Herb-Drug Interactions: Senna

2011

Cassia senna L, Cassia angustifolia Vahl. (Fabaceae)

Synonym(s) and related species

Indian senna.

Cassia acutifolia Delile, Senna alexandrina Mill.

Senna obtained from Cassia senna is also known as Alexandrian senna or Khartoum senna, and senna obtained from Cassia angustifolia is also known as Tinnevelly senna.

Pharmacopoeias

Alexandrian Senna Fruit (British Ph 2009); Senna Fluid Extract (US Ph 32); Senna Leaf (British Ph 2009, European Ph 2008, US Ph 32); Senna Liquid Extract (British Ph 2009); Senna Oral Solution (US Ph 32); Senna Pods (US Ph 32); Senna Pods, Alexandrian (European Ph 2008); Senna Pods, Tinnevelly (European Ph 2008); Senna Tablets (British Ph 2009); Sennosides (US Ph 32); Standardised Senna Granules (British Ph 2009); Standardised Senna Leaf Dry Extract (British Ph 2009, European Ph 2008); Tinnevelly Senna Fruit (British Pharmacopoeia 2009).

Constituents

Anthraquinone glycosides are major components of senna. In the leaf the anthraquinones include sennosides A, B, C and D, and palmidin A, rhein anthrone and aloe-emodin glycosides. The fruit contains sennosides A and B and a closely related glycoside, sennoside Al. Senna is usually standardised to the content of sennosides, generally calculated as sennoside B.

Senna also contains naphthalene glycosides in the leaves and pods, mucilage (arabinose, galactose, galacturonic acid) and various other constituents such as flavonoids, volatile oil and resins.

Use and indications

Senna leaf or fruit is used as a laxative.

Pharmacokinetics

For information on the pharmacokinetics of an anthraquinone glycoside present in senna, see under aloes.

Interactions overview

Although senna has been predicted to interact with a number of drugs that lower potassium (such as the corticosteroids and potassium-depleting diuretics), or drugs where the effects become potentially harmful when potassium is lowered (such as digoxin), there appears to be little or no direct evidence that this occurs in practice. Senna may slightly reduce quinidine levels.

Senna + Corticosteroids

Theoretically, the risk of hypokalaemia might be increased in patients taking corticosteroids, who also regularly use, or abuse, anthraquinone-containing substances such as senna.

Clinical evidence

Chronic diarrhoea as a result of long-term use, or abuse, of stimulant laxatives such as senna can cause excessive water and potassium loss; one paper (cited as an example) describes a number of cases of this. Systemic corticosteroids with mineralocorticoid effects can cause water retention and potassium loss. The effect of senna over-use combined with systemic corticosteroids is not known, but, theoretically at least, the risk of hypokalaemia might be increased. Although this is mentioned in some reviews on herbal interactionsthere do not appear to be any case reports of such an interaction.

It has also been suggested that senna, by increasing gastrointestinal transit times, might theoretically reduce the absorption of oral corticosteroids. However, there appears to be no published clinical data suggesting that that the absorption of corticosteroids is affected by senna or other drugs that alter gastrointestinal transit time, such as metoclopramide or loperamide.

Experimental evidence

No relevant data found.

Mechanism

In theory the additive loss of potassium caused by anthraquinone-containing substances and systemic corticosteroids may result in hypokalaemia.

Importance and management

The interaction between senna and corticosteroids is theoretical, but be aware of the potential in patients who regularly use, or abuse, anthraquinone-containing substances such as senna. However, note that, if anthraquinone laxatives are used as recommended (at a dose producing a comfortable soft-formed motion), then this interaction would not be expected to be clinically relevant.

Senna + Digitalis glycosides

Theoretically, digitalis toxicity could develop if patients regularly use, or abuse, anthraquinone-containing substances such as

Clinical evidence

For the risk of digitalis toxicity including cardiac arrhythmias because of hypokalaemia induced by abuse of anthraquinone laxatives, see Aloes + Digitalis glycosides. For mention of a case of digoxin toxicity and mild hypokalaemia in a patient taking digoxin and furosemide, who started to take a laxative containing rhubarb and liquorice, see Liquorice + Digitalis glycosides.

Experimental evidence

The effects of anthraquinones found in senna (rhein 100 micromoles, danthron 100 micromoles, sennidins A and B, sennosides A and B), and senna leaf infusion (senna tea) 10 mg/mL, on the absorption of digoxin was examined in human cell lines. Rhein and danthron decreased the absorptive permeability of digoxin, whereas the other anthraquinones and the senna leaf infusion had no effect.

Mechanism

Little understood. Digoxin is a substrate of P-glycoprotein, a drug transporter protein, and it is thought that the relatively small molecular size of rhein and danthron alters the fluidity of the apical membrane and interferes with the action of P-glycoprotein.

Importance and management

Determining the clinical relevance of the in vitro absorption study results is difficult. The authors suggest that an effect of anthraquinone-containing laxatives on the absorption of poorly permeable drugs such as digoxin cannot be excluded. More study is required before any clinical recommendations can be made.

Senna + Diuretics; Potassium-depleting

Theoretically, patients taking potassium-depleting diuretics could experience excessive potassium loss if they also regularly use, or abuse, anthraquinone-containing substances such as senna.

Clinical evidence

For information on the additive risk of hypokalaemia with the use of potassium-depleting diuretics and abuse of anthraquinone-containing laxatives. See Aloes + Diuretics; Potassium-depleting.

Experimental evidence

The effects of the anthraquinones found in senna (rhein, danthron, sennidins A and B, sennosides A and B), and senna leaf infusion (senna tea), on the absorption of furosemide 100 micromoles, a poorly permeable drug, was examined in human cell lines. Rhein and danthron increased the absorptive permeability of furosemide by about 3.6- and 3-fold, respectively. Furosemide permeability was reduced by more than a third by the sennidins and sennosides, but senna leaf infusion had little effect.

Mechanism

Little understood. The changes in furosemide absorptive permeability may be caused by interference with P-glycoprotein or other transporter proteins.

Importance and management

Determining the clinical relevance of the in vitro absorption results is difficult. The authors suggest that an effect of anthraquinone-containing laxatives on the absorption of poorly permeable drugs such as furosemide cannot be excluded. More study is required before any clinical recommendations can be made.

Senna + Estradiol

Senna does not appear to affect the pharmacokinetics of estradiol.

Clinical evidence

In a clinical study in 19 women, the maximum daily tolerated dose of senna tablets (Senokot) was taken for 10 to 12 days with a single 1.5-mg dose of estradiol glucuronide given 4 days before the end of the assessment period. Senna had no significant effect on the median AUC of estradiol or estrone.

Experimental evidence

No relevant data found.

Mechanism

It was thought that reducing intestinal transit time with senna might lead to reduced blood levels of estradiol.

Importance and management

Limited evidence suggests that there is unlikely to be a clinically relevant pharmacokinetic interaction between anthraquinone-containing laxatives and estradiol.

Senna + Food

No interactions found.

Senna + Herbal medicines; Liquorice

Consider Liquorice + Laxatives, for the potential additive effects of anthraquinone-containing laxatives and liquorice.

Senna + Ketoprofen

The interaction between senna and ketoprofen is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

The effects of the anthraquinones found in senna (rhein, danthron, sennidins A and B, sennosides A and B), and senna leaf infusion (senna tea), on the absorption of ketoprofen 100 micromoles was examined in human cell lines. Danthron reduced the absorptive permeability of ketoprofen by almost 30% and the senna leaf infusion enhanced ketoprofen permeability by about 1.5-fold.

Mechanism

Little understood. The reduction in absorptive permeability of ketoprofen caused by danthron may be due to reduced ATP production in the cells. The enhanced permeability caused by senna leaf infusion is more difficult to explain because of the many different active compounds contained within the extract.

Importance and management

Evidence is sparse, but what is known suggests that the use of anthraquinone-containing laxatives is unlikely to affect the intestinal permeability of ketoprofen.

Senna + Paracetamol (Acetaminophen)

The information regarding the use of senna with paracetamol is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

The effects of the anthraquinones found in senna (rhein, danthron, sennidins A and B, sennosides A and B), and senna leaf infusion (senna tea), on the absorption of paracetamol 100 micromoles was examined in human cell lines. The in vitro absorption of highly permeable drugs such as paracetamol was not significantly altered.

Mechanism

No mechanism expected.

Importance and management

Evidence is sparse, but what is known suggests that the use of anthraquinone-containing laxatives is unlikely to affect the intestinal permeability of paracetamol (acetaminophen).

Senna + Propranolol

The information regarding the use of senna with propranolol is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

The effects of the anthraquinones found in senna (rhein, danthron, sennidins A and B, sennosides A and B), and senna leaf infusion (senna tea), on the absorption of propranolol 100 micromoles, was examined in human cell lines. The in vitro absorption of highly permeable drugs such as propranolol was not significantly altered.

Mechanism

No mechanism expected.

Importance and management

Evidence is sparse, but what is known suggests that the use of anthraquinone-containing laxatives seems unlikely to affect the intestinal permeability of propranolol.

Senna + Quinidine

Quinidine plasma levels can be reduced by the anthraquinone-containing laxative senna.

Clinical evidence

In a study in 7 patients with cardiac arrhythmias taking sustained-release quinidine bisulfite 500 mg every 12 hours, senna reduced plasma quinidine levels, measured 12 hours after the last dose of quinidine, by about 25%.

Experimental evidence

No relevant data found.

Mechanism

Not understood.

Importance and management

The modest reduction in quinidine levels might be of clinical importance in patients whose plasma levels are barely adequate to control their arrhythmia.

Senna + Verapamil

The information regarding the use of senna with verapamil is based on experimental evidence only.

Clinical evidence

No interactions found.

Experimental evidence

The effects of the anthraqumones found in senna (rhein, danthron, sennidins A and B, sennosides A and B), and senna leaf infusion (senna tea), on the absorption of verapamil 100 micromoles was examined in human cell lines. The in vitro absorption of highly permeable drugs such as verapamil was not significantly altered.

Mechanism

No mechanism expected.

Importance and management

Evidence is sparse, but what is known suggests that the use of anthraquinone-containing laxatives seems unlikely to affect the intestinal permeability of verapamil.