Therapeutic Drug Monitoring

Total Parenteral Nutrition

Handling Cytotoxic Drug
Wahyu Utaminingrum
 Therapeutic Drug Monitoring (TDM)
TDM is based on the principle that for some
drugs there is a close relationship between the Farmako
plasma level of the drug and its clinical effect logi
Farmako
kinetik
The International Association for Therapeutic
Drug Monitoring and Clinical Toxicology 
TDM didefinisikan sebagai pengukuran yang Patologi
dilakukan di laboratorium dengan parameter
yang sesuai yang dapat mempengaruhi
prosedur pelaksanaan terapi

TDM is one of tools to support pharmacotherapy,

helping to administration regimen and contributing Interpretasi kadar obat
to the rational use of drugs. dlm cairan tubuh

TUJUAN : Mengoptimalkan terapi

Kecurigaan adanya toksisitas
Sub-therapeutic response

Potential drug interaction

Sejarah reaksi dan toksisitas obat

Evaluasi terapi

Manifestasi penyakit dan toksisitas mirip

 TDM is unnecessary when...
1) clinical outcome is unrelated either to dose or to plasma
concentration
2) dosage need not be individualized
3) the pharmacological effects can be clinically quantified
4) when concentration effect relationship remains
unestablished
5) drugs with wide therapeutic range (such as beta blockers
and calcium channel blockers)
Obat indeks terapi • Digoxin, Aminoglycosides,
sempit Theophylline, Anticonvulsant

Obat yg efek
farmakologinya • Salicylates, Lithium
sulit dihitung

• Anticonvulsants,
Obat profilaksis
Antiarrhytmics

Hub antara dosis-

konsentrasi
• Phenytoin, Salicylates
plasma sulit
diprediksi
• Observasi • Preparasi
klinisi sampel
• Permasalahan • Analisis
• Verifikasi hasil
• Pengambilan
sampel
Pre analisis Analisis

Pengaturan Post
lingkungan analisis

• Kondisi dan • Pelaporan

atmosfer • Dugaan 
proses TDM solusi
• Tindakan
1. Lakukan skala prioritas untuk memilih pasien
yang diindikasikan untuk dilakukan TDM
2. Berikan perhatian pada pasien yang
menerima obat yang perlu perhatian khusus
3. Lakukan sampling
4. Interpretasi hasil
5. Diskusikan dengan dokter ttg hasil dan
monitoring terapi yg dilakukan
• Penderita yang • Obat-obat yg perlu
berpotensi terhadap
perubahan disposisi
obat:
– Gangguan ginjal
– Gangguan hati
– Usia muda/neonatus
dan usia lanjut
– Obesitas dan kekurangan
nutrisi
perhatian khusus:
– Narrow therapeutic index
– Insiden ES dan ADR tinggi
– IO
– Multiple intravenous
therapy
– Drug-induce
reactions/hypersensitivity
– Obat baru
• Sampling: • Interpretasi hasil:
– Waktu sampling (steady
state)
– Waktu dosis terakhir
– Durasi pemberian obat
– Tipe sampel (plasma,
urin, saliva)
– Pelabelan,
pengumpulan,
penyimpanan sampel
– Obat/dosis/formulasi/
jadwal pemberian/cara
pemberian
– Indikasi
– Durasi pengobatan
– Waktu dosis terakhir
– Waktu sampling
– Hasil lab sebelum TDM
– Fungsi organ,umur, BB,dll
 Pasien Neonatus Pasien HIV/AIDS
1. Masa perkembangan 1. Perbedaan individu dan intraindividu
2. Tidak bisa mengkomunikasikan adanya yg besar dalam disposisi obat ARV 
adverse effect sulit membuat prediksi
3. Respon seringkali tidak dapat 2. RTIs dan PIs menunjukan hubungan
diprediksi konsentrasi-efek
4. Resiko kesalahan dosis 3. Mayoritas ARV memiliki IT sempit
an appropriate route of nutrition support when patients with identified
malnutrition or significant risk of malnutrition cannot meet their nutritional
requirements through the gastrointestinal (GI) tract

Pheriperal Parenteral Nutrition

Total Parenteral Nutrition

The intravenous provision of all nutritional
requirements, without the use of the
gastrointestinal tract

Allows great caloric intake

More expensive
More complications
Needs more technical expertise
• Impossibility for enteral nutrition
• Inadequacy for enteral nutrition
• Increment of the severity of disease by enteral
nutrition
• Anticipated to have PN for more than 7 days
Liver disease
Renal
Pancreatitis
Sepsis ad Injury
Respiratory
Cardiac
Diabetes mellitus
Cancer
• Fluid. Fluid is an essential component of parenteral
nutrition
• Carbohydrate. Glucose is the main source
• Protein. This is delivered as a synthetic crystalline
amino acid solution. Adverse effects of excess protein
include a rise in urea and ammonia
• Intralipid. An oil-in-water emulsion derived from egg
phospholipid, soyabean and glycerol.
• Minerals. Sodium, potassium, chloride, calcium,
magnesium and phosphorus levels need to be closely
monitored
• Trace Elements. Zinc, copper, manganese, selenium,
fluorine and iodine are provided in a number of
commercial TPN preparations.
• Vitamins. The daily requirements for both water and
fat soluble vitamins can be provided in TPN
 Complications of TPN Therapy (1)
 Glucose abnormalities are common.
Hyperglycemia can be avoided by monitoring blood
glucose often
 Abnormalities of serum electrolytes and minerals
should be corrected by modifying subsequent
infusions
 Volume overload (suggested by > 1 kg/day weight
gain) may occur when high daily energy
requirements require large fluid volumes.
 Metabolic bone disease, or bone demineralization
(osteoporosis or osteomalacia), develops in some
patients receiving TPN for > 3 mo. The mechanism
is unknown
 Complications of TPN Therapy (2)

 Adverse reactions to lipid emulsions (eg,

dyspnea, cutaneous allergic reactions, nausea,
headache, back pain, sweating, dizziness) are
uncommon but may occur early
 Hepatic complications include liver dysfunction,
painful hepatomegaly, and hyperammonemia
 Gallbladder complications include
cholelithiasis, gallbladder sludge, and
cholecystitis
 Catheter-related infection may lead to sepsis
 Nutritional assesment

Venous access evaluation

Baseline weight

Baseline lab investigations

 Monitoring TPN

Clinical Lab
Review Investigations

• Progress should be followed on a flowchart. An

interdisciplinary nutrition team, if available, should monitor
the patient.
• Weight, CBC, electrolytes, and BUN should be monitored
often (eg, daily for inpatients).
• Blood glucose should be monitored q 6 h until stable.
• Fluid intake and output should be monitored continuously.
• When the patient becomes stable, blood tests can be done
much less often.
• Clinical examination
• Vital signs
• Fluid balance
• Catheter care
• Sepsis review
• Blood sugar profile
• Body weight
• Full blood count • Weekly (unless indicated)
• Renal function • Daily until stable, then 2x/week
• Ca++ , Mg++ , PO42- • Daily until stable, then 2x/week
• Liver function test • Weekly
• Iron panel • Weekly
• Lipid panel • 1-2x/week
• Nitrogen balance • Weekly
 PICC
(Peripherally inserted central catheters)
Pediatrics Parenteral Nutrition
KONTAMINASI

• Preparasi
• Transportasi
• Penyimpanan
• Pemberian obat
 TUJUAN
• Produk harus terlindungi dari kontaminasi
mikroba dengan teknik aseptis
• Personel yang terlibat harus terlindung dari
exposure
• Lingkungan harus terhindar dari paparan
bahan berbahaya
Paparan obat sitostatika
ke dalam tubuh, melalui:
INHALASI
ABSORPSI
INGESTION
 Standar Prosedur Kerja
• Fasilitas fisik yang dibutuhkan untuk
melindungi operator dan produk
• Pakaian pelindung yang melindungi
operator dan produk
• Prosedur pelatihan untuk personel
• Teknik khusus yang diperlukan untuk
safe handling cytotoxic
• Prosedur pembersihan tumpahan obat
• Prosedur pemberian label,
pengemasan, transportasi dan
pembuangan limbah cytotoxic
Safe Preparation of Cytotoxic Drugs

A. All procedures involved in the preparation of cytotoxic drugs

should be performed in a Class 1, Type A or Type B laminar
flow biological safety cabinet.
B. The work surface of the safety cabinet should be covered with
plastic-backed absorbent paper. This will reduce the potential
for dispersion of droplets and spills and facilitate cleanup. This
paper should be changed after any overt spill and at the end
of each work shift.
C. Personnel preparing the drugs should wear :
• unpowdered latex surgical gloves and a disposable gown with
elastic or knit cuffs.
• Gloves should be changed regularly and immediately if torn or
punctured.
• Protective clothing should not be worn outside of the drug
preparation area.
D. Vials containing drugs requiring reconstitution
should be vented to reduce the internal pressure
with a venting device using a 0.22 micron
hydrophobic filter or other appropriate means such
as a chemotherapy dispensing pin. This reduces the
probability of spraying and spillage.
E. If a chemotherapy dispensing pin is not used, a
sterile alcohol pad should be carefully placed
around the needle and vial top during withdrawal
from the septum.
F. The external surfaces contaminated with a
drug should be wiped clean with an alcohol
pad prior to transfer or transport.
G. When opening the glass ampoule, wrap it and then
snap it at the break point using an alcohol pad to
reduce the possibility of injury and to contain the
aerosol produced. Use a 5 micron filter needle or
straw when removing the drug solution.
H. Syringes and I.V. bottles containing cytotoxic
drugs should be labeled and dated. Before
these items leave the preparation area, an
additional label is recommended.
"Caution-chemotherapy, Dispose of Properly"
I. After completing the drug preparation process, wipe
down the interior of the safety cabinet with water (for
injection or irrigation) followed by 70% alcohol using
disposable towels. All wastes are considered
contaminated and should be disposed of properly.
J. Contaminated needles and syringes, I.V.
tubing, butterfly clips, etc., should be
disposed of intact to prevent aerosol
generation and injury
• Place these items in a puncture resistant container,
then be placed in a box labeled "Cytotoxic waste only,"
sealed and disposed of according to Federal, state and
local requirements.
• Linen contaminated with drugs, patient excreta or
body fluids should be handled separately.
• K. Hands should be washed between glove changes
and after glove removal.

• L. Cytotoxic drugs are categorized as regulated

wastes and therefore, should be disposed of
according to Federal, state and local requirements.
 TUGAS
1. Jelaskan tujuan penanganan obat sitostatika !
2. Jelaskan cara pembersihan BSC setelah digunakan untuk
pengoplosan obat sitostatika !
3. Jelaskan cara menghindari terjadinya tumpahan dan
semprotan obat dari wadah pengemas obat sitostatika !
4. Jelaskan kondisi pasien yang memerlukan Therapeutic
Drug Monitoring !
5. Jelaskan tahapan dalam melakukan Therapeutic Drug
Monitoring !
6. Jelaskan indikasi pemberian nutrisi parenteral !
7. Jelaskan cara melakukan monitoring dalam pemberian
nutrisi parenteral !