Correct Dosing Newsletter July 2023

A Mediterranean Diet as mentioned in the Correct Dosing newsletter. Photo by Jez Timms on Unsplash

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There appears to be an increasing focus in the journals and some commentaries on drug safety and lower drug doses, as long as treatment is sufficient.

Although dose response is in the first lecture and is emphasised in every pharmacology course, it seems to get lost in busy clinics and the modern abundance of data and information when drugs are prescribed.


The website is now packed with content showing the principles and means of identifying safer,
optimal dose.

Surprisingly, satisfactory doses have often been discovered by patients and prescribers
to be below the strength of available tablets.

They find they feel best missing days or dividing tablets.

Although lower doses may appear sufficient, side effects can still occur. Close clinical monitoring for toxicity and the effectiveness is essential. You can read more in our blog.

The deeper, paid content on this website is for enthusiasts, clinical trialists and researchers.

It includes latest estimates of clinical dose response for common drug classes, along with a wide variety of relevant published papers and material.

Interesting Recent Journal Publications

Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized
clinical trial.
Hong S-J, Lee Y-J, Lee S-J, et al. JAMA 2023; 329: 1078-87.

This recent randomised study showed improved outcomes in coronary patients whose statin treatment was targeted for satisfactory dose response (‘treat-to-target’), compared with highest tolerated dose.

The lower doses in the ‘treat-to-target’ group were both significantly safer, with 25% less adverse
events, and also more effective, with 7% fewer cardiovascular events. It would have been interesting to see comparisons with outcomes on even smaller doses.

For example, total serum cholesterols of less than 5 mmol/L in untreated populations were associated with increased mortality. But the target cholesterol in this study was below 3 mmol/L and therefore may have involved higher doses than warranted.

An increase in simvastatin from 20mg to 80 mg (equivalent to 3 and 12 mg of atorvastatin) increased muscle pains (myopathy) 10-fold in one large study. Without a placebo group, overall safety is difficult to ascertain.

Sadly, any side effects may discourage patients from continuing statins, which are usually useful in
anyone with coronary disease.

Comparison of seven popular structured dietary programmes and risk of mortality and major
cardiovascular events in patients at increased cardiovascular risk: systematic review and
network meta-analysis.
Karam G, Agarwal A, Sadeghirad B, et al. BMJ 2023; 380: e072003.

This recent comprehensive and authoritative overview of popular diets concluded that Mediterranean and low fat diets are of the greatest benefit, in particular with respect to coronary heart disease.

Mediterranean diet mainly comprises increased fish, fruit, and vegetables, along with increased
monounsaturated fats (e.g. olive oil). Mediterranean diet, but not low fat diet, was in addition
associated with reduced stroke and thereby potentially less dementia.

Calcium channel blockers versus other drugs for hypertension.
Zhu J, Chen N, Zhou M, et al. Cochrane Database Syst Rev 2022; 1(1): CD003654

Calcium channel blockers (CCBs) such as Amlodipine (Nordip is one brand) and Felodipine (Felodur) have been popular antihypertensives. CCBs suffered ‘bad press’ related to side effects, like ankle fluid (oedema), flushing and headache, less seen on lower doses.

The advantage of CCBs, highlighted in this Review, are the cardiovascular benefits shown in trials, especially reduction in stroke.

Although CCBs can reduce angina they are not ideal in heart failure. This Review confirmed that with respect to outcomes, diuretics are superior to CCBs. Diuretics in modest doses are useful in most hypertensive patients, especially the elderly with falling renal function, because they help increase elimination of sodium (salt) and fluid. CCBs, overall, were found to be as effective as other antihypertensive drug classes.


Controversy regularly arises in relation to prescribing regulation and safety!

Shortages of pharmaceuticals related to COVID prompted thinking about sufficient and convenient drug supplies for patients. The Australian government is moving an option to dispense drugs for 2 months and longer periods. The pressure on pharmacies adjusting their business, with which they should be supported, is offset by the potential savings in money and time for prescribers and patients.

Concerns about the safety of vaping is getting attention. We must not underestimate the pressing need for options for smokers who genuinely wish to reduce their intake. Alternative nicotine substitutes have been available for many years.

It has been pleasing to see the public comfortable with annual COVID vaccines, which continue to be improved.

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