Drug Dosing

Introduction

It may sound laughable when a fresh pharmacy graduate asked you, is the dosing of a particular drug to give half a tablet or two tablets a day acceptable or not.

• After working for a while, you probably realise not all drugs should be dosed one tablet a day (though lots of them are).
• Many years later, with experience, you may also become familiar with most common drugs dosing.

However, before becoming a senior pharmacist, we should learn on drug dosing by actively checking drug references.

• When we are dispensing medications to patients, it is better to check each time whenever you are in doubt. Once the medication is dispensed, we bear part of responsibility.

References

Ideally, we would like to have a single extensive medicine reference exists which covers all the drugs marketed in Malaysia. But, it does not exist, not even MIMS Malaysia.

• This is because the list of drugs marketed in each country is slightly different.

Nonetheless, the commonly used drug references are

• United States: Lexicomp, Micromedex, Medscape, Epocrates
• United Kingdom: British National Formulary, emc
• Australia: Australian Medicines Handbook, Frank Shann Drug Doses
• Multinational: Lexicomp Multinational, Martindale

Whenever a drug information cannot be found, we may check another country reference.

• For example, etoricoxib is not marketed in US, but marketed in UK and Australia.
• Bromhexine is not marketed in US and UK, but available at Australia.
• Oral sultamicillin is not found in US references

If the drug is still not found, then product leaflets are our only reference.

• To illustrate, trimetazidine and ambroxol is not found in Lexicomp, British National Formulary and Australian Medicines Handbook.
• Hence, you may want to look up physical product, MIMS Malaysia or NPRA Quest 3+ Product Search.

Nonetheless, there are also circumstances where we have to read up the clinical practice guidelines or clinical journals to justify the dosing of a particular drug, especially those off-label indications. For example,

• Cabergoline in Ovarian Hyperstimulation Syndrome (OHSS)
• Acetylcysteine for non-paracetamol acute liver failure

Difference in Drug Dosing Recommendations

When you compare the drug dosing across countries, you will be surprised to realise that dosing information for the same drug could be different.

• Though this may not mean much to you today, it is a good thing to be aware of at the very start of your provisional registered pharmacist training.

To illustrate, in the management of nausea and vomiting induced by cytotoxic chemotherapy or radiotherapy, the dose of IV granisetron is 10 mcg/kg in Lexicomp, but 10-40 mcg/kg (max per dose 3 mg) in British National Formulary.

• Two different studies in 2012 actually reached the same conclusion: 1 mg granisetron is not inferior to 3 mg in the prevention of chemotherapy-induced acute emesis. Hence, with a dosing of 1 mg, an ampoule of 3 mg granisetron can be used for 3 patients, making it very cost effective.
  
• Comparison of 1 mg/body and 3 mg/body of intravenous granisetron for the prevention of chemotherapy-induced nausea and vomiting and adverse events in haematological malignancy patients, 2012
• Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial, 2012

Another example will be the dosing of oral colchicine in the flare treatment of gout.

• The suggested dosing in Lexicomp is 1.2 mg at the first sign of glare, followed in 1 hour with a single dose of 0.6 mg or 0.6 mg 3 times daily on the first day, and 0.6 mg once or twice daily until flare resolves.
• British National Formulary suggests 500 micrograms 2-4 times a day until symptoms relieved, maximum 6 mg per course, do not repeat course within 3 days.

Both Lexicomp and British National Formulary suggested a dosing of oral sumatriptan 50-100 mg per dose for acute moderate to severe migraine.

• However, the maximum dose per 24 hours is 200 mg in Lexicomp and 300 mg in British National Formulary.

In acute diarrhoea, adult dosing of diphenoxylate 2.5 mg and atropine sulphate 0.025 mg tablet is 2 tablets 4 times daily until control achieved (maximum daily dose of 8 tablets) in Lexicomp, but initially 4 tablets, then 2 tablets 4 times a day in British National Formulary.

Summary

Many drug labels lack dosage recommendations for a significant portion of real-world patients for whom the drug is prescribed.

• Population studied in pivotal trials typically exclude patients who are very young or old, emaciated or morbidly obese, pregnant or have multiple characteristics likely to influence dosing.