Avapro

7 The safety and efficacy of concurrent use with angiotensin converting enzyme inhibitors has not been established. CONTRAINDICATIONS AVAPRO irbesartan ; is contraindicated in patients who are hypersensitive to any component of this product. WARNINGS Pregnancy Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. When pregnancy is detected, AVAPRO irbesartan ; should be discontinued as soon as possible. The use of drugs that act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug. These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to an angiotensin Il receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of irbesartan as soon as possible. Rarely probably less often than once in every thousand pregnancies ; , no alternative to an angiotensin II receptor antagonist will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment. If oligohydramnios is observed, irbesartan should be discontinued unless it is considered life-saving for the mother. Contraction stress testing CST ; , a non-stress test NST ; , or biophysical profiling BPP ; may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion may be required as means of reversing hypotension and or substituting for disordered renal function. Irbesartan is not removed by hemodialysis. Hypotension - Volume Depleted Patients Occasionally, symptomatic hypotension has occured after administration of irbesartan, in some cases after the first dose. It is more likely to occur in patients who are volume depleted by. Metoprolol succ er metoprolol tartrate nadolol propranolol hcl COREG TOPROL XL INNOPRAN XL 4.5.1 VASODILATOR ANTIHYPERTENSIVES doxazosin mesylate hydralazine hcl prazosin hcl terazosin hcl CARDURA XL 4.5.2 CENTRALLY ACTING ANTIHYPERTENSIVES clonidine hcl guanfacine hcl methyldopa 4.5.4.1 ANGIOTENSIN CONVERTING ENZYME INHIBITORS benazepril hcl captopril enalapril maleate fosinopril sodium lisinopril quinapril quinapril hcl The following drugs are not covered by the Plan: ACCUPRIL ACEON ALTACE MAVIK UNIVASC 4.5.4.2 ANGIOTENSIN II RECEPTOR ANTAGONISTS BENICAR DIOVAN ATACAND AVAPRO COZAAR MICARDIS TEVETEN and capoten. Indication Rheumatoid arthritis1 Crohn's disease2 Pediatric Crohn's disease Ulcerative colitis Number of patients3 placebo 375 173 N A infliximab 1087 703 139 Median follow-up wks ; 4 placebo infliximab 58.1 58.3 54.1 N A 54.1 53.0 3 x ULN placebo 3.2% 3.5% N A infliximab 3.9% 5.1% 4.4% x ULN placebo 0.8% 0.0% N A infliximab 0.9% 1.7% 1.5.

In FY06 the Headquarters supported several professional meetings. Selected examples follow: International Conference on Emerging Infectious Diseases Atlanta, GA ; , Force Health Protection Conference Albuquerque, NM ; , Army National Guard medical team seminar Dallas, TX ; , EWORS symposium in December 2005 at WRAIR Silver Spring, MD ; , and American Society of Tropical Medicine and Hygiene symposium in Washington DC. In addition to delivering peer-reviewed presentations, GEIS support included participation on program planning committees, critical review of submitted abstracts, provision of speakers for invited presentations and session moderators, and administrative and financial assistance. In addition, the report of a GEIS-sponsored workshop entitled "Emerging Infectious Disease Modeling: Epidemiologic Applications in the Department of Defense, " held on 3 August 2005 at WRAIR, was completed and published in a peer-reviewed journal and cardizem.

Exhibit 31.1 INSPIRE PHARMACEUTICALS, INC. CERTIFICATIONS I, Christy L. Shaffer, certify that: 1. I have reviewed this annual report on Form 10-K of Inspire Pharmaceuticals, Inc.; 2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; 3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report; 4. The registrant's other certifying officer s ; and I are responsible for establishing and maintaining disclosure controls and procedures as defined in Exchange Act Rules 13a-15 e ; and 15d-15 e and internal control over financial reporting as defined in Exchange Act Rules 13a-15 f ; and 15d-15 f for the registrant and have: a ; Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared; b ; Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles; c ; Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and d ; Disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent fiscal quarter the registrant's fourth fiscal quarter in the case of an annual report ; that has materially affected, or is reasonably likely to materially affect, the registrant's internal control over financial reporting; and 5. The registrant's other certifying officer s ; and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant's auditors and the audit committee of the registrant's board of directors or persons performing the equivalent functions ; : a ; All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant's ability to record, process, summarize and report financial information; and b ; Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control over financial reporting. Date: March 14, 2008 s CHRISTY L. SHAFFER.
A Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation. B Requires the availability of well conducted clinical studies but no randomised clinical trials on the topic of recommendation.Or systematic review of case-control or cohort studies. C Based on non-experimental descriptive studies e.g. correlation or case control studies ; . D Evidence obtained from expert committee reports or opinions and or clinical experiences of respected authorities. Indicates an absence of directly applicable clinical studies of good quality and cardura.

Management guideline S.2.2 Falls assessment and management guideline Resource list S.3 ASSESSMENT INFORMATION S.3.1 Falls risk assessment tool Community S.3.2 Falls prevention: Risk assessment action plan Community S.3.3 References to other risk assessment tools and literature S.3.4 Individual environmental audit tool and action plan - Suitable for immediate use S.3.4.1 Falls prevention: Environmental audit Community S.3.4.2 Falls prevention: Environmental audit action plan Community S.3.5 References to other environmental assessment tools S.3.6 Guidelines on how to develop a risk assessment tool S.4 S.5 HEALTH PROMOTION INTERVENTIONS REQUIRING FURTHER ATTENTION S.5.1 Falls Clinics S.5.2 Patient sitter programs S.5.3 Response systems S.6 S.7 S.8 FALLS PREVENTION: YOUR SAFETY CHECKLIST AND GUIDE REFERENCES. Table 6. Referral of assault cases to social services and law enforcement. Referral to Social Services * No. % ; 6 7.1 ; 4 7.7 ; 2 4.0 ; 4 40.0 ; 1 20.0 ; 1 2.8 ; 18 7.6 ; Citation of Police Involvement * No. % ; 54 34 32 ; 65.4 ; 64.0 ; 100.0 ; 80.0 ; 44.4 and coreg and Avapro online.
Pharmaceuticals In 2003, worldwide Pharmaceuticals sales increased 16% to , 925 million, reflecting a 2% price increase, a 9% volume increase and a 5% increase in foreign exchange. Domestic sales in 2003 increased 16% to , 431 million primarily due to increased sales of Plavix, the Pravachol franchise, Abilify total revenue ; , Glucovance and Paraplatin and partly due to the impact on 2002 sales from the workdown of non-consignment wholesaler inventory, partially offset by decreased sales of Glucophage IR and TAXOL primarily due to generic competition. Reyataz was launched in July 2003, with million in domestic sales. International sales in 2003 increased 17% to , 494 million, including an 11% favorable foreign exchange impact, primarily due to increased sales of Pravachol, TAXOL , Plavix, Avapro Avalide and Analgesic products in Europe partially offset by price declines principally in Germany and Italy. In 2002, worldwide pharmaceuticals sales decreased 6% to , 812 million, reflecting a 4% price decline, a 2% volume decline, and no foreign exchange impact. Domestic sales declined 14% to , 273 million, primarily due to generic competition in the United States on Glucophage IR, TAXOL and BuSpar, partially offset by increased sales of Plavix and the addition of products acquired from the DuPont Pharmaceuticals acquisition, which was completed on October 1, 2001. In addition, the decrease in domestic pharmaceutical sales was impacted by the buildup in the prior period of inventory levels at those U.S. wholesalers not accounted for under the consignment model and the subsequent workdown in 2002. Approximately , 395 million of sales calculated net of discounts, rebates and other adjustments ; recognized in the year ended December 31, 2002 had been reversed from prior years. International sales increased 9% to , 539 million with no significant foreign exchange impact ; primarily due to increased sales of Pravachol and Plavix in Europe, TAXOL in Japan and the addition of products acquired from the DuPont Pharmaceuticals acquisition. Key pharmaceutical products and their sales include the following: Total revenue for Abilify, which is primarily domestic alliance revenue for the Company's 65% share of net sales in copromotion countries with Otsuka Pharmaceutical Co., Ltd. Otsuka ; , was 3 million. The schizophrenia agent was introduced in the United States in November 2002 and by December 2003, had achieved more than a 7% weekly new prescription share of the U.S. antipsychotic market. The Company received approval for a Supplemental New Drug Application sNDA ; for Abilify for maintaining stability in patients with schizophrenia, and has announced that it submitted an sNDA for Abilify for the treatment of acute mania in patients with bipolar disorder to the U.S. Food and Drug Administration FDA ; . Abilify is being developed and marketed by Bristol-Myers Squibb and its partner Otsuka. Sales of the Pravachol franchise increased 25%, including a 7% favorable foreign exchange impact, to , 827 million in 2003. Domestic sales increased 22% to , 605 million in 2003, while international sales increased 28.

Consider the possibility of a genetic lipid disorder if TC 8 mmol L or if there is a family history of premature coronary heart disease. See Appendix A for definitions and management of genetic lipid disorders and cozaar. DETAILED PATIENT PACKAGE INSERT This product like all oral contraceptives ; is intended to prevent pregnancy. Oral contraceptives do not protect against HIV infection AIDS ; and other sexually transmitted diseases. YAZ is different from other birth control pills because it contains the progestin drospirenone. Drospirenone may increase potassium. Therefore, you should not take YAZ if you have kidney, liver or adrenal disease because this could cause serious heart and health problems. Other drugs may also increase potassium. If you are currently on daily, long-term treatment for a chronic condition with any of the medications below, you should consult your healthcare provider about whether YAZ is right for you, and during the first month that you take YAZ, you should have a blood test to check your potassium level. NSAIDs ibuprofen [Motrin, Advil], naprosyn [Aleve and others] when taken long-term and daily for treatment of arthritis or other problems ; Potassium-sparing diuretics spironolactone and others ; Potassium supplementation ACE inhibitors Capoten, Vasotec, Zestril and others ; Angiotensin-II receptor antagonists Cozaar, Diovan, Avapro and others ; Heparin Aldosterone antagonists YAZ is an oral contraceptive, also known as a "birth control pill" or "the Pill." Oral contraceptives are taken to prevent pregnancy, and, when taken correctly without missing any pills, have a failure rate of approximately 1% per year 1 pregnancy per 100 women per year of use ; . The typical failure rate in pill users is approximately 5% per year 5 pregnancies per 100 women per year of use ; when women who miss pills are included. Forgetting to take pills considerably increases the chances of pregnancy. YAZ may also be taken to treat premenstrual dysphoric disorder PMDD ; if you choose to use the Pill for birth control. Unless you have already decided to use the Pill for birth control, you should not start YAZ to treat your PMDD because there are other medical therapies for PMDD that do not have the same risks as the Pill. PMDD is a mood disorder related to the menstrual cycle. PMDD significantly interferes with work or school, or with usual social activities and relationships with others. Symptoms include markedly depressed mood, anxiety or tension, mood swings, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD may include breast tenderness, headache, joint and muscle pain, bloating and weight gain. These symptoms occur regularly before menstruation starts and go away within a few days following the start of the period. Diagnosis of PMDD should be made by healthcare providers. You should only use YAZ for treatment of PMDD if you: Have already decided to use oral contraceptives for birth control, and Have been diagnosed with PMDD by your healthcare provider. YAZ has not been shown to be effective for the treatment of premenstrual syndrome PMS ; , a less serious cluster of symptoms occurring before menstruation. If you or your healthcare provider believes you have PMS, you should only take YAZ if you want to prevent pregnancy; and not for the treatment of PMS. YAZ may also be taken to treat moderate acne in women who are able to and wish to use the pill for birth control. INTRODUCTION Any woman who needs contraception birth control ; and chooses to use an oral contraceptive should understand the benefits and. Over recent years, taking medicines by inhalation has evolved to include a variety of approaches for different diseases. Today, small molecules are delivered by inhalation both locally to the lungs and systemically via the lungs. 40. Creager MA, Liang CS, Coffman JD. Beta adrenergic-mediated vasodilator response to insulin in the human forearm. J Pharmacol Exp Ther. 1985; 235: 709 Vierhapper H. Effect of exogenous insulin on blood pressure regulation in healthy and diabetic subjects. Hypertension. 1985; 7 suppl II ; : II49 II-53. 42. Renkin EM. Control of microcirculation and blood-tissue exchange. In: Handbook of Physiology: The Cardiovascular System: Microcirculation. Bethesda, Md: American Physiological Society; 1984: 627 687. Grubb B, Snarr JF. Effect of flow rate and glucose concentration on glucose uptake rate by the rat limb. Proc Soc Exp Biol Med. 1977; 154: 3336. Mather K, Laakso M, Edelman S, Hook G, Baron A. Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow. J Physiol. 2000; 279: E1264 E1270. 45. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man: a novel mechanism for insulin resistance. J Clin Invest. 1990; 85: 1844 Laakso M, Edelman SV, Brechtel G, Baron AD. Impaired insulinmediated skeletal muscle blood flow in patients with NIDDM. Diabetes. 1992; 41: 1076 Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 2000; 404: 787790. Maddux BA, See W, Lawrence JC Jr, Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes. 2001; 50: 404 Rudich A, Tirosh A, Potashnik R, Hemi R, Kanety H, Bashan N. Prolonged oxidative stress impairs insulin-induced GLUT4 translocation in 3T3-L1 adipocytes. Diabetes. 1998; 47: 15621569. Haber CA, Lam TK, Yu Z, Gupta N, Goh T, Bogdanovic E, Giacca A, Fantus IG. N-Acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress. J Physiol. 2003; 285: E744 E753. 51. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004; 114: 17521761. Gao Z, Hwang D, Bataille F, Lefevre M, York D, Quon MJ, Ye J. Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem. 2002; 277: 48115 Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature. 2002; 420: 333336. Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005; 120: 649 Miele C, Riboulet A, Maitan MA, Oriente F, Romano C, Formisano P, Giudicelli J, Beguinot F, Van Obberghen E. Human glycated albumin affects glucose metabolism in L6 skeletal muscle cells by impairing insulin-induced insulin receptor substrate IRS ; signaling through a protein kinase C alpha-mediated mechanism. J Biol Chem. 2003; 278: 47376 Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. J Physiol. 2001; 280: E685E694. 57. Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100 calgranulin polypeptides. Cell. 1999; 97: 889 Buse mg. Hexosamines, insulin resistance, and the complications of diabetes: current status. J Physiol. 2006; 290: E1E8. 59. Veerababu G, Tang J, Hoffman RT, Daniels MC, Hebert LF Jr, Crook ED, Cooksey RC, McClain DA. Overexpression of glutamine: fructose6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance. Diabetes. 2000; 49: 2070 Rossetti L. Perspective: hexosamines and nutrient sensing. Endocrinology. 2000; 141: 19221925. HTN is a highly prevalent, modifiable CV disease risk factor affecting approximately 65 million adults in the US total prevalence of 31.3% ; and 1 billion people worldwide Fields et al, 2004; Kearny et al, 2005 ; . The relationship between BP and risk of CV disease events is continuous, consistent, and independent of other risk factors. The higher the BP, the greater the chance of myocardial infarction, heart failure, stroke, and kidney diseases, such as DN JNC 7, 2003 ; . BP remains uncontrolled in two-thirds of hypertensive adults in the US JNC 7, 2003 ; and therefore substantial public health returns could be expected from improved treatment of HTN. Indications Avapro and Avalide are indicated for the treatment of HTN. Avalide, the fixed-dose combination of irbesartan and HCTZ, is not indicated for initial therapy, but is indicated for the treatment of HTN in patients whose BP is not adequately controlled with monotherapy. Avapro is also indicated for treatment of DN with an elevated serum creatinine and proteinuria 300 mg day ; in patients with type 2 diabetes and HTN. Hypertension The efficacy and safety of irbesartan and the fixed combination of irbesartan and HCTZ were established on the results of several pivotal trials as described in the Avapro and Avalide prescribing information. Head-to-head studies further demonstrate the efficacy of irbesartan and irbesartan HCTZ. Head-to-head studies In head-to-head studies, irbesartan demonstrated significantly greater reductions in BP than losartan and valsartan Kassler-Taub et al, 1998; Oparil et al, 1998; Mancia et al, 2002 ; . Irbesartan had comparable BP reductions relative to olmesartan with the exception of office DBP Oparil et al, 2001 ; . Furthermore, irbesartan demonstrated comparable reductions in BP with antihypertensive therapies of other mechanistic classes, such as the BB atenolol, the CCB amlodipine, and the ACE-I enalapril Stumpe et al, 1998; Neutel et al, 1999; Mimran et al, 1998 ; . Overall, the incidence of AEs was similar between irbesartan and these comparative antihypertensives. The most commonly reported AEs were headache, fatigue, and dizziness. In regards to combination therapy, the fixed combination of irbesartan HCTZ produced greater reductions in BP compared to valsartan HCTZ and losartan HCTZ Bobrie et al, 2005; Neutel and Smith, 2005 ; . The incidence of AEs was similar between treatment groups.
Trent Bower, Bristol Myers Squibb: Mr. Bower stated that Avapro was significant in reducing systolic and diastolic blood pressures in patients in a study. In clinical trials in patients with hypertension, Avapro has demonstrated overall safety and tolerability similar to placebo therapy. Emmanuel Mahlis, M.D., Merck: Dr. Mahlis stated that cardiovascular disease is the leading cause of death in West Virginia. He said that Cozaar has been proven to reduce organ failure in addition to lowering blood pressure. Russell Clayton, M.D., Pediatric Pulmonologist, Merck: Dr. Clayton stated that Singular has been shown in placebo control studies to be as effective as monotherapy in adults and children with mild persistent asthma. Singular reduces symptoms, increases lung function and has an excellent safety profile. Larry Green, Dey Labs: Mr. Green spoke to the Committee about Accuneb and Duoneb. He stated that lower dosing enables children to be able to sleep at night and it has fewer side effects. He also discussed Duoneb, which is used in COPD patients, and how they get better results from this drug. Mr. Green asked the Committee to consider putting these drugs on the Preferred Drug List and buy tenormin.
P n lim ina n "Treatment Plan : T he patient will be o ffered med ication s but he re fu ses an y rncdiHe refuses 10 stay in the hospital. His guard ian insists that the patient meet s gran : di sab ility criteria and is unable to provi de for his needs for his o wn safe ty. We will seek co urt cl arifica uon as to whether the patient is gra vely d isa bled or nor. We will seck a med icat ion petiti o n so that we ca n treat him. as o therwis e there wou ld be no benefit from him be ing: ho spitalized . W\." will atte mpt to help the patient resolve a plan for pro visioning: o f his g ocer ies. We will attempt r to encoura ge the pat ient 10 accept an assisted living facility placement wit h 2-t-ho ur supe rvi sion. Th ere ap pear s to be noth ing we can do about the unfort unate chain o f events in which the patient has bec ome in volved in litigation and this process ha s prod uced considerable de triment in his t: funct ioning due to the encouragement of his delusio nal gran diosi ty by the process. The Performance Drug List specifies drugs that help maximize clinical results and economic value. The List is not a formulary and lists only select therapeutic categories. Thirty products and medications have been added to the List for 2002, and some medications have been removed. The 2002 Performance Drug List can be viewed on M-CARE's website at mcare . For members covered by M-CARE's three-tier prescription drug benefit, the following medications will change from a Preferred drug copayment to a Non-Preferred drug copayment starting on January 1: Actonel Adalat CC Alesse Avalide Avapro Azmacort Effexor Effexor XR Glucophage Lo Ovral Maxair Monopril Monopril HCT Nordette Plendil Pravachol Protonix Prozac Relafen Serzone Sular Suprax Triphasil Xalatan. Irbesartan is a white to off-white crystalline powder with a molecular weight of 428.5. It is a nonpolar compound with a partition coefficient octanol water ; of 10.1 at pH of 7.4. Irbesartan is slightly soluble in alcohol and methylene chloride and practically insoluble in water. AVAPRO is available for oral administration in unscored tablets containing 75 mg, 150 mg, or 300 mg of irbesartan. Inactive ingredients include: lactose, microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, poloxamer 188, silicon dioxide and magnesium stearate. CLINICAL PHARMACOLOGY Mechanism of Action Angiotensin II is a potent vasoconstrictor formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme ACE, kininase II ; . Angiotensin II is the principal pressor agent of the. 157 data, since there are several sources of data that we use for post-marketing surveillance, we did use the PharMetrics database to conduct an epidemiologic study looking at the adverse events of special interest that you have seen previously. This is a very large managed care claims database which includes approximately 12 million patients from the U.S. general population. This study actually allowed us to compare initial use of Avalide to irbesartan, because we excluded patients who had any antihypertensive use six months prior to the start of the study. The study compared the estimated relative risks of the adverse events between Avalide and Avapro users from 1995 to 2006. Now, there are.