ATACAND (candesartan cilexetil 4 mg) Dailymed

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 ATACAND 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 uled 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.

11 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.

12 Clinical Pharmacology

12.1 Mechanism 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 AT₁ 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 AT₂ receptor found in many tissues, but AT₂ is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity (>10,000-fold) for the AT₁ receptor than for the AT₂ 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.

12.2 Pharmacodynamics

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 0.13 L/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 ¹⁴C-labeled candesartan cilexetil, approximately 33% of radioactivity is recovered in urine and approximately 67% in feces. Following an intravenous dose of ¹⁴C-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 AT₁ 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 ATACAND. 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 the pharmacokinetics of candesartan between male and female subjects.

Renal Insufficiency

In hypertensive patients with renal insufficiency, serum concentrations of candesartan were elevated. After repeated dosing, the AUC and C_max were approximately doubled in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73m²) compared to patients with normal kidney function. The pharmacokinetics of candesartan in hypertensive patients undergoing hemodialysis are similar to those in hypertensive patients with severe renal impairment. Candesartan cannot be removed by hemodialysis. No initial dosage adjustment is necessary in patients with renal insufficiency [see Dosage and Administration (2.1) ].

In heart failure patients with renal impairment, AUC_0-72h was 36% and 65% higher in mild and moderate renal impairment, respectively. C_max was 15% and 55% higher in mild and moderate renal impairment, respectively.

Pediatrics

ATACAND pharmacokinetics have not been determined in children with renal insufficiency.

Hepatic Insufficiency

The pharmacokinetics of candesartan were compared in patients with mild and moderate hepatic impairment to matched healthy volunteers following a single oral dose of 16 mg candesartan cilexetil. The increase in AUC for candesartan was 30% in patients with mild hepatic impairment (Child-Pugh A) and 145% in patients with moderate hepatic impairment (Child-Pugh B). The increase in C_max for candesartan was 56% in patients with mild hepatic impairment and 73% in patients with moderate hepatic impairment. The pharmacokinetics after candesartan cilexetil administration have not been investigated in patients with severe hepatic impairment. No initial dosage adjustment is necessary in patients with mild hepatic impairment. In hypertensive patients with moderate hepatic impairment, consideration should be given to initiation of ATACAND at a lower dose[see Dosage and Administration (2.1) ].

Heart Failure

The pharmacokinetics of candesartan were linear in patients with heart failure (NYHA class II and III) after candesartan cilexetil doses of 4, 8, and 16 mg. After repeated dosing, the AUC was approximately doubled in these patients compared with healthy, younger patients. The pharmacokinetics in heart failure patients is similar to that in healthy elderly volunteers [see Dosage and Administration (2.3) ].

13 Nonclinical Toxicology

13.1 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).

14 Clinical Studies

14.1 Hypertension

Adult

The antihypertensive effects of ATACAND 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 ATACAND 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 ATACAND in a ratio of 1: 2: 2: 2. For children who weighed < 50 kg the doses of ATACAND were 2, 8, or 16 mg once daily. For those > 50 kg the ATACAND 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 were too few individuals in the age group of 1 - 6 years old to determine whether Blacks respond differently than other patients to ATACAND.

14.2 Heart Failure

Candesartan was studied in two heart failure outcome studies: 1. The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity trial in patients intolerant of ACE inhibitors (CHARM–Alternative), 2. CHARM–Added in patients already receiving ACE inhibitors. Both studies were international double-blind, placebo-controlled trials in patients with NYHA class II - IV heart failure and LVEF ≤40%. In both trials, patients were randomized to placebo or ATACAND (initially 4-8 mg once daily, titrated as tolerated to 32 mg once daily) and followed for up to 4 years. Patients with serum creatinine > 3 mg/dL, serum potassium > 5.5 mEq/L, symptomatic hypotension or known bilateral renal artery stenosis were excluded. The primary end point in both trials was time to either cardiovascular death or hospitalization for heart failure.

CHARM–Alternative included 2028 subjects not receiving an ACE inhibitor due to intolerance. The mean age was 67 years and 32% were female, 48% were NYHA II, 49% were NYHA III, 4% were NYHA IV, and the mean ejection fraction was 30%. Sixty-two percent had a history of myocardial infarction, 50% had a history of hypertension, and 27% had diabetes. Concomitant drugs at baseline were diuretics (85%), digoxin (46%), beta-blockers (55%), and spironolactone (24%). The mean daily dose of ATACAND was approximately 23 mg and 59% of subjects on treatment received 32 mg once daily.

After a median follow-up of 34 months, there was a 23% reduction in the risk of cardiovascular death or heart failure hospitalization on ATACAND (p<0.001), with both components contributing to the overall effect (Table 1).

Table 1. CHARM — Alternative: Primary Endpoint and its Components

Endpoint (time to first event)	ATACAND (n= 1013)	Placebo (n=1015)	Hazard Ratio (95% CI)	p-value (logrank)
CV death or heart failure hospitalization	334	406	0.77 (0.67–0.89)	<0.001
CV death	219	252	0.85 (0.71–1.02)	0.072
Heart failure hospitalization	207	286	0.68 (0.57–0.81)	<0.001

In CHARM–Added, 2548 subjects receiving an ACE inhibitor were randomized to ATACAND or placebo. The specific ACE inhibitor and dose were at the discretion of the investigators, who were encouraged to titrate patients to doses known to be effective in clinical outcome trials, subject to patient tolerability. Forced titration to maximum tolerated doses of ACE inhibitor was not required.

The mean age was 64 years and 21% were female, 24% were NYHA II, 73% were NYHA III, 3% were NYHA IV, and the mean ejection fraction was 28%. Fifty-six percent had a history of myocardial infarction, 48% had a history of hypertension, and 30% had diabetes. Concomitant drugs at baseline in addition to ACE inhibitors were diuretics (90%), digoxin (58%), beta-blockers (55%), and spironolactone (17%). The mean daily dose of ATACAND was approximately 24 mg and 61% of subjects on treatment received 32 mg once daily.

After a median follow-up of 41 months, there was a 15% reduction in the risk of cardiovascular death or heart failure hospitalization on ATACAND (p=0.011), with both components contributing to the overall effect (Table 2). There was no evident relationship between dose of ACE inhibitor and the benefit of ATACAND.

Table 2. CHARM — Added: Primary Endpoint and its Components

Endpoint (time to first event)	ATACAND (n=1276)	Placebo (n=1272)	Hazard Ratio (95% CI)	p-value (logrank)
CV death or heart failure hospitalization	483	538	0.85 (0.75–0.96)	0.011
CV death	302	347	0.84 (0.72–0.98)	0.029
Heart failure hospitalization	309	356	0.83 (0.71–0.96)	0.014

In these two studies, the benefit of ATACAND in reducing the risk of CV death or heart failure hospitalization (18% p<0.001) was evident in major subgroups (see Figure), and in patients on other combinations of cardiovascular and heart failure treatments, including ACE inhibitors and beta-blockers.
Figure. CV Death or Heart Failure Hospitalization in Subgroups – LV Systolic Dysfunction Trials

16 How Supplied/storage And Handling

Product: 63629-4462

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 ATACAND during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible.

Manufactured under the license

from Takeda Pharmaceutical Company, Ltd.

by: AstraZeneca AB, SE-151 85 Södertälje, Sweden

for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

ATACAND is a registered trademark of the AstraZeneca group of companies.

©AstraZeneca 2016

Patient Information

ATACAND^® (at-a-cand)

(candesartan cilexetil)

Tablets

Read the Patient Information that comes with ATACAND 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 ATACAND, ask your doctor or pharmacist.

What is the most important information I should know about ATACAND?

ATACAND 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 ATACAND, tell your doctor right away.

What is ATACAND?

ATACAND is a prescription medicine called an angiotensin receptor blocker (ARB).

ATACAND is 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.

ATACAND must not be used in children less than 1 year of age for high blood pressure.

Who should not take ATACAND?

Do not take ATACAND if you:

• •are allergic to any of the ingredients in ATACAND. See the end of this leaflet for a complete ul of ingredients in ATACAND.
• •are diabetic and taking aliskiren.

What should I tell my doctor before taking ATACAND?

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 “What is the most important information I should know about ATACAND?”
• • are breast-feeding or plan to breast-feed. It is not known if ATACAND passes into your breast milk. You and your doctor should decide if you will take ATACAND 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. 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 ul 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 ATACAND?

• •Take ATACAND exactly as prescribed by your doctor.
• •Do not change your dose or stop ATACAND 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 ATACAND as a liquid suspension for your child. If your child switches between taking the tablet and the suspension, your doctor will change the dose as needed. Shake the bottle of suspension well before each dose.
• •ATACAND is taken by mouth with or without food.
• •If you miss a dose of ATACAND, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose. Take the next dose on time. Do not take 2 doses at one time. If you are not sure about your dosing call your doctor or pharmacist.
• •If you take more ATACAND than prescribed, call your doctor, local poison control center, or go to the nearest emergency room.

What should I avoid while taking ATACAND?

ATACAND can cause you to feel dizzy or tired. Do not drive, operate machinery, or do other dangerous activities until you know how ATACAND affects you.

What are the possible side effects of ATACAND?

ATACAND may cause serious side effects, including:

• • Injury or death to your unborn baby. See “What is the most important information I should know about ATACAND?
• • Low blood pressure (hypotension). Low blood pressure is most likely to happen if you:
  • ∘take water pills (diuretics)
  • ∘are on a low salt diet
  • ∘get dialysis treatments
  • ∘are dehydrated (decreased body fluids) due to vomiting and diarrhea
  • ∘have heart problems

If you feel dizzy or faint lie down and call your doctor right away.

Low blood pressure can also happen if you have major surgery or anesthesia. You will be monitored for this and treated if needed. See “What should I tell my doctor before taking ATACAND?”

• • Worsening kidney problems. Kidney problems may get worse in people that already have kidney disease or heart problems. Your doctor may do blood tests to check for this.
• • Increased potassium in your blood. Your doctor may do a blood test to check your potassium levels as needed.
• • Symptoms of allergic reaction. Call your doctor right away if you have any of these symptoms of an allergic reaction:
  • ∘swelling of your face, lips, tongue or throat
  • ∘rash
  • ∘hives and itching

The most common side effects of ATACAND are:

• •back pain
• •dizziness
• •cold or flu symptoms (upper respiratory tract infection)
• •sore throat (pharyngitis)
• •nasal congestion and stuffiness (rhinitis)

Tell your doctor or pharmacist about any side effect that bothers you or that does not go away.

These are not all the side effects of ATACAND. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You can report side effects to FDA at 1-800-FDA-1088.

How should I store ATACAND?

• •Do not keep medicine that is out of date or that you no longer need.
• •Store ATACAND tablets at room temperature below 86°F (30°C).
• •Store ATACAND oral suspension at room temperature below 86°F (30°C).
• •Use the oral suspension within 30 days after first opening the bottle. Do not use after the expiration date stated on the bottle.
• •Do not freeze.
• •Keep the container of ATACAND closed tightly.

Keep ATACAND and all medicine out of the reach of children.

General information about ATACAND

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use ATACAND for a condition for which it was not prescribed. Do not give ATACAND to other people, even if they have the same problem you have. It may harm them.

This leaflet summarizes the most important information about ATACAND. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about ATACAND that is written for health professionals.

For more information, go to www.atacand-us.com or call 1 800-236-9933.

What are the ingredients in ATACAND?

Active ingredient: candesartan cilexetil.

Inactive ingredients in ATACAND tablets and ATACAND oral suspension are: 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.

In addition to the above, ATACAND oral suspension also includes the following inactive ingredients: Ora Plus, Ora Sweet or Ora-Blend.

How does ATACAND work?

ATACAND is a type of medicine called angiotensin receptor blocker, which blocks the effect of the hormone angiotensin II, causing the blood vessels to relax. This helps lower blood pressure. Medicines that lower your blood pressure lower your chance of having a stroke or heart attack.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Manufactured under the license

from Takeda Pharmaceutical Company, Ltd.

by: AstraZeneca AB, SE-151 85 Södertälje, Sweden

for: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

ATACAND is a registered trademark of the AstraZeneca group of companies.

Ora-Plus^®, Ora-Sweet SF^®, and Ora-Blend SF^® are registered trademarks of Paddock Laboratories, Inc.

Issued: 07/2016

©AstraZeneca 2016

Candesartan Cilexetil