Clinical pharmacology and prescribing: Prescribing in special groups

• Organ impairment: Prescribing in Kidney Disease | Medicines in Acute Kidney Injury | Prescribing in Liver Disease | Heart Failure and Other Conditions
• Pregnancy and breastfeeding: Principles of Prescribing in Pregnancy | Drugs to Avoid in Pregnancy | Treating Common Problems in Pregnancy | Prescribing in Breastfeeding | Teratogens, Contraception and Pregnancy Prevention
• Age and size: Prescribing for Children | Drugs to Avoid or Use Carefully in Children | Prescribing for Older People | Prescribing in Obesity and Low Body Weight
• Surgery: Medicines Around Surgery
• Revision: Special Groups at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🩺 Prescribing in special groups -page 4 of the Clinical Pharmacology and Prescribing chapter. The same dose can be safe in one patient and dangerous in another. Kidney and liver disease, pregnancy, breastfeeding, childhood, older age, extremes of weight and surgery all change how drugs behave -and the BNF has a section on each. Detailed older-person prescribing is in the Medicine of the Older Person chapter; obstetric medicine is in the Obstetrics chapters.
Your four questions for every prescription: How well are the kidneys and liver working? Could the patient be pregnant or breastfeeding? Is the dose right for their age and weight? Are there any medicines to stop, start or adjust around surgery or acute illness?

Prescribing in Kidney Disease

• Why it matters -renally cleared drugs accumulate; some drugs damage the kidneys; some drugs don't work when kidney function is low; patients with CKD are sensitive to fluid and electrolyte effects.
• Assess kidney function -eGFR for most drugs; creatinine clearance (Cockcroft–Gault) for DOACs, narrow therapeutic index drugs, older people and extremes of weight; consider trends.
• Approaches -reduce the dose, extend the interval, monitor levels, or choose another drug. Loading doses usually stay the same; maintenance doses are reduced.
• Drugs needing dose reduction or avoidance:

  Drug	Issue
  Metformin	Review dose if eGFR under 45; stop under 30 (lactic acidosis)
  Sulphonylureas, insulin	Hypoglycaemia (reduced clearance)
  DOACs	Dose by creatinine clearance; dabigatran most renally dependent
  LMWH (enoxaparin)	Reduce treatment dose if CrCl under 30; consider UFH
  Gentamicin, vancomycin	Level-guided dosing; nephrotoxic and ototoxic
  Morphine, codeine	Active metabolites accumulate -drowsiness, myoclonus, respiratory depression; use oxycodone carefully or alfentanil/fentanyl in severe CKD
  Gabapentin, pregabalin	Accumulate -sedation, falls
  Digoxin	Toxicity -reduce dose, monitor
  Lithium	Toxicity; also causes CKD
  Nitrofurantoin	Avoid if eGFR under 45 (may be used short-term down to 30 with caution) -ineffective and toxic
  Trimethoprim	Hyperkalaemia; raises creatinine (reduced secretion -not true GFR fall)
  Aciclovir, valaciclovir	Neurotoxicity and crystal nephropathy -reduce dose
  Allopurinol	Start low; hypersensitivity risk
  Methotrexate	Toxicity -reduce or avoid
  Bisphosphonates	Avoid alendronate if eGFR under 35; zoledronate if CrCl under 35
  SGLT2 inhibitors	Glucose-lowering effect falls with eGFR, but still used for kidney and heart protection (check current thresholds)
  Penicillins, cephalosporins, carbapenems	High doses -seizures in severe CKD; dose adjust

• Nephrotoxic drugs to avoid -NSAIDs, aminoglycosides, IV contrast (risk in AKI and CKD -hydrate), lithium, ciclosporin and tacrolimus, amphotericin.
• Hyperkalaemia risk -ACE inhibitors, ARBs, spironolactone, amiloride, trimethoprim, potassium supplements -monitor potassium.
• Dialysis -some drugs are removed (give after dialysis); seek renal pharmacy advice.

Medicines in Acute Kidney Injury

• Review all medicines in AKI (NICE NG148):
  • Stop or withhold drugs that worsen kidney function -NSAIDs, ACE inhibitors and ARBs, diuretics (if hypovolaemic), aminoglycosides, contrast (where possible).
  • Stop or reduce drugs that accumulate and cause harm -metformin (lactic acidosis), sulphonylureas (hypoglycaemia), DOACs and LMWH (bleeding), digoxin, lithium, opioids (morphine), gabapentinoids, methotrexate, SGLT2 inhibitors.
  • Adjust antibiotic and antiviral doses.
• eGFR is unreliable in AKI (creatinine isn't at steady state) -assume kidney function is worse than the number suggests.
• Restart withheld medicines (with a clear plan) when kidney function recovers and the patient is eating and drinking -don't forget ACE inhibitors in heart failure.
• "Sick day rules" -during dehydrating illness (vomiting, diarrhoea, fever), temporarily stop "SADMANS" -Sulfonylureas, ACE inhibitors, Diuretics, Metformin, ARBs, NSAIDs, SGLT2 inhibitors; restart after 24–48 hours of normal eating and drinking.
• Iodinated contrast -assess risk (eGFR under 30, AKI); IV hydration for high-risk patients; review metformin per local policy.

Prescribing in Liver Disease

• Liver disease affects drugs in several ways:
  • Reduced metabolism -drugs and metabolites accumulate (especially in cirrhosis); LFTs don't predict this well -albumin, INR and bilirubin (Child–Pugh score) are better guides.
  • Low albumin -more free drug (phenytoin, warfarin).
  • Clotting problems -higher bleeding risk with anticoagulants and antiplatelets.
  • Fluid retention -worsened by NSAIDs, steroids and sodium-containing preparations (IV antibiotics, effervescent tablets).
  • Hepatic encephalopathy -precipitated by sedatives, opioids, constipation, diuretics (electrolyte changes), infection, GI bleeding.
  • Kidney function -hepatorenal syndrome; creatinine overestimates kidney function (low muscle mass).
  • Hepatotoxic drugs can worsen liver damage.
• Drugs to avoid or use with great care in cirrhosis:
  • NSAIDs -GI bleeding, kidney failure, fluid retention -avoid.
  • Opioids and sedatives (benzodiazepines, Z-drugs) -encephalopathy; if needed, low doses (e.g. short-acting, lorazepam over diazepam; oxycodone or fentanyl with care).
  • Paracetamol -safe at reduced dose (e.g. maximum 2–3 g/day in cirrhosis, low weight, malnutrition or alcohol excess).
  • Anticoagulants -bleeding (DOACs contraindicated in some Child–Pugh classes).
  • ACE inhibitors and ARBs -avoid in decompensated cirrhosis with ascites (hypotension, kidney failure).
  • Metformin -avoid in severe liver disease (lactic acidosis).
  • Statins -usually safe in compensated liver disease and fatty liver; avoid in decompensated disease.
  • Hepatotoxic drugs -methotrexate, high-dose amiodarone, valproate, some antibiotics (co-amoxiclav) -consider alternatives.
• Drugs used in liver disease -lactulose and rifaximin (encephalopathy), spironolactone (ascites), non-selective beta-blockers (carvedilol, propranolol -varices), terlipressin (variceal bleeding, hepatorenal syndrome), antibiotics (SBP prophylaxis).

Heart Failure and Other Conditions

• Heart failure -avoid drugs that cause fluid retention or depress the heart:
  • NSAIDs, pioglitazone, non-dihydropyridine calcium channel blockers (verapamil, diltiazem -in reduced EF), class I antiarrhythmics (flecainide), dronedarone (severe HF), tricyclics, itraconazole, high-sodium preparations, some chemotherapy (anthracyclines, trastuzumab).
• Asthma -avoid non-selective beta-blockers (propranolol, including eye drops -timolol); use cardioselective beta-blockers cautiously when strongly indicated; NSAID and aspirin sensitivity in some (especially with nasal polyps).
• Myasthenia gravis -many drugs worsen weakness: aminoglycosides, macrolides, quinolones, magnesium, beta-blockers, neuromuscular blockers, quinine, botulinum toxin.
• Epilepsy -drugs lowering seizure threshold: tramadol, bupropion, quinolones, carbapenems (with valproate -also lowers valproate levels), high-dose penicillins, tricyclics, antipsychotics, theophylline, withdrawal of benzodiazepines or alcohol.
• Parkinson's disease -avoid dopamine antagonists -metoclopramide, prochlorperazine, typical antipsychotics (haloperidol); use domperidone (antiemetic), quetiapine or clozapine (psychosis).
• G6PD deficiency -avoid oxidant drugs (primaquine, dapsone, nitrofurantoin, quinolones, sulfonamides, rasburicase).
• Porphyria -many drugs can trigger attacks -check the porphyria drug database.
• Glaucoma (angle-closure) -anticholinergics and some antidepressants can trigger acute attacks.
• Prostatic enlargement -anticholinergics, antihistamines, decongestants can cause retention.

Principles of Prescribing in Pregnancy

• Most drugs cross the placenta; effects depend on the drug, dose and timing:
  • First 2 weeks after conception -"all or nothing" (miscarriage or no effect).
  • Weeks 3–8 (organogenesis) -highest risk of structural malformations.
  • Second and third trimesters -effects on growth and function (e.g. kidneys, ductus arteriosus), and on the neonate around delivery (withdrawal, respiratory depression, hypoglycaemia).
• Think about pregnancy in every woman of childbearing potential -ask about the last period, contraception and plans; test if in doubt before teratogenic drugs.
• Principles:
  • Avoid drugs in the first trimester unless the benefit clearly outweighs the risk.
  • Use drugs with the longest safety record, at the lowest effective dose, for the shortest time.
  • Don't stop essential treatment without advice -untreated disease (epilepsy, asthma, depression, hypertension, thyroid disease, diabetes, inflammatory disease) often harms mother and baby more than the drug.
  • Check the BNF and the UK Teratology Information Service (UKTIS) and its patient resource (bumps).
  • Pre-pregnancy counselling for women with chronic diseases -switch to safer drugs before conception; high-dose folic acid 5 mg where indicated (epilepsy drugs, diabetes, obesity, previous neural tube defect, sickle cell disease, coeliac disease).
• Physiological changes -larger blood volume, higher GFR (lower levels of renally cleared drugs -e.g. lamotrigine and levetiracetam levels fall, needing dose increases), altered protein binding.

Drugs to Avoid in Pregnancy

Treating Common Problems in Pregnancy

• Vaccines recommended in pregnancy -influenza (any stage), pertussis (from 16 weeks), COVID-19, RSV (from 28 weeks -UK programme).

Prescribing in Breastfeeding

• Most drugs pass into breast milk in small amounts -most are compatible with breastfeeding; encourage breastfeeding where possible.
• Factors increasing infant exposure -high maternal doses, long half-life, lipid-soluble, low protein binding, active metabolites; premature or very young babies (immature metabolism).
• Generally compatible -paracetamol, ibuprofen, most penicillins and cephalosporins, LMWH, warfarin, insulin, metformin, levothyroxine, labetalol, nifedipine, enalapril, prednisolone (low dose), sertraline, inhalers, most vaccines.
• Avoid or use with caution:
  • Codeine -contraindicated (ultra-rapid metabolisers → infant opioid toxicity and death) (MHRA); tramadol -caution.
  • Aspirin (analgesic doses) -Reye's syndrome risk.
  • Lithium -infant toxicity (specialist only).
  • Amiodarone, radioactive iodine, cytotoxics (methotrexate, cyclophosphamide), mycophenolate, leflunomide, retinoids.
  • Benzodiazepines (long-acting -infant sedation), sedating antihistamines.
  • Combined oral contraceptives -reduce milk supply (use progestogen-only methods in the first 6 weeks).
  • Ciprofloxacin, tetracyclines (short courses often acceptable), chloramphenicol, carbimazole (high doses).
• Resources -BNF, UK Drugs in Lactation Advisory Service (UKDILAS) (Specialist Pharmacy Service), LactMed.
• Advice -take doses just after a feed; watch the baby for drowsiness, poor feeding, rashes or diarrhoea.

Teratogens, Contraception and Pregnancy Prevention

• Pregnancy Prevention Programmes (MHRA) -required for:
  • Valproate -not to be started in patients under 55 (male or female) unless two specialists agree there's no alternative; women of childbearing potential need highly effective contraception and an annual risk acknowledgement form.
  • Isotretinoin (and other oral retinoids) -pregnancy tests and highly effective contraception.
  • Topiramate (2024) -pregnancy prevention programme for women of childbearing potential.
  • Thalidomide, lenalidomide, pomalidomide; mycophenolate (contraception and pregnancy testing).
• Highly effective contraception -the LARC methods (copper IUD, levonorgestrel IUS, implant) -failure under 1% a year; user-dependent methods (pill) are less reliable.
• Enzyme-inducing drugs (rifampicin, carbamazepine, phenytoin, topiramate at higher doses, St John's wort, some antiretrovirals) reduce the effectiveness of combined pills, progestogen-only pills, implants and oral emergency contraception -use a copper IUD, LNG-IUS or progestogen injection; continue for 28 days after stopping the inducer.
• Emergency contraception with enzyme inducers -copper IUD preferred; or double-dose levonorgestrel (3 mg); ulipristal is not recommended.
• Lamotrigine and combined pills -oestrogen lowers lamotrigine levels (seizure risk; toxicity in the pill-free week).
• Men -some drugs affect sperm or fertility (e.g. methotrexate -men can usually continue; mycophenolate -condoms advised; cyclophosphamide -sperm banking; finasteride -avoid exposure of pregnant partners to crushed tablets).

Prescribing for Children

• Children are not small adults -absorption, body water, liver enzymes and kidney function change rapidly with age, especially in neonates (immature liver and kidneys -longer half-lives).
• Use the BNF for Children (BNFC) and local paediatric guidance.
• Dosing:
  • Usually by weight (mg/kg) or age band; sometimes by body surface area (chemotherapy).
  • Always weigh the child (estimated weights cause errors) and record the weight on the chart.
  • Never exceed the adult dose -overweight children may need doses based on ideal weight.
  • Double-check calculations -tenfold errors are a major risk (decimal points, mg vs micrograms).
• Formulations -liquids (check strength -mg per 5 mL; sugar-free if long-term), dispersible tablets, suppositories; use oral syringes for oral liquids.
• Off-label use is common and accepted (GMC) -use the BNFC.
• Involving children -explain at the right level; consent (Gillick competence for under 16s); adherence (taste, school-time doses -choose once- or twice-daily regimens).
• Paracetamol and ibuprofen -weight- or age-based dosing; avoid giving both "just in case" for fever alone (NICE -consider swapping if distress persists).

Drugs to Avoid or Use Carefully in Children

• Accidental poisoning -common in toddlers (iron, paracetamol, button batteries, laundry capsules, family members' medicines) -child-resistant containers, safe storage.

Prescribing for Older People

• Older people are the largest users of medicines and suffer the most ADRs -see the Medicine of the Older Person chapter page on Prescribing and Deprescribing.
• Key points:
  • Kidney function is often lower than creatinine suggests -use creatinine clearance for dosing.
  • Increased sensitivity to sedatives, opioids, anticholinergics and antihypertensives -start low, go slow.
  • Polypharmacy -review regularly using STOPP/START; deprescribe.
  • Falls-risk drugs, anticholinergic burden, hyponatraemia (thiazides, SSRIs), hypoglycaemia.
  • Practical issues -swallowing, dexterity, vision, cognition, packaging.

Prescribing in Obesity and Low Body Weight

• Obesity changes drug distribution (more fat, larger blood volume, higher clearance for some drugs).
• Which weight?:
  • Actual body weight -LMWH (treatment doses, up to a cap -check local guidance; monitor anti-Xa in extremes), some antibiotics.
  • Ideal body weight -drugs that distribute mainly into lean tissue (e.g. some anaesthetic drugs, digoxin).
  • Adjusted body weight -aminoglycosides (gentamicin) in obesity: IBW + 0.4 × (actual − IBW).
• Thromboprophylaxis -higher doses of LMWH in obesity (e.g. BMI over 40 or weight over 100–150 kg per local protocol).
• Fixed doses may be too low (e.g. some antibiotics, emergency contraception -levonorgestrel less effective over BMI 26 or weight 70 kg -copper IUD preferred or double-dose levonorgestrel).
• Creatinine clearance -Cockcroft–Gault overestimates in obesity if actual weight is used -use adjusted weight per local guidance.
• Low body weight (under 50 kg) -reduce paracetamol (e.g. 15 mg/kg per dose; maximum per local guidance), DOAC dose criteria (apixaban -weight 60 kg or less is one criterion; edoxaban 60 kg or less), care with nephrotoxic and sedating drugs.
• After bariatric surgery -reduced absorption of some drugs (modified-release preparations, oral contraceptives -use non-oral), avoid NSAIDs (ulcers), lifelong vitamin and mineral supplements.

Medicines Around Surgery

Special Groups at a Glance