Safe Prescribing

1. Introduction
2. Why Prescribing Errors Matter
3. The Five Rs of Prescribing
   • Right Patient
   • Right Drug
   • Right Dose
   • Right Route
   • Right Time
4. Prescribing in Special Populations
   • Paediatrics
   • Older Adults
   • Pregnancy and Breastfeeding
   • Renal Impairment
   • Hepatic Impairment
5. Writing a Prescription in the UK
6. Controlled Drug Prescriptions
7. The PReSCRIBER Checklist
8. Common Errors to Avoid
9. Summary
10. Quiz

• In a large study of 20 hospitals in north-west England, about 1 in 11 medication orders contained a prescribing error. An estimated 5% to 8% of unplanned hospital admissions are due to medication problems.
• The traditional safety check is the Five Rs: right patient, right drug, right dose, right route, right time. Each step has predictable failure modes worth recognising.
• Special populations (children, older adults, pregnant women, and patients with renal or hepatic impairment) have different pharmacokinetics (how the body absorbs, distributes and removes a drug) and pharmacodynamics (how a drug acts on the body), so they have different prescribing rules.
• UK prescriptions follow specific legal and practical requirements. The legal rules are in the Human Medicines Regulations 2012 and the Misuse of Drugs Regulations 2001, and the British National Formulary (BNF) summarises them. The PReSCRIBER mnemonic is a memory aid for completing a hospital drug chart safely. It appears in revision material for the Prescribing Safety Assessment (PSA), an online assessment of prescribing aimed mainly at medical students near the end of their training.

Introduction

Medicines are the most commonly used clinical intervention in healthcare, and prescribing them is also one of the most error-prone tasks a doctor performs. In the large hospital study described below, foundation doctors (doctors in their first two years after qualifying) wrote 68% of the medication orders, so even a small error rate produces a steady stream of adverse events. Safe prescribing is therefore not a separate clinical skill but an attitude. Writing a drug, a dose, a route and a frequency is a high-risk act that deserves full attention every time.

This article covers the principles taught at UK pre-clinical level. The two foundational sciences are covered separately in Pharmacokinetics and Pharmacodynamics: both are essential to understanding why the rules below exist.

Why Prescribing Errors Matter

The EQUIP study, funded by the GMC, looked at prescribing errors in 20 NHS hospitals in north-west England. Pharmacists checked 124,260 inpatient medication orders and found an error in 8.8% of them, about 1 in 11. Errors were not limited to the most junior doctors, although doctors in training had higher error rates than consultants. Of the errors, 7.3% were judged serious or potentially life-threatening.

A Department of Health report cited by NICE estimated that 5% to 8% of unplanned hospital admissions are due to medication problems. In a study in two large hospitals in Merseyside, England, 6.5% of admissions were related to an adverse drug reaction (harm caused by a medicine), and most of these reactions were definitely or possibly avoidable. In medication incident reports from England and Wales (2005 to 2010) that led to death or severe harm, opioids were involved in 89 incidents, antibiotics in 48, low-molecular-weight heparins (injected anticoagulants) and insulin in 46 each, and warfarin in 45. Drugs to recognise as high risk include:

• Anticoagulants: warfarin and the direct oral anticoagulants (DOACs).
• Insulins.
• Opioids (morphine and related painkillers).
• Antibiotics, particularly through allergy oversights.
• Methotrexate (a drug used for rheumatoid arthritis, psoriasis and some cancers; weekly, not daily, dosing).
• Chemotherapy (anti-cancer drugs).

The drugs in this list are worth recognising as a group. Most of them are prescribed often, many have a narrow therapeutic index (a small gap between a dose that works and a dose that harms), and a wrong dose can cause serious harm.

The Five Rs of Prescribing

The classical safety checklist taught throughout UK undergraduate teaching is the Five Rs: right Patient, right Drug, right Dose, right Route, right Time. Each is a place where a prescription can go wrong.

Right Patient

Confirm the patient's identity by name, date of birth and a unique identifier (hospital or NHS number) at every prescribing event. Look at the wristband, not the chart cover. Patients are at higher risk of being misidentified (mistaken for another patient) at handovers and when care is transferred.

Right Drug

Two failure modes dominate this step:

• Look-alike, sound-alike (LASA) errors. Generic names that differ by a letter or two (clobazam vs clonazepam, hydralazine vs hydroxyzine, vinblastine vs vincristine) are a documented source of harm.
• Allergy oversights. Always check the patient's allergy status before prescribing: on the chart, by asking the patient, and by clarifying what kind of reaction occurred. A "rash with penicillin in childhood" is not the same as anaphylaxis, so ask what the rash was like and when it started. The BNF advises that anyone who had anaphylaxis, urticaria (hives) or a rash immediately after a penicillin should not receive a penicillin. A minor rash (not itchy, in separate spots and limited to a small area of the body), or a rash that started more than 72 hours after the dose, probably does not mean a penicillin allergy.

Always prescribe by the generic name, except for biological products, where the brand name matters. Biological medicines are made by or derived from a biological source using biotechnology. Examples include insulins and biosimilars (biological medicines that are highly similar and clinically equivalent to an existing one). The BNF says biological medicines, including biosimilars, must be prescribed by brand name to avoid switching the patient by accident. Also state the brand where different manufacturers' versions of a product differ in clinical effect. Never invent a generic name for a modified-release (slow-release) preparation, because the invented name can be confused with formulations that act for a different length of time.

Right Dose

Dose errors are common. In the EQUIP study, under-dosing (10.9% of errors) and over-dosing (8.4%) were the most common errors after failing to prescribe a needed medicine on admission. Calculation errors are particularly common in:

• Paediatric prescribing (weight-based dosing, see below).
• Renally cleared drugs at low GFR (glomerular filtration rate, a measure of kidney function), such as digoxin, gentamicin and low-molecular-weight heparins. The principles are explained in Glomerular Filtration Rate and the Measurement of Kidney Function.
• Drugs given as a fraction of a vial: insulin, opioids and chemotherapy.
• Drugs with multiple strengths or formulations: modified-release versus immediate-release preparations are not interchangeable.

Three rules for writing doses on a UK drug chart:

• Always write "micrograms" in full: the abbreviation "µg" can be misread as "mg", a thousand-fold error.
• Always write "units" in full for insulin and heparin: "U" can be misread as a zero, producing a tenfold overdose.
• Never use a trailing zero (write "1 mg", not "1.0 mg") or a naked decimal (write "0.5 mL", not ".5 mL"). A missed decimal point can cause a tenfold dose error. Write doses below 1 mg in micrograms (for example, "100 micrograms", not "0.1 mg").

Right Route

Confirm that the route written matches the formulation prescribed and the clinical indication. Several drugs are dangerous if given by the wrong route. The most notorious is vincristine (a chemotherapy drug), which is usually fatal if given intrathecally (into the fluid around the spinal cord) instead of intravenously. This error has caused multiple deaths in the UK. One safeguard is to give vincristine and related drugs (the vinca alkaloids) in small intravenous bags (minibags) rather than syringes.

If a patient is nil by mouth (allowed nothing to eat or drink) or is vomiting, an oral prescription is the wrong route. Alternatives such as buccal (placed between the cheek and gum), sublingual, rectal, intramuscular, subcutaneous or intravenous administration may be required.

Right Time

Frequency and timing matter for two reasons. First, a drug given at the wrong frequency cannot keep a steady-state plasma concentration (a stable level in the blood) within its therapeutic window (the range between too little to work and too much to be safe). Second, certain drugs have time-dependent rules. Methotrexate is given weekly for rheumatological conditions (such as rheumatoid arthritis), not daily, and daily prescription has caused fatalities. Oral bisphosphonates (bone-strengthening drugs) such as alendronic acid have strict timing rules. Alendronic acid is taken on an empty stomach with plenty of water, at least 30 minutes before breakfast or any other medicine, while sitting or standing. The patient then stays upright for at least 30 minutes. Food and other drinks reduce how much is absorbed. Levothyroxine is preferably taken 30 to 60 minutes before breakfast, caffeine-containing drinks (such as tea or coffee) or other medicines.

Prescribing in Special Populations

Drug handling differs substantially in five groups, each with its own pre-clinical principles.

Paediatrics

Children are not small adults. Doses are generally based on body weight (mg/kg) or on age ranges. Occasionally they are based on body surface area (mg/m²). Two reference resources are used in the UK:

• The BNF for Children (BNFc) for paediatric doses. It also gives advice on unlicensed medicines and on off-label use (using a licensed medicine outside the terms of its licence).
• Local trust paediatric prescribing guidelines, which also cover off-label use.

Important principles:

• Neonates (babies in their first 28 days of life) have immature hepatic enzymes and renal function, so drug clearance is slow.
• Infants and small children have a higher proportion of body water, increasing the volume of distribution (how widely a drug spreads through the body's fluids and tissues) of water-soluble drugs.
• Several drugs are contraindicated or restricted in specific paediatric age groups:
  • Aspirin below age 16, because of the risk of Reye's syndrome (a rare, serious illness that affects the brain and liver).
  • Tetracyclines below age 12 (tooth and bone effects).
  • Codeine below age 12. Codeine is converted to morphine in the liver by the enzyme CYP2D6, and the amount converted varies between people. Some people make too much morphine, which can cause severe effects on the brain and breathing. The Medicines and Healthcare products Regulatory Agency (MHRA) advises that codeine is used only for acute moderate pain in children aged 12 to 17 years. Even then, it should be used only if paracetamol or ibuprofen alone has not relieved the pain. Codeine is also contraindicated in all children under 18 who have their tonsils or adenoids removed to treat obstructive sleep apnoea (repeated blockage of the airway during sleep).
• Systemic fluoroquinolones (such as ciprofloxacin, given by mouth or injection) are restricted at all ages, not just in children. The MHRA says they must only be prescribed when other commonly recommended antibiotics are inappropriate, because of the risk of disabling and potentially long-lasting or irreversible side effects involving tendons, muscles, joints, nerves or mental health.

Older Adults

Older patients have reduced renal clearance (the estimated glomerular filtration rate, eGFR, falls with age), reduced hepatic blood flow, lower lean body mass with relatively more fat tissue, and frequently have several comorbidities (other long-term conditions). The combination produces marked sensitivity to many drugs.

Particular caution is required with:

• Benzodiazepines (sedative drugs such as diazepam): increased fall and confusion risk.
• Anticholinergics (drugs that block the action of acetylcholine): cognitive impairment and constipation.
• NSAIDs (non-steroidal anti-inflammatory drugs, such as ibuprofen): renal impairment, gastrointestinal bleeding and heart failure.
• Opioids: reduced clearance, increased sensitivity.

Polypharmacy (commonly described as regular use of five or more medicines) can increase medication-related harm. The risk for an individual depends on the medicines, their indications, interactions, renal function and other clinical factors. Review the regimen with the patient to balance benefit, harm and treatment burden. The STOPP-START tool helps identify medicines that should be stopped (potentially inappropriate) and others that should be started in older adults. It was developed in Ireland, and its third version (2023) was agreed by a European expert panel. STOPP-START is covered in detail in the article on Poisoning and STOPP-START.

Pregnancy and Breastfeeding

Drugs can harm the embryo or fetus at any time during pregnancy. Few drugs have been shown for certain to cause birth defects in humans, but no drug is safe beyond all doubt in early pregnancy. The risks vary by trimester (one of the three stages of pregnancy, each about three months long). In the first trimester, while the organs are forming (organogenesis), drugs can cause birth defects (teratogenesis). The greatest risk is from the third to the eleventh week of pregnancy. In the second and third trimesters, drugs can affect the growth or development of the fetus, or be toxic to fetal tissues.

Notable teratogens that pre-clinical students are expected to know include:

• ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (drugs for high blood pressure and heart failure; fetal renal failure; oligohydramnios, which is too little amniotic fluid)
• Warfarin (warfarin embryopathy, a pattern of birth defects caused by warfarin)
• Sodium valproate (neural tube defects such as spina bifida, and neurodevelopmental effects on the child's learning and behaviour: now strictly controlled by the MHRA Pregnancy Prevention Programme, a set of measures to prevent pregnancy while taking the drug)
• Lithium (fetal heart malformations, including Ebstein's anomaly, a malformation of the tricuspid valve of the heart; the size of the risk is uncertain)
• Methotrexate (multiple defects)
• Retinoids (drugs related to vitamin A, such as isotretinoin; multiple defects; they require a Pregnancy Prevention Programme)
• Tetracyclines (tooth and bone effects after the first trimester)
• Aminoglycosides (antibiotics such as gentamicin; ototoxicity, which is damage to hearing and balance)

The principle in clinical practice is that drugs should be prescribed in pregnancy only if the expected benefit to the mother is thought to be greater than the risk to the fetus, and all drugs should be avoided if possible during the first trimester. The BNF gives guidance on prescribing in pregnancy, and each drug's entry says where care is needed. The UK Teratology Information Service (UKTIS) also provides information on drugs in pregnancy.

In breastfeeding, the amount of a drug that passes into breast milk is rarely enough to have a noticeable effect on the baby. For many drugs, however, there is not enough evidence to guide prescribing, so it is advisable to give a breastfeeding mother only essential drugs. Each drug's BNF entry says where care is needed in breastfeeding.

Renal Impairment

Renal impairment requires dose adjustment of renally excreted drugs. The general approach is to estimate the patient's renal function and then check the BNF for the dose change needed. For most drugs, and for most adults of average build and height, eGFR can be used. Creatinine clearance (another estimate of kidney function), calculated with the Cockcroft-Gault formula (a formula using age, weight, sex and the blood creatinine level), is used instead for toxic drugs, in older people and in people at extremes of muscle mass. The MHRA also advises using creatinine clearance for direct oral anticoagulants (DOACs) and for drugs with a narrow therapeutic index that are mainly excreted by the kidneys, such as digoxin, gentamicin and vancomycin.

Drugs that require particular care in renal impairment include the aminoglycosides, vancomycin, low-molecular-weight heparins, metformin, digoxin, lithium, and most NSAIDs. The principles are covered in Acute Kidney Injury and Chronic Kidney Disease.

Hepatic Impairment

The liver is the major site of drug metabolism, and significant hepatic impairment can prolong the half-life (the time taken for the drug level in the blood to fall by half) of many drugs. There is no equivalent of eGFR for the liver: routine liver function tests are a poor guide to how well the liver can metabolise drugs. The BNF advises caution and dose reduction based on clinical assessment, with the Child-Pugh classification (a score of how severe liver disease is) used in specialist settings.

Drugs that require particular caution include opioids (reduced clearance, sedation), benzodiazepines, statins (cholesterol-lowering drugs), paracetamol (in chronic alcohol use), and any drug with significant first-pass metabolism (breakdown in the gut wall and liver before the drug reaches the general circulation). See Hepatic, Biliary and Pancreatic Pathology for the underlying disease processes.

Writing a Prescription in the UK

A legally and practically valid UK prescription contains the following elements, as summarised in the BNF. Some are legal requirements (described after the list) and the rest are good practice:

• Patient identification: full name, date of birth, address (for FP10 prescriptions, the NHS prescription forms used in primary care in England) or hospital number (for inpatient charts).
• Date.
• Drug name: in lower case, generic (use the brand name for biological medicines, or where brands differ in clinical effect), written legibly or printed.
• Dose, with clear units. Write "micrograms", "nanograms" and "units" in full; "mg" is acceptable. Avoid trailing zeros and naked decimals.
• Route.
• Frequency: the BNF advises that directions should preferably be in English without abbreviations, although some Latin abbreviations are still used (e.g. od, once daily; bd, twice daily; tds, three times daily; qds, four times daily; prn, when required). Writing directions in full is safer, because abbreviations can be misread. For a medicine taken "as required", state the minimum interval between doses.
• Duration or quantity.
• Prescriber's signature, printed name, GMC number and contact details (a bleep number on a hospital chart).

For a paper community prescription (such as an FP10) for a prescription-only medicine, regulation 217 of the Human Medicines Regulations 2012 sets the legal conditions. The prescription must be signed in ink by the prescriber and written so as to be indelible (impossible to rub out). It must also give the prescriber's address, the date, the kind of prescriber (for example, a doctor), the patient's name and address, and the patient's age if they are under 12. Electronic prescriptions signed with an advanced electronic signature (a digital signature that is uniquely linked to the prescriber and can identify them) are covered by regulation 219.

Preview the Safe Prescribing quiz