Senna

Publication Details

OVERVIEW

Introduction

Senna (Cassia species) is a popular herbal laxative that is available without prescription. Senna is generally safe and well tolerated, but can cause adverse events including clinically apparent liver injury when used in high doses for longer than recommended periods.

Background

Senna (sen’ a) belongs to a large genus of flowering plants found throughout the tropics, commonly used species being Cassia acutifolia (Alexandrian senna) and C. angustifolio (Indian or Tinnevelly senna). Extracts of the leaves, flowers and fruit of senna have been used for centuries in folk medicine as a laxative and stimulant. Senna is also included in several herbal teas, used for purging and in weight loss. The active components in senna extracts are anthraquinone derivatives and their glucosides, referred to as senna glycosides or sennosides. The sennosides are not absorbed but are hydrolyzed by colonic bacteria releasing the active moieties, rhein and rhein-anthrone which appear to act as local irritants on the colon, promoting peristalsis and evacuation. Sennosides and their metabolites may also enhance intestinal fluid accumulation and increase the moisture content of stool by inhibiting electrolyte and water reabsorption and increasing chloride secretion from the colon. Senna is minimally absorbed. Senna is used in many over-the-counter laxatives in combination with other agents under trade names such as Ex-lax, Fletcher’s Castoria and Senokot. The typical dose is 15 to 30 mg of sennosides twice a day, but is recommended for short term use only (less than one week). Side effects include abdominal cramps and electrolyte imbalance. Long term use or abuse can lead to “cathartic” colon with diarrhea, cramps, weight loss and darkened pigmentation of the colonic mucosa.

Hepatotoxicity

Use of senna in the recommended doses for a limited period of time has been associated with few side effects, most of which are mild and transient and related to its laxative action. With longer term and higher dose use of senna, however, adverse events have been described including several cases of clinically apparent liver injury. The time to onset of liver injury was usually after 3 to 5 months of use, and the pattern of serum enzyme elevations was hepatocellular. The liver injury was usually mild-to-moderate in severity and resolved rapidly with discontinuation. In at least one instance, reexposure led to rapid recurrence of liver injury. Immunoallergic features and autoimmune markers were not present in the published cases.

In addition, a related plant commonly known as coffee senna or Cassia orientalis has been linked to many instances of acute, severe toxicity with encephalopathy, myopathy and hepatic dysfunction. Outbreaks of “hepato-myo-encephopathy” of unknown cause among children occurred yearly in Uttar Pradesh, India typically between September and November. Investigation eventually identified Cassia occidentalis ingestion as the probable cause, typically occurring in children who eat the leaves or pods of the common flowering weed. While Cassia occidentalis has also been used to prepare tea, the amount ingested was minimal. In children, and rarely in adults, the presentation was precipitous with nausea, vomiting, tremor, abnormal and violent behavior, grimacing and self-mutilation followed by stupor and coma at which time serum aminotransferase and bilirubin levels were typically elevated. In severe instances, the liver injury was progressive, serum ammonia and INR levels rose and patients developed coma, convulsions and status epilepticus that was unresponsive to therapy. Autopsies revealed hepatic necrosis and cholestasis. A similar pattern of symptoms and injury occurs in animals that consume Cassia occidentalis. Whether this syndrome has a similar pathogenesis to the rare instance of hepatic injury attributed to typical senna (Cassia acutifolia or angustifolio) that is used as a laxative is unknown.

Likelihood score: D (possible rare cause of clinically apparent liver injury).

Mechanism of Injury

The liver injury due to senna has been attributed to the anthraquinone derivatives present in the herbal extract, and most cases have been associated with taking excessive doses suggesting a direct hepatotoxic rather than idiosyncratic etiology. Other anthraquinones used to treat constipation have been implicated in causing liver injury with long term use, including cascarosides (cascara) and hydroxyanthraquinone.

Outcome and Management

Liver injury from long term senna use is rare, and most cases have been self-limited and rapidly reversible upon stopping the laxative. However, cases with a severe course with signs of acute liver failure have been described. There is no evidence of cross sensitivity to hepatic damage with other laxatives. Restarting senna after hepatotoxicity has been associated with recurrence of liver injury and should be avoided.

Drug Class: Herbal and Dietary Supplements

Other Drugs in the Subclass, Anthraquinones: Cascara

CASE REPORT

Case 1. Acute liver injury due to Senna [Cassia angustifolia].(1)

A 52 year old woman was developed anorexia and progressive weakness followed by confusion and jaundice, having used large amounts of tea prepared from dry senna products to treat chronic constipation for several years. On presentation she was confused, weak and mildly jaundiced. Blood testing revealed serum glucose of 40 mg/dL, bilirubin 6.2 mg/dL, ALT 9160 U/L, AST 6640 U/L, GGT 160 U/L and INR 5.7. She also had lactic acidosis and renal insufficiency. She was admitted to the intensive care unit and soon required ventilation. Her coagulopathy worsened and she developed polyuria and phosphate wasting. She received intensive support and after several days began to improve. She was discharged after a 3 week hospitalization and, when seen one month later, was asymptomatic and all laboratory tests had returned to normal. Tests for hepatitis A, B and C, for autoantibodies and for acetaminophen levels were not reported. The botanicals used for making tea were analyzed and found to represent Cassia angustifolio without metal or other contaminants.

Key Points

Laboratory Values

Comment

The sudden onset of hepatic failure, lactic acidosis and encephalopathy is characteristic of acute hepatic necrosis due to a direct toxin. In this instance, the patient had been taking an excessive about of senna over a prolonged period, and it was not clear what precipitated this acute decompensation. Possible explanations are that it was triggered by a coincidental infection or dehydration or a change in the formulation of the Senna product. The general features of this clinical case report resemble those of hepato-myo-encephalopathy described from India in children who consume the pods or fruit of Cassia occidentalis. Conventional senna used as a laxative is quite safe, but these reports suggest that an overdose can cause acute hepatic failure with early signs of encephalopathy.

Case 2. Acute liver injury due to coffee senna [Cassia occidentalis].(2)

A 75 year old woman developed nausea, vomiting, diarrhea and low grade fever after medicating herself for two weeks with leaves of Senna occidentalis. She was seen at a local hospital and found to have a mildly elevated white blood cell count (12,000) with 80% neutrophils but normal serum bilirubin, ALT and alkaline phosphatase (Table). She was sent home but continued to worsen, developing confusion and jaundice and was admitted to a tertiary referral center 2 days later with stupor, deep jaundice and anasarca. Blood testing showed a serum bilirubin of 12.9 mg/dL (direct 10.4), ALT 130 U/L, Alk P 43 U/L, INR 2.68 and ammonia 127 µmol/L. Ultrasound revealed a normal sized liver and spleen and mild ascites. A lumbar puncture was normal. Tests for hepatitis A, B, C and E were negative. She was intubated and given antibiotics and fresh frozen plasma. She continued to deteriorate and developed coma, seizures, status epilepticus and died 2 days later, 5 days after her initial presentation.

Key Points

Laboratory Values

Comment

The sudden onset of nausea, vomiting and diarrhea followed shortly after by confusion, stupor and jaundice is typical of the syndrome of “hepato-myo-encephalopathy” described from India among children who consumed the fruit or pods of the common local weed Cassia occidentalis (coffee senna). This case was unusual in that it occurred in an adult and was not due to acute consumption but to several weeks of intake of the botanical as pain relief from chronic knee osteoarthritis. The liver injury is typical of acute hepatic necrosis or hyperacute liver failure with early signs of hepatic failure even when the bilirubin is normal or only mildly elevated. Hyperammonemia and coagulopathy arise early. This syndrome also has prominent neurologic signs and deaths are often due to encephalopathy rather than hepatic failure. The syndrome is not always fatal and, in some cases, intensive medical support appears to tide patients over the acute toxic effects. Recovery is rapid and seemingly complete. At issue is whether this syndrome is similar or related to the cases of acute liver injury that have been attributed to other Senna species such as Cassia angustifolia or acutifolia, which are used to produce the laxative commonly referred to as Senna (see Case 1).

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Senna – Generic

DRUG CLASS

Herbal and Dietary Supplements

SUMMARY INFORMATION

Fact Sheet at MedlinePlus, NLM

CHEMICAL FORMULA AND STRUCTURE

CITED REFERENCES

1.
Beuers U, Spengler U, Pape GR. Hepatitis after chronic abuse of senna. Lancet. 1991;337:372–3. [PubMed: 1671276]
2.
Ish P, Rathi S, Singh H, Anuradha S. Senna Occidentalis poisoning: an uncommon cause of liver failure. ACG Case Rep J. 2019;6:e00035. [PMC free article: PMC6658039] [PubMed: 31616727]

ANNOTATED BIBLIOGRAPHY

References updated: 01 April 2020

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  • Izzy M, Malieckal A, Little E, Anand S. Review of efficacy and safety of laxatives use in geriatrics. World J Gastrointest Pharmacol Ther. 2016;7:334–42. [PMC free article: PMC4848256] [PubMed: 27158549]
    (Systematic review of 9 randomized controlled trials of laxatives in geriatric patients suggested that senna was the preferred agent in the elderly in regards to efficacy and safety; no mention of hepatotoxicity or restriction in the duration of therapy).
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    (Listing of published cases of liver injury from HDS products, but does not list or mention cases attributed to senna).
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    (Description of an online compendium of cases of liver toxicity attributed to HDS products, lists 4 reports of liver injury attributed to senna).
  • Vega M, Verma M, Beswick D, Bey S, Hossack J, Merriman N, Shah A, et al. Drug Induced Liver Injury Network (DILIN). The incidence of drug- and herbal and dietary supplement-induced liver injury: preliminary findings from gastroenterologist-based surveillance in the population of the State of Delaware. Drug Saf. 2017;40:783–7. [PMC free article: PMC5699929] [PubMed: 28555362]
    (A prospective, population based registry of cases of drug induced liver injury occurring in Delaware during 2014, identified 20 cases [2.7 per 100,000] overall, including 6 due to HDS products, all of which were proprietary multiingredient products, none specifically listing senna as a component).
  • Alsalimy N, Madi L, Awaisu A. Efficacy and safety of laxatives for chronic constipation in long-term care settings: A systematic review. J Clin Pharm Ther. 2018;43:595–605. [PubMed: 29885259]
    (Systematic review of 7 controlled trials of laxatives in 444 adults with chronic constipation found all agents equally effective and with no serious adverse events, common side effects being gastrointestinal discomfort, flatulence and diarrhea).
  • Vilanova-Sanchez A, Gasior AC, Toocheck N, Weaver L, Wood RJ, Reck CA, Wagner A, et al. Are Senna based laxatives safe when used as long term treatment for constipation in children? J Pediatr Surg. 2018;53:722–7. [PubMed: 29429768]
    (Among 640 children with chronic constipation treated with senna long term, 16 had side effects, most commonly abdominal pain and cramps or diarrhea, typically during the first few weeks of treatment, resolving spontaneously or with changing laxatives; 2% of children developed perineal rash or blisters, all with diarrhea and diaper use due to exposure to stool; no instances of liver injury reported).
  • Chhapola V, Kanwal SK, Sharma AG, Kumar V. Hepatomyoencephalopathy secondary to Cassia occidentalis poisoning: report of three cases from North India. Indian J Crit Care Med. 2018;22:454–6. [PMC free article: PMC6020631] [PubMed: 29962748]
    (Clinical course of 3 children with hepatomyoencephalopathy due to ingestion of Cassia Occidentalis seeds with fever, vomiting and stupor [bilirubin 2.8 to 5.1 mg/dL, ALT 1749 to 3310 U/L, Alk P 369 to 1331 U/L, INR 1.74 to 3.95], all receiving supportive care and surviving, but all 3 had a sibling who had recently died of a similar syndrome at home).
  • Ish P, Rathi S, Singh H, Anuradha S. Senna Occidentalis poisoning: an uncommon cause of liver failure. ACG Case Rep J. 2019;6:e00035. [PMC free article: PMC6658039] [PubMed: 31616727]
    (75 year old woman developed liver injury after 2 weeks of self-medication with Cassia occidentalis for osteoarthritis [bilirubin 0.8 rising to 18.7 mg/dL, ALT 42 rising to 542 U/L, Alk P 105 rising to 184 U/L, ammonia 127 µg/L, INR 1.28], dying of intractable status epilepticus and liver biopsy showing massive necrosis [Case 2]).