Laboratorium Farmakologi Klinik

Telaah Leaflet Obat

Fakultas Kedokteran
Universitas Mulawarman

Obat Anti Hiperlipidemia

Dan NSAID

Oleh

Listyono Wahid Rhomadani

Muhammad Farlyzhar Yusuf
Endang Yuli Angraini
Pembimbing

dr. Lukas D. Leatemia, M. Kes

Dibawakan Dalam Rangka Tugas Kepaniteraan Klinik

Laboratorium Farmakologi Klinik

Fakultas Kedokteran
Universitas Mulawarman
2012

MODALIM
CIPROFIBRATE

COMPOSITION
Each caplet contains :
Ciprofibrate..................................................................................................................100 mg
Critic
Ciprofibrate merupakan golongan asam fibrat yang memiliki berbagai macam
derivat dan sediaan (1). Jenis-jenis derivat dan sediaan asam fibrat adalah sebagai
berikut : -

Klofibrat,
Gemfibrozil,
Fenofibrat,
Ciprofibrat,

500 mg (1)
300 mg, 600 mg, dan 900 mg (2)
100 mg, 145 mg, 200 mg, dan 300 mg (2)
100 mg

DESCRIPTION
Ciprofibrate is a broad spectrum lipid modulating agent. Ciprofibrate is chemically
designated as 2- ( 4 (2.2 dichlorocy chlorophyll) phenol ) 1-2 methyl propanic acid.
Critic
Ciprofibrate merupakan derivat asam fibrat selain klofibrat, gemfibrozil, dan
fenofibrat. Dibawah ini adalah gambar struktur kimia dari keempat derivat asam
fibrat tersebut.
Gambar 1. Klofibrat, 2-(4-chlorophenoxy)-2-methyl-propanoic acid (3)

Gambar 2. Gemfibrozil, 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid (4)

Gambar 3. Fenofibrat,2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-propanoic acid (5)

Gambar 4.

Ciprofibrate, 2-(4 2.2 dichlorocy chlorophyl) phenol) 1-2 methyl

propanic acid (6)

CLINICAL PHARMACOLOGY
Pharmacodynamic Properties
AIC Code : C10AB08
Pharmacotherapeutic group : Serum lipid reducing agents-fibrates.
Ciprofibrate is a new derivative of phenoxyisobutyric acid which has a marked
hypolipidaemic action. It reduces both LDL and VLDL and hence the levels of triglyceride
and cholesterol associated with these lipoprotein fractions. It also increaseslevels of HDL
cholesterol.
Ciprofibrate is effective in the treatment of hyperlipidaemia associated with high plasma
concentrationsof LDL and VLDL (types IIa, IIb, III, and IV according to Fredirckson
Classification). In clinical studies ciprofibrate hase been shown to be effective in
complementing the dietary treatment of such conditions.
Critic

Secara garis besar penjelasan obat siprofibrat sudah benar dan tepat, hanya saja
tidak terlalu mendetail pembahasannya dalam ulasan farmakodinamik pada leaflet
obat ciprofibrat. Yaitu kurang dalam pembahasan mekanisme kerjanya.
Seharusnya dapat dijelaskan mekanisme kerja dari obat ciprofibrat ini terutama
berfungsi sebagai ligan untuk transkripsi nuklear yaitu dengan cara berikatan
dengan peroxisome proliferator-activated receptor-alpha (PPAR-). Yang akan
meningkatkan lipolisis lipoprotein trigliserida melalui LPL. Lipolisis intrasel dalam
jaringan adipose berkurang. Kadar VLDL menurun, sebagian disebabkan oleh
penurunan sekresinya oleh hati.(7)
Dalam pembahasan lain farmakodinamiknya perlu dijelaskan juga,bahwa derivat
asam fibrat ini pada penderita hyperlipidemia campuran, kadar LDL sering kali
meningkat seiring menurunnya trigliserida.(7)
Pharmacokinetic Properties
Ciprofibrate is really absorbed in man, with maximum plasma concentrations occurring
mainly between one and four hours following an oral dose. Following a single dose of 100
mg in volunteers. Maximum plasma concentration of ciprofibrate was between 21 and 36
mcg/ml. in patients on chronic therapy., maximum levels from 53 to 165 g/ml have been
measured.
Terminal elimination half-life in patients on long term therapy varies 38 to 86 hours. The
elimination half-life in subjects with moderate renal insufficiency was slightly increased
compared with normal subjects (116.7h compared with 81.1h). In subjects with severe
renal impairment. A significant increase was noted (171.9h).
Approximately 30-75% of a single dose administered to volunteers was excreted in the
urine in 72 hours, either as unchanged ciprofibrate (20-25% of the total excreted) or as a
conjugated.
Subjects with moderate renal impairment excreted on average 7.0% of a single dose as
unchanged ciprofibrate over 96 hours. Compared with 6.9% in normal subjects. In subjects
with severe insufficiency this was reduced to 4.7%.
Critic
Dalam pembahasan farmakokinetik pada obat ciprofibrat ini sudah cukup
lengkap,dan menjelaskan dengan cukup terinci, tetapi belum menjelaskan
bahwa absorbsi dari obat ini secara cepat dan lengkap (>90%) di absorbsi di
usus, terutama bila diberikan bersama makanan (1). Untuk selanjutnya di

tahap distribusi, metabolisme, hingga ekskresi pembahasannya sudah cukup

lengkap.
INDICATIONS
Therapeutic Indications
Modalim tablets are recommended for the treatment of primary dyslipoproteinaemias,
including types IIa, IIb, III7 appropriate dietary treatment.
Dietary measures should be continued during therapy.
Critic
Asam Fibrat adalah pilihan terapi pada pasien hiperlipoproteinemia tipe II,
hipertrigliseridemia berat, keadaan yang didominasi VLDL, mungkin bermanfaat
untuk hipertrigliseridemia akibat terpai penghambat protease virus (1) (7).
POSOLOGY
Posology and Method of Administration
Adults
The recommended dosage is one tablet (100 mg Ciprofibrate) per day. This dose should not
be exceeded ( see precautions).
Elderly patients
As for adults, but see precautions and warnings.
Use in case of impaired renal function
In moderate renal impairment it is recommended that age be reduced to one tablet every
other day. Patients should be carefully monitored. Modalim should not be use in severe
renal impairment.
Use in children
Not recommended since safety and efficacy in children has not be established. Modalim
tablets are for oral administration only.

Critic
Dalam sediaan dewasa fenofibrat diberikan tunggal 200 400 mg/hari.bezafibrat
diberikan 1-3 kali 200 mg sehari (1) ciprofibrat untuk dewasa 100 mg/hari (8).
WARNINGS AND PRECAUTIONS
Special Warnings and Special Precautions for use

Special warnings
Myalgia/myopathy
Patients should be advised to report unexplained muscle pain, tenderness or weakness
immediately. CPK levels should be assessed immediately in patients reporting these
symptomps. Treatment should be discontinued if CPK levels are greater than ten times the
upper limit of the normal range, if levels rise progressively or if there is other evidence of
myopathy.
Dose of 200 mg Modalim per day or greater have been associated with a high risk of
rhabdomyolysis. Therefore the daily dose should not exceed 100 mg.
Impaired real function and any situation of hypoalbuminemia such as nephrotic syndrome,
high alcohol intake or hypothyroidism may increase the risk of myopathy.
Periodic hepatic function tests are recommended. Modalim treatment should be
discontinued if significant transaminases abnormalities persist or if cholestatic liver injury
is evidenced.
Secondary causes of dyslipidaemia, such as hypothyroidism, should be excluded or
corrected prior to commencing any lipid lowering drug treatment.
Special precautions for use
Association with oral anticoagulant therapy concomitant oral anticoagulant therapy should
be given at reduced dosage and adjusted according to INR (See section interaction with
Other Medicinal Products and Other Forms of Interaction).
If after a period of administration lasting several months a satisfactory reduction in serum
lipid concentrations has not been ebtained, additional or different therapeutic measures
must be considered.
Critic
Untuk peringatan dan pencegahan sudah sangat lengkap jika dibandingkan dengan
buku sebagai sumber referensi.

ADVERSE REACTIONS
Undesirable Effects
Cutaneous disorders
Cutaneous reactions mainly allergic have been reported : rashes, urticarial and pruritus, and
very rarely photosensitivity.
As with other drugs in this class, alow occurrence of alopecia has been reported.

Muscular disorders
As with other fibrates, elevation of serum creatine phosphokinase (CPK), myalgia and
myopathy including myositis and rare cases of rhabdomyolysis have been reported. In the
majority of cases muscle toxicity is reversible when treatment is withdrawn (see special
warnings and special warning for use)
Neurological disorders
Occasional reports of headache, vertigo, dizziness, drowsiness have only rarely been
reported in association with ciprofibrate.
As with other drugs of this class, a low occurrence of impotence has been reported.
Gastrointestinal disorders
There have been occasional reports of gastrointestinal symptoms including nausea,
vomiting, diarrhea, dyspepsia, and abdominal pain, generally, these side effects were mild
to moderate in nature an occurred early on, becoming less frequent as treatment
progressed.
Hepato-biliary disorders
As with other fibrates, abnormal liver function test have been observed occasionally . very
rare case of cholestiasis or cytolysis have been reported (see special warning and special
precautions for use). Exceptional cases with chronic evolution have been observed
Pulmonary disorders
Isolated cases of pneumonitis or pulmonary fibrosis have been reported.
General disorders
Tiredness has only rarely been reported in association with ciprofibrate.
OVERDOSE
Overdose with ciprofibrate has been rarely reported, associated adverse events reflect those
seen in routine use. There are no specific antidotes to ciprofibrate. Treatment of
overdoseage should be sympatomatic. Gastric lavage and appropriate supportive care may
be instituted if necessary ciprofibrate is non dialysable.
CONTRAINDICATION
Severe hepatic impairment.
Severe renal impairment.
Pregnancy and lactation.
Concurrent use with another fibrate.

Hypersensitivity to the active substance or to any component of the product.

Critic
Secara garis besar efek samping, dan kontraindikasi yang dijelaskan pada leaflet
obat sudah cukup lengkap, hanya saja perlu ditambahkan bahwa, golongan asam
fibrat umumnya ditoleransi secara baik oleh tubuh. Efek samping yang sering
ditemukan adalah gangguan saluran cerna (mual, mencret, perut kembung, dll)
yang terjadi pada 10% pasien. Gangguan umumnya berkurang setelah beberapa
waktu (1) sehingga dapat menjelaskan bahwa gannguan dari efek samping diatas ini
dapat berkurang setelah beberapa waktu.
DRUG INTERACTIONS
Interaction with other medicaments and other forms of

Contra-indicated combination
Other fibrates : as with other fibrates, the risk of rhabdomyolysis and
myoglobinuria may be increased if ciprofibrate is used combination with other

fibrates (see contraindication and special warnings).

Not recommended combination
HMG CoA reductase inhibitors : as with other fibrates, The risk of rhabdomyolysis
and myoglobinuria may be increased if ciprofibrate is used combination with HMG

CoA reductase inhibitors (see contraindication and special warnings).

Combination requiring caution
Oral anticoagulant therapy : Ciprofibrat is highly protein bound and therefore likely
to displace other drugs from plasma protein binding sites. Ciprofibrate has been
shown to potentiate the effect of warfarin, indicating that concomitant oral
anticoagulant therapy should be given at reduce dosage and adjusted according to

INR (see special precaution for use)

Combination to be taken into account
Oral hypoglycaemics : A possible interaction should be considered.
Oestrogens : oestrogens can raise lipid levels, although a pharmacodynamics
interaction may be suggested, no clinical data are currently available.
Critic
Dari penjelasan interaksi obat diatas sudah cukup jelas dan lengkap, hanya saja
perlu dijelaskan golongan fibrat lain yang mempunyai interaksi dengan ciprofibrat.
Risiko myositis meningkat bila digunakan bersama statin (1).

Pregnancy and Lactation

There is no evidence that ciprofibrate is eratogenik but signs of embryotoxicity were

observed at high dose in animals. Ciprofibrate is excreted in the breast milk of lactating
rats. There are no data on the use of the drug in human pregnancy or lactation. Therefore
the use of ciprofibrate is contraindicated during pregnancy and in nursing mothers.
Critic
Penjelasan untuk amannya ciprofibrat dalam kehamilan dan laktasi sudah cukup
jelas dengan menyebutkan selama kehamilan dan menyusui pada wanita merupakan
kontraindikasi pada ciprofibrat, seperti pada Klofibrat juga dikontraindikasikan
pada pasien dengan gangguan hati dan ginjal, serta pada wanita hamil masa
menyusui (1).
Effects on Ability to Drive and Use Machines
Dizziness, drowsiness, and tirednesshave only rarely been reported in association with
ciprofibrate. Patients should be warned that if they are affected they should not driver or
operated machinery.
How Supplied
Box of 2 blister packs of 14 caplet
Reg. No. DKI10894000704A1
Do not store above 25o C
Critic
Informasi tambahan yang diberikan mengenai efek dalam berkendara dan
menjalankan mesin sudah sangat baik, karena pada buku referensi tidak cukup
banyak penjelasan tentang hal tersebut. Teknik penyimpanan obat tidak
membutuhkan perlakuan khusus, hanya disimpan pada suhu normal ruangan.
DAFTAR PUSTAKA
1. FKUI. Farmakologi dan Terapi. Jakarta: Balai Penerbit FKUI; 2009.
2. UBM Medica. MIMS Indonesia Petunjuk Konsultasi. 11th ed. Jakarta: BIP; 2011.
3. Clofibrate (CAS 637-07-0) || Cayman Chemical | Supplier [Internet]. [cited 2012 Nov
4]. Available from:
https://www.caymanchem.com/app/template/Product.vm/catalog/10956
4. GEMFIBROZIL (GEMFIBROZIL) TABLET [WATSON LABORATORIES, INC.]
[Internet]. [cited 2012 Nov 4]. Available from:
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=2791
5. LOFIBRA (fenofibrate tablets), 54 mg and 160 mg691692 [Internet]. [cited 2012
Nov 4]. Available from:
http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=3016

6. Ciprofibrate | CAS 52214-84-3 | Santa Cruz Biotech [Internet]. [cited 2012 Nov 4].
Available from: http://www.scbt.com/datasheet-204689-ciprofibrate.html
7. Katzung BG. Farmakologi Dasar dan Klinik. 10th ed. Jakarta: EGC; 2010.
8. Yahya F. Menaklukkan Pembunuh No. 1: Mencegah dan Mengatasi Penyakit Jantung
Koroner Secara Tepat dan Cepat. Bandung: Qanita; 2010.

KLOTAREN
Diclofenac Sodium
KOMPOSISI
Tiap tablet salut enterik mengandung Natrium Diklofenak 25 mg atau 50 mg
KHASIAT
Klotaren mengandung suatu zat derivat asam fenil asetat dengan khasiat analgenik, antipiretik
dan anti inflamasi. Obat ini terutama digunakan untuk pengobatan reumatoid artritis dan
beberapa penyakit reumatik lainnya.
Critic
Natrium diklofenak merupakan derivat dari asam fenilasetat yang berfungsi untuk
menghambat cyclooxygenase pada COX-2 preferential, serta obat ini dapat
mengurangi bioavaibilitas asam arakidonat sehingga prostaglandin , tromboxane dan
prostacyclin tidak terjadi (1)(2).
Gambar 1. Struktur kimia diklofenak (1)

Gambar 2. Pembentukkan metabolit asam arakhidonat dan peranannya dalam inflamasi (3)

INDIKASI
Mengurangi rasa sakit, kekakuan sendi dan pembengkakan pada penyakit reumatoid artritis
dan sejenisnya serta penyakit degeneratif reumatik seperti osteoartritis.
Critic
Diklofenak dapat berfungsi sebagai analgesik, antipiretik dan anti inflamasi (1).
Walaupun memiliki efek sebagai antipiretik, namun efek ini akan terlihat jika dosis
lebih besar dibandingkan dosis untuk analgesik dan anti inflamasi. Penggunaan dosis
yang lebih besar dapat menyebabkan toksik sehingga obat ini hanya digunakan
sebagai analgesik dan anti inflamasi (2).
Obat ini diabsorpsi di saluran cerna yang berlangsung cepat dan lengkap. Obat ini
terikat sebanyak 99% pada protein plasma memiliki bioavailabilitas antara 30 70 %
karena mengalami metabolisme lintas pertama. Waktu paruh untuk obat ini singkat
yaitu 1-3 jam, namun obat ini akan menumpuk di cairan sinovial dengan paruh
waktu 2-6 jam. Oleh karena itu, efek terapi di sendi lebih lama dibandingkan waktu
paruh obat tersebut (1)(2).

KONTRA INDIKASI

Penderita dengan riwayat ulkus peptikum

Penderita yang hipersensitif
Penderita dengan gangguan fungsi hati dan ginjal yang berat
Wanita hamil

EFEK SAMPING
Sakit kepala, pusing, edema perifer, ruam kulit, pruritus, gangguan saluran cerna seperti :
dispepsia, mual dan muntah.
Critic
Karena kerja obat ini sebagai penghambat cyclooksigenase maka pembentukkan
prostaglandin (PG), tromboxane dan prostacyclin dihambat. Prostaglandin
sebenarnya berfungsi untuk relaksasi otot polos, sitoprotektif untuk pencegahan
ulkus peptikum. Tromboxane mempunyai sifat sebagai agregasi platelet dan
vasonkontriksi. Sedangkan prostacyclin sendiri memiliki vasodilator yang kuat dan
penghambat agregasi platelet. Apabila obat ini tetap menyebabkan nyeri ulu hati
maka bisa ditambahkan obat mesoprostol untuk mengurangi peptikum, namun obat
ini juga dapat menyebabkan diare (1).
Umumnya obat anti inflamasi non steroid akan menghambat dari biosintesis PG di
ginjal, terutama PGE2 sehingga aliran darah ginjal dan kecepatan filtrasi glomeruli
akan berkurang bahkan dapat menimbulkan gagal ginjal akut. Selain itu, penggunaan
obat ini pada sebagian orang dapat menimbulkan reaksi hipersensitivitas. Reaksi ini
dapat menyebabkan rinitis vasomotor, edema angioneuritik, urtikaria luas, asma
bronkial, hipotensi sampai keadaan presyok dan syok. Hal ini kemungkinan
diakibatkan oleh tergesernya metabolisme asam arakidonat ke arah jalur
lipoksigenase yang menghasilkan leukotrien. Produksi leukotrien yang berlebihan ini
yang dapat menyebabkan reaksi hipersensitivitas (2).
DOSIS DAN CARA PEMAKAIAN
Dewasa

: 75150 mg per hari, diberikan dalam 3-6 bagian

Anak-anak (>6 tahun)

: 2-3 mg/kgBB/hari, diberikan dalam 2-3 bagian

Tablet harus ditelan utuh sewaktu atau sesudah makan

Critic
Pada dosis orang dewasa diberikan 100 150 mg sehari dan diberikan 2-3 dosis (2).
PERHATIAN
Hati hati bila diberikan pada penderita porfiria.

KEMASAN
Dua berisi 5 strip @10 tablet salut enterik 25 mg atau 50 mg.

DAFTAR PUSTAKA
1. Frust, D. E., Munster, T. (2002). Obat-obat Antiinflamasi Nonsteroid, Obat-obat
Antireumatik Pemodifikasi Penyakit, Analgesik Nonopioid dan Obat-obat untuk Pirai
in Katzung, B.G. Farmakologi Dasar dan Klinik Edisi VIII Jilid 2. Salemba Medika,
Jakarta
2. Wilmana, P. F., Gan, S. (2007). Analgesik-Antipiretik, Analgesik Anti-inflamasi
Nonsteroid dan Obat Gangguan Sendi Lainnya. Farmakologi dan Terapi. FKUI,
Jakarta.
3. Mitchell, R. N., Cotran, R. S. (2007). Inflamasi Akut dan Kronik. In Kumar, V.,
Contran, R. S., Robbins, S. L. (Ed). Buku Ajar Patologi Edisi 7 Vol 1. EGC, Jakarta.