Atacand

Name: Atacand

Do I need a prescription for candesartan?

Yes

Side effects

Dizziness or lightheadedness may occur as your body adjusts to the medication. If either of these effects persists or worsens, tell your doctor or pharmacist promptly.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: fainting, unusual change in the amount of urine, symptoms of a high potassium blood level (such as muscle weakness, slow/irregular heartbeat).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Pregnancy & Lactation

Pregnancy Category: D

Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, drugs that act directly on the renin-angiotensin have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death

Lactation: Not known if excreted in breast milk; not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Atacand Drug Class

Atacand is part of the drug class:

  • ANGIOTENSIN II ANTAGONISTS, PLAIN

Atacand Interactions

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Atacand and other medicines may affect each other causing serious side effects. Atacand may affect the way other medicines work, and other medicines may affect how Atacand 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.

 

Inform MD

Before you take Atacand, 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 Atacand and have major surgery and anesthesia.
  • have any other medical conditions
  • are pregnant or planning to become pregnant . See "Drug Precautions".
  • are breastfeeding or plan to breastfeed . It is not known if Atacand passes into your breast milk. You and your doctor should decide if you will take Atacand or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Atacand and other medicines may affect each other 

Atacand Dosage

Take Atacand exactly as prescribed. Follow the directions on your prescription label carefully.

Atacand can be taken once or twice daily with total daily adult doses ranging from 8 mg to 32 mg.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking candesartan?

Drinking alcohol can further lower your blood pressure and may increase certain side effects of candesartan.

Do not use potassium supplements or salt substitutes while you are taking candesartan, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Introduction

Angiotensin II receptor (AT1) antagonist (i.e., angiotensin II receptor blocker, ARB).1 2 9

Interactions for Atacand

Not substantially metabolized by CYP isoenzymes; has no effect on CYP isoenzymes at therapeutic concentrations.1

Specific Drugs

Drug

Interaction

Comment

ACE inhibitors

Increased risk of renal impairment, hyperkalemia, and hypotensiona

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantlya

Aliskiren

Increased risk of renal impairment, hyperkalemia, and hypotensiona 550

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantlya 550

Concomitant use contraindicated in patients with diabetes mellitusa 550

Avoid concomitant use in patients with GFR <60 mL/minutea 550

Angiotensin II receptor antagonists

Increased risk of renal impairment, hyperkalemia, and hypotensiona

Generally avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantlya

Cardiac drugs (e.g., digoxin, nifedipine)

Pharmacologic interactions unlikely1 2 3

Contraceptives, oral

Pharmacokinetic interaction unlikely1 2 3

Glyburide

Pharmacologic interaction unlikely1 2

Lithium

Increased serum lithium concentrations; possible toxicity1

Closely monitor serum lithium concentrations1

Warfarin

Pharmacologic interaction unlikely1 2 3

Uses For Atacand

Candesartan is used alone or together with other medicines to treat high blood pressure (hypertension) in adults and children 1 to 16 years of age. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure can reduce the risk of strokes and heart attacks.

Candesartan is also used to treat heart failure in adults and cut down on the number of hospital visits for heart problems.

Candesartan is an angiotensin II receptor blocker (ARB). It works by blocking the action of a substance in the body that causes the blood vessels to tighten. As a result, candesartan relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

This medicine is available only with your doctor's prescription.

Precautions While Using Atacand

It is very important that your doctor check the progress of you or your child at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using this medicine, tell your doctor right away.

Dizziness, lightheadedness, or fainting may also occur, especially when you get up from a lying or sitting position or if you have been taking a diuretic (water pill). Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert. If you feel dizzy, lie down so you do not faint. Then sit for a few moments before standing to prevent the dizziness from returning.

Check with your doctor right away if you or your child become sick while taking this medicine, especially with severe or continuing nausea, vomiting, or diarrhea. These conditions may cause you to lose too much water or salt and may lead to low blood pressure. You can also lose water by sweating, so drink plenty of water during exercise or in hot weather.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the doctor or dentist in charge that you are taking this medicine.

Ask your doctor before you use medicines, supplements, or salt substitutes that contain potassium.

Black patients may have a smaller response to the blood pressure-lowering effects of candesartan.

Do not take other medicines unless they have been discussed with your doctor. This especially includes prescription or nonprescription (over-the-counter) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, since they may tend to increase your blood pressure.

Contraindications

Atacand is contraindicated in patients who are hypersensitive to candesartan.

Do not co-administer aliskiren with Atacand in patients with diabetes [see Drug Interactions (7.4)].

Warnings and Precautions

Fetal Toxicity

Pregnancy Category D

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 Atacand as soon as possible [see Use in Specific Populations (8.1)].

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 given to pregnant rabbits at an oral dose of 3 mg/kg/day (approximately 1.7 times the MRHD on a mg/m2 basis) 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 maternal toxicity or adverse effects on fetal development were observed when oral doses up to 1000 mg of candesartan cilexetil/kg/day (approximately 138 times the MRHD on a mg/m2 basis) were administered to pregnant mice.

Morbidity in Infants

Children < 1 year of age must not receive Atacand for hypertension. Drugs that act directly on the renin-angiotensin system (RAS) can have effects on the development of immature kidneys.

Hypotension

Atacand 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 Atacand, diuretic or both, and volume repletion. Volume and/or salt depletion should be corrected before initiating therapy with Atacand.

In the CHARM program (heart failure patients), hypotension was reported in 18.8% of patients on Atacand versus 9.8% of patients on placebo. The incidence of hypotension leading to drug discontinuation in Atacand-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 Atacand 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 Atacand, 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.

Impaired Renal Function

Monitor renal function periodically in patients treated with Atacand. 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 Atacand. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Atacand.

In the CHARM program (heart failure patients), the incidence of abnormal renal function (e.g., creatinine increase) was 12.5% in patients treated with Atacand versus 6.3% in patients treated with placebo. The incidence of abnormal renal function (e.g., creatinine increase) leading to drug discontinuation in Atacand-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 Atacand versus 9% in patients treated with placebo [see Drug Interactions (7.3)].

Hyperkalemia

Drugs that inhibit the renin-angiotensin system can cause hyperkalemia.
Concomitant use of Atacand with drugs that increase potassium levels may increase the risk of hyperkalemia [see Drug Interactions (7.1)].

Monitor serum potassium periodically.

In the CHARM program (heart failure patients), the incidence of hyperkalemia was 6.3% in patients treated with Atacand versus 2.1% in patients treated with placebo. The incidence of hyperkalemia leading to drug discontinuation in Atacand-treated patients was 2.4% compared with 0.6% in placebo-treated patients. In the CHARM-Added program where candesartan or placebo was given in addition to ACE inhibitors, the incidence of hyperkalemia was 9.5% in patients treated with Atacand versus 3.5% in patients treated with placebo [see Drug Interactions (7.1)].

Atacand Description

Atacand (candesartan cilexetil), a prodrug, is hydrolyzed to candesartan during absorption from the gastrointestinal tract. Candesartan is a selective AT1 subtype angiotensin II receptor antagonist.

Candesartan cilexetil, a nonpeptide, is chemically described as (±)-1-Hydroxyethyl 2-ethoxy-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]-7-benzimidazolecarboxylate, cyclohexyl carbonate (ester).

Its empirical formula is C33H34N6O6, and its structural formula is:

Candesartan cilexetil 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 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.

Atacand 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, polyethylene glycol, lactose, corn starch, carboxymethylcellulose calcium, and magnesium stearate. Ferric oxide (reddish brown) is added to the 8-mg, 16-mg, and 32-mg tablets as a colorant.

Nonclinical Toxicology

Carcinogenesis, 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).

PRINCIPAL DISPLAY PANEL – 4 mg

NDC 0186-0004-31

30 tablets

Atacand®

candesartan cilexetil

4 mg tablets

Rx only

Manufactured for:

AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

By: AstraZeneca AB, SE-151 85

Södertälje, Sweden Product of Italy

AstraZeneca

  • ACE Inhibitors
  • Angiotensin Receptor Blockers (ARBs)

Before taking this medicine

You should not use Atacand if you are allergic to candesartan.

If you have diabetes, do not use Atacand together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo).

You may also need to avoid taking candesartan with aliskiren if you have kidney disease.

To make sure Atacand is safe for you, tell your doctor if you have:

  • kidney disease;

  • liver disease;

  • congestive heart failure;

  • an electrolyte imbalance;

  • if you are on a low-salt diet; or

  • if you are dehydrated.

Do not use Atacand if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away. Candesartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

It is not known whether candesartan passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using Atacand.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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