Consumer medicine information

APO-Mebeverine

Mebeverine hydrochloride

BRAND INFORMATION

Brand name

APO-Mebeverine

Active ingredient

Mebeverine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Mebeverine.

What is in this leaflet

This leaflet answers some common questions about mebeverine. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What this medicine is used for

Mebeverine is used to relieve the symptoms of irritable bowel syndrome. It belongs to a group of medicines called antispasmodic agents.

How it works

Mebeverine works by relaxing the muscles in the gut, thereby relieving the symptoms of irritable bowel syndrome.

Ask your doctor if you have any questions about why it has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor's prescription.

This medicine is not addictive.

There is not enough information to recommend the use of this medicine in children.

Before you take this medicine

When you must not take it

Do not take this medicine if you have an allergy to:

  • mebeverine
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty in breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take this medicine after the expiry date printed on the pack or if the packaging is damaged or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have any allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • angina or other heart conditions
  • liver problems
  • kidney problems
  • lactose intolerance

Tell your doctor if you are pregnant, intend to become pregnant, or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start taking mebeverine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food store.

How to take this medicine

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

The usual dose is one tablet taken three times a day.

How to take it

Swallow the tablets whole with a glass of water.

When to take it

Take this medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

It does not matter if you take this medicine before or after food.

How long to take it

Continue taking your medicine for as long as your doctor tells you. It is important to keep taking your medicine even if you feel well.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) or go to Accident and Emergency at your nearest hospital, if you think you or anyone else may have taken too much mebeverine. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using this medicine

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking mebeverine.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you become pregnant while you are taking this medicine, tell your doctor immediately.

Things you must not do

Do not use this medicine to treat any other complaints unless your doctor or pharmacist tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Do not stop taking mebeverine, or change the dosage, without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how mebeverine affects you.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking mebeverine. Mebeverine helps most people with irritable bowel syndrome, but it may have unwanted side effects in a few people. All medicines have some unwanted side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side- effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • indigestion or heartburn
  • constipation
  • dizziness
  • headache
  • tiredness
  • difficulty sleeping
  • loss of appetite

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • swelling of the face, lips or tongue, difficulty swallowing or breathing (signs of an allergic reaction)

The above list includes very serious side effects that may need urgent medical attention. These side effects are rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may occur in some people.

Storage and Disposal

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack, they may not keep well.

Keep the medicine in a cool, dry place where the temperature stays below 25°C.

Do not store it or any other medicine in the bathroom, near a sink, or on a windowsill. Do not leave it in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and- a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

White, round biconvex film coated tablets and plain on both sides.

Available in boxes of 10, 30 and 90 tablets. AUST R 288817

Ingredients

Each tablet contains 135 mg of mebeverine hydrochloride as the active ingredient.

It also contains the following:

  • microcrystalline cellulose
  • lactose monohydrate
  • sodium starch glycolate type A
  • povidone
  • purified talc
  • magnesium stearate
  • OPADRY complete film coating system 03F58763 WHITE

This medicine contains sugars as lactose.

This medicine does not contain gluten.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113
Australia

This leaflet was prepared in September 2021.

Published by MIMS November 2021

BRAND INFORMATION

Brand name

APO-Mebeverine

Active ingredient

Mebeverine hydrochloride

Schedule

S4

 

1 Name of Medicine

Mebeverine hydrochloride.

2 Qualitative and Quantitative Composition

Each APO-Mebeverine tablet contains mebeverine hydrochloride 135 mg.

Excipients with known effect.

Contains sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO-Mebeverine tablets are white, round, biconvex, film coated and plain on both sides.

4 Clinical Particulars

4.1 Therapeutic Indications

APO-Mebeverine tablets are indicated in the management of the irritable bowel syndrome ('irritable colon', 'spastic colon', 'functional bowel disorders', 'spastic constipation', 'nervous diarrhoea'). APO-Mebeverine is used to treat the symptoms of this condition - i.e. abdominal pain and cramps, persistent, non-specific diarrhoea (with or without alternating constipation) and flatulence.

4.2 Dose and Method of Administration

The recommended adult dose is one APO-Mebeverine, mebeverine hydrochloride 135 mg (1 tablet) three times daily, preferably before or with food. In case one or more doses are missed, the patient should continue with the next dose as prescribed, the missed doses are not to be taken in addition to the regular dose.
After a period of several weeks when the desired effect has been obtained, the dosage may be gradually reduced.

4.3 Contraindications

Hypersensitivity to any component of the product.

4.4 Special Warnings and Precautions for Use

Although not reported, APO-Mebeverine tablets should be used with caution in patients with the following conditions on the basis of potential clinical significance: cardiac dysrhythmia; in particular patients with partial or complete atrioventricular heart block, and/or angina or severe ischaemic heart disease.

Pharmaceutical precaution.

APO-Mebeverine tablets contain lactose monohydrate and consideration should be given to patients with a potential diagnosis of lactose intolerance simulating irritable bowel syndrome. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use in hepatic impairment.

Hepatic dysfunction i.e. patients with advanced liver disease e.g. cirrhosis (because of metabolic pathway). Liver function tests may be indicated if patient develops gastrointestinal symptoms or jaundice suggesting hepatic sensitivity.

Use in renal impairment.

Advanced renal disease (because of excretory pathway).

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No data available.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B2)
Safe use in pregnancy has not been established relative to adverse effects on foetal development. Therefore, APO-Mebeverine tablets are not recommended during the first trimester of pregnancy, and otherwise risk-benefit must be considered in its use in pregnant women.
 Mebeverine is secreted in breast milk (< 10 microgram/mL following an oral dose of 100 mg mebeverine hydrochloride). Although problems have not been documented, as a general rule APO-Mebeverine tablets should not be given to a woman who is breast feeding unless the anticipated benefits outweigh possible risks.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Because of the low incidence of adverse drug effects reported a meaningful estimate of adverse reactions is difficult to obtain.
The following side effects have been reported in clinical studies: indigestion, heartburn, dizziness, insomnia, anorexia, headache, decrease in pulse rate, constipation, general malaise.
In very rare cases allergic reactions have been reported, in particular hypersensitivity, urticaria, angioedema, face oedema and exanthem.
Adverse effects reported during post-marketing use have been consistent with those reported in clinical studies, with the following additional side effect reported:

Immune system disorders.

Hypersensitivity (anaphylactic reactions).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

On theoretical grounds, it may be predicted that CNS excitability might occur in cases of overdosage. Observed symptoms of overdose have included those of neurological and cardiovascular nature.
No specific information is available on the treatment of overdosage of mebeverine hydrochloride and no specific antidote is available. Therapy with APO-Mebeverine tablets should be discontinued, and the patients vital functions monitored closely. Treatment is symptomatic and supportive.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Category: Antispasmodic; smooth muscle relaxant.

Mechanism of action.

Mebeverine has a direct non-specific relaxant effect on vascular, cardiac, and other smooth muscle. Studies indicate that the spasmolytic activity of mebeverine is not restricted to one particular system, but the compound possesses a polyvalent spasmolytic action in which at least three types of mechanisms are involved:
a direct musculotropic action involving calcium ion exchange and stabilization of excitable membranes;
a competitive antimuscarinic activity of about 0.05 - 0.1 times that of atropine;
a local anaesthetic activity together with potentiation of sympathetic inhibitory influences due to blockade of noradrenaline uptake into sympathetic nerve endings.
In in vitro studies mebeverine hydrochloride has been shown to have a papaverine-like spasmolytic effect on the smooth muscle of the ileum, uterus and the gall bladder. It possesses a strong local anaesthetic activity.
When tested in vivo in various species, mebeverine hydrochloride was found to be three to five times more powerful than papaverine in blocking spasm of smooth muscle and in relieving the carbachol-induced spasm of the sphincter of Oddi in rabbits, mebeverine hydrochloride proved to be twenty times more active than papaverine. In vivo studies also demonstrate that mebeverine has only minor effects on normal intestinal peristalsis but possesses spasmolytic activity when hypermotility is induced. The spasmolytic activity is found in all parts of the gastrointestinal tract and in some experiments has been found to be more active on colonic smooth muscle.
Studies with mebeverine hydrochloride 100 mg tablets indicate that mebeverine is free of central anticholinergic effects, and practically free of peripheral effects with an activity of less than 0.001 times that of atropine. Mebeverine does not show central depressant or analgesic effects, and only in high doses are some central stimulating effects observed. No ganglion blocking or interference with neuromuscular transmission occurs.
Mebeverine injected intravenously in animals produces transient cardiac arrhythmias, bradycardia and ECG changes.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration of 3H and 14C labelled mebeverine hydrochloride in man, absorption was followed by the appearance in the plasma of veratric acid and an oxidised metabolite of the mebeverine alcohol moiety of the drug, mebeverinic acid.

Distribution.

Maximum plasma radioactivity levels were found 1-3 hours after dosing. Binding of mebeverine to human serum albumin was 75%.

Metabolism.

The primary metabolic step in mebeverine degradation is hydrolysis of the ester function.

Excretion.

The major route of excretion of the metabolites is via the urine (95%) and the peak rate of excretion usually occurs within two hours. Virtually 98% urinary recovery of the conjugated and unconjugated metabolites was observed after a period of 24 hours. No unchanged mebeverine was excreted with the urine.

5.3 Preclinical Safety Data

Genotoxicity.

Teratogenicity has not been demonstrated in teratology studies in rats and rabbits.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each tablet contains microcrystalline cellulose, lactose monohydrate, sodium starch glycolate A, povidone, magnesium stearate, purified talc and Opadry complete film coating system 03F58763 White.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

APO-Mebeverine tablets are available in cartons of 10, 30 and 90 tablets in PVC/PVDC/Al blister packs.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Mebeverine hydrochloride is 4-[ethyl-[2-(4-methoxyphenyl)-1-methylethyl] aminobutyl veratrate hydrochloride, a derivative of phenylethylamine. It is a white to almost white, crystalline powder having a very bitter taste, very soluble in water, freely soluble in ethanol and practically insoluble in ether. The empirical formula is C25H35NO5.HCl. MW: 466.0.

CAS number.

2753-45-9.

7 Medicine Schedule (Poisons Standard)

Schedule 4: Prescription Only Medicine.

Summary Table of Changes