What is the first‑line medication, dosage, and contraindications for preventing or treating acute mountain sickness in healthy adults ascending above 2500 m?

Medication for Altitude Sickness Prevention and Treatment

First-Line Prophylaxis

Acetazolamide 125-250 mg twice daily is the first-line medication for preventing acute mountain sickness, started the night before ascent and continued for 2-3 days after reaching terminal altitude. 1

Dosing Regimen

• Standard dose: 250 mg twice daily or 500 mg once daily 1
• Lower effective dose: 125 mg twice daily has adequate evidence and may reduce side effects while maintaining efficacy 2
• Start the night before ascent (preferred timing) rather than day-of-ascent, as day-of dosing shows 9% higher AMS incidence 3
• Continue for 2-3 days after arrival at terminal altitude; prolonged use beyond this is unnecessary and increases cumulative side effects 1

Mechanism and Efficacy

• Acetazolamide is a carbonic anhydrase inhibitor causing mild diuresis and metabolic acidosis, which stimulates ventilation and improves oxygenation 1
• Reduces AMS incidence significantly compared to placebo across multiple trials 4, 2
• Increases minute ventilation at altitude (24.9 L/min vs 16.9 L/min with placebo) 4
• May reduce subendocardial ischemia risk at high altitude 1

Common Side Effects

• Paresthesias (tingling in extremities) 1
• Vertigo 1
• Unpleasant taste 1
• These effects are generally mild but dose-related, supporting use of 125 mg twice daily when tolerated 1, 2

Alternative Prophylactic Medications

Dexamethasone

• Use when acetazolamide is contraindicated (e.g., sulfa allergy) 1
• Effective for AMS prevention but typically reserved as second-line 2
• May be combined with other agents in high-risk individuals 5

Ibuprofen

• Reduces AMS incidence compared to placebo 2
• Particularly effective for preventing altitude-related headache 2
• May be considered as alternative or adjunct therapy 2

High-Altitude Pulmonary Edema (HAPE) Prevention

For patients with prior HAPE history, nifedipine extended-release 20 mg every 8 hours is the medication of choice, started with ascent and continued for 3-4 days after arrival. 5, 1, 6

Nifedipine Efficacy

• Reduces HAPE incidence from 64% (7 of 11) to 10% (1 of 10) in HAPE-susceptible individuals 5
• Reduces exaggerated hypoxic pulmonary vasoconstriction and lowers pulmonary artery pressure 6
• Only use extended-release formulations; rapid-release carries severe hypotension risk 6

Alternative HAPE Prophylaxis

• PDE5 inhibitors (sildenafil, tadalafil) may be used but have been associated with severe acute mountain sickness in some subjects 5, 1
• These should be considered second-line to nifedipine 1

Contraindications and Special Populations

Acetazolamide Contraindications

• Sulfonamide allergy (use dexamethasone instead) 1
• Severe renal impairment 1
• Caution when combining with other diuretics in heart failure patients due to dehydration and electrolyte imbalance risk 1

Cardiovascular Disease Patients

• Continue pre-existing cardiovascular medications throughout altitude exposure 1
• Acetazolamide can be safely added for AMS prevention using the same 2-3 day post-arrival duration 1
• Hypertensive patients may benefit from acetazolamide, which can lower blood pressure at high altitude while improving oxygen saturation 1

Pediatric Considerations

• No randomized trials exist for children; all recommendations are based on adult trials 5, 6
• Same principles apply: slow ascent, proper acclimatization, and similar medication dosing adjusted for weight 1

Non-Pharmacological Prevention (Essential Foundation)

Gradual ascent remains the most effective prevention method and should never be replaced by medication alone. 1

• Ascend at 300-600 m/day above 2500 m 5, 1
• Include a rest day for every 600-1200 m of elevation gained 5, 1
• Avoid vigorous exertion before proper acclimatization 5, 1
• Delay further ascent if initial symptoms appear 5, 1

Acute Treatment of Established AMS/HAPE

Immediate Interventions

• Immediate descent to lower altitude is the primary therapy 5, 6
• Administer supplemental oxygen to maintain saturation >91% (ideally 94-98%) 6
• Use reservoir mask at 15 L/min initially 6
• Absolute rest is fundamental while organizing descent 6

Adjunctive Pharmacotherapy for HAPE

• Nifedipine extended-release 20 mg every 8 hours when descent or oxygen not immediately available 6
• Produces rapid clinical improvement, lowering pulmonary artery pressure within hours 6

Critical Pitfalls to Avoid

• Never rely on medication alone without gradual ascent strategy 1
• Never use rapid-release nifedipine formulations due to severe hypotension risk 6
• Inadequate hydration worsens symptoms 1
• Underestimating the importance of proper acclimatization 1
• Continuing ascent despite early symptoms 5
• Assuming medication eliminates all risk in HAPE-susceptible individuals (62% recurrence rate with rapid ascent even with prophylaxis) 1