KOMPOSISI :
Tiap PROLEVOX® 250 tablet salut selaput mengandung,
Levofloxacin hemihidrat setara dengan Levofloxacin..... 250 mg

Tiap PROLEVOX® 500 tablet salut selaput mengandung,
Levofloxacin hemihidrat setara dengan Levofloxacin..... 500 mg

FARMAKOLOGI :
Levofloxacin merupakan S -(-) isomer Ofloxacin. Levofloxacin memiliki efek antibakterial dengan spektrum luas, aktif terhadap bakteri gram-positif dan gram-negatif termasuk bakteri anaerob. Levofloxacin telah menunjukkan aktifitas antibakterial terhadap Chlamydia pneumonia dan Mycoplasma pneumonia. Mekanisme kerja dari Levofloxacin adalah melalui penghambatan topoisomerase type II DNA gyrase, yang menghasilkan penghambatan replikasi dan transkripsi DNA bakteri.
Levofloxacin didistribusikan ke seluruh tubuh dalam konsentrasi yang tinggi dan berpenetrasi ke dalam jaringan paru-paru dengan baik. Konsentrasi dalam jaringan paru-paru biasanya lebih tinggi 2-5 kali dari konsentrasi dalam plasma, dan berkisar antara 2,4 sampai 11,3 µg/g selama 24 jam setelah pemberian tunggal dosis oral 500 mg.

INDIKASI :
PROLEVOX® diindikasikan untuk infeksi-infeksi sebagai berikut :
- Sinusitis maksilaris akut.
- Bronkitis kronis eksaserbasi bakterial akut.
- Community acquired pneumonia.
- Infeksi kulit dan jaringan kulit yang tidak terkomplikasi.
- Infeksi saluran kemih terkomplikasi.
- Pyelonephritis akut.

KONTRA INDIKASI :
Penderita yang hipersensitif terhadap levofloxacin, antimikroba golongan kuinolon dan komponen dari obat ini.

EFEK SAMPING :
Efek samping yang dapat terjadi : diare, mual, kembung, konstipasi, nyeri perut, sakit kepala, insomnia, agitasi, anorexia, ansietas, arthralgia, mulut kering, dyspnea, edema, lelah, demam, genital pruritus, keringat berlebih, gelisah, rhinitis, gangguan kulit, somnolence dan hilang rasa.

PERHATIAN :
- Keamanan dan manfaat dari levofloxacin pada anak-anak, dewasa dibawah usia 18 tahun, wanita hamil dan menyusui belum terbukti.
- Kolitis pseudomembranosa telah dilaporkan pada penggunaan beberapa antibiotika termasuk levofloxacin, dari gejala yang ringan sampai yang mengancam jiwa, oleh karena itu perlu dipertimbangkan diagnosis keadaan tersebut pada penderita yang mengalami diare sehubungan dengan pemberian antibiotika.
- Penggunaan jangka panjang dapat menyebabkan flora usus normal terbunuh dan pertumbuhan berlebih dari bakteri clostridia yang dapat menghasilkan toxin.
- Konvulsi dan toxic psikosis pernah dilaporkan pada penggunaan antibiotika kuinolon termasuk levofloxacin.
- Reaksi hipersensitif yang fatal pernah dilaporkan, hentikan penggunaan levofloxacin apabila timbul gejala-gejala hipersensitif.
- Reaksi fototoksisitas ringan sampai berat telah diamati pada penderita yang terkena sinar matahari langsung selama menerima obat-obat golongan ini.
- Sama dengan golongan kuinolon lainnya, levofloxacin harus digunakan dengan hati-hati pada penderita yang diketahui atau dicurigai menderita gangguan SSP karena dapat menjadi faktor predisposisi bangkitan kejang atau menurunkan ambang bangkitan kejang (seperti pada arteriosklerosis serebral berat, epilepsi) atau adanya faktor risiko lain yang dapat mempengaruhi bangkitan kejang atau menurunkan ambang bangkitan kejang.
- Sama dengan golongan kuinolon lainnya, gangguan glukosa darah, termasuk hiper dan hipoglikemia telah dilaporkan, biasanya pada penderita diabetes, yang menerima pengobatan bersama-sama dengan obat oral hipoglikemik atau dengan insulin.

INTERAKSI OBAT :
- Levofloxacin potensial membentuk chelat dengan beberapa ion logam, misalnya dengan Al, Cu, Zn dan Ca, dimana urutan potensial pembentukan chelat adalah Al3+ > Cu2+ > Zn2+ > Ca2+. Antasid yang mengandung alumunium atau magnesium dan obat yang mengandung besi menurunkan absorpsi levofloxacin. Pemberian obat-obat ini sebaiknya 2 jam sebelum atau sesudah pemberian PROLEVOX® .
- Pemberian bersama-sama obat AINS dengan kuinolon termasuk PROLEVOX® dapat meningkatkan risiko stimulasi SSP dan bangkitan kejang.
- Bioavailabilitas levofloxacin secara bermakna akan menurun apabila diberikan bersama-sama dengan sucralfate.
- Probenisid dan Cimetidine secara statistik bermakna mempengaruhi eliminasi levofloxacin.
- Cyclosporin : waktu paruh cyclosporin meningkat 33% apabila diberikan bersamaan dengan levofloxacin.
DOSIS :
Dosis lazim untuk :
- Penderita dengan fungsi ginjal normal :
250 mg - 500 mg per oral. Satu kali sehari selama 7 - 14 hari tergantung dari beratnya penyakit, seperti pada infeksi sebagai berikut :

- Penderita dengan gangguan fungsi ginjal :
Bersihan kreatinin 50 - 80 ml/menit : tidak memerlukan penyesuaian dosis.
Bersihan kreatinin 20 - 49 ml/menit : dosis awal 500 mg dosis selanjutnya 250 mg setiap 24 jam.
Bersihan kreatinin 10 - 19 ml/menit, hemodialisa, dialisa peritonial kronis : dosis awal 500 mg dosis selanjutnya 250 mg setiap 48 jam.

KEMASAN :
PROLEVOX® 250 tablet salut selaput
Dus, 1 strip @ 10 tablet salut selaput
No. Reg. : DKL 0315617417 A1

PROLEVOX® 500 tablet salut selaput
Dus, 1 strip @ 10 tablet salut selaput
No. Reg. : DKL 0315617417 B1

HARUS DENGAN RESEP DOKTER

Simpan pada suhu kamar (25 - 30)º C, kering dan terlindung dari cahaya

ENGLISH VERSION

COMPOSITION:
- PROLEVOX 250 film-coated tablet, each tablet contains:
Levofloxacin ……………………. 250 mg
- PROLEVOX 500 film-coated tablet, each tablet contains:
Levofloxacin ……………………. 500 mg

MECHANISM OF ACTION:
Prolevox, an oral fluoroquinolone, is the S-(-)isomer of ofloxacin. It has a wide-spectrum antibacterial effect. Prolevox is active against gram-positive and gram-negative bacteria including anaerobs. Moreover, levofloxacin has shown antibacterial activity against Chlamydia pneumoniae and Mycoplasma penumoniae. The main mechanism of action of Prolevox is through the inhibition of DNA gyrase, a type II topoisomerase, resulting in inhibition of bacterial DNA replication and transcription.

PHARMACOKINETIC:
Prolevox is rapidly and completely absorbed after oral administration. Peak plasma concentrations are usually attained 1-2 hours after oral dosing. The absolute bioavailability of a 500 mg oral dose of levofloxacin is approximately 99%. Levofloxacin is widely distributed throughout the body in high concentration. Levofloxacin also penetrates well into lung tissue. Lung tissue concentrations were generally 2-5 fold higher than plasma concentrations and range from approximately 2.4-11.3 mcg/g over a 24 hours period after a single 500 mg oral dose.

INDICATIONS:
Infections caused by susceptible microorganisms, eg:
- Acute Maxillary Sinusitis
- Acute Bacterial exacerbations of chronic bronchitis
- Community acquired pneumonia
- Uncomplicated Skin and skin Structure Infections
- Complicated Urinary Tract Infections
- Acute Pyelonephritis

CONTRA-INDICATIONS:
Hypersensitivity to levofloxacin and other quinolone derivates. Pregnant or breastfeeding women, children and adolescents in the growth phase.

ADVERSE REACTIONS:
Diarrhoea, nausea, flatulence, constipation, abdominal pain, headache, insomnia, agitation, anorexia, anxiety, arthralgia, dry mouth, dyspnoea, oedema, fatigue, fever, genital pruritus, increased sweating, nervousness, rhinitis, skin disorder, somnolence, taste perversion.

PRECAUTIONS AND WARNINGS:
- The safety and efficacy of levofloxacin in children, adolescents (<18 years), pregnant and nursing mothers have not been established.
- Pseudomembranous colitis has been reported with nearly all antibacterial agents, including levofloxacin, and may range in severity from mild to the life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the adminitration of any antibacterial agent. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic-associated colitis”. After the diagnosis of pseudomembranous colitis has been established, therapeutic measure should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis.
- Convulsions and toxic psychoses have been reported in patients receiving quinolones, including levofloxacin.
- Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones. The drug should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity and supportive measures instituted.
- Moderate to severe phototoxicity reactions have been observed in patients exposed to direct sunlight while receiving drugs in this class.
- As with other quinolones, levofloxacin should be used with caution in any patient with known or suspected CNS disorder that may predispose to seizures or lower the seizure threshold (eg, severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that ay predispose to seizures or lower the seizure threshold.
- As with other quinolones, disturbances of blood glucose, including symptomatic hyper and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent or with insulin.

DRUG INTERACTIONS:
- Levofloxacin has potential to form stable coordination compounds with many metal ions. This in vitro chelation potential has following formation with Al+3>Cu+2>Zn+2>Ca+2. Antacids containing aluminium or magnesium and drugs containing iron decrease absorption of levofloxacin. The administration of these drugs are recommended at least 2 hours before or after Prolevox administration.
- The concomitant administration of a non steroidal anti-inflammatory drug with a quinolone including Prolevox, may increased the risk of CNS stimulation and convulsive seizures.
- The concomitant administration of levofloxacin with sucralfate, may reduced the bioavailability of levofloxacin.
- The cyclosporin half time will increased 33% if given concomitantly with levofloxacin.

DOSAGE AND ADMINISTRATION:
- Patients with normal renal function: 250-500 mg once daily for 7-14 days depending on the severity of the disease.
- Patients with impaired renal function:
Creatinine clearance of 50-80 mL/min: no dosage adjustment required.
Creatinine clearance of 20-49 mL/min: Initially 500 mg, subsequent dose 250 mg every 24 hours.
Creatinine clearance of 10-19 mL/min, haemodialysis and chronic ambulatory peritoneal dialysis: Initially 500 mg, subsequent dose 250 mg every 48 hours.

PRESENTATIONS:
PROLEVOX 250: Box of 1 strip @ 10 film-coated tablets
PROLEVOX 500: Box of 1 strip @ 10 film-coated tablets