Polypharmacy prescribing guidance - draft: consultation

14. Appendix C: Polypharmacy National Therapeutic Indicators

Table 38: List of Polypharmacy National Therapeutic Indicators

National Therapeutic Indicators

Risk of opioid dependency:

Number of people prescribed an opioid at an average daily dose of opioid equivalent to ≥ 120mg per day of oral morphine over the previous 6 months as a percentage of all people prescribed weak and strong opioids

Number of people prescribed an opioid at an average daily dose of opioid equivalent to ≥ 90mg per day of oral morphine over the previous 6 months as a percentage of all people prescribed weak and strong opioids

Number of people prescribed an opioid at an average daily dose of opioid equivalent to ≥ 50mg per day of oral morphine over the previous 6 months as a percentage of all people prescribed step 2 and strong opioids

Number of people prescribed strong opioids (including tramadol preparations) long term (>1 year) as a percentage of all people prescribed strong opioids

Rationale

The benefits of opioids in chronic pain are limited to lower doses. Opioids should only be considered for short to medium-term treatment (less than three months) for carefully selected individuals with non-malignant pain, when other therapies have been insufficient and the benefits are greater than the risks of serious harms, such as addiction, overdose and death.156^,159^,160^,161

The risk of harm substantially increases at doses over 100mg MED/day with no increase in benefit.170 Additional support and monitoring may be necessary when prescribing for individuals at risk of opioid misuse. Individuals who require particular consideration include:

- history of substance use

- those with or at risk of renal impairment

- recently discharged following surgery

- older/frail adults

National Therapeutic Indicators

Risk of gabapentinoid dependency when used in the management of pain and anxiety disorders:

Number of people prescribed a gabapentinoid at an average daily dose equivalent to >3600mg gabapentin over the previous 6 months as a percentage of all people prescribed a gabapentinoid

Rationale

Much of the trial data for the effectiveness of gabapentinoids is limited to 12-16 weeks duration.155 If an individual requires longer treatment for neuropathic pain, the clinical status should be assessed, and additional therapy considered.

Gabapentinoids are associated with significant risk of adverse effects including drowsiness or somnolence, dizziness, nausea, risk of dependency and risk of severe respiratory depression (sometimes even without the concomitant use of opioids).179^,180^,186^,188

National Therapeutic Indicators

Falls, Fractures and Delirium:

Number of people aged ≥75 years dispensed > 10 items of strong or very strong anticholinergics (mARS 2&3) per annum as a percentage of all people aged ≥75 years

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

The cumulative exposure to multiple medicines with anticholinergic properties is known as anticholinergic burden. Higher anticholinergic burden in older people is associated with greater risk of morbidity and mortality, longer hospital length of stay (LOS), institutionalisation, functional and cognitive decline. They are associated with other adverse effects in older people such as increased fall and fracture risk, cardiovascular events, and delirium. Blurred vision, urinary retention, and constipation are known peripheral adverse effects of anticholinergic medication.122

National Therapeutic Indicators

Antimicrobial Resistance: Antibiotics:

Number of people prescribed > 4 prescriptions for antibiotics per annum as a percentage of all people prescribed antibiotics

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

The main driver for the development of antimicrobial resistance is exposure to antibiotics; high levels of antibiotic use correlate with high levels of resistance. ^[353] A key antimicrobial stewardship approach to optimising antibiotic use in primary care is minimising their use for symptoms such as coughs, colds, sore throats, and earache in otherwise fit and healthy people. [354]

National Therapeutic Indicators

Antimicrobial Resistance: Antibiotics:

Number of 3-day course of acute UTI antibiotics prescribed to women as a percentage of all acute UTI antibiotic courses prescribed to women

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

Evidence shows an association between antibiotic prescribing for suspected urinary tract infections (UTI) and antimicrobial resistance. ^[355] Antibiotics for urinary tract infections is the second most common reported indication for antibiotic prescription.355

The main driver for the development of antimicrobial resistance is exposure to antibiotics; high levels of antibiotic use correlate with high levels of resistance.353

The recommended course duration for uncomplicated lower UTI in non-catheterised women is 3 days.355^,354

National Therapeutic Indicators

Self-monitoring of glucose:

Number of people prescribed glucose self-monitoring products who are not prescribed insulins and/ or sulfonylureas as a percentage of all people prescribed glucose self-monitoring products

Rationale

Self-monitoring of glucose (SMG) should not be routinely offered to those with T2DM unless the person is prescribed insulin; there is evidence of hypoglycaemic episodes; the person is on oral medication that may increase their risk of hypoglycaemia while driving or operating machinery (sulfonylureas); or the person is pregnant or is planning to become pregnant. ^[356]

National Therapeutic Indicators

Self-monitoring of glucose:

Number of people prescribed insulin not prescribed glucose self-monitoring products as a percentage of people prescribed insulin

Rationale

Insulin is used in the management of both Type 1 and Type 2 diabetes mellitus and individuals should undertake self-monitoring of glucose:

- to minimise the risk of hypoglycaemia, ketoacidosis and hyperglycaemia

- to allow driving (see DVLA guidance for specific advice on blood glucose monitoring)

- to support adjustment of insulin doses in basal bolus regimes (in Type 1 diabetes only)

National Therapeutic Indicators

Increase Falls Risk: Sulfonylurea use in frail older adults:

Number of people aged ≥ 75 years prescribed sulfonylureas as a percentage of all people aged ≥ 75 years prescribed an anti-diabetic drug

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

In frail adults, especially those with comorbidities, sulfonylurea use is associated with an increased risk of hypoglycaemia and the consequences of falls and hospitalisation. It will often be appropriate to adjust the target HbA1c and review treatment.

National Therapeutic Indicators

Polypharmacy in Diabetes:

Number of people prescribed three or more categories of diabetes medication as a percentage of all people prescribed an anti-diabetic drug

Rationale

Polypharmacy can be appropriate, ensuring that people with diabetes achieve target HbA1c levels, but different anti-diabetic medications have differing effects on glycaemic control, and therefore those less effective in achieving the target HbA1c should be reviewed.356

National Therapeutic Indicators

Risk of acute kidney injury:

Number of people prescribed metformin and NSAID, and either a diuretic or ACEI/ARB as a percentage of all people prescribed metformin

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

The prescribing of a non-steroidal anti-inflammatory drug (NSAID) with metformin, diuretic and ACEI/ARB is considered a ‘triple whammy’ with increased risk of acute kidney injury.

Many people are prescribed metformin (for type 2 diabetes mellitus), ACEI/ARB (to treat hypertension, heart failure or for renal protective purposes in diabetes) and diuretics (to treat oedema, heart failure or hypertension).273 However additional prescribing of an NSAID can increase the risk of acute kidney injury, especially during dehydrating illness, and should be avoided.272

National Therapeutic Indicators

Risk of acute kidney injury:

Number of people co-prescribed a NSAID and an ACE inhibitor/ angiotensin receptor blocker and a diuretic as a percentage of all people prescribed an ACE inhibitor/angiotensin receptor blocker and a diuretic

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

Wherever possible, do not prescribe NSAIDs to individuals already taking ACE inhibitors or ARBs with a diuretic, known as ‘triple whammy’. Addition of an NSAID to concomitant ACEI/ARB and diuretic therapy almost doubles the risk of AKI and may cause the ACEI /ARB and diuretic to be less effective.272

National Therapeutic Indicators

GI Bleed risk: Oral anticoagulant:

Number of people prescribed an antiplatelet also prescribed an oral anticoagulant but without gastroprotection as a percentage of all people prescribed an oral anticoagulant

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

Very high-risk combination. Should only be prescribed following specialist advice and normally include a specific time limitation.

Bleeding risk can be increased by co-prescription of agents that increase the risk of bleeding. The use of gastroprotection should be considered to manage bleeding risk.

There is little randomised controlled trial evidence examining to what degree bleeding risk is reduced by the addition of gastroprotection.270 Guidelines and meta-analyses (largely based on observational trials) generally advise addition of gastroprotection if there is increased risk of bleed, including concomitant use of medicines known to increase risk of gastrointestinal bleed, and use of a combination of blood thinners.

National Therapeutic Indicators

Gastrointestinal risk:

NSAID prescribing in combination with antiplatelet without gastroprotection as a percentage of all people

NSAID prescribing to people aged over 65 years without gastroprotection as a percentage of all people

Variant: Care home (≥50 years as a proportion of the total care home population)

NSAID prescription to people prescribed an oral anticoagulant without gastroprotection as a percentage of all people prescribed an oral anticoagulant (Very high-risk combination. Should only be prescribed following specialist advice)

Rationale

Bleeding risk can be increased by co-prescription of agents that increase the risk of bleeding. There is little randomised controlled trial evidence examining to what degree bleeding risk is reduced by the addition of gastroprotection.270 Guidelines and meta-analyses (largely based on observational trials) generally advise addition of gastroprotection if there is increased risk of bleed, including concomitant use of medicines known to increase risk of gastrointestinal bleed, and use of combination blood thinners.

National Therapeutic Indicators

Bone Marrow Suppression:

Number of people prescribed methotrexate without co-prescription of folic acid as a percentage of all people prescribed methotrexate

Rationale

Methotrexate is associated with significant side effects such as life-threatening hepatotoxicity, pulmonary damage, and myelosuppression as well as nephrotoxicity. ^[357] Folic acid decreases mucosal and gastrointestinal side-effects of methotrexate and may prevent hepatotoxicity.

National Therapeutic Indicators

Falls, Fractures and Delirium:

Number of people prescribed a long-term oral steroid without co- prescription of a bone protecting agent as a percentage of all people prescribed a long-term oral steroid

Rationale

Long term or repeated courses of steroids can lead to an increased risk of osteoporosis.357

National Therapeutic Indicators

Increased risk of medication related harm:

When prescribed an antipsychotic in combination with two or more of the following: antidepressants, benzodiazepines/z-drugs, opioids, gabapentinoids as a percentage of all people receiving an antipsychotic

Number of people prescribed three or more of the following: antipsychotics, antidepressants, benzodiazepines/z-drugs, opioids, gabapentinoids per 1,000 list size

Care home (≥50 years as a proportion of the total care home population)

Rationale

Central Nervous System (CNS) depressants (antipsychotics, antidepressants, benzodiazepines/z-drugs, opioids and gabapentinoids) are associated with serious adverse effects including falls, sedation, respiratory depression, dependence and/or withdrawal.357 The use of CNS depressants in combination can further increase the risk of adverse events including CNS depression.30^,105^,227

National Therapeutic Indicators

Increase in harm from antipsychotics use:

Number of people aged ≥75 years prescribed an antipsychotic as a percentage of all people aged ≥75 years

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

Older adults are particularly vulnerable to side effects of antipsychotics such as extrapyramidal effects, sedation and anticholinergic effects. In older adults with dementia use of antipsychotics can lead to an increased risk of cerebrovascular adverse events and greater mortality.244^,[358],357

Antipsychotics should be prescribed as a last resort for symptoms of stress and distress in dementia or delirium, if non-pharmacological approaches have failed. They should be prescribed at the lowest effective dose for the shortest duration possible.357

National Therapeutic Indicators

Risk of benzodiazepine/ z-hypnotic dependency:

Number of people prescribed long-term (>8 weeks) benzodiazepines/z-drugs as a percentage of all people prescribed benzodiazepines/z-drugs

Variant:

Care home (≥50 years as a proportion of the total care home population)

Rationale

Benzodiazepines and z-drugs are used for the short-term relief of severe insomnia and some anxiety disorders.357 People can quickly become tolerant to the therapeutic effects of benzodiazepines and z-drugs, rendering them ineffective.357 Long-term use exposes people to avoidable adverse drug effects and harms such as falls, cognitive dysfunction, dependence and tolerance.357

National Therapeutic Indicators

High Dose Corticosteroid Inhalers:

High dose corticosteroid inhalers as a percentage of all corticosteroid inhalers (items) using BTS/NICE/SIGN classification

Rationale

There are safety concerns regarding the continued use of high dose corticosteroid inhalers without review. There is limited clinical benefit at doses greater than 800 micrograms beclometasone equivalent per day, but a greater risk of side effects, e.g. adrenal suppression, osteoporosis, pneumonia (including pneumonia requiring hospitalisation). Prescribing high dose ICS in children, aged under 12 years, is of particular concern due to side effects and should only be used under the care of a specialist paediatrician.

National Therapeutic Indicators

Poor Asthma Control:

Number of people prescribed a SABA in quarter without prescribing of other respiratory medication in the same or previous quarter as a proportion of people prescribed a SABA in quarter

Rationale

BTS/NICE/SIGN does not recommend treatment with short acting beta₂ agonist (SABA) alone for asthma. (See MHRA drug safety update). For newly diagnosed asthma and those with poorly controlled asthma consider anti-inflammatory reliever (AIR) or maintenance and reliever therapy (MART). ^[359] There are limited instances where SABA alone may be prescribed, for example occasional breathlessness in COPD.359

National Therapeutic Indicators

Poor Asthma Control:

Number of people prescribed 3 or more short-acting beta-agonist (SABA) inhalers per annum as a percentage of all people prescribed SABAs

Number of people prescribed 6 or more short-acting beta-agonist (SABA) inhalers per annum as a percentage of all people prescribed SABAs

Rationale

In people with asthma, high or increasing use of SABA therapy is an indicator of poor control, associated with a moderately increased risk of asthma attack and asthma death. A MHRA drug safety update highlights the risk of overreliance on SABA.

Updated asthma guidance359 recommends considering anti-inflammatory Reliever (AIR) or Maintenance and Reliever Therapy (MART) for poorly controlled asthma.