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,

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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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