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KONSEP TERKINI PELAYANAN KEFARMASIAN PADA TUBERKULOSIS

KONSEP TERKINI PELAYANAN KEFARMASIAN PADA TUBERKULOSIS. Dr. Widyati , MClin Pharm , Apt. Pokok Bahasan. Epidemiologi Farmakoterapi pada berbagai situasi Farmakoterapi pada berbagai populasi Pharmaceutical care. PENDAHULUAN.

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KONSEP TERKINI PELAYANAN KEFARMASIAN PADA TUBERKULOSIS

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  1. KONSEP TERKINI PELAYANAN KEFARMASIAN PADA TUBERKULOSIS Dr. Widyati, MClinPharm, Apt

  2. Pokok Bahasan • Epidemiologi • Farmakoterapi pada berbagai situasi • Farmakoterapi pada berbagai populasi • Pharmaceutical care

  3. PENDAHULUAN • Tuberculosis tetap menjadi penyebab kematian utama di seluruh dunia. • The rise and spread of drug resistance and synergistic interaction with the HIV epidemic are posing difficult challenges and threatening global efforts at tuberculosis control. • In 2011, there were 8.7 million new cases of active tuberculosis worldwide (13% of which involved coinfection with the human immunodeficiency virus [HIV]) and 1.4 million deaths, including 430,000 deaths among HIV-infected patients (WHO, 2012)

  4. REJIMEN OAT

  5. LATENT Vs ACTIVE INFECTION TREATMENT LATENT TB INFECTION ACTIVE INFECTION OAT Standar: INH, Rif, PZA, Ethambutol • (+) Tuberculin test, tanpagejala • Risikotinggiuntukjadiinfeksiaktif • INH 5-10mg/kg selama 9 bulanatau 2x900mg/mingguselama 9 bulan • Minumsaatlambungkosonghindariantasida 2 jam • Bilaresisten INH, intoleransi INH: Rifampicin 600mg 4 bulan

  6. Relapse • Biasanyaterjadi 6-12 bulansetelahterapiberakhir • Risk factors:cavitation, extensive diseaseimmunosuppression, and a sputum culture that remains positive at 8 weeks. • If any of these risk factors is present, therapy may be extended for up to 9 months. • Resisten? • Non-adherence? • INH, RIF, and PZA plus an additional two (Fluoroquinolon + Streptomycin/Kanamycin)

  7. MDR - TB • MDR TB disebabkanolehbakteri yang sudahbermutasi yang mampumenolak 2 OAT ataulebih . • Rejimenbaru: minimal mengandung 4 obat • Bilaresisten INH & Rif : Z , E, Fluoroquinolon (levofloxacin, ciprofloxacin, moxifloxacin) + streptomycin/amikacin • Lama terapi 18-24 bulan

  8. Extrapulmonary tuberculosis • TB can occur outside the lungs, which is known as extrapulmonary TB. • The risk of extrapulmonary tuberculosis and mycobacteremia increases with advancing immunosuppression. • Macam: • lymph nodes (lymph node TB) • bones and joints (skeletal TB) • the digestive system (gastrointestinal TB) • the bladder and reproductive system (genitourinary TB) • the nervous system (central nervous system TB) 4. Perlu periksa HIV 5. Chest X-ray biasanya normal, Mantoux test (+)

  9. Limfadenitis TB • The most commonly occurring form of extrapulmonary tuberculosis. • Cervical adenopathy is most common, but inguinal, axillary, mesenteric, mediastinal, and intramammary • Patients without HIV infection typically present with chronic, nontenderlymphadenopathy.1 • During therapy affected nodes may enlarge or new nodes may appear, representing an immune response to killed mycobacteria. • A six- to nine-month regimen (two months of INH, rifampin, PZA, and ethambutol, followed by 4-7months of INH+Rif ) is recommended as initial therapy for all forms of extrapulmonary tuberculosis

  10. Tuberculous Meningitis • Meningitis results from intense inflammation following rupture of a subependymal tubercle into the subarachnoid space. • Cerebral edema causes impairment of consciousness, seizures, and raised intracranial pressure, whereas tuberculomas can manifest as space-occupying lesions. • R/H therapy selama 9-12 bulan.8 • Adjunctive corticosteroid therapy with dexamethasone for the initial 6-8weeks in patients with tuberculous meningitis has been associated with reduced mortality and fewer neurologic sequelae. • Earlyinitiation of ARVtherapy in coinfected with HIV does not improve outcomes and resultsin an increased risk of adverse events (WHO, 2012)

  11. TB in HIV • Risikoterinfeksi MDR-TB tinggidaripadapasien dg immunocompetent. Sebaiknya ditest TB setiap tahun • Seringkali undiagnosed karena asimtomatik, presentasi atipikal • Infeksilaten: INH 1x300/hari or 2x900mg/minggu selama 9 bulan =Vit B6 50mg (Kaplan JE, Benson C, Holmes KK, et al, 2009) • Manifestasiextrapulmonallebihsering • Infeksi aktif: Faseawal H/R/Z/E selama 2 bulan, dilanjutkan H/R 4 bulan.

  12. TB in HIV • Pasiendengan CD4+ <100/µl harusmendapatRejimen 1/1A atauRejimen 3/3A setiaphariatau 3x seminggu • CD4 counts ≥ 100/µl terapi 2x seminggu • Lama terapi minimum 6 bulanmeskipun culture-negative TB. • Perpanjangterapimenjadi 9 bulan (extend continuation phase to 7 months) biladelayed response (culture positive setelah 2 bulan)

  13. TB in HIV • Pada HIV dengan CD-4 < 50 sel/mm3 ARV dimulai setelah OAT 2 minggu pada pasien ARV- naive (STRIDE trial, CAMELIA study, SAPiT Trial) • HIV dengan CD-4 >50 sel/mm3 ARV ditunda setelah OAT 8-12 minggu • HIV yang sedang mendapat ARV terinfeksi TB perlu mengbuah rejimen TB atau menghentikan ARV. • RIF is also the most potent inducer of the CYP3A4 enzyme yang akan mengurangi efektivitas PI and NNRTIs sehingga OAT yang mengandung R tidakboleh digunakan pada HIV yg mendapat PI and/or NNRTI therapy.

  14. TB IN SPECIAL POPULATION

  15. TB IN PREGNANCY • The initial treatment regimen should consist of INH, RIF, and EMB. • Hindari Streptomycin karena congenital deafness • PZA safely during pregnancy and is recommended by WHO • Bila PZA tidakmasukrejimenawal, maka lama terapi 9 bulan.

  16. TB in BREASTFEEDING • Teruskanmenyusuikarenakonsentrasiobatdalam ASI tidakmenyebabkantoksisitaspadabayi. • Kadar obatdalam ASI tidakbisaberfungsisebagaiterapiinfeksilatenbagibayi. • Suplementasi Pyridoxine 25 mg/day padaibu yang mendapat INH

  17. TB IN ELDERLY • Infeksilaten: INH 300mg selama 6-9 bulanatau RIF 4 bulan • InfeksiAktif: samasepertirejimendewasaatau INH+RIF+PZA+EMB setiaphariselama 2 minggudiikuti 2x semingguselama 6 minggu, kemudian INH+RIF 2x semingguselama 16 minggu

  18. TB IN PEDIATRICS • Secaraumumrejimen= rejimendewasakecuali EMB karenajarangdijumpairesistensi • EMB can be used safely at a dose of 15--20 mg/kg per day. • Streptomycin, kanamycin, or amikacin also can be used as the fourth drug, when necessary.

  19. TB in Pediatrics

  20. TB in CKD • LTBI: INH 6 bulan or HR 3bulan or R 4-6bulan • Active TB: lihat tabel berikut • In general, isoniazid and rifampicin can be used in normal doses in renal impairment, during dialysis and following transplantation • CKD Stages4 and 5, dosing intervalsethambutol, pyrazinamidadanaminoglikosida menjadi 3x seminggu • Kemoprofilaksis sebelum atau sesudah transplantasi dengan H 300 mg/hari selama 6 bulan +Vit B6 10-25 mg/hari atau H+R+VitB6 selama 3 bulan atau R 4-6 bulan.

  21. Active TB in CKD

  22. END-STAGE RENAL DISEASE • Hemodialisis, dosing intervalsditingkatkan menjadi 3x seminggu untuk mengurangi risiko akumulasi obat dan toksisitasy. Obat diberikan setelah dialisis atau 4-6 jam sebelum dialisis • There is little information concerning the effects of peritoneal dialysis on clearance of antituberculosis drugs.

  23. TB in Liver disease • INH, RIF, and PZA dapatmenyebabkan hepatitis yang memperparah preexisting liver disease. • Namunkarenaefektivitasketiga OAT tersebutsebaiknyatetapdigunakanbilamungkin. • Bila SGOT > 3x: R/E/Z 6 bulanhindari INH atau H/ R 9 bulan + E sampai H/R susceptibility are demonstrated, thereby avoiding PZA. • For severe liver disease : R/E 12 bulan, + fluoroquinolone, for the first 2 months; however, there are no data to support this recommendation.

  24. POTENTIAL ADVERSE DRUG REACTION

  25. NeuropatiPerifer • Dijumpaipada INH karenapersainganmetabolismepyridoxin • Terjadipadadosis>6mg/kg/hari • Pasiendengan underlying DM, HIV, malnutrisi, gagalginjalharusmendapatpyridoxin • Pregnancy and Lactation harusmendapatpyridoxin.

  26. Thrombocytopenia • Terjadipadapemakaian RIF yang terputusatauintermitten • Mekanisme: pembentukanIgGdanIg M antibody terhadap RIF yang akanmelekatpada platelet sehinggadestruksi platelet • Bilaterjadi thrombocytopenia hentikanterapigantikerejimen lain • Penggunaanulangdapatmenyebabkan thrombocytopenia berulang

  27. Reaksi Lain • Alergidijumpaipada INH dg manifestasi: rash, pembengkakanlidah, demam, arthritis. • Mual, muntah , demam, rash dijumpaiakibat RIF • Acute Kidney Injury (AKI) akibat RIF • Optic Neuritis akibat EMB, tergantungdosis > 15mg/kg dandurasi • Asymptomatic hyperuricemiaoleh PZA,EMB

  28. Hepatitis • INH memiculebihbesarhepatotoksisitasdaripada RIF. • Terjadidalammingguan-bulananterapiawal • RIF lebihmenyebabkancholestasissehinggamanifestasidisertai jaundice denganatautanpapeningkatantransaminase. • Insiden hepatitis lebihbesarpadakombinasi INH-RIF daripada INH tunggal • High risk: manula, alkoholik, pasien yang mendapathepatotoxic lain, disfungsi liver (CH, Hepatoma, PBC)

  29. Drug Interactions • Relatively few drug interactions substantially change concentrations of antituberculosis drugs • Antituberculosis drugs sometimes change concentrations of other drugs -Rifamycins can decrease serum concentrations of many drugs, (e.g., most of the HIV-1 protease inhibitors), to subtherapeutic levels -Isoniazid increases concentrations of some drugs (e.g., phenytoin) to toxic levels

  30. InteraksiObat • INH menghambat CYP2C9, CYP2C19, CYP2E1 • INH menghambatmetabolismeFenitoin, CBZ • RIF menginduksi CYP3A4 • RIF meningkatkanmetabolisme ARV (Protease inhibitor, NNRTI), makrolida, antijamurAzole, kortikosteroid, warfarin,OC, teofilin, fenitoin, SU, nifedipin, verapamil, diltiazem,enalapril, simvastatin

  31. Pelaksanaan Pharmaceutical Care • Pengumpulan Data: Subyektif, Obyektif • Analisis terapi obat dikaitkan dengan data suyektif, obyektif menghasilkan DRP (Asesmen) • Penyusunan Rencana Pelayanan (Plan): penyusunan rekomendasi, rencana monitoring dan konseling. • Implementasi Rencana Pelayanan: menyampaikan/mengkomunikasikan rekomendasi, melaksanakan monitoring dan konseling.

  32. Pengumpulan Data Subyektif, Obyektif Fungsi ginjal, liver? Kehamilan, menyusui? HIV? Minum obat lain? Penggunaan kontrasepsi oral? Ada pengawas di rumah? Pekerjaan? Alamat? Keluhan selama minu obat pada kunjungan ulang?

  33. Asesmen • Cek adherence pada kunjungan ulang • Ada mual yang menetap setelah minum obat? Rujuk ke dokter untuk memastikan apakah terjadi ESO. • Cek ketepatan obat, dosis pada CKD dan CLD, kehamilan dan menyusui • Cek potensi interaksi dengan obat lain yang diminum. • Cek keluhan selama minum obat

  34. Monitoring Terapi Obat • EfektivitasTerapi: • Sputum BTA setelahterapi2 dan6 bulan • If positive at two months, repeat at 3 • If still smear positive at 3 months, continuation phase (4HR) is still started while awaiting DST results • Continue drug-susceptibility tests if smear-positive after 3 months of treatment • Considernoncompliance, malabsorption, and drug resistance as possible reasons for delayed or suboptimal response to appropriate therapyESO: • ESO: SGOT/SGPT, Vision test, audiometri, hematologi, neuropati

  35. KONSELING OBAT • PasienBaru: • Motivasipasienuntukmauminumobat, tidakmalu • Kontinuitasterapi • Interaksidenganobat lain danpengatasannya • Cara minumobat: lambungkosonguntuk INH, RIF • Dampakketidakpatuhan • Tandahepatotoksisitas: mualmenetap, urine gelap, jaundice padakulit/mata • Pasien Lama: • Motivasiuntuktetap adhere thd OAT

  36. Penutup • Penyebaran dan meningkatnya TB yang resisten seiring dengan epidemi HIV mempersulit penatalaksanaan. • Farmasis dapat berperan aktif dalam penatalaksanaan TB melalui Pharm care

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