VI.2
ELEMENTS FOR A PUBLIC SUMMARY
VI.2.1
Overview of disease epidemiology
High blood pressure is one of the most important causes of premature death worldwide killing nearly 9.4 million people every year globally, and the problem is growing.Over 1 billion people are living with high blood pressure. In 2008, globally, the overall prevalence of high blood pressure (including those on medication for high blood pressure) in adults aged 25 and above was around 40%.Among all WHO regions, the prevalence of raised blood pressure was highest in the African Region (46%) and lowest in the Region of the Americas (35%). In the South-East Asia Region, 36% of adults have hypertension.In all WHO regions, males had a slightly higher prevalence of raised blood pressure than females, but this difference was only statistically significant in the Region of the Americas and the European Region.The prevalence of raised blood pressure in low, lower-middle and upper-middle income countries is higher (40%) than in high-income countries (35%)1. Hypertension represents a major risk factor for myocardial infarction and the most important risk factor for stroke. Two thirds of strokes and half of myocardial infarctions arise from a systolic blood pressure > 115 mmHg. The relationship between blood pressure and cardiovascular diseases is log linear. Hypertension is the leading risk factor of preventable deaths worldwide. High blood pressure accounts for 26% of the total mortality in Germany. The prevalence of hypertension in Germany (55%) is twice the rate in Canada and the USA. Health care indicators such as hypertension awareness, treatment and control in Germany trail behind when compared internationally. Hypertension treatment and control in Germany amount to 26% and 8%, respectively2. Hypertension is highly prevalent in the elderly. Several epidemiological surveys conducted in the USA and Europe conclude that hypertension prevalence in the elderly ranges between 53% and 72%. Same prevalence patterns have been observed in Greece for this specific age group. High blood pressure values in the presence of several risk factors (obesity, diabetes mellitus, increased salt intake, hyperlipidemia, smoking, lack of physical activity, psychological factors, advanced age, sex) lead to a further increase of cardiovascular disease risk. Regular physical activity, the implementation of a healthy diet and medication are some of the preventive measures that can be adopted for the reduction of high blood pressure levels3. The prevalence was highest in Germany (55%), followed by Finland (49%), Spain (47%), England (42%), Sweden (38%), and Italy (38%). Prevalences in the United States and Canada were half of the rate in Germany (28% and 27%, respectively). The prevalence of hypertension for the European average was 44.2% compared with 27.6% in North America.Hypertension treatment in the European countries was on average lower than in the North American countries. The rank order for the proportion of persons undergoing treatment with a BP lower than 140/90 mm Hg in the European countries was England, Italy, Germany, Finland, Sweden, and Spain; however, the variation was small, ranging from 5% to 9%. For the European countries, on average only 8% of hypertensive individuals had their condition controlled compared with 23% in Canada and the United States
1http://www.searo.who.int/entity/world_health_day/leaflet_burden_hbp_whd_2013.pdf. 2Prugger
C, Heuschmann PU, Keil U.Epidemiology of hypertension in Germany and worldwide,Herz. 2006 Jun;31(4):287-93. of hypertension in the elderly.Health Science JournalVOLUME 4, ISSUE 1
3FotoulaBabatsikou,AssiminaZavitsanou,Epidemiology
(2010)
(persons 35-64 years of age).The average mortality rate from stroke in the European countries was 41.2 per 100 000 population vs 27.6 per 100 000 in Canada and the United States4. In a large Spanish epidemiologic study over a 10-year period, investigators found that despite an increase in the intensity of hypertensive therapy, the prevalence of uncontrolled hypertension (systolic BP [SBP] ≤140 mm Hg and/or diastolic BP [DBP] ≤90 mm Hg) did not change significantly over time. In addition, there appeared to be worse control in at-risk individuals (SBP ≤130 mm Hg and/or DBP ≤80-85 mm Hg) who had comorbidities5. In England, 32% of men and 30% of women, aged 16 years or over, have hypertension.6 The equivalent figures for Scotland are 33% of men and 28% of women.20 There are no exactly comparable figures for Wales or Northern Ireland. However, 15% of adults in Wales reported being treated for high blood pressure. In Northern Ireland, 19% of men and 27% of women reported having been diagnosed with high blood pressure6. Until age 45 years, a higher percentage of men than women have hypertension; from age 45 years onward, the percentages are nearly equal between men and women. In women, those who use oral contraceptives, particularly obese and older women, have a 2- to 3-fold higher risk of hypertension than women not using these agents.Globally, black adults have among the highest rates of hypertension, with an increasing prevalence. Although white adults also have an increasing incidence of high BP, they develop this condition later in life than black adults and have much lower average BPs. In fact, compared to hypertensive white persons, hypertensive black individuals have a 1.3-fold higher rate of nonfatal stroke, a 1.8-fold higher rate of fatal stroke, a 1.5-fold higher mortality rate due to heart disease, and a 4.2-fold higher rate of end-stage renal disease (ESRD)7. There are several types of drugs used to treat high blood pressure, including: •
Angiotensin-converting enzyme (ACE) inhibitors
•
Angiotensin II receptor blockers (ARBs)
•
Diuretics
•
Beta-blockers
•
Calcium channel blockers
•
Alpha-blockers
•
Alpha-agonists
•
Renin inhibitors
•
Combination medications
4Katharina
Wolf-Maier, MD; Richard S. Cooper, MD; José R. Banegas, MD; SimonaGiampaoli, MD; Hans-Werner Hense, MD; Michel Joffres, MD, PhD; Mika Kastarinen, MD; Neil Poulter, MD, MSc; Paola Primatesta, MD, PhD; Fernando RodríguezArtalejo, MD; BirgittaStegmayr, MD, PhD; Michael Thamm, MD; JaakkoTuomilehto, MD, PhD; Diego Vanuzzo, MD; FeniciaVescio, MD, MSc, MFPHM,Hypertension Prevalence and Blood Pressure Levels in 6 European Countries, Canada, and the United States ,JAMA. 2003;289(18):2363-2369 5http://emedicine.medscape.com/article/241381-overview#a0156 6http://www.fph.org.uk/uploads/bs_hypertension.pdf 7http://emedicine.medscape.com/article/241381-overview#a0156
Diuretics are often recommended as the first line of therapy for most people who have high blood pressure8. Hypertension and diabetes mellitus are common diseases.In patients with either mild or more severe hypertension and in both type 1 and type 2 diabetes, the established practice of choosing an ACE inhibitor as the first-line agent in most patients with diabetes is reasonable. In patients with microalbuminemia or clinical nephropathy, both ACE inhibitors and ARBs are considered first-line therapy for the prevention of and progression of nephropathy. Comorbid conditions that influence the choice of antihyper- tensivetherapy.Thecomorbid conditions in hypertensive patients such as diabetes mellitus, coronary heart disease,cerebral vascular disease, dyslipidaemia,peripheral vascular disease,proteinuriaand renal insufficiency. VI.2.2
SUMMARY OF TREATMENT BENEFITS
Lsoartan is used for Treat high blood pressure (essential hypertension in adults and in children and adolescents 6-18 years of age). Protect the kidney in diabetic patients with both high bloob pressure and reduced kidney function. Treat heart failure when treatment with other medicines called Angiotensin converting enzyme (ACE) inhibitors is not considered suitable due to incompatibility, especially cough, or contraindication. Decrease the risk of a stroke in adults with high blood pressure and a heart condition that causes thickening of the walls of heart.
No additional studies were conducted as lsoartanAurobindois a generic medicine that is given by oral and contains the same active substance as the reference medicine. Because lsoartanAurobindois a generic, its beneficial treatment effects are taken as being the same as the reference medicine’s. VI.2.3
UNKNOWNS RELATING TO TREATMENT BENEFITS
There are limited data on the efficacy and safety of losartan in children and adolescents aged 6 -18 years old for the treatment of hypertension. Limited pharmacokinetic data are available in hypertensive children above one month of age.[eMCSmPC (2013)] VI.2.4
SUMMARY OF SAFETY CONCERNS
Risk Important identified risks Hyperkalaemia
What is known
Preventability
Electrolyte imbalances are common in patients with renal impairment, with or without diabetes, and should be
Physician supervision and care.
8http://www.webmd.com/hypertension-high-blood-pressure/guide/hypertension-treatment-overview
Hypotension
Foetotoxicity
Important potential risks Elevation of liver function values
Renal impairment
addressed. In a clinical study conducted in type 2 diabetic patients with nephropathy, the incidence of hyperkalemia was higher in the group treated with losartan as compared to the placebo group .Therefore, the plasma concentrations of potassium as well as creatinine clearance values should be closely monitored, especially patients with heart failure and a creatinine clearance between 30-50 ml/ min should be closely monitored. Symptomatic hypotension, especially after the first dose and after increasing of the dose, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. These conditions should be corrected prior to administration of losartan, or a lower starting dose should be used. This also applies to children 6 to 18 years of age. Exposure to AIIA therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) Liver function abnormalitieshave been reported in patients with losartan. As a consequence of inhibiting the rennin-angiotensin system, changes in renal function including renal failure have been reported (in particular, in
Physician supervision and care.
Physician supervision and care.
Physician supervision and care.
Physician supervision and care.
Hypersensitivity reactions incl. angioedema
Decrease in haemoglobin and/or hematocrit
Missing information Use in children < 6 years
Exposure during breast feeding
VI.2.5
patients whose renal function is dependent on the reninangiotensin-aldosterone system such as those with severe cardiac insufficiency or preexisting renal dysfunction). As with other medicinal products that affect the renninangiotensin-aldosterone system, increases in blood urea and serum creatinine have also been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; these changes in renal function may be reversible upon discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Angio-oedema. Patients with a history of angio-oedema (swelling of the face, lips, throat, and/ or tongue) should be closely monitored. In repeated dose toxicity studies, the administration of losartan induced a decrease in the red blood cell parameters (erythrocytes, haemoglobin, haematocrit).
Physician supervision and care.
Physician supervision and care.
There are limited data on the efficacy and safety of losartan in children and adolescents aged 6 18 years old for the treatment of hypertension .Limited pharmacokinetic data are available in hypertensive children above one month of age. Because no information is available regarding the use of losartan during breastfeeding, losartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.
Summary of additional risk minimisation measures by safety concern
Not applicable
VI.2.6
Planned post authorisation development plan
List of studies in post authorisation development plan Not applicable Studies which are a condition of the marketing authorisation None. VI.2.7
Summary of changes to the Risk Management Plan over time
Major changes to the Risk Management Plan over time Version 2.0
Date
Safety Concerns
Comment
11 December 2013
Version 01 is amended by including the safety concerns as per GVP Module V – Risk Management Systems as suggested by assessor
RMP is prepared in accordance with new EU format for RMP.