Pilocarpine Dosing
For Sjögren's syndrome, the recommended dose is 5 mg orally four times daily (20 mg/day total), while for radiation-induced xerostomia in head and neck cancer patients, start with 5 mg three times daily and titrate up to 10 mg three times daily (30 mg/day maximum) based on response and tolerability. 1
Dosing by Indication
Sjögren's Syndrome (Dry Mouth and Dry Eyes)
- Standard dose: 5 mg orally four times daily 1
- Efficacy is typically established by 6 weeks of treatment 1
- This 20 mg/day regimen produces significant improvement in symptoms of dry mouth, dry eyes, and other xeroses 2
- Salivary flow increases 2- to 3-fold after the first dose and is maintained throughout treatment 2
Radiation-Induced Xerostomia (Head & Neck Cancer)
- Initial dose: 5 mg three times daily 1
- Titration range: 15-30 mg per day (not to exceed 10 mg per dose) 1
- At least 12 weeks of uninterrupted therapy may be necessary to assess beneficial response 1
- The 5 mg three times daily regimen produces the best clinical results when balancing efficacy and side effects 3
- Some patients may experience additional benefit by increasing to 10 mg three times daily, though adverse events increase with dose 3
Special Populations
Hepatic Impairment
- Moderate hepatic impairment: Start at 5 mg twice daily, then adjust based on response and tolerability 1
- Mild hepatic impairment: No dosage reduction required 1
- Severe hepatic impairment: Use is not recommended 1
Clinical Considerations
Timing and Duration
- Peak salivary flow levels are maintained for at least 1-2 hours after administration 4
- Mean salivary flow rates are 2- to 10-fold higher than placebo 4
- No evidence of tolerance develops during prolonged administration up to 5 months 4, 5
- Best results require continuous treatment for more than 8 weeks with doses greater than 2.5 mg three times daily 3
Dose Selection Strategy
Use the lowest dose that is tolerated and effective for maintenance 1. The incidence of adverse events increases with dose 1, 3, with sweating being the most common side effect, occurring in over 40% of patients 6. Approximately 2% of patients withdraw due to drug-related side effects 6.
Important Caveats
- The 2020 EULAR guidelines note that evidence for pilocarpine in primary Sjögren's syndrome is limited, with an unfavorable safety profile, recommending it primarily for patients with moderate glandular dysfunction who are refractory to non-pharmacological stimulation 6
- The 2015 ESMO guidelines suggest against using systemic pilocarpine to prevent oral mucositis in radiation therapy patients 6
- Most clinical studies demonstrate greater improvement in dry mouth than dry eye symptoms 6
- Visual symptom improvements (focusing during reading, blurred vision) may be related to the miosis effect of pilocarpine rather than tear production 6