Farmakol-Anti Jamur New
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A. ANTI JAMUR UNTUK INFEKSI
SISTEMIK
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1. AMFOTERICIN B
Hasil fermentasi Streptomyces nodosus
Kristal seperti jarum atau prisma berwarna kuning jingga, tidak berbau, tidak terasa, tidak larut dalam air, tidak stabil, tidak tahan suhu > 37oC, dpt bertahan sampai berminggu-minggu pada suhu 4oC
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• Pada pH 6,0 – 7,5 berkurang pada pH <
• Bersifat fungistatik / fungisidal• Kadar 0,3 – 1,0
g/ml ,menghambat : H.capsulatum, C.neoformans, C.immitis, spesies Candida, Paracoccidiodes braziliensis , Sporotrichum schenckii, M.audiouini, spesies Aspergillus & spesies Trichophyton
• Pemberian bersama rifampisin atau minosiklin sinergisme
Aktivitas Anti Jamur
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• Terikat pada ergosterol kerusakan fungsi barier membran, kehilangan beberapa bahan intrasel, kerusakan membran kematian sel
• Resistensi terjadi perubahan reseptor sterol pada membran sel
Mekanisme Kerja
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• Sedikit di absorbsi melalui sal. cerna
• Waktu paruh 24 – 48 jam pada dosis awal, diikuti eliminasi fase ke-2 dgn waktu paruh 15 hari
• Distribusi luas ke seluruh jaringan
95% terikat pada lipoprotein
• Dapat menembus sawar uri, CSS, humor vitreus, cairan amnion
• Ekskresi via ginjal lambat
Farmakokinetik
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• Amfoterisin B IV kulit panas, keringatan, sakit kepala, demam, menggigil, anoreksia, nyeri otot, flebitis, kejang, penurunan fungsi ginjal
• Anemia normositik normokrim (pada pemakaian jangka panjang)
Efek Samping
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• Terapi awal untuk infeksi jamur serius
• Drug of choice untuk blastomikosis
• Amfoterisin B topikal korneal & keratitis mikotik
Indikasi
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• Vial berisi 50 mg bubuk lipofilik dilarutkan dgn 10 mg aquades steril kmd diencerkan dgn dextrose 5% sehingga didapat kadar 0,1 mg/ml amfoterisin B konvensional / amfoterisin B deoksikolat
Dosis efektif : 0,3 – 0,5 mg/kgBB• Infus intratekal 0,5 mg
amfoterisin B dilarutkan dlm 5 ml cairan spinal u/ pasien meningitis oleh Coccidiodes
Sediaan & Posologi
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• Amfoterisin B formulasi baru (amfoterisin B liposomal / formulasi lipid) tdd :1.Amfoterisin B formulasi
dispersi koloid (ABCD) dosis 3 – 4 mg/kgBB/hr dlm btk infus 3 – 4 jam
2.Amfoterisin B formulasi vesikel unilamelar (Ambisome) dosis 3 mg/kgBB/hr
Sediaan & Posologi
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3.Amfoterisin B kompleks lipid (ABLC) dosis 5 mg/kgBB/hr dalam infus dextrosa 5% selama 2 jam
• Tersedia juga amfoterisin B dalam bentuk krim, losio & salep 3%.
Sediaan & Posologi
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Merupakan anti jamur sintetik dari fluorinasi pirimidin
Bentuk kristal putih, tidak bau, sedikit larut dalam air, mudah larut dalam alkohol
2. FLUSITOSIN
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• Spektrum anti jamur agak sempit
• Efektif untuk terapi kriptokokosis, kandidiasis, kromomikosis, torulopsis & aspergillosis
Aktivitas Anti Jamur
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Flusitosin sel jamur sintesis protein sel jamur terganggu oleh penghambatan langsung sintesis DNA oleh metabolit fluorourasil
Mekanisme Kerja
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• Absorbsi baik & cepat, diperlambat oleh makanan, antasida & neomisin
• Kadar puncak 70 – 80 g/ml dlm 1 – 2 jam stlh dosis 37,5 mg/kgBB
• Kadar dlm cairan otak 60 – 90%• Dlm saliva kadar flusitosin ½
kadar dlm darah• 90% dikeluarkan mll filtrasi
glomerulus• Masa paruh eliminasi 3 – 6 jam• Dpt dikeluarkan melalui
hemodialisis atau peritoneal dialisis
Farmakokinetik
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• Anemia, leukopenia & trombositopenia
• Mual, muntah, diare, enterokolitis hebat
• SGOT/SGPT, hepatomegali• Sakit kepala, pusing,
mengantuk & halusinasi
Efek Samping
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• Pemakaian tunggal untuk infeksi Cryptococcus neoformans, spesies Candida dan kromoblastomikosis
• Untuk infeksi lain di kombinasi dengan amfoterisin B
Indikasi
• Kapsul 250 & 500 mg• Dosis : 50 – 150
mg/kgBB /hr dalam 4 dosis
Sediaan & Posologi
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3. IMIDAZOL & TRIAZOL
Imidazol Ketokonazol,
Mikonazol,
Klotrimazol
Triazol Itrakonazol,
Flukonazol,
Vorikonazol
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A. Ketokonazol
• Aktif sebagai anti jamur sistemik maupun non sistemik
• Efektif terhadap C.neoformans, H.capsulatum, B.dermatititidis, Aspergillus & Sporothrix spp
Bersifat lipofilik & larut dlm air pd pH asam
Aktivitas Anti Jamur
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• Absorbsi bervariasi antar individu, berkurang pada pH lambung ↑, pemberian bersama AH2 atau antasida
• Ditemukan dlm urin, kelenjar lemak, liur, kulit yg infeksi, tendo, cairan sinovial, cairan vaginal
• Sebagian besar mengalami metabolisme lintas pertama
Farmakokinetik
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• 84% berikatan dengan protein plasma (albumin), 15% dengan eritrosit, 1% bentuk bebas
• Ekskresi bersama cairan empedu, sebagian kecil via urin
Farmakokinetik
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• Mual, muntah, sakit kepala, vertigo, nyeri epigastrik, fotofobia
• Pruritus, parestesia, gusi berdarah, erupsi kulit, trombositopenia
• Peningkatan aktivitas enzim hati hepatotoksisitas
• Ginekomastia pada pria• Gangguan haid• KI : wanita hamil & menyusui
Efek Samping
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• Histoplasmosis paru, tulang, sendi & jaringan lemak
• Kriptokokkus non meningeal
• Parakoksidiomikosis, dermatomikosis, kandidiasis (mukokutan, vaginal & oral)
Indikasi
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• Pemberian bersama rifampisin, INH, fenitoin penurunan kadar ketokonazol
• Ketokonazol dapat meningkatkan kadar siklosporin, warfarin, midazolam
Interaksi Obat
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Pemberian bersama terfenadin, astemizol, cisaprid perpanjangan interval QT dan aritmia ventrikel jantung
Kontraindikasi
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• Tablet 200 mg, krim 2%, shampo 2%
• Dosis : dewasa 200 – 400 mg/hr, anak-anak 3,3 – 6,6 mg/kg/hr
• Lama terapi bervariasi : Kandidiasis vulvovaginal &
Pt.versicolor 5 hariMikosis profunda 6 – 12 bln.
Posologi
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• Dapat diberikan per oral & IV
• Aktivitas anti jamur > & efek samping > daripada ketokonazol
• Absorbsi sempurna bila bersama makanan
• Rifampisin menurunkan kadar plasma itrakonazol
B. Itrakonazol
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• Mual• Muntah• Kemerahan• Pruritus• Lesu• Pusing• Edema kaki• Parestesia• Kehilangan
libido
Efek Samping
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• Blastomikosis• Histoplasmosis• Koksidioidomiko
sis• Tinea versicolor• Kandidiasis
Indikasi
Sediaan• Kapsul 100 mg, suspensi
10 mg/ml
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• Dermatofitosis : 100 mg/hr (T.kapitis, T.korporis/krutis selama 2 mgg; T.pedis et manus selama 4 mgg)
• Tinea unguium : 200 mg/hr 3 bln. Pulse therapy : 400 mg/hr 1 mgg, kuku tangan 2 PT, kuku kaki 3 PT
• Tinea versicolor : 200 mg/hr 1 mgg
• Vaginal candidosis : 2x200 mg/hr atau 1x200 mg/hr selama 3 hr
• Mikosis profunda : itrakonazol IV 2x200 mg/hr, diikuti 200 mg/hr 12 hr
Dosis
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St. fluorinated bis – triazol• Absorbsi sempurna• Kadar plasma setelah
pemberian oral = IV• Kadar dalam cairan
serebrospinal 50 – 90% kadar plasma
• Waktu paruh eliminasi 25 jam
C. Flukonazol
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• Gangguan saluran cerna• Urtikaria, eosinofilia, SSJ,
gangguan fungsi hati, trombositopenia
Efek Samping
Interaksi ObatPemberian bersama
akan : • ↑ kadar plasma
fenitoin & sulfonilurea• ↓ kadar plasma
warfarin & siklosporin
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• Kapsul 50 & 150 mg
Berguna mencegah relaps meningitis oleh Cryptococcus
pada AIDS
Sediaan
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• T.kapitis : 6 mg/kgBB/hr 2-3 mgg
• T.korporis/kruris : 150 mg/mgg 2-4 mgg
• T.pedis et manus : 150 mg/mgg 2-6 mgg
• T.unguium : 150 mg/mgg (kuku tangan : 3-6 bln ; kuku kaki : 9-12 bln)
• T.versicolor : 300 mg diulangi 2 mgg kemudian
• Kandidosis kutis : 250 mg/mgg 2-4 mgg
• Vaginal kandidosis : 150 mg single doses
Dosis
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• Aspergillosis sistemik• Infeksi jamur berat oleh
Scedosporium aplospermun & Fusarium sp
• Candida sp, Cryptococcus sp & Dermatophyte sp
D. Vorikonazol Anti jamur baru golongan triazol
Indikasi
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Absorbsi baik, kadar puncak 2 jam
80% di ekskresi via urin
60% terikat dengan proteinKadar dalam CSS : 30 – 68%
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• Gangguan penglihatan sementara (pandangan kabur, fotofobia)
• Reaksi fotosensitivitas• Kenaikan kadar
transaminase serum sementara
Efek Samping
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• Jangan diberi bersma rifampisin, karbamazepin, kuinidin
• Pemberian bersama ranitidin, omeprazole, fenitoin, benzodiazepin dan golongan statin penyesuaian dosis
Interaksi Obat
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• Tablet 50 & 200 mg• Suspensi oral (40
mg/ml)• Bubuk untuk IV 200
mg
Sediaan
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• Dosis oral :BB > 40 kg : 400 mg (intrval
12 jam)BB < 40 mg : 200 mg
(intrval 12 jam)Dilanjutkan
BB> 40 mg : 200 mg tiap 12 jam
BB < mg : 2x100 mg/hr
Dosis
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• Pasien dengan gangguan fungsi hati ringan-sedang : dosis muat seperti biasa tetapi dosis pemeliharaan dikurangi 50%
• Pasien dengan klirens kreatinin < 50 mL/mnt/mengalami dialisis hanya boleh vorikonazol IV
Dosis
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• Bekerja menghambat sintesis B (1,3)-D-glukan, st komponen esensial yg membtk dinding sel jamur
• 97% terikat protein, masa paruh eliminasi 9 – 11 jam
• Metabolisme lambat via hidrolisis & asetilasi
• Ekskresi via urin sedikit
4. KASPOFUNGIN Anti jamur sistemik kelas baru : Ekinokandin
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• Kandidiasis invasif• Kandidiasis
esofagus• Kandidiasis
orofarings• Aspergillosis
invasif
Indikasi
Efek Samping• Demam• Mual• Muntah• Flushin
g• Pruritus
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• ↓ konsentrasi takrolimus & siklosporin
• ↓ kadar kaspofungin bila diberi bersama karbamazepin, deksametason, fenitoin, rifampisin
Interaksi Obat
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• Hari pertama 70 mg IV dosis tunggal dilanjutkan 50 mg dosis tunggal IV (1 jam), 14 hari
• Untuk pasien insufisiensi hati sedang dosis pemeliharaan 35 mg/hr
Dosis
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• Absorbsi baik, bioavailabilitas 40%
• 90% terikat protein plasma, terakumulasi di kulit, kuku & jaringan lemak
• Waktu paruh : 12 jam
5. TERBINAFIN Derivat alilamin sintetik ≈ struktur naftitin
Farmakokinetik
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• Bersifat fungisidal• Bekerja mempengaruhi
biosintesis ergosterol dinding sel jamur melalui penghambatan enzim skualen epoksidase pada jamur
Aktivitas Anti Jamur
• Gangguan saluran cerna, sakit kepala, rash.
• SSJ / NET, hepatotoksisitas, neurotropenia
Efek Samping
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Sediaan• Tablet oral 250 mg, krim &
gel 1%
• T.Pedis : 250 mg/hr 2 mgg• T.korporis/kruris : 250 mg/hr 2
– 4 mgg• T.pedis et manus : 250 mg/ht
2 – 6 mgg• T.unguium : 250 mg/hr (kuku tangan 6 mgg ; kuku kaki
12 mgg)
Dosis
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B. ANTI JAMUR UNTUK INFEKSI DERMATOFIT
& MUKOKUTAN
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• Efektif terhadap jamur dermatofit (Trichophyton, Epidermophyton, Microsporum)
1. GRISEOFULVIN diisolasi dari Penicillium griseovulfin dierckxAktivitas Anti Jamur
• Menghambat mitosis sel jamur dgn menganggu sintesis & polimerisasi asam nukleat
Mekanisme Kerja
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Farmakokinetik• Absorbsi kurang baik, ↑ bila
diberi bersama makanan berlemak
• Di metabolisme di hati, metabolit utama 6-metilgriseofulvin
• Waktu paruh 24 jam, 50% dari dosis oral dikeluarkan via urin dalam bentuk metabolit
• Dpt ditemukan dalam lapisan tanduk 4 – 8 Jam setelah pemberian oral
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• Leukopenia, granulositopenia• Demam, pandangan kabur,
insomnia• ↓ fungsi motorik, sinkop,
pusing• Mual, muntah, diare,
flatulensi• Albuminuria• Reaksi fotosensitivitas,
urtikaria, eritema multiforme
Efek Samping
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• ↑ metabolisme warfarin, kontrasepsi oral
• Barbiturat menghambat absorbsi griseofulvin
Interaksi Obat
Sediaan• Tablet 125 mg & 500
mg• Ultramicrokristal
350 mg
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• Dewasa : 500 – 1000 mg/hr
• Anak-anak : < 25 kg 10
mg/kgBB/hr, > 25 kg 250 – 500
mg/kgBB/hr▼
untuk dermatofitosis pada :
rambut & kulit 4 mgg ;
kuku 6 – 12 mgg
Dosis
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Turunan imidazol sintetik yg relatif, spektrum anti jamur lebar
Bentuk kristal putih, tidak berwarna, tidak berbau, sebagian kecil larut dalam air, lebih larut dalam pelarut organik
2. IMIDAZOL & TRIAZOL
A. Mikonazol
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• Menghambat Trichophyton, Epidermophyton, Microsporum, Candida, M.furfur
• In vitro efektif terhadap beberapa kuman Gram (+)
Aktivitas Anti Jamur
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• Menyebabkan kerusakan dinding sel jamur permeabilitas terhadap zat intrasel ↑
• Gangguan sintesis asam nukleat atau penimbunan peroksida dlm sel jamur
Mekanisme Kerja
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• Iritasi• Rasa
terbakar• Maserasi
Indikasi
Efek Samping
• Dermatofitosis• T.versicolor• Kandidiasis
mukokutan
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• Krim 2%, bedak tabur 2xsehari selama 2 – 4 mgg
• Krim 2% intravaginal 1xsehari (malam) selama 7 hari
• Gel 2% : kandidiasis oral
Sediaan
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• Bentuk bubuk tidak berwarna, tidak larut dalam air, larut dalam alkohol & kloroform, sedikit larut dalam eter
• Memiliki efek anti jamur & anti bakteri
• Mekanisme kerja ≈ mikonazol
B. Klotrimazol
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• T.korporis, T.kruris, T.pedis• T.Versikolor• Infeksi kulit &
vulvovaginitis oleh C.albicans
Indikasi
• Rasa terbakar, eritema, edema, gatal, urtikaria
Efek Samping
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• Krim & larutan 1% 2xsehari
• Krim vaginal 1%, tablet vaginal 100 mg sekali sehari (malam) selama 7 hari
• Tablet vaginal 500 mg dosis tunggal.
Sediaan
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Tolnaftat St. tiokarbamat, efektif
untuk dermatofitosis• Tersedia dlm btk krim, gel, bubuk,
cairan aerosol, lar. topikal 1% digunakan 2xsehari
• Lesi interdigital sembuh dlm 7 – 21 hr
• Lesi dgn hiperkeratosis, diberi bergantian dgn asam salisilat 10%
Toksiklat diturunkan dari tiokarbamat,
spektrum sempit
3. TOLNAFTAT & TOLSIKLAT
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dihasilkan oleh Strept. Noursei
Bubuk berwarna kuning kemerahan, higroskopis, berbau khas, sukar larut dalam kloroform & eter, mudah terurai dalam air
4. NISTATIN
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• Menghambat pertumbuhan berbagai jamur & ragi
• Tdk aktif terhadap protozoa, bakteri, virus
Aktivitas Anti Jamur
Mekanisme Kerja• ≈ amfoterisin B• Lebih toksik• Tidak diserapi via sal.
cerna, kulit maupun vagina
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• Infeksi kandida di kulit, selaput lendir & sal. cerna
Indikasi
Efek SampingMual, muntah, diare ringan
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• Krim, bubuk, salep, suspensi, obat tetes 100.000 U/gr atau mL
• Tablet 250.000 & 500.000 U• Tablet vagina 100.000 U
Sediaan
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• Kandidosis mulut & esofagus 3 – 4 x 500.000 – 1.000.000 U
• Tablet vagina 1 – 2 x sehari 14 hr
Indikasi
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C. ANTI JAMUR TOPIKAL LAIN
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• Kombinasi asam benzoat & asam salisilat 2 : 1 (biasanya 6% & 3%) whitefield salep
• Asam benzoat fungistatik• Asam salisilat : keratolitik
1. ASAM BENZOAT DAN ASAM SALISILAT
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Cairan kuning, bau khas yg tajam
• Dosis biasa fungistatik• Dosis ↑↑ fungisidal• Tersedia :
Salep campuran 5% undesilenat dan 20% seng undesilenat
Bedah & aerosol 2% undesilenat & 20% seng undesilenat
2. ASAM UNDESILENAT
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• St. anti jamur sintetik, btk kristal putih kekuningan, sukar larut dlm air, larut dlm alkohol
• Bersifat fungisidal terhadap Epidermophyton, Trichophyton, Microsporum & M.furfur
• Absorbsi sedikit melalui kulit• ES : iritasi lokal, rasa terbakar,
vesikel, meluasnya maserasi & sensitisasi
• Tersedia : krim & lotion 1%
3. HALOPROGIN
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• Anti jamur berspektrum luas
• Indikasi : dermatofitosis, kandidiasis, T.versicolor
• Tersedian : krim1% dioles 2xsehari
4. SIKLOPIROKS OLAMIN
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Recommended Cutaneous Antifungal Therapy__________________________________________________________
Condition Topical TherapyOral Therapy __________________________________________________________• T.capitis, localized Azole, Allylamines - widespread -Griseofulvin,
Fluconazole• T.corporis, localized Azole, Allylamines Griseofulvin, widespread - Terbinafine,
Itraconazole,Fluconazole
• T.pedis Azole, AllylaminesGriseofulvin,
Terbinafine,
Itraconazole,Fluconazole
__________________________________________________________
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__________________________________________________________Condition Topical TherapyOral Therapy __________________________________________________________• Onychomycosis -Griseofulvin,
Terbinafine,
Itraconazole,Fluconazole
• Candidiasis localized Azole-
• Candidiasis,widespread -Ketoconazole, and mucocutaneous Itraconazole,
Fluconazole• T.versicolor, localized Azole, Allylamines
- widespread -Ketoconazole,
Itraconazole,Fluconazole
__________________________________________________________
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