Consumer medicine information

Plenvu

Ascorbic acid; Sodium ascorbate; Macrogol 3350; Potassium chloride; Sodium chloride; Sodium sulfate

BRAND INFORMATION

Brand name

Plenvu

Active ingredient

Ascorbic acid; Sodium ascorbate; Macrogol 3350; Potassium chloride; Sodium chloride; Sodium sulfate

Schedule

S3

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Plenvu.

What is in this Leaflet

This leaflet answers some common questions about Plenvu powder for oral solution.

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.

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 Plenvu is used for

Plenvu is a type of medicine called a bowel preparation. It makes your bowels clean so that they are ready for examination or surgery. Plenvu works by emptying the contents of your bowels, so you should expect to have lots of watery bowel movements.

Plenvu is a dual flavoured laxative with two doses contained in three sachets. There is one sachet for Dose 1 (‘Dose 1 Sachet’) and two sachets for Dose 2 (‘Dose 2 Sachet A’ and ‘Dose 2 Sachet B’). You need to take all three sachets for one treatment. Dose 1 is mango flavour, Dose 2 is fruit punch flavour.

Plenvu is intended for adults (18 years of age and older), including the elderly, before any clinical procedure that needs a clean bowel.

Ask your doctor if you have any questions about why this medicine has been recommended for you.

Before you take Plenvu

When you must not take it

If you are in poor health or have a serious medical condition, you should be particularly aware of the possible side effects listed in the ‘Side Effects’ section. Contact your doctor, pharmacist or nurse if you are concerned.

Do not take Plenvu:

  • if you are allergic (hypersensitive) to the active ingredients or any of the other ingredients of Plenvu (listed in ‘Product Description’)
  • if you have a blockage in your bowel (bowel obstruction)
  • if you have an opening in the wall of your stomach or bowel (bowel perforation)
  • if you experience problems with food and fluid emptying from your stomach (gastric retention)
  • if you have paralysis of the gut (ileus)
  • if you suffer from phenylketonuria. This is a hereditary inability of the body to use a particular amino acid. Plenvu contains a source of phenylalanine
  • if your body is unable to produce enough glucose-6-phosphate dehydrogenase
  • if you have severe inflammatory bowel disease, like ulcerative colitis, Crohn’s disease, or toxic megacolon
  • if you have severe dehydration
  • if you have a decreased level of consciousness unless you have suitable medical supervision.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn 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, seek medical advice.

Before you start to take it

To maintain good health, you should hydrate adequately before the use of any bowel preparation. If you develop significant vomiting, or signs of fluid loss (dehydration) tell your doctor, see ‘Side Effects’ section.

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

Tell your doctor, pharmacist or nurse before taking Plenvu if any of the points below apply to you. If you:

  • have an allergy to any of the ingredients in Plenvu
  • have heart problems and/or heart rhythm problems
  • have kidney problems
  • have problems with swallowing
  • have a high or low blood salt level (e.g. sodium, potassium)
  • have diabetes
  • have any other medical conditions

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

Tell you doctor if you are breastfeeding. It is not known if Plenvu passes into your breast milk. You and your doctor should decide if you will take Plenvu while breastfeeding.

If you have not told your doctor about any of the above, tell him/her before you start taking Plenvu.

Taking other medicines

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines (e.g. oral contraceptives, diuretics, calcium channel blockers, corticosteroids), as well as any you get without a prescription from your pharmacy, supermarket or health food shop.

Medicines taken by mouth may not be absorbed properly when taken within 1 hour before the start of Plenvu.

Your doctor and pharmacist have more information on which medicines to be careful with or avoid while taking this medicine.

If you need to thicken fluids in order to swallow them safely, Plenvu may counteract the effect of the thickener.

Plenvu with food and drink

Continue to drink clear fluids before, during, and after you take Plenvu, to help prevent fluid loss (dehydration). It is important for you to drink the additional recommended amounts of clear fluids. Your Doctor will tell you a ‘Nil By Mouth’ time when you should stop drinking.

Examples of clear fluids are water, clear soups, herbal tea, black tea or coffee (without milk), soft drinks/diluted cordials and clear fruit juices (without pulp).

When taking Plenvu you should continue to take plenty of clear fluids. The fluid content of Plenvu does not replace your regular fluid intake.

Important: Do not drink alcohol, milk, anything coloured red or purple (e.g. blackcurrant juice) or any other drinks containing pulp material and do not eat while taking Plenvu and until after your clinical procedure.

Two-day split dosing schedule and day before dosing schedule
On the day before the clinical procedure you can eat a light breakfast followed by a light lunch and must finish eating this meal at least 3 hours before you start taking Plenvu, after which you may only consume clear fluids.

Morning only dosing schedule
On the day before the clinical procedure you can eat a light breakfast followed by a light lunch, and clear soup and/or plain yogurt for dinner (which should be completed by approximately 8 pm). You may only consume clear fluids from after dinner on the evening before the clinical procedure. No breakfast is allowed on the morning of the clinical procedure.

Your Doctor may give you additional dietary advice which you should follow.

How to take Plenvu

Unless your doctor has given you specific instructions, please follow these dosage and dietary instructions. Check with your doctor, pharmacist or nurse if you are not sure.

You must read, understand and follow the instructions for use.

Your doctor may prescribe the two-day split dosing schedule, the morning only dosing schedule or the day before dosing schedule depending on the scheduling of your clinical procedure.

Before you take Plenvu, please read carefully the following instructions. You need to know:

  • When to take Plenvu
  • How to prepare Plenvu
  • How to drink Plenvu
  • What you should expect to happen

When to take Plenvu

Your treatment with Plenvu must be completed before your clinical procedure.

This course of treatment may be taken as divided doses as described below:

Two-day split dosing schedule
Take 500 mL of Dose 1 of Plenvu (followed by an additional 500 mL of clear fluid) in the evening before the clinical procedure (at approximately 6 pm) and 500 mL of Dose 2 of Plenvu (followed by an additional 500 mL of clear fluid) in the early morning of the day of the clinical procedure (approximately 6 am), or

Morning only dosing schedule
Take 500 mL of Dose 1 of Plenvu (followed by an additional 500 mL of clear fluid) and 500 mL of Dose 2 of Plenvu (followed by additional 500 mL of clear fluid) in the morning of the day of the clinical procedure (Dose 1 at approximately 5 am); the time between finishing the first dose and starting the second dose should be separated by a minimum 1 hour interval, or

Day before dosing schedule
Take 500 mL of Dose 1 of Plenvu (followed by an additional 500 mL of clear fluid) and 500 mL of Dose 2 of Plenvu (followed by an additional 500 mL of clear fluid) in the evening of the day before the clinical procedure (Dose 1 at approximately 6 pm); the time between finishing the first dose and starting the second dose should be separated by a minimum 1 hour interval.

Your doctor will tell you which dosing schedule to follow. DO NOT add any other ingredients to the doses.

How to prepare Plenvu Dose 1

  • Open the carton and remove the Dose 1 sachet.
  • Pour the contents of Dose 1 into a measuring container that can hold 500 mL of fluid.
  • Add water (not chilled) to make up to 500 mL and stir until all the powder has dissolved. This may take up to approximately 8 minutes.

How to drink Plenvu Dose 1

Drink the 500 mL Plenvu Dose 1 solution slowly over 30 minutes. Try to drink a glassful every 10 to 15 minutes. Drink an additional 500 mL of clear fluid over the next 30 minutes. Water, clear soup, diluted cordials/clear fruit juice (without pulp), herbal tea, black tea or coffee (without milk) are all suitable.

How to prepare Plenvu Dose 2

  • When you are ready to take Dose 2 pour the contents of Dose 2 Sachet A and Dose 2 Sachet B into a measuring container that can hold 500 mL of fluid.
  • Add water (not chilled) to make up to 500 mL and stir until all the powder has dissolved. This may take up to approximately 8 minutes.

How to drink Plenvu Dose 2

At the time you were given, based on the recommended dosing schedule, drink the 500 mL Plenvu Dose 2 solution slowly over 30 minutes. Drink an additional 500 mL of clear fluid over the next 30 minutes.

In addition to Plenvu and the additional clear fluid after each dose, you are encouraged to drink extra clear fluid as needed to avoid thirst. Drinking clear fluids will help prevent fluid loss (dehydration). You must stop drinking all fluids at least 2 hours prior to your clinical procedure. Your doctor should tell you your ‘NIL BY MOUTH’ time.

What you should expect to happen
When you start drinking the Plenvu solution, it is important that you stay close to a toilet. At some point, you will start to experience watery bowel movements. This is quite normal and indicates that the Plenvu solution is working. You may have stomach area bloating before you have your first bowel movement.

If you follow these instructions, your bowel will be clean, and this will help you to have a successful clinical procedure. You should allow sufficient time after your bowel movements have subsided to travel to the clinic/ hospital.

If you forget to take it

If you forget to take Plenvu as instructed, take it as soon as you realise you have not taken it and contact your doctor, pharmacist or nurse for advice prior to the clinical procedure. It is important that you have allowed sufficient time to complete your course of Plenvu in order to ensure your bowel is fully cleaned at least 2 hours prior to the clinical procedure.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26 in Australia or 0800 764 766 in New Zealand) for advice, or go to the Accident and Emergency department at the nearest hospital, if you think that you or anyone else may have taken too much Plenvu.

While you are using Plenvu

Things you must do

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

Things you must not do

Do not use Plenvu for any other conditions unless your doctor tells you to.

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

Side effects

Tell a doctor or pharmacist as soon as possible if you do not feel well while you are using Plenvu.

All medicines can have unwanted effects. Sometimes they are serious, most of the time they are not. Do not be alarmed by this list of possible side effects. You may not experience any of them.

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

It is normal to get diarrhoea when you take Plenvu. If you do not have a bowel movement within 6 hours of taking Plenvu, stop the intake and contact your doctor immediately.

As with other medicines there is a small risk of serious allergic reactions. Stop your intake and tell your doctor immediately or go to the Accident & Emergency department of your nearest hospital if you notice any of the following side effects, as these may be symptoms of a severe allergic reaction:

  • extreme fatigue
  • palpitations
  • sudden or severe itching, skin rash, hives
  • shortness of breath, asthma, wheezing
  • swelling of your face, lips or tongue (which may make swallowing or breathing difficult), ankles or other part of your body

Tell your doctor immediately if you have any of these symptoms of a loss of too much body fluid (dehydration) while taking Plenvu:

  • confusion
  • dizziness
  • excessive thirst
  • headache
  • urinating less often than normal or dark coloured urine
  • vomiting

Also, tell your doctor right away if you have severe stomach-area (abdomen) pain.

If you experience sudden abdominal pain or rectal bleeding when taking Plenvu for bowel preparation, contact your doctor or seek medical advice immediately.

Rarely, serious heart rhythm problems may occur (i.e. heart may feel like it’s pounding, fluttering or beating irregularly, often for a few seconds or possibly a few minutes) with the use of laxatives for bowel preparation, especially in patients with underlying heart disease or salts disturbance.

Other side effects by frequency:

Common side effects (may affect up to 1 in 10 people): Dehydration, nausea (feeling sick), vomiting.

Uncommon side effects (may affect up to 1 in 100 people): Abdominal bloating and pain, aches and pains, allergic reaction, chills, fatigue, headache or migraine, hot flushes, increased blood glucose level in diabetic patients, increased heart rate, palpitations, soreness of the anus, sleepiness, temporary increase in blood pressure, temporary increase in liver enzymes, thirst, various salt (electrolyte) imbalances and weakness.

You also may be feeling generally unwell.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

Storage

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.

Do not use this medicine after the expiry date which is stated on the sachets and carton, after “EXP”. The expiry date refers to the last day of that month.

Please note that the expiry dates may be different for each of the sachets and carton.

Before use, store Plenvu sachets below 25°C. After you have dissolved Plenvu in the water, the solution may be stored (keeping covered) at or below 25°C. It may also be stored in the refrigerator (2°C to 8°C). Do not keep it for more than 24 hours.

Do not store Plenvu or any other medicines in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some 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 medicine that is left over.

Product description

What it looks like

What Plenvu contains

Dose 1 Sachet contains the following active substances:

  • Macrogol 3350 100 g
  • Sodium sulfate 9 g
  • Sodium chloride 2 g
  • Potassium chloride 1 g

The concentration of electrolyte ions when the first dose is made up to 500 mL of solution is as follows:

  • Sodium 160.9 mmol/500 mL
  • Sulfate 63.4 mmol/500 mL
  • Chloride 47.6 mmol/500 mL
  • Potassium 13.3 mmol/500 mL

Dose 1 also contains 0.79 g of sucralose (E955).

Dose 2 (Sachets A and B) contains the following active substances:

Sachet A:

  • Macrogol 3350 40 g
  • Sodium chloride 3.2 g
  • Potassium chloride 1.2 g

Sachet B:

  • Sodium ascorbate 48.11 g
  • Ascorbic acid 7.54 g

The concentration of electrolyte ions when the second dose (Sachets A and B) is made up to 500 mL of solution is as follows:

  • Sodium 297.6 mmol/500 mL
  • Ascorbate 285.7 mmol/500 mL
  • Chloride 70.9 mmol/500 mL
  • Potassium 16.1 mmol/500 mL

Dose 2 (Sachet A) also contains 0.88 g of aspartame (E951).

The other ingredients in Plenvu are: sucralose (E955), aspartame (E951) mango flavouring, fruit punch flavouring, citric acid, and maltodextrin.

Supplier

Plenvu is supplied in Australia by:

Norgine Pty Ltd
Suite 3.01 Building A
20 Rodborough Road
Frenchs Forest NSW 2086
AUSTRALIA
Phone: 1800 766 936
www.norgine.com.au

Plenvu is supplied in New Zealand by:

Pharmacy Retailing (NZ) Ltd
Trading as Healthcare Logistics
58 Richard Pearse Drive
Mangere, Auckland
Phone: 0800 404 178 (Medical Information)

This Leaflet was prepared in September 2020

Australian Registration No. AUST R 298344

PLENVU, NORGINE and the sail logo are registered trademarks of the Norgine group of companies.

Published by MIMS November 2020

BRAND INFORMATION

Brand name

Plenvu

Active ingredient

Ascorbic acid; Sodium ascorbate; Macrogol 3350; Potassium chloride; Sodium chloride; Sodium sulfate

Schedule

S3

 

1 Name of Medicine

Macrogol 3350, sodium sulfate, ascorbic acid, sodium ascorbate, sodium chloride and potassium chloride.

2 Qualitative and Quantitative Composition

The ingredients of Plenvu are contained in three separate sachets. The first dose is supplied in one sachet and the second dose is supplied in two sachets, A and B.
Dose 1 sachet contains the following active substances (see Table 1).
The concentration of electrolyte ions when the first dose is made up to 500 mL of solution is as follows (see Table 2).
Dose 2 (Sachets A and B) contains the following active substances (see Table 3).
The concentration of electrolyte ions when the second dose (Sachets A and B) is made up to 500 mL of solution is as follows (see Table 4).
Dose 1 contains 790 mg of sucralose. Dose 2 (Sachet A) contains 875 mg of aspartame.
The complete treatment contains 10.5 g of sodium and 1.1 g of potassium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for oral solution.
One pack of Plenvu contains a single treatment of three sachets.
Dose 1 (mango flavour) Sachet contains 115.96 g of white to off-white powder.
Dose 2 (fruit punch flavour) Sachet A contains 46.26 g of white to off-white powder and Dose 2 Sachet B contains 55.65 g of white to yellow powder.

4 Clinical Particulars

4.1 Therapeutic Indications

Plenvu is indicated for bowel cleansing prior to any procedure requiring a clean bowel.

4.2 Dose and Method of Administration

Adults (18 years of age and over), including the elderly.

A course of treatment consists of two separate non-identical 500 mL doses of Plenvu. At least 500 mL of additional clear fluid, which may include water, clear soup, fruit juice without pulp, soft drinks, tea and/or coffee without milk must be taken with each dose.
This course of treatment can be taken according to any of the three schedules specified below:
Two-day split dosing schedule with the first 500 mL dose of Plenvu (including additional 500 mL of clear fluid) taken in the evening before the clinical procedure (approximately 6 pm) and the second 500 mL dose (including additional 500 mL of clear fluid) in the early morning of the day of the clinical procedure (approximately 6 am); or
Morning only dosing schedule with both doses taken in the morning of the day of the clinical procedure [the first 500 mL dose (including additional 500 mL of clear fluid) taken at approximately 5 am]; the time between finishing the first dose (including additional clear fluid) and starting the second 500 mL dose (including additional 500 mL of clear fluid) should be separated by a minimum 1 hour interval; or
Day before dosing schedule with both doses taken in the evening before the clinical procedure [the first 500 mL dose (including additional 500 mL of clear fluid)] taken at approximately 6 pm]; the time between finishing the first dose (including additional clear fluid) and starting the second 500 mL dose (including additional 500 mL of clear fluid) should be separated by a minimum 1 hour interval. A time interval of more than 12 hours between preparation administration and colonoscopy may reduce the bowel cleansing efficacy.
Patient should be warned to expect frequent, loose bowel movements.
Patients should be reminded of the importance of hydration while taking these products and to seek medical attention if they experience any signs of severe dehydration, such as excessive thirst, dizziness, confusion and decreased urine output or dark coloured urine.

Use in renal impairment.

No special dosage adjustment of Plenvu is deemed necessary in patients with mild to moderate renal impairment. Patients with mild to moderate renal impairment were included in clinical studies.

Use in hepatic impairment.

No special dosage adjustment of Plenvu is deemed necessary in patients with mild to moderate hepatic impairment. Patients with elevated liver function tests were included in clinical studies.

Use in the elderly.

See Section 4.2 Dose and Method of Administration. Elderly patients were included in the clinical trial program, see Section 5.1 Pharmacodynamic Properties, Clinical trials.

Paediatric use.

The safety and efficacy of Plenvu in children below 18 years of age has not yet been established. Plenvu is therefore not recommended for use in this population.

Preparation instructions.

Dose 1.

The contents of the single sachet for Dose 1 should be made up to 500 mL with water (not chilled). The reconstituted solution should be taken over a period of 30 minutes, followed by 500 mL of clear fluid over the next 30 minutes.

Dose 2.

The contents of the two sachets (sachets A and B together) for Dose 2 should be made up to 500 mL with water (not chilled). The reconstituted solution should be taken over a period of 30 minutes, followed by 500 mL of clear fluid over the next 30 minutes.
Reconstitution of Plenvu in water (not chilled) may take up to approximately 8 minutes and is best performed by adding the powder to the mixing vessel first followed by the water (not chilled). The patient should wait until all the powder has dissolved before drinking the solution.
After reconstitution in water Plenvu consumption may begin immediately or if preferred, it may be refrigerated before use.
In addition to the fluids taken as part of the course of treatment, any amount of supplementary clear fluid (e.g. water, clear soup, fruit juice without pulp, soft drinks, tea and/or coffee without milk) may be taken.

Note.

Patients should avoid any fluid coloured red or purple (e.g. blackcurrant juice) as this can stain the bowel.
Consumption of all fluids should be stopped at least:
two hours before the clinical procedure when under general anaesthesia, or
one hour before the clinical procedure without general anaesthesia.

Information regarding meals.

Two-day split dosing schedule and day before dosing schedule.

The day before the clinical procedure, patients can have a light breakfast followed by a light lunch which must be completed at least 3 hours prior to the start of the first dose. No solid food should be taken from the start of the course of treatment until after the clinical procedure.

Morning only dosing schedule.

The day before the clinical procedure, patients can have a light breakfast followed by a light lunch, and clear soup and/or plain yogurt for dinner, which should be completed by approximately 8 pm. No solid food should be taken from the start of the course of treatment until after the clinical procedure.
Patients should be advised to allow adequate time after bowel movements have subsided to travel to the clinical unit.

4.3 Contraindications

Do not use in patients with known or suspected:
hypersensitivity to the active or inactive ingredients;
gastrointestinal obstruction or perforation;
ileus;
disorders of gastric emptying (e.g. gastroparesis, gastric retention, etc.);
phenylketonuria (due to the presence of aspartame);
glucose-6-phosphate dehydrogenase deficiency (patients may be at risk of acute haemolysis due to the presence of ascorbate);
unconsciousness;
severe dehydration;
severe inflammatory conditions of the intestinal tract, such as Crohn's disease, ulcerative colitis and toxic megacolon.

4.4 Special Warnings and Precautions for Use

Identified precautions.

The fluid content of Plenvu when reconstituted with water does not replace regular fluid intake and adequate fluid intake must be maintained.
Patients should be advised to hydrate adequately before, during, and after the use of any bowel preparation. If a patient develops significant vomiting or signs of dehydration after taking Plenvu, consider performing post-colonoscopy laboratory tests.
As with other macrogol containing products, allergic reactions including rash, urticaria, pruritus, angioedema and anaphylaxis are a possibility.
Caution should be used with the administration of Plenvu to frail or debilitated patients.
Plenvu should also be used with caution in patients with:
impaired gag reflex, with the possibility of regurgitation or aspiration, or with diminished levels of consciousness. Such patients should be closely observed during administration especially if given via a nasogastric route;
renal impairment whose creatinine clearance is less than 30 mL/minute/1.73 m2;
grade III or IV cardiac failure;
those at risk of arrhythmia, for example those with or on treatment for cardiovascular disease, thyroid disease or electrolyte imbalance.
In debilitated fragile patients, patients with poor health, those with clinically significant renal impairment, arrhythmia and those at risk of electrolyte imbalance, the physician should consider performing a baseline and post-treatment electrolyte, renal function test and ECG as appropriate. Any suspected dehydration should be corrected for before use of Plenvu.
There have been rare reports of serious arrhythmias including atrial fibrillation associated with the use of ionic osmotic laxatives for bowel preparation. These occur predominantly in patients with underlying cardiac risk factors and electrolyte disturbance.
If patients develop any symptoms indicating arrhythmia or shifts of fluid/electrolytes during or after treatment (e.g. oedema, shortness of breath, increasing fatigue, cardiac failure), plasma electrolytes should be measured, ECG monitored and any abnormality treated appropriately.
Plenvu contains 458.5 mmol (10.5 g) sodium per course of treatment. This should be taken into consideration for patients on a controlled sodium diet.
Plenvu contains 29.4 mmol (1.1 g) potassium per course of treatment. This should be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.
If patients experience severe bloating, abdominal distension, or abdominal pain, administration should be slowed or temporarily discontinued until the symptoms subside.

Ischaemic colitis.

Post-marketing cases of ischaemic colitis, including serious cases, have been reported in patients treated with macrogol for bowel preparation. Macrogol should be used with caution in patients with known risk factors for ischaemic colitis or in case of concomitant use of stimulant laxatives (such as bisacodyl or sodium picosulfate). Patients presenting with sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis should be evaluated promptly.

Use in hepatic impairment.

No special dosage adjustment of Plenvu is deemed necessary in patients with mild to moderate hepatic impairment. Patients with elevated liver function tests were included in clinical studies.

Use in renal impairment.

No special dosage adjustment of Plenvu is deemed necessary in patients with mild to moderate renal impairment. Patients with mild to moderate renal impairment were included in clinical studies.
Plenvu should be used with caution in patients with renal impairment whose creatinine clearance is less than 30 mL/minute/1.73 m2.
In those with clinically significant renal impairment, arrhythmia and those at risk of electrolyte imbalance, the physician should consider performing a baseline and post-treatment electrolyte, renal function test and ECG as appropriate.

Use in the elderly.

See Section 4.2 Dose and Method of Administration. Elderly patients were included in the clinical trial program, see Section 5.1 Pharmacodynamic Properties, Clinical trials.
Caution should be used with the administration of Plenvu to frail or debilitated patients.

Paediatric use.

The safety and efficacy of Plenvu in children below 18 years of age has not yet been established. Plenvu is therefore not recommended for use in this population.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Medicinal products taken orally (e.g. oral contraceptive pill) within one hour of starting colonic lavage with Plenvu may be flushed from the gastrointestinal tract unabsorbed.
Medications such as diuretics, calcium channel blockers or corticosteroids, may affect electrolyte levels or may exacerbate hypokalaemia.
Medications such as diuretics may exacerbate volume depletion associated with bowel cleansing.
Plenvu may have a potential interactive effect when used with starch-based food thickeners. The macrogol ingredient counteracts the thickening effect of starch, effectively liquefying preparations that need to remain thick for people with swallowing problems.

Note.

For more information, see Section 4.4 Special Warnings and Precautions for Use.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no data on the effects of Plenvu on fertility.
(Category B1)
Macrogol is designated Australian Pregnancy Category B1 Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.
There are no data on the use of Plenvu during pregnancy. The preparation should only be used during pregnancy if considered essential by the physician.
There are no data on the use of Plenvu during lactation. The preparation should only be used during lactation if considered essential by the physician.

4.7 Effects on Ability to Drive and Use Machines

Plenvu has no influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Diarrhoea is an expected outcome of bowel preparation. Due to the nature of the intervention, undesirable effects occur in the majority of patients during the process of bowel preparation. Whilst these vary between preparations, nausea, vomiting, bloating, abdominal pain, anal irritation and sleep disturbance commonly occur in patients undergoing bowel preparation.
Data from clinical studies are available in a population of over a thousand subjects treated with Plenvu in which undesirable effect data were actively elicited.
Table 5 is a list of causally related treatment emergent adverse events reported in the clinical studies of Plenvu.
The frequency of adverse reactions to Plenvu is defined using the following convention:
Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data).

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

Overdosage may cause severe diarrhoea. In case of overdose, fluid replacement and electrolyte correction may be necessary. For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia) or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The pharmacodynamic properties of this osmotically-acting bowel preparation are a combination of the direct synergistic osmotic action of the components of Plenvu (macrogol 3350 plus sodium sulfate components in Dose 1 and ascorbate plus macrogol 3350 components in Dose 2) and the induction of propulsive contractions of the smooth muscle of the bowel, which induce the laxative effect. The physiological consequence is a propulsive colonic transportation of the softened stools.
The electrolytes present in the formulation and the supplementary clear fluid intake are included to prevent clinically significant variations of sodium, potassium or water, and thus reduce dehydration risk.
Macrogol 3350 is chemically inert and highly soluble in water. The principal action of macrogol 3350 is to increase the water content of the bowel by exerting an osmotic action. Macrogol 3350 is able to hold water in the ratio of 100 molecules of water to every one molecule of macrogol 3350 and it has been shown that increasing osmotic loads of macrogol 3350 results in a near linear increase in stool weight and stool water output.
The human body usually contains about 1.5 g of ascorbic acid with excess rapidly excreted by glomerular filtration. Unabsorbed ascorbic acid/sodium ascorbate passes into the faecal water.
The bulk of sulfate is not absorbed and remains in the intestine adding to the synergistic osmotic action in Dose 1. The osmotic action of sodium sulfate is brought about by irritation of the intestinal mucosa by high intraluminal concentrations of sulfate ions.

Clinical trials.

The colon cleansing efficacy, safety and tolerability of Plenvu was evaluated in three randomized, parallel group, multi-centre, investigator-blinded, Phase III studies in patients undergoing colonoscopy.
The three studies, NER1006-01/2014 (NOCT), NER1006-02/2014 (MORA) and NER1006-03/2014 (DAYB) were designed with many similarities to allow for optimum comparability of data. The primary focus of the Phase III clinical program was to compare the bowel cleansing ability of Plenvu against a different comparator using different dosing regimen(s):
Two-Day split-dosing allowing for an overnight gap between doses;
One-Day Morning dosing giving both doses the morning of the day of colonoscopy; and
One-Day Day Before dosing giving both doses the day before colonoscopy.
Details of which regimen was used in each study for Plenvu and each of the comparators are provided in Table 6.

Design of studies.

The alternative primary endpoints were the same across all three studies and were as follows:
The overall bowel cleansing success rate of Plenvu is non-inferior to that of the comparator using the Harefield Cleansing Scale (HCS), wherein success corresponds to Grades A and B, and failure corresponds to Grades C and D.
The 'Excellent plus Good' cleansing rate in the ascending colon of Plenvu is non-inferior to that of the comparator using the segmental cleansing scoring system of the HCS, wherein the ordinal score of 4 corresponds to Excellent cleansing and score of 3 corresponds to Good cleansing.
The alternative primary efficacy endpoint was judged by blinded central readers (gastroenterologists) on the basis of video recordings of the colonoscopy.
The patient population consisted of male and female patients aged 18 to 85 years inclusive, who were scheduled to undergo a screening, surveillance or diagnostic colonoscopy.

NOCT study.

The NOCT study was a multicentre, randomized, parallel group Phase III study in adults comparing the bowel cleansing efficacy, safety and tolerability of Plenvu versus a trisulfate bowel cleansing solution containing sodium sulfate, potassium sulfate, and magnesium sulfate using an overnight Two-Day split-dosing regimen.
A total of 516 patients [255 patients in the Plenvu treatment group and 261 patients in the trisulfate solution treatment group] completed the study. Overall, the demographic characteristics were well balanced between the two treatment groups.
A similar percentage of patients achieved successful bowel cleansing in the overall colon in both treatment groups (85.1% in the Plenvu treatment group versus 85.0% in the trisulfate solution treatment group). With regard to the cleansing rate in the ascending colon, a greater percentage of patients achieved an "Excellent plus Good" cleansing rate in the Plenvu treatment group (35.9% in the Plenvu treatment group versus 29.3% in the trisulfate solution treatment group). Plenvu was shown to be non-inferior to the trisulfate solution with regard to both alternative primary endpoints of HCS results in the overall colon and the ascending colon.

MORA study.

The MORA study was a multicentre, randomized, parallel group Phase III study in adults comparing the bowel cleansing efficacy, safety and tolerability of Plenvu (Two-Day split-dosing and One-Day Morning dosing regimens) versus a 2 litre Macrogol + electrolytes (MOVIPREP) Two-Day split-dosing regimen.
A total of 781 patients [260 patients in the Two-Day Plenvu split-dosing group, 262 in the One-Day Plenvu morning dosing group and 259 patients in the 2L Macrogol+E treatment group] completed the study. Overall, the demographic characteristics were well balanced between the three treatment groups.
Similar percentages of patients achieved a successful bowel cleansing in the overall colon in the three treatment groups (92.0% in the Plenvu 2-day split-dosing group, 89.1% in the Plenvu 1-day split-dosing group and 87.5% in the 2L Macrogol+E treatment group), confirming non-inferiority for the Plenvu Two-Day split-dosing and Plenvu One-Day split-dosing groups versus the 2L Macrogol+E group. With regard to the cleansing rate in the ascending colon, both Plenvu groups met the criteria for superiority versus the 2L Macrogol+E group. The Plenvu Two-Day and One-Day dosing groups achieved "Excellent plus Good" cleansing rates of 31.6% and 33.8% respectively, whilst the 2L Macrogol+E group achieved a rate of 15.1%.

DAYB study.

The DAYB study was a multicentre, randomized, parallel group Phase III study in adults comparing the bowel cleansing efficacy, safety and tolerability of Plenvu versus a Sodium Picosulfate and Magnesium Salt (SP+MS) solution, using a One-Day Day Before dosing regimen.
A total of 473 patients [233 patients in the Plenvu treatment group, and 240 patients in the SP+MS treatment group] completed the study. Overall, the demographic characteristics were well balanced between the two treatment groups.
The percentage of patients who achieved successful bowel cleansing in the overall colon in the Plenvu group was numerically higher compared to the SP+MS group (62.0% versus 53.8% respectively), this difference did not reach statistical significance. Regarding the cleansing rate in the ascending colon, the percentage of patients achieved an "Excellent plus Good" cleansing rate (4.4% in the Plenvu treatment group versus 1.2% in the SP+MS treatment group). Plenvu was shown to be non-inferior to SP+MS with regard to both alternative primary endpoints in the overall colon and the ascending colon.

Demographics and results.

In general, the demographic characteristics were well balanced across the Plenvu patients in all three studies. However, there were two notable differences in 1) patients aged over 65: MORA (26% Two-Day and 22% One-Day), NOCT (18%) and DAYB (17%) and 2) the ratio of female and male patients: MORA (males 42% Two-Day and 46% One-Day), NOCT (males 51%) and DAYB (males 35%).
The alternative primary endpoint results are provided in Table 7.

5.2 Pharmacokinetic Properties

The vast majority (> 99.7%) of macrogol 3350 is not absorbed by the gastro-intestinal tract and is excreted in faeces. Literature reports that any macrogol 3350 that is absorbed is excreted via the urine.
Ascorbic acid/sodium ascorbate is an essential vitamin in humans with a daily requirement of 50 - 100 mg. At physiological doses, it is actively absorbed from the jejunum, with a bioavailability of 60-75%.
The bulk of oral sulfate is not absorbed, and by establishing an electrochemical gradient, prevents the absorption of accompanying sodium ions. Small amounts of sulfate ions are absorbed throughout the gastrointestinal tract, which adds to the pool of essential inorganic sulfate formed from the breakdown of sulfur containing amino acids. The bulk of absorbed inorganic sulfate is eliminated unchanged by glomerular filtration and is subject to saturable tubular reabsorption.
Osmotically-acting bowel preparations lead to a copious diarrhoea, resulting in extensive elimination of most of the product via the faeces. They can also lead to changes in electrolyte balance in the body, often with depletion of sodium and potassium. The additional sodium and potassium included in Plenvu formulation help to balance the electrolytes. While some absorption of sodium takes place, the bulk of sodium is expected to be excreted in the faeces as the sodium salts of sulfate and ascorbate, the osmotic active ingredients included in the Plenvu composition.
No pharmacokinetic studies were performed in patients with renal or hepatic insufficiency.

5.3 Preclinical Safety Data

Preclinical studies provide evidence that macrogol 3350, ascorbic acid and sodium sulfate have no significant systemic toxicity potential.

Genotoxicity.

No studies have been carried out on the genotoxicity, or toxic effect on reproduction with this product. However, available data on macrogols of relevant size, sodium sulfate and ascorbic acid did not reveal any special hazard for humans based on studies of genotoxicity, and reproductive toxicity.

Carcinogenicity.

No studies have been carried out on the carcinogenicity of this product. However, available data on macrogols of relevant size, sodium sulfate, and ascorbic acid did not reveal any special hazard for humans based on studies of carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Plenvu contains the following inactive ingredients: aspartame (E951), sucralose (E955), encapsulated citric acid (contains citric acid and maltodextrin), mango flavour and fruit punch flavour.

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

Sachets.

Store below 25°C.

Reconstituted solution.

Store below 25°C, or store in refrigerator. Keep solution covered. Shelf life of solution 24 hours.

6.5 Nature and Contents of Container

One pack of Plenvu contains a single treatment of three sachets. Dose 1 (mango flavour) Sachet contains 115.96 g of powder. Dose 2 (fruit punch flavour) Sachet A contains 46.26 g of powder and Dose 2 Sachet B contains 55.65 g of powder.
The three sachets are contained in a clear secondary overwrap within a cardboard carton. The cardboard carton also contains the patient information leaflet.

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.

Macrogol 3350.
Ascorbic acid: C6H8O6.
Sodium chloride: NaCl.
Sodium sulfate: Na2SO4.
Potassium chloride: KCl.
Sodium ascorbate: NaC6H7O6.

CAS number.

Ascorbic acid: 50-81-7.
Macrogol 3350: 25322-68-3.
Sodium chloride: 7647-14-5.
Sodium sulfate: 7757-82-6.
Potassium chloride: 7447-40-7.
Sodium ascorbate: 134-03-2.

7 Medicine Schedule (Poisons Standard)

Schedule 3. Pharmacist Only Medicine.

Summary Table of Changes