg, with a renal clearance of 0.19 mL/min/kg. When candesartan is administered orally, about 26% of the dose is excreted unchanged in urine. Following an oral dose of 14 C-labeled candesartan cilexetil, approximately 33% of radioactivity is recovered in urine and approximately 67% in feces.
Following an intravenous dose of 14 C-labeled candesartan, approximately 59% of radioactivity is recovered in urine and approximately 36% in feces. Biliary excretion contributes to the elimination of candesartan. Adults Candesartan cilexetil is rapidly and completely bioactivated by ester hydrolysis during absorption from the gastrointestinal tract to candesartan, a selective AT 1 subtype angiotensin II receptor antagonist.
Candesartan is mainly excreted unchanged in urine and feces (via bile). It undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite. The elimination half-life of candesartan is approximately 9 hours.
After single and repeated administration, the pharmacokinetics of candesartan are linear for oral doses up to 32 mg of candesartan cilexetil. Candesartan and its inactive metabolite do not accumulate in serum upon repeated once-daily dosing. Following administration of candesartan cilexetil, the absolute bioavailability of candesartan was estimated to be 15%.
After tablet ingestion, the peak serum concentration (C max ) is reached after 3 to 4 hours. Food with a high fat content does not affect the bioavailability of candesartan after candesartan cilexetil administration. Pediatrics In children 1 to 17 years of age, plasma levels are greater than 10-fold higher at peak (approximately 4 hours) than 24 hours after a single dose.
Children 1 to < 6 years of age, given 0.2 mg/kg had exposure similar to adults given 8 mg. Children > 6 years of age had exposure similar to adults given the same dose. The pharmacokinetics (C max and AUC) were not modified by age, sex or body weight.
Candesartan cilexetil pharmacokinetics have not been investigated in pediatric patients less than 1 year of age. From the dose-ranging studies of candesartan cilexetil, there was a dose related increase in plasma candesartan concentrations. The renin-angiotensin system (RAS) plays a critical role in kidney development.
RAS blockade has been shown to lead to abnormal kidney development in very young mice. Children < 1 year of age must not receive candesartan cilexetil. Administering drugs that act directly on the renin-angiotensin system (RAS) can alter normal renal development.
Geriatric and Sex The pharmacokinetics of candesartan have been studied in the elderly (≥ 65 years) and in both sexes. The plasma concentration of candesartan was higher in the elderly (C max was approximately 50% higher, and AUC was approximately 80% higher) compared to younger subjects administered the same dose. The pharmacokinetics of candesartan were linear in the elderly, and candesartan and its inactive metabolite did not accumulate in the serum of these subjects upon repeated, once-daily administration.
No initial dosage adjustment is necessary [see Dosage and Administration ( 2.1 )]. There is no difference in t… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Candesartan inhibits the pressor effects of angiotensin II infusion in a dose-dependent manner. After 1 week of once daily dosing with 8 mg of candesartan cilexetil, the pressor effect was inhibited by approximately 90% at peak with approximately 50% inhibition persisting for 24 hours. Plasma concentrations of angiotensin I and angiotensin II, and plasma renin activity (PRA), increased in a dose-dependent manner after single and repeated administration of candesartan cilexetil to healthy subjects, hypertensive, and heart failure patients.
ACE activity was not altered in healthy subjects after repeated candesartan cilexetil administration. The once-daily administration of up to 16 mg of candesartan cilexetil to healthy subjects did not influence plasma aldosterone concentrations, but a decrease in the plasma concentration of aldosterone was observed when 32 mg of candesartan cilexetil was administered to hypertensive patients. In spite of the effect of candesartan cilexetil on aldosterone secretion, very little effect on serum potassium was observed.
Hypertension Adults In multiple-dose studies with hypertensive patients, there were no clinically significant changes in metabolic function, including serum levels of total cholesterol, triglycerides, glucose, or uric acid. In a 12-week study of 161 patients with non-insulin-dependent (type 2) diabetes mellitus and hypertension, there was no change in the level of HbA 1c . Heart Failure In heart failure patients, candesartan ≥ 8 mg resulted in decreases in systemic vascular resistance and pulmonary capillary wedge pressure.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Hypertension Adult The antihypertensive effects of candesartan cilexetil were examined in 14 placebo-controlled trials of 4-to 12-weeks duration, primarily at daily doses of 2 to 32 mg per day in patients with baseline diastolic blood pressures of 95 to 114 mm Hg. Most of the trials were of candesartan cilexetil as a single agent, but it was also studied as add-on to hydrochlorothiazide and amlodipine. These studies included a total of 2350 patients randomized to one of several doses of candesartan cilexetil and 1027 to placebo.
Except for a study in diabetics, all studies showed significant effects, generally dose related, of 2 to 32 mg on trough (24 hour) systolic and diastolic pressures compared to placebo, with doses of 8 to 32 mg giving effects of about 8-12/4-8 mm Hg. There were no exaggerated first-dose effects in these patients. Most of the antihypertensive effect was seen within 2 weeks of initial dosing and the full effect in 4 weeks.
With once-daily dosing, blood pressure effect was maintained over 24 hours, with trough to peak ratios of blood pressure effect generally over 80%. Candesartan cilexetil had an additional blood pressure lowering effect when added to hydrochlorothiazide. The antihypertensive effects of candesartan cilexetil and losartan potassium at their highest recommended doses administered once-daily were compared in two randomized, double-blind trials.
In a total of 1268 patients with mild to moderate hypertension who were not receiving other antihypertensive therapy, candesartan cilexetil 32 mg lowered systolic and diastolic blood pressure by 2 to 3 mm Hg on average more than losartan potassium 100 mg, when measured at the time of either peak or trough effect. The antihypertensive effects of twice daily dosing of either candesartan cilexetil or losartan potassium were not studied. The antihypertensive effect was similar in men and women and in patients older and younger than 65.
Candesartan was effective in reducing blood pressure regardless of race, although the effect was somewhat less in blacks (usually a low-renin population). This has been generally true for angiotensin II antagonists and ACE inhibitors. In long-term studies of up to 1 year, the antihypertensive effectiveness of candesartan cilexetil was maintained, and there was no rebound after abrupt withdrawal.
There were no changes in the heart rate of patients treated with candesartan cilexetil in controlled trials. Pediatric The antihypertensive effects of candesartan cilexetil were evaluated in hypertensive children 1 to < 6 years old and 6 to < 17 years of age in two randomized, double-blind multicenter, 4-week dose ranging studies. There were 93 patients 1 to < 6 years of age, 74% of whom had renal disease, that were randomized to receive an oral dose of candesartan cilexetil suspension 0.05, 0.20 or 0.40 mg/kg once daily.
The primary method of analysis was slope of the change in systolic blood pressure (SBP) as a function of dose. Since there was no placebo group, the change from baseline likely overestimates the true magnitude of blood pressure effect. Nevertheless, SBP and diastolic blood pressure (DBP) decreased 6.0/5.2 to 12.0/11.1 mmHg from baseline across the three doses of candesartan.
In children 6 to < 17 years, 240 patients were randomized to receive either placebo or low, medium, or high doses of candesartan cilexetil in a ratio of 1: 2: 2: 2. For children who weighed < 50 kg the doses of candesartan cilexetil were 2, 8, or 16 mg once daily. For those > 50 kg the candesartan cilexetil doses were 4, 16 or 32 mg once daily.
Those enrolled were 47% Black and 29% were female; mean age +/-SD was 12.9 +/-2.6 years. The placebo subtracted effect at trough for sitting systolic blood pressure/sitting diastolic blood pressure for the different doses were from 4.9/3.0 to 7.5/6.2 mmHg. In children 6 to < 17 years there was a trend for a lesser blood pressure effect for Blacks compared to other patients.
There… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility There was no evidence of carcinogenicity when candesartan cilexetil was orally administered to mice and rats for up to 104 weeks at doses up to 100 and 1000 mg/kg/day, respectively. Rats received the drug by gavage, whereas mice received the drug by dietary administration. These (maximally-tolerated) doses of candesartan cilexetil provided systemic exposures to candesartan (AUCs) that were, in mice, approximately 7 times and, in rats, more than 70 times the exposure in man at the maximum recommended daily human dose (32 mg).
Candesartan and its O-deethyl metabolite tested positive for genotoxicity in the in vitro Chinese hamster lung (CHL) chromosomal aberration assay. Neither compound tested positive in the Ames microbial mutagenesis assay or the in vitro mouse lymphoma cell assay. Candesartan (but not its O-deethyl metabolite) was also evaluated in vivo in the mouse micronucleus test and in vitro in the Chinese hamster ovary (CHO) gene mutation assay, in both cases with negative results.
Candesartan cilexetil was evaluated in the Ames test, the in vitro mouse lymphoma cell and rat hepatocyte unscheduled DNA synthesis assays and the in vivo mouse micronucleus test, in each case with negative results. Candesartan cilexetil was not evaluated in the CHL chromosomal aberration or CHO gene mutation assay. Fertility and reproductive performance were not affected in studies with male and female rats given oral doses of up to 300 mg/kg/day (83 times the maximum daily human dose of 32 mg on a body surface area basis).
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility There was no evidence of carcinogenicity when candesartan cilexetil was orally administered to mice and rats for up to 104 weeks at doses up to 100 and 1000 mg/kg/day, respectively. Rats received the drug by gavage, whereas mice received the drug by dietary administration. These (maximally-tolerated) doses of candesartan cilexetil provided systemic exposures to candesartan (AUCs) that were, in mice, approximately 7 times and, in rats, more than 70 times the exposure in man at the maximum recommended daily human dose (32 mg).
Candesartan and its O-deethyl metabolite tested positive for genotoxicity in the in vitro Chinese hamster lung (CHL) chromosomal aberration assay. Neither compound tested positive in the Ames microbial mutagenesis assay or the in vitro mouse lymphoma cell assay. Candesartan (but not its O-deethyl metabolite) was also evaluated in vivo in the mouse micronucleus test and in vitro in the Chinese hamster ovary (CHO) gene mutation assay, in both cases with negative results.
Candesartan cilexetil was evaluated in the Ames test, the in vitro mouse lymphoma cell and rat hepatocyte unscheduled DNA synthesis assays and the in vivo mouse micronucleus test, in each case with negative results. Candesartan cilexetil was not evaluated in the CHL chromosomal aberration or CHO gene mutation assay. Fertility and reproductive performance were not affected in studies with male and female rats given oral doses of up to 300 mg/kg/day (83 times the maximum daily human dose of 32 mg on a body surface area basis).
📄 Patient Package Insert ▾
PATIENT INFORMATION Candesartan Cilexetil (kan" de sar' tan sye lex'e til) Tablets Read the Patient Information that comes with candesartan cilexetil tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.
If you have any questions about candesartan cilexetil tablets, ask your doctor or pharmacist. What is the most important information I should know about candesartan cilexetil tablets? Candesartan cilexetil tablets can cause harm or death to an unborn baby.
Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant. If you get pregnant while taking candesartan cilexetil tablets, tell your doctor right away. What are candesartan cilexetil tablets?
Candesartan cilexetil tablets are a prescription medicine called an angiotensin receptor blocker (ARB). Candesartan cilexetil tablets are used to: · treat high blood pressure in adults and children, 1 to 17 years of age · treat certain types of heart failure in adults, to reduce death and hospitalization for heart damage and heart failure Heart failure is a condition where the heart does not pump blood as well as it should. Candesartan cilexetil tablets must not be used in children less than 1 year of age for high blood pressure.
Who should not take candesartan cilexetil tablets? Do not take candesartan cilexetil tablets if you: · are allergic to any of the ingredients in candesartan cilexetil tablets. See the end of this leaflet for a complete list of ingredients in candesartan cilexetil tablets. · are diabetic and taking aliskiren.
What should I tell my doctor before taking candesartan cilexetil tablets? Before you take candesartan cilexetil tablets, tell your doctor if you: · have heart problems · have liver problems · have kidney problems · currently have vomiting or diarrhea · are scheduled for surgery or anesthesia. Low blood pressure can happen in people who take candesartan cilexetil tablets and have major surgery and anesthesia. · have any other medical conditions · are pregnant or planning to become pregnant .
See “What is the most important information I should know about candesartan cilexetil tablets?” are breast-feeding or plan to breast-feed . It is not known if candesartan cilexetil passes into your breast milk. You and your doctor should decide if you will take candesartan cilexetil tablets or breast-feed.
You should not do both. Tell your doctor about all the medicines you take , including prescription and non-prescription medicines, vitamins and herbal supplements. Candesartan cilexetil tablets and other medicines may affect each other causing serious side effects.
Candesartan cilexetil tablets may affect the way other medicines work, and other medicines may affect how candesartan cilexetil tablets works. Especially tell your doctor if you take: · lithium carbonate (Lithobid) or lithium citrate, medicines used in some types of depression · other medicines for high blood pressure, especially water pills (diuretics) · potassium supplements · salt substitutes non-steroidal anti-inflammatory drugs (NSAIDs) Know the medicines you take. Keep a list of your medications with you to show your doctor and pharmacist when a new medication is prescribed.
Talk to your doctor or pharmacist before you start taking any new medicine. Your doctor or pharmacist will know what medicines are safe to take together. How should I take candesartan cilexetil tablets ? · Take candesartan cilexetil tablets exactly as prescribed by your doctor. · Do not change your dose or stop candesartan cilexetil tablets without talking to your doctor, even if you are feeling well. · If your child cannot swallow tablets, or if tablets are not available in the prescribed strength, your pharmacist will prepare candesartan cilexetil tablets as a liquid suspension for your child.
If your child switches between taking the tab… [Excerpted — this section continues on DailyMed.]
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 33342-114-07 Candesartan Cilexetil Tablets 4 mg Bottle Label Rx only 30 Tablets PRINCIPAL DISPLAY PANEL NDC 33342-114-10 Candesartan Cilexetil Tablets 4 mg Bottle Label Rx only 90 Tablets NDC 33342-114-12 Candesartan Cilexetil Tablet 4 mg carton label Rx only Unit dose package of 100 Tablets NDC 33342-115-07 Candesartan Cilexetil Tablets 8 mg Bottle Label Rx only 30 Tablets NDC 33342-115-10 Candesartan Cilexetil Tablets 8 mg Bottle Label Rx only 90 Tablets NDC 33342-115-12 Candesartan Cilexetil Tablets 8 mg Carton Label Rx only Unit dose package of 100 Tablets NDC 33342-116-07 Candesartan Cilexetil Tablets 16 mg Bottle Label Rx only 30 Tablet NDC 33342-116-10 Candesartan Cilexetil Tablets 16 mg Bottle Label Rx only 90 Tablets NDC 33342-116-12 Candesartan Cilexetil Tablets 16 mg carton Rx only Unit dose package of 100 Tablets NDC 33342-117-07 Candesartan Cilexetil Tablets 32 mg Bottle Label Rx only 30 Tablets NDC 33342-117-10 Candesartan Cilexetil Tablets 32 mg Bottle Label Rx only 90 Tablets NDC 33342-117-12 Candesartan Cilexetil Tablets 32 mg Carton Label Rx only Unit dose package of 100 Tablets 505 505 505 505 505 505 505 505 505 505 505 505 505 505 505 505 505 505 505 505