Proposed warning and advisory statements relating to the harm of long-term use and overuse of stimulant laxatives

I am an academic and clinical gastroenterologist, and clinical pharmacologist, in Christchurch and run the gastrointestinal motility service for most of the South Island, in which I see and treat many patients with constipation, often severe in nature. For 8 years from 2002-2010 I contributed to the BMJ Clinical Evidence Handbook, writing the section Constipation in Adults, with Prof Frank Frizelle, where we annually reviewed all evidence related to laxatives. I am submitting on behalf of the Department of Clinical Pharmacology at CDHB.
We are interested in the MARC response to the UK MHRA changes recommended for stimulant laxatives and in the evidence base for these recommendations. We have studied the MHRA report and would have to say that we find the report surprisingly superficial, especially with regard to the evidence of harm from stimulant laxatives. Any laxative that causes loose frequent stools carries risk of electrolyte disturbance and dehydration and so can cause indirect risk of organ damage or death, although this is very rare. However, this risk applies also to non-stimulant laxatives such as osmotic laxatives.
The MHRA report provides no evidence that stimulant laxatives are directly harmful long term. The report describes patients with gross overdose over many years with no harm. For the rare cases of fatality reported there is no evidence presented that this was due directly to the stimulant laxative and these patients were described as being on other medications or the stimulant laxative was part of a combination therapy with other substances. The denominator population from which these cases are drawn is large, the prevalence of chronic laxative use is reported to be 1-18% of adults (1).
In the past, it was hypothesised that chronic stimulant laxative use might result in disordered gut function with tolerance and cathartic colon in the most severe form. This was never proven and it is now believed that the natural history of the underlying constipation condition led to gradual worsening of constipation, despite being on stimulant laxatives, rather than because of the laxatives (2). Animal studies have clearly shown no evidence of neuromuscular toxicity from stimulant laxatives (3) and clinicians are now reassured and happier to use these laxatives long-term without concern for long-term toxicity or risk to the patient. More patients appear to die from severe constipation or the consequences of severe constipation than from stimulant laxatives.
I treat many patients with very severe constipation. My first line treatments are osmotic laxatives but there is a group of patients who cannot tolerate these medications or find them ineffective and they require chronic stimulant laxatives. And so the larger box size is entirely suitable for them and small supply quantities would be inconvenient for these patients. There is wide use of docusate and sennosides in the elderly without complications.
We agree there is a group of laxative-abusing patients who use laxatives inappropriately and sometimes in large quantities. We agree with the statement that laxatives are not effective for weight loss.
One useful clinical practice point here is, for patients who seem to need laxatives chronically, medical assessment is recommended to diagnose the cause of the constipation. Causes such as bowel cancer should be considered. Some causes of constipation can be managed without laxatives, with treatment options like diet change, ceasing constipating drugs, biofeedback for anismus and others.
In summary:
(1) There may be unforeseen inconvenience by reducing stimulant laxative pack size for those with a genuine reason to use stimulant laxatives longterm,
(2) We agree with the statement ‘does not help with weight loss’
(3) There is insufficient evidence for the statement ‘prolonged or excessive use can be harmful’, although the statement ‘excessive use can be harmful’ can be justified and is likely to be helpful. However, if this statement is to be added for stimulant laxatives, it would also need to be added to any other laxatives that cause frequent loose stools as the risk is the same, in the form of electrolyte disturbance and dehydration

A separate but related issue is that there are many complementary and alternative products sold as laxative treatments. These are heavily used by consumers and many contain sennosides and other active ingredients. Thought should be given to managing this risk also.
Following from the above, if stimulant laxatives are to be reclassified, an argument could easily be made to reclassify osmotic laxatives similarly, or indeed any laxative that resulted in frequent, loose motions.
References
1. Werth BL, Christopher SA. Laxative Use in the Community: A Literature Review. J Clin Med. 2021 Jan 4;10(1):143.
2. Müller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol. 2005 Jan;100(1):232-42.
3. Wald A. Is chronic use of stimulant laxatives harmful to the colon? J Clin Gastroenterol. 2003 May-Jun;36(5):386-9.

I am an academic and clinical gastroenterologist, and clinical pharmacologist, in Christchurch and run the gastrointestinal motility service for most of the South Island, in which I see and treat many patients with constipation, often severe in nature. For 8 years from 2002-2010 I contributed to the BMJ Clinical Evidence Handbook, writing the section Constipation in Adults, with Prof Frank Frizelle, where we annually reviewed all evidence related to laxatives. I am submitting on behalf of the Department of Clinical Pharmacology at CDHB.
We are interested in the MARC response to the UK MHRA changes recommended for stimulant laxatives and in the evidence base for these recommendations. We have studied the MHRA report and would have to say that we find the report surprisingly superficial, especially with regard to the evidence of harm from stimulant laxatives. Any laxative that causes loose frequent stools carries risk of electrolyte disturbance and dehydration and so can cause indirect risk of organ damage or death, although this is very rare. However, this risk applies also to non-stimulant laxatives such as osmotic laxatives.
The MHRA report provides no evidence that stimulant laxatives are directly harmful long term. The report describes patients with gross overdose over many years with no harm. For the rare cases of fatality reported there is no evidence presented that this was due directly to the stimulant laxative and these patients were described as being on other medications or the stimulant laxative was part of a combination therapy with other substances. The denominator population from which these cases are drawn is large, the prevalence of chronic laxative use is reported to be 1-18% of adults (1).
In the past, it was hypothesised that chronic stimulant laxative use might result in disordered gut function with tolerance and cathartic colon in the most severe form. This was never proven and it is now believed that the natural history of the underlying constipation condition led to gradual worsening of constipation, despite being on stimulant laxatives, rather than because of the laxatives (2). Animal studies have clearly shown no evidence of neuromuscular toxicity from stimulant laxatives (3) and clinicians are now reassured and happier to use these laxatives long-term without concern for long-term toxicity or risk to the patient. More patients appear to die from severe constipation or the consequences of severe constipation than from stimulant laxatives.
I treat many patients with very severe constipation. My first line treatments are osmotic laxatives but there is a group of patients who cannot tolerate these medications or find them ineffective and they require chronic stimulant laxatives. And so the larger box size is entirely suitable for them and small supply quantities would be inconvenient for these patients. There is wide use of docusate and sennosides in the elderly without complications.
We agree there is a group of laxative-abusing patients who use laxatives inappropriately and sometimes in large quantities. We agree with the statement that laxatives are not effective for weight loss.
One useful clinical practice point here is, for patients who seem to need laxatives chronically, medical assessment is recommended to diagnose the cause of the constipation. Causes such as bowel cancer should be considered. Some causes of constipation can be managed without laxatives, with treatment options like diet change, ceasing constipating drugs, biofeedback for anismus and others.
In summary:
(1) There may be unforeseen inconvenience by reducing stimulant laxative pack size for those with a genuine reason to use stimulant laxatives longterm,
(2) We agree with the statement ‘does not help with weight loss’
(3) There is insufficient evidence for the statement ‘prolonged or excessive use can be harmful’, although the statement ‘excessive use can be harmful’ can be justified and is likely to be helpful. However, if this statement is to be added for stimulant laxatives, it would also need to be added to any other laxatives that cause frequent loose stools as the risk is the same, in the form of electrolyte disturbance and dehydration

A separate but related issue is that there are many complementary and alternative products sold as laxative treatments. These are heavily used by consumers and many contain sennosides and other active ingredients. Thought should be given to managing this risk also.
Following from the above, if stimulant laxatives are to be reclassified, an argument could easily be made to reclassify osmotic laxatives similarly, or indeed any laxative that resulted in frequent, loose motions.
References
1. Werth BL, Christopher SA. Laxative Use in the Community: A Literature Review. J Clin Med. 2021 Jan 4;10(1):143.
2. Müller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol. 2005 Jan;100(1):232-42.
3. Wald A. Is chronic use of stimulant laxatives harmful to the colon? J Clin Gastroenterol. 2003 May-Jun;36(5):386-9.

I'm not sure what conditions are being referred to in the question

As in previous sections:
Dear MARC
I am an academic and clinical gastroenterologist, and clinical pharmacologist, in Christchurch and run the gastrointestinal motility service for most of the South Island, in which I see and treat many patients with constipation, often severe in nature. For 8 years from 2002-2010 I contributed to the BMJ Clinical Evidence Handbook, writing the section Constipation in Adults, with Prof Frank Frizelle, where we annually reviewed all evidence related to laxatives. I am submitting on behalf of the Department of Clinical Pharmacology at CDHB.
We are interested in the MARC response to the UK MHRA changes recommended for stimulant laxatives and in the evidence base for these recommendations. We have studied the MHRA report and would have to say that we find the report surprisingly superficial, especially with regard to the evidence of harm from stimulant laxatives. Any laxative that causes loose frequent stools carries risk of electrolyte disturbance and dehydration and so can cause indirect risk of organ damage or death, although this is very rare. However, this risk applies also to non-stimulant laxatives such as osmotic laxatives.
The MHRA report provides no evidence that stimulant laxatives are directly harmful long term. The report describes patients with gross overdose over many years with no harm. For the rare cases of fatality reported there is no evidence presented that this was due directly to the stimulant laxative and these patients were described as being on other medications or the stimulant laxative was part of a combination therapy with other substances. The denominator population from which these cases are drawn is large, the prevalence of chronic laxative use is reported to be 1-18% of adults (1).
In the past, it was hypothesised that chronic stimulant laxative use might result in disordered gut function with tolerance and cathartic colon in the most severe form. This was never proven and it is now believed that the natural history of the underlying constipation condition led to gradual worsening of constipation, despite being on stimulant laxatives, rather than because of the laxatives (2). Animal studies have clearly shown no evidence of neuromuscular toxicity from stimulant laxatives (3) and clinicians are now reassured and happier to use these laxatives long-term without concern for long-term toxicity or risk to the patient. More patients appear to die from severe constipation or the consequences of severe constipation than from stimulant laxatives.
I treat many patients with very severe constipation. My first line treatments are osmotic laxatives but there is a group of patients who cannot tolerate these medications or find them ineffective and they require chronic stimulant laxatives. And so the larger box size is entirely suitable for them and small supply quantities would be inconvenient for these patients. There is wide use of docusate and sennosides in the elderly without complications.
We agree there is a group of laxative-abusing patients who use laxatives inappropriately and sometimes in large quantities. We agree with the statement that laxatives are not effective for weight loss.
One useful clinical practice point here is, for patients who seem to need laxatives chronically, medical assessment is recommended to diagnose the cause of the constipation. Causes such as bowel cancer should be considered. Some causes of constipation can be managed without laxatives, with treatment options like diet change, ceasing constipating drugs, biofeedback for anismus and others.
In summary:
(1) There may be unforeseen inconvenience by reducing stimulant laxative pack size for those with a genuine reason to use stimulant laxatives longterm,
(2) We agree with the statement ‘does not help with weight loss’
(3) There is insufficient evidence for the statement ‘prolonged or excessive use can be harmful’, although the statement ‘excessive use can be harmful’ can be justified and is likely to be helpful. However, if this statement is to be added for stimulant laxatives, it would also need to be added to any other laxatives that cause frequent loose stools as the risk is the same, in the form of electrolyte disturbance and dehydration

A separate but related issue is that there are many complementary and alternative products sold as laxative treatments. These are heavily used by consumers and many contain sennosides and other active ingredients. Thought should be given to managing this risk also.
Following from the above, if stimulant laxatives are to be reclassified, an argument could easily be made to reclassify osmotic laxatives similarly, or indeed any laxative that resulted in frequent, loose motions.
References
1. Werth BL, Christopher SA. Laxative Use in the Community: A Literature Review. J Clin Med. 2021 Jan 4;10(1):143.
2. Müller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol. 2005 Jan;100(1):232-42.
3. Wald A. Is chronic use of stimulant laxatives harmful to the colon? J Clin Gastroenterol. 2003 May-Jun;36(5):386-9.