What household medicine can be lethal and cause death, particularly in individuals with certain genetic polymorphisms or impaired metabolic function?

Household Medicines with Lethal Potential in Genetic Poor Metabolizers

Antidepressants—particularly fluoxetine, paroxetine, and venlafaxine—can be lethal in individuals with CYP2D6 poor metabolizer (PM) status, causing cardiac arrest, seizures, and death through toxic drug accumulation. 1

High-Risk Antidepressants in CYP2D6 Poor Metabolizers

Documented Fatal Cases

Fluoxetine has caused documented fatalities in CYP2D6 poor metabolizers:

• A 9-year-old child with OCD on high-dose fluoxetine (80-100 mg/day) developed metabolic toxicity, seizures, status epilepticus, cardiac arrest, and death—autopsy confirmed CYP2D6 PM genotype 1
• The PM phenotype prevents normal drug clearance, leading to 419% higher plasma concentrations compared to extensive metabolizers 1

Venlafaxine has similarly proven lethal:

• A 34-year-old man died from cardiac arrest with toxic venlafaxine blood concentration (4.5 mg/kg) attributed to CYP2D6 PM status confirmed by genetic testing 1

Paroxetine carries identical risks:

• PM phenotype produces markedly elevated plasma concentrations 1
• Higher doses required for OCD treatment (compared to depression) amplify toxicity risk 1

Mechanism of Lethality

These medications cause death through multiple pathways in poor metabolizers:

• QT prolongation leading to ventricular arrhythmias and sudden cardiac death 1
• Seizures progressing to status epilepticus 1
• Cardiac arrest from toxic blood concentrations 1
• Blood pressure changes contributing to cardiovascular collapse 1

Codeine: Opposite Genetic Risk Pattern

Codeine presents lethal risk in CYP2D6 ultrarapid metabolizers (UM), not poor metabolizers:

• Ultrarapid metabolizers convert codeine to excessive morphine, causing fatal respiratory depression 2, 3
• Multiple pediatric deaths occurred after tonsillectomy in children with CYP2D6 gene duplications 3
• A toddler died from codeine after adenotonsillectomy due to ultrarapid metabolism 3
• Adult case of life-threatening intoxication from small codeine doses in patient with 3+ functional CYP2D6 alleles 4

Poor metabolizers experience the opposite problem with codeine:

• No analgesic effect because codeine cannot convert to morphine 5, 6
• Still experience full adverse effects (nausea, constipation, sedation) without pain relief 5

Critical Clinical Pitfalls

Genetic Prevalence Varies by Ethnicity

• CYP2D6 poor metabolizers: 5-10% of European Caucasians, lower in Asian populations 1, 6
• Ultrarapid metabolizers: higher prevalence in Eastern African populations 7

Drug-Drug Interactions Amplify Risk

• CYP2D6 inhibitors (e.g., fluoxetine itself) can create "phenocopy" poor metabolizer status even in normal metabolizers 1
• Combining these antidepressants with other CYP2D6 substrates increases toxicity risk 1

High-Dose Scenarios Are Particularly Dangerous

• OCD treatment requires higher SSRI doses than depression, increasing toxicity risk in poor metabolizers 1
• Dose escalation in non-responders may reflect unrecognized PM status rather than treatment resistance 1

Other Household Medications with Genetic Lethality Risk

Tramadol shares codeine's risk profile:

• Requires CYP2D6 conversion to active metabolite M1 for analgesia 6
• Ultrarapid metabolizers risk excessive opioid effects and respiratory depression 6
• Should be avoided entirely in both poor metabolizers (ineffective) and ultrarapid metabolizers (toxic) 6

Tricyclic antidepressants can cause fatal arrhythmias:

• Sodium channel blockade produces QRS prolongation and Brugada-pattern ECG 1
• Risk amplified in patients with underlying cardiac substrate 1