What over‑the‑counter medications should be avoided in individuals with Down syndrome due to their common comorbidities such as congenital heart disease, thyroid disease, infection susceptibility, seizure tendency, and altered drug metabolism?

OTC Medications to Avoid in Down Syndrome

Individuals with Down syndrome should avoid anticholinergic OTC medications (antihistamines like diphenhydramine, doxylamine), NSAIDs (ibuprofen, naproxen), and decongestants (pseudoephedrine, phenylephrine) due to their high prevalence of congenital heart disease, hypothyroidism, seizure disorders, and early-onset dementia.

High-Risk OTC Anticholinergics

• Avoid sedating antihistamines (diphenhydramine, doxylamine, chlorpheniramine) as these are high-risk medications in populations prone to cognitive impairment and should be eliminated when risk outweighs benefit 1
• Anticholinergic medications pose particular concern given the markedly elevated incidence of early-onset dementia in Down syndrome (incidence rate ratio 92.1 in adults ≥30 years) 2
• The cognitive impairment risk is compounded by the fact that 158-fold higher rates of intellectual disability persist into adulthood in this population 2
• Sleep aids containing diphenhydramine or doxylamine should be avoided given the 4.8-fold increased incidence of sleep disorders in children with Down syndrome ages 3-6 years 2

NSAIDs and Cardiovascular Concerns

• NSAIDs (ibuprofen, naproxen, aspirin at analgesic doses) should be avoided or used with extreme caution due to congenital heart disease present in up to 50% of individuals with Down syndrome 3, 4
• NSAIDs are specifically contraindicated in congestive heart failure and can exacerbate cardiac conditions 1
• Up to 50% of individuals with Down syndrome have congenital heart defects, particularly atrioventricular septal defects, patent ductus arteriosus, and atrial septal defects 3, 4
• The cardiovascular risk is further elevated by the 35.5-fold increased incidence of congenital heart malformations that persists from childhood through adulthood 2

Decongestants and Cardiac Risk

• Avoid sympathomimetic decongestants (pseudoephedrine, phenylephrine) in individuals with Down syndrome and known or suspected heart disease 1
• These agents are contraindicated in uncontrolled hypertension and heart disease, and can cause palpitations, tachycardia, elevated blood pressure, and ischemic events 1
• Given that cardiac arrhythmias may indicate underlying hemodynamic abnormalities in this population, sympathomimetic agents pose unacceptable risk 3

Thyroid-Related Medication Interactions

• Avoid iron supplements and multivitamins containing iron taken concurrently with levothyroxine, as hypothyroidism occurs at 13.1-fold higher rates in Down syndrome and remains elevated throughout life 2
• Levothyroxine absorption can be impaired by iron, calcium, and other supplements, requiring separation by at least 4 hours 1
• The American College of Cardiology recommends that cardiologists screen for hypothyroidism in all adults with Down syndrome, as thyroid dysfunction can cause cardiac impairment 3, 5

Laxatives and Gastrointestinal Considerations

• While not strictly contraindicated, stimulant laxatives should be used cautiously given the 7.9-fold increased incidence of gastrointestinal diseases in children ages 3-6 years (with laxative prevalence ratio of 4.7) 2
• The high baseline use of laxatives suggests chronic gastrointestinal issues that may be worsened by certain OTC medications

Seizure Disorder Considerations

• Avoid medications that lower seizure threshold, including high-dose diphenhydramine and doxylamine, given the 15.2-fold increased incidence of epilepsy in adults with Down syndrome over age 30 2
• Bupropion-containing OTC smoking cessation products should be avoided as they lower seizure threshold 1

Critical Drug Interaction Monitoring

• Digoxin toxicity risk is elevated in Down syndrome due to frequent hypothyroidism (which potentiates toxicity), renal impairment risk, and potential drug interactions with OTC medications 6
• Macrolide antibiotics (clarithromycin, erythromycin) available OTC in some regions increase digoxin levels and should be avoided if the patient takes digoxin 6
• Visual disturbances from digoxin toxicity may be harder to detect in individuals with Down syndrome who have 3.1-fold higher rates of eye disorders 2

Safer OTC Alternatives

• For pain/fever: Acetaminophen is the preferred first-line analgesic, avoiding NSAID-related cardiac and renal risks
• For allergies: Non-sedating antihistamines (loratadine, cetirizine, fexofenadine) are preferred over anticholinergic first-generation agents
• For sleep: Melatonin may be considered as a safer alternative to anticholinergic sleep aids, though should be discussed with the patient's physician
• For congestion: Saline nasal sprays and humidification are preferred over sympathomimetic decongestants

Essential Monitoring Considerations

• All adults with Down syndrome should have established cardiology follow-up, with frequency ranging from annual (for repaired defects with minimal residua) to every 3-12 months (for complex lesions) 3
• Mandatory cervical spine imaging is required before any procedure requiring sedation or anesthesia, including dental procedures where OTC analgesics might be used 3
• The 2.6-fold increased incidence of obesity in Down syndrome necessitates careful consideration of weight-based dosing for all medications 2