High Risk Drugs

Overview
Drug Therapeutic range Signs and symptoms of toxicity
Lithium 0.4-1mmol/litre Gastro-intestinal disturbances, visual disturbances, polyuria (excessive
passing of urine), tremor, bradycardia, renal impairment and seizures

Digoxin 1 – 2micrograms/litre Nausea, vomiting, dizziness, fatigue and bradycardia

Methotrexate Monitor Bone marrow suppression - signs include sore throat, bruising, mouth
ulcers. Gastro-intestinal toxicity. Liver toxicity - signs include nausea,
vomiting, yellowing of the skin and whites of the eyes, fatigue, loss of
appetite.

Warfarin Dose dependent on INR Haemorrhage

Theophylline 10-20mg/L Severe vomiting, agitation, hyperglycaemia
restlessness, dilated pupils and sinus tachycardia

Phenytoin 10-20mg/L Nystagmus, diplopia (double vision), slurring of speech, ataxia,

confusion and hyperglycaemia

Ciclosporin Monitor Tremor, gingival hyperplasia, hypertrichosis

Gentamicin 5-10mg/L “peak” 2mg/L “trough” Nephrotoxicity and irreversible ototoxicity
Vancomycin 10-15mg/L “trough” Ototoxicity (discontinue if tinnitus occurs), “red man” syndrome, rash,
blood disorders
Lithium
• Treatment/prophylaxis of mania, bipolar disorder, recurrent depression, aggressive or self-
harming behaviour.
• Contraindications for lithium treatment include - Addison’s disease; cardiac
insufficiency; dehydration; low sodium diets; untreated hypothyroidism
• Cautions - Avoid abrupt withdrawal; cardiac disease; may lower seizure threshold; risk of toxicity
with diuretic treatment; reduce dose for elderly; QT interval prolongation
• Long-term use - associated with thyroid disorders and mild cognitive and memory impairment
• Female patients of child bearing age should use effective contraception
• Pregnancy & breastfeeding – should be avoided if possible (teratogenic in first trimester) and
present in breastmilk
• Narrow therapeutic index – aim for serum-lithium concentration of 0.4–1 mmol/litre (lower end of the
range for maintenance therapy and elderly patients)
• Monitoring – body-weight or BMI, serum electrolytes, eGFR and thyroid function every 6 months
• Slow withdrawal – abrupt discontinuation increases the risk of relapse. The dose should be reduced
gradually over a period of at least 4 weeks (preferably over a period of up to 3 months)
• Maintain adequate fluid intake and avoid dietary changes which reduce or increase sodium intake

Reference: [Link]
Digoxin
• Treatment for atrial fibrillation, flutter, heart failure
• Dosage – reduce by half with amiodarone, dronedarone or quinine.
Increase by 20-33% when swapping from IV to oral route
• Contraindications for digoxin treatment include – intermittent complete heart
block, myocarditis
• Cautions – risk of digitalis toxicity with hypercalcaemia, hypokalaemia,
hypomagnesaemia, hypoxia
• Pregnancy & breastfeeding – dose may need adjustment in pregnancy.
Amount too small in breastmilk to be harmful
• Monitoring – renal function and electrolytes (toxicity increased by electrolyte
imbalance)
Methotrexate
• Treatment for Crohn’s disease, rheumatoid arthritis, neoplastic
disease and psoriasis
• Dosage – WEEKLY
• Contraindications – active infection, immunodeficiency
• Cautions – blood disorders (sore throat, bruising, mouth ulcers), liver toxicity
(nausea, vomiting, abdominal discomfort, dark urine), respiratory effects
(pulmonary toxicity, shortness of breath), photosensitivity, stomatitis
• Blood count – drop in white cell or platelet count requires immediate
withdrawal.
• Contraception – needed for duration of treatment and 3 months after for
both male/female
• Pregnancy & breastfeeding – avoid as teratogenic and present in breast
milk
• Monitoring – FBC, renal and liver function tests before and during treatment
Warfarin
• Prophylaxis of embolisation in rheumatic heart disease and atrial
fibrillation, after insertion of prosthetic heart valve, treatment and
prophylaxis of venous thrombosis and pulmonary
embolism, treatment of transient ischaemic attacks
• Contraindications – within 48 hours post partum, haemorrhagic stroke,
significant bleeding
• Cautions – history of GI bleeding, hyper/hypothyroidisim, uncontrolled
hypertension, recent ischaemic stroke, changes in diet (intake of vitamin K)
• Pregnancy & breastfeeding – danger of teratogenicity, should not be given
in first trimester. Can be used during breastfeeding.
• Monitoring – INR up to every 12 weeks depending on changes in the
patient’s clinical condition
Theophylline
• Treating chronic asthma, reversible airway obstruction, severe acute
asthma, chronic asthma
• Cautions – cardiac arrhythmias, elderly, epilepsy, hypertension, peptic ulcer
• Smoking – can increase clearance of theophylline therefore increased dose
needed. Patients starting/stopping smoking needs to be monitored
• Overdose – vomiting, agitation, restlessness, tachycardia, hyperglycaemia
• Pregnancy & breastfeeding – can be taken as normal in pregnancy and
breastfeeding but can cause adverse effects
• Monitoring – theophylline has a narrow therapeutic index so serum
concentration is kept between 10-20mg/litre for satisfactory bronchodilation
but adverse effects increase as dose increases over 20mg/litre
• Patient should be maintained on specific brand as modified release
preparations differ
Phenytoin
• Treatment for tonic-clonic seizures, focal seizures, prevention and
treatment of seizures during or following neurosurgery or severe head
injury, status epilepticus, acute symptomatic seizures associated with
head trauma or neurosurgery
• Contraindications – second/third degree heart block, sinus bradycardia,
Stokes-Adams syndrome
• Cautions with IV use – heart failure, hypotension and respiratory depression
• Overdose – nystagmus, slurred speech, confusion, hyperglycaemia
• Pregnancy & breastfeeding – doses adjusted depending on plasma
concentration, small amount in breast milk but not known to be harmful
• Monitoring – Patients of Thai origin or Han Chinese patients pre-screened
for HLAB*1502 allele. Monitor blood counts, for IV use ECG and blood
pressure should be monitored
Ciclosporin
• Treatment for keratitis, ulcerative colitis, rheumatoid arthritis, atopic
dermatitis, organ/bone marrow transplant
• Contraindications – peri-ocular infection (if used in eye), with systemic use:
abnormal renal function, uncontrolled hypertension
• Cautions – glaucoma (if used in eye), with systemic use: hyperuricaemia,
malignancy, in the elderly monitor renal function
• Pregnancy & breastfeeding – avoid
• Monitoring – reduce dose if eGFR decreases by more than 25%, reduce
dose by 25-50%. Monitor blood concentration, liver function, potassium,
magnesium, blood lipids, kidney function, blood pressure
• Brands – patients on oral ciclosporin should be maintained on the same
brand due to changes in blood-ciclosporin concentration
Gentamicin
• Treatment for septicaemia, meningitis and other CNS
infections, biliary-tract infection, acute pyelonephritis,
endocarditis, pneumonia in hospital patients, adjunct in listerial
meningitis, prostatitis
• Dose – ideal body weight used for obese patients
• Contraindications – via injection: myasthenia gravis, when used in the ear:
patent grommet, perforated tympanic membrane
• Cautions – dose related side effects, conditions with muscular weakness,
correct dehydration before starting
• Pregnancy & breastfeeding – avoid due to risk of auditory and vestibular
nerve damage in infant when used in second and third trimester
• Monitoring – serum concentration in renal impairment as drug excreted
through the kidney, auditory and vestibular function
Vancomycin
• Complicated skin and soft tissue infections, bone infections, joint
infections, community-acquired pneumonia, hospital-acquired
pneumonia, infective endocarditis, acute bacterial meningitis,
bacteraemia, Clostridium difficile infection
• NOT to be given by mouth for systemic infection due to lack of absorption
• Contraindications – previous hearing loss with IV use
• Cautions – absorption can be enhanced with inflammatory disorders of
intestinal mucosa
• Pregnancy & breastfeeding – only to be used in pregnancy if the benefit
outweighs the risk. It is excreted in breastmilk but significant absorption by
the infant via oral administration is unlikely
• Monitoring – auditory function, blood count, hepatic and renal function,
leucocyte count (risk of neutropenia or agranulocytosis with long term use)
Further reading…
The GPhC has a list of high risk drugs that are likely to be assessed in the registration
exam:
• antibiotics
• anticoagulants
• antihypertensives
• chemotherapy
• insulins
• antidiabetic drugs
• drugs with a narrow therapeutic index
• non-steroidal anti-inflammatory drugs
• methotrexate
• opiates
• parenteral drugs

We have gone into detail about some of the main drugs you may see in practice but it is
advised to know the full list of drugs in good detail too.