FARMASI HOSPITAL BEAUFORT ISSUE 05/2022

PHARMACY BULLETIN:
MEDICATION SAFETY EDITION WORLD PATIENT SAFETY DAY
17 SEPTEMBER 2022

IN THIS ISSUE: STATINS RELATED MUSCLE PAIN

1 STATIN RELATED - Tharani A/P Gunasakaran, Pharmacist UF 44-
MUSCLE PAIN -
Statins remain among the most widely prescribed drugs for the correction of dyslipidaemia
-pg 1-
and prevention of cardiovascular events. The drugs work as a reversible inhibitors of HMG-
2 VANCOMYCIN CoA reductase aid in lowering the production of low-density lipoprotein (LDL) (“bad”)
INFUSION REACTION cholesterol in liver. (1)

(VIR) @ RED MAN Simvastatin, Lovastatin, and Atorvastatin are

SYNDROME metabolized by isoenzyme cytochrome
-pg 3- MUSCULAR P4503A4 (CYP3A4). Drugs of CYP3A4
inhibitors (as listed in Table 1) can interact
3 COUGH & COLD ADVERSE with these statins and increase the plasma
MEDICATIONS IN concentration, thus increasing the risk of
PAEDS EFFECT muscular adverse effects.
-pg 5-
Whereas, Fluvastatin, Rosuvastatin &
4 LOOK ALIKE SOUND Statins may affect a protein in muscle cells, Pravastatin are relatively insensitive to
ALIKE (LASA) which; CYP3A4 inhibitors and therefore clinically
MEDICATION Muscle growth significant interactions are less likely. (2)
(6)
-pg 8-
OR
5 SAFETY OF
Levels of Coenzyme Q10
ANTIEMETICS: (Natural substance in body)
METOCLOPRAMIDE
& DOMPERIDONE
-pg 10- Leading to symptoms like muscle weakness,
cramps, myalgia with and without CK
elevations and clinically serious events such
EDITORIAL TEAM: as myositis and rhabdomyolysis.

Advisor:
Strong CYP3A4 inhibitors Moderate CYP3A4 inhibitors
Pn Norehan Abd Rashid
● HIV protease inhibitors (e.g. ● Amlodipine
Editor: ritonavir, boceprevir, telaprevir) ● Amiodarone
Ainaa Izzati binti Jalani ● Azole antifungals (e.g.Itraconazole, ● Verapamil
ketoconazole, posaconazole, ● Diltiazem
Contributors: voriconazole) ● Warfarin
 Tharani Gunasakaran ● Macrolide antibiotics (e.g. ● Niacin (>1g/day)
 Su Yi Xiang erythromycin, clarithromycin)
 Gan Siaw Thing ● Danazol
 Mohd Aizat bin Jamil ● Cyclyosporine
 Muhammad Aidil Izmi ● Gemfibrozil
Table 1: Examples of CYP3A4 inhibitors that interact with statins 1
bin Umar Baki
 STATINS WITH CALCIUM CHANNEL ANTAGONIST
Simvastatin with calcium channel blockers is also commonly co-prescribed. Concurrent use causes
significant increase in blood levels of Simvastatin. In patients on Amlodipine 10mg with Simvastatin
20mg, the effect is similar to receiving Simvastatin 40mg alone.

Consideration for patient taking Amlodipine + Simvastatin 40mg

40mg4040mg
Reduce Simvastatin dose to 20mg

Staying on Simvastatin
- to discuss risk and benefit of this ‘off label’ option. Be aware that, exposure to adverse effect is
similar to that associated with Simvastatin 80mg.

Change to alternative statin

- Pravastatin*, Fluvastatin* or Rosuvastatin* do not interact with Amlodipine. Atorvastatin is less
susceptible with CYP3A4 and can be given at dose (20mg/40mg) if more potent statin is needed.
*Not available in Hospital Beaufort Formulary

NOTES FOR HEALTHCARE PROFESSIONALS

1. Since cholesterol biosynthesized peaks at midnight, statins with shorter half-lives (Lovastatin, Simvastatin &
Fluvastatin) should be administered in the evening. In contrast, statins with longer half-lives (Atorvastatin,
Rosuvastatin & Pravastatin) can be administered during the day.

2. Hepatic transaminases should be measured at baseline and at 1 to 3 months after starting treatment and/or
following a change in dose of statins.

3. Care should be taken when prescribing high doses of Simvastatin (>20 mg/daily) together with certain other
medications that inhibit the cytochrome P450 pathway.

4. When a statin myopathy is suspected, discontinue for 2-3 weeks. If symptoms have not resolved, it is unlikely to be
statin related and the patient should be continued on the same dose of statin. If symptoms have resolved, lowering
the dose or decreasing the frequency to less than daily or alternate dosing such as every other day (EOD) or twice a
week (2x/week) with atorvastatin or rosuvastatin.

5. Fibrates (Gemfibrozil or fenofibrate) should preferably be taken in the morning and statins in the evening to
minimize peak dose concentrations and decrease the risk of myopathy.
(5)
6. Please report all adverse events suspected to be associated with statins.

References:
1. Roland, a. (2012, May 16). Healthline. Retrieved from Healthline.com: https://www.healthline.com/health/what-is-statin-induced-
myopathy-or-muscle-pain#myotoxicity
2. Chet, L. S. (Aug 2014). Statins: Important Safety Labeling Changes. Malaysian Adverse Drug Reaction Newsletter, 7-8.
3. Sharma S, V. H. (2017, March). Study of Adverse Drug Reaction of Low dose Atorvastatin in Patients With Metabolic Syndrome and
Comparison With the usual Care Group. Biomedical and Pharmacolgy Journal, 165 -172.
4. Randall, C. (September 2012). MHRA recommendations on simvastatin interactions: What are the implications for patients taking
amlodipine? Liverpool: NHS North West Medicines Information Centre.
th
5. 5 Edition of Clinical Practice Guideline by MOH, Management of Dyslipidaemia 2017
6. Vaughan, Carl J., and Antonio M. Gotto. “Update on Statins: 2003.” Circulation, vol. 110, no. 7, 17 Aug. 2004, pp. 886–892,
10.1161/01.cir.0000139312.10076.ba.
2
Vancomycin Infusion
.

Reaction (VIR) aka

Red Man Syndrome
- Su Yi Xiang, Pharmacist UF41-

What is VIR?

VIR is an infusion-related anaphylactoid reaction independent of IgE-mediated

mechanism. The direct degranulation of mast cells and basophils by vancomycin
results in release of histamine, hence causing the associated symptoms.

Risk of VIR:

 Route of Vancomycin Administration: Intravenous > Oral *> Topical

 Rapid infusion rate (1g in <1 hour)
 Concomitant administration with medication† which predispose to mast
cell activation
*Oral vancomycin has poor systemic absorption, however detectable serum
level may occur in some patients with poor renal function or inflamed
gastrointestinal tract, high doses with prolonged duration and etc

Symptoms of VIR?
 Flushing
 Erythema, and pruritus, usually affecting the upper body, neck,
and face more than the lower body.
 Pains and muscle spasms in the back and chest
 Dyspnoea, and hypotension
Symptoms may manifest as soon as 4 minutes after the start of
vancomycin administration. Delayed reactions near the end of infusion
have been seen in those receiving therapy longer than 7 days.
Although rarely life-threatening, severe cardiovascular toxicity and
cardiac arrest can occur

Reaction Severity:

 Mild: tolerable flushing and other symptoms

 Moderate: uncomfortable flushing or pruritus but hemodynamically
stable and does not have chest pain or muscle spasms
 Severe: presence of muscle spasms, chest pain, and/or hypotension

3
 Prevention of Initial Reaction Examples of Predisposing
Medication†:
Slower infusion rate
1. Antibiotics (eg. Vancomycin,
•Vancomycin injection should be infused at a rate NO HIGHER THAN 10 fluoroquinolones)
mg/minute
2. Barbiturates (eg. thiopental)
•Even slower rates of infusion is suggested for patients who are also
receiving opioids or other predisposing medications† 3. Narcotic analgesics (eg.
morphine, meperidine)*
Empiric Premedication 4. Neuromuscular antagonist (eg.
quaternary amine-
•Oral or IV H1 antihistamines (eg. diphenhydramine 50mg) monotherapy or succcinylcholine,
combination of both an H1 and H2 antihistamine (eg. ranitidine 50mg, or
benzylisoquinoinium
famotidine 20mg) can be given prior to vancomycin infusion
compounds- atracurium)
•They are not usually necessary, and may be considered if more rapid
infusions of vancomycin (>10mg/min) are required in emergency or 5. Plasma expander (eg. Dextran,
presurgical settings Polygeline)
6. Radiocontrast agents
Treatment of VIR
*Fentanyl rarely induces
Mild reaction histamine release

•Symptoms typically resolve in minutes, vancomycin infusion discontinuation When possible, avoid administering
and antihistamines may not be necessary.
these medications simultaneously or
•Infusion rate can be halved
in close approximation with
Vancomycin
Moderate Reaction

•Interrupt the infusion

•Treat with antihistamine
•Symptoms usually subside promptly.
•The infusion can then be restarted at one-half the original rate or 10
mg/minute, whichever is slower

Severe reaction

•Stop the infusion Vancomycin has acidic pH,

•Treat with antihistamine administration of concentrated
•Give IV fluids if hypotension is present solution may lead to higher risk of
•Once symptoms have resolved, restart vancomycin infusion over four or phlebitis.
more hours/ continuous infusion
It should be diluted to a
•Premedication with antihistamines can be repeated prior to next doses,
together with prolonged infusion and close hemodynamic monitoring. concentration of 5mg/mL, and
administer slowly with rate not
•Check and stop unnecessary predisposing medicine, if any.
exceeding 10mg/min.
Some patients with mast cell disorder may experience recurrent and persistent Concentration up to 10 mg/mL may
symptoms, despite premedication and slower infusion rates. In these individuals, be used in those with fluid
alternative antibiotics have to be considered, or desensitisation can be attempted if restriction; however risk of infusion-
there is no alternative available related reactions is increased.
References:
1. Vancomycin Infusion Reaction: A Clinical and Thearpeutic Overview (2022), Journal of Hematology and Oncology Pharmacy, Retrieved from:
https://www.jhoponline.com/jhop-issue-archive/2022-issues/june-2022-vol-12-no-3/19349-vancomycin-infusion-reaction-a-clinical-and-therapeutic-overview
2. Vancomycin Hypersensitivity (2021) , In UpToDate, Retrieved from: https://www.uptodate.com/contents/vancomycin-
hypersensitivity?search=vancomycin%20infusion%20reaction&source=search_result&selectedTitle=1~45&usage_type=default&display_rank=1
3. Red man Syndrome (2003), in National Library of Medicine, retrieved from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC270616/#:~:text=Vancomycin%20can%20cause%20two%20types,impurities%20found%20in%20vancomycin%20prepar
ations.
4. Vancomycin Flushing Syndrome(2022), In Statpearl, Retrieved from: https://www.statpearls.com/ArticleLibrary/viewarticle/28290
5. Vancomycin Product Leaflet, vivocin(2019), In NPRA product search, Retrieved from https://quest3plus.bpfk.gov.my/front- 4
end/attachment/624/pharma/72705/V_39479_20200130_172909_D3.pdf
 Cough and Cold AAA..
Medications (CCMs) CHOOO!!

in Pediatrics
- Gan Siaw Thing, Pharmacist UF44-

Cough and cold are often distressing to children, In Malaysia, CCMs such as antihistamine, anti-tussives
prompting parents to seek for symptom-relieving- and decongestants are categorized as Group C Poison,
medication for solution. CCMs, however, are not which can be supplied by registered medical
recommended for use in young children. In fact, health practitioner without prescription. Some of the
agencies worldwide including United Sates Food and preparations such as topical aromatics can be sold
Drug Agency (USFDA), Health Canada and New Zealand over-the-counter (OTC), where they can be bought
Medicines and Medical Devices Safety Authority without prescription in departmental stores,
(MEDSAFE) have released their statements to restrict convenience stores or sundry shops.8
CCMs usage in young pediatrics1 (age restriction might
differ among agencies), here’s why: In February 2008, National Pharmaceutical Control
Bureau under Ministry of Health Malaysia has issued
1. Efficacy an advisory letter on the prescribing of CCMs to
There is no sufficient strong evidence from children less than 2 years old9. Besides, Malaysian Drug
studies or systemic review on Control Authority (DCA) in 2009 has made it
efficacy of these medications compulsory to include safety warning in the labels and
as compared to placebo in package inserts of all CCMs containing anti-histamine,
children 2,3,4,5 anti-tussive, expectorant and decongestant. These
medications are not to be used in children less than 2
2. Safety years old; whereas those aged between 2-6 years may
 CCMs usage have been associated with be prescribed with these products with caution and
emergency department visits, either due to qualified medical practitioners advice10.
overdose or adverse events5; fatal
A study conducted by CC Yong et al in Kuala Lumpur
overdose in children younger than two
(2015) has shown that knowledge significantly affects
years of age may occur6
parents’ perceptions on safety and effectiveness of
 Dosing guidelines for these medications are
CCMs, as well as the attitude towards the use of such
mostly extrapolated from adult data;
medications11.
toxicity may be enhanced in this population
due to varying pharmacokinetics profiles7
48.4% admitted to give CCMs to their ill
3. High potential for medication error children for sleepiness effect
(overdose/ drug interaction)6
 Failure to use proper
11.3% administer CCMs to their children aged
<2 years old
57.6% rated CCMs as safe/
measuring devices for
dose measurement
 Erroneous use of very safe
products intended for adults 59.6% thought CCMs are
 Polypharmacy, especially with combination
effective/ very effective for their
products
children
CC Yong et al (2015)

5
 Active ingredients Potential Adverse Events
Antihistamine  Sedation
 Paradoxic excitability (irritability, insomnia, tremor, convulsion)
Chlorpheniramine,  Dizziness
Diphenhydramine,  Respiratory depression
Promethazine  Hallucination
 Tachycardia, heart block, arrhythmia
 Anticholinergic effect: Dry mouth, Urinary retention, Blurred vision
 Dystonic Reactions

Narcotic Antitussives  Respiratory depression

 Nausea and vomiting, Constipation
Codeine  Dizziness
 Palpitation

Non-narcotic  Neurobehavioral changes (including euphoria, hallucinations, psychosis,

Antitussives agitation and coma)
 CNS depression
Dextromethorphan  Serotonin syndrome (tachycardia, mydriasis, ataxia)
 Respiratory depression

Oral decongestants  Hypertension (may be severe and associated with seizures, altered mental
status and organs damage)
Pseudoephedrine,  Tachycardia or dysrhythmias
Phenylephrine  Anorexia, nausea, vomiting
 Headache
 Irritability, agitation, sleeplessness

Topical decongestants  Coma, bradycardia, respiratory depression, sedation (if accidentally ingested)
 Rebound nasal congestion (rhinitis medicamentosa)
Oxymetazoline,  Nose bleeds
phenylephrine  Drying of nasal membrane

Topical Aromatics  GI and CNS effects if accidentally ingested

 Mild irritation of skin, nose or eyes
Menthol,  Neurotoxicity (agitation and seizures) if overdose
Camphor,
Eucalyptus Oil *toxicity from topical absorption of camphor is less common than from
ingestion but has been described before. Camphor is lipophilic and well-
absorbed through skin and mucous membranes, especially in young infants

Expectorants  Gastrointestinal irritation

Guaifenesin

Mucolytics  Brochospasm,
 GI disturbance
N-Acetylcysteine,  Fever
bromhexine

Table 2: Possible adverse event of cough and cold medications 12

6
 Vicks Vaporub, an OTC product easily available at sundry shops,
SHOULD NOT be used in paediatrics below 2 years old due to its
aromatics content!

Considering the higher risk than benefit, the use of these products in children < 2
years old should not be encouraged; for children of other age group, overdose
should be avoided. Parent education about the self-limiting nature of coughs and
colds, as well as the rational use of these drugs has to be emphasized. They can also
be advised on other supportive therapies such as humidified air, bulb suctioning,
saline nasal drops and increased fluid intake.

References:

1. MEDSAFE. Use of Cough and Cold Medicines in Childre-Updated Advice. Retrieved from
https://www.medsafe.govt.nz/hot/alerts/coughandcold/infooct2009.asp
2. Mieke L van Driel et al (2018). What Treatments are Effective for Common Cold in Adults and Children? BMJ 2018;363:k3786
3. Samuel H.F.Lam et al (2021). Use of Antitussive Medications in Acute Cough in Young Children. Journal of the American
College of Emergency Physicians Open; 2(3): e12467
4. Isbister GK (2010). Restricting Cough and Cold Medicines in Cildren. Journal of Pediatrics and Child Health; 48: 91-98.
5. Woo T et al (2007). Pharmacology of Cough and Cold Medicines. Journal of Pediatric Health Care; 22(2): 73-79
6. Shefrin AE et al (2009). Use of over-the-counter Cough and Cold Medications in Children. Can Fam Physician; 55(11): 1081-
1083.
7. Dolansky G et al (2008). What is the Evidence for the Safety and Efficacy of Over-the-counter Cough and Cold Preparations for
Children Younger than Six Years of Age? Paediatr Child Health; 13(2): 125-127
8. Poison Act 1952
9. BPFK KKM (21 Feb 2008). Amaran Dari U.S.Food & Drug Administration (USFDA) Berkaitan Penggunaan Ubat untuk Rawatan
‘Cough and Cold’ pada Kanak-kanak. Retrieved from https://www.npra.gov.my/images/Press-release/2008/usfda/usfda.pdf
10. Summary of Policies of the Drug Control Authority (DCA): 2009. Retrieved from
https://www.npra.gov.my/images/PDF/DCA%20News/SUMMARY_OF_POLICIES_THE_DRUG_CONTROL_AUTHORITY_2009_2.
pdf
11. CC Yong et al (2015). Knowledge, Attitude and Perceptionof Parents on the Use of Cough and Cold Medications in Children.
Southeast Asian J Trop Med Public Health; 46(3): 512-525.
th
12. UpToDate. Over-the-Counter Cough and Cold Preparations: Approach to Pediatric Poisoning. Last accessed 24 Aug 2022

7
 LOOK ALIKE, SOUND ALIKE (LASA)
MEDICATIONS
-Mohd. Aizat bin Jamil, Pharmacist UF 52 -

Look Alike Sound Alike (LASA) medications involve medications that are visually similar in physical appearance
or packaging and names of medications that have spelling similarities and/or similar phonetics. Confusing
medication names and similar product packaging may lead to potentially harmful medication errors.

STRATEGIES TO AVOID ERRORS

STORAGE LABELLING USING TALLMAN LETTERING

Tall Man lettering is the practice of writing part of a medicines name in upper case letters to help
distinguish sound- alike, look-alike medications from one another to avoid medication errors.

Example: BISOprolol – METOprolol - ATEnolol

Drug Name With Tall Confused With Drug Name With Tall Confused With
Man Letters Man Letters
BISOprolol ATEnolol cefOTAXime cefTAZIDime
METOprolol cefTRIAXONE
LABEtolol ceFAZOLIN
CARVEdilol ceFUROXime
PROPRAnolol ceFEPime
AMLOdipine FELOdipine DOBUTamine DOPamine
NIFEdipine streptoKINASE streptoMYCIN
TRIMETAzidine iron SUCROSE Iron DEXTRAN
PERINdopril CAPTOpril fluPENTIXOL fluPHENAZINE
BENZYLpenicillin BENZATHINE
proCHLORperazine proMETHAzine penicillin

STORAGE LABELLING BOXING STRENGTH READ & CHECK LABELS

FOR MEDS WITH MULTIPLE STRENGTH
Emphasize the need to read labels rather than
For medication with multiples strength, it is relying on visual recognition and location.
recommended to box the strength of the meds to Check actual medicines against medication labels
highlight multiple strength availability. and against the prescriptions.
Example of Boxing Strength: Pharmacist and person in charge of meds in ward
Tab Bisoprolol 5mg, Tab Bisoprolol 2.5mg must familiarize with the appearance of meds.
Tab Prazosin 1mg, Tab Prazosin 2mg, Tab Prazosin
Do not skip procedure of counter checking and
5mg dispensing.
8
 LOOK ALIKE MEDICATIONS:
EXAMPLES

Inj Inj Inj Inj

Inj Inj Inj Inj Inj Inj
Pantoprazole Omeprazole Inj Frusemide Inj
Ranitidine Haloperidol Vitamin K Adrenaline Nalbuphine Naloxone Hyoscine
Metoclopramide Dexamethasone

Inj Ampicillin Inj Benzylpenicillin Inj Ceftazidime Inj Ceftriaxone Inj Cefuroxime Inj Cefotaxime Inj Cefuroxime Inj Ceftazidime
Inj Cloxacillin
500mg 1MIU 1gm 1gm 750mg 1gm 1.5gm 2gm
500mg

Tab Perindopril 4mg

Tab Allopurinol 100mg

Inj Hepatitis B Vaccine (Adult)

Tab Clopidogrel 75mg

Tab Amlodipine 10mg

Inj Hepatitis B Vaccine (Peadiatric)

Tab Pantoprazole 40mg

References:

Guides on Handling Look Alike, Sound Alike Medications, First Edition (2021). Ministry of Health Malaysia.

9
 SAFETY OF ANTIEMETICS:
METOCLOPRAMIDE AND DOMPERIDONE
- Muhammad Aidil Izmi bin Umar Baki, Pharmacist UF 48-
-
METOCLOPRAMIDE

Metoclopramide is a substituted benzamide, which has After reviewing the benefit and risk of this medicine in
antiemetic and prokinetic properties. all age groups, the European Medicines Agency (EMA),
in December 2013, has recommended restrictions to the
Its activity results from antagonism of dopaminergic D2 use of metoclopramide to reduce the risk of
receptors, antagonism of serotonergic 5-HT3 receptors, neurological side effect:
and agonism of 5-HT4 receptors.
 Restricted indications in adults and children
ADVERSE EVENTS aged between 1-18 years
 Contraindication in children below 1 year of age
Metoclopramide crosses the blood-brain barrier and is
 Restricted doses (body weight-based) and
associated with serious neurological adverse events,
treatment duration, as well as modified dose
mainly extrapyramidal disorders (including oculogyric
intervals (Table 2)
crisis) which are of particular concern in children. Elderly
using metoclopramide at high doses or long-term
treatment are also at risk of tardive dyskinesia.

In Malaysia, after safety review of metoclopramide conducted by NPRA in 2015, the Malaysian Drug Control
Authority (DCA) had issued a directive for product registration holders to update metoclopramide package inserts
with the aforementioned information.

Route Adult Pediatric (1-18 years)*

INDICATION
Parenteral  Prevention of PONV 2nd line** option in:
 Symptomatic treatment of nausea and vomiting  Prevention of delayed CINV
(including that induced by migraine attacks)  Prevention of PONV
 Prevention of RINV

Oral  Prevention of delayed CINV 2nd line** option in prevention of delayed CINV
 Prevention of RINV
 Symptomatic treatment of nausea and vomiting
(including that induced by migraine attacks)

Rectal  Prevention of delayed CINV CONTRAINDICATED

 Prevention of RINV
DOSE & ADMINISTRATION
Parenteral 10mg/ dose, repeated up to 3 times per day 0.1-0.15mg/kg, repeated up to 3 times per day
Max daily dose: 30mg or 0.5mg/kg (refer Table 4)
Max daily dose: 0.5mg/kg
Parenteral metoclopramide can be given IV/ IM. IV
doses must be administered as slow bolus over at Tablets may not be suitable for use in children
Oral
least 3 min. weighing less than 30kg (risk of inaccurate dose)

Rectal CONTRAINDICATED

10
 Route Adult Pediatric (1-18 years)*
DURATION OF TREATMENT
Parenteral As short as possible, switch to oral or rectal  Prevention of CINV: max duration up to 5
route as quickly as possible days
 Prevention of PONV: max duration up to 48
hours
Oral Max recommended duration: 5 days Prevention of CINV: max duration up to 5 days

Rectal CONTRAINDICATED
FREQUENCY OF ADMINISTRATION
All dosage form A minimum interval of 6 hours between 2 administration is to be respected, even if vomiting or
rejection of the dose occurs

DOSE ADJUSTMENT
All dosage form Renal impairment:
 CrCl <15ml/min: reduce daily dose by 75%
 CrCl 15-60ml/min: reduce daily dose by 50%

Liver impairment (severe): reduce daily dose by 50%

CONTRAINDICATION
All dosage form  Hypersensitivity to the active substance/ excipients
 Gastrointestinal haemorrhage, mechanical obstruction or gastro-intestinal perforation for
which the stimulation of gastrointestinal motility constitutes a risk
 Confirmed or suspected pheochromocytoma (risk of severe hypertension episodes)
 History of neuroleptic or metoclopramide-induced tardive dyskinesia
 Epilepsy (increased crises frequency and intensity)
 Parkinson disease
 Combination with levodopa or dopaminergic agonists
 Known history of methaemoglobinaemia with metoclopramide or NADH cytochrome-b5
deficiency

Table 3: Metoclopramide Prescribing Information

PONV: Post operative nausea and vomiting

RINV: radiotherapy-induced nausea and vomiting
CINV: chemothearapy-induced nausea and vomting
*contraindicated in children < 1 year old
st
** 1 line treatment: serotonin antagonists (eg. ondansetron, granisetron )

Age Body Weight Dose Frequency

1-3 years 10-14kg 1mg Up to 3 times daily
3-5 years 15-19kg 2mg (min interval 6 hours between
5-9 years 20-29kg 2.5mg doses, even if vomiting or
9-18 years 30-60kg 5mg rejection of dose occurs
15-18 years >60kg 10mg

Table 4: Metoclopramide paediatric dose

DOMPERIDONE

However, domperidone has been repeatedly associated

Domperidone is a prokinetic agent and a dopamine with causing serious cardiovascular adverse effects, such
antagonist with anti-emetic properties. as QT interval prolongation, ventricular arrhythmias and
It is thought to exert its antiemetic effect through sudden cardiac death.
antagonism of dopamine receptors in the gut and the This risk was found to be higher in the following groups:
chemoreceptor trigger zone.
 those aged above 60 years
Studies have shown that oral domperidone increases  total daily dose of domperidone above 30mg/day
lower oesophageal pressure, improves antroduodenal  concomitantly using other QT-prolonging drugs or
motility and accelerates gastric emptying. CYP3A4 inhibitors

Previously, domperidone can be given to children and adolescents weighing

<12y/o <35kg
less than 35kg at a dose of 0.25mg/kg up to 3 times daily, capping at 10mg up
to 3 times daily in adults and adolescents weighing more than 35kg.

Research

Later in 2019, a randomised control study by Leitz G et al showed that the use
of domperidone in children below 12 years of age with acute gastroenteritis
showed no difference in efficacy when compared to placebo.

Since then, domperidone is no longer suggested for use in children below

12 years old weighing less than 35kg

National Pharmaceutical Regulatory Agency (NPRA), Ministry of Health Malaysia in year 2020 has issued a
directive for registration holders of domperidone products to update the local package inserts and consumer
medication leaflet on this safety information:

Population Dosage (for acute nausea/ vomiting)

Adults and adolescents ≥12 Typically 30mg/day (10mg TDS)
years of age and weighing ≥
35kg Max: 40mg/day (10mg QID)
Use the lowest effective dose
Children <12 years of age and
weighing ≥ 35kg For acute nausea and vomiting, treatment duration should not exceed 1
week. Patients should consult their physician if symptoms persist.
Adults and adolescents (≥12 Weight- dependent dose: 0.25mg/kg TDS- QID
years of age) weighing <35kg
Max: 1mg/kg/day
Use the lowest effective dose

For acute nausea and vomiting, treatment duration should not exceed 1
week. Patients should consult their physician if symptoms persist.

Due to the need for accurate dosing, tablets may not be suitable for use in
this population

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 Population Dosage (for acute nausea/ vomiting)
Infants and children < 12 years The efficacy has not been established (not recommended)
of age and weighing <35kg

Renal impairment (serum Reduce dosing frequency to OD or BD, dose may need to be reduced.
creatinine > 0.6mmol/L)
To review patient regularly

Hepatic Impairment Mild (Child-Pugh 5-6): no dosage adjustment necessary

Moderate-Severe (Child Pugh ≥7): Contraindicated

Table 5: Dose of Domperidone based on Population

CONTRAINDICATION
 Known hypersensitivity to domperidone or any of the excipients
 Prolactin-release pituitary tumour (prolactinoma)
 Known existing prolongation of cardiac conduction intervals, particularly etc
 Significant electrolyte disturbance or underlying cardiac diseases
 Concomitantly taking qt-prolonging drugs or potent CYP3A4 inhibitors
 Whenever stimulation of gastric motility might be dangerous (eg. Gastro-
intestinal haemorrhage, mechanical obstruction or perforation)

REFERENCES
1. National Pharmaceutical Regulatory Agency, MOH Malaysia (2020): Reminder on the Risk of Oculogyric
Crisis with Metoclopramide Use. Retrieved from https://www.npra.gov.my/index.php/en/health-
professionals/recent-updates/419-english/safety-alerts-main/safety-alerts-2020/1527118-reminder-on-
the-risk-of-oculogyric-crisis-with-metoclopramide-use.html
2. European Medicines Agency: Metoclopramide-containing medicines. Retrieved from
https://www.ema.europa.eu/en/medicines/human/referrals/metoclopramide-containing-medicines
3. Leitz G et al (2019). Safety and Efficacy of Low-dose Domperidone for Treating Nausea and Vomiting Due
to Acute Gastroenteritis in Children. Pediatr Gastroenteral Nutr; 69(4): 425-430.
4. National Pharmaceutical Regulatory Agency, Ministry of Health Malaysia. Domperidone: Restriction of
use in Pediatric Patients Less than 12 years of Age. Retrieved from
https://www.npra.gov.my/index.php/en/industry-news-announcements/more-recent-updates/419-
english/safety-alerts-main/safety-alerts-2020/1527109-domperidone-restrictions-of-use-in-paediatric-
patients-less-than-12-years-old.html

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