What is the dose of thalidomide (generic name) for intractable cough in adults?

Thalidomide Dosing for Intractable Cough in Adults

For adults with intractable cough, thalidomide should be initiated at 50 mg daily, with potential increase to 100 mg daily if no improvement is seen after 2 weeks, along with sodium docusate and vitamin B supplementation. 1

Evidence for Thalidomide in Intractable Cough

• Thalidomide has demonstrated significant efficacy in treating intractable cough, particularly in patients with idiopathic pulmonary fibrosis (IPF), with statistically significant improvements in cough-related quality of life measures 1
• In the key randomized crossover trial by Horton et al., patients received 12 weeks of treatment with thalidomide starting at 50 mg daily, increasing to 100 mg daily in all but one patient if there was no improvement in cough after 2 weeks 1, 2
• This regimen led to significant improvements in Cough Quality of Life Questionnaire scores (decreased by 11.37 points; P < .001) and cough Visual Analogue Scale scores (decreased by 31.2 mm; P < .001) 1, 2
• All patients receiving thalidomide should routinely receive sodium docusate and vitamin B supplementation to mitigate side effects 1

Important Safety Considerations

• Thalidomide has a concerning side effect profile, including its well-known teratogenicity, requiring strict precautions in women of childbearing potential 1
• In clinical trials, significantly more patients receiving thalidomide reported adverse events compared to placebo (77% vs 22%; P = .001) 1
• The most common side effects include constipation, dizziness, and malaise 1, 2
• Despite these side effects, in the Horton trial, all participants accepted the offer to continue thalidomide treatment at the end of the study, suggesting the benefits outweighed the adverse effects 1, 2
• Dose reduction may be necessary in some patients (required in 3 of 23 patients in the key trial) 1

Clinical Context and Placement in Treatment Algorithm

• Thalidomide should be considered for intractable cough only after ruling out and treating other potential causes of cough 1
• The American College of Chest Physicians (ACCP) guidelines suggest thalidomide be considered specifically in patients with IPF and chronic cough where alternative causes have been ruled out, though this recommendation did not achieve consensus among the expert panel 1
• Thalidomide should be positioned as a later-line option after trying:
  • First-line options: gabapentin therapy and multimodality speech pathology therapy 3
  • Second-line options: low-dose controlled-release morphine 3
  • For patients with lung cancer and intractable cough, thalidomide is suggested as an N-of-1 trial option when other approaches have failed 1

Monitoring and Follow-up

• Regular monitoring for adverse events is essential during thalidomide treatment 1
• Assess response to treatment after 2 weeks to determine if dose escalation from 50 mg to 100 mg daily is warranted 1, 2
• Consider dose reduction if side effects are intolerable but cough improvement is observed 1
• Treatment duration in the key clinical trial was 12 weeks, providing guidance for an initial treatment course 1, 2

Special Considerations

• Thalidomide may have a role in treating cough through anti-inflammatory mechanisms and possibly reduced cough sensory nerve activity 1
• While the CHEST Expert Cough Panel did not formally approve thalidomide for IPF-related cough, they did encourage further study as it shows promise 1
• For patients with lung cancer experiencing intractable cough, thalidomide is suggested as an option when other approaches have failed, using an N-of-1 trial approach 1