What is the recommended gabapentin dosing regimen for an adult with chronic refractory cough, and how should the dose be adjusted in patients with reduced creatinine clearance?

Gabapentin Dosing for Chronic Refractory Cough

For adults with chronic refractory cough, start gabapentin at 300 mg once daily and titrate upward by adding 300 mg each day as tolerated to a maximum of 1,800 mg daily in two divided doses, with mandatory dose adjustment based on creatinine clearance in patients with renal impairment. 1

Standard Dosing Regimen

The American College of Chest Physicians provides explicit dosing guidance for gabapentin in unexplained chronic cough 1:

• Day 1: 300 mg once daily
• Day 2: 300 mg twice daily (600 mg/day total)
• Day 3 onward: Continue adding 300 mg increments daily as tolerated
• Target dose: 1,800 mg daily in two divided doses (900 mg twice daily)
• Maximum dose: 1,800 mg/day for cough indication 1

This differs from the FDA-approved dosing for postherpetic neuralgia or epilepsy, where doses up to 3,600 mg/day may be used 2. However, for chronic cough specifically, the evidence supports a maximum of 1,800 mg/day 1, 3.

Renal Dose Adjustment (Critical)

Gabapentin is renally cleared and requires mandatory dose reduction in patients with reduced creatinine clearance to prevent accumulation and toxicity. 4, 2

The FDA label provides specific adjustments for patients ≥12 years 2:

Creatinine Clearance	Total Daily Dose Range	Dosing Frequency
≥60 mL/min	900-1800 mg	300-600 mg TID
30-59 mL/min	400-1400 mg	200-700 mg BID
15-29 mL/min	200-700 mg	100-700 mg once daily
<15 mL/min	100-300 mg	100-300 mg once daily
Hemodialysis	Maintenance dose based on CrCl + supplemental post-HD dose	125-350 mg after each 4-hour dialysis session

2

Use the Cockcroft-Gault equation to estimate creatinine clearance in outpatients with stable renal function 2:

For males: CrCl = [(140 - age) × weight in kg] / (72 × serum creatinine)
For females: Multiply result by 0.85

Clinical Efficacy and Patient Selection

The landmark randomized controlled trial demonstrated that gabapentin improved cough-specific quality of life (Leicester Cough Questionnaire) by 1.80 points compared to placebo (p=0.004), with a number needed to treat of 3.58 3. The therapeutic success rate in clinical practice is approximately 66% 5.

Patients most likely to respond have features of laryngeal hypersensitivity: 5, 6, 7

• Hull Airway Reflux Questionnaire (HARQ) score >21.5 (sensitivity 84.6%, specificity 63.6%) 5
• Symptoms of "tickle or lump in throat," "cough upon waking," or "cough with eating" 5
• Vocal fold motion asymmetry on videostroboscopy (94% response rate vs 56% without) 6
• History of laryngeal paresthesia, hypertussia (excessive coughing), or allotussia (cough triggered by non-tussive stimuli) 7, 8

Treatment Algorithm

1. Confirm diagnosis: Chronic cough >8 weeks duration, unexplained after guideline-based assessment including objective testing for bronchial hyperresponsiveness and eosinophilic bronchitis 1

2. Consider speech pathology first: Multimodality speech pathology therapy is recommended as initial treatment (Grade 2C) 1, 9

3. Initiate gabapentin if speech pathology unavailable or fails: 1

   • Discuss potential side effects and risk-benefit profile before starting
   • Calculate creatinine clearance and adjust dose accordingly
   • Start 300 mg once daily, titrate as outlined above
   • Maximum 1,800 mg/day in two divided doses

4. Monitor and reassess: 1

   • Evaluate response after 4-8 weeks
   • Mandatory reassessment of risk-benefit profile at 6 months before continuing 1
   • If inadequate response, consider low-dose morphine (5 mg twice daily) as alternative 9

Common Pitfalls and Side Effects

Most common adverse effects are somnolence, dizziness, nausea, and fatigue 3, 7:

• Occurred in 31% of patients in the pivotal trial 3
• Side effects limited dose escalation in 25-44% of patients 6
• Respiratory compromise can occur, particularly with renal impairment leading to drug accumulation 4

Critical safety considerations:

• Never discontinue abruptly—taper over minimum 1 week to prevent withdrawal 2
• For patients on >14 days, reduce by 10-20% every 24-48 hours 10
• Avoid concurrent CNS depressants when possible 10
• Monitor elderly patients closely due to higher likelihood of decreased renal function 2

When Gabapentin Fails

If gabapentin is ineffective or not tolerated after 4-6 weeks at maximum tolerable dose 9:

• Reassess for GERD (can improve LCQ score from 14.3 to 17.9) 9
• Consider low-dose slow-release morphine 5 mg twice daily if quality of life severely impaired 9
• Tricyclic antidepressants (amitriptyline 10-25 mg at bedtime) are alternatives, though less studied for cough 9