ibersartan

1. Canadian standards you can trust
Prpms-IRBESARTAN
Product Information Deck
July 2014

2. Pharmascience, International Division
TABLE OF CONTENT
Hypertension (HT)
About Hypertension ...…………………………….....………………………….
Types of Hypertension .…….…………………….....………………………….
Risk Factors and Incidence Rates……………………………………………...
Treatment Options……………………………………………………………….
Irbesartan
Therapeutic Indication…………………….…………………………….....……
Posology, Drug Administration & Dosage……………………………………..
Clinical Efficacy Studies..…………………………………………………….....
Adverse Drug Reaction Overview…………………………………………..….
pms-Irbesartan
pms-Irbesartan – Bioequivalence Study……………….……….…..…………
pms-Irbesartan – Dosage Forms Composition and Packaging…………….
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HYPERTENSION (HT)
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4. Pharmascience, International Division
ABOUT HYPERTENSION1
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What is Arterial Hypertension?
● Commonly known as “high blood pressure”
● "Blood pressure” is a measurement of the force against the walls of the arteries as the
heart pumps blood through the body
● Asymptomatic until overt organ damage occurs. Routine check ups with a healthcare
professional are essential for early diagnosis
Source: 1 http://www.nlm.nih.gov/medlineplus/ency/article/000468.htm
If Left Untreated…
Chronically elevated blood pressure can lead to many health problems such as
coronary heart disease, myocardial infarction, heart failure, stroke, and kidney
failure.

5. Pharmascience, International Division
ABOUT HYPERTENSION (CON’T)1
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Understanding Blood Pressure:
● Blood Pressure is recorded in 2 numbers:
1. Systolic:
● The pressure in the arteries when the heart muscles contract, during
heart beat
2. Diastolic:
● The pressure in the arteries when the heart muscles relax, between
heart beats
Source: 1 http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/AboutHighBloodPressure/Understanding-Blood-Pressure-
Readings_UCM_301764_Article.jsp
Normal Blood Pressure: High Blood Pressure:
<
120
────
80
≥
140
────
90
mmHg mmHg

6. Pharmascience, International Division
TYPES OF HYPERTENSION1
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Source: 1 http://www.nlm.nih.gov/medlineplus/ency/article/000468.htm
2. Secondary Hypertension
● High blood pressure caused by another medical condition or medication
such as:
1. Essential Hypertension
● High blood pressure with no identifiable cause
● Most common
● Chronic Kidney Disease
● Disorders of the Adrenal Gland
● Hyperparathyroidism
● Pregnancy
● Renal Artery Stenosis
● Birth control pills
● Diet pills
● Some cold medicines
● Migraine medicines

7. Pharmascience, International Division
RISK FACTORS1 AND INCIDENCE RATES2
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There is a increased risk of Hypertension if … 1
Source: 1 http://www.nlm.nih.gov/medlineplus/ency/article/000468.htm
2 http://apps.who.int/iris/bitstream/10665/79059/1/WHO_DCO_WHD_2013.2_eng.pdf?ua=1
Worldwide Incidence Rates 2
● Affects 40% of adults aged 25 and above
● Hypertension is estimated to kill 9.4 million people worldwide each year
● Hypertension is responsible for:
● 45% of deaths due to Heart Disease
● 51% of deaths due to Stroke
● Early diagnosis and treatment of hypertension is far less costly, and far safer for
patients than resulting medical intervention if left untreated.
● African American
● Obesity
● Poor stress management
● Salt-rich diet
● Alcohol abuse
● Family history of Hypertension
● Diabetes
● Smoking

8. Pharmascience, International Division
HYPERTENSION TREATMENTS1
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● Lifestyle changes
● Ex: Exercise, quit smoking, reduce stress, limit alcohol, healthy diet
● Sympathoplegic Drugs
● Ex: Carvedilol, Propanolol hydrochloride, Methyldopa, Prazosin
hydrochloride
● Diuretics
● Ex: Irbesartan/HCTZ*, Furosemide
● Vasodilators
● Ex: Amlodipine*/Atorvastatin, Minoxidil, Hydralazine hydrocholoride
● Angiotensin Antagonists
● Ex: Irbesartan, Quinapril, Valsartan, Captopril
Source: 1 http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/PreventionTreatmentofHighBloodPressure/Types-of-
Blood-Pressure-Medications_UCM_303247_Article.jsp
* Combination drug, star indicates specific category
Note: Pharmascience Inc. products in blue

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IRBESARTAN
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10. Pharmascience, International Division
THERAPEUTIC INDICATION1
Irbesartan is a Angiotensin Receptor (AT1-type) Inhibitor indicated for
adults with:
1. Essential Hypertension
2. Kidney Disease treatment in patients with Hypertension and Type-
2 Diabetes [Hypertension + type 2 diabetic nephropathy]
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Source: 1 https://www.medicines.org.uk/emc/medicine/27608

11. Pharmascience, International Division
POSOLOGY
DRUG ADMINISTRATION & DOSAGE1
Method of Administration
• Oral administration once daily, with or without food
1. Essential Hypertension
• Recommended dose: 150 mg
• Initiation Dose: 150 mg (75 mg in elderly and hemodialysed patients)
• Max dose: 300 mg, or 150 mg + Diuretic (HCTZ)
2. Kidney Disease: Hypertensive Type-2 Diabetes Patients
• Recommended dose: 300 mg
• Initiation Dose: 150 mg
• Max dose: 300 mg
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Source: 1 https://www.medicines.org.uk/emc/medicine/27608

12. Pharmascience, International Division
POSOLOGY
DRUG ADMINISTRATION & DOSAGE (CON’T)1
Drug Use within Special Populations
Renal Impairment: No dose adjustment required
Hepatic Impairment: Mild: No dose adjustment required
Moderate: No dose adjustment required
Severe: No clinical data available
Elderly: No dose adjustment required
Pediatrics: Safety and efficacy not estabilished
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Source: 1 https://www.medicines.org.uk/emc/medicine/27608

13. Pharmascience, International Division
CLINICAL STUDIES: DOSE-RELATED
EFFICACY FOR HYPERTENSION1
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Irbesartan vs. Placebo
Source: 1 http://hyper.ahajournals.org/content/31/6/1311.full
8 Multicenter Clinical Studies:
• 2,955 hypertensive patients randomized, double blindly, to 1 of the
following 2 regimens:
1. Irbesartan once daily (1 to 900 mg) for 6-8 weeks
2. Placebo once daily, for 6-8 weeks
Results:
• Administration of Irbesartan to patients with essential hypertension resulted
in significant reduction of blood pressure, in comparison to placebo
• Antihypertensive effects increased with increasing doses, reaching a
plateau at ≥300 mg
• No clinically or statistically significant changes in heart rate with any
Irbesartan dose

14. Pharmascience, International Division
CLINICAL STUDIES: HYPERTENSION AND TYPE 2
DIABETIC NEPHROPATHY1
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Irbesartan vs. Amlodipine
Irbesartan Diabetic Nephropathy Trial (IDNT) :
• Examined 1,715 patients with hypertension and type 2 diabetes, on the long-term
effects of Irbesartan on the progression of Kidney disease
• Patients randomized double blindly, and titrated to 1 of the following 3 regimens:
1. Irbesartan once daily (300 mg), for a mean 2.6 years
2. Amlodipine once daily (10 mg), for a mean 2.6 years
3. Placebo once daily, for a mean 2.6 years
Results:
• The risk of developing a doubling of serum creatinine or End Stage Renal
Disease was reduced by 26% relative to placebo with an absolute risk
reduction of 6.2%.
• This renal protective effect of irbesartan appears to be independent of systemic
blood pressure reduction.
Placebo
vs.
Source: 1 Prpms-Irbesartan Product Monograph. Health Canada. February 17, 2011

15. Pharmascience, International Division 15
Irbesartan on MicroAlbuminuria Study (IRMA2):
• 590 hypertensive patients with type 2 diabetes, microalbuminuria (loss of
protein Albumin in urine) and normal renal function (based on creatinine levels)
• Patients with microalbuminuria have a 10-20 fold higher risk of developing
diabetic nephropathy than healthy patients
• Patients randomized double blindly, to 1 of the following 2 regimens:
1. Irbesartan once daily (150 mg or 300 mg), for a mean 1.5 years
2. Placebo once daily, for a mean 1.5 years
Results:
• Irbesartan 300 mg demonstrated a 70% relative risk reduction in the
development of clinical proteinuria/microalbuminuria, compared to placebo
• Irbesartan 300 mg reduced the level of urinary albumin excretion at 24 months
by 43%
• Relative risk reduction in the development of proteinuria with 150 mg Irbesartan
was not statistically significant
Source: 1 Prpms-Irbesartan Product Monograph. Health Canada. February 17, 2011
CLINICAL STUDIES: HYPERTENSION AND TYPE 2
DIABETIC NEPHROPATHY1
Irbesartan vs. Placebo

16. Pharmascience, International Division
ADVERSE REACTIONS1
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Source: 1 https://www.medicines.org.uk/emc/medicine/23161/SPC/Diovan+160mg+Capsules/#UNDESIRABLE_EFFECTS
In controlled clinical studies in patients:
Adverse reactions:
1. Incidence comparable with placebo
2. Discontinuation of treatment less than with placebo
3. Not dose-related
4. Showed no association with gender, age, race or duration of treatment
For a complete list of adverse reactions, please refer to:

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PrPMS-IRBESARTAN
17

18. Pharmascience, International Division
BIOEQUIVALENCE STUDY1
● A single center, randomized, blinded, 2-way crossover study
● Both tablets administered as: single 300 mg dose
● 21 healthy males under fasting conditions
vs.
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pms-IRBESARTAN
Pharmascience Inc.
300 mg tablets
AVAPRO
Sanofi-Synthelabo Canada
Inc.
300 mg tablets
Source: 1 Prpms-Irbesartan Product Monograph. Health Canada. February 17, 2011

19. Pharmascience, International Division
BIOEQUIVALENCE STUDY: SUMMARY TABLE OF THE
COMPARATIVE BIOAVAILABILITY DATA
Irbesartan
(1 x 300 mg tablet)
From measured data
Uncorrected for potency
Geometric Mean
Arithmetic Mean (CV %)
Parameter Test* Reference† % Ratio of
Geometric
Means
90% Confidence
Interval
AUCT
(ng·h/mL)
19409.28
20847.82 (37.29)
19672.29
20813.02 (34.75)
98.66 88.56 – 109.92
AUCI
(ng·h/mL)
22490.59
23763.90 (31.74)
22269.26
23251.43 (30.07)
100.99 91.95 – 110.92
Cmax
(ng/mL)
3613.1
3693.8 (21.55)
3643.2
3832.9 (31.12)
99.17 91.29 – 107.74
Tmax
§
(h)
1.25
(0.500 – 5.00)
1.25
(0.500 – 5.00)
T½
€
(h)
12.82
(41.09)
13.23
(49.74)
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* pms-IRBESARTAN , Pharmascience Inc., Montréal, Québec, Canada
† AVAPRO® , Sanofi- Synthelabo Canada Inc., purchased in Canada
§ Expressed as the median (range) only
€ Expressed as the arithmetic mean (CV%) only
$ % ratios of the geometric means and 90% confidence intervals are based on the 'least squares mean estimates'.
Source: 1 Prpms-Irbesartan Product Monograph. Health Canada. February 17, 2011

20. Pharmascience, International Division
DOSAGE FORMS, COMPOSITIONS AND PACKAGING
Storage:
● Store at controlled room temperature (15°C to 30°C)
Dosage forms:
● 75 mg: White to off-white, oval and biconvex tablet, debossed
with “IS” on one side and “75” on the other side.
● Packaging: Bottles of 100 tablets
● 150 mg: White to off-white, oval and biconvex tablet, debossed
with “IS” on one side and “150” on the other side.
● Packaging: Bottles of 100 tablets
● 300 mg: White to off-white, oval and biconvex tablet, debossed
with “IS” on one side and “300” on the other side.
● Packaging: Bottles of 100 tablets
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