Inurec AMERICAN CRANBERRY IN THE PREVENTION OF URINARY INFECTION CHEWABLE TABLETS. Vaccinium macrocarpon

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1 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 1 Inurec IN THE PREVENTION OF URINARY INFECTION CHEWABLE TABLETS AMERICAN CRANBERRY Vaccinium macrocarpon -

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3 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 3 Inurec summary URINARY TRACT INFECTION 4 PATHOGENESIS OF URINARY INFECTION 5 Routes of invasion 5 Etiología de la infección urinaria. 5 Mechanism of Escherichia coli virulence 6 Risk factors for urinary infection 7 Treatment of urinary tract infection 9 AMERICAN CRANBERRY 10 with American cranberry 10 Mechanism of action of the American cranberry 11 Pharmacokinetics of American cranberry 12 Data security 13 Clinical Studies. 14 REFERENCES 16 19

4 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 4 URINARY TRACT INFECTION The recurrent urinary tract infection (ITUR) is very common and poses a therapeutic challenge. The incidence in men is low, with more frequent during childhood (due to urogenital malformations) and after 60 years (due to obstructive prostatic disease). In women, the incidence is higher, and well-defined situations, such as sexually active women, pregnant women, postmenopausal women, and patients with underlying urological and gynecological pathology, add a greater degree of difficulty in handling. A study in young women with urinary tract anatomically and functionally normal showed that, after the first urinary tract infection, 27% experienced at least one recurrence confirmed by urine culture, within 6 months after the first infection (1). The 2.7% of these had a second recurrence in the same period. When you compare the Escherichia coli with that produced by other bacterial agents (2), it is observed that the presence of E. Coli is a factor facilitating second relapse: This fact is clearly demonstrated in a Finnish study involving women whose age was between 17 and 82 years: the group that had urinary tract infection by Escherichia coli, 44% had recurrence in the following year (3). The classification of recurrent urinary tract infections in relapse and re-infection is essential to determine the diagnostic and therapeutic approach of these (4), so that: Relapses are usually caused by the same germ that the first infection, and usually occur within 2 weeks after the apparent cure of urinary tract infection. Re-infections are new urinary tract infections, caused by a different strain which caused the first UTI. In recurrent urinary tract infection in menopausal women, is added 4 very common conditions such as: a) urinary incontinence, b) presence of cystocele and urethrocele, c) presence of residual urine d) uterine prolapse. The residual urine is also observed in the first two cases. The residue favors infection by prolonging the contact of urine with the urothelium germs. Treatment and prophylaxis of ITUR represents complex, unwieldy reasons including the use of antibiotics, which is associated with resistance and side effects, particularly in long term treatments. The cranberry preventive administration is an effective alternative to prophylactic antibiotics in ITUR. 4

5 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 5 P ATH OGENES I S OF URINARY INFECTION Routes of invasion The majority of urinary tract infections are caused by an ascending, microorganisms from So eventually, these organisms may reach the bladder via ascending (90% of infections) adhering to the urethral epithelium. This colonization can be asymptomatic; generating what is called asymptomatic bacteriuria. When the microorganism attached to the epithelial tissue damage occurs, an infection occurs with the appearance of symptoms. Very rarely, can get through the blood. It is under discussion, that there is the possibility of colonization via the lymphatic system. Etiology of urinary tract infection The most common microorganisms causing urinary tract infections are Gram negative. Of these, the most common organisms are Escherichia coli, followed by Klebsiella, Aerobacter, Proteus, Pseudomonas aeruginosa and Acinetobacter. For hospitalized patients and carriers of Pseudomonas aeruginosa. Predominates urethral catheter.. - rococcus, Staphylococcus aureus and Streptococcus hemolíticus rarely. 5

6 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 6 P ATH OGENES I S OF URINARY INFECTION Virulence mechanism of Escherichia coli Bacterial virulence factors urinary tract infection, may produce only those bacteria endowed with a number of properties or virulence factors that confers the ability to adhere to the host and urothelium / or vaginal cells in women. All strains of Escherichia coli that cause urinary tract infection most belong to serogroup O, k, and H. (5, 6). receptors on epithelial cells. Fimbriae (or pillis) are peptide structures located in the bacterial cell wall, which made adherence to certain cell membrane receptors of the urothelium. functional and antigenic properties. May be Type I (inhibited by fructose and mannose sensitive) and type P (not inhibited by fructose, mannose-resisstrains (7, 8). Genetic Factors Non-secreting urothelial cells present in patients with blood group A, B, H, show a stronger adhesion uropathogens (Escherichia coli) compared with secretory cells. This bias is related to a located in urothelial cells (9). 6

7 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 7 OF URINARY INFECTION P A T H O G ENESIS Risk factors for urinary infection The unique anatomy of the female urethra, much shorter than the male, probably explains why UTI is more common in females. It has been found that in most cases, women with ITUR, infection is preceded by the presence of bacteria in urine. These bacteria come from the colonization of the introitus and perineal region, by microorganisms from the intestine and excreted in the feces. Sexual activity development of urinary tract infection, because the vaginal massage leads to dissemination of the microorganisms. In fact, with the onset of sexual intercourse in women starts the time when the risk of acquiring a urinary tract infection is higher (10). Factors related to sexual activity such as the number of relations in the last month before infection, the use of spermicide and partner change, are risk factors for acquiring an infection (11). During pregnancy primarily it is estimated that 4.7% of women infection, the clinical picture increases the likelihood of pregnancy complications (hypertension, toxemia gravidarum, eclampsia, etc.). (11). Genetic and family factors support predisposing infections presenting in adulthood when girls these women developed infections. Hygienic, nutritional, and other important risk factors - 7

8 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 8 P A T HOG ENESI S OF URINARY INFECTION Also an increased risk of urinary tract infection in diabetic patients, resulting in part to poor bladder emptying the medium. Besides urinary infection in diabetics causes complications in greater proportion than in the general population, so treating it is even more important. Patients with a neurogenic bladder, when the bladder does not empty properly due to a neurological condition. Patients with asymptomatic bacteriuria are common especially among the elderly and pregnant women, although the evolution of this disease is only unfavorable in pregnancy. In general, it is not necessary to apply antimicrobials, since in most patients with asymptomatic bacteriuria would promote the emergence of resistant strains. Patients with complicated urinary tract infections due to catheterization, instrumentation, urologic anatomic or functional anatomy, stones, obstruction, immunosuppressant, renal disease. These infections are usually caused by bacteria acquired in the hospital. Many strains are resistant to antibiotics. 8

9 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 9 OF URINARY INFECTION PATHOGENESIS ITUR Treatment Currently, treatment of urinary tract infections is based on antibiotics. For the prophylaxis of new antimicrobial infection prophylaxis is used continuously. We present a table with the main antimicrobial guidelines (Table I). In the scheme of continuous antibiotic prophylaxis, it is noted that the higher recurrence with trimethoprim regimen is associated with the development of resistance. In pregnant women post-coital strategy should consist of a single dose of 250 mg Nitrofurantoin or Kefloridina 50 mg (12). In menopausal women it has been suggested, as prophylaxis, Estriol intra-vaginal use to reduce ITUR. In a double-blind randomized placebo-controlled trial in 93 postmenopausal women with a history of ITUR, a high reduction in the incidence of ITUR in intra-vaginal application receiving estrogen compared with those who received placebo 5.9% vs. 0.5% episodes per patient-year p <0.001 (13). This study further demonstrated that topical application of estrogen increases the level of Lactobacilli in vagina and decreased vaginal ph and vaginal colonization of Escherichia coli. Table 1 - Outline of antimicrobial prophylaxis continues ITUR ESQU EMA DE PROFI L AXIS ANTIMICROBIANA POSTCOITAL PARA MUJ ERES CON ITU R ESQUEMAS DOSIS ITU Espectativa anual Trimetropim / Sulfa 40mg. / 200mg. 0,30 Trimetropim / Sulfa 80mg. / 400mg. 0,00 Nitrofurantoin 50 a 100mg. 0,10 Cefalexin 250mg. 0,03 Ciprofloxacin 125mg. 0,00 Norfloxacin 200mg. 0,00 Ofloxacin 100mg. 0,06 ESQU EMA DE PROFI L AXIS ANTIMICROBIANA POSTCOITAL PARA MUJ ERES CON ITU R ESQUEMAS DOSIS ITU Espectativa anual Trimetropim / Sulfa 40mg. / 200mg. 1 diario 0 a 0,20 Trimetropim / Sulfa 40mg. / 200mg. 3 semanal 0,1 Trimetropim 100mg. 1 diario 0 a 1,5* Nitrofurantoín 50mg. 1 diario 0 a 0,6 Nitrofurantoín 100mg. 1 diario 0 a 0,7 Ceflacor 250mg. 1 diario 0,1 Cefalexin 250mg. 1 diario 0,2 Norfloxacin 200mg. 1 diario 0 Ciprofloxacin 125mg. 1 diario 0 * high recurrence rates observed, are associated with resistance to trimethoprim The multitude of patterns used in the treatment and prophylaxis of ITUR reinforce the idea that it is not easy to manage the ITUR. In most cases, regular use of antibiotics leads to gastrointestinal intolerance, especially in long term treatment and the occurrence of fungal infections such as side effect. An alternative to prophylactic antibiotics in ITUR MANAGEMENT IS THE AMERICAN CRANBERRY, INUREC. 9

10 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 10 AMERICAN CRANBERRY The American Cranberry (Vaccinium macrocarpon) is a small berry, bright red, with an acid taste that comes from the east of America. The fruits have been traditionally consumed in juice and sauce by Native Americans as food and for medicinal purposes. The use of preparations of American cranberry for UTI started becoming popular in the 20s in the U.S. Since in preventing ITUR caused by Escherichia coli. Presently, research continues Vaccinium macrocarpon properties, which is indicative of the potential in the prevention of ITUR and improving urinary tract health. No doubt, antibiotics are the mainstay of treatment of urinary tract infections and prophylactic patterns. But its frequent adverse reactions and complications (resistance, fungal colonization, etc.) make it advisable preventive treatments based non-antimicrobial, such as the American cranberry. In the case of ITUR, an antibiotic treatment should be initiated being recommended a combination therapy with American cranberry throughout treatment. Children with ITUR Women who are sexually active with ITUR Pregnant with ITUR Menopausal Women ITUR Patients with underlying urological and gynecological Diabetics Injured core 10

11 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 11 Mechanism o f action of American cranberry cranberry in prevention of urinary tract infections. The theory proposed in 1923, according to which the mechanism of action is based on the ability of the American cranberry acidify the urine, is now dismissed. On the other hand, there has been no detection of bactericidal and bacteriostatic components in American cranberry, so rejecting a possible antimicrobial action (14, 15, and 16). However, from the American cranberry components (80% water, 10% carbohydrate and 10% of a mixture of proanthocyanidins (PAC) that are known to be primarily responsible for the prophylactic urinary tract. This structure gives the ability Nonstick action rather than mere physical obstacle in binding to complementary structures, appears to be mediated by changes on the bacteria (19, 20, 21) changes the shape of the bacteria (rod shaped to form In vitro 11

12 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 12 P harma c o kine tics of American cranberry After administration of American cranberry, anthocyanidins are absorbed and transported to the circulatory system pass intact into the urine. Anthocyanidins maximum levels are reached after 3-6 hours after ingestion of American cranberry. Anthocyanidins total recovery in urine after 24 hours is about 5% of the intake (22). In urine, has been observed after administration of 83 mg of PAC from American cranberry, nonstick activity persists for at least 8-10 hours (23, 24). These pharmacokinetic characteristics, which justify two divided doses dosage spread throughout the day, one night, this administration schedule allows PACs act all night on the urine accumulated in the bladder. Anti-adhesion Activity (%) pre Hours after ingestion Cranberry Juice Cocktail Apple Juice Purple Grape Juice Tea Dark Chocolate Fig.1. Detection of anti bacterial adhesion of human urine before and after consumption of cranberry juice containing PAC. Recorded the percent inhibition for a period of 8 hours. Phytochemistry Sep, 66 (18): bioactivity from micrograms of CAP / ml (23, 24). In the case of ITUR start a prophylactic treatment with cranberry once treated and controlled urinary infection, alone or concomitantly with antibiotics. 12

13 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 13 Dat a s e c u rit y The intake of American cranberry products at high doses and for long periods showed no serious except for those with nephrolithiasis (25): existing preliminary evidence that seem to indicate that American cranberry products might promote stone formation in the kidney, due to the presence of oxalates in the composition (26) mended not to administer high doses (27). - Preparations with American cranberry should not be administered with warfarin; to interact by inhibition of cytochrome P450 enzymes responsible for the metabolism of warfarin (28), resulting in increased bleeding. A clinical study showed that co-administration with cyclosporine produces a pharmacokinetic interaction, but no clinical interaction (14). 13

14 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 14 Scientific evidence clinical studies Fruit of the great interest that is awakening this product are underway that seek new trials continue to demonstrate the usefulness and effectiveness of the American cranberry in the prophylactic treatment of ITUR. We list some of the highlights: In a randomized, open, conducted in 150 Finnish women with previous UI, the administration of 50 ml of cranberry juice concentrate (7.5 g) reduced the incidence of recurrence from 39 to 16%, while the administration of 100 ml of a preparation containing Lactobacillus was ineffective (29) Porcentaje Cranberry Lactobacillus Control Months Fig. 2. Ratio ITUR accumulated during the 12 months following treatment with American cranberry juice (6 months), Lactobacillus drink GC (12 months), or no treatment. The frequency of UTI in the cranberry group American is significantly lower. BMJ 2001; 322:1571. In a clinical study (30) in which prospective showed statistically significant differences in the reduction in patients taking ITUR American cranberry, regarding those who did not have an intake, observing a reduction in bacteriuria and pyuria 50% in patients who took cranberry extract than the other group. In the Cochrane review, 2009, Preventing Cranberries for urinary tract infections (31), ten studies with 1049 patients were included, 5 parallel and 5 crossed groups. 14

15 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 15 clinical studies Two included women with recurrent UTI (32, 33) One included women with symptomatic UTI (29) Three studies evaluated cranberry juice for the prevention of UTI in the elderly (30, 34, 35) with neurogenic bladder (36, 37) spinal cord injury (38,39). tract infections. preventing relapse of ITUR. Use instead of antimicrobial cranberry may reduce the risk of developing resistance to antibiotics. the American cranberry in prevention of urinary tract infections. Farmasierra Laboratories has developed and presented INUREC, chewable tablets; a product based American cranberry extract with a high concentration of proanthocyanidins (PAC 120 mg 2 tablets) for the prevention and concomitant recurrent urinary tract infections. 15

16 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 16 bibliography 1. Foxman, B. Recurring urinary tract infection: incidence and risk factors. Am J Public Health 1990;80: Foxman, B,Gillespie,B,Koopman,J,et al.risk factors for second urinary tract infection among college women. Am J Epidemiol 2000;151: Ikaheimo,R, Siitonen,A,Heiskanen,T,et al.recurrence of urinary tract infection in a primary care setting: análisis of a 1-year follow-up of 179 women. Clin infect Dis1996;22:91 4. Pigrau-Serrallach,C.Infecciones urinarias recurrentes. Enferm Infecc Microbiol.2005;23: Orskov,I,Orskov F, Birch-Andersen,A.O,K,H and fimbrial antigens in Escherichia coli serotypes associated with pyelonephritis and cystitis. Scand J Infect Dis Suppl1982;33: Johnson JR, Orskov F, O,K, and H antigens predict virulence factors, carboxylesterase B pattern, antimicrobial resistance, and host compromise among Escherichia coli strains causing urosepsis. J Infect Dis Jan; 169(1): Otto G, Sandberg T, Marklund BI, Ulleryd P, Svanborg C. Virulence factors and pap genotype in Escherichia coli isolates from women with acute pyelonephritis, with or without bacteraemia. Clin Infect Dis Sep ; 17(3) : J,A. Delgado Martin,J.Blazquez Izquierdo,A Gomez Vegas. La infeccion urinaria recurrente en urologia:pautas diagnosticas y terapéuticas.ucm,madrid 1997; Cordon Cardo C, Lloyd KO, Finstad CL. Immunoanatomic distribution of blood group antigens in the human urinary tract. Influence of secretor status.lab Invest.1985;55: Hooton TM, Scholes D, Hughes JP, Winter C, Roberts PL, Stapleton AE, Stergachis A, Stamm WE A prospective study of risk factors for symptomatic urinary tract infection in young women N Engl J Med Aug 15;335(7): C.Hernández Fernández,F.Verdu Tartajo, A.de Palacio España.urgencias urologicas Servicio de Urologia del Hospital General Universitario Gregorio Marañon de Madrid ;1996 : Phau,A,Sacks,TG.Effective prophylaxis for recurrent urinary tract infections during pregnancy.clin Infect Dis 1992;14: Raz R AControlled Trial of Intravaginal Estriol in Postmenopausal women with Recurrent Urinary Tract Infections. N Engl J Med.1993;329: Nowack, Rainer; Schmitt, Wilhelm. Cranberry juice for prophylaxis of urinary tract infections - conclusions from clinical experience and research., Phytomedicine Sep;15(9): Denise P.S. Leitão, Ana Cristina M. Polizello, Izabel Y. Ito, Augusto César C. Spadaro. Antibacterial Screening of Anthocyanic and Proanthocyanic Fractions from Cranberry Juice. Journal of Medicinal Food. Spring 2005, 8(1): Monroy-Torres R, Macias AE. Does cranberry juice have bacteriostatic activity? Rev Invest Clin May-Jun;57(3):

17 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 17 bibliography 17. B. Howell, N. Vorsa, A. Der Marderosian, L. Y. Foo: Inhibition of the adherence of ated Escherichia coli to uroepithelialcell surfaces by proantho-cyanidin extracts from cranberries. New England Journal of Medicine 339 (1998), págs B. Howell, J. D. Reed, B. McEniry, C. G. Krueger, D. G. Cunningham: Bacterial anti-adhesion activity of cranberry vs. other foods. American Chemical Society National Meeting Sobota AE. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol May;131(5): Ahuja S, Kaack B, Roberts J. Loss of adhesion with the addition of Vaccinum macrocarpon to the growth medium of P ated Escherichia coli. J Urol Feb;159(2): Liu Y, Black MA, Caron L, Camesano TA. Role of cranberry juice on molecular-scale surface characteristics and adhesion behavior of Escherichia coli. Biotechnol Bioeng Feb 5;93(2): Ohnishi R, Ito H, Kasajima N, Kaneda M, Kariyama R, Kumon H, Hatano T, Yoshida T. Urinary Excretion of Anthocyanins in Humans after Cranberry Juice Ingestion. Biosci Biotechnol Biochem Jul;70(7): Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M. A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity. Phytochemistry Sep;66(18): Howell AB, Foxman B. Cranberry Juice and Adhesion of Antibiotic-Resistant Uropathogens. JAMA / volume:287 (page: 3082) June 19, Terris MK, Issa MM, Tacker JR. Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis. Urology Jan;57(1): Gettman MT, Ogan K, Brinkley LJ, Adams-Huet B, Pak CY, Pearle MS. E ect of cranberry juice consumption on urinary stone risk factors. J Urol Aug;174(2):590-4; quiz Guay DR. Cranberry and urinary tract infections. Drugs. 2009;69(7): Suvarna R, Pirmohamed M, Henderson L. Possible interaction between warfarin and cranberry juice. BMJ Dec 20;327(7429): Kontiokari, T, Sundqvist,K,Nuutinen, M.Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001; 322: Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. A. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA Mar 9;271(10): Jepson RG, Craig JC: Cranberries for preventing urinary tract infections.cochrane Datebase of Systematc Reviews Stothers L. A randomized trial to evaluate e ectiveness and cost e ectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Canadian Journal of Urology 2002; 9(3):

18 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 18 bibliography 33. Walker EB, Barney DP, Mickelsen JN, Walton RJ, Mickelsen RA Jr.Cranberry concentrate: UTI prophylaxis [letter]. Journal of FamilyPractice 1997; 45(2): Haverkorn MJ, Mandigers J. Reduction of bacteriuria and pyuria using cranberry juice [letter]. JAMA 994; 272(8): McMurdo ME, Bissett LY, Price RJ, Phillips G, Crombie IK. Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind placebo controlled trial. Age & Ageing 2005; 34(3): Foda MM, Middlebrook PF, Ga CT, Potvin G, Wells G,Schillinger JF. E of cranberry in prevention of urinary tract infection in a susceptible pediatric population. Canadian Journal of Urology 1995; 2(1): Schlager TA, Anderson S, Trudell J, Hendley JO. E ect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization. Journal of Pediatrics 1999; 135(6): Linsenmeyer TA, Harrison B, Oakley A, Kirshblum S, Stock JA, Millis SR. Evaluation of cranberry supplement for reduction of urinary tract infections in individuals with neurogenic bladders secondary to spinal cord injury.a prospective, double-blinded, placebocontrolled, crossover study. Journal of Spinal Cord Medicine 2004; 27(1): Waites KB, Canupp KC, Armstrong S, DeVivo MJ. E ect of cranberry extract on bacteriuria and pyuria in persons with neurogenic bladder secondary to spinal cord injury. Journal of Spinal Cord Medicine 2004; 27(1):

19 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 19 DEFINITIONS BACTERIURIA: the presence of bacteria in the urine. BACTERIURIA ASYMPTOMATIC: The presence of bacteria in the urine that occurs without usual symptoms such as burning during urination or frequent urination. SIGNIFICANT BACTERIURIA: when the number of bacteria is greater than 100,000 per ml of urine. PYURIA: detection of more than 10 cells per mm3 or un-centrifuged urine over 5 leukocytes per field in centrifuged urine. POLAQUIURIA: increased frequency, which is generally low urine volume per micturition. URINARY INFECTION (UTI) : infection caused by microorganisms that affects the urinary system. Classically presupposes the discovery of significant bacteria in urine high titles: more than 100,000 colonies / ml. However, this is not exclusive and that in some situations the titles found are low. FIMBRIA: bacterial wall structure responsible for the adherence of bacteria to the uroepithelium. RELAPSE: recurrence, relapse or re-infection from an illness. RECURRING URINARY INFECTION ITUR: are defined as 3 episodes of urinary tract infections (UTI) in the last 12 months or 2 episodes in the last 6 months. AMERICAN CRANBERRY (Cranberry, Vaccinium macrocarpon): dwarf shrub with stems 10 cm or less, fine, small evergreen leaves and dark pink flowers. The fruit is a berry that is, larger than those of the leaves, initially white, which turns a deep red when ripe. Native North America. PAC (PROANTHOCYANIDINS): American cranberry components. Polyphenolic flavonols are stable, consisting of catechin and epicatechin oligomers. The oligomers are joined by a link type A, which differentiates CAP structurally from other fruits. 19

20 FOLLETO INUREC :FOLLETO INUREC /07/11 16:02 Página 20 cranberry Composition Active ingredient: concentrated extract of American cranberry (Vaccinium macrocarpon) containing 60 mg of proanthocyanidins (PAC). Excipients: mannitol, isomalt, and neohespiridina. Both the composition in active substances and excipients used in the formulation, are free of gluten and lactose, so we can say that people with gluten intolerance and lactose, can take INUREC. INUREC is suitable for diabetics. Main action Proanthocyanidins (PAC) American cranberry prevent pathogenic bacteria (primarily E. coli), is secured to the through the urine, and preventing them from causing infection. The American cranberry action is dose-dependent, so that the more concentrated, more action exerted, a higher concentration of proanthocyanidins (PAC) produced a greater inhibition of the adherence of Escherichia coli. Indications Contributes to decreased binding of bacteria to the wall of the urinary tract, which promotes good urinary tract health. Posology Recommended 2 tablets daily for a minimum period of 3-6 months and may be prolonged administration. One of the tablets will be administered preferably in the evening; INUREC allows taken without water, to avoid excessive consumption of water before bed, reduces the frequency of nocturnal mictions. Contraindications No contraindications. Avoid concurrent use of American cranberry with warfarin (anticoagulant). gastrointestinal disorders). It is therefore ideal as long-term treatment to prevent relapse of urinary tract infections. Presentations facilitates administration in people with swallowing problems. Allows administration without drinking water.