What are the principal collateral effects of neuromodulators, Domperidone (antiemetic and prokinetic agent) and Baclofen (muscle relaxant), in patients with various underlying medical conditions and age groups?

Principal Collateral Effects of Domperidone and Baclofen

Domperidone Side Effects

Domperidone's most serious adverse effect is cardiac arrhythmia due to QTc prolongation, particularly in patients over 60 years and at doses exceeding 30 mg/day, requiring mandatory ECG monitoring with long-term use. 1

Cardiac Effects

• QTc prolongation is the primary safety concern, with increased risk of fatal cardiac arrhythmias, especially when combined with other QT-prolonging medications or in patients with underlying cardiac conditions 1
• Arrhythmias, sudden death, and cardiac arrest were documented with high intravenous doses historically 2
• Doses above 30 mg/daily should only be used with special caution due to cardiotoxic effects 2
• Palpitations and tachycardia occur commonly as reported side effects 3

Central Nervous System Effects

• Extrapyramidal side effects are minimal compared to metoclopramide because domperidone does not readily cross the blood-brain barrier 4
• CNS side effects (somnolence, reduced mental acuity, akathisia) occur significantly less frequently than with metoclopramide 5
• Somnolence affects 29% of patients (compared to 49% with metoclopramide) 5
• Reduced mental acuity occurs in 20% of patients (compared to 33% with metoclopramide) 5

Other Common Side Effects

• Headache is among the most frequently reported adverse effects 3
• Diarrhea occurs commonly 3
• Gastrointestinal symptoms are generally mild 4
• Side effects necessitate discontinuation in approximately 12% of patients 3

---

Baclofen Side Effects

Baclofen's most common adverse effect is transient drowsiness occurring in 10-63% of patients, with the most dangerous complication being life-threatening withdrawal syndrome if abruptly discontinued after prolonged use. 6

Central Nervous System Effects (Most Common)

• Transient drowsiness is the predominant side effect, affecting 10-63% of patients 6
• Dizziness occurs in 5-15% of patients 6
• Weakness and fatigue affect 5-15% and 2-4% of patients respectively 6
• Confusion develops in 1-11% of patients 6
• Headache (4-8%), insomnia (2-7%), and rarely euphoria, excitement, depression, hallucinations, paresthesia, tremor, rigidity, dystonia, ataxia, and seizures 6
• Visual disturbances including blurred vision, nystagmus, strabismus, miosis, mydriasis, and diplopia 6

Cardiovascular Effects

• Hypotension occurs in up to 9% of patients 6
• Rare instances of dyspnea, palpitation, chest pain, and syncope 6

Gastrointestinal Effects

• Nausea affects 4-12% of patients 6
• Constipation occurs in 2-6% of patients 6
• Rarely: dry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhea 6

Genitourinary Effects

• Urinary frequency occurs in 2-6% of patients 6
• Rarely: enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, hematuria 6

Critical Safety Warnings

• Abrupt discontinuation causes life-threatening withdrawal syndrome including delirium, seizures, hallucinations, fever, tachycardia, CNS irritability, and potentially death, requiring slow tapering over weeks 7, 8
• Severe neurotoxicity and hemodynamic instability occur in patients with renal impairment because baclofen is primarily renally excreted 9
• Dose reduction is mandatory in patients with estimated glomerular filtration rate 30-60 mL/min/1.73m², and baclofen should be avoided entirely when eGFR <30 mL/min/1.73m² or in patients on dialysis 9
• Elderly patients rarely tolerate doses greater than 30-40 mg/day (significantly lower than the 80 mg/day maximum adult dose) 7, 8
• Starting dose in elderly should be 5 mg three times daily, titrated gradually to minimize adverse effects 7, 8

Laboratory Abnormalities

• Increased SGOT, elevated alkaline phosphatase, and elevation of blood sugar have been documented 6

Other Effects

• Rash, pruritus, ankle edema, excessive perspiration, weight gain, nasal congestion 6
• May worsen obstructive sleep apnea by promoting upper airway collapse 10

---

Key Clinical Pitfalls to Avoid

For Domperidone:

• Never use long-term without QTc monitoring due to cardiac arrhythmia risk 1
• Avoid in patients over 60 years or with cardiac conditions without careful risk assessment 2
• Do not exceed 30 mg/day without compelling indication and close monitoring 2

For Baclofen:

• Never discontinue abruptly - always taper slowly over weeks to prevent potentially fatal withdrawal syndrome 7, 8
• Reduce dose or avoid entirely in renal impairment - start at 5 mg/day in patients with eGFR 30-60 mL/min/1.73m² and avoid if eGFR <30 mL/min/1.73m² 9
• Use extreme caution with other CNS depressants due to additive sedation 7
• In elderly patients, start at 5 mg three times daily and rarely exceed 30-40 mg/day total 7, 8