SUMMARY CMI

Trental^® 400

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Trental 400?

Trental 400 contains the active ingredient pentoxifylline. Trental 400 is used to improve the circulation of the blood.

For more information, see Section 1. Why am I using Trental 400? in the full CMI.

2. What should I know before I use Trental 400?

Do not use if you have ever had an allergic reaction to Trental 400, caffeine, theobromine theophylline or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Trental 400? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Trental 400 and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Trental 400?

• The standard dose is one tablet three times a day. Your doctor may have prescribed a different dose.
• Take Trental 400 at about the same time each day. Take the tablet during or immediately after a meal.
• Swallow the tablet whole with a full glass of water or other liquid. Do not crush or chew the tablets.

More instructions can be found in Section 4. How do I use Trental 400? in the full CMI.

5. What should I know while using Trental 400?

For more information, see Section 5. What should I know while using Trental 400? in the full CMI.

6. Are there any side effects?

Common side effects include nausea, vomiting or an upset stomach, indigestion, diarrhoea, dizziness, headache, problems sleeping, blurred vision, and drowsiness. Serious side effects include bleeding or bruising more easily than normal, yellowing of the skin and eyes (jaundice), tremor, and symptoms of an allergic reaction, which include swelling of the face, lips, mouth or throat, which may cause difficulty in swallowing or breathing. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

Trental^® 400

Active ingredient: pentoxifylline

Consumer Medicine Information (CMI)

This leaflet provides important information about using Trental 400. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Trental 400.

Where to find information in this leaflet:

1. Why am I using Trental 400?
2. What should I know before I use Trental 400?
3. What if I am taking other medicines?
4. How do I use Trental 400?
5. What should I know while using Trental 400?
6. Are there any side effects?
7. Product details

1. Why am I using Trental 400?

Trental 400 contains the active ingredient pentoxifylline. Trental 400 is a type of medicine used to improve the circulation of the blood.

Trental 400 is used to treat the symptoms of a condition called chronic occlusive arterial disease. Symptoms of this disease can include lameness and pain, usually in the leg muscles.

Trental 400 is a slow release tablet, which means that the active ingredient is released slowly over several hours.

2. What should I know before I use Trental 400?

Warnings

Do not use Trental 400 if:

• you are allergic to pentoxifylline, or any of the ingredients listed at the end of this leaflet.
  Always check the ingredients to make sure you can use this medicine.
• you have had a recent operation
• you have bleeding problems
• you have heart problems, such as having suffered a heart attack
• you have kidney or liver problems
• you have stomach ulcers or a history of stomach ulcers
• you have had an allergic reaction to caffeine, theobromine or theophylline (a medicine used to treat asthma)

Check with your doctor if you:

• have allergies to any other substances, such as foods, preservatives or dyes
• have any other medical conditions, especially the following:
  - kidney or liver problems
  - problems with your blood pressure
  - problems with your heart eg. an irregular or rapid heart beat
• take any medicines for any other condition
• plan to have surgery.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant.

Like most medicines of this kind, Trental 400 is not recommended to be used during pregnancy. Your doctor or pharmacist will discuss the risks and benefits of taking it if you are pregnant.

Tell your doctor or pharmacist if you are breastfeeding or planning to breastfeed.

Trental 400 passes into breast milk and there is a possibility your baby may be affected. Your doctor will discuss the risks and benefits of taking it if you are breastfeeding or planning to breastfeed.

Children and adolescents

Do not give Trental 400 to a child or adolescent. There is no experience with its use in children or adolescents under 18 years old.

3. What if I am taking other medicines?

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

Some medicines may interfere with Trental 400 and affect how it works. These include:

• warfarin and other medicines used to stop blood clots
• medicines used to treat high blood pressure
• theophylline, a medicine used to treat asthma
• some medicines used to treat diabetes
• some medicines used to treat the symptoms of cough and colds
• ciprofloxacin
• cimetidine, a medicine used to treat reflux and ulcers

These medicines may be affected by Trental 400, or may affect how well it works. You may need to use different amounts of your medicine, or take different medicines. Your doctor or pharmacist will advise you.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Trental 400.

4. How do I use Trental 400?

How much to take

• Your doctor or pharmacist will tell you how many tablets you will need to take each day. This depends on your condition and whether or not you are taking any other medicines.
• The standard dose for this medicine is one tablet three times a day. Your doctor may have prescribed a different dose.
• Follow the instructions provided and use Trental 400 until your doctor tells you to stop.

How to take it

• Swallow the tablet whole with a full glass of water or other liquid.
• Do not crush or chew the tablets.
• Each Trental 400 tablet has been especially designed to slowly release the right dose of medicine. If you crush, chew or divide Trental 400 tablets they will not work properly.

When to take Trental 400

• Trental 400 should be taken during or immediately after a meal. If you take it on an empty stomach, it may cause stomach upset.
• Take Trental 400 at about the same time each day. Taking your tablets at the same time each day will have the best effect. It will also help you remember when to take the tablets.
• If you are not sure when to take it, ask your doctor or pharmacist.

How long to take it

• Continue taking your medicine for as long as your doctor or pharmacist tells you.
• The medicine helps control your condition, but it does not cure it. Therefore, you must take it every day.
• Trental 400 can take time to work. Your symptoms may improve within 2-4 weeks, however it can take up to 8 weeks to take effect.
• As your doctor or pharmacist if you are not sure how long to take the medicine for.

If you forget to take Trental 400

Trental 400 should be taken regularly at the same time each day. If you miss your dose at the usual time, do not try to make up for missed doses by taking more than one dose at a time.

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

Do not take a double dose to make up for the dose you missed.

• If there is still a long time to go before your next dose, take it as soon as you remember, and then go back to taking it as you would normally.

If you use too much Trental 400

If you think that you have used too much Trental 400, you may need urgent medical attention.

You should immediately:

• phone the Poisons Information Centre
  (by calling 13 11 26 in Australia or 0800 POISON or 0800 764 766 in New Zealand), or
• contact your doctor, or
• go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

If you take too much Trental 400, you may feel flushed, light-headed or dizzy, drowsy or you may also feel faint.

5. What should I know while using Trental 400?

Things you should do

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Trental 400.

Remind any doctor, dentist or pharmacist you visit that you are using Trental 400.

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking this medicine.

Call your doctor straight away if you:

• become pregnant while you are taking this medicine, and stop taking it.

Things you should not do

• Do not stop taking Trental 400, or lower the dosage, without checking with your doctor.
• Do not stop taking your tablets because you are feeling better, unless advised by your doctor or pharmacist.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Trental 400 affects you.

Trental 400 may cause dizziness or light-headedness in some people, especially after the first dose.

Make sure you know how you react to it before you drive a car, operate machinery, or do anything else that could be dangerous if you feel dizzy.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

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

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight where the temperature stays below 25°C; for example, do not store it:

• in the bathroom or near a sink, or
• in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Trental 400 contains

Do not take this medicine if you are allergic to any of these ingredients.

What Trental 400 looks like

Trental 400 - oblong, pink, film-coated tablets with 'ATA' on one side.

Trental 400 is available in boxes of 50 tablets (Aust R 81197).

Who distributes Trental 400

Trental 400 is distributed in Australia by:

Clinect Pty Ltd
120 - 132 Atlantic Drive
Keysborough VIC 3173
Australia
Free Call Australia: 1800 899 005

Trental 400 is distributed in New Zealand by:

Clinect NZ Pty Limited
C/- Ebos Group Limited
108 Wrights Road
Christchurch 8024
New Zealand
Free Call New Zealand: 0800 138 803

This leaflet was prepared in September 2023.

Published by MIMS November 2023

1 Name of Medicine

Pentoxifylline.

2 Qualitative and Quantitative Composition

Trental 400 tablets contain 400 mg of pentoxifylline.
Oxpentifylline and Pentoxifylline are interchangeable and refer to the same molecule.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Modified release tablet.
Oblong, biconvex, pink film-coated tablets with the 'ATA' stamp on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

The treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. Trental 400 can thus improve function and symptoms but is not intended to replace more definitive therapy, such as vascular surgery, or removal of arterial obstructions when treating peripheral vascular disease.

4.2 Dose and Method of Administration

The usual dosage of Trental 400 in controlled release tablet form is one tablet (400 mg) three times a day with or after meals, to be swallowed whole with some liquid. While the effect of Trental 400 may be seen within 2 to 4 weeks, it is recommended that treatment be continued for at least 8 weeks. Efficacy has been demonstrated in double blind clinical studies of 6 months duration.
Digestive and central nervous system side effects are dose related. If patients develop these side effects it is recommended that the dosage be lowered to one tablet twice a day (800 mg/day). If side effects persist at this lower dosage, the administration of Trental 400 should be discontinued.
In patients with low or labile blood pressure or hepatic dysfunction, an individual dosage adjustment is required. This also applies to patients with renal dysfunction (creatinine clearance of less than 30 mL/min) where, according to individual tolerance, a dosage adjustment of 30 to 50% may be necessary.

4.3 Contraindications

Patients who have previously exhibited intolerance to this product; other methylxanthines such as caffeine, theophylline and theobromine; or any of the excipients of Trental 400.
Trental 400 should not be given to patients with recent or severe haemorrhage, e.g. massive retinal haemorrhage, cerebral haemorrhage, acute myocardial infarction or patients with peptic ulcer or a recent history thereof.

4.4 Special Warnings and Precautions for Use

Since pentoxifylline is extensively metabolised in the liver and eliminated through the kidneys, the use of this drug is not recommended in patients with marked impairment of kidney or liver function. Patients with less severe impairment of these organs should be closely monitored during Trental 400 therapy and may require lower doses.
Patients with chronic occlusive arterial disease of the limbs frequently show other manifestations of arteriosclerotic disease. Trental 400 has been used safely for treatment of peripheral arterial disease in patients with concurrent coronary artery and cerebrovascular diseases, but there have been occasional reports of angina, hypotension, and arrhythmia. Controlled trials do not show that Trental 400 causes such adverse effects more often than placebo, but, as it is a methylxanthine derivative, it is possible that some individuals will experience such responses. Careful monitoring is required in patients with acute arrhythmias or in patients with myocardial infarction.
Caution should be exercised and careful monitoring undertaken when administering Trental 400 to patients with low or labile blood pressure, for example patients with severe coronary heart disease or relevant stenoses of blood vessels supplying the brain. In such patients any dose increase should be done gradually.
Hypersensitivity reactions such as pruritus, rashes and urticaria do occur, but progression to anaphylactoid shock and angioedema are rare. At the first signs of an anaphylactic/ anaphylactoid reaction, Trental 400 must be discontinued, and a physician must be informed.
Trental 400 may exacerbate bleeding; careful patient selection and monitoring of at risk patients via haematocrit and/or haemoglobin determinations are recommended.
Particular careful monitoring is required in patients treated concomitantly with antivitamin K, platelet aggregation inhibitors, antidiabetic agents or ciprofloxacin.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There have been reports of bleeding (e.g. skin, mucosa, gastrointestinal tract) and/or prolonged prothrombin time in patients treated with Trental 400 with and, rarely, without anticoagulants or platelet aggregation inhibitors. Patients on warfarin should have more frequent monitoring of prothrombin times, while patients with other risk factors complicated by haemorrhage (e.g. recent surgery, peptic ulceration) should have periodic examinations for bleeding including haematocrit and/or haemoglobin.
Trental 400 has been used concurrently with digitalis and antiarrhythmics without observed problems. Small decreases in blood pressure have been observed in some patients treated with Trental 400. Periodic systemic blood pressure monitoring is recommended for patients receiving Trental 400 concomitantly with antihypertensive medicines, beta-blockers, diuretics and other medicines with blood pressure lowering potential as their blood pressure lowering effects may be increased. If indicated, dosage of the antihypertensive agents should be reduced.
Combined use with other xanthines or with sympathomimetics may cause excessive CNS stimulation.
An increase in levels of theophylline and therefore an increase in the intensity and frequency of adverse events associated with theophylline may result from concomitant use with Trental 400.
Concomitant administration with ciprofloxacin may increase the serum concentration of pentoxifylline in some patients. Therefore, there may be an increase in and intensification of adverse effects associated with coadministration.
The blood sugar lowering effect of insulin or oral antidiabetics may be potentiated. In patients treated with hypoglycaemic agents, a moderate decrease in the dose of these agents may be required when Trental 400 is prescribed. Patients undergoing such therapy should be monitored closely.
Postmarketing cases of increased anticoagulant activity have been reported in patients concomitantly treated with pentoxifylline and antivitamin K. Monitoring of anticoagulant activity in these patients is recommended when pentoxifylline is introduced or the dose is changed.
Potential additive effect with platelet aggregation inhibitors. Due to the increased risk of bleeding, the concomitant administration of a platelet aggregation inhibitor with pentoxifylline should be undertaken with caution.
Concomitant administration with cimetidine may increase the plasma concentration of pentoxifylline and the active metabolite I.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

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)

Clinical trials with Trental 400 have been conducted in Australia, the United States and in Europe. The slow release formulation, Trental 400, was used in studies in Australia and Europe, while in the United States, studies were conducted using the capsule formulation, containing 200 mg pentoxifylline. In these studies, dosages used were 400 mg (tablets) two to three times daily or 200 mg - 400 mg (capsules) three times daily. Treatment periods for studies with Trental 400 ranged up to 60 weeks. The following adverse effects have been reported in clinical trials or postmarketing.

Gastrointestinal.

Central nervous system.

Cardiovascular.

Hepatic.

Haemic and lymphatic.

Respiratory.

Hypersensitivity.

Miscellaneous.

Reporting suspected adverse effects.

4.9 Overdose

Overdosage with Trental 400 has been reported in children and adults.

Symptoms.

Treatment.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Purine derivatives, ATC code: C04AD03.

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

After oral administration in aqueous solution, pentoxifylline is almost completely absorbed. It undergoes a first-pass effect and the various metabolites appear in plasma very soon after dosing.
Peak plasma levels of the parent compound and its metabolites are reached within 1 hour. The major metabolites are metabolite I (1-[5-hydroxy-hexyl] -3,7-dimethylxanthine), and metabolite V (1-[3-carboxypropyl] -3,7-dimethylxanthine), and plasma levels of these metabolites are 5 and 8 times greater, respectively, than of pentoxifylline. Following oral administration of aqueous solutions containing 100 to 400 mg of pentoxifylline, the pharmacokinetics of the parent compound and metabolite I are dose related and not proportional (nonlinear), with half-life and area under the blood level time curve (AUC) increasing with dose. The elimination kinetics of metabolite V are not dose dependent. The apparent plasma half-life of pentoxifylline varies from 0.4 to 0.8 hours and the apparent plasma half-lives of its metabolites vary from 1 to 1.6 hours. There is no evidence of accumulation or enzyme induction (cytochrome P450) following multiple oral doses.
Excretion is almost totally urinary; the main biotransformation product is metabolite V. Essentially no parent drug is found in the urine. Despite large variations in plasma levels of parent compound and its metabolites, the urinary recovery of metabolite V is consistent and shows dose proportionality. Less than 4% of the administered dose is recovered in faeces. Food intake shortly before dosing delays absorption of an immediate release dosage form but does not affect total absorption. The pharmacokinetics and metabolism of Trental 400 have not been studied in patients with renal and/or hepatic dysfunction, but AUC was increased and elimination rate decreased in an older population (60-68 years) compared to younger individuals (22-30 years). After administration of the 400 mg controlled release Trental 400 tablet, plasma levels of the parent compound and its metabolites reach their maximum within 2 to 4 hours and remain constant over an extended period of time. The controlled release of pentoxifylline from the tablet eliminates peaks and troughs in plasma levels for improved gastrointestinal tolerance.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hyetellose, povidone, purified talc, magnesium stearate, hypromellose, titanium dioxide, erythrosine, macrogol 8000.

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. Protect from light. Protect from moisture.

6.5 Nature and Contents of Container

Trental 400 is available in blister packs of 30 or 50 tablets.
Not all pack sizes may be marketed.

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

A trisubstituted xanthine derivative designated chemically as 1-(5-oxohexyl)-3, 7-dimethylxanthine, IUPAC name: 3,7-dimethyl-1-(5-oxohexyl)-3.7-dihydro-1H-purine-2,6-dione. Pentoxifylline is soluble in water and ethanol, and sparingly soluble in toluene.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

Summary Table of Changes