levofloxacino
Medicamento genérico Lei nº 9.787, de 1999

250mg e 500 mg

FORMA FARMACÊUTICA E APRESENTAÇÕES
Comprimidos de 250 mg. Embalagem contendo 7 comprimidos revestidos.
Comprimidos de 500 mg. Embalagem contendo 3, 7 ou 10 comprimidos revestidos.
USO ORAL
USO ADULTO

COMPOSIÇÃO
Cada comprimido revestido de 250 mg contém:
levofloxacino hemidratado ………………………………………………………………………… 256,23 mg
(equivalente a 250 mg de levofloxacino anidro)
excipientes q.s.p. …………………………………………………………………… 1 comprimido revestido
(lactose monoidratada, povidona, amidoglicolato de sódio, talco, dióxido de silício,
croscarmelose sódica, glicerol dibehenato, hipromelose, hiprolose, macrogol, óxido de ferro
amarelo, óxido de ferro vermelho, dióxido de titânio)

Cada comprimido revestido de 500 mg contém:
levofloxacino hemidratado ………………………………………………………………………… 512,46 mg
(equivalente a 500 mg de levofloxacino anidro)
excipientes q.s.p. ……………………………………………………………………. 1 comprimido revestido
(lactose monoidratada, povidona, amidoglicolato de sódio, talco, dióxido de silício,
croscarmelose sódica, glicerol dibehenato, hipromelose, hiprolose, macrogol, óxido de ferro
amarelo, óxido de ferro vermelho, dióxido de titânio)

INFORMAÇÕES AOS PACIENTES
Leia atentamente este texto antes de começar a tomar o medicamento, ele informa
sobre as propriedades deste medicamento. Se persistirem dúvidas ou estiver inseguro
fale com seu médico.
Antes de utilizar o medicamento, confira o nome do rótulo e não administre caso haja
sinais de violação e/ou danos na embalagem.
COMO ESTE MEDICAMENTO FUNCIONA?
O levofloxacino é um medicamento pertencente ao grupo dos antibióticos.
É indicado no tratamento de infecções causadas por germes sensíveis ao levofloxacino. O
levofloxacino administrado por via oral é rapidamente e quase completamente absorvido
com pico de concentração plasmática obtido aproximadamente em 1,3 horas.
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POR QUE ESTE MEDICAMENTO FOI INDICADO?
O levofloxacino é indicado no tratamento de infecções causadas por microrganismos
sensíveis ao levofloxacino, como: infecções do trato respiratório superior e inferior,
incluindo sinusite, exacerbações agudas de bronquite crônica e pneumonia; infecções da
pele e tecido subcutâneo, como impetigo, abscessos, furunculose, celulite e erisipela;
infecções do trato urinário, incluindo pielonefrite; osteomielite; septicemia/bacteremia
relacionadas às indicações acima; infecções intra-abdominais.
QUANDO NÃO DEVO USAR ESTE MEDICAMENTO?
Contra-Indicações: o levofloxacino não deve ser utilizado por pacientes com alergia ao
levofloxacino, outras quinolonas ou a quaisquer outros componentes da fórmula do produto;
pacientes com epilepsia; pacientes com história de problemas no tendão relacionadas à
administração de fluorquinolona; crianças ou adolescentes; durante a gravidez e lactação. O
uso em crianças e adolescentes, durante a gravidez e em mulheres lactantes está contra-
indicado devido ao risco de danos causados na cartilagem de organismos em crescimento, o
que não pode ser excluído completamente, considerando os testes em animais. Este
medicamento é contra-indicado na faixa etária pediátrica.
Advertências: informe ao seu médico caso você tenha ou já tenha apresentado problemas
de saúde ou alergias, problemas no tendão ou caso você utilize medicamentos para
convulsão. Prevenção da fotossensibilização: Embora a sensibilização a luz com uso de
levofloxacino seja muito rara, é recomendado que os pacientes não se exponham
desnecessariamente a excessiva luz solar direta ou aos raios U.V. artificiais (por exemplo:
luz ultravioleta, solarium) a fim de previnir a fotossensibilização. Superinfecção: da mesma
forma que com outros antibióticos, o uso de levofloxacino, especialmente uso prolongado,
pode resultar em um crescimento excessivo de organismos não susceptíveis. É essencial
que avaliações repetidas das condições dos pacientes sejam feitas pelo médico que tomará
medidas apropriadas caso ocorra superinfecção durante o tratamento. Em caso de suspeita
de infecção por microrganismo anaeróbio, o uso de levofloxacino deve ser associado ao
uso de fármacos anaerobicidas, devido à baixa eficácia em anaeróbios, que são comuns em
infecções intra-abdominais. Colite pseudomembranosa: a ocorrência de diarréia,
particularmente grave, persistente e/ou com sangue, durante ou após o tratamento com
levofloxacino, pode ser indicativa de colite pseudomembranosa devido ao microrganismo
Clostridium dificile. Na suspeita de colite pseudomembranosa, o tratamento com
levofloxacino deve ser interrompido imediatamente e deve ser iniciado tratamento com
antibiótico específico apropriado (por exemplo: vancomicina oral, teicoplanina oral ou
metronidazol). Produtos que inibem o peristaltismo, ou seja, inibem a motilidade
gastrintestinal, são contra-indicados nesta situação. Tendinite: a tendinite, raramente
observada com quinolonas, pode ocasionalmente levar a ruptura envolvendo particularmente
o tendão de Aquiles. Este efeito indesejado pode ocorrer nas 48 horas do início do
tratamento e pode ser bilateral. Os pacientes idosos estão mais predispostos à tendinite. O
risco de ruptura de tendão pode ficar aumentado na administração concomitante de
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corticosteróides. Na suspeita de tendinite, o tratamento deve ser interrompido imediatamente
e tratamento de suporte (por ex.: imobilização) deve ser iniciado no tendão afetado.
Efeitos sobre a capacidade de dirigir e operar máquinas: algumas reações adversas (por
exemplo: tontura/vertigem, sonolência, distúrbios visuais) podem prejudicar a habilidade dos
pacientes em se concentrar e reagir; portanto, podem constituir um risco em situações onde
essas habilidades são de extrema importância (por exemplo: dirigir veículos ou operar
máquinas).
Risco de uso por via de administração não recomendada: não há estudos dos efeitos de
levofloxacino administrado por vias não recomendadas. Portanto, por segurança e para
eficácia deste medicamento, a administração deve ser somente pela via oral.
Gravidez: estudos de reprodução em animais não levantaram qualquer preocupação
específica. Entretanto, esta contra-indicação é baseada na ausência de dados humanos e
devido ao risco de danos em estudos experimentais utilizando fluorquinolonas, incluindo o
levofloxacino, nas cartilagens de organismos em crescimento.
Amamentação: o levofloxacino não deve ser utilizado por mulheres que estejam
amamentando. Na ausência de dados humanos e devido ao risco de danos demonstrado em
estudos experimentais, causados por fluorquinolonas, incluindo o levofloxacino, nas
cartilagens de organismos em crescimento, esta atitude restritiva é justificada. (Ver item
Contra-indicações).
Não deve ser utilizado durante a gravidez e a amamentação, exceto sob orientação
médica. Informe ao seu médico se ocorrer gravidez ou iniciar amamentação durante o
uso deste medicamento.
Informe ao médico o aparecimento de reações indesejáveis.
Informe ao seu médico se você está fazendo uso de algum outro medicamento.
Não use medicamento sem o conhecimento do seu médico. Pode ser perigoso para a
sua saúde.
COMO DEVO USAR ESTE MEDICAMENTO?
Aspecto físico e características organolépticas:
O levofloxacino apresenta-se em comprimidos revestidos de uso oral, com as seguintes
características:
Levofloxacino 250 mg - Comprimidos revestidos de cor rosa, octagonais, biconvexos e com
vinco em ambas as faces.
Levofloxacino 500 mg ­ Comprimidos revestidos de cor rosa, octagonais, biconvexos e com
vinco em uma das faces.
Dosagem
O tratamento deve ser iniciado e acompanhado pelo médico. Os comprimidos podem ser
administrados 1 ou 2 vezes ao dia, por via oral. A dose depende do tipo e severidade da
infecção e da sensibilidade do patógeno. A duração do tratamento varia de acordo com o
resultado clínico, com o período máximo de duração de 14 dias.
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Os comprimidos de levofloxacino devem ser engolidos sem mastigar e com quantidade de
líquido suficiente e administrados pelo menos 2 horas antes ou depois da administração de
sais de ferro, antiácidos e sulcralfatos, pois pode ocorrer redução na absorção.
Não existe interação clinicamente significativa de levofloxacino com alimentos, portanto,
pode ser administrado concomitante a alimentos.
Conduta necessária caso haja esquecimento de administração: caso você se esqueça
de tomar uma das doses, tome-a assim que possível, no entanto, se estiver próximo do
horário da dose seguinte, espere por este horário, respeitando sempre o intervalo
determinado pela posologia. Nunca tome duas doses de uma só vez.
Não interromper o tratamento sem o conhecimento do seu médico.
Siga a orientação de seu médico, respeitando sempre os horários, as doses e a
duração do tratamento.
Não use o medicamento com o prazo de validade vencido. Antes de usar observe o
aspecto do medicamento.
Mantenha esta bula em seu poder enquanto durar o tratamento com este
medicamento. Você pode querer lê-la novamente.

QUAIS OS MALES QUE ESTE MEDICAMENTO PODE CAUSAR?
Informe ao seu médico o aparecimento de reações desagradáveis, tais como: diarréia,
náusea e vômito. Também podem ocorrer, embora menos freqüentemente, dor de cabeça,
dor abdominal, erupção da pele, coceira, dispepsia, insônia e tontura.
O QUE FAZER SE ALGUÉM USAR UMA GRANDE QUANTIDADE DESTE
MEDICAMENTO DE UMA SÓ VEZ?
De acordo com estudos de toxicidade em animais, os sinais mais importantes após a
ocorrência de superdose oral aguda com levofloxacino são: sintomas no Sistema Nervoso
Central como confusão, vertigens, alterações de consciência e convulsões. Podem ocorrer
reações gastrintestinais como náuseas e erosões da mucosa.
Em estudos de farmacologia clínica realizados com superdoses foram observados aumento
do intervalo QT.
Em caso de superdose acidental, procure imediatamente um centro de intoxicação ou
atentimento médico de emergência.
ONDE E COMO DEVO GUARDAR ESTE MEDICAMENTO?
Os comprimidos de levofloxacino devem ser mantidos em sua embalagem original, em
temperatura ambiente (entre 15°C e 30°C).

TODO MEDICAMENTO DEVE SER MANTIDO
FORA DO ALCANCE DAS CRIANÇAS.
INFORMAÇÕES TÉCNICAS AOS PROFISSIONAIS DE SAÚDE

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CARACTERÍSTICAS FARMACOLÓGICAS
Propriedades Farmacodinâmicas: o levofloxacino é um agente antibacteriano sintético de
amplo espectro pertencente à classe das fluorquinolonas, para administração oral ou
intravenosa. O levofloxacino é o enantiômero S(-) (forma levorotatória) da substância
ofloxacino racêmica.
Modo de ação: como um agente antibacteriano da classe das fluorquinolonas, o
levofloxacino age no complexo da DNA girase e topoisomerase IV.
Pontos de Corte: os pontos de corte preliminares de CIM recomendados pelo NCCLS
(Comitê Nacional Americano de Padrões Clínicos Laboratoriais) para levofloxacino, que
distinguem os microrganismos susceptíveis dos intermediariamente susceptíveis e bem
como dos microrganismos resistentes, são:
Classe de
Concentração inibitória mínima
Zona de inibição (mm)
microrganismos
CIM (mg/L)
Susceptíveis
2
17
Intermediariamente
4
16 – 14
susceptíveis
Resistentes
8
13

Espectro antibacteriano
O levofloxacino é altamente bactericida in vitro. Este espectro antibacteriano cobre muitas
bactérias Gram-positivas e Gram-negativas, como: Staphylococci, Streptococci incluindo
Pneumococci, Enterobacteriaceae, Haemophilus influenzae, bactérias Gram-negativas não
fermentativas e microrganismos atípicos.
O espectro antibacteriano do levofloxacino é listado abaixo (a sensibilidade ao
levofloxacino pode variar, dependendo da epidemiologia e do nível de resistência relativo
no país).
Microrganismos habitualmente susceptíveis
- Aeróbios Gram-positivos:
Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus faecalis,
Enterococcus spp, Listeria monocytogenes, Staphylococcus coagulase negative methi-S(1),
Staphylococcus aureus methi-S, Staphylococcus epidermidis methi-S, Staphylococcus spp
(CNS), Streptococci grupo C e G, Streptococcus agalactiae, Streptococcus pneumoniae
peni-I/S/R,Streptococcus pyogenes, Viridans streptococcus peni-S/R
- Aeróbios Gram-negativos:
Acinetobacter baumannii, Acinetobacter spp, Actinobacillus actinomycetemcomitans,
Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter
agglomerans, Enterobacter cloacae, Enterobacter spp, Escherichia coli, Gardnerella
vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R, Haemophilus para-
influenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella spp,
Moraxella catarrhalis B+ / B-, Morganella morganii, Neisseria gonorrhoeae non PPNG/PPNG,
Neisseria meningitidis, Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida,
Pasteurella spp, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii,
setembro/2008



Providencia spp, Pseudomonas aeruginosa, Pseudomonas spp, Salmonella spp, Serratia
marcescens, Serratia spp
- Anaeróbios:
Bacteroides fragilis, Bifidobacterium spp, Clostridium perfringens, Fusobacterium spp,
Peptostreptococcus, Propionibacterium spp, Veillonella spp.
- Outros microrganismos:
Bartonella spp, Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis,
Legionella pneumophila, Legionella spp, Mycobacterium spp, Mycobacterium leprae,
Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp,
Ureaplasma urealyticum
Microrganismos habitualmente com susceptibilidade intermediária
- Aeróbios Gram-positivos
Corynebacterium urealyticum; Corynebacterium xerosis; Enterococcus faecium;
Staphylococcus epidermidis methi-R; Staphylococcus haemolyticus methi-R.
- Aeróbios Gram-negativos
Burkholderia cepacia; Campylobacter jejuni/coli.
- Anaeróbios
Bacteroides thetaiotaomicron; Bacteroides vulgatus; Bacteroides ovatus; Prevotella spp e
Porphyromonas spp
Microrganismos habitualmente resistentes
- Aeróbios Gram-positivos
Corynebacterium jeikeium; Staphylococcus aureus methi-R; Staphylococcus coagulase
negative methi-R.
- Aeróbios Gram-negativos
Alcaligenes xylosoxidans
- Anaeróbios
Bacteroides thetaiotaomicron
- Outros microrganismos
Mycobacterium avium
Patógenos tratados clinicamente com êxito:
As infecções causadas pelos seguintes patógenos foram tratadas com êxito nos ensaios
clínicos:
- Aeróbios Gram-positivos
Enterococcus faecalis; Staphylococcus aureus; Streptococcus pneumoniae; Streptococcus
pyogenes.
- Aeróbios Gram-negativos
Citrobacter freundii; Enterobacter cloacae; Escherichia coli; Haemophilus influenzae;
Haemophilus parainfluenzae; Klebsiella pneumoniae; Moraxella (Branhamella) catarrhalis;
Morganella morganii; Proteus mirabilis; Pseudomonas aeruginosa; Serratia marcescens.
- Outros
Chlamydia pneumoniae; Legionella pneumophila; Mycoplasma pneumoniae.
Outras informações:
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O principal mecanismo de resistência é devido à mutação gyr-A.
Devido ao mecanismo de ação, geralmente não há resistência cruzada entre o
levofloxacino e outras classes de agentes antibacterianos.
Em infecções nosocomiais causadas por Pseudomonas aeruginosa pode ser necessária a
terapia combinada.
PROPRIEDADES FARMACOCINÉTICAS
Pacientes com função renal normal
Absorção
O levofloxacino administrado pela via oral é rapidamente e quase completamente absorvido
com pico de concentração plasmática obtido dentro de 1,3 h (Cmáx: 5,2 a 6,9 µg/mL após
doses únicas de 500 mg de levofloxacino). A biodisponibilidade absoluta é de
aproximadamente 100%. O levofloxacino apresenta uma farmacocinética linear variando
entre 150 mg a 600 mg. O efeito da absorção do levofloxacino é pouco alterado com a
ingestão de alimentos.
Distribuição
Aproximadamente 30% a 40% de levofloxacino está ligado às proteínas séricas. Doses
múltiplas de 500 mg de levofloxacino, uma vez ao dia, mostraram acumulação
insignificante. Há um modesto, mas previsível acúmulo de levofloxacino após doses de 500
mg, duas vezes ao dia. O estado de equilíbrio é atingido em período de 3 dias.
Penetração nos tecidos fluido corpóreo/Penetração na mucosa brônquica e fluido de
revestimento epitelial
As concentrações máximas de levofloxacino na mucosa brônquica e no fluido de
revestimento epitelial após 500 mg por via oral foram de 8,3 µg/g e 10,8 µg/mL,
respectivamente com níveis de penetração na mucosa brônquica e fluido de revestimento
epitelial sérico de 0,9 a 1,8 e 0,8 a 3, respectivamente. Estas concentrações foram
alcançadas em aproximadamente uma hora após a administração.
Penetração nos tecidos pulmonares
As concentrações máximas de levofloxacino no tecido pulmonar após 500 mg por via oral
foram de aproximadamente 11,3 µg/g e foram alcançadas entre 4 a 6 horas após a
administração com níveis de penetração no plasma do tecido pulmonar variando entre 2 a 5
horas. As concentrações nos pulmões conseqüentemente excederam às do plasma.
Penetração nos fluidos de vesículas
Nos fluidos de vesículas as concentrações máximas de levofloxacino foram de 4,0 e 6,7
µg/mL, alcançadas 2 a 4 horas após a administração, após 3 dias de tratamento com doses
de 500 mg, uma ou duas vezes ao dia, respectivamente com uma proporção (fluido
vesical/plasma) de aproximadamente 1.
Penetração no tecido ósseo
O levofloxacino apresenta boa penetração no tecido cortical e esponjoso, tanto no fêmur
proximal quanto distal, com níveis de penetração (osso/plasma) de 0,1 a 3,0. A penetração
no osso é rápida, levando-se aproximadamente 2 horas para alcançar a concentração
máxima.
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Penetração no fluido cérebro-espinhal
O levofloxacino apresenta baixa penetração no fluido cérebro-espinhal.
Concentração urinária
As concentrações urinárias médias, 8 a 12 horas após a administração de uma dose oral
única de 150 mg, 300 mg ou 600 mg de levofloxacino foram de 44 µg/mL, 91 µg/mL e 162
µg/mL, respectivamente.
Metabolismo
O levofloxacino é metabolizado numa proporção muito pequena, sendo os metabólitos: o
desmetil-levofloxacino e N-óxido levofloxacino. Menos de 5% da dose desses metabólitos
são excretados na urina. O levofloxacino é estereoquimicamente estável e não sofre
inversão quiral.
Eliminação
Após administrações oral e intravenosa, o levofloxacino é eliminado de modo relativamente
lento no plasma (t1/2: 6h a 8h). A excreção é principalmente por via renal (maior do que 85%
da dose administrada).
Não houve diferenças significativas na farmacocinética de levofloxacino após
administrações oral e intravenosa, sugerindo que as vias oral e intravenosa são
intercambiáveis.
Pacientes com insuficiência renal
A farmacocinética do levofloxacino é afetada pela insuficiência renal. Quando a função
renal está reduzida, a eliminação renal e o clearance são diminuídos, e a meia-vida de
eliminação é aumentada.
CLCr
[mL/min]
< 20
20 – 40
50 – 80
CRL* [mL/min] 13 26
57
t 1/2
[h]
35
27
9
*CRL = taxa de clearance renal do levofloxacino
Pacientes idosos
Não há diferenças significativas na cinética do levofloxacino entre jovens e pacientes
idosos, exceto aquelas diferenças associadas ao clearance de creatinina.
Diferenças de sexo
As análises separadas de pacientes do sexo masculino e feminino não mostraram nenhuma
diferença clínica relevante na farmacocinética do levofloxacino.
DADOS DE SEGURANÇA PRÉ-CLÍNICA
Toxicidade aguda
Os valores da dose letal média (DL50) obtidos em camundongos e ratos após administração
oral de levofloxacino foram de 1500 a 2000 mg/kg. A administração de 500 mg/Kg, por via
oral em macacos induziram poucos efeitos além de vômito.
Toxicidade em doses repetidas
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Foram conduzidos estudos com gavagem em ratos e macacos com duração de um e seis
meses. As doses foram de 50, 200, 800 mg/kg/dia e 20, 80, 320 mg/kg/dia durante 1 e 6
meses em ratos e 10, 30, 100 mg/kg/dia e 10, 25, 62,5 mg/kg/dia durante 1 e 6 meses em
macacos.
Os sinais de reações ao tratamento foram discretos em ratos, com efeitos leves
principalmente na dose de 200 mg/kg/dia ou mais, com discreta redução no consumo de
alimentos e alteração leve dos parâmetros hematológicos e bioquímicos. Foi concluído
nesse estudo que o NOEL (Nível de Efeito Adverso Não Observado) foi de 200 e 20
mg/kg/dia após 1 e 6 meses, respectivamente.
A toxicidade após dose oral em macacos foi mínima com redução no peso corpóreo de 100
mg/kg/dia concomitante com salivação, diarréia e diminuição do pH urinário em alguns
animais nesta dose. Não foi observada toxicidade no estudo de 6 meses. Os NOELS foram
definidos como sendo 30 e 62,5 mg/kg/dia após 1 e 6 meses, respectivamente.
No estudo de seis meses, o NOEL foi definido como sendo 20 e 62,5 mg/kg/dia em ratos e
macacos, respectivamente.
Toxicidade reprodutiva
O levofloxacino não causou dano na fertilidade ou no desenvolvimento reprodutivo em ratos
com doses orais tão altas quanto 360 mg/kg/dia ou com doses intravenosas até 100
mg/kg/dia. O levofloxacino não foi teratogênico em ratos com doses orais tão altas quanto
810 mg/kg/dia ou com doses intravenosas tão altas quanto 160 mg/kg/dia. Não foi observada
terotogenicidade quando coelhos receberam doses orais até 50 mg/kg/dia ou doses
intravenosas até 25 mg/kg/dia. O levofloxacino não apresentou efeito na fertilidade, e seu
único efeito no feto foi a maturação retardada como resultado de toxicidade materna.
Genotoxicidade
Na ausência de ativação metabólica, o levofloxacino não induziu mutações gênicas em
células bacterianas ou de mamíferos, porém induziu aberrações cromossômicas em células
de pulmão de hamster chinês in vitro em concentrações iguais ou superiores a 100 µg/mL.
Testes in vivo (micronúcleos, alteração de cromátides irmãs, síntese de DNA não
programada e testes letais dominantes) não mostraram qualquer potencial genotóxico.
Potencial fototóxico
Estudos em ratos após ambas as administrações oral e intravenosa mostraram que o
levofloxacino apresenta atividade fototóxica apenas em doses muito elevadas. O
levofloxacino não demonstrou qualquer potencial genotóxico nos ensaios de
fotomutagenicidade e reduziu o potencial de desenvolvimento de tumor nos ensaios de
fotocarcinogenicidade.
Potencial carcinogênico
Não houve indicação de potencial carcinogênico em um estudo de dois anos em ratos com
administração na dieta (0, 10, 30 e 100 mg/kg/dia).
Toxicidade nas articulações
Em comum com outras fluorquinolonas, o levofloxacino mostrou efeito na cartilagem
(vesículas e cavidades) em ratos e cães. Estes efeitos foram mais característicos em
animais jovens.
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INDICAÇÕES
O levofloxacino é indicado no tratamento de infecções bacterianas causadas por agentes
sensíveis ao levofloxacino, como:
- infecções do trato respiratório superior e inferior, incluindo sinusite, exacerbações agudas
de bronquite crônica e pneumonia;
- infecções da pele e tecido subcutâneo, como impetigo, abscessos, furunculose, celulite e
erisipela;
- infecções do trato urinário, incluindo pielonefrite;
- osteomielite;
- septicemia/bacteremia relacionadas às indicações acima;
- infecções intra-abdominais.

CONTRA-INDICAÇÕES:
O levofloxacino não deve ser utilizado em:
- pacientes com hipersensibilidade ao levofloxacino, a outras quinolonas ou a quaisquer
outros componentes da fórmula do produto;
- pacientes com epilepsia;
- pacientes com história de problemas no tendão relacionadas à administração de
fluorquinolona;
- crianças ou adolescentes;
- durante a gravidez e por mulheres lactantes.
O uso em crianças e adolescentes, durante a gravidez e em mulheres lactantes está contra-
indicado devido ao risco de danos causados na cartilagem de organismos em crescimento, o
que não pode ser excluído completamente, considerando os experimentos em animais.

MODO DE USAR E CUIDADOS DE CONSERVAÇÃO DEPOIS DE ABERTO
Os comprimidos de levofloxacino devem ser engolidos sem mastigar com suficiente
quantidade de líquido e administrados pelo menos 2 horas antes ou depois da administração
de sais de ferro, antiácidos e sucralfato, pois pode ocorrer redução na absorção.
Depois de aberto, o levofloxacino ser mantido em sua embalagem original, em temperatura
ambiente (entre 15°C a 30°C).

POSOLOGIA
Os comprimidos de levofloxacino podem ser administrados 1 ou 2 vezes ao dia, por via
oral. A dose depende do tipo e severidade da infecção e da sensibilidade do patógeno.
A duração do tratamento varia de acordo com o resultado clínico, com o período máximo de
duração de 14 dias. Assim como para outros antibióticos, o tratamento com o levofloxacino
deve ser continuado por um período mínimo de 48 a 72 horas após a febre ceder e quando
há evidência de erradicação do patógeno.
As tabelas a seguir trazem orientações sobre as doses e a duração do tratamento, de acordo
com o tipo de infecção e de acordo com a função renal.
setembro/2008




- Pacientes com função renal normal (clearance de creatinina (CLcr) > 50 mL/min)
Infecção
Dose
Freqüência
Duração
unitária
Exacerbação de branquite crônica
500 mg
cada 24 horas
5 – 7 dias
Pneumonia
500 mg
cada 24 horas
7 – 14 dias
Sinusite
500 mg
cada 24 horas
10 – 14 dias
Infecção da pele e tecido subcutâneo
500 mg
cada 24 horas
7 – 10 dias
Infecções do trato urinário e pielonefrite aguda.
250 mg
cada 24 horas
10 dias
Infecções não-complicadas do trato urinário
250 mg
cada 24 horas
3 dias
Osteomielite
500 mg
cada 24 horas
6 -12 semanas
Septicemia/ bacteremia
500 mg
cada 12 ou 24 horas
10 – 14 dias
Infecções intra-abdominais*
500 mg
cada 24 horas
7 – 14 dias
*Em combinação com antibiótico de cobertura anaeróbia

- Pacientes com insuficiência renal (clearance de creatinina (CLcr) < 50 mL/min)
Clearance de Creatinina
Dose inicial
Doses subseqüentes
CLcr de 20 a 49 mL/min
500 mg
250 mg cada 24 horas
CLcr de 10 a 19 mL/min
500 mg
250 mg cada 48horas
Hemodiálise
500 mg
250 mg cada 48 horas
CAPD*
500 mg
250 mg cada 48 horas
Infecção do trato urinário / pielonefrite aguda
Clearance de Creatinina
Dose inicial
Doses subseqüentes
CLcr > 20 mL/min
não é necessário ajuste de dose
CLcr de 10 a 19 mL/min
250 mg
250 mg cada 48 horas
*CAPD = diálise peritoneal ambulatorial crônica

Conduta necessária caso haja esquecimento da administração de alguma dose.
Caso o paciente esqueça de tomar uma das dose, ele deverá tomá-la assim que possível, no
entanto, se estiver próximo do horário da dose seguinte o paciente deverá esperar por este
horário, respeitando sempre o intervalo determinado pela posologia. Nunca devem ser
administradas duas doses ao mesmo tempo.

ADVERTÊNCIAS
Prevenção da fotossensibilização
Embora a fotossensibilização seja muito rara com levofloxacino, é recomendado que os
pacientes não se exponham desnecessariamente a excessiva luz solar direta ou aos raios
U.V. artificiais (por exemplo: luz ultravioleta, solarium) a fim de prevenir a fotossensibilização.
Superinfecção
Como outros antibióticos, o uso de levofloxacino, especialmente se prolongado, pode
resultar em um crescimento excessivo de organismos não susceptíveis. Avaliações repetidas
setembro/2008

das condições dos pacientes são essenciais. Devem ser tomadas medidas apropriadas,
caso ocorra superinfecção durante o tratamento.
Devido à baixa eficácia em anaeróbios, que são comuns em infecções intra-abdominais, em
caso de suspeita de infecção por microrganismo anaeróbio, o uso de levofloxacino deve ser
associado ao uso de fármacos anaerobicidas.
Colite pseudomembranosa
A ocorrência de diarréia, particularmente grave, persistente e/ou com sangue, durante ou
após o tratamento com levofloxacino pode ser indicativa de colite pseudomembranosa
devido a Clostridium dificile. Na suspeita de colite pseudomembranosa, a administração de
levofloxacino deve ser interrompida imediatamente.
O tratamento com antibiótico específico apropriado deve ser iniciado imediatamente (por
exemplo: vancomicina oral, teicoplanina oral ou metronidazol). Produtos que inibem o
peristaltismo são contra-indicados nesta situação.
Tendinite
A tendinite, raramente observada com o uso de quinolonas, pode ocasionalmente levar a
ruptura envolvendo particularmente o tendão de Aquiles. Este efeito indesejado pode ocorrer
nas 48 horas do início do tratamento e pode ser bilateral. Os pacientes idosos estão mais
predispostos à tendinite. O risco de ruptura de tendão pode ficar aumentado na
administração concomitante a corticosteróides. Na suspeita de tendinite, o tratamento com
levofloxacino deve ser interrompido imediatamente.
O tratamento apropriado (por exemplo: imobilização) deve ser iniciado no tendão afetado.
Efeitos sobre a capacidade de dirigir e operar máquinas
Algumas reações adversas (por exemplo: tontura/vertigem, sonolência, distúrbios visuais)
podem prejudicar a habilidade dos pacientes em se concentrar e reagir; portanto, podem
constituir um risco em situações onde essas habilidades são de extrema importância (por
exemplo: dirigir veículos ou operar máquinas).
Gravidez
Este medicamento não deve ser utilizado por mulheres grávidas sem orientação
médica ou do cirurgião-dentista.
Categoria de risco na gravidez: categoria C
Estudos de reprodução em animais não levantaram qualquer preocupação específica.
Entretanto, esta contra-indicação é baseada na ausência de dados humanos e devido ao
risco de danos em estudos experimentais utilizando fluorquinolonas, incluindo o
levofloxacino, nas cartilagens de organismos em crescimento.
Lactação
O levofloxacino não deve ser utilizado por mulheres lactantes. Na ausência de dados
humanos e devido ao risco de danos demonstrado em estudos experimentais, causados por
fluorquinolonas, incluindo o levofloxacino, nas cartilagens de organismos em crescimento,
esta atitude restritiva é justificada. (Ver itens Contra-indicações e Dados de segurança pré-
clínica).
USO EM IDOSOS, CRIANÇAS E OUTROS GRUPOS DE RISCO.
setembro/2008



Idosos: as doses recomendadas são válidas também para pacientes idosos. Não há
necessidade de ajuste das doses, desde que esses pacientes não tenham alterações na
função renal.
Crianças e adolescentes: o uso em crianças e adolescentes menores de 18 anos está
contra-indicado devido ao risco de danos causados na cartilagem de organismos em
crescimento, o que não pode ser excluído completamente, considerando os testes em
animais.
Restrições a grupos de risco
Pacientes com insuficiência renal: a dose de levofloxacino deve ser ajustada nos
pacientes com insuficiência renal, uma vez que o levofloxacino é excretado principalmente
pelos rins.
Pacientes com deficiência na enzima glicose-6-fosfato desidrogenase: pacientes com
defeito latente ou atual na atividade da glicose-6-fosfato desidrogenase podem estar
predispostos a reações hemolíticas quando tratados com agentes antibacterianos
quinolônicos, e isto tem que ser levado em consideração quando da utilização do
levofloxacino.
Pacientes predispostos à convulsão: como com qualquer outra quinolona, o
levofloxacino deve ser utilizado com extrema cautela em pacientes predispostos à
convulsão. Estes pacientes podem estar com lesão pré-existente do sistema nervoso central,
ou em tratamento concomitante com fenbufeno e antiinflamatórios não-esteroidais similares
ou com fármacos que diminuem o limiar da convulsão cerebral, como a teofilina (ver item
Interações medicamentosas).
INTERAÇÕES MEDICAMENTOSAS
Sais de ferro ou antiácidos contendo magnésio e alumínio: é recomendado que
preparações contendo cátions bivalentes ou trivalentes como sais de ferro ou antiácidos
contendo magnésio e alumínio sejam administradas duas horas antes ou depois da
administração de levofloxacino. Não foi observada interação com carbonato de cálcio.
Sucralfato: a biodisponibilidade de levofloxacino é significativamente reduzida na
administração concomitante a sucralfato. Caso o paciente esteja recebendo sucralfato e
levofloxacino, é recomendável administrar o sucralfato 2 horas após a administração de
levofloxacino.
Teofilina, fenbufeno ou antiinflamatórios não-esteroidais similares: nos estudos
clínicos, não houve interação farmacocinética com levofloxacino e teofilina. Entretanto,
pode ocorrer uma redução pronunciada no limiar da convulsão cerebral na administração
concomitante de quinolonas e teofilina, fármacos antiinflamatórios não-esteroidais ou outros
agentes que diminuem o limiar da convulsão. As concentrações de levofloxacino foram
cerca de 13% mais altas na presença de fenbufeno do que quando administrados
separadamente.
Probenecida e cimetidina: deve-se ter cautela na administração concomitante de
levofloxacino e drogas que afetam a secreção tubular renal, como probenecida e
cimetidina, especialmente em pacientes com insuficiência renal. A probenecida e cimetidina
setembro/2008



causaram um efeito estatisticamente significativo na eliminação do levofloxacino. O
clearance renal do levofloxacino foi reduzido pela cimetidina (24%) e probenecida (34%).
Isto ocorre porque ambas as drogas são capazes de bloquear a secreção tubular renal de
levofloxacino. Entretanto, nas doses testadas no estudo, as diferenças cinéticas
estatisticamente significativas não têm relevância clínica.
Ciclosporina: a meia-vida da ciclosporina é aumentada em 33% quando administrada
concomitantemente a levofloxacino. Não é requerido o ajuste de dose da ciclosporina, uma
vez que este aumento não é clinicamente relevante.
Antagonistas da vitamina K: tem-se relatado em pacientes tratados concomitantemente
com levofloxacino e antagonistas da vitamina K (ex.: varfarina), alteração nos testes de
coagulação (tempo de protrombina corrigido) e/ou sangramento, os quais podem ser graves.
Portanto, os parâmetros de coagulação devem ser monitorados em pacientes tratados com
antagonistas da vitamina K.
Outros: foram conduzidos estudos clínicos farmacológicos para investigar possíveis
interações farmacocinéticas entre levofloxacino e algumas drogas comumente prescritas. A
farmacocinética do levofloxacino não foi afetada em qualquer proporção clinicamente
significante quando esta foi administrada concomitantemente às seguintes drogas: carbonato
de cálcio, digoxina, glibenclamida, ranitidina e varfarina.
Alimentos: não existe interação clinicamente significativa entre levofloxacino e alimentos.
Os comprimidos de levofloxacino podem, portanto, ser administrados concomitante a
alimentos (ver item Propriedades farmacocinéticas).
Testes laboratoriais: o levofloxacino pode inibir o crescimento do Mycobacterium
tuberculosis e, portanto, pode fornecer resultados falso-negativos nos diagnósticos
bacteriológicos da tuberculose.

REAÇÕES ADVERSAS A MEDICAMENTOS
As informações fornecidas abaixo estão baseadas nos dados de estudos clínicos, em 5244
pacientes tratados com levofloxacino e em extensa experiência pós-comercialização. De
acordo com as recomendações da CIOMS, têm-se utilizado os seguintes índices de
freqüência:
Muito Comum: acima de 10%
Comum: de 1% a 10%
Incomum: de 0,1% a 1%
Raro: de 0,01% a 0,1%
Muito raro: menos que 0,01%
Casos isolados
- Reações anafiláticas/anafilactóides, reações cutâneas
Incomum: prurido, erupção cutânea.
Raro: urticária, broncospasmo/dispnéia.
Muito raro: angioedema, hipotensão, choque anafilático/anafilactóide, fotossensibilização.
Casos Isolados: erupções bolhosas graves como Síndrome de Steven’s Johnson, necrólise
epidermal tóxica (Síndrome de Lyell’s) e eritema multiforme exsudativo.
setembro/2008



Algumas vezes, as reações anafiláticas/anafilactóides e mucocutâneas podem ocorrer
mesmo após a primeira dose.
- Gastrintestinal, metabolismo
Comum: náusea, diarréia.
Incomum: anorexia, vômito, dor abdominal, dispepsia.
Raro: diarréia com sangue, que em casos muito raros pode ser indicativa de enterocolite,
incluindo colite pseudomembranosa.
Muito raro: hipoglicemia, particularmente em pacientes diabéticos.
- Neurológica/Psiquiátrica
Incomum: cefaléia, tontura/vertigem, sonolência, insônia.
Raro: depressão, ansiedade, reações psicóticas (por exemplo: alucinações), parestesia,
tremor, agitação, confusão, convulsão.
Muito raro: hipoestesia, distúrbios visuais e auditivos, distúrbios no paladar e olfato.
Casos isolados: reações psicóticas com comportamentos de auto-risco, incluindo atos ou
idealizações suicidas.
- Cardiovascular
Raro: taquicardia, hipotensão.
Muito raro: choque (anafilático/anafilactóide).
Casos isolados: prolongamento do intervalo QT (Ver item Superdose).
- Músculo-esquelética
Raro: artralgia, mialgia, problemas no tendão incluindo tendinite (por exemplo: tendão de
Aquiles).
Muito raro: ruptura do tendão (por exemplo: tendão de Aquiles). Fraqueza muscular, que
pode ser de extrema importância em pacientes com miastenia grave.
Casos isolados: rabdomiólise.
- Problemas hepáticos e renais
Comum: aumento de enzimas hepáticas (por exemplo: TGP/TGO).
Incomum: aumentos da bilirrubina e creatinina sérica.
Muito raro: reações hepáticas como hepatite, insuficiência renal aguda (por exemplo: devido
a nefrite intersticial).
- Problemas sangüíneos
Incomum: eosinofilia, leucopenia.
Raro: neutropenia, trombocitopenia.
Muito raro: agranulocitose.
Casos isolados: anemia hemolítica, pancitopenia.
- Outros
Comum: dor, vermelhidão no local da infusão e flebite (referente somente para infusão).
Incomum: astenia, supercrescimento de fungos e proliferação de outros microrganismos
resistentes.
Muito raro: pneumonite alérgica, febre.
- Outros efeitos indesejáveis possivelmente relacionados à classe das fluorquinolonas
setembro/2008



Muito raro: sintomas extrapiramidais e outras alterações na coordenação muscular,
vasculite de hipersensibilidade e crises de porfiria em pacientes com porfiria.
SUPERDOSE
Sintomas
De acordo com estudos de toxicidade em animais, os sinais mais importantes após a
ocorrência de superdose oral aguda com levofloxacino são: sintomas no Sistema Nervoso
Central como confusão, vertigens, alterações de consciência e convulsões. Podem ocorrer
reações gastrintestinais como náuseas e erosões da mucosa.
Em estudos de farmacologia clínica realizados com uma dose supraterapêutica foram
observados aumento do intervalo QT.
Tratamento
Em caso de superdose, o paciente deve ser observado cuidadosamente (incluindo
monitorização do ECG) e tratamento sintomático deve ser implementado.
Se ocorrer superdose aguda, deve-se considerar também a lavagem gástrica e pode-se
utilizar antiácidos para a proteção da mucosa gástrica.
A hemodiálise, incluindo diálise peritoneal e CAPD (diálise peritoneal ambulatorial contínua)
não são efetivas em remover o levofloxacino do corpo. Não existe antídoto específico.
“Para sua segurança, não descarte a bula e o cartucho até o uso total deste
medicamento”.

VENDA SOB PRESCRIÇÃO MÉDICA

Lote, data de fabricação e validade: vide cartucho.

Reg. MS ­1.0047.0434
Farm. Resp.: Luciana A. Perez Bonilha
CRF-PR nº 16.006
Logo SAC 0800 4009192

Uma decisão saudável

Fabricado por:
LEK Pharmaceuticals
1526, Ljubljana – Verovskova 57
setembro/2008



Eslovênia
Para:
Sandoz GmbH (Uma empresa do grupo Novartis)
Kundl ­ Áustria.
Importado por:
Sandoz do Brasil Indústria Farmacêutica Ltda.
Rod. Celso Garcia Cid (PR-445), Km 87
Cambé-PR
CNPJ: 61.286.647/0001-16
Indústria Brasileira


setembro/2008


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    {but|except|however} the audio {quality|feature} for audio songs {current|present|existing} at this {website|web site|site|web page} is {really|actually|in fact|truly|genuinely} {marvelous|wonderful|excellent|fabulous|superb}.|
    {Howdy|Hi there|Hi|Hello}, i read your blog {occasionally|from time to time} and i own a similar one and i was just {wondering|curious} if you get a lot of spam
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    {It is the|It’s the} little changes {that make|which will make|that produce|that
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    {Thanks a lot|Thanks|Many thanks} for sharing!|
    {I really|I truly|I seriously|I absolutely} love {your
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    Did you {create|develop|make|build} {this website|this site|this web site|this amazing site} yourself?
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    own personal} {blog|website|site} and {would like to|want to|would love to}
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    {is called|is named}. {Thanks|Many thanks|Thank you|Cheers|Appreciate it|Kudos}!|
    {Hi there|Hello there|Howdy}! This {post|article|blog post} {couldn’t|could not} be written {any better|much better}!
    {Reading through|Looking at|Going through|Looking through} this {post|article} reminds me of my previous roommate!
    He {always|constantly|continually} kept {talking about|preaching about} this.
    {I will|I’ll|I am going to|I most certainly will} {forward|send} {this article|this
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    {Thank you for|Thanks for|Many thanks for|I appreciate you for}
    sharing!|
    {Wow|Whoa|Incredible|Amazing}! This blog looks {exactly|just} like my old one!
    It’s on a {completely|entirely|totally} different {topic|subject} but it has pretty much the same {layout|page
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    choice of colors!|
    {There is|There’s} {definately|certainly} {a lot to|a great deal to} {know about|learn about|find out about} this {subject|topic|issue}.
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    {You made|You’ve made|You have made} some {decent|good|really good} points there.

    I {looked|checked} {on the internet|on the web|on the net} {for more info|for more information|to find out more|to learn more|for additional
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    will go along with your views on {this website|this site|this web site}.|
    {Hi|Hello|Hi there|What’s up}, I {log on to|check|read} your {new stuff|blogs|blog} {regularly|like every week|daily|on a regular basis}.

    Your {story-telling|writing|humoristic} style
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    {Hi there|Hello}, I enjoy reading {all of|through} your {article|post|article post}.
    I {like|wanted} to write a little comment to support you.|
    I {always|constantly|every time} spent my half
    an hour to read this {blog|weblog|webpage|website|web site}’s {articles|posts|articles
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    {cup|mug} of coffee.|
    I {always|for all time|all the time|constantly|every time}
    emailed this {blog|weblog|webpage|website|web site} post page to all my {friends|associates|contacts},
    {because|since|as|for the reason that} if like to read it
    {then|after that|next|afterward} my {friends|links|contacts} will
    too.|
    My {coder|programmer|developer} is trying to {persuade|convince}
    me to move to .net from PHP. I have always disliked the idea because of the {expenses|costs}.

    But he’s tryiong none the less. I’ve been using {Movable-type|WordPress} on {a number of|a variety of|numerous|several|various}
    websites for about a year and am {nervous|anxious|worried|concerned} about switching to another platform.

    I have heard {fantastic|very good|excellent|great|good} things about blogengine.net.
    Is there a way I can {transfer|import} all my wordpress {content|posts} into it?
    {Any kind of|Any} help would be {really|greatly} appreciated!|
    {Hello|Hi|Hello there|Hi there|Howdy|Good day}!
    I could have sworn I’ve {been to|visited} {this blog|this web site|this website|this
    site|your blog} before but after {browsing through|going through|looking at} {some of the|a few
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    {Anyways|Anyhow|Nonetheless|Regardless}, I’m {definitely|certainly} {happy|pleased|delighted} {I found|I discovered|I came across|I stumbled upon} it and I’ll be {bookmarking|book-marking} it
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    {Terrific|Great|Wonderful} {article|work}! {This is|That is} {the type
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    {Disgrace|Shame} on {the {seek|search} engines|Google} for {now not|not|no longer} positioning this {post|submit|publish|put up} {upper|higher}!
    Come on over and {talk over with|discuss with|seek
    advice from|visit|consult with} my {site|web site|website} .
    {Thank you|Thanks} =)|
    Heya {i’m|i am} for the first time here. I {came across|found} this board and I find It {truly|really} useful & it helped me out {a
    lot|much}. I hope to give something back and {help|aid}
    others like you {helped|aided} me.|
    {Hi|Hello|Hi there|Hello there|Howdy|Greetings}, {I think|I
    believe|I do believe|I do think|There’s no doubt that} {your site|your website|your web site|your blog} {might
    be|may be|could be|could possibly be} having {browser|internet browser|web
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    {When I|Whenever I} {look at your|take a look at your} {website|web site|site|blog} in Safari,
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    opening in {Internet Explorer|IE|I.E.}, {it has|it’s got} some overlapping issues.
    {I just|I simply|I merely} wanted to {give you a|provide you with a} quick heads up!
    {Other than that|Apart from that|Besides that|Aside from that},
    {fantastic|wonderful|great|excellent} {blog|website|site}!|
    {A person|Someone|Somebody} {necessarily|essentially} {lend a hand|help|assist} to
    make {seriously|critically|significantly|severely}
    {articles|posts} {I would|I might|I’d} state. {This
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    {create|make} {this actual|this particular} {post|submit|publish|put up} {incredible|amazing|extraordinary}.
    {Great|Wonderful|Fantastic|Magnificent|Excellent} {task|process|activity|job}!|
    Heya {i’m|i am} for {the primary|the first} time here. I {came across|found} this board and I {in finding|find|to
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    {I just|I simply} {would like to|want to|wish to} {give you a|offer
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    {I will be|I’ll be|I am} {coming back to|returning to} {your
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    I {always|all the time|every time} used to {read|study} {article|post|piece of writing|paragraph} in news papers but now as I
    am a user of {internet|web|net} {so|thus|therefore} from now I am using net
    for {articles|posts|articles or reviews|content}, thanks
    to web.|
    Your {way|method|means|mode} of {describing|explaining|telling} {everything|all|the whole thing} in this
    {article|post|piece of writing|paragraph} is {really|actually|in fact|truly|genuinely} {nice|pleasant|good|fastidious},
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    aware of} it, Thanks a lot.|
    {Hi|Hello} there, {I found|I discovered} your {blog|website|web site|site} {by means of|via|by the
    use of|by way of} Google {at the same time as|whilst|even as|while} {searching
    for|looking for} a {similar|comparable|related}
    {topic|matter|subject}, your {site|web site|website} {got here|came} up, it {looks|appears|seems|seems to be|appears
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    {Hello|Hi} there, {simply|just} {turned into|became|was|become|changed into} {aware of|alert to} your
    {blog|weblog} {thru|through|via} Google, {and found|and
    located} that {it is|it’s} {really|truly} informative.
    {I’m|I am} {gonna|going to} {watch out|be careful} for brussels.

    {I will|I’ll} {appreciate|be grateful} {if you|should you|when you|in the event you|in case you|for those who|if you happen to} {continue|proceed} this {in future}.
    {A lot of|Lots of|Many|Numerous} {other folks|folks|other people|people} {will be|shall be|might be|will
    probably be|can be|will likely be} benefited {from your|out of your}
    writing. Cheers!|
    {I am|I’m} curious to find out what blog {system|platform} {you
    have been|you happen to be|you are|you’re} {working with|utilizing|using}?
    I’m {experiencing|having} some {minor|small} security {problems|issues} with my latest {site|website|blog} and {I would|I’d} like to
    find something more {safe|risk-free|safeguarded|secure}.
    Do you have any {solutions|suggestions|recommendations}?|
    {I am|I’m} {extremely|really} impressed with your writing skills {and also|as well
    as} with the layout on your {blog|weblog}. Is this a paid theme or did you {customize|modify} it yourself?

    {Either way|Anyway} keep up the {nice|excellent} quality writing, {it’s|it is} rare
    to see a {nice|great} blog like this one {these
    days|nowadays|today}.|
    {I am|I’m} {extremely|really} {inspired|impressed} {with your|together with your|along with your} writing {talents|skills|abilities} {and also|as {smartly|well|neatly} as} with the {layout|format|structure} {for
    your|on your|in your|to your} {blog|weblog}. {Is this|Is that this} a paid
    {subject|topic|subject matter|theme} or did you
    {customize|modify} it {yourself|your self}? {Either way|Anyway} {stay|keep} up the {nice|excellent} {quality|high quality} writing, {it’s|it is} {rare|uncommon} {to peer|to see|to look} a {nice|great} {blog|weblog} like this one {these days|nowadays|today}..|
    {Hi|Hello}, Neat post. {There is|There’s} {a problem|an issue} {with your|together
    with your|along with your} {site|web site|website} in {internet|web} explorer,
    {may|might|could|would} {check|test} this? IE {still|nonetheless} is
    the {marketplace|market} {leader|chief} and {a large|a good|a big|a huge} {part of|section of|component to|portion of|component of|element of} {other folks|folks|other people|people} will {leave out|omit|miss|pass over} your {great|wonderful|fantastic|magnificent|excellent} writing {due to|because of} this problem.|
    {I’m|I am} not sure where {you are|you’re} getting your {info|information}, but {good|great} topic.
    I needs to spend some time learning {more|much more} or understanding more.
    Thanks for {great|wonderful|fantastic|magnificent|excellent} {information|info} I was looking for this
    {information|info} for my mission.|
    {Hi|Hello}, i think that i saw you visited
    my {blog|weblog|website|web site|site} {so|thus} i came to “return the favor”.{I
    am|I’m} {trying to|attempting to} find things to
    {improve|enhance} my {website|site|web site}!I suppose its ok to use
    {some of|a few of} your ideas!!\

  47. Dancewear disse:

    Hi, i believe that i saw you visited my website thus i got here to go back
    the favor?.I am trying to find issues to enhance my web site!I guess its ok to use a few
    of your ideas!!

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