drug use flow charts - formularydformulary.h.usm.my/assets/flow_chart_2019_final...-calcium channel...

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COMPILED BY:

UNIT FARMASI

KLINIKAL DAN

MAKLUMAT DRUG

HOSPITAL USM Drug Use Flow Charts

2019

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Contents GUIDELINES FOR USING PROTON PUMP INHIBITOR (PPI) HUSM .......................................................1 FLOW CHART USAGE OF PPI IN HUSM ...........................................................................................................3 LIPID LOWERING THERAPY USM GUIDELINES ............................................................................................4 INDICATION OF USING AMLODIPINE (AND FELODIPINE) IN HUSM (SUGGESTION) ..............9 PROPOSAL GUIDELINES ON PLAVIX PRESCRIPTION FOR CARDIOLOGY PATIENTS HUSM..... 15 SIMPLIFIED NOVOSEVEN PROTOCOL FOR HAEMATOLOGY USM ................................................... 16 SIMPLIFIED NOVOSEVEN PROTOCOL FOR NEUROSURGERY USM ................................................... 16 GUIDELINE FOR OFF-LABEL USE OF RECOMBINANT ACTIVATED FACTOR VII (rFVIIa) ........... 18 GUIDELINE FOR THE USE OF RECOMBINANT ACTIVATED FACTOR VII (RFVIIA) IN NON-HEMOPHILIC PATIENTS WITH LIFE-THREATENING HEMORRHAGE ............................................... 21 GUIDELINES FOR OUTPATIENT TREATMENT OF CHRONIC ASTHMA DEPARTMENT OF MEDICINE HOSPITAL USM ............................................................................................................................... 30 GUIDELINES FOR USING INFLUENZA VACCINE ....................................................................................... 33 FLOW CHART PENGGUNAAN DRUG UNTUK RAWATAN ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) ............................................................................................................ 34 ALGORITHM FOR MEDICATIONS OF SCHIZOPHRENIA ........................................................................ 36 ACUTE TREATMENT OF MANIA ...................................................................................................................... 38 ACUTE TREATMENT OF BIPOLAR DEPRESSION......................................................................................... 39 PSYCOPHARMACOLOGICAL TREATMENT ALGORITHM FOR GENERALUIZED ANXIETY DISORDER (GAD) .................................................................................................................................................. 40 ALGORITHM (2) FOR THE PHARMACOTHERAPY OF MAJOR DEPRESSIVE DISORDER (MDD) ..................................................................................................................................................................................... 41 ALGORITHM FOR MANAGEMENT OF DEMENTIA ................................................................................... 42 ALZHEIMER’S DISEASE TREATMENT STRATEGY ....................................................................................... 43 PARKINSON DISEASE ........................................................................................................................................... 44 FLOW CHART FOR TREATMENT HEPATITIS B IN TREATMENT NAÏVE PATIENTS ........................ 45 FLOW CHART OF CHRONIC VIRAL HEPATITIS B PRE CORE MUTANT HBEAG NEGATIVE ....... 46 FLOW CHART FOR GENITAL ULCER SYNDROME ..................................................................................... 47 TREATMENT FOR SYPHILIS AND CHANCROID ......................................................................................... 47 FLOW CHART FOR VAGINAL DISCHARGE SYNDROME ......................................................................... 48 FLOW CHART FOR URETHRAL DISCHARGE SYNDROME IN MEN ..................................................... 49 OUTPATIENT TREATMENT OF CAP ................................................................................................................ 50 FLOW CHART OF USING SULPERAZONE IN ICU ...................................................................................... 52 GUIDELINES FOR USING NOVOMIX 30 FLEXPEN HOSPITAL UNIVERSITI SAINS MALAYSIA .. 53 FLOWCHART FOR USE OF GLUCOPHAGE XR ............................................................................................ 54 FLOWCHART FOR USE OF INSULIN DETEMIR ........................................................................................... 55 ALGORITHM FOR THE MANAGEMENT OF POSTMENOPAUSAL OSTEOPOROSIS ....................... 56 ZOLENDRONIC ACID PRESCRIPTION FLOW CHART .............................................................................. 57

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FLOW CHART FOR USING IMATINIB IN CHRONIC MYELOID LEUKEMIA (CML), PH+ ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) ............................................................................................................... 58 ARCOXIA PRESCRIPTION FLOW CHART ...................................................................................................... 59 OUTPATIENT PAIN PRESCRIPTION FLOW CHART .................................................................................... 60 FLOWCHART OF PATIENTS DIAGNOSED WITH BACTERIAL CONJUNCTIVITIS ........................... 61 FLOWCHART OF PATIENTS DIAGNOSED WITH BACTERIAL KERATITIS ......................................... 62 FLOWCHART OF PATIENTS REQUIRING PRE AND POST CATARACT SURGERY ANTIBIOTIC PROPHYLAXIS ......................................................................................................................................................... 63 FLOW CHART FOR USING OLOPATADINE 0.1% ....................................................................................... 64 TREATMENT ALGORITHM OF ALLERGIC RHINITIS (AR) ........................................................................ 65 FLOW CHART OF THALASSAEMIA PATIENT WITH IRON OVERLOAD ............................................. 66 INTERFERON BETA-1B FLOWCHART ............................................................................................................ 67 FLOW CHART FOR INSULIN ANALOGUE AT KRK ..................................................................................... 68

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GUIDELINES FOR USING PROTON PUMP INHIBITOR (PPI) HUSM

Upper GIT bleed

Mucosal break lesion

Treatment Prophylatic / suspected

Upper GIT bleed confirm on OGDS Tab / IV PPI 40 mg OD

Chronic

T. PPI 40mg OD x 3-6/12

Long term – if has other risk factors eg:

- Age > 65 years - On anti-platelet / NSAIDs /

STEROIDs

Acute

IV PPI 80 mg stat

Emergency OGDS within 24 hour

IV PPI 8mg/hr x 72 hours

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Maintenance T. PPI 40 mg BD x 4-6/52 therapy

If not properly heal

If symptom persisted

Maintenance T. PPI OD x 3-6/12

Remarks:

1st line Pantoprazole

2nd line Esomeprazole

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FLOW CHART USAGE OF PPI IN HUSM ENDOSCOPY MEETING ON 7/2/12

Bleeding cases (Non variceal bleed) 1st Endoscopic procedure, then 2nd Proton pump inhibitor (PPI), then 3rd Mucosal protective therapy (oral sucralfate), then 4th Surgival intervention Bleeding cases (variceal bleed) 1st line I/V Octreotide 25-50mcg, then 25-50mcg/hr Or Somatostatin 250mcg stat then 250mcg/hr 2nd line PPI infusion PPI 1st line I/V PPI 80 mg stat, then I/V PPI 8 mg/hr for 3 – 5/7, then I/V PPI 40 mg BD Follow-up by tab.PPI 40 mg BD x 8 – 12/52 and to repeat endoscopy if rebleed or after complete treatment. Mucosal break lesion (Prophylaxis) 1st line I/V Pantoprazole 40mg stat 2nd line I/V Esomeprazole 40 mg BD 3rd line Oral Sucralfate 4th line I/V Ranitidine or tablet Peptic Ulser disease (PUD) 1st line Tab. Pantoprazole 40mg OD/BD, then 2nd line Tab. Esomeprazole 40 mg OD/BD, then 3rd line Tab. Omeprazole 20 mg BD

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In cases of PUD (No. OGDS) (No. PPI test) Tab. Ganaton 50 mg BD/TDS with 1st line Tab. Pantoprazole 40 mg OD/BD 2nd line Tab. Esomeprazole 40 mg OD/BD If not improve after 2/52 refer results endoscopy investigation (Gastro/Surgical) In cases of no OGDS for PPI test 1st line Tab. Pantoprazole 40 mg BD x 2/52 then decision OR 2nd line Tab. Esomeprazole 40 mg BD x 2/52 then decision. In Cases of Biliary gastritis/ recurrent GERD/ GERD (Gastrooesophageal disease)

1) T. Ganaton 50 mg BD/TDS with 1st line T. Esomeprazole 40 mg BD/TDS

2) T. Ganaton 50 mg BD/TDS with 2 nd line T. Pantoprazole 40 mg BD

In Cases of PUD with normal OGDS/ NERD (non erosive gastritis) T. Ganaton 50 mg BD/TDS WITH 1st line Tab. Esomeprazole 40 mg OD/BD 2 nd line Tab. Pantoprazole 40 mg OD/BD

Last Update: February 2012

LIPID LOWERING THERAPY USM GUIDELINES

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Indications for use

1. Coronary heart disease (CHD) 2. CHD disease equivalent

a) Diabetes Mellitus b) Carotid artery disease c) Peripheral artery disease d) Abdominal aortic aneurysm

3. Familial hyperlipidaemia (or total chol > 8, LDL chol > 6) 4. CHD high risk individuals

a) Individuals with 2 or more risk factors 5. CHD low risk

a) Individuals with less than 2 risk factors 6. If asymptomatic but total cholesterol ≥ 5.0 mmol/l, LDL cholesterol ≥ 3.0

mmol/l and total CVD risk of projected CVD risk at 60 years of age is ≥ 5%. 7. Others

a) Individuals with chronic renal disease (Creatinine > 133 umol/L or GFR < 60 ml/min/1.73 m2)

b) Metabolic syndrome

Drug Dose range ( mg )

LDL reduction Cost for 1/12 rx RM

Pravastatin 10 - 40 19 – 40 %

Simvastatin 10 - 80 28 - 48 %

Lovastatin 20 - 80 29 – 48 %

Atorvastatin 10 - 80 38 – 54 %

Rosuvastatin 10 - 40 52 – 63 %

Indications 1-4

• Aggressive lipid lowering therapy required

• High dose and high potency drug required

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• Suggestion

Indications 5-7:

• Lipid lowering therapy can be step wise intensification

• Suggestions

1. Coronary heart disease (CHD) 2. CHD disease equivalent

i) Diabetes Mellitus ii) Carotid artery disease iii) Peripheral artery disease iv) Abdominal aortic aneurysm

3. Familial hyperlipidaemia (or total chol > 8, LDL, chol >6) 4. CHD high risk individuals- Individuals with 2 or more

Check FLP

Start atorvastatin

10 – 20 mg od

Check FLP after

3/12

TLC

Total C > 4.5 or

LDL > 2.5

Total C < 4.5 or

LDL < 2.5

Intensification of Rx

Increase dose of

Atovarstatin or change

to Rosuvastatin

Continue medication or

consider de-escalation of Rx

ie change to Simvastatin or

Pravastatin as per indicated TLC

TLC = Therapeutic lifestyle changes

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Drug therapy indicated

1. CHD low risk

a) Individuals with less than 2 risk factors

2. If asymptomatic but total cholesterol ≥ 5.0 mmol/l, LDL cholesterol ≥ 3.0

mmol/l and total CVD risk of projected CVD risk at 60 years of age is ≥ 5 %.

3. Others

a) Individuals with chronic renal disease

(Creatinine > 1.33 umol/L or GFR < 60 ml/min/1.73 m2)

b) Metabolic syndrome

Total chol

Risk score: 10 year risk for CV death

Total risk 5.0

LDL chol > 3.0

Continue TLC Continue TLC

Reassess risk yearly

Start drug

therapy If risk ≥ 5 % and

Total chol < 4.5 and

LDL chol < 2.5

TLC = Therapeutic

lifestyle changes

Consider drug

therapy

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Prepared by Dr Tee Meng Hun & AP Dr Zulkurnai Yusof, Med Dept

Total chol 5.0 – 5.9

LDL chol 2.5 – 3.5

Total chol 6.0 – 6.9

LDL chol 3.5- 4.5

Total chol 7.0

LDL chol 4.5

Pravastatin or

simvastatin

Simvastatin or

atorvastatin

Atorvatatin or

rosuvastatin

If targets not achieved : Total chol > 4.5 or LDL > 2.5

CHECK COMPLIANCE TO TLC AND DRUG THERAPY

Consider intensifying treatment

Simvastatin

Ezetimide

Or

Atorvastatin

Or

Rosuvastatin

Combination therapy

Atorvastatin

Or

Rosuvastatin

And or

Ezetimibe

And or

Fibrates etc

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INDICATION OF USING AMLODIPINE (AND FELODIPINE) IN HUSM (SUGGESTION) 1. Introduction Calcium channel blockers work by blocking the initial calcium influx into myocytes and vascular smooth muscle cells. Amlodipine and felodipine are long acting second generation dihydropyridine that have vascular smooth muscle relaxing activity with no or minimal negative inotropic effects. They have a greater selectivity for vascular smooth muscle compared to the myocardium. They vasodilate coronary arteries reduce coronary resistance, increase coronary blood flow and may enhance the development of coronary collaterals. 2.Indication of using calcium channel blocker (CCB) 2a. The use of CCB as anti-ischemic agent -calcium channel blocker has been shown to exert anti-angina properties in various ways such as reduction in heart rate, reduction in contractility, reduction in afterload and direct vasodilatation. -calcium channel blocker should be considered if there are contraindications or adverse reactions to either beta blockers of nitrates or if symptoms are not well controlled with a combination of these agents. 2b.The use in acute coronary syndrome (ACS) patients. - The potential benefits of either amlodipine or felodipine in acute MI has not been examined directly. - Amlodipine is often used in patients with acute MI when hypertension is not adequately controlled by other therapy of proven benefit (beta blockers and ACE inhibitors ). - Study in stable coronary heart disease (PREVENT trial) found no or little benefit of amlodipine but also has no harm. - Therefore amlodipine is not indicated as first line therapy on ACS patients unlike ACE inhibitors and beta blockers. 2c. The use of CCB in patients with heart failure - The potential benefit of either amlodipine or felodipine in acute MI has not been examined directly. However, clinical trial that have evaluated these drugs in heart failure (V- HeFT III and the PRAISE trials) found no or little benefit but also no harm. - In patient with heart failure, amlodipine in at a drug choice as compared to ACE inhibitors, beta blockers and aldosterone antagonist.

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2d.The use of CCB in hypertension patients. - Although recommendations for initiating medical therapy in essential hypertension have been proposed, there is no uniform agreement on which antihypertensive agent should be given as initial therapy. A variety of different classes of drugs can be used in this setting. These include the thiazide diuretics, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers and calcium channel blockers. - There have been limited data as to whether different antihypertensive drugs have variable effects upon patient outcomes, particularly cardiovascular morbidity and mortality. However, an increasing number of trials have provided evidence that at the same level of blood pressure control, most antihypertensive drugs provide the same degree of cardiovascular protection provided there are no other compelling indications. - The choice of drug should be based on the patient’s individual risk profile and the tolerability of the drugs. - “First-line” drugs should have the following properties : 1. reduce long-term morbidity and mortality 2. high efficacy of once-daily administration 3. no adverse effects on concomitant risk factor 4. good tolerability - based on JNC VII guidelines, hypertensive naïve patient should receive diuretics as first line drug. 2e. The use of CCB in anti-arrythmic agents -the use of amlodipine as anti- arrythmic agents therapy was not well studied unlike verapamil and diltiazem, therefore it is not recommended as anti-arrythmic therapy. 2f. The use of CCB in patients with renal disease/nephropathy - Hypertension is common in chronic renal disease and is risk factor for progression of renal damage, and reduction of blood pressure (BP) is an efficient way of preventing or slowing the progression of this damage. BP – lowering effects are common to all antihypertensive drugs, but intra-renal effects differ between classes and between individual drugs within certain classes. Angiotensin – converting enzyme (ACE) inhibitors and angiotensin receptors blockers (ARB) have beneficial effects on proteinuria and declining renal function that appear to be mediated by factors additional to their effects on BP. These RAS inhibitors are recommended as first-line antihypertensive approach in patients with chronic kidney disease. - Calcium channel antagonist are highly a heterogenous class of compounds, and it appears that some agents are more suitable for use in patients with chronic renal disease than others. Most common calcium channel blockers are nondihydropyridine group like verapamil and diltiazem. - Dihydropyridine calcium channel blockers (eg nifedipine and amlodipine) may worsen proteinuria and accelerate the progression of disease in patients with nondiabetic or diabetic nephropathy. 2g. The use of CCB in peripheral vascular disease (PVD) patient.

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- Unlike verapamil, the use of amlodipine and felodipine in treating peripheral

vascular disease patients are not well studied. Therefore, it is not recommended to use these drugs to treat PVD patients.

2h. The use of CCB in Pulmonary Artery Hypertension patients.

- The oral vasodilators of choice are the calcium channel blockers nifedipine and diltiazem. Verapamil is not recommended, since it tends to posses significant negative inotropic properties.

- Amlodipine has been a useful alternative for patients who are intolerant of the other agents (eg. Because of edema, bradycardia, tachycardia, or hypotension)

- The use of Felodipine in pulmonary artery hypertension is not well studied. 3. Advantages of Amlodipine (and felodipine) above other antihypertensive. 3a.Single daily dose, therefore this will improve patient compliance. 3b. No need for renal function monitoring. 3c. Among the least side effects compared to other anti-hypertensive. 3d. In comparison between amlodipine and felodipine, on of the retrospective study has shown that amlodipine has better patient’s adherence compared to felodipine. 4. Disadvantages of CCB above other antihypertensive. 4a. The potential benefit of either amlodipine or felodipine in ACS has not been examined directly in ACS patients. A systematic analysis of all randomized calcium blocker trials in unstable angina suggests calcium channel blockers that as a class do not prevent the development of acute myocardial infarction or reduce mortality, and it also has no harm to these group of patients. 4b. Short-acting CCB (i.e. Nifedipine) has a relatively high incidence of adverse side effects, including peripheral edema (not related to heart failure), flushing, headaches, and lightheadedness, which is due to peripheral vasodilatation. 4c. There was a study (cross sectional) showed that there was a higher rate of depression among hypertensive patients who were on calcium channel blocker as compared to other anti-hypertensive. 4d. Both amlodipine and felodipine are long acting calcium channel blockers, therefore it is not recommended as first line therapy for hypertensive urgency. List of Tables Table 1 Comparative pharmacokinetics of selected dihydropyridine calcium channel antagonists

Nifedipine Nisoldipine Felodipine Amlodipine Diodipine

Oral absorption >90 >90 >90 >90 >90

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Oral bioavailability

30-50 5-15 10-25 60-65 5-15

Elimination half-life

3-5 4-10 2-8 35-50 3-15

Table-Dosing and costs of the Calcium Channel Blockers

Drug Initial Dose Usual Dosage Range Cost x 30 days

Verapamil - regular (Isoptia® generic) - long acting (Isoptin SR®)

(Varelan®)

80mg TID 180 mg daily 180 mg daily

80-160 mg TID 120 mg daily-240mg BID 120-480 mg daily

$37.33-$68.15 $37.52-$99.94 $32.87-$85.92

Diltiazem - regular (Cardizem® generic) - long acting (Cardizem

SR®)** (Cardizem CD®)

30mg TID 60 mg BID 120 mg daily

30mg TID-90 mg QID 60-80 mg BID 120 mg-300mg daily

$28.51- $83.61 $51.63- $126.31** $47.12- $95.89

Felodipine (Plendil®, Renedil®) Nifedipine - regular capsules

(Adalat®generic) - long acting (Adalat PA®)** (Adalt XL®) Amlodipine (Norvasc®) Nicardipine (Cardene®)

5mg daily 10mg TID 10 mg BID 30 mg daily 5 mg daily 10mg TID

2.5-20 mg daily 10mg TID-30 mg QID 10-40mg BID 30-120 mg daily 5-10 mg daily 20-40 mg TID

$23.13-$83.61 $27.25-$89.52 $37.90-$104.72** $37.81-$104.72 $46.14-$65.34 $62.04-$117.58

**Base on wholesale acquisition cost Feb. 1995 of least expensive product and professional fee of $6.50 as April 1, 1995. Pharmcare no longer covers Cardizem SR and Adalat PA

5. References

1. Antiischemic Agents in the Management of Unstable Angina and Acute Non-ST Elevation (Non-Q Wave) Myocardial Infarction. Michael Simons, MD. Up to date version 13.3

2. Calcium Channel Blockers in Acute Myocardial Infarction. Robert S Rosenson,

MD Harold L Keneddy, MD, MPH. Up to date version 13.3.

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3. Calcium Channel Blockers in the Management of Stable Angina Pectoris.

Joseph P. Kannam, MD. Julian M Aroesty, MD. Bernard J Gersh, MB, ChB, DPhil, FRCP. UpToDate version 13.3.

4. Choice of Therapy in Essential Hypertension: Clinical Trials. Norman M Kaplan,

MD, Burton D Rose, MD. UpToDate version 13.3.

5. Wenzel, Rene R. Renal Protection in Hypertensive Patients: Selection of Antihypertensive Therapy. (Review). Dugs. 65 (Suppl 2):29-39, 2005.

6. JNC VII guidelines. 7. Medical Management of Claudication. UpToDate version 13.3.

8. Non Diabetic Kidney Disease (Andrew S) N Engl J Med. VOl 347. No 19.

November 7, 2002. 9. Nephropathy in Patient with Type 2 Diabetes. Remuzzi et al. N Engl J Med. Vol.

346, No. 15 April 11, 2002.

10. Adherence to Calcium Channel Blocker Therapy in Older Adults: A Comparison of Amlodipine and Felodipine. Menzin J et al. J Int Med Res. 2004 May-June; 32(3) :233-9.

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FLOW CHART

Diagnosis of hypertension

Initiate lifestyle modification

If still not achieve BP target (100mmHg) –

consider 2 drugs

Use appropriate

anti-hypertensive

agent

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PROPOSAL GUIDELINES ON PLAVIX PRESCRIPTION FOR CARDIOLOGY PATIENTS HUSM

ACUTE CORONARY SYNDROME

PERCUTANEOUS CORONARY

INTERVENTION (PCI)

INTRACEPT ASD CLOSURE DEVICE

CABG

• NSTEMI/UA = 9 months

• STEMI = 8 days

• Bare metal stent = 3-4 weeks

• Drug eluting stent (DES) = 6-12 months

• Plavix x 3 months

• No indication

* Contraindication for aspirin, ticlopidine is a substitution

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SIMPLIFIED NOVOSEVEN PROTOCOL FOR HAEMATOLOGY USM

FLOW CHART

1. HAEMOPHILIA A OR B WITH INHIBITOR 2. CONGENITAL FACTOR VII DEFICIENCY 3. GLANZMANN’S THROMBASTHENIA

4. AN INHERITED PLATELET FUNCTION DISORDER (ANY OTHER HAEMOTOLOGICAL CONDITIONS: SEE OFF-LABEL USE PROTOCOL FOR

NOVOSEVEN)

IN SEVERE DIVC OR COAGULOPATHY AND THREATEN LIFE OF THE PATIENT

GIVE NOVOSEVEN (THE DOSAGE: HAEMATOLOGIST’S DECISION)

DIVC OR COAGULOPATHY CORRECTED Last update: 24 JANUARY 2012

SIMPLIFIED NOVOSEVEN PROTOCOL FOR NEUROSURGERY USM

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FLOW CHART

(POLY)TRAUMA PATIENT

IN SEVERE DIVC OR COAGULOPATHY. AND FOR URGENT/EMERGENCY LIFE-SAVING

SURGERY

GIVE NOVOSEVEN (GENERALLY THE DOSAGE: 1-3 AMPOULES DEPENDS ON: SEVERITY AND PATIENT’S BODY WEIGHT)

DIVC CORRECTED

SURGERY Last update: 24 JANUARY 2012

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GUIDELINE FOR OFF-LABEL USE OF RECOMBINANT ACTIVATED FACTOR VII (rFVIIa) Jan 2010

Malaysian Society of Haematology

Algorithm for use of rFVIIa

Massive

Haemorrhage

- Control of bleeding source with surgery or embolisation - Blood components therapy

- Reversal of any anticoagulation

[PPH: Uterine massage/compression, uterotonic agents]

Attempt to correct:

Hct to > 24%

Fibrinogen > 0.5-1.0g/L

Platelets > 50 x 109/L

pH ≥ 7.2

Bleeding

Stopped

- Consider rFVIIa - Discuss with on-call Consultant in-charge - Fill up registry form for off-label use of

rFVIIa

Administer rFVIIa (Single bolus over 3-5mins – Dose as per

institution practice)

Persistent bleeding & generalized oozing

despite surgical control

Consider after 30-60mins



Bleeding

Stopped

Guideline for the use of rFVIIa

1. Use of rFVIIa in non-haemophilic patients and any decision to use

rFVIIa rests exclusively with the

prescribing clinicians.

2. Appropriate medical and surgical interventions should be carried out to

reduce the magnitude of critical

bleeding before initiating

administration of rFVIIa.

3. RFVIIa should only be used where the clinician considers the benefit

outweighs the risk of thrombosis.

4. The algorithm provided here serves as a guide only. Adherence to this

guideline is encourage but not

mandatory.

5. Following administration of rFVIIa, all patients should be monitored for

signs of improvement and adverse

events.

6. The prescribing clinican should report all off-label use of rFVIIa to the

rFVIIa Registry in Managing

Critical Bleeds in Non-Haemophilia

Patients through completion of the

relevant data collection form.

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Control of bleeding source with surgery or embolisation

Re-administer rFVIIa

[PPH: Consider hysterectomy if

bleeding persists after 2 doses of

rFVIIa]

Attempt to correct:

Hct to > 24%



pH ≥ 7.2

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GUIDELINE FOR OFF-LABEL USE OF RECOMBINANT ACTIVATED FACTOR VII (rFVIIa)

Malaysian Society of Haematology

(Member in USM preparing this new protocol: AP Dr Zamzuri Idris; Neurosains)

Jan 2010

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GUIDELINE FOR THE USE OF RECOMBINANT ACTIVATED FACTOR VII (RFVIIA) IN NON-HEMOPHILIC PATIENTS WITH LIFE-THREATENING HEMORRHAGE

Introduction

Recombinant FVIIa (Novoseven) was developed for the treatment of bleeding in patients with hemophilia who have inhibitors against factor VIII or IX. It is manufactured by recombinant technology using baby hamster kidneys.1

Licensed indications 2 It is currently licensed for the treatment of bleeding episodes and for controlling bleeding during surgery in the following conditions: 5. Inherited or acquired hemophilia with inhibitors 6. Congenital factor VII deficiency and 7. Glanzmann’s thrombasthenia, an inherited platelet function disorder Out-of license or off-label use There is a growing trend for out-of license use of rFVIIa in non-hemophilic patients with life-threatening or massive hemorrhage* such as from trauma, surgery, post-partum, liver transplant/ failure and intracerebral hemorrhage. Definition of massive hemorrhage* 3

▪ replacement of total blood volume within 24 hours (>10 units of packed red cell in a 70kg patient)

▪ loss of 50% of circulating blood volume in 3 hours or ▪ loss of 150 ml of blood per minute

Mode of action Administration of pharmacologic doses of exogenous rFVIIa directly enhances thrombin generation on the platelet surface at the site of injury independently of factor VIII or IX resulting in a stable fibrin clot. Recombinant FVIIa has a short half-life of 2.5 hours.1,4,5

Recommended dose The recommended dose of rFVIIa for hemophilia with inhibitors is 90 to 120 ug/kg by slow iv bolus over 2 to 5 minutes. The optimal dosing for off-label use is not known. A second dose can be repeated after 1 to 2 hours if bleeding is still not controlled.1,4

* Note that inhibitors in hemophilia patients render factor VIII/ IX concentrates or plasma useless by neutralizing the coagulation factors VIII or IX. The recommended dose of 90 to 120 ug/kg is the amount of rFVIIa required to generate enough thrombin to form a tight fibrin clot in these patients. This dose cannot be extrapolated to patients with life-threatening bleeding with otherwise normal coagulation or in whom any abnormal coagulation can be corrected with plasma. Furthermore tissue injury following trauma, surgery or post-partum releases tissue factor which activates the coagulation system; hence by giving the recommended dose of rFVIIa (for inhibitor patients) for life-threatening hemorrhage in these patients may result in thrombotic

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complications. Smaller doses between 30 to 60 ug/kg have been used with good response in these situations.6,7

Contraindications 3 Absolute

▪ Unsalvageable patients ▪ Allergy to mouse, hamster or bovine proteins

Relative ▪ Known thrombophilia ▪ History of recent thromboembolic events within the last 6 months eg. myocardial

infarction, stroke or deep vein thrombosis Precautions 3

▪ Patients with prosthetic heart valve ▪ Patients with recent coronary angioplasty and stent insertion ▪ Patients with coronary artery disease ▪ Patients with cerebrovascular disease ▪ Patients on ECMO or VAD ▪ Patients with disseminated intravascular coagulation or sepsis

Preconditions before rFVIIa administration 3

▪ Appropriate surgical interventions to secure hemostasis have been carried out if indicated

▪ Appropriate blood component therapy has been instituted in abnormal coagulation states to attempt to achieve a fibrinogen level >1 g/L and platelet count >50 x109/L

▪ Attempt to correct anaemia to keep Hb >7 g/dL or Hct >24% with blood transfusion

▪ Keep pH ≥ 7.2 ▪ Core temperature ≥ 34°C ▪ Normal serum calcium

Timing and appropriateness of administration For best outcome, consider rFVIIa early after the first blood component replacement fails to control the hemorrhage or after failing appropriate surgical intervention. Do not use in non-salvageable patients or if the overall outlook of the patient is so poor that arresting the hemorrhage does not alter the outcome.3

Monitoring There is no specific laboratory test to monitor the efficacy of rFVIIa. The clinical response of cessation of bleeding, the amount of blood loss and transfusion requirement are monitored and recorded.1,4

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Complications There is a continuing concern that rFVIIa can cause thromboembolic complications because it is an activated factor given in doses to cause a non-physiological rise in factor VII levels by more than 1000-fold. In hemophilia with inhibitors there is a 1% incidence of thromboembolic events eg. myocardial infarction, ischemic stroke, deep vein thrombosis or pulmonary embolism.5 Similar events have been reported in non-hemophilic patients but the true incidence is not known. Hence, administration of rFVIIa should be used with caution in patients who have a predisposition to thrombosis such as diabetes mellitus, cardiovascular disease, cancer, obesity and the elderly.4,6 Specific situations Disseminated intravascular coagulation A literature review found 15 uncontrolled studies with 32 cases on the use of rFVIIa for disseminated intravascular coagulation due to postpartum hemorrhage. A single dose of rFVIIa was able to control bleeding in 80% of patients with a median dose of 67.6 ug/kg (range 30-120 ug/kg). In another series of 18 patients with DIC associated with metastatic cancer, 80% of patients responded to a median of 5 doses of rFVIIa at 90 ug/kg with no thromboembolic complications. 7, 8

Intracerebral hemorrhage Following an intracerebral hemorrhage, evidence shows that there is expansion of the hematoma mass in 50% of patients for up to 6 hours. This suggests that early arrest of hematoma growth would improve outcome. In a double-blind, placebo-controlled trial of 399 patients with intracerebral hemorrhage diagnosed within 3 hours of onset by CT scan, patients were randomly included to receive placebo or rFVIIa at doses of 40 ug/kg, 80 ug/kg or 160 ug/kg. Treatment with rFVIIa was found to limit the growth of the hematoma, reduce mortality by 35% and improve functional outcome at 90 days in all 3 dosing groups but with an increase frequency of thromboembolic events with the highest dose. Best outcomes are seen in patients treated early with a Glasgow Coma Scale of ≥13.9,10

This study was followed by a larger phase III randomized, multicenter, double-blind, placebo-controlled trial to confirm the above findings. Eight hundred and forty one patients with inracerebral hemorrhage were randomized to receive placebo or rFVIIa at doses of 20 ug/kg or 80 ug/kg within 4 hours after the onset of stroke. The hemostatic effect was similar but there was no difference in severe disability or mortality at 90 days between the placebo and rFVIIa treatment arms.11 Liver transplant/ failure There have been anecdotal reports of the successful use of rFVIIa in controlling bleeding in patients with liver disease but failures and recurrent bleeding have also been reported. Recombinant FVIIa has been successfully used in controlling bleeding in liver transplant in non-cirrhotic patients.6,12,13

24 | P a g e

Postpartum hemorrhage (PPH) There are no randomized studies, only case series of the use of rFVIIa in PPH reporting good response with cessation of bleeding in > 80% at a mean dose of 1.9 and a dose range between 30-120 ug/kg.6, 8,14,15,16 Prostatectomy Prostatectomy is often associated with major blood loss due to a high content of fibrinolytic activators in the prostate gland. In a double-blind, placebo-controlled trial with 36 patients undergoing retropubic prostatectomy, patients were randomly assigned to receive placebo or a single dose of rFVIIa at 20 ug/kg or 40 ug/kg in the early operative phase. More than 50% of the placebo group required red cell transfusion while none in the rFVIIa required any transfusion.17

Surgery There are reports of successful use of rFVIIa in controlling hemorrhage following general and cardiac surgery as well as some suggesting that it is not always effective.18,19,20. In a trial on spinal surgery, it was reported that there were no statistically significant differences in mortality, serious adverse events or thromboembolic adverse events between patients who were treated with 30μg/kg, 60μg/kg and 120μg/kg and those treated with placebo.21 After adjusting for factors (duration of surgery, number of vertebral segments fused and estimated blood volume); the volume and percentage of estimated blood volume lost, total transfusion volumes, mean number of allogenic blood products transfused and number of RBC units transfused in spinal surgery were statistically significantly lower for all three dosages of rFVIIa relative to placebo. 21 A meta-analysis of 5 clinical trials that included 298 patients undergoing cardiac surgery using rFVIIa porphylactically or for refractory bleeding showed a non-significant reduction in the rate of surgical re-exploration.22 Gill et al. reported in their study involving 172 patients that patients receiving rFVIIa for bleeding in post cardiac surgery had significantly fewer re-operations and significantly less transfusion of allogenic blood and blood products. However, these results must be interpreted cautiously because the trial is underpowered.23 Thrombocytopenia There are several reports showing variable success with the use of rFVIIa in patients with thrombocytopenia and uncontrolled bleeding.24,25 Only one randomized placebo-controlled study looked at bleeding complications in 100 thrombocytopenic patients following bone marrow transplantation. Bleedings in these patients were triggered by aplasia, septicemia and graft-versus-host disease. The most common were gastrointestinal hemorrhage and hemorrhagic cystitis. The results showed that there was no overall effect of rFVIIa administration at doses of 40, 80 or 160 ug/kg 6 hourly for 36 hours.26

25 | P a g e

Trauma In a randomized, placebo-controlled double-blind trial of 301 trauma patients, treatment with rFVIIa at doses of 200 ug/kg initially followed by 100 ug/kg, 1 and 3 hours later showed a reduced requirement for red cell transfusion but no reduction in overall mortality.27 The risk of ARDS alone in patients with blunt trauma was statistically significantly reduced compared to placebo. 27 There are other several reports on the successful use of rFVIIa in patients with extensive trauma and uncontrolled hemorrhage while there were no response in some. Patients with acidosis and profound shock were less likely to respond.3 Guideline for the use of rFVIIa 1. Use of rFVIIa in non-haemophilic patients and any decision to use rFVIIa rests

exclusively with the prescribing clinicians. 2. Appropriate medical and surgical interventions should be carried out to reduce the

magnitude of critical bleeding before initiating administration of rFVIIa. 3. RFVIIa should only be used where the clinician considers the benefit outweighs the

risk of thrombosis. 4. The algorithm provided here serves as a guide only. Adherence to this guideline is

encourage but not mandatory. 5. Following administration of rFVIIa, all patients should be monitored for signs of

improvement and adverse events. 6. The prescribing clinican should report all off-label use of rFVIIa to the rFVIIa Registry

in Managing Critical Bleeds in Non-Haemophilia Patients through completion of the relevant data collection form.

26 | P a g e

Algorithm for use of rFVIIa 28, 29

Control of bleeding source with surgery or embolisation

References:

Massive

Haemorrhage

- Consider rFVIIa - Discuss with on-call Consultant in-charge - Fill up registry form for off-label use of rFVIIa

Administer rFVIIa (Single bolus over 3-5mins – Dose as per

institution practice)



Re-administer rFVIIa

[PPH: Consider hysterectomy if bleeding

persists after 2 doses of rFVIIa]

Consider after 30-60mins

- Control of bleeding source with surgery or embolisation

- Blood components therapy

- Reversal of any anticoagulation

[PPH: Uterine massage/compression, uterotonic agents]

Attempt to correct:

Hct to > 24%



pH ≥ 7.2


despite surgical control Bleeding

Stopped

Attempt to correct:

Hct to > 24%



pH ≥ 7.2

Bleeding

Stopped

27 | P a g e

1. Hedner U. Mechanism of action of factor VIIa in the treatment of coagulopathies. Semin Hemost Thromb 2006;vol 32, suppl 1

2. NovoSeven Approved Package Insert (Malaysia), 2008

3. Martinowitz U, Michaelson M. Guidelines for the use of recombinant activated

factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force. J Thromb Haemost 2005;3:640-648

4. Negrier C, Lienhart A. Overall experience with NovoSeven. Blood Coagul

Fibrinolysis 2000;11(suppl 1)

5. Abshire T, Kenet G. Recombinant VIIa: review of efficacy, dosing regimens and safety in patients with congenital or acquired factor VIII or IX inhibitors. J Haemost Thromb 2004;2:899-909

6. Roberts HR, Monroe DM, White GC. The use of recombinant factor VIIa in the

treatment of bleeding disorders. Blood 2004;104:3858-3864

7. Sobieszczyk S, Breborowicz G, Platicanov V, et al. Recombinant factor VIIa in the management of postpartum bleeds: an audit of clinical use. Acta Obstet Gynecol 2006;85:1239-1247

8. Franchini M, Manzato F, Salvagno GL, et al. Potential role of recombinant

activated factor VII for the treatment of severe bleeding associated with disseminated intravascular coagulation: a systemic review. Blood Coagul Fibrinolysis 2007:18:589-593

9. Mayer SA, Brun NC, Begtrup K, et al. Recombinant Activated Factor VII for Acute

Intracerebral Hemorrhage. N Engl J Med 2005;352:777-785 10. Broderick JP, Brott TG, Duldner JE, Tomsick T, et al. A powerful and easy-to-use

predictor of 30-day mortality. Stroke 1993;24:987-993

11. Mayer SA et al. Can a subset of Intracerebral Hemorrhage Patients Benefit from Hemostatic Therapy with Recombinant Activated Factor VII? Stroke 2009;40:833-840.

12. Caldwell SH, Chang C, Macik BG. Recombinant activated factor VIIa as a

hemostatic agent in liver disease: a break from convention in need of controlled trials. Hepatology 2004;39:592-598

13. Hendriks HG, Meijer K, de Wolf JT et al. Reduced transfusion requirements by

recombinant factor VIIa in orthotropic liver transplantation: a pilot study. Transplantation 2001;71:402-405

28 | P a g e

14. Segal S, Shemesh IY, Blumenthal R, et al. Treatment of obstetric hemorrhage with

recombinant activated factor VII (rFVIIa) Arch Gynecol Obstet 2003;268:266-267

15. Bouma SL, Bolte CA, van Geijn PH. Use of recombinant activated factor VII in massive postpartum haemorrhage. Eu J Obs Gyn Repr Biol 2008;137:172-177

16. Ahonen J, Jokela R. Recombinant factor VIIa for life-threatening post-partum

haemorrhage. Br J Anaesth 2005; 94:592-595

17. Friederich PW, Henry CP, Messelink EJ, et al. Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomized trial. Lancet 2003;361:201-205

18. Dietrich W, Spannagl M. Caveat against the use of recombinant activated factor

VII for intractable bleeding in cardiac surgery. Anesth Anagl 2002;94:1369-70

19. Eikelboom JW, Bird R, Blythe D, et al. Recombinant activated factor VII for the treatment of life-threatening hemorrhage. Blood Coagul Fibrinolysis 2003;14:713-717

20. Tanaka KA, Waly AA, Cooper WA. Treatment of excessive bleeding in Jehovah’s

witness patients after cardiac surgery with recombinant factor VIIa (NovoSeven). Anesthesiology 2003; 98:1513-1515

21. Pohar SL, Tsakonas E, Murphy G et al. Recombinant activated factor VII in

treatment of hemorrhage unrelated to haemophilia. The Cochrane Database of Systematic Reviews, 2009;4

22. Zangrillo A et al. Recombinant Activated Favtor VII in Cardiac Surgery: A Meta-

analysis. J Cardiothor Vasc Anesth 2009;23:34040

23. Gill R, Herbertson M, Vuylsteke A. Et al. Safety and efficacy of recombinant activated factor VII. A randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation. 2009; 120: 21-27

24. Goodnough LT. Experiences with human recombinant factor VIIa in patients with

thrombocytopenia. Semin Hematol 2004;41:25-29

25. Vidarsson B, Onundarson PT. Recombinant factor VIIa for bleeding in refractory thrombocytopenia. Thromb Haemost 2000;83:634-635

29 | P a g e

26. Pihusch M, Bacigalupo A, Szer J, et al. Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation. J Thromb Haemost 2005;1935-1944

27. Boffard KD, Riou B, Warren B, et al. Recombinant factor VIIa as adjunctive therapy

for bleeding control in severely injured trauma patients: two parallel, randomized, placebo-controlled, double-blind clinical trials. J Trauma 2005; 59:8-15

28. Vincen JL, Rossaint R, Riou B, Ozier Y, Zideman D and Spahn DR,

Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding – a European perspective. Critical Care 2006, 10:R120

29. Welsh A, McLintock C, Gatt S, Somerset D, Popham P and Ogle R, Guidelines for

the use of recombinant activated factor VII in massive obstetric haemorrhage, Australian and New Zealand Journal of Obstetrics and Gynaecology 2008; 48; 12-16

30 | P a g e

GUIDELINES FOR OUTPATIENT TREATMENT OF CHRONIC ASTHMA DEPARTMENT OF MEDICINE HOSPITAL USM CLASSIFICATION BY SEVERITY1

CLASSIFY SEVERITY Clinical Feature Before Treatment

Symptoms Nocturnal Symptoms

FEV1 or PEF

STEP 4 Severe

Persistent

Continuous Limited physical activity

Frequent ≤ 60% predicted Variability > 30%

STEP 3 Moderate Persistent

Daily attack affect activity

> 1 time a week 60-80% predicted Variability > 30%

STEP 2 Mild Persistent

> 1 time a week but < 1 time a day

> 2 times a month ≥ 80% predicted Variability 20-30%

STEP 1 Intermittent

< 1 time a week Asymptomatic and normal PEF between attacks

≤ 2 times a month ≥ 80% predicted Variability < 20%

TREATMENT

STEP 1- Salbutamol Inhaler as required STEP 2- Move to step 2 if symptoms as above or failure of step 1

Does the patient has:

Allergic rhinitis?

Definite aspirin allergy?

Exercise induced asthma?

Yes

No

T. Montelukast 10 mg daily2

Salbutamol inhaler as required

Budesonide MDI/Turbuhaler 100-800ug BD

Beclomethasone MDI 50-500 ug BD/TDS

Ciclesonide MDI 160 ug OD/BD

Salbutamol MDI as required

Start steroid at high dose, taper down later1

31 | P a g e

STEP 3- Move to step 3 if symptoms as above or failure of step 2 STEP 4 – Move to step 4 if step 3 fails

Treatment options:

Formoterol/ Budesonide

4.5/160Turbuhaler (Symbicort®) 1 inh BD

or

Salmeterol/ Fluticasone 50/250 Accuhaler

(Seretide®) 1 inhalation BD


Consider Symbicort® if patient is educated

because

• the dose can be adjusted according

to the patients need i.e. 1 inhalation

BD when symptomatic and 1

inhalation daily if stable3

• Symbicort® may be used as rescue

medication

Treatment options:

Formoterol/ Budesonide

4.5/160Turbuhaler (Symbicort®) 1 inh BD

or

Salmeterol/ Fluticasone 50/250 Accuhaler

(Seretide®) 1 inhalation BD


Plus

Montelukast 10 mg daily

KIV

Theophyline SR 250 mg BD

Still symptomatic

32 | P a g e

Please note:

• Do reversibility test if diagnosis of asthma is questionable

• Do spirometry as baseline before starting any treatment

• Do spirometry before any change of treatment regime

• Discuss with chest physician before starting daily prednisolone References:

1. Global Initiative For Asthma 2002. www.ginaasthma.com 2. Mastalertz L, et al. Clin Exp Allergyu 2002 Sep;32(9):1360-5 3. Aalbers R, et al. Curr Med Res Opin 2004;20:225-240

Prepared by: Dr. Che Wan Aminud-din Hashim Respiratory Physician Department of Medicine

Version 1 Nov 2006

Add

Prednisolone 5-10 mg OD

http://www.ginaasthma.com/

33 | P a g e

GUIDELINES FOR USING INFLUENZA VACCINE Indication: Patients with the following criteria:-

1. Moderate to severe Chronic Obstructive Pulmonary Disease (Defined by GOLD guideline, HUSM guideline)

2. Asthma with recurrent exacerbation due to flu / URTI 3. Moderate to severe bronchiectasis with recurrent exacerbation 4. Any other chronic lung disease eg. Post-tuberculosis infection, insterstitial lung

disease, etc with recurrent secondary infection. Management Plan: Influenza vaccine will be administered as yearly basis. Prepared by: Dr. Che Wan Aminud-din b Hashim Repiratory Physician HUSM

34 | P a g e

FLOW CHART PENGGUNAAN DRUG UNTUK RAWATAN ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD)

• METHYLPHENIDATE IR (IMMEDIATE RELEASE)

• METHYLPHENIDATE SR (SLOW RELEASE)

• METHYLPHENIDATE LA (LONG ACTING)

• METHYLPHENIDATE (EXTENDED RELEASE) OR CONCERTA

• ATOMOXETINE (STRATERA)

Pesakit dirujuk ke klinik

Diagnosa ADHD

Disediakan oleh:

‘Pure ADHD’ ‘ADHD with comorbidities’

Umur di atas 6 tahun Umur di bawah 6 tahun

IR Methylphenidate (dly-tds)

Methylphenidate (dly-bd)

Methylphenidate LA (single dose)

Concerta (single dose)

Behavior modification

Adult ADHD

Epilepsy

Tics

Gilles de la

Tourette

Complicated

Pervasive SR

Development

Disorders

Severe untoward

events due to

methylphenidate

Atomoxetine (Stratera)

35 | P a g e

Dr Mohd Jamil Yaacob, Klinik Psikiatri Kanak-kanak & Remaja. 12 Mac 2012

Lampiran A Departmental policy on the use of antipsychotics* and non-standard drugs

1. Since olanzapine and quetiapine are currently available as original products which are expensive; please evaluate the cost-effectiveness of the treatment when prescribing these drugs as a first line in the management of patients with schizophrenia; especially in unproductive and chronic patients.

2. The use of expensive drugs such as olanzapine and quetiapine in poor compliance patients are also discouraged. Typical antipsychotics combined with depot preparation should be strongly considered.

3. Any patient treated with a new non-standard drug (not in the formulary), it is the responsibility of the drug company to supply the drug till the patient completed treatment. In such situation the department cannot guarantee that the new drug would be approved as a standard drug in the formulary.

*Note: this policy may be not relevant any more in future if olanzapine and quetiapine are supplied as generic products.

36 | P a g e

ALGORITHM FOR MEDICATIONS OF SCHIZOPHRENIA

37 | P a g e

38 | P a g e

ACUTE TREATMENT OF MANIA

39 | P a g e

ACUTE TREATMENT OF BIPOLAR DEPRESSION

40 | P a g e

PSYCOPHARMACOLOGICAL TREATMENT ALGORITHM FOR GENERALUIZED ANXIETY DISORDER (GAD)

41 | P a g e

ALGORITHM (2) FOR THE PHARMACOTHERAPY OF MAJOR DEPRESSIVE DISORDER (MDD)

42 | P a g e

ALGORITHM FOR MANAGEMENT OF DEMENTIA

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ALZHEIMER’S DISEASE TREATMENT STRATEGY Mild to moderate cases a) F.D.A. Approval drugs (cholinestherase inhibitors) b) Use Supported by Clinical Trials Moderate to severe cases a) NMDA. Antagonist- Memantine 10-20mg/day

b) Combination of cholinestherase inhibitors + N.M.D.A. Antagonist ‘

1) Donepezil 5-10mg/day

2) Rivastigmine 6-12mg/day

3) Galantamine 16-24mg/day

1) Seligeline 5mg BD.

2) Vit. E 2000I.U./day

44 | P a g e

PARKINSON DISEASE

Last update: February 2012

1 Consider Surgical Treatment

Deep Brain Stimulation

Very advanced motor

Complications of Levodopa Therapy

Severe Symptoms-Motor

Complications of L. Dopa

Moderate motor symptoms

interfering with activities

Early stage with minimal symptoms-

sign

1 Add on Dopamine Receptor

agonist and reduce dose of

Levodopa

2 Add on COMT Inhibitor Ento

Capone (COMTAN)

3 Starton STALLEVO a

combination of Levodopa-

carbidopa Entocaps

4 Adjunctivies – Amantadine Anti-

Cholinergics

1 Add small titrating dose of

Levodopa- dopa de carboxylase

Inhibitor Combination

(L-Dopa-Carbidopa) – Madopar

(L-Dopa-Benzeraside)-Sinement

1 Defer use of Levodopa if age below

60

2 Seligeline

3 Amantadine

4 Dopamine Receptor Agonists

Ropinerol

Pramipexol

Peribedil

5 Anti-cholinergics

45 | P a g e

FLOW CHART FOR TREATMENT HEPATITIS B IN TREATMENT NAÏVE PATIENTS

HBSAg positive

HBeAg status Positive HBeAg Negative HBeAg Is ALT Elevated Is ALT Elevated

End points of treatment 1. ALT Normalisation 2. HBeAg Seroconversion/ HBeAntibody 3. HBVDNA (PCR) suppression x 2 undetected 6 months apart (less than 300 copies/ml x 2)

YES

ALT less

2x normal

ALT more than

2x normal

NO YES

NO

ALT less 2x

normal

ALT more than

2x normal

Oral therapy 18 months (minimum)

First choice:

1. Lamivudine 100 mg OD 2. Entecavir 0.5 mg OD 3. Telbivudine 600 mg OD

Second choice:

1. Interferon Alpha (injection)

Liver Biopsy

Ishak Score >2.0

HBVDNA (PCR)

Quantitative more than

100,000 copies/ml

Oral therapy

Minimum duration 2

years

Liver Biopsy

Ishak Score >2.0

HBVDNA (PCR)

Quantitative more

than 10,000 copies/ml

No treatment.

Monitor ALT

every 1-3

months.

46 | P a g e

FLOW CHART OF CHRONIC VIRAL HEPATITIS B PRE CORE MUTANT HBEAG NEGATIVE

HBSAg POSITIVE MORE THAN 6 MONTHS

LIVER ENZYME ALT > 2 × NORMAL

HBVDNA (PCR) QUANTITATIVE HBVDNA > 10,000 COPIES/ML

LIVER BIOPSY

HPE BIOPSY SCORE > 2 ISHAK SCORE

THERAPY FOR MINIMUM 18 MONTHS 1. LAMIVUDINE 100 MG OD 2. TELBIVUDINE 600 MG OD

3. ENTECAVIR 0.5 MG OD 4. PEGYLATED INTERFERON 48 WEEKS

HBVDNA (PCR) QUANTITATIVE

MONITORED AT 24, 48, 72 WEEKS OF THERAPY

THERAPY STOPPED AFTER MINIMUM 18 MONTHS IF HBVDNA (PCR) UNDETECTABLE X 2 AT 6 MONTHS APART

(HBVDNA (PCR) LESS THAN 300 COPIES/ML X 2)

Prepared by: Dr. Amry A. Rahim Physician / Clinical Specialist Gastroenterology / Hepatology HUSM January 2012

47 | P a g e

FLOW CHART FOR GENITAL ULCER SYNDROME Treatment Protocol For Genital Ulcer Syndrome TREATMENT FOR SYPHILIS AND CHANCROID

1ST FIRST CHOICE: IM BenzathinePenicillin 2.4 million units weekly x 2

(once a week x 2 weeks) PLUS Azythromycin 1.0 gm single oral dose

2nd SECOND CHOICE: IM Benzathine Penicilin 2.4 million units weekly x 2 (once a week x 2 weeks) PLUS Cotrimoxazole 2 tablets orally twice daily x 7 days

3rd THIRD CHOICE: IM Benzathine Penicillin 2.4 million units weekly x 2 (once a week x 2 weeks) PLUS IM Ceftriaxone 250mg single dose

Note: If patient develops allergic reaction to the 1st dose of IM Benzathine Penicillin, DO NOT give the second dose.If patient is allergic to Penicillin, use EITHER Doxycycline 100mg orally bd x 15 days OR Erythromycin ES 800 mg bd x 15 days.

Patient complains of GENITAL ULCER or SORE

Take history and examine

INVESTIGATIONS NEEDED:-

1. Dark ground microscopy for syphilis (IF AVAILABLE) 2. Gramstain for haemophilus ducreyi 3. Tzanck’s smear 4. VDRL, TPHA 5. HIV Ab.

Ulser present? Multiple superficial erosions or vesicular lesions

PRESENT?

• Treat for SYPHILIS and CHANCROID

• Educate for behaviour change

• Partner management

• Follow-up regime For confirmed syphilis

√ 2 weeks for results

√ monthly x 3 visits

√ 3 monthly x 3 visits

√ 3 monthly x 2 visits

• 3 months repeat HIV Ab. And VDRL/TPHA if initial results were negative

• Health Education


• TCA x 2 weeks and review results of inv.

• Genitial herpes management


• TCA x 2 weeks and review results

YES

48 | P a g e

NO

FLOW CHART FOR VAGINAL DISCHARGE SYNDROME

Treatment Protocol For Vaginal Discharge Syndrome (Cervicitis And Vaginitis) 1st FIRST CHOICE: Azithromycin 1 gm single oral dose 2nd SECOND CHOICE: IM Ceftriaxone 250 mg single dose

+ Doxycycline 100 mg bd x 10 –14 days

3rd THIRD CHOICE: IM Ceftriaxone 250 mg single dose +

Erythromycin ES 800 mg bd x 10 – 14 days PLUS Metronidazole 2 gm STAT PLUS Nystatin pessaries 100,000 units daily x 14 days On follow-up: If no improvement or not effective to

continue Metronidazole 400 mg bd x 7 days OR TREATMENT FOR VAGINITIS ONLY

Patient complains of VAGINAL DISCHARGE

Take history and do physical examination

INVESTIGATION NEEDED:-

• Vaginal swab √ Wet mount for trichomonas vaginalis

√ Gram stain for candidia albicans and clue cells

• Cervical swab √ Gram stain for gonococci and pus cells

√ Culture for gonococci ( using Amies charcoal transport media )

• VDRL, TPHA, and HIV ab.

Refer to NEAREST Hospital

Patient has LOWER

ABDOMINAL PAIN?

RISK ASSESSMENT

• Partner has symptoms OR

• Risk factor positive

• Treat for VAGINITIS


• Follow up for 2 weeks for results

• Treat for CERVICITIS and Vaginitis



• Follow- up ---2 weeks for result 3 months to repeat VDRL, TPHA & HIV Ab,

IF INITIAL TEST WERE NEGATIVE

RISK FACTORS

1. Less than 21 years old 2. Single 3. Recent partner ( less than 3

monts)

4. Multiple partners

Treatment for Vaginal Discharge Syndrome ( Cervicitis)

Treatment for Vaginal Discharge Syndrome ( Cervicitis)

YES

NO

YES

49 | P a g e

Discharge

PRESENT?

Traetment for CHLAMYDIA

FLOW CHART FOR URETHRAL DISCHARGE SYNDROME IN MEN Treatment Protocol for Urethral Discharge Syndrome 1st CHOICE: Azithromycin 1gm orally single dose 2nd CHOICE: IM Ceftriaxone 250mg single dose + Erythromycin ES800mg orally bd x 10-14 days 3rd CHOICE: IM Ceftriaxone 250mg single dose + Erythromycin ES 800mg orally bd x 10-14 days IM Spectinomycin 2gm STAT + Doxycycline 100mg orally bd x 10-14 days OR IM Spectinomycin 2gm STAT +Erythromycin ES 800 mg orally bd x 10-14 days

Patient complains of Urethal

Discharge/Dysuria or irritation

Take history and examine (milk URETHRA

if necessary)

INVESTIGATIONS NEEDED:-

- Urethral smear √ Gram stain for gonococci & pus cells

√ Culture for gonococci (use AMIE’S

charcoal transport media)

- 2 glass urine test

- VDRL,TPHA & HIV Ab

1. Do 2 glass test

2. result POSITIVE? ULCER PRESENT?

• Treat for GONORRHEA and CHLAMYDIA



• Follow-up √ Two weeks for result

√ Three months to repeat

VDRL, TPHA & HIV Ab.

REFER TO

Appropriate

flow chart

Health Education

Follow-up for 2 weeks

No

No

No

Yes Yes

Yes

Treatment for Gonorhea and Chlamvdia

If Patient is allergic to penicillin and azithromycin is not available

50 | P a g e

OUTPATIENT TREATMENT OF CAP

TREATMENT PLAN

YES

YES

NO

PRIMARY CARE OF EMERGENCY DEPT

VISIT Patient presents w/ symptoms suggestive of

community-acquired pneumonia (CAP)

DIAGNOSIS

Does history, physical

Exam & chest x-ray

confirm CAP ?

SITE OF CARE

DECISION

Does patient have any of

the core adverse prognistic

factors?

ALTERNATIVE

DIAGNOSIS

Treat patient appropriately

NO

Yes, 2 core

adverse prognostic

factors are present No core adverse

prognostic factors

are present

EVALUATION

Does patient have

preexisting adverse

prognostic factors?

CLINICAL DECISION

Should patient be admitted to hospital?

Base decision on clinical judgement,

additional adverse prognostic factors,

the patient’s social circumstances &

patient preferences

OUTPATIENT TREATMENT

Non-pharmacological

• Patient education ➢ Avoid smoking ➢ Adequate hydration &

nutrition

Pharmacotherapy

• Symptomatic therapy ➢ Analgesics for pleuritic

pain

• Antibiotics therapy

NO

Yes, 1 core adverse prognostic

factors are present

HOSPITAL

ADMISSION

YES

51 | P a g e

TREATMENT PLAN (CONT’D)

EMPIRIC OUTPATIENT CAP

ANTIBIOTIC THERAPY

EMPIRIC ORAL ANTIBIOTICS

Local epidemiologic patterns need to be considered to target the antimicrobial therapy against the likely pathogens

Previously healthy individual

Any one of the following :

• High-dose Amoxycillin

• Doxycycline

• Macrolide – Erythromycin ➢ Preferred agent in many guidelines

Comorbidity is present (DM, renal insufficiency, CHF, alcohol abuse, COPD)


• Advanced macrolide - Azithromycin

• Beta-lactam or beta lactam-beta-lactamase inhibitor

• Quinolone Patient has multiple medical condirions , has COPD & received antibiotics or oral steriods in the last 3 months or any other risk factors for Gram –ve organisms

• Macrolide (Azithromycin) + beta lactam or beta-lactam (beta – lactamase inhibitor)

• Quinolone (alone) Suspected aspiration pneumonia


• Beta-lactam, beta-lactamase inhibitor w/ or w/o macrolide (Azithromycin)

• (Clindamycin or metronidazole w/ quinolone)

FOLLOW UP • Follow up will depend on initial severity assessment

• Recommended follow up in 48-72 hr

• If patient fails to improve consider the following : ➢ Chest X-ray ➢ Hospital admission

• Possible reasons for failure to improve ➢ Host factors associated w/ a delayed response ➢ Inadequate antimicrobial selection (eg. Resistant organism or bacteria not covered by initial antibiotic therapy) ➢ Metastatic infections (eg. Meningitis, endocarditis, empysema etc) ➢ Noninfections illness

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FLOW CHART OF USING SULPERAZONE IN ICU

ICU Patient

Ventilated/NonVentilated

Nosocomial Infection

Acinetobacter Non Acinetobacter

Non-Drug Multi Resistance

Multi-Drug Resistance (MDR) Quinolones or

3rd Generation or

4th Generation or

Carbapename

Sulperazone Unasyn

±Aminoglycoside

±Aminoglycoside

Responding

Non-Responding Within 24-48 Hr or Suspicious of MDR

Continue Treatment

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GUIDELINES FOR USING NOVOMIX 30 FLEXPEN HOSPITAL UNIVERSITI SAINS MALAYSIA

PRE-MIXED INSULIN

Mixtard 30 Penfill NovoMix 30

FlexPen

OAD’s

failures

OAD’s failure

1. elderly

2. hypoglycaemic prone

3. fasting (ramadhan) or puasa

sunat)

Patients on Mixtard (switch

to)

1. frequent hypoglycaemia

2. poor control

3. post prandial

hyperglyacemic

4. fasting (ramadhan) or puasa

sunat)

OAD Failure

PRE-MIX INSULIN

(eg: Mixtard, Humulin 30/70)

NovoMix30

1. Hypoglycemia 2. Poor glycemic control

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FLOWCHART FOR USE OF GLUCOPHAGE XR

Type 2 Diabetes Mellitus

Metformin (immediate release) BID/TID

Poor compliance or

Gastro-intestinal side-effects

Metformin (extended release)

(Glucophage XR) once daily

55 | P a g e

FLOWCHART FOR USE OF INSULIN DETEMIR

Insulin requiring diabetes mellitus

NPH insulin

Hypoglycemia

Insulin Detemir/Glargine

Last update: February 2012

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ALGORITHM FOR THE MANAGEMENT OF POSTMENOPAUSAL OSTEOPOROSIS

Clinical Assessment

Patients with risk General measures: Patients with prior factor but no - Calcium intake (B) incidental low

fracture - Physical activity (B) trauma fracture In the elderly: - Vitamin D + calcium (A) - Prevention of falls (B) BMD measurement

T score: T score: T score:

≥ -1 -2.5 ≤ -2.5

NORMAL OSTEOPENIA* OSTEOPOROSIS OSTEOPOROSIS (BMD if available)

Monitor If multiple risk factor present (C) Treatment options: Treatment options:

-Strontium ranelate -Strontium ranelate -SERMs/ - Bishosphonate (A) -Bishosphonates (A) -SERMs (A) -Activated vitamin D (A) -Activated vitamin D (A) -Calcitonin (A)

-rPTH**(A) Reassess with BMD after 2 years (A) NO YES

Follow up with BMD if available If BMD

deteriorates Reassess Treatment options: BMD yearly (C) - Strontium ranelate - SERMs (A) - Alendronate (A) - HRT (A)

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ZOLENDRONIC ACID PRESCRIPTION FLOW CHART

Bone Metastasis –Confirmed By Bone Scan

Primary By:

1) Breast Carcinoma

2) Nasopharyngeal Carcinoma

3) Lung Carcinoma (NSCLC)

4) Prostate Carcinoma

1st Line

IV Zolendronic Acid 4 mg

over 15 minutes every 4

weeks for 6 months.

Palliative Intension.

To stop and reduce bone

metastases/damage

especially when bone

involvement is wide

spread

+/- Hypercalcaemia

Severe pain. Scale > 7/10

2nd Line

IV Zolendronic Acid 4

mg over 15 minutes

every 4 weeks for 6

months

Further pain +/-

Hypercalcaemia

1st Line

IV Pamidronate 90 mg

Over 2 hours every 4/52

For 6 months

Severe Hypercalcaemia Mild To Moderate Pain

Symptoms of Pain

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FLOW CHART FOR USING IMATINIB IN CHRONIC MYELOID LEUKEMIA (CML), PH+ ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Patients with Ph+CML (all phases)

Begin imatinib at 400mg daily

Assess response at 3, 6, 12, 18 months as

per European Leukemia Net guidelines

Good response

Suboptimal

response

Poor / No

response

Continue imatinib

400 mg daily Increase imatinib to

600-800 mg daily

Stop imatinib

Consider alternative

treatment

Good response

Poor / No

response

Continue imatinib

600-800 mg daily

Stop imatinib

Consider alternative

treatment

NB

1. Chronic phase CML patients responding to imatinib should continue treatment indefinitely until disease progression (expected rate of

progression 1-5 %/year)

2. In accelerated, blast phase CML and Ph+ALL imatinib is usually used as induction +/- chemotherapy prior to more definitive treatment like

stem cell with an anticipated duration of imatinib use of 4-8 weeks.

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Lampiran1 Dr. Shamsul Kamaruljan

ARCOXIA PRESCRIPTION FLOW CHART

*Prescription: Maximum only for 3/52 Dose: 60mg, 90mg and 120mg (Depends on severity of the pain and condition of the pain)

Lampiran 2 Setelah diubahsuai oleh Jabatan Ortopedik

1st line:

T. Celebrex 200-400mg dly

T. Meloxicam 7.5mg bd

T. Tramadol 50-100mg tds

Oral opiods e.g. T. DF118,

Oral morphine

1st line:

NSAIDS e.g Voltaren, Mefenamic

acid, Ibuprofen

History of Gastritis

2nd line:

T. Celebrex 200-400mg dly

T. Meloxicam 7.5mg bd

Oral opiods e.g. T.DF118, Oral

morphine

2nd line:

T. Arcoxia 60-120mg dly

T. Oxycontin 10-40mg bd

3rd line:



Yes No

Pain not

relieved

Pain not

relieved

Pain not

relieved

Acute/chronic pain

60 | P a g e

OUTPATIENT PAIN PRESCRIPTION FLOW CHART

*COX2 Prescription for acute pain: Maximun only for 3/52 Arcoxia Dose: 60mg (OA), 90mg (RA) and 120mg (Acute pain e.g. gouty arthritis) (Depends on severity of the pain and condition of the pain) 3rd line is same in both pathways

1st line:

AC: T. Celebrex 200-400mg dly

AC Gouty arthritis : T Arcoxia

120mg daily

CHR: T. Meloxicam 7.5mg dly

T Celebrex 200mg dly

1st line:

AC: Voltaren, Mefenamic acid,

Ibuprofen

CHR: Feldene, Neprosyn

Acute/chronic pain

History of Gastritis

2nd line:

AC: Oral opiods e.g. T.DF118,

T. Arcoxia 120mg dly

CHR: T. Celebrex 200 dly

T. Meloxicam 7.5mg dly

2nd line:

Oral opiods e.g. T.DF118,


3rd line:

Oral morphine


3rd line:

Oral morphine


Yes No

Pain not

relieved

Pain not

relieved

Pain not

relieved

AC – acute

CHR - chronic

61 | P a g e

FLOWCHART OF PATIENTS DIAGNOSED WITH BACTERIAL CONJUNCTIVITIS

Bacterial Conjunctivitis

1st line:

Gutt. Chloramphenicol

Perform Culture and Sensitivity test Not resolved

2nd line:

Gutt. Ciprofloxacin (Ciloxan)

Not resolved

3rd line:

Gutt. Moxifloxacin (Vigamox)

62 | P a g e

FLOWCHART OF PATIENTS DIAGNOSED WITH BACTERIAL KERATITIS

Bacterial Keratitis

1st line:

Gutt. Ciprofloxacin (Ciloxan)

Perform Cornea Scrapping/ Culture Not resolved and Sensitivity test

2nd line:

Gutt. Moxifloxacin (Vigamox)

63 | P a g e

FLOWCHART OF PATIENTS REQUIRING PRE AND POST CATARACT SURGERY ANTIBIOTIC PROPHYLAXIS

Cataract Surgery

Prophylaxis

Pre–op prophylaxis:

• Gutt. Moxifloxacin 0.5 % (Vigamox) 1 drop every 15 minutes 1 hour prior to surgery.

• 5 % Povidone – iodine ( 1 drop ) on the ocular surface.

Intra-cameral injection:

• 1mg in 0.1 mL cefuroxime* or

• 0.1 mL Gutt. Moxifloxacin 0.5% (Vigamox)1 - at the end of surgery *Dilution is required as standard cefuroxime injection is 100 mg/mL.

Reference:

1) CRG Espiritu et. al. Safety of Prophylactic Intracameral Moxifloxacin 0.5% Opthalmic Solution in Cataract Surgery Patients. J Cataract Refract Surg 2007: 33: 63-68

Post–op prophylaxis:

• Gutt. Moxifloxacin 0.5% (Vigamox) 4 times daily for 1 month.

64 | P a g e

FLOW CHART FOR USING OLOPATADINE 0.1%

i. Kegunaan ubat tersebut adalah untuk rawatan kes “Allergic conjunctivitis” terutama “Vernal kerato conjunctivitis” di kalangan kanak-kanak dan remaja.

“Flow chart” penggunaan kedua-dua drug bagi membezakan kes-kes tersebut seperti berikut; Last update: January 2012

Ubat titis Olopatadine

Pesakit “Allergic conjunctivitis”

terutama “Vernal kerato

conjunctivitis”

Pesakit

65 | P a g e

TREATMENT ALGORITHM OF ALLERGIC RHINITIS (AR)

Intermittent Symptoms Persistent Symptoms

Xyzal * (Bachert C et al. J. Allergy Clin. Immunol 2004; 114: 838-844) The XPERT, Xyzal in Persistent Allergic Rhinitis Trial – Published RCT data. Indication approved by FDA / DCA.

Diagnosis of AR

Allergen Avoidance

Drug Therapy (Antihistamines)

Moderate - Severe

Moderate - Severe

Mild Mild

Xyzal Xyzal * Xyzal Xyzal *

1st & 2nd generation antihistaminics

1st & 2nd generation antihistaminics (No clinical data

available to support this indication

66 | P a g e

FLOW CHART OF THALASSAEMIA PATIENT WITH IRON OVERLOAD

DIAGNOSIS OF THALASSAEMIA ON REGULAR BLOOD TRANSFUSION

REGULAR 3-4 MONTHLY FOLLOW-UP IN PAEDIATRIC HAEMATOLOGY CLINIC

REGULAR 3-4 WEEKLY FOLLOW-UP IN THALASSAEMIA DAY CARE UNIT FOR BLOOD

TRANSFUSION

3 MONTHLY MONITORING SERUM FERRITIN LEVEL

EVIDENCE OF IRON OVERLOAD, SERUM FERRITIN > 1000 MCG/L

INTRODUCE TO SUBCUTANEOUS DESFERAL (deferoxamine) WITH TRAINING AND

MONITORING

ASSESSMENT OF COMPLIANCE TO DESFERAL (Growth, Se Ferritin, yearly echo of heart)

POOR COMPLIANCE GOOD COMPLIANCE TO DESFERAL TO DESFERAL Se Ferritin Se Ferritin < 2500mcg/L > 2500mcg/L CONTINUE DESFERAL

DEFERASIROX DEFERIPRONE

67 | P a g e

INTERFERON BETA-1B FLOWCHART

Multiple Sclerosis

1) Remitting and Relapsing type.

2) Clinically Isolated syndrome with MRI evidence of multiple

plaques.

DIAGNOSIS ESTABLISHED AS PER Mc DONALD CRITERIA

TREAT THE ACUTE EPISODE WITH I.V METHYL PREDNISOLONE

THEN CONSIDER THE THERAPEUTIC OPTION OF STARTING BETA-INTERFERON

THERAPY.

(Beta interferon is the only evidence based treatment for the above condition, to reduce the risk of relapses and slow down the disease progression).

68 | P a g e

FLOW CHART FOR INSULIN ANALOGUE AT KRK

Type 2 Diabetes Mellitus patient requiring insulin

Start with:

Human intermediate acting insulin prebed (NPH)

Or Human premixed insulin predinner

Change to :

*Analogue Insulin : Long Acting analogue

(Glargine / Determir)

Change to :

*Analogue Insulin : Long Acting analogue

(Glargine / Determir)

Start with:

Human Premixed Insulin

(Mixtard 30/70 or Humulin 30/70)

Start with:

Human Premixed Insulin

(Mixtard 30/70 or Humulin 30/70)

Change to:

*Premixed Analogue Insulin :

Ex: Novomix 30/70 or Humalog 25/75

Humalog 50/50

Change to:

*Premixed Analogue Insulin :

Ex: Novomix 30/70 or Humalog 25/75

Humalog 50/50

Start with:

Short acting Human Insulin

(Actrapid/Humulin R OD/BD /TDS)

Start with:

Short acting Human Insulin

(Actrapid/Humulin R OD/BD /TDS)

Change to:

*Rapid acting Analogue Insulin

Novorapid/Apidra/glulisine/Lispro

Change to:

*Rapid acting Analogue Insulin

Novorapid/Apidra/glulisine/Lispro

Need BD dose insulin

Need Basal plus (+1 or +2)/Basal

bolus

Need Basal plus (+1 or +2)/Basal

bolus

if ≥ 40 unit change to Toujeo

(option)

if ≥ 40 unit change to Toujeo

(option)

HYPOGLYCEMIA

HYPOGLYCEMIA

HYPOGLYCEMIA

HYPOGLYCEMIA

69 | P a g e

Notes:

1. Patients that require insulin :

i) HbA1c > 10%

ii) Maximum dosage of two or three ODA with HbA1c > 7%

2. Patients who required insulin should be started with human insulin first.

3. Optimize and/or intensify the Human insulin dose according to SMBG/ DM

4. Indication to switching to analogue insulin regime ONLY when patient

develop hypoglycemia on human insulin.

References

1) CPG Management of Type 2 Diabetes Mellitus (5th Edition) 2) Practical guide to Insulin Therapy in Type 2 Therapy in Type 2 DM

Committee members:

1 AP Dr Rosediani Muhamad

2 Dr Nani Draman

3 Dr Siti Suhaila Muhamad

drug use flow charts - formularydformulary.h.usm.my/assets/flow_chart_2019_final...-calcium channel...

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