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HOSPITAL KUALA KUBU BHARU PHARMACY BULLETIN
1st edition /Jun2015 DIS HKKB 03-60641333 ext 279
ISSUE OF THE MONTH : RAMADHAN IS HERE AGAIN!
(PAGE 1-5) Self monitoring blood glucose during fasting Dosage adjustment for Oral Antidiabetic and insulin during
fasting
Updated list of medication that cannot be taken by muslim during fasting.
CURRENT ISSUES (PAGE 6-7) Accepted abbreviations for prescription writing in HKKB Abbreviation that should be avoided
Tamiflu (Children)
A GLANCE OF PHARMACEUTICAL SCIENCE (PAGE 9-12) Introduction to Pharmacokinetics : ADME process
The workflow of Therapeutic Drugs Monitoring (TDM) service
in HKKB
KNOW YOUR MEDICINE (PAGE 13-16) Asthma & Medication
PHARMACY EDUCATION (PAGE 17-19) Idiopathic nephrotic Syndrome in Children
EDITORIAL BOARD
ADVISOR : Ratna Suny Mohamed Esa
CHIEF EDITOR : Noor Haslina Zainor Abidin
EDITOR : Ainur Fadlina Nadzir
Nurzafirah Mustafa Kamal
CONTRIBUTORS: 1) Tan Hwei Yuin
2) Syazyanti Izyanti Mohd Ariffin
3) Azwa Abdullah
4) Mohamad Shafawie Mohamad Sidik
RAMADHAN
&
DIABETES Ramadhan is the 9th month in the Islamic calendar. In this month, Muslims worldwide perceives this-
month as the fasting month. The practice of fasting lasts for 29-30 days. During this month, Muslims will
fast from dawn until dusk daily. Fasting is believed to clean the soul by freeing it from harmful impurities
and inculcate the practice of self-discipline, self-control, sacrifice, and compassion for those who are less
fortunate. Thus, Muslims are encouraged to practice the act of generosity and charity especially during
Ramadhan.
The practice of fasting during Ramadhan is compulsory for all Muslims once puberty is reached. However,
there are certain exceptional like those with chronic diseases such as diabetes mellitus. Fasting in diabetec
patients may be associated with adverse outcomes like dehydration, hypoglycaemia and hyperglycaemia.
Thus, diabetic patients are required to be monitored and given necessary medical advice if patient insist to
fast. However, there are certain diabetic patients who are not encouraged to fast as they have higher risk of
developing the adverse effects than other normal diabetic patients [refer Table 1].
The criteria that FORBIDS Diabetic patients to fast:
1. Uncontrolled diabetes (may lead to various complication– dehydration, infection and coma)
2. Non compliance to diet restrientions and medication
3. Suffering from serious diabetes complications (Coronary heart disease and uncontrolled hypertension)
4. History of severe diabetes complication with 3 months prior to fasting
Ketoacidosis
Hyperosmolar hypoglycemic coma
Recurrent hypoglycemia
5. Suffering bacterial infection
6. Elderly who lives alone
7. Pregnant women who is suffering from Gestational Diabetes Mellitus
8. Children under the age of 12 years old. (Haven’t reached puberty)
9. Type 1 Diabetes patient
By : TAN HWEI YUIN
Table 1:
1
Pathophysiology of Fasting during Ramadhan
Owing to the abstaining from eating, drinking and smoking from predawn to sunset during the
Ramadhan period, the metabolism of glucose is altered from the normal physiology. When fasting,
the body will finish up the available glucose storage (glycogen) in the liver and gradually transit to
fat as the main source of energy. During fasted state, liver glycogen will deplete within the first 18
to 24 hours via glycogenolysis. Once glycogen stores are depleted, fats will be mobilized in the form
of triglycerides and subjected to lipolysis for generation of energy. After a prolonged period of fast-
ing (days-weeks), protein becomes the next source of energy via catabolism of muscle.
However, Ramadan fast only last from dawn till dusk, thus; there is ample opportunity to re-
plenish energy stores at pre-dawn and dusk meals. Therefore, this will ensure sufficient supply of
glycogen or fats as the source of energy, and prevents the breakdown of muscle for protein.
Pathophysiology of fasting in diabetes patient
2
To Known the Signs of Hypoglycemia, Hyperglycemia and Dehydration
Signs of HYPOGLYCEMIA:
Signs of HYPERGLYCEMIA:
Signs of DEHYDRATION:
Shivering Fatigue Hungry Cold
Sweats Palpitation Anxious
Frequent
urination
Extreme
thirst
Drowsiness Decrease
healing
Extreme
thirst
Very dry skin
& tongue
Time Target
Pre-sahur 4.4 - 6.1 mmol/L
2 hours post SAHUR 4.4 – 8 mmol/L
Midday 4.4 - 6.1 mmol/L
2 hours post IFTAR 4.4 - 6.1 mmol/L
Right before IFTAR 4.4 - 6.1 mmol/L
Patients are encouraged to self-monitor blood glucose during fast, sugguested at the following time :
Stop fasting IMMEDIATELY if :
Experiencing signs of hypoglycemia or blood glucose <3.3mmol/L
Blood glucose <3.9mmol/L in the first few hours of fasting [especially in
patient taking sulfonylureas, meglitinides or insulin]
Blood glucose >16.7 mmol/L
Sick (fever, infections etc)
Pale
Coma
3
Medicine Name and Strength Regime for Ramadhan month
Metformin 500mg
(Biguanides)
Eg: T. Metformin 500mg three times daily
Once/Twice daily
No dosage adjustment required
Three times daily
Take 2/3 from the TOTAL DAILY DOSE during IFTAR
Take1/3 from the TOTAL DAILY DOSE during SAHUR (Max dose: 1g)
* Metformin 1g during IFTAR, 500mg during SAHUR
Gliclazide / Glibenclamide
(Sulphonylureas)
Eg: T. Gliclazide 80mg twice daily
No dosage adjustment required during IFTAR
Reduce or omit during SAHUR
* Gliclazide 40mg during SAHUR, 80mg during IFTAR
Gliclazide MR
(Sulphonylureas)
Eg: T. Gliclazide MR 60mg once daily
No dosage adjustment required (Take during IFTAR)
Rosiglitazone / Pioglitazone
(Thiazolidinediones)
Eg: T. Rosiglitazone 4mg once daily
No dosage adjustment required (Take during IFTAR)
Acarbose
(Alpha-glucosidase inhibitors)
Eg: T. Acarbose 50mg three times daily
No dosage adjustment required. Omit midday dose.
Acarbose 50mg during SAHUR, 50mg during IFTAR. Midday dose can be omitted during fasting
Repaglinide/Nateglinide
(Rapid acting insulin secretagogues)
Eg: T. Repaglinide 2mg per meal (maximum 4 meal)
Twice daily
No dosage adjustment required during IFTAR
Take HALF dose during SAHUR
Sitagliptin
(Dipeptidyl peptidase-4-inihibitors)
Eg: T. Sitagliptin 100mg once daily
No dosage adjustment required
Insulatard®, Humulin N®, Lantus®,
Levemir® , Insuman Basal®
(Basal insulin)
No dosage adjustment required . (Inject before going to
bed)
Can reduce 20% (2unit) of the normal dose if
hypoglycaemia had occurred before
Mixtard® 30/70, Humulin® 30/70, No-
vomix® 30, Insuman Comb 30®
(Pre-mixed insulin)
Eg: S/C Mixtard® 30/70– 30unit morning
& 20 unit evening
Reverse dose—Morning dose take during IFTAR dan
evening dose at SAHUR
Evening dose can be reduced from 20-50% based on the in-
dividualized blood glucose level
* S/C Humulin 30/70 10 unit during SAHUR, 30unit during IFTAR
Actrapid®, Humulin ®, Insuman Rapid®
(Rapid acting insulin)
Eg: S/C Humulin® 16unit three times daily
No changes or REDUCE SAHUR dose up to 50% if one is
suffering from hypoglycemia.
Midday dose can be omitted during fasting
No changes during IFTAR
S/C Humulin® 16unit BEFORE SAHUR and 16unit BEFORE IFTAR
Dose ADJUSTMENT for Oral AntiDiabetic and insulin during Ramadhan
4
REFERENCES:
1. Puasa & Ubat,2015, Bahagian Perkidmatan Farmasi, Kementerian Kesihatan
Malaysia.
2. Prof Nor Azmi Kamaruddin. Pengurusan Diabetes Ketika Berpuasa. Peroncean
Endocrin & Metabolisma Malaysia (MEMS). 2015.
3. Kementerian Kesihatan Malaysia & MEMS. Practical Guide to Diabetes Management
in Ramadan. 2015.
Medication that DOES NOT BREAK Fast Medication that BREAK Fast
Eyedrop, Eardrop & nasal spray (with the
condition of not reaching the base of eardrum,
throat)
Sublingual tablet (under the tongue); with the
condition of not swallowing
All forms of injection
Topical (cream/ointment) and plaster
Mouthwash gargle
Local anesthetic
Tablet
Syrup
Inhaler
Pessary (Including vaginal wash)
Suppository & Enema (any medicine that is
inserted into anus
General anesthetic (involves inhaling gas)
Types of Drug that ALLOW/CANCEL Fasting
5
ACCEPTED ABBREVIATIONS IN PRESCRIPTION WRITING, HKKB
Abbreviation Intended meaning Example of prescribing
Stat. Immediate T. Captopril 50mg stat.
PRN When necessary Oint. Methyl salicylate PRN X 1/52
Syr. Syrup Syr. Paracetamol 120mg tds X 1/52
Gutt. Eye drop Gutt. Gentamicin 0.3% 1 drop tds, BE X 1/12
Oint. Ointment Oint. Methyl salicylate PRN X 1/52
Mist. Mixture Mist. Potassium Citrate 10ml tds X 1/52
od Once a day T. Prednisolone 30mg od x 5/7
bd Twice daily T. Metformin 1g bd X 1/12
tds Three times a day T. Nifedipine 10mg tds X 1/12
mg Milligram T. Amlodipine 10mg od X 1/12
mcg microgram T. Levothyroxine 50mcg od X 1/12
ml Milliliter Mist. Potassium Citrate 10ml tds X 1/52
OM Morning T. Valproic acid 200mg OM, 400mg ON X 1/12
ON Night
ORS Oral Rehydration Salt ORS per purge X 3/7
Vit. Vitamin T. Vit. C 100mg od X 1/52
GTN Glyceryl Trinitrate T. GTN 1tab PRN X 1/12
ACCEPTED SYMBOLS IN PRESCRIPTION WRITING, HKKB
Symbol Meaning
↑ Increase or high
↓ Decrease or low
@ At
X Times
6
Current Issues
ABBREVIATIONS THAT SHOULD BE AVOIDED
Abbreviation Intended meaning Suggestion for prescribing Reason
St. stat (immediate) stat Not a standard abbrevia-
tion
cc Milliliter ml May be mistaken as ‘oo’
if poor handwriting
BVC Betamethasone Betamethasone cream for
LA
Not a standard abbrevia-
tion
HCTZ Hydrochlorothia-
zide
T. Hydrochlorothiazide
25mg od
Not a standard abbrevia-
tion. May be confused
with Hydrocortisone
(HCT)
MVT Multivitamin Syr. Multivitamin 5ml od May be confused with
MMT
CMC Chloramphenicol Gutt. Chloramphenicol 2
drop tds
Not a standard abbrevia-
tion
MTF Metformin T. Metformin 500mg bd Not a standard abbrevia-
tion
CPZ Chlorpromazine T. Chlorpromazine 100mg
ON
May be confused with
carbamazepine (CBZ)
BE/Bena Diphenhydramine Syr. Diphenhydramine 10ml
tds
Not a standard abbrevia-
tion
ASA Acetylsalicylic Acid T. Acetylsalicylic Acid
150mg od
Not a standard abbrevia-
tion
OMS Ointment Methyl
salicylate Oint. Methyl salicylate PRN
May be confused with
ORS
HCT Hydrocortisone IV Hydrocortisone 100mg
QID
May be confused with
Hydrochlorthiazide
(HCTZ)
7
Current Issues
Compounding of oral suspension from
Tamiflu 75mg Capsule
Carefully open one capsule and pour all the powder into the bowl. (Handle the powder carefully as it may cause irritation to skin and eyes).
1) Add 5ml of water to the bowl and mix it with powder for 2 minutes.
2) Add 7.5ml of Syrup Simplex to the bowl. 3) Stir the mixture well before giving the dose (Please refer
the table below for dose measurement). Note : Final concentration : 6mg/ml.
Preparation is to be made for each dose, not in bulk.
Shake well before use.
Store the capsules below 25ºC and protect from moisture.
WEIGHT
PROPHYLAXIS (7 DAYS)
TREATMENT (5 DAYS) VOLUME
(ML) DOSE DOSE
< 15kg 30mg OD 30mg BD 5.00
16-23 kg 45mg OD 45mg BD 7.50
24-40 kg 60mg OD 60mg BD 10.00
≥41 kg 75mg OD 75mg BD 12.50
NOTE
<3 months old : not recommended < 1 year old :
3mg/kg/dose BD
3 months – 1 year
old : 3mg/kg/dose OD
References : www.cdc.gov : Influenza Antiviral Medications: Summary for Clinicians
Product Leaflet : Osmivir Capsule 75mg (Royce ™)
Antiviral Medication Recommended for Treatment of Influenza
8
A GLANCE OF PHARMACEUTICAL SCIENCE
What is pharmacokinetics?
Study of absorption,
distribution, metabolism
and excretion of drugs
in the body
THERAPEUTIC DRUG MONITORING
Measurement of drug concentration in body fluids to
aid in optimizing drug therapy.
Why is it necessary?
Certain drugs have narrow therapeutic range In concentrations above the upper limit of the
range, the drug can be toxic In concentrations below the lower limit of the
range, the drug can be ineffective Not all patients have same response at similar doses
PHARMACOKINETIC TERMS
Volume
distribution (Vd)
The amount of blood, per Kg body weight necessary to
contain all of the body bur-den of drug at equilibrium
concentration
Steady state The point at which drug intake and elimination reach
an equilibrium, and the height of the peak and the
depth of the trough are predictable
Half Life (T1/2) Time required for the drug concentrations to
Decrease by to 50%
BY : SYAZYANTI IZYANTI MOHD ARIFFIN
9
GUIDELINES OF SAMPLING TIME
Drug Time to steady state Sampling time
Digoxin (Oral)
Without LD: 7-14 days (ESRF: 15-20days) With LD: 24 hours
30 minutes or just before the next dose
Theophylline (Oral)
Oral: 2days LD IV: 24hours
IV: 2days
30 minutes or just before the next dose
Phenytoin Without LD: 7 days With LD: 12-24hours
30 minutes or just before the next dose
Carbamazepine 2-3 weeks (Induction phase)
4-7 days (MD)
30 minutes or just before the next dose
Valproic acid 3-5 days 30 minutes or just before the next dose
Phenobarbitone Adult: 1 month Children: 2 weeks
30 minutes or just before the next dose
1. Laryn A. Bauer (2006) The Mc-Graw Hill companies, Clinical Pharmacokinetic Handbook, United States
2. Therapeutic Drug Monitoring, Clinical Guide. Accessed online on 24th May 2014 at: https://
www.abbottdiagnostics.com/enus/staticAssets/learningGuide/public/IA_09_23773v2_Ther_Drug_Guide_120910_E_Brochure.pdf
3. Therapeutic Drug Monitoring, An Educational Guide. Accessed online on 24th May 2014 at:
http://www.healthcare.siemens.com/siemens_hwem-hwem_ssxa_websites-context-root/wcm/idc/groups/public/@global/@clinicalspec/documents/download/mdaw/mtu3/~edisp/tdm_guide_final-00028657.pdf
REFERENCES
10
Receive TDM request form from ward/ verbal
request from Dr/ informed by ward BEFORE
blood is taken
Clinical Pharmacist
HKKB (EXT 209)
No
Any
problem?
Screen the request and conduct
initial patient assessment in the
ward (CLERK CASE)
Consult the requester
and rectify the problem
Yes
Send specimen together with the TDM
form to Pathology Lab HKKB for regis-
tration, serum extraction & preservation
Keep pink copy of the TDM form before
dispatch to Selayang Hospital
Dispatch the specimen together with the
TDM form (original and yellow copy) to
Biochemical Lab Selayang Hospital for
analysis
Register the request
Prepare carousel, reagent and sample for
assay
Run the assay
Keep the yellow copy and return the
original copy with results to HKKB
Pathology
Lab HKKB
Biochemical
Lab Selayang
Hospital
Pharmacy
HKKB
Collect the pink copy of the TDM
Register the request with HKKB
Pharmacy Reference Number
Obtain the results from Biochemi-
cal Lab Selayang Hospital via
phone call; obtain the original copy
from Pathology Lab HKKB
Interpret the results
Discuss the results and recommen-
dations with the prescriber
Send the original copy of the
TDM form to the requester, rec-
ord & file the pink copy
Flow Chart of Clinical Pharmacokinetic Service
(From In-Patient Department)
11
Pathology Lab
HKKB
No
Any problem?
Screen the request
Consult the
requester and recti-
fy the problem
Yes
Receive specimen & TDM
request form
Pathology Lab
Biochemical
Lab Selayang
Hospital
Pharmacy
HKKB
Register the request, extract and pre-serve the serum
Keep pink copy of the TDM form
before dispatch to Selayang Hospital
Dispatch the specimen together with
the TDM form (original and yellow
copy) to Biochemical Lab Selayang
Hospital for analysis
Register the request
Prepare carousel, reagent and sample
Run the assay
Keep the yellow copy and return the
original copy with results to HKKB
Collect the pink copy of the TDM form
Register the request with HKKB
Obtain the results from Biochem-
ical Lab Selayang Hospital via
phone call; obtain the original
copy from Pathology Lab HKKB
Interpret the results
Discuss the results and recom-
mendations with the prescriber
Send the original copy of the
TDM form to the requester,
record & file the pink copy
Flow Chart of Clinical Pharmacokinetic Service
(From out-Patient Department, a&e and out of
working hour)
12
Asthma is a chronic (long-term) inflammation disorder of the lung where the airways be-come inflamed, swollen, narrowing and very sensitive. Cells in the airway might produce more mucus than usual. Mucus is a sticky, thick liquid that can further narrow the airways.
Asthma causes recurring periods of wheezing (a whistling sound while breathing), chest tightness, shortness of breath, and coughing. The coughing often occurs at night or early in the morning.
The location of the lungs and airways in the body. Figure B shows a cross-section of a normal airway.
Figure C shows a cross-section of an airway during asthma symptoms.
Two types of inhaler
Asthma is usually treated with inhalers. Inhaler is a device that will deliver the drug
straight into the lungs. There are many type of inhalers that works in a slightly different way but briefly it can be divided into two categories as follow ;.
ASTHMA & METERED DOSE INHALERS (MDI) : WHAT YOU SHOULD KNOW?
BY : AZWA BT ABDULLAH KNOW YOUR MEDICINE
RELIEVER (“PELEGA”) PREVENTER (“PENCEGAH”)
Quick relief of asthma symptoms Take longer time to show effect on asthma symptoms
Relax the muscle around the narrowed airway that will open the airway wider and make the patient breathe easier
Reduce airway sensitivity , redness and swelling and help to dry up mucus
Short term treatment Long term treatment
13
Reliever should not be used regularly, if pa-tient use them three or more times a week it indicates patient asthma condition is worsening.
Preventers need to be taken every day to reduce symptoms and asthma attacks, and it may take a few weeks before they reach their full effect.
There are two main categories of reliever medication:
Short-acting beta-agonists Salbutamol Levobuterol
Anticholinergics Ipratropium bromide (usually
use in COPD) Tiotropium bromide
Preventer consist of inhaled corticosteroid Budesonide Beclomethasone Fluticasone Triamcinolone acetonide
Possible side effects include: Increased heart rate (felt as palpita-
tions) Muscle tremor (shaking, especially
in the hands), and/or slight feelings of anxiety or nervous-
ness Upset stomach (rare) Sleeping troubles (rare)
Possible side effect: Candiasis/ oral trush – rinse mouth
after use Sore throat Hoarse voice skin bruising (rare) cataract (rare) glaucoma (rare) adrenal suppression (rare) growth suppression (rare)
RELIEVER (“PELEGA”) PREVENTER (“PENCEGAH”)
Differences between available Meter Dose Inhaler (MDIs) in HKKB
VENTOLIN/BUVENTOL EASYHALER
BUDESONIDE/FLIXOTIDE/ BECLOMET EASYHALER
BERODUAL SERETIDE
Example
Content Salbutamol 100 mcg/puff
Salbutamol 200 mcg/puff
(Easyhaler)
Budesonide 200 mcg /puff Fluticasone 125 mcg/puff
Beclomethasone 200 mcg/puff (Easyhaler)
Ipratropium bro-mide 21 mcg and Fenoterol hydro-bromide 50 mcg
Salmeterol 25mcg and Fluticasone
Propionate 50mcg Inhalation
14
MOA
Short acting beta 2 agonist
Inhaled corticosteroid
Anticholinergic and
Long acting beta 2 agonist
Short acting beta 2 agonist and in-
haled corticoster-oid
How to use
1. Remove the mouthpiece cover. Remain standing/seated upright to ob-tain the full dose of each actuation.
2. Shake the inhaler 3-5 times in up-down motion 3. Prime new inhalers 4. To administer 1 puff:
Hold the inhaler in a upright position. Breathe out fully Place the mouthpiece between the teeth and close the lip (Do not
bite the pump). Ensure that lip fully cover the mouthpiece. Begin to breathe in and press down on the canister simultane-
ously. Continue inhalation 3-5 minutes. Hold breathe for 10 second Remove pump and exhale through mouth.
5. If the dose is two puffs, patient need to repeat procedure no (4). Do not press two times simultaneously. Wait a few second between this two puffs. 6. Close the cover and keep inhaler in dry place. 7. Clean the MDIs every week.
Addition-al
counsel-ling point
In acute attack:
After 5 minutes of first dose (2 puffs) patient are allowed to take another 2 puffs.
Then if the symptoms still not re-
solved in 5 minutes, patient may take another 2 puff.
But however highly recommended
to consult doctor in nearest hospi-tal.
MUST rinse mouth after use. Use every day and do not stop with-
out doctor’s instruction.
When to use
When necessary Every day with the dose prescribed
by doctor
Both – when nec-essary and/or eve-
ry day
Every day with the dose prescribed by
doctor
VENTOLIN
BUDESONIDE/FLUTICASONE BERODUAL SERETIDE
15
Other types of inhaler available in Malaysia
Type Picture Example
Easyhaler
Budesonide Easyhaler
(Giona)
Turbohaler
Symbicort turbohaler
(Budesonide & Salmeterol) Pulmicort Turbohaler
(Budesonide)
Accuhaler
Seretide Accuhaler Flixotide Accuhaler
Handihaler Spiriva (Tiotropium bromide)
References Lexicomp drug information handbook 23
rdedition (2014-2015)
Pharmacotherapy Handbook
Mims Malaysia
Product leaflet
British Guideline on the Management of Asthma May 2011
http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/
http://www.medicalnewstoday.com/info/asthma/
http://www.asthmaaustralia.org.au/preventers.aspx
16
Nephrotic syndrome is a clinical syndrome of massive proteinuria defined by : Oedema
Proteinuria > 40mg/m²/hour (>1g/m²/day) or an early morning urine protein
creatinine index of >200 mg/mmol
Hypoalbuminaemia <25g/l
Hypercholesterolameia
WHAT IS IDIOPHATIC NEPHROTIC SYNDROME? Idiophatic (primary) nephrotic syndrome is one class of nephrotic syndrome which include
minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and diffuse
mesangial proliferation (DMP)
Common definitions to define the coarse of nephrotic syndrome
Nephrotic syndrome Oedema, hypoalbuminaemia, proteinuria, hypercholesterolameia
Relapse Urinary protein excretion > 40mg/m²/h; ≥ 3+ by dipstick for 3 consecutive day
Remission Urinary protein excretion < 40mg/m²/h; nil or trace by dipstick on spot sample for 3
consecutive day
Frequent relapse Two or more relapse in 6 months of initial response; 4 or more relapse in any 12
month period
Steroid dependence Occurrence of 2 consecutive relapse during steroid therapy or within 2 weeks of its
cessation
Steroid resistance Failure to achieve remission after 4 weeks of daily therapy with oral prednisolone
at a dose of 2mg/kg/day
TREATMENT OF INITIAL PRESENTATION OF NEPHROTIC SYNDROME
Prednisolone dose:
60mg/m²/day for 4 weeks (maximum 80mg)
40mg/m²/on alternate day for 4 weeks (maximum 60mg)
Reduce dose by 5-10mg/m² each week for another 4 weeks then stop
Prednisolone can be given as a single dose in the morning with food, or as divided dose during the day. If
prednisolone cause gastric irritation, start ranitidine 2mg/kg twice daily for the duration of steroid treat-
ment.
Response to treatment:
A remission occur when urinary protein excretion < 40mg/m²/h; nil or trace by dipstick on spot sam-
ple for 3 consecutive day.
Treatment is contimued for a total of 12 weeks
If proteinuria persists beyond the first 4 weeks of steroid treament , patient should be referred for
renal biopsy
PHARMACY EDUCATION BY : MOHAMAD SHAFAWIE BIN MOHAMAD SIDIK
17
TREATMENT OF RELAPSES IN NEPHROTIC SYNDROME
Prednisolone induction dose:
60mg/m²/day (maximum 80mg) until remission followed by
40mg/m²/on alternate day (maximum 60mg) for 4 weeks
Breakthrough proteinuria may occur with intercurrent infection and usually does not require cor-
ticosteroids induction if the child has no oedema, remain well and proteinuria remits with the
resolution of the infection. However, if proteinuria persists, treat as relapse
FREQUENTLY RELAPSING NEPHROTIC SYNDROME THERAPHY OPTIONS
Prednisolone 2mg/kg per day until proteinuria nor-
malize for 3 consecutive days followed by 1.5 mg/
kg on alternate days for 4 weeks, then taper over 2
months by 0.5 mg/kg on alternate days
Oral cyclophosphamide 2mg/kg per day for 12
weeks (cumulative dose : 168 mg/kg) based on ideal
body weight started during prednisolone induced
remission, decrease prednisolone to 1.5mg/kg on
alternate days for 4 weeks then taper over 4 weeks
Mycophenolate mofetil 25-36mg/kg per day
(maximum 2g/day) divided twice daily for 1 to 2
years with a tapering dose of prednisolone
Cyclosporine A 3 to 5 mg/kg per day divided in
BID for an average of 2 to 5 years
Malaysian Pediatric Protocol 2013 only rec-
ommend prednisolone as treatment of fre-
quent relapses and later is commonly use in
steroid dependent nephrotic syndrome.
Prednisolone induction dose:
60mg/m²/day (maximum 80mg) until
remission followed by
40mg/m²/on alternate day (maximum
60mg) for 4 weeks
Taper prednisolone dose every 2 weeks
and keep on as low an alternate day dose
as possible for 6 months. Should child
relapse while on low dose alternate day
prednislone, the child should be re-
induced with prednisolone as for relapse
TREATMENT OF STEROID DEPENDENT NEPHROTIC SYNDROME
Glucocorticoids are preferred treatment in the absence of steroid toxicity
Cytotoxic drugs ex : cyclophosphamide, chlorambucil
Levamisole
Calcineurin inhibitor ex: Cyclosporine, Tacrolimus
Mycofenolate Mofetil
STEROID-RESISTANT NEPHROTIC SYNDROME MANAGEMENT
Goal of therapy : complete resolution of proteinuria
and preservation of kidney function
3 major categories of therapy for SRNS :
-Immunosuppressive
-Immunostimulatory
-Nonimmunosuppressive
Immunosuppresive
The most commonly used immunosuppressive therapy include calccineurin inhibitor, MMF,
pulse intravenous methylprednisolone and cytotoxic agent
Less commonly used include plasma exchange and immunoabsorption
Immunostimulatory
The only reported immunostimulatory is levamisole however it is not universally available
Nonimmunosuppressive
Consider as supportive treatment and include ACE-I, ARB and vitamin E
ACE-I and ARB reduce proteinuria by decreasing the transcapillary glomerular hysrostatic
pressure and altering glomerular permeability
ACE-I decrease synthesis of transforming growth factor (TGF)-β and plasminogen activator
inhibitor (PAI)-1. TGF-β and PAI-1 are important profibrotic cytokines promoting glomeru-
losclerosis
Kidney biopsy
Tailor therapeutic regimen according to
kidney histology
Supportive therapy
18
THIAZOLIDINEDIONES
ADALIMUMAB
GALACTOSE
RITUXIMAB
MONITORING RECOMMENDATIONS FOR
CHILDREN WITH NEPHROTIC SYNDROME
SOURCES : S. Gipson, D., F. Massengill, S., Yao, L., Nagaraj, S., E. Smoyer, W., D. Mahan, J., Wigfall, D., Miles, P., Poswell, L., Lin, J., Trachtman, H. and A. Greenbaum, L. 2008. Management of Childhood Onset Nephrotic Syndrome. Journal of The American Acede-
my of Pediatrics, 27 (124), p. 747
REFERENCES
1. Bangga, A. and Mantan, M. 2005. Nephrotic syndrome in children. Indian J Med Res, 122 pp. 13-28.
2. Kodner, C. 2009. Nephrotic Syndrome in Adults : Diagnosis and Management. American Family Physician,
80 (10)
3. A. Greenbaum, L., Benndorf, R. and E. Smoyer, W. 2012. Childhood nephrotic syndrome-current an future
therapies. Nature Reviews Nephrology, 8 pp. 445-448
4. Guideline for Management of Nephrotic Syndrome, Renal unit Royal Hospital for Sick Children Yorkhill Di-
vision
5. S. Gipson, D., F. Massengill, S., Yao, L., Nagaraj, S., E. Smoyer, W., D. Mahan, J., Wigfall, D., Miles, P.,
Poswell, L., Lin, J., Trachtman, H. and A. Greenbaum, L. 2008. Management of Childhood Onset Nephrotic
Syndrome. Journal of The American Acedemy of Pediatrics, 27 (124), p. 747
6. Paediatric protocols for Malaysian Hospitals 3rd Edition
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