Prescribing Advice for GPs

Non-steroidal Anti-inflammatories (NSAIDs)

The MHRA advice regarding the safety of NSAIDs has already been summarised on this site.

The following recommendations apply in relation to the safe prescribing of NSAIDs:

1. Review the patient for the overall risks involved with NSAID treatment - this should include an assessment of gastro-intestinal risk, cardio-vascular risk, renal risk as well as pre-treatment assessment of blood pressure and renal function. Where possible use Paracetamol based analgesia as first line with a ladder approach if initial analgesia fails.
2. Where the overall risks are low or NSAID treatment is absolutely necessary despite moderate to high risk, the NSAID of lowest risk should be used at the lowest possible dose and for the shortest possible duration.
3. This will usually mean that Ibuprofen is the first line NSAID.
4. If Ibuprofen therapy fails or is not tolerated, re-assess the patient for an NSAID before trying an alternative. Suitable alternatives would include diclofenac and naproxen.

Analgesia

The safety of NSAIDs is under constant review at the moment following the concerns raised by the withdrawal of some of the newer COX-II Selective NSAIDs. The MHRA review has already been reported on this site.

All interventions made by the NHS, including prescribing drugs, involves an assessment of the risks of the intervention and the likely benefits. The spotlight on NSAID safety has made us all aware of the gastro-intestinal, renal and cardio-vascular risks associated with all NSAIDs.

It is therefore timely to consider a greater use of analgesics that are not NSAIDs. Using a stepped approach to analgesia with Paracetamol as a core component would be a rational approach in all conditions that are not inflammatory for the majority of the time, for example osteoarthritis.

Action: Where analgesia is required for uncomplicated pain, use the following ladder approach before considering NSAIDs or other alternative treatments.

1. Paracetamol 500mg tablets, Two four times a day when required
2. Co-codamol 8/500mg tablets, Two four times a day when required
3. Co-dydramol 10/500mg tablets, Two four times a day when required
4. Co-codamol 30/500mg tablets, Two four times a day when required

Note: This approach does not apply to complicated pain, for example Rheumatoid Arthritis, Cancer Pain and Trigeminal Neuralgia

Hypertension

NICE published a Clinical Guideline for Hypertension in August 2004. This guideline was based on the evidence available at the time and was probably dramatically influenced by the ALLHAT Study¹.

This Study was conducted in about 42,000 patients and compared active treatments as follows:

• Thiazide Diuretic (Chlorthalidone)
• ACE Inhibitor (Lisinopril)
• Calcium Channel Blocker (Amlodipine)
• Alpha Blocker (Doxazosin)

Based upon the results of this trial there are two key findings that altered (or should alter) daily practice. Firstly, the Doxazosin arm of this study was stopped early as patients in this group were suffering more outcome events than any other arm. It was therefore decided it was unethical to continue this arm of the study and as a consequence of these steps Doxazosin is a fifth line antihypertensive agent.

The ultimate finding of the study was that there is little to choose between the remaining three arms in terms of clinical efficacy in terms of "hard" outcomes like fatal and non-fatal MI. There were differences in blood pressure control between the groups where the Thiazide Diuretic performed well against the other drugs with amlodipine proving better in diastolic pressure only. While the differences are statistically significant, the clinical differences are negligible (0.8 - 2mmHg difference).

This then leaves the only difference for evaluation between the drug arms to be that of cost. As Thiazide Diuretics as the most cost effective option there simply must be the first line treatment for hypertension.

Second line options are added based upon emerging evidence around the risk of diabetes when Beta Blockers are used in conjunction with Thiazide Diuretics. Angiotensin Converting Enzyme Inhibitors (ACEIs) are preferential in those patients who are at higher risk of developing diabetes.

Action: The NICE Guideline is evidence based and should be followed by all clinicians treating Hypertension in Primary Care. For full details of the algorithm, see the Clinical Guideline Quick Reference.

For each of the NICE recommended drug classes the following drugs are recommended:

• Thiazide Diuretic - Bendroflumethiazide 2.5mg
• Beta Blocker - Atenolol 50mg or Bisoprolol 5mg
• ACE Inhibitor - Ramipril or Perindopril (Titrated to maximum tolerated dose)
• Calcium Channel Blocker - Amlodipine (as Mesilate) or Felodipine

ONLY if ACE Inhibitor is not tolerated

• Angiotensin II Receptor Blockers - Candesartan or Irbesartan or Valsartan

References

1. Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group JAMA 2002;288:2981-2997

MHRA SSRI Advice

The MHRA have issued a press statement regarding the safety and efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs), specifically Paroxetine (Seroxat).

This press release is timed in response to media criticism aimed at regulatory authorities over the handling of the licensing and continued availability of Paroxetine.

In summary, the MHRA advice on the safe use of SSRIs is as follows:

• Clinical trial data do not support a dose response above the recommended daily dose, therefore use the lowest efficacious dose
• Careful and frequent monitoring is important (for assessing efficacy and side effects)
• There is little association between dose or drug and the risk of suicide and there are insufficient data to conclude if there are differences between individual drugs

Additionally, the MHRA specifically reviewed the safety of Venlafaxine (Efexor)

• Venlafaxine should not be started in new patients, unless by a specialist of a GP with a special interest in Mental Health
• Venlafaxine should not be used in any patient with heart disease, electrolyte imbalance or hypertension

New Category - Prescribing Formulary

A new Category has been added to the site today. Prescribing Formulary is available with immediate effect in the sidebar menus to the left of the page.

This section of the site will collate information into a single topic area regarding the prescribing of medicines in discreet disease areas. The collection of articles will grow over time and will be revised when there are changes in the evidence base or in current practice.

For example, the two articles that have been published to launch this new section cover prescribing of Antiplatelets and Statins. You can subscribe for free to notifications of new articles by following these instructions.