O. Rossi

ANTISTAMINICI UN CARDINE DELLA TERAPIA
DELLE MALATTIE ALLERGICHE
I COSTI DELL’ ALLERGIA
sono in costante incremento
In
Europa,
il
costo
dell’allergia è stato stimato
in 100 miliardi di €/anno
EU Summit Report, 2008
Gli antistaminici anti-H1 orali di II generazione sono i farmaci
di I linea raccomandati dalle Linee Guida per la Rinite allergica
e l’Orticaria
2014
( REVISIONE ANNUALE )
RINO-CONGIUNTIVITE
ALLERGICA E ORTICARIA
PATOLOGIE MOLTO COMUNI IL CUI CONTROLLO CLINICO
RISULTA FREQUENTEMENTE UN OBBIETTIVO NON RAGGIUNTO
RINITE ALLERGICA: ENTITÀ DEL FENOMENO
PROBLEMA SANITARIO
GLOBALE
10-50%
COSTI SOCIO
SANITARI
RILEVANTI
RINITE
ALLERGICA
INFLUISCE
FORTEMENTE
SULLA QUALITÀ
DELLA VITA
ARIA 2014
RAPPRESENTA UN
FATTORE DI
RISCHIO PER ASMA
BRONCHIALE
E’ SPESSO UNA
COMORBIDITA’ DELL’
ASMA E NE CONDIZIONA
IL CONTROLLO CLINICO
LA RINITE ALLERGICA : «REAL LIFE»
Largo ricorso al «fai da te» (prodotti
da «banco», decongestionanti nasali,
terapie della medicina “alternativa”, ecc.)
Il medico di medicina generale viene
consultato solo dal 40% dei pazienti con
rinite allergica.
Il paziente richiede un
consulto allergologico, solo
nel 10 % dei casi
Il medico di medicina
generale invia il paziente
dallo specialista allergologo
otorino nel 20-25 % dei
casi
Un report dell’OMS segnala che nei
paesi sviluppati, in media il 50%
dei pazienti non assume le medicine
come prescritto.
Allergy 2008,63,1008-1014
World Health Organization.. adherence to long-term therapies: evidence for action. 2003
LA RINITE ALLERGICA : «REAL LIFE»
MAGGIO 2014
« TERAPIA DELLE ACQUE »
La produzione di istamina diminuisce con l’aumento dell’assunzione
giornaliera di acqua. “Dal legame tra l’istamina e il nostro metabolismo
dell’acqua si è osservato che le persone con allergie reagiscono
positivamente, in media entro un lasso di tempo che va da una a
quattro settimane, alla regolazione idrica del corpo”
%
2.330 patients (88.3%) of 2.638 adults
9
10
10
Quali sono i fattori che contribuiscono al mancato
controllo della rinite
Allergy 68 (2013) 1–7
RINITE ALLERGICA
Migliorare l’appropriatezza del trattamento
e l’aderenza
© 2013 PROGETTO
LIBRA •
11
GLI SPECIALISTI SEGUONO LE LINEE-GUIDA?
Methods: All (598) Belgian Otorhinolaryngologists were invited to complete a
questionnaire, covering demographic and professional characteristics, knowledge, use
and perception of the ARIA guidelines and 4 clinical case scenarios of AR.
Results: Of the 258 (44%) Belgian Otorhinolaryngologists who participated, almost 90%
had ever heard about ARIA and 64% had followed a lecture specifically dedicated to the
ARIA guidelines. Furthermore, 62% stated to always or mostly follow the ARIA
treatment algorithms in the daily management of AR patients.
In the clinical case section, adherence to the ARIA guidelines raised with increased
self-reported knowledge and use of the ARIA guidelines and among participants that
considered the guidelines more userfriendly. Of the respondents, 51% were considered
12
as good compliers. Younger age was a significant
predictor for good compliance.
Rhinology. 2010;48(1):28-34
ORTICARIA : IMPATTO CLINICO
Il 15-25% della popolazione ha avuto almeno un episodio di orticaria nel corso della vita
Orticaria :Classificazione
Curr Opin Allergy Clin Immunol 2012, 12:406–411
Chronic
ChronicUrticaria
Urticariaisisaarather
ratherfrequent
frequentdisease
diseasewith
withan
anestimated
estimated
prevalence
prevalenceofof0.5–1%
0.5–1%
Clin
ClinRev
RevAllergy
AllergyImmunol
Immunol33:134–143
33:134–1432007
2007
Persistenza orticaria cronica
Condizione clinica invalidante
Allergy 2004: 59: 869–873
Il 70% dei pazienti con CU
continuano ad avere sintomi
dopo un anno .
E NEL 43 % DOPO TRE ANNI
Persistenza orticaria cronica
Condizione clinica invalidante
• > 6 mesi: 50%
• > 10 anni: 20%
In Europe alone, more than five million people suffer
from persistent urticaria symptoms which severely
impair quality of life, with negative effects on sleep,
daily activities, school/work life and social
interactions. Reductions in quality of life similar
to patients with heart disease
Maurer et al., Allergy 2011
Metz et.al .Journal of Dermatological Science 2013
ORTICARIA CRONICA : IMPATTO SULLA QUALITA’
DELLA VITA E SUI COSTI
Annual Direct and Indirect Health Care Costs of Chronic Idiopathic Urticaria
Arch Dermatol. 2008;144(1):35-39.
Perdita della produttività
→ Riduzione del 25%-30% della
produttività lavorativa/scolastica
O'Donnell et al. Br J Dermatol. 1997;136:197.
Thompson et al. J Am Acad Dermatol. 2000;43:24.
Persistenza orticaria cronica
Trattamento antistaminico protratto
Continuing treatment over 3 years in
50% of the patients who experienced
a very severe onset of urticaria
In more than 50% of the patients, symptoms
persist with standard dosing of antihistamines
ORTICARIA
AllergyPIU’
2004;59:869–873.
NECESSITA’ DI ANTISTAMINICI
EFFICACI E SICURI
ORAL ANTIHISTAMINES: EVOLUTION TIMELINE
First-generation
Second-generation
Newer agents
<1970
1980s
Cetirizine
1987
Ebastine
1992
Hydroxyzine
Diphenhydramine
Chlorpheniramine
Terfenadine
1979
1990s
Loratadine
1987
Fexofenadine
1995
2000+
Desloratadine
2002
Levocetirizine
2002
Bilastina
2011
Rupatadina
2007
Anti-histaminic effect
Anti-cholinergic effect
Sedative effect
(J Allergy Clin Immunol September 2014;134:530-44.
•
It has recently been shown that a combination of antihistamines
targeting H1R and H4R has synergistic therapeutic effects in a
mouse model of chronic dermatitis.
A mouse
thatcan
a combination
of H4
• At model
high doses,suggests
H1-antihistamines
also reduce MC functions,
as MC stabilizers.
and H1acting
receptor
antagonism might be a new strategy
to treat pruritus related to allergic diseases.
Exp Dermatol 2009;18:57-63.
OMALIZUMAB: EFFICACIA E SICUREZZA D’IMPIEGO NEL
PAZIENTE CON CSU
Maurer M, et al. NEJM 2013;368(10):924935
ORAL ANTIHISTAMINES: EVOLUTION TIMELINE
Non tutti gli antistaminici sono uguali
H1 antihistamines have been used
for treatment of allergic rhinitis
for more than 5 decades.
They differ in :
•Chemical structure
•Pharmacokinetics
•Pharmacodynamics
•Clinical efficacy
•Onset of action
•Adverse effects
E.A.A.C.I. (European Academy of Allergy and Clinical Immunology)
A.R.I.A. (Allergic Rhinitis and its Impact on Asthma)
Allergy 2008; 63 (Suppl 86):8-16 ; Allergy 2003; 58: 192; Allergy 2006; 61:1086-1096
ANTISTAMINICI : AFFINITA’ RECETTORIALE
Legame al recettore H1 vs cetirizina e fexofenadina
nel cervelletto di cavia
Antagonista
anti-H1
Ki (nM)
Bilastina
44
Cetirizina
143
Fexofenadina
246
Ki: costante di inibizione, che denota l’affinità di un ligando per un
recettore
L’affinità di bilastina per il recettore H1 è rispettivamente 5 e 3 volte maggiore di
quella di fexofenadina e cetirizina
Maggiore affinita’ recettoriale
Maggiore attivita’ antistaminica ed efficacia clinica
Corcóstegui R. et al.; Drugs R D 2005; 6 (6): 371-384; Bachert C Allergy 2010; 65 1-13
ANTISTAMINICI : AFFINITA’ RECETTORIALE
BILASTINA
CETIRIZINA
Bilastine : H1 mixed antagonist
•competitive up to 33 Nm
•not competitive from 100 nM
•Competitive antagonist : 5.5 times more powerful than cetirizine
•noncompetitive antagonist : 10 times more powerful than
cetirizine
•In vivo studies in rats demonstrated a significant reduction in
histamine-stimulated endothelial permeability, microvascular
extravasation, and inhibition of smooth muscular contraction and
bronchospasm
11 times that of cetirizine
Orcóstegui R, et al. Preclinical pharmacology of bilastine, a new selective histamine H1 receptor
antagonist: receptor selectivity and in vitro antihistaminic activity. Drugs R D. 2005;6:371–84.
Corcóstegui R, et al. In vivo pharmacological characterisation of bilastine, a potent and selective
histamine H1 receptor antagonist.
Drugs R D. 2006;7:219–31.
ANTISTAMINICI : MECCANISMI D’AZIONE
ANTI-H1
ISTAMINA
Agonista inverso
ASSETTO
CONFORMAZIONALE
INATTIVO
CONTRAZIONE
FIBRE MUSCOLARI
R-H1
PERMEABILITA’
VASALE
PRODUZIONE
MUCO
PRURITO
Amplificazione istaminodipendente via NF-kB
IL-1; IL-4; IL-8;
GM-CSF; TNF-
ASSETTO
CONFORMAZIONALE
INATTIVO
R-H1
In: Romagnani S, Matucci A, Rossi O:
ASMA BRONCHIALE – Ed. S.E.E.
Firenze 2004
IkB NF-kB
Bachert C Allergy 2010; 65 1-13
VCAM-1; ICAM-1
EOTASSINE
F
L
O
G
O
S
I
A
C
U
T
A
F
L
O
G
O
S
I
C
R
O
N
I
C
A
RINITE ALLERGICA PERSISTENTE E
ORTICARIA CRONICA : COMPLESSI MECCANISMI
PATOGENETICI
RINITE ALLERGICA PERSISTENTE E
ORTICARIA CRONICA : COMPLESSI MECCANISMI
PATOGENETICI
Adapted from Pawankar R et al. Curr Opin Allergy Clin Immunol 2012;2:1-5.
RINITE ALLERGICA PERSISTENTE E
ORTICARIA CRONICA : COMPLESSI MECCANISMI
PATOGENETICI
Orticaria cronica: non solo mastociti
«Ruolo degli eosinofili»
Chronic urticaria may have infiltration of eosinophils
and/or neutrophils without evidence of vasculitis.
Ambiente extra-cellulare
citoplasma
ANTISTAMINICI
V
IkB
Inibisce la sforilazione
di I kBNon distacco da NF-kB
nucleo
Blocco di NF-kB
Non trascrizione del gene
DNA
In: Romagnani S, Matucci A, Rossi O:
ASMA BRONCHIALE – Ed. S.E.E. Firenze 2004
Corcóstegui R, et al. Drugs R D. 2006;7:219–31.
Riduzione di TNF-; IL-1, IL-4
GM-CSF; ICAM-1; VCAM-1;
EOTASSINA
INIBIZIONE FLOGOSI
ALLERGICA
ANTISTAMINICI : EFFETTO IMMUNOMODULANTE
(J Allergy Clin Immunol 2001;107:81-6.)
Venom immunotherapy is known to be highly effective
profound changes in T-cell reactivity are observed during BVIT: T-cell
proliferation after allergen stimulation is strongly reduced, and cytokine
secretion by TH2 cells is downregulated.
It has been reported that terfenadine specifically inhibits TH2 cytokine secretion
from human peripheral T-cell cultures in vitro. This indicates that H1 receptors
are also involved in the modulation of the T-cell response
In conclusion, these results indicate that antihistamine premedication does not reduce
but may rather enhance the effectiveness of BVIT.
This finding might be of considerable interest, especially if confirmed during IT for
other IgE-mediated allergies like asthma or allergic rhinitis caused by pollen, mites,
or animal dander.
ANTISTAMINICI : EFFETTO IMMUNOMODULANTE
(J Allergy Clin Immunol 2008;122:1001-7.)
Premedication with antihistamines in the early phase of
immunotherapy remains very valuable by increasing safety and
preventing dropouts, especially
during BVIT.
This study also demonstrates that continuous administration of an H1
antagonist effectively modulates Histamine Receptor expression in
specific T cells.
The clinical and immunologic effect of antihistamine preventive
medication results from regulation of the immune response through
allergen-specific T-cell tolerance and activation of HR-dependent
pathways.
Efficacia clinica degli antistaminici anti-H1
Journal of Allergy and Clinical Immunology 128, 6, 2011, 1139–1150.e4
Efficacia clinica degli antistaminici anti-H1
Gli antistaminici anti-H1 agiscono direttamente sui recettori H1
periferici nelle terminazioni nervose e nei piccoli vasi
Rinite allergica
Orticaria
↓starnuti
↓secrezione e prurito nasale
↓prurito
↓numero, dimensioni e
durata dei pomfi e
dell’eritema
↓ lacrimazione
↓ prurito, eritema ed edema
oculari
Simons FE , J Allergy Clin Immunol 2011; 128:1139-50
Simons FE NEngl J Med 2004; 2004;351:2203-17
BioMed Research International 2013
Bilastine is efficacious in all nasal symptoms including obstruction
and in eye symptoms in patients with allergic rhinoconjunctivitis.
Bilastine as a potential treatment in allergic
rhinitis
American Journal of Rhinology & Allergy 28, 4, 28
July/August 2014, pp. 312-316(5)
Conclusion:
•Bilastine is a novel H1 antihistamine with anti-allergic properties
which is highly effective in the treatment of symptoms of allergic
rhinitis.
• It has a favorable pharmacokinetic and pharmacodynamics profile
and is generally well tolerated.
RAPIDITA’ D’AZIONE DELLA BILASTINA
During the 4 h of exposure of asymptomatic SAR subjects to grass pollen following medication, bilastine
20 mg provided statistically significant protection against the development of nasal symptoms, as
assessed with TNSS, when compared to placebo. Bilastine began to be significantly effective 1 h after
administration. That it was also significantly effective between 22 and 26 h after drug ntake indicates
that its duration of activity is at least 26 h after administration.
Similar results were obtained with cetirizine 10 mg. Although the effects of bilastine and fexofenadine
120 mg were similar during the first 4 h after administration, bilastine and cetirizine were significantly
more effective than fexofenadine between 22 and 26 h after drug intake suggesting bilastine to have a
longer duration of action
Bilastina 20 mg ha un’azione rapida (< di 1 ora) e duratura
(maggiore di 26 ore) sui sintomi della RAS
Horak F. et al.; Inflamm Res 2010; 59 (5): 391-398
BILASTINA : EFFICACIA CLINICA
BILASTINA
CETIRIZINA
Conclusions
Bilastine 20 mg once daily was significantly superior to
placebo and comparable to cetirizine 10 mg in relieving
symptoms of SAR, although it demonstrated a
significantly better AE profile than cetirizine
Rupatadine in Allergic Rhinitis
Review
EFFICACY AND SAFETY OF RUPATADINE FOR ALLERGIC
RHINO-CONJUNCTIVITIS: A SYSTEMATIC REVIEW OF
RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED
STUDIES WITH META-ANALYSIS
E. Compalati, G. W. Canonica
Allergy 2013, 29, 11 , 1539-1551
Randomized double-blind controlled trials show a favorable
risk–benefit ratio in rupatadine for the treatment of allergic
rhino-conjunctivitis. This evidence is strengthened when data
are pooled in the form of meta-analysis, where accurate and
robust effect estimations are derived from a large population.
ANTISTAMINICI IN PEDIATRIA
Pediatr Allergy Immunol 2013:24: 144–150.
360 patients between 6 and 11 yr with a diagnosis of PER according to
ARIA criteria were randomized to receive either rupatadine (180 pts) oral
solution (1 mg/ml) or placebo (180pts) over 6 wk. The primary efficacy
end-point was the change from baseline of the total nasal symptoms score (T4SS)
after 4 wk of treatment.
CONCLUSIONS:
Rupatadine oral solution (1 mg/ml) was significantly more effective than
placebo in reducing nasal symptoms at 4 and 6 wk and was well
tolerated overall. This is the first large clinical report on the efficacy of
an H1 receptor antagonist in children with PER in both symptoms and
quality of life.
ORTICARIA CRONICA :
TRATTAMENTO
2014
BILASTINA : EFFICACIA CLINICA NELL’ORTICARIA
Allergy 65 (2010) 516–528
Results:
Bilastine reduced patients’ mean reflective and instantaneous
TSS from baseline to a significantly greater degree than placebo
(P < 0.001); from day 2 onwards of treatment. The DLQI,
general discomfort, and sleep disruption were also improved
significantly in bilastine-treated patients as compared with
placebo treated patients (P < 0.001 for all parameters).
Conclusions:
Bilastine 20 mg is a novel effective and safe treatment option
for the management of CU.
BILASTINA : SICUREZZA ED EFFICACIA CLINICA
NELL’ORTICARIA
Bilastine for the treatment of urticaria
Drug Evaluations 2013, Vol. 14, No. 11,1537-1544
This article reviews the medical literature on the effectiveness and
safety of bilastine in urticarial syndromes, either spontaneous or
inducible, by means of a Medline search from 1990 to present,
completed with some nonpublished data provided by the
Profilo di sicurezza di Bilastina migliore
manufacturer.
rispetto
a Levocetirizina
Expert
opinion:
Once-daily treatment with bilastine 20 mg is effective in managing
symptoms and improving patient's quality of life in chronic
urticaria, with at least comparable efficacy to levocetirizine.
Bilastine's safety profile is adequate, appearing to be entirely free
from cardiovascular effects, and not impairing psychomotor
performance or actual driving, even at twice the therapeutic dose.
Rupatadina
Proprietà anti-allergiche aggiuntive
ANTISTAMINICI : « SICUREZZA »
ANTISTAMINICO
«IDEALE»
-assenza di sedazione
-non provocare alterazioni
cognitive o psicomotorie
-assenza di effetti anticolinergici
-possibilità d’impiego
durante la gravidanza e
l’allattamento…
Effetti indesiderati degli antistaminici di prima generazione:
Scarsa selettività recettoriale, permeabilità della membrana
ematoencefalica
Antistaminici
(J Allergy Clin Immunol 2011;128:1139-50)
In caso di
sovradosaggio
© 2013 PROGETTO
LIBRA •
45
Bilastina : La sicurezza
«studi preclinici in vitro»
Bilastina è altamente selettiva per i recettori H1
Bilastine has a high specific affinity for the H1-receptor but it
has no or very low affinity for 30 other tested receptors
I modelli in vitro hanno mostrato come Bilastina:
– non si lega agli altri recettori per l’istamina (H2, H3 e H4)
– La molecola presenta una elevata affinità per i recettori H1
periferici mentre è priva di affinità per i recettori
muscarinici
Alta selettività per recettore H1
Minori effetti collaterali
Corcóstegui R. et al.; Drugs R D 2005; 6 (6): 371-384; Church MK Expert Opin Drug Saf. 2011 Sep;10(5):779-93
ANTISTAMINICI « ALCOL»
E CAPACITA’ DI GUIDA
British Journal of Clinical
PharmacologyAccepted Articles Accepted
manuscript online: 15 MAY 2014
Bilastine vs.Hydroxyzine: Occupation of Brain
Histamine H1 Receptors Evaluated by Positron
Emission Tomography in Healthy Volunteers
A close correlation exists between positron emission
tomography(PET)-determined histamine H1-receptor occupancy
(H1RO) and the incidence of sedation. Antihistamines with HRO
<20% are classified as nonsedating. The objective was to
measure H1 RO of bilastine, a new second-generation
antihistamine, compared with that of hydroxyzine
A single oral dose of bilastine 20 mg had minimal H1RO, was not
linked with subjective sedation or objective impairment of
psychomotor performance, and was devoid of treatment-related
sedative AEs, thus satisfying relevant subjective, objective, and
PET criteria as a nonsedating antihistamine
Bilastina + Alcol non altera le capacità
psicomotorie e di guida
Hum. Psychopharmacol Clin Exp 2014;29: 120 –13
This clinical trial compared the psychomotor and sub-jective effects of acute
alcohol (0.8g/kg) taken alone or together with a single concomitant intake of
hydroxyzine 25mg, cetirizine 10mg, or two doses of bilastine (20mg and
80mg) versus placebo, in healthy volunteers and in laboratory conditions.
Conclusion
Concomitant administration of bilastine (at therapeutic dose) and alcohol does not
produce greater central nervous system depressant effects than ACL alone
Bilastina e Rupatadina
Buon profilo di sicurezza cardiovascolare
Studi in volontari sani hanno
dimostrato che Bilastina non
causa nessun prolungamento
significativo del QTc anche a
dosi fino a 10-11 volte quella
terapeutica
Durante gli studi clinici di fase II e
fase III l’incidenza di eventi avversi
cardiaci è stata dello 0.69% (vs
0.81% del placebo), non vi sono
stati report di significative
alterazioni ECG o di torsione di
punta
RCP; Church MK Expert Opin Drug Saf. 2011 Sep;10(5):779-93; Tyl B et al; J Clin Pharmacol. 2012 Jun;52(6):893-903.
SICUREZZA ANTISTAMINICI IN GRAVIDANZA
Large-scale analysis to examine a range of antihistamine products ( 1st and 2nd
generation) in relation to a range of major malformations and employed Bayesian
methods.
Overall, the results were consistent with a lack of association of birth defects with
the use of antihistamines during early pregnancy.
CONCLUSIONS:
CONCLUSIONS:
The
results
of
this
study
generally
The results of this study generallywere
wereconsistent
consistentwith
withno
noassociation
associationbetween
between
birth
defects
and
antihistamine
use
during
early
pregnancy
birth defects and antihistamine use during early pregnancy
WHICH
WHICHDRUGS
DRUGSARE
AREDANGEROUS
DANGEROUSTO
TOAAFETUS,
FETUS,AND
ANDWHICH
WHICHARE
ARENOT
NOT??
•
•
•
•
•
Pregnancy category “A” medications are medications in which there are good studies
in pregnant women showing the safety of the medication to the baby in the first
trimester. There are very few medications in this category, and no asthma medications.
Category “B” medications show good safety studies in pregnant animals but there
are no human studies available.
Pregnancy category “C” medications may result in adverse effects on the fetus when
studied in pregnant animals, but the benefits of these drugs may out weight the
potential risks in humans.
Category “D” medications show clear risk to the fetus, but there may be instances in
which the benefits outweigh the risks in humans.
Category “X” medications show clear evidence of birth defects in animals and/or
human studies and should not be used in pregnancy.
THE FDA HAS PROPOSED A
CLASSIFICATION OF DRUGS
BASED ON RISKS FOR THE
MOTHER AND THE FETUS. THE
CATEGORY A AND B ARE AT
LOWER RISK FOR BOTH 52
BILASTINA IN GRAVIDANZA
Preclinical toxicity profile of oral bilastine
• Bilastine (up to 1,000 mg/kg/day) was: well tolerated in
pregnant/lactating rats and in their offspring and
subsequent generations.
• With respect to effects on embryofoetal development in
rabbits, bilastine at 400 mg/kg/day (the highest dose
evaluated) was assessed to be the no observed adverse effects
level.
• Overall, bilastine demonstrated a favorable toxicity profile
in all animal models investigated and at higher doses than the
corresponding recommended daily human dosage.
Antistaminici orali
Sicurezza degli antistaminici in gravidanza
CETIRIZINA
CETIRIZINA
Gravidanza e allattamento
Le conoscenze sull´uso di cetirizina durante la gravidanza sono
limitate.
Come per altri farmaci, la sua somministrazione nella donna in stato di
gravidanza deve essere evitata. Qualora il farmaco venga
inavvertitamente assunto durante la gravidanza non sono attesi effetti
dannosi, ma il trattamento deve essere sospeso immediatamente. L
´assunzione di cetirizina è controindicata durante l'allattamento, in
quanto viene escreta nel latte materno.
54
Antistaminici orali
Sicurezza degli antistaminici in gravidanza
RUPATADINA
Gravidanza e allattamento
Dati su un numero limitato (2) di gravidanze esposte al
farmaco non indicano alcun evento avverso della rupatadina
sulla gravidanza o sulla salute del feto/neonato. Ad oggi, non
sono disponibili altri dati epidemiologici di rilievo. Gli studi
sugli animali non indicano effetti nocivi diretti o indiretti in
relazione a gravidanza, sviluppo embrionale/fetale, parto o
sviluppo postnatale
È necessario essere prudenti nel prescrivere il medicinale a
donne in stato di gravidanza.
La rupatadina è escreta nel latte degli animali. Non è noto se la rupatadina
venga escreta nel latte materno. A causa della mancanza di dati nell’uomo, è
necessario essere prudenti nel prescrivere il medicinale a donne che allattano.
55
BILASTINA E RUPATADINA : PROFILO
DI SICUREZZA OTTIMALE
- assenza di sedazione
- non provocare alterazioni cognitive o
psicomotorie
- assenza di effetti anti-colinergici
- possibilità d’impiego durante la
gravidanza e l’allattamento…
POSSIBILITA’ D’IMPIEGO IN MANIERA
PROLUNGATA A DOSAGGI MEDIO ALTI
LA RINITE ALLERGICA : IL TRATTAMENTO PUO’ ESSERE
COMPLESSO E NON RISULTARE EFFICACE
Necessità terapeutiche insoddisfatte dalle attuali terapie per la RA: SCUAD
• Fino al 20% dei pazienti con Rinite Allergica in trattamento
farmacologico ottimale (secondo linee guida) presenta ancora
sintomi gravi (pazienti polisensibili, comorbidità, ecc.)
• Questi pazienti sono identificati come pazienti con Severe
Chronic Upper Airway Disease (SCUAD)
Bousquet et al, 2009 & 2010
2012
H1-Antihistamine Up-Dosing in Chronic Spontaneous
Urticaria: Patients’ Perspective of Effectiveness and Side
Effects – A Retrospective Survey Study
Allergy 2013
Up-dosing to 80 mg daily supports the urticaria treatment guidelines by showing excellent safety
and no sedation while increasing its efficacy and antiinflammatory properties.
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