Dulcolax Twelve Plus 5 mg Gastro-resistant Tablets (P)

For the short-term relief of occasional constipation.

Adults and children over 12 years: 1 to 2 coated tablets (5 - 10 mg) daily before bedtime.

Should not be used in children and adolescents under the age of 12 years.

It is recommended to start with the lowest dose. The dose may be adjusted up to the maximum recommended dose to produce regular stools.

The maximum daily dose should not be exceeded.

In the management of constipation, once regularity has been restarted dosage should be reduced and can usually be stopped.

Instructions for use

It is recommended to take the coated tablets at night to have a bowel movement the following morning. They should be swallowed whole with an adequate amount of fluid.

The coated tablets should not be taken together with products which reduce the acidity of the upper gastrointestinal tract, such as milk, antacids or proton pump inhibitors, in order not to prematurely dissolve the enteric coating.

No specific information on the use of this product in the elderly is available. Clinical trials have included patients over 65 years and no adverse reactions specific to this age group have been reported.

DULCOLAX is contraindicated in patients with ileus, intestinal obstruction, acute abdominal conditions including appendicitis, acute inflammatory bowel diseases, and severe abdominal pain associated with nausea and vomiting which may be indicative of the aforementioned severe conditions.

DULCOLAX is also contraindicated in severe dehydration and in patients with Known hypersensitivity to bisacodyl or any other component of the product.

In case of hereditary conditions that may be incompatible with an excipient of the product (please refer to “ Special warnings and special precautions for use” ) the use of the product is contraindicated.

Should not be used in children and adolescents under the age of 12 years.

As with all laxatives, bisacodyl should not be taken on a continuous daily basis for more than five days without investigating the cause of constipation.

Long-term everyday use of stimulant laxatives may harm the intestinal function and should be avoided. If laxatives are needed every day the cause of the constipation should be investigated. This product should only be used if a therapeutic effect cannot be achieved by a change of diet or the administration of bulk forming agents.

Prolonged excessive use may lead to fluid and electrolyte imbalance and hypokalaemia.

Intestinal loss of fluids can promote dehydration. Symptoms may include thirst and oliguria. In patients suffering from fluid loss where dehydration may be harmful (e.g. renal insufficiency, elderly patients) bisacodyl should be discontinued and only be restarted under medical supervision.

Stimulant laxatives (including bisacodyl) do not help with weight loss (see section 5.1 Pharmacodynamic properties).

Patients may experience haematochezia (blood in stool) that is generally mild and self-limiting.

If the symptoms worsen during the use of the medicinal product, a doctor or pharmacist should be consulted.

Dizziness and / or syncope have been reported in patients who have taken DULCOLAX. The details available for these cases suggest that the events would be consistent with defaecation syncope (or syncope attributable to straining at stool), or with a vasovagal response to abdominal pain related to the constipation, and not necessarily to the administration of bisacodyl itself.

There have been isolated reports of abdominal pain and bloody diarrhoea occurring after taking bisacodyl. Some cases have been shown to be associated with colonic mucosal ischaemia.

DULCOLAX Tablets contain a small amount of lactose (33.2 mg) and sucrose (23.4 mg) in each tablet. Patients with rare hereditary problems of fructose intolerance, galactose intolerance,total lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

The leaflet will state:

“ Before you take this medicine” section

Does this help with weight loss?

Stimulant laxatives (including bisacodyl) do not help with weight loss. They do not reduce the absorption of calories or nutrients. They can cause watery stools (diarrhoea), abdominal cramps and dehydration. Dehydration can seem like weight loss.

Overuse of laxatives may damage your health by:

• Causing disturbances of electrolyte and mineral balances. Sodium, potassium, magnesium, and phosphorus are electrolytes and minerals that are present in very specific amounts necessary for proper functioning of the nerves and muscles, including those of the colon and heart. Upsetting this delicate balance can cause incorrect functioning of these vital organs.

• Severe dehydration may cause tremors, weakness, blurry vision, fainting, kidney damage, and, in extreme cases, death. Dehydration often requires medical treatment.

• Overuse of laxatives must be avoided as it may harm the intestinal function.

The label will state:

Front of pack:

• Does not help with weight loss.

• Overuse can be harmful.

The concomitant use of antacids and milk products may reduce the resistance of the coating of the tablets and result in dyspepsia and gastric irritation.

The concomitant use of diuretics or adreno-corticosteroids may increase the risk of electrolyte imbalance if excessive doses of DULCOLAX are taken.

Electrolyte imbalance may lead to increased sensitivity to cardiac glycosides.

The concomitant use of other laxatives may enhance the gastrointestinal side effects of DULCOLAX.

Fertility

No studies on the effect on human fertility have been conducted.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Long experience has shown no evidence of undesirable or damaging effects during pregnancy.

Lactation

Clinical data show that neither the active moiety of bisacodyl (BHPM or bis- (p-hydroxyphenyl)-pyridyl-2-methane) nor its glucuronides are excreted into the milk of healthy lactating females.

Nevertheless, as with all medicines, DULCOLAX should not be taken in pregnancy, especially the first trimester, and during breast feeding unless the expected benefit is thought to outweigh any possible risk and only on medical advice.

No studies on the effects of DULCOLAX on the ability to drive and use machines have been performed.

However, patients should be advised that due to a vasovagal response (e.g. to abdominal spasm) they may experience dizziness and / or syncope. If patients experience abdominal spasm they should avoid potentially hazardous tasks such as driving or operating machinery.

The most commonly reported adverse reactions during treatment are abdominal pain and diarrhoea.

Adverse events have been ranked under headings of frequency using the following convention: Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10000, <1/1000); very rare (<1/10000).

Immune system disorders

Rare: anaphylactic reactions, angioedema, hypersensitivity.

Metabolism and nutrition disorders

Rare: dehydration.

Nervous system disorders

Uncommon: dizziness.

Rare: Syncope.

Dizziness and syncope occurring after taking bisacodyl appear to be consistent with a vasovagal response (e.g. to abdominal spasm, defaecation).

Gastrointestinal disorders

Uncommon: haematochezia (blood in stool), vomiting, abdominal discomfort, anorectal discomfort.

Common: abdominal cramps, abdominal pain, diarrhoea and nausea.

Rare: colitis including ischaemic colitis.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms

If high doses are taken watery stools (diarrhoea), abdominal cramps and a clinically significant loss of fluid, potassium and other electrolytes can occur.

Laxatives when taken in chronic overdose may cause chronic diarrhoea, abdominal pain, hypokalaemia, secondary hyperaldosteronism and renal calculi. Renal tubular damage, metabolic alkalosis and muscle weakness secondary to hypokalaemia have also been described in association with chronic laxative abuse.

Therapy

After ingestion of oral forms of DULCOLAX, absorption can be minimised or prevented by inducing vomiting or gastric lavage. Replacement of fluids and correction of electrolyte imbalance may be required. This is especially important in the elderly and the young. Administration of antispasmodics may be of value.

ATC code: A06AB02

Bisacodyl is a locally acting laxative from the diphenylmethane derivatives group having a dual action. As a contact laxative, for which also antiresorptive hydragogue effects have been described, bisacodyl stimulates after hydrolysis in the large intestine, the mucosa of both the large intestine and of the rectum. Stimulation of the mucosa of the large intestine results in colonic peristalsis with promotion of accumulation of water, and consequently electrolytes, in the colonic lumen. This results in a stimulation of defecation, reduction of transit time and softening of the stool. Bisacodyl showed improvements in constipation-related symptoms like straining, stool consistency, abdominal discomfort and bloating compared with placebo, based on patient self-assessment questionary. Normalization of evacuatory function by bisacodyl treatment was accompanied by a relative normalization of the microflora.

The results of two-phase IV clinical trials with a total of 29 patients treated by low dose (5mg) of bisacodyl indicate that the transit through the colon, assessed through MRI, is promoted by stimulating propulsive colon motor activity with bisacodyl. In addition, repeated doses of bisacodyl 5mg during three consecutive days showed an increase in the water content in the gut. These trials demonstrated that there was no change in the underlying physiology which showed to return to baseline values 24 hours after ceasing treatment with bisacodyl.

Stimulation of the rectum causes increased motility and a feeling of rectal fullness. The rectal effect may help to restore the "call to stool" although its clinical relevance remains to be established.

As a laxative that acts on the colon, bisacodyl specifically stimulates the physiological natural evacuation process in the lower region of the gastrointestinal tract. Because its main effect is on the distal part of the gut, bisacodyl is ineffective in altering the digestion or absorption of calories or essential nutrients in the small intestine.

Following either oral or rectal administration, bisacodyl is rapidly hydrolyzed to the active principle bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), mainly by esterases of the enteric mucosa.

Administration as an enteric coated tablet was found to result in maximum BHPM plasma concentrations between 4 – 10 hours post administration whereas the laxative effect occurred between 6 – 12 hours post administration. In contrast, following the administration as a suppository, the laxative effect occurred on average approximately 20 minutes post administration; in some cases it occurred 45 minutes after administration. The maximum BHPM-plasma concentrations were achieved 0.5 – 3 hours following the administration as a suppository. Hence, the laxative effect of bisacodyl does not correlate with the plasma level of BHPM. Instead, BHPM acts locally in the lower part of the intestine and there is no relationship between the laxative effect and plasma levels of the active moiety. For this reason, bisacodyl coated tablets are formulated to be resistant to gastric and small intestinal juice. This results in a main release of the drug in the colon, which is the desired site of action.

After oral and rectal administration, only small amounts of the drug are absorbed and are almost completely conjugated in the intestinal wall and the liver to form the inactive BHPM glucuronide. The plasma elimination half-life of BHPM glucuronide was estimated to be approximately 16.5 hours. Following the administration of bisacodyl coated tablets, an average of 51.8% of the dose was recovered in the faeces as free BHPM and an average of 10.5% of the dose was recovered in the urine as BHPM glucuronide. Following the administration as a suppository, an average of 3.1% of the dose was recovered as BHPM glucuronide in the urine. Stool contained large amounts of BHPM (90% of the total excretion) in addition to small amounts of unchanged bisacodyl.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Tablet core:

Lactose

Maize starch

Soluble maize starch

Glycerol

Magnesium stearate

Tablet coating:

Magnesium stearate

Sucrose

Talc

Acacia

Titanium dioxide (E171)

Methacrylic acid-methylmethacrylate copolymer (1:1)

Methacrylic acid-methylmethacrylate copolymer (1:2)

Castor oil

Macrogol 6000

Yellow iron oxide (E172)

White beeswax

Carnauba wax

Shellac.

None stated.

3 years

Do not store above 25° C.

Keep container in the outer carton.

Blister packs consisting of opaque white PVC/PVDC blister foil and aluminium foil (covering foil). Pack sizes 20, 40, 60, 80 and 100.

Blister packs consisting of colourless PVC blister foil and aluminium foil (covering foil). Pack sizes 20, 40, 60, 80, and 100.

Not all pack sizes may be marketed.

None stated.