Paeds SAQs · clinical-pharmacology-and-therapeutics
Drug interactions and medication reconciliation — formative SAQs
Two MedVellum formative short-answer questions on anticipating cytochrome P450-mediated drug interactions in children and reconciling every medicine at transitions of care: recognising a tacrolimus-azole interaction, predicting the direction and timing of inhibition versus induction, building a Best Possible Medication History, and performing a safe discharge reconciliation. The marks and timing support transparent self-assessment. They are not an official board format or pass standard.
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Target exams
SAQ 1 — A tacrolimus-azole interaction
Question 1 — 10 formative marks; suggested time 15 minutes [1]
A six-year-old girl, four months after liver transplantation, is on a stable twice-daily oral tacrolimus dose with trough levels in target range. She develops oral candidiasis and is started on oral fluconazole by the on-call team. One week later she presents with tremor, headache, and a rising creatinine, and her tacrolimus trough is well above target. [1] [2]
- Explain the mechanism of this interaction and why it occurred. (3 marks)
- State the direction and the expected timing of the effect, and contrast this with enzyme induction. (3 marks)
- How should this interaction have been prevented, and how will you manage it now? (4 marks) [1]
Full-credit answer — SAQ 1
Reveal full-credit answer for SAQ 1
1. Mechanism
Tacrolimus is a substrate of the cytochrome P450 3A4 enzyme with a narrow therapeutic window. Fluconazole is a potent CYP3A4 inhibitor, so it reduces the hepatic and intestinal metabolism of tacrolimus, causing the tacrolimus level to rise. The combination of a narrow-therapeutic-index substrate with a powerful inhibitor is one of the highest-risk paediatric interactions, particularly in transplant and oncology patients. [1] [2]
2. Direction and timing
The direction of inhibition is a rise in substrate concentration, and the onset is fast — within hours to days of starting the inhibitor — because inhibition acts directly on existing enzyme. This is the opposite of enzyme induction, where a drug such as rifampicin increases enzyme protein synthesis and lowers the substrate level over one to two weeks. State both: inhibition is fast and causes toxicity; induction is slow and causes loss of efficacy. [1] [2]
3. Prevention and management
The interaction should have been anticipated before the prescription was signed. The preferred approach is to avoid the combination by using a non-azole antifungal such as nystatin for oral candidiasis. If an azole is unavoidable, the tacrolimus dose should be reduced preemptively — often by a substantial fraction — and a level checked within a few days with close clinical and renal review. Now that toxicity has occurred, I stop the fluconazole, reduce the tacrolimus dose, check the level, treat the tremor and renal dysfunction supportively, and arrange early transplant-team liaison. Azithromycin is the safer macrolide when a similar inhibition concern arises with antibiotics. [1] [2]
SAQ 2 — Reconciliation for a complex child
Question 2 — 10 formative marks; suggested time 15 minutes [7]
A 12-year-old boy with cerebral palsy, epilepsy, and a gastrostomy is admitted with aspiration pneumonia. He is discharged on twelve medicines. The admission list was taken from the referral letter alone, and at discharge two anticonvulsants were inadvertently duplicated and a regular laxative was omitted. [7] [6]
- Describe how you would build the Best Possible Medication History at admission, naming the sources and the data points you would record. (3 marks)
- Why does this child carry particularly high interaction and reconciliation risk, and where in the admission do reconciliation errors concentrate? (3 marks)
- Describe a safe discharge reconciliation, including how you would communicate the list to the family. (4 marks) [7]
Full-credit answer — SAQ 2
Reveal full-credit answer for SAQ 2
1. Best Possible Medication History
I build the Best Possible Medication History from at least two sources: the family interview, the community pharmacy record, the general practitioner summary, and any prior discharge or transfer letter. For every medicine I record the name, dose, route, frequency, the time of the last dose, and adherence, and I ask specifically about over-the-counter, herbal, and as-needed products, because St John's wort and other inducers are easily missed. I never accept a single source such as a referral letter as a complete reconciliation. [7]
2. High-risk child and error concentration
This child is at high risk because of polypharmacy — twelve medicines — combined with complex chronic disease and a gastrostomy. Polypharmacy is the single strongest driver of interaction risk because every added medicine multiplies the possible interacting pairs combinatorially, not linearly. Reconciliation errors concentrate at the transitions of care: admission, transfer between wards or units, and discharge. A single-source admission list and an unverified discharge list are exactly the failures that produce the duplication and omission seen here. [6] [7]
3. Safe discharge reconciliation
At discharge I produce a verified, reconciled list that resolves every change made during the admission, removing the duplicate anticonvulsant and restoring the omitted laxative. I explain the list to the family in plain language, provide it in writing, and confirm it has reached the general practitioner and the community pharmacy before the child leaves — plain-language, health-literacy-informed communication has been shown to reduce discharge medication errors in hospitalised children. I set explicit monitoring review points for any interacting combination and document the indication, dose, and duration for each new or changed medicine. [9] [10]
References
- [1]Li, Ting; Hu, Bo; Ye, Lin Clinically Significant Cytochrome P450-Mediated Drug-Drug Interactions in Children Admitted to Intensive Care Units International journal of clinical practice, 2022.PMID 36081809
- [2]de Wildt, Saskia N; Kearns, Gregory L; Leeder, J Steven Cytochrome P450 3A: ontogeny and drug disposition Clinical pharmacokinetics, 1999.PMID 10628899
- [4]Lu, Hong; Rosenbaum, Sara Developmental pharmacokinetics in pediatric populations The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2014.PMID 25762871
- [6]Feudtner, Chris; Dai, Dongyang; Hexem, Kelly R Prevalence of polypharmacy exposure among hospitalized children in the United States Archives of pediatrics and adolescent medicine, 2012.PMID 21893637
- [7]Merandi, Jacqueline; Sapko, Michael; Catt, Carmen Medication Reconciliation Pediatrics in review, 2017.PMID 28044039
- [9]Adducchio, Stefano; Grant, Evan D; Fonseca, Lais D Reducing Discharge Medication Reconciliation Errors at a Pediatric Neurology Inpatient Unit Neurology. Clinical practice, 2024.PMID 38524835
- [10]Carroll, Athena R; Johnson, Jeffrey A; Stassun, Jonathan C Health Literacy-Informed Communication to Reduce Discharge Medication Errors in Hospitalized Children: A Randomized Clinical Trial JAMA network open, 2024.PMID 38227315