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Indikasi Tuberkulosis, dalam kombinasi dengan obat lain. Infeksi M. Leprae. Profilaksis meningitis meningococcal dan infeksi haemophilus influenzae. Brucellosis, penyakit legionnaires, endocarditis dan infeksi staphylococcus yang berat dalam kombinasi dengan obat lain Dosis, Cara Pemberian dan Lama Pemberian Oral ( Dosis IV infusi sama dengan pemberian peroral) Terapi Tuberkulosis Catatan : Regimen empat obat ( isoniazid, rifampisin, pirazinamid dan etambutol) lebih disukai untuk pengobatan awal, empirik TB Bayi dan anak-anak < 12 tahun Terapi harian : 10 – 20 mg/kg/hari biasanya sebagai dosis tunggal (maksimal 600 mg/hari) Dua kali seminggu DOT (directly observed therapy) : 10 – 20 mg/kg (maksimal 600 mg/hari) Dewasa Terapi harian : 10 mg/kg/hari biasanya sebagai dosis tunggal (maksimal 600 mg/hari) Dua kali seminggu DOT (directly observed therapy) : 10 mg/kg (maksimal 600 mg/hari) ; 3 kali/minggu : 10 mg/kg (maksimal 600 mg/hari) Infeksi tuberkulosis latent (yang belum nampak): sebagai alternatif untuk isoniazid : Anak-anak : 10 – 20 mg/kg/perhari (maksimal : 600 mg/hari) selama 6 bulan Dewasa : 10 mg/kg/hari (maksimal : 600 mg/hari) selama 4 bulan Profilaksis H. Influenzae (unlabeled use) Bayi dan anak-anak : 20 mg/kg/hari tiap 24 jam selama 4 hari, tidak lebih dari 600 mg/dosis Dewasa : 600 mg setiap 24 jam selama 4 hari Leprosy (unlabeled use) : dewasa : Multibacillary : 600 mg sekali sebulan selama 24 bulan dalam kombinasi dengan ofloksasin dan minosiklin Paucibacillary : 600 mg sekali sebulan selama 6 bulan dalam kombinasi dengan dapson Lesi tunggal : 600 mg sebagai dosis tunggal dalam kombinasi dengan ofloksasin 400 mg dan minosiklin 100 mg Profilaksis meningitis meningococcal. Bayi , 1 bulan : 10 mg/kg/hari dalam dosis terbagi tiap 12 jam selama 2 hari Bayi = 1 bulan dan anak-anak : 20 mg/kg/hari dalam dosis terbagi tiap 12 jam selama 2 hari (maksimal 600 mg/dosis) Dewasa : 600 mg tiap 12 jam selama 2 hari Staphylococcus aureus pada nasal carrier (unlabeled use): Anak-anak: 15 mg/kg/hari dibagi tiap 12 jam selama 5 – 10 hari dalam kobinasi dengan antibiotik lain Dewasa : 600 mg/hari selama 5 – 10 hari dalam kombinasi dengan antibiotik lain Penyesuaian dosis pada pasien dengan kerusakan hepar : penurunan dosis diperlukan untuk meurunkan hepatotoksisitas Hemodialysis atau peritoneal dialysis : konsentreasi plasma rifampisin tidak signifikan dipengaruhi oleh hemodialisis atau dialisis peritoneal Farmakologi Durasi : < 24 jam Absorbsi : Oral : diabsorpsi dengan baik; makanan dapat mengakibatkan penundaan absorpsi (delay) atau sedikit menurunkan kadar puncak Distribusi : sangat lipofilik , dapat menembus sawar darah otak (bood-brain barrier) dengan baik Difusi relatif dari darah ke dalam cairan serebrospinal : adekuat dengan atau tanpa inflamasi CSF : inflamasi meninges : 25% Metabolisme : Hepatik; melalui resirkulasi enterohepatik Ikatan protein : 80% T½ eliminasi : 3-4 jam; waktu tersebut akan memanjang pada gagal hepar; gagal ginjal terminal : 1,8-11 jam. Waktu untuk mencapai kadar puncak, serum: oral : 2-4 jam Ekskresi : Feses (60% - 65%) dan urin (~ 30%) sebagai obat yang tidak berubah Stabilitas Penyimpanan Serbuk rifampisin berwarna merah kecoklatan. Vial yang utuh harus disimpan pada suhu kamar dan dihindarkan dari cahaya dan panas yg berlebihan. Rekonstitusi serbuk untuk injeksi dengan SWFI; untuk injeksi larutkan dalam sejumlah volume yg tepat dengan cairan yang kompatibel (contoh : 100 ml D5W). Vial yang telah direkontitusi stabil selama 24 jam pada suhu kamar.Stabilitas parenteral admixture pada penyimpanan suhu kamar (25°C) adalah 4 jam untuk pelarut D5W dan 24 jam untuk pelarut NS Kontraindikasi Hipersensitivitas terhadap rifampisin atau komponen lain yang terdapat dalam sediaan; penggunaan bersama amprenavir, saquinafir/rotonavir (kemungkinan dengan proease inhibitor), jaundice (penyakit kuning) Efek Samping Gangguan saluran cerna seperti anoreksia, mual, muntah, diare (dilaporkan terjadi kolitis karena penggunaan antibiotika); sakit kepala, drowsiness; gejala berikut terjadi terutama pada terapi intermitten termasuk gelala mirip influenza ( dengan chills, demam, dizziness, nyeri tulang), gejala pada respirasi (termasuk sesak nafas), kolaps dan shock, anemia hemolitik, gagal ginjal akut, dan trombositopenia purpura; gangguan fungsi liver, jaundice(penyakit kuning); flushing, urtikaria dan rash; efek samping lain dilaporkan : edema, muscular weakness dan myopathy, dermatitis exfoliative, toxic epidermal necrolysis, reaksi pemphigoid, leucopenia, eosinophilia, gangguan menstruasi; urin, saliva dan sekresi tubuh yang lain berwarna orange-merah; tromboflebitis dilaporkan pada penggunaan secara infus pada periode yang lama. Interaksi
Efek Cytochrome P450 : substrat CYP2A6, 2C8/9, 3A4 (major) ; Induksi CYP1A2 (kuat) ,2A6 (kuat), 2B6 (kuat), 2 C8/9(kuat), 2C19 (kuat), 3A4 (kuat). Meningkatkan efek/toksisitas : Rifampisin dapat meningkatkan efek terapeutik clopidogrel, penggunaan bersama dengan isoniazid pyrazinamide atau protease inhibitor (amprenavir saquinavir/ritonavir) dapat meningkatkan resiko hepatotoksisitas; antibiotika makrolida dapat meningkatkan kadar/toksisitas rifampin. Menurunkan efek : Rifampisin dapat menurunkan efek/kadar obat-obat berikut: asetaminofen, alfentanil, amiodaron,angiotensin II receptor blocker (irbesartan dan losartan), 5-HT3 antagonis, antifungi imidazol, aprepitant, barbiturat, benzodiazepin (dimetabolisme melalui oksidasi), beta blocker, buspiron, calsium channel blocker, kloramfenikol, kortikosteroid, siklosporin; substrat CYP1A2, 2A6, 2B6, 2C8/9, 2C19 DAN 3A4 (contoh : aminofilin, amiodaron, bupropion, fluoksetin, fluvoksamin, ifosfamid, methsuksimid, mirtazapin, nateglinid, pioglitazon, promethazin, inhibitor pompa proton, ropinirol, rosiglitazon, selegilin, sertralin, teofilin, venlafaxin dan zafirlukast; dapson, disopiramid, kontrasepsi estrogen dan progestin, feksofenadin, flukonazol, asam fusidat, HMG-CoA reductase inhibitor, metadon, morfin, fenitoin, propafenon, inhibitor protease, quinidin, repaglinid, inhibitor reverse transkriptase (non-nucleoside), sulfonilurea, takrolimus, tamoksifen, terbinafin, tocainide, antidepresan trisiklik, warfarin,zaleplon, zidovudin, zolpidem. Efek rifampisin diturunkan oleh inducer CYP2A6, 2C8/9, dan 3A4 (seperti : aminoglutethimide, barbiturat, karbamazepin, nafcillin, nevirapin dan fenitoin) - Dengan Makanan : Makanan menurunkan absorbsi; konsentrasi rifampin dapat diturunkan jika digunakan bersama dengan makanan. Hindari ethanol (dapat meningkatkan resiko hepatotoksisitas) St. John’s wort dapat menurunkan kadar rifampisin
Fungsi hati (AST, ALT, bilirubin), CBC, hepatic status dan mental status, kultur sputum, x-ray dada Bentuk Sediaan Kapsul, Kaptab, Sirup Peringatan Kerusakan hati ( periksa tes fungsi hati dan pemeriksaan darah pada gangguan hati, ketergantungan alkohol, dan pada terapi dalam jangka waktu yang lama); kerusakan ginjal (jika digunakan dosis di atas 600 mg sehari); kehamilan dan menyusui; porfiria; Penting : pasien yang menggunakan hormon kontrasepsi disarankan untuk menggantinya dengan alternatif kontrasepsi lain seperti IUD, karena efek obat kontrasepsi menjadi tidak efektif akibat adanya interaksi obat. Kasus Temuan Dalam Keadaan Khusus - Informasi Pasien Jumlah dan frekuensi penggunaan obat tergantung dari beberapa faktor, seperti kondisi pasien, umur dan berat badan. Bila anda mempunyai pertanyaan yang berkaitan dengan jumlah dan/ frekwensi pemakaian obat tanyakan pada dokter atau apoteker. Obat ini menyebabkan warna merah pada urin, keringat, saliva dan air mata. Obat ini juga dapat menimbulkan noda permanen pada lensa kontak. Mempengaruhi efektifitas kontrasepsi oral, gunakan metoda KB yang lain. Rifampisin harus digunakan pada saat lambung kosong, gunakan 1 jam sebelum atau 2 jam sesudah makan dengan segelas air. Gunakan obat ini sedikitnya 1 jam sebelum menggunakan antasida. Segera memeriksakan diri ke dokter bila timbul demam, hilang nafsu makan, tidak enak badan, mual, muntah, urin berwarna gelap, perubahan warna kulit dan mata menjadi kekuningan atau nyeri atau bengkak pada persendian. Pasien harus menggunakan obat hingga habis. Jangan sampai terdapat dosis yang terlewat. Jangan menghentikan pemakaian obat ini tanpa berkonsultasi dengan dokter. Jangan menggunakan obat melebihi jumlah yang telah diresepkan, kecuali atas anjuran dokter. Jangan menggunakan OTC atau obat resep yang lain tanpa memberitahu dokter yang merawat. Jika pasien lupa minum obat, segera mungkin minum obat setelah ingat. Jika terlewat beberapa jam dan telah mendekati waktu minum obat berikutnya jangan minum obat dengan dosis ganda, kecuali atas saran dari tenaga kesehatan . Jika lebih dari satu kali dosis terlewat, mintalah nasehat dokter atau apoteker. Obat ini hanya digunakan oleh pasien yang mendapat resep. Jangan diberikan pada orang lain. Mekanisme Aksi Menghambat sintesis RNA bakteri dengan mengikat subunit beta dari DNA-dependent RNA polymerase, menghambat transkripsi RNA Monitoring Penggunaan Obat Periodik (sebelum pengobatan dan tiap 2 – 4 minggu selama terapi) monitoring fungsi hati (AST, ALT, bilirubin), CBC; status fungsi hati dan mental , kultur sputum, x-ray dada 2 – 3 bulan pengobatan |
Antibiotika Rifampicin dapat mengurangi efektivitas dari berbagai pil kontraseptif. Sehingga ibu-ibu yang menggunakan pil KB sebaiknya berhati-hati ketika mengonsumsi antibiotika. Bisa-bisa pil KB-nya tidak bekerja pada saat Ibu diterapi dengan rifampicin, sehingga program KB nya bisa gagal. Kombinasi rifampicin-pil KB ini juga dapat meningkatkan ririko terjadinya perdarahan.
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