Polypharmacy prescribing guidance - draft: consultation

Proton Pump Inhibitor

Step 3: If long-term treatment is necessary, ensure dose does not exceed usual maintenance doses (exception Barrett’s oesophagus). Use the minimum dose required to treat symptoms

Step 5: Caution: Clostridium difficile, osteoporosis, hypomagnesaemia

H2 blocker

Step 5: Caution: Anticholinergic ADRs. (see anticholinergic table)

Laxative

Step 3: Has previous constipation causing medication stopped

Step 4: Unmet need: prevention of opioid induced constipation

Step 4: Unmet need: clozapine induced constipation which can be life threatening – prescribe even if not constipated

Step 4: If >1 laxative, do not stop abruptly. Reduce stimulant first and monitor effect

Step 5: Caution: Vicious cycle of fluid loss > hypokalaemia > constipation

Step 5: Avoid lactulose in the elderly

Step 6: Consider non-pharmacological options (see constipation hot topic)

Antispasmodic

Step 3: Rarely effective, rarely indicated long-term

Step 5: Caution: Anticholinergic side effects (see anticholinergic table)

Anticoagulant

Step 3: Check for expired indications (e.g. temporary loss of mobility, treatment for PE/DVT)

Step 4: Much more effective for stroke prevention in AF than antiplatelets, check CHA2DS2VASc

Step 5: Caution: Bleeding events. Avoid combination with antiplatelets and/or NSAIDs

Step 5: Is patient unfit for anticoagulation (warfarin) for cognitive reasons

Step 5: Safety: use creatinine clearance rather than eGFR (DOACs)

Step 7: Ensure adherence to dosing and monitoring regimen

Antiplatelet

Step 3: Antiplatelets are no longer indicated for primary prevention of CHD (incl. T2DM)

Step 3: Dual antiplatelets: check indication for duration, e.g. NSTEMI, stent insertion, ACS

Step 4: Consider antiplatelets as part of secondary prevention strategy after CVD events

• First line antiplatelet for secondary stroke prevention is clopidogrel

Step 5: Consider PPI in those with additional GI risk factors (consider lansoprazole or pantoprazole in preference to (es)omeprazole in patients taking clopidogrel)

Step 5: Caution: Bleeding events. Avoid combination of anticoagulants, antiplatelets and NSAIDs (see hot topic)

Step 5: Caution: ticagrelor: breathlessness – use with caution in asthma/COPD

Diuretic

Step 2: Usually essential for symptom control in heart failure

Step 3: Not indicated for iatrogenic ankle oedema (consider medication causes, e.g. CCBs)

Step 5: Caution: AKI and electrolyte disturbances

- Medication sick day guidance: advise to stop during dehydrating illness

Step 5: Avoid use of thiazides in history of gout – can precipitate gout

Step 5: Ensure U&E monitoring

Spironolactone/ eplerenone

Step 2: Recommended in moderate to severe LVSD: Drug Efficacy (NNT) table

Step 5: Caution: Hyperkalaemia. Risk factors include CKD (CI if eGFR<30ml/min), check dose, co-treatment with ACEI/ARBs, amiloride, triamterene, potassium supplements

- Ensure regular monitoring including potassium levels

Step 5: Caution: AKI. Avoid combination with NSAIDs

- Medication Sick Day Guidance: advise to stop during dehydrating illness

Digoxin

Step 5: Caution: Toxicity. Risk factors: CKD, dose>125 micrograms daily, poor adherence, hypokalaemia

Peripheral vasodilator

Step 3: Rarely effective; rarely indicated long-term

Quinine

Step 3: Use short-term only when nocturnal leg cramps cause regular disruption of sleep

Step 4: Review effectiveness regularly

Step 5: Caution: Thrombocytopenia, blindness, deafness (MHRA warning)

Step 7: Provide advice on stretching exercises and muscle massaging

Antianginal

Step 4: Consider reducing antianginal treatment if mobility has decreased

Step 5: Caution: Hypotension (consider use of other BP lowering drugs; avoid the combination of nitrates with PDE-5 inhibitors)

Antiarrhythmic

Step 2: Dronedarone limited indication

Step 3: In AF: Rate control usually has better benefit/risk balance than rhythm control

Step 5: Caution: Amiodarone overdosing: maintenance should be max 200mg/day

Step 5: Caution: Thyroid complications. Ensure monitoring tests are completed (inc. LFTs)

Step 5: MHRA alert: amiodarone risk of serious adverse effects and monitoring required

Statin

Step 3: Recommended for primary and secondary prevention in patients at high risk of CVD

Step 4: Consider need for and intensity of treatment reflecting life expectancy and ADR risk

Step 5: Caution: Rhabdomyolysis: Interactions (e.g. fibrates, dihydropyridines, anti-infectives)

Antihypertensives - BP control

Step 3: Individualise BP targets for primary and secondary prevention of CVD

Step 4: Consider intensity of treatment reflecting CVD risk life expectancy and ADR risk

Step 7: Limited evidence supporting tight BP control in frailty

Beta-blocker

Step 4: May be required for rate control in AF

Step 4: BNF recommends up-titration of dose in LVSD to evidence-based target

Step 5: Caution: Bradycardia in combination with diltiazem/verapamil, digoxin and amiodarone

Step 5: Caution: asthma (especially non-cardioselective e.g. propranolol)

Step 5: Caution: risk of harm from toxicity and rapid deterioration due to propranolol overdose^[351]

ACEI/ARB

Step 4: Often indicated for in LVSD, post MI, diabetic CKD

Step 4: BNF recommends up-titration of ACEI/ARB doses in CHF to evidence-based target

Step 5 Caution: AKI. Avoid combination with NSAIDs

- Medication sick day guidance: advise to stop during dehydrating illness

Step 5: Avoid concurrent use of two or more angiotensin system inhibitors, e.g. ACEi and ARB and aliskiren. See MHRA alert

Step 6: No benefit of perindopril arginine over perindopril erbumine

CCB

Step 5: Caution: Constipation, ankle oedema

Step 5: Dihydropyridines – Caution: Reflex tachycardia/cardiodepression:

- Avoid nifedipine in CHD/CHF

Step 5: Diltiazem/verapamil – Caution: Bradycardia in combination with beta-blockers or digoxin

Inhaler

Step 4: See Respiratory Conditions Quality Prescribing Guide

Step 4: Assess symptom control

Step 5: High SABA use (three or more inhalers per year) indicates poor asthma control. Consider MART

Step 6: Consider dry powder inhalers rather than metered dose inhalers as lower environmental impact

Step 6: Use combinations inhalers where appropriate

Step 7: Assess inhaler technique and adherence to dosing schedule

Theophylline

Step 3: Monotherapy in COPD is not appropriate – safer, more effective alternatives are available

Step 5: Caution: Toxicity (tachycardia, CNS excitation) due to narrow therapeutic index

Step 5: Avoid combination with macrolides or quinolones

Corticosteroids

Step 3: Long-term oral use for respiratory disease is rarely indicated.

- Withdraw gradually if: > 3 weeks; prednisolone 40mg daily more than one week

Step 3: Stepping down steroid inhalers in asthma: reduce slowly (by 50% every three months)

Step 3: ICS in COPD: only indicated if exacerbations (two or more in 12 months) or raised eosinophil count (>0.3x10⁹ cells/litre), or asthmatic features

Step 5: Caution: Consider bone protection if long-term treatment necessary

Step 5: Steroid alert card if more than three short courses prednisolone; high dose ICS; moderate dose ICS and other steroid, e.g. injected, intranasal, topical

Step 5: Caution: if oral thrush, dysphonia – check inhaler technique with ICS

Montelukast

Step 3: Only indicated in asthma with raised eosinophils, and check responsiveness after four to eight weeks

Step 5: MHRA warning of neuropsychiatric reactions

Antihistamine (1st generation)

Step 3: Rarely indicated long-term

Step 5: Caution: Anticholinergic ADRs. (see anticholinergic table)

Benzodiazepines /

z-drugs

Step 3: See Quality prescribing for benzodiazepine and z-drugs guidance

Step 3: Do not prescribe for more than eight weeks

Step 5: Gradual withdrawal often required

Step 5: Caution: Risk of falls/fractures, confusion, memory impairment

Step 5: Caution: Risk of dependency

Step 5: High risk combinations if prescribed with opioids, antidepressants, gabapentinoids, antipsychotics. See hot topic

Antipsychotic

Step 2: May be essential in schizophrenia and severe mental illness. Seek specialist advice in these indications before altering dose/stopping

Step 4: Unmet need: clozapine induced constipation which can be life threatening – prescribe even if not constipated

Step 5: Caution: Worsening of Parkinson’s disease (specialist advice is recommended)

Step 5: Caution: Risk of stroke and death in elderly patients with dementia. See hot topic

Step 5: Caution: Anticholinergic ADRs for phenothiazines (e.g. chlorpromazine). See anticholinergic table

Step 5: High risk combinations if prescribed with opioids, antidepressants, gabapentinoids, antipsychotics. See hot topic

Step 5: Risk of QTc prolongation with haloperidol and phenothiazines

Dementia medication

Step 3: Formally assess benefit: continue if functional or behavioural symptoms improve, see hot topic

Step 3: Cognitive scores e.g. MMSE can help as a guide

Step 5: Can cause bradycardia – caution in history and/or concurrent medication which reduces heart rate

Antidepressant

Step 3: Ongoing indication: First episode: treat for six to nine months; second and subsequent episodes: treat for ≥2 years

Step 3: Consider dose: 20s plenty (fluoxetine, citalopram, paroxetine) 50’s enough (sertraline) see Quality Prescribing for Antidepressants guidance

Step 5: Caution: anticholinergic ADRs (see anticholinergic table)

- SSRIs better tolerated than TCAs

Step 5: Caution: Risk of GI bleeding may be increased with SSRIs

Step 5: High risk combinations if prescribed with opioids, antidepressants, gabapentinoids, antipsychotics. See hot topic

Step 5: Avoid combination with MAOIs because of the risk of serotonin syndrome

Step 5: Risk of QTc prolongation with (es)citalopram

Step 5: Withdrawal may need to be gradual to avoid discontinuation effects

Step 6: Dosulepin and trimipramine: see achieving value and sustainability in prescribing: guidance

Metoclopramide

Step 3: Only licensed for a maximum of five days (does not apply to use in palliative care)

Step 5: Caution: Worsening of Parkinson’s disease

Antihistamine

Step 3: Rarely indicated for long-term treatment of vertigo

Step 5: Anticholinergic ADRs (see anticholinergic table)

Opioids

Step 4: Low evidence of effectiveness in chronic pain (>3 months)

Step 4: See chronic pain hot topic

Step 4: Be aware of OTC purchases

Step 5: Caution: Constipation. Use laxatives, but not bulk forming

Step 5: Caution: Cognitive impairment and respiratory depression, dependency, immunosuppression, suppression of sex hormones, adrenal suppression

- Risk increases as dose increases more than 60mg MED

Step 5: High-risk combinations if prescribed with benzodiazepines/z-drugs, antidepressants, gabapentinoids, antipsychotics. See high-risk combinations hot topic

Step 5: Gradual withdrawal to avoid discontinuation effects

Step 6: Buprenorphine patches (7-day) and fentanyl immediate release – see achieving value and sustainability in prescribing: guidance

Step 6: Oxycodone/naloxone combination product: see achieving value and sustainability in prescribing: guidance

Paracetamol

Step 5: Caution: Overdosing: ensure awareness of minimum interval between doses and maximum daily dose

Step 5: Avoid more than one paracetamol containing product

Step 5: Dose reduction where low body weight (<50kg) or renal or hepatic impairment

Antiseizure drugs

Step 2: If used as antiseizure medication, seek expert advice regarding changes in dose

Step 2: Ensure prescribed by brand name where appropriate in line with MHRA advice

Step 4: See hot topic for pain management

Step 4: Assess effectiveness/dose if used for pain management

Step 5: Caution: Dizziness, blurred vision and sedation.

Step 5: Check renal function. Reduce dose in CKD (using creatinine clearance)

Step 5: MHRA advice on valproate in pregnancy/pregnancy prevention

Step 5: Topiramate often indicated in migraine prophylaxis, but MHRA warning

Step 5: High-risk combinations if prescribed with opioids, antidepressants, gabapentinoids, antipsychotics. See hot topic

Antibacterial

(Oral)

Step 3: No benefit for treating asymptomatic bacteriuria (ASB) except in pregnancy^[352]

Step 3: Lack of evidence for antibiotic use in preventing catheter-associated ASB

Step 3: Review use of long-term antibiotics for recurrent UTI (every six months)

Step 5: Caution: Nitrofurantoin: pulmonary/renal ADRs; avoid in renal impairment; contra-indicated if eGFR<30ml/min

Step 6: Minocycline less suitable – risk of hepatotoxicity (see achieving value and sustainability in prescribing: guidance)

Antifungal

Step 5: Caution: Risk of exacerbation of heart failure with azole antifungals

Step 5: Caution: Many serious drug interactions with azole antifungals

Antidiabetics

Metformin

Sulfonylureas

Glitazones

SGLT-2i

GLP-1RA

Step 2: Refer to Quality Prescribing Guide for Diabetes

Step 2: Indicated to control symptoms of hyperglycaemia (metformin is first line in T2DM)

Step 2: Note: It takes years for the benefit (microvascular) of tight HbA1C

Step 4: Establish individual HbA1C targets balancing any benefits vs hypoglycaemia risk

Step 4: See NNT table

Step 4: Consider comorbidities, e.g. ASCVD, CKD, cHF and prescribe SGLT-2i or GLP-1RA

Step 5: Pioglitazone: avoid in patients with heart failure

Step 5: Caution: sulfonylurea: risk of hypoglycaemia especially in frailty

Step 5: Caution: Metformin: risk of lactic acidosis. Avoid if eGFR < 30 ml/min. Stop with dehydration

Step 5: Medication Sick Day Guidance: advise to stop during dehydrating illness for sulfonylureas, SGLT-2i, metformin

Step 6: If injectable is required, can reusable pens and cartridges be used rather than disposable pens

Step 6: Ensure any blood glucose test strips are indicated. See also achieving value and sustainability in prescribing: guidance

Steroids

Step 3: Confirm long-term indication. Consider dose reduction/withdrawal where possible

Step 5: Withdraw gradually if: > 3 weeks; prednisolone 40mg daily more than one week

Step 5: Steroid alert card if more than three short courses prednisolone; high dose ICS; moderate dose ICS and other steroid, e.g. injected, intranasal, topical

Step 5: Caution: Consider bone protection if long-term treatment necessary

Bisphosphonates

Step 3: See hot topic

Step 4: Consider need for treatment regarding risk factors for osteoporotic fractures: previous osteoporotic fragility fracture, parental history of hip fracture, alcohol intake ≥ 4 units/d, rheumatoid arthritis, oral steroids, BMI<22kg/m2), ankylosing spondylitis, Crohn’s disease, prolonged immobility, untreated menopause

Step 4: Therapy is most likely to benefit those who have a life expectancy greater than 12.4 months. See NNT table

Step 3: Consider duration of bisphosphonate use and consider whether there is option for bisphosphonate holiday

Step 5: Continue calcium and vitamin D

Step 7: Check ability and willingness to take bisphosphonates (and calcium) as instructed

Alpha-blockers

Step 3: Generally not indicated if has a long-term catheter

Finasteride

Step 3: Generally not indicated if has a long-term catheter – discuss with urology

Antimuscarinics

Step 3: Review continued need/effectiveness after three to six months

Step 5: Caution: Anticholinergic ADRs (oxybutynin may decrease MMSE score in dementia) See anticholinergic table

Step 5: If mirabegron (beta-3-adrenoceptor agonist) is used to reduce anticholinergic ADR, caution if existing hypertension and regular monitoring required. Contra-indicated if severe uncontrolled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg)

Hormone replacement therapy

Step 3: Discuss with patient individual balance of benefits and risk

Step 5: Caution: Consider need for progesterone replacement and appropriate dose, to reduce risk of endometrial cancer

- Mirena® coil: differing duration of use for contraception and HRT

Step 5: Consider formulation – topical versus oral

Chemotherapy/systemic anticancer therapy (SACT)

Step 3: Is treatment still consistent with treatment objectives? Refer to initiating prescriber

Step 3: Consider duration of therapy, e.g. tamoxifen/anastrozole for five years for breast cancer prevention if moderate/high risk

Supplements, including oral nutritional, iron, vitamins, potassium

Step 3: Confirm continued need/effectiveness after three to six months – monitor weight where required

Step 5: Caution: potassium: hyperkalaemia. Risk factors: Use without stop/review date, CKD, co-treatment with ACEI/ARBs, spironolactone, amiloride, triamterene, trimethoprim

Non-steroidal anti-inflammatory drugs (NSAIDs)

Step 5: Caution: Gastro-intestinal ADRs. Risk factors: age>65, GI ulcer, antiplatelets, anticoagulants, steroids, SSRIs, high alcohol use.

- If NSAIDs are essential: Consider gastro-protection with a PPI

Step 5: Caution: Cardiovascular ADRs: risk factors: CVD risk>20%, previous CVD events, HF

Step 5: Caution: Renal ADRs: risk factors: age>65, on ACEI, ARBs and/or diuretics, CKD or HF

- If NSAIDs are essential: Monitor eGFR; stop during intercurrent illness

Step 5: Medication sick day guidance: advise to stop during dehydrating illness

Skeletal muscle relaxants

Step 3: Rarely indicated long-term (except for spasticity)

Step 5: Caution: Anticholinergic ADRs See anticholinergic table

Disease-modifying antirheumatic drugs

Step 4: Assess effectiveness and discuss any need for changes with secondary care specialist

Step 5: Caution: Methotrexate overdosing. Avoid preparations with different strengths

Step 7: Ensure adherence to dosing/monitoring regimen

Drops, sprays, ointments

Step 3: Set a review/stop date for topical antibacterials/antifungals and sympathomimetics

Step 6: Review need for preservative free eye drops (e.g. previous preservative toxicity)