Consumer medicine information

Colazide

Balsalazide sodium

BRAND INFORMATION

Brand name

Colazide

Active ingredient

Balsalazide sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Colazide.

What is in this leaflet

This leaflet answers some of the common questions people ask about Colazide®. It does not contain all the information that is known about Colazide®.

It does not take the place of talking to your doctor or pharmacist.

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

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

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

What Colazide® is for

Colazide® capsules are used to treat active ulcerative colitis and for maintenance of remission in patients who are intolerant to sulfasalazine. Ulcerative colitis is when the lining of the lower bowel becomes inflamed (swollen and irritated). Colazide® reduces the swelling and irritation.

Your doctor will have explained why you are being treated with Colazide® and told you what dose to take.

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

Your doctor may prescribe this medicine for another use. Ask your doctor if you want more information.

Colazide® capsules are not addictive.

Before you take Colazide®

When you must not take it

Do not take Colazide® if you

  • are allergic to any ingredient in Colazide®
  • have a history of hypersensitivity to aspirin-type products
  • are very prone to bleeding
  • have severe liver problems
  • have moderate to severe kidney problems
  • are taking any medications that prevent blood clotting
  • have an active peptic ulcer
  • are in the last weeks of pregnancy.

Pregnant women should not take Colazide® unless your doctor says so. Ask your doctor about the risks and benefits involved.

Do not take Colazide® while you are breastfeeding. Your baby can take in Colazide® from breast milk if you are breastfeeding.

Do not use Colazide® after the use by (expiry) date printed on the pack. It may have no effect at all, or worse, an entirely unexpected effect if you take it after the expiry date.

Do not use Colazide® if the packaging is torn or shows signs of tampering.

Do not use it to treat any other complaints unless your doctor says it is safe.

Do not give this medicine to anyone else.

Before you start to take it

You must tell your doctor if:

  1. you have any allergies to
  • any ingredient listed at the end of this leaflet
  • aspirin and aspirin-type products
  • other medicines used to treat ulcerative colitis
  • any other medicines, foods, dyes or preservatives.

If you have an allergic reaction, you may get a skin rash or hay fever, have difficulty breathing or feel faint.

  1. you have any of these medical conditions
  • mild liver problems
  • mild or history of kidney problems
  • asthma
  • stomach ulcer
  • bleeding problems.

It may not be safe for you to take Colazide® if you have any of these conditions.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

  • digoxin
  • methotrexate or similar-type drugs
  • oral antibiotics
  • any other medicine that you buy at the chemist, supermarket or health food shop.

These medicines may affect the way Colazide® works.

Your doctor or pharmacist can tell you what to do if you are taking any of these medicines.

If you have not told your doctor about any of these things, tell them before you take any Colazide®.

Taking Colazide®

How to take it

When you have symptoms:
The usual dose is 3 capsules taken 3 times a day (a total of 9 a day). Take this until your symptoms are better. Do not take this dose for more than 12 weeks without discussing it with your doctor.

To prevent symptoms returning:
The usual dose is 2 capsules taken twice daily. Your doctor may adjust this dose up or down depending on how you respond.

Swallow Colazide® capsules whole, with food.

If you forget to take it

If you forget to take a dose, take it as soon as you remember as long as it is 4 hours before it is due, and then go back to taking it as normal.

If it is less than 4 hours until 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 that you missed.

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

If you take too much (Overdose)

Telephone your doctor, the Poisons Information Centre (13 11 26) or go to casualty at your nearest hospital immediately if you think that you or anyone else may have taken too much Colazide® even if there are no signs of discomfort or poisoning.

If you take too many Colazide® capsules you may have a headache and stomach pains.

While you are taking Colazide®

Things you must do

You must contact your doctor if you notice any unusual bleeding or bruising. Unusual bleeding or bruising may be a sign that you are experiencing a serious side effect of Colazide®.

Use Colazide® exactly as your doctor has prescribed.

Tell all doctors, dentists and pharmacists who are treating you that you are taking Colazide®.

Tell your doctor if you become pregnant while you are taking Colazide®.

Please talk to your doctor or pharmacist about these possibilities if you think they may bother you.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Colazide®.

Colazide® helps most people with ulcerative colitis, but it may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

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

  • headache
  • stomach pain or heartburn
  • diarrhoea
  • nausea (feeling sick) or vomiting
  • bloating or wind
  • worsening of colitis.

These are all mild side effects of Colazide®.

Tell your doctor immediately or go to casualty at your nearest hospital if you notice any of the following:

  • unusual bleeding or bruising sudden signs of allergic reactions such as rash, itching or hives, shortness of breath, wheezing, coughing, or swelling of limbs, face, lips, mouth, tongue or throat which may cause difficulty swallowing or breathing
  • fever
  • excessive tiredness
  • muscle aches or pains.

These are all serious side effects. You may need urgent medical attention.

Serious side effects are rare.

Tell your doctor if you notice anything else that is making you feel unwell. Some people may get other side effects while taking Colazide®.

After using it

Storage

Keep your capsules in the bottle until it is time to take them. If you take Colazide® out of the bottle it will not keep well.

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

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

Keep it where young 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 leave it in the car on hot days.

Disposal

Ask your pharmacist what to do with any capsules you have left over if your doctor tells you to stop taking them, or you find that the expiry date has passed.

Product description

What Colazide® looks like

Colazide® capsules are beige and are marked with "CZ" in black.

Ingredients

Each Colazide® capsule contains 750 mg balsalazide sodium as the active ingredient, plus the excipients:
Magnesium stearate (E 572)
Silica-colloidal anhydrous
Gelatin (E 441)
Shellac

The gelatin capsules are coloured with titanium dioxide (E 171), iron oxide red CI77491 (E 172), iron oxide yellow CI77492 (E 172), and iron oxide black CI77499 (E 172).

Colazide® is registered in bottles of 130, 180 and 280 capsules (not all pack sizes are available).

Colazide® does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Manufacturer

Fresenius Kabi Australia Pty Limited
Level 2, 2 Woodland Way,
Mount Kuring-gai NSW 2080
Australia
Tel: (02) 9391 5555

This leaflet was prepared 7 April 2017

Australian Registration Number

AUST R 77358

® Registered trademark

Published by MIMS October 2017

BRAND INFORMATION

Brand name

Colazide

Active ingredient

Balsalazide sodium

Schedule

S4

 

1 Name of Medicine

Balsalazide sodium.

2 Qualitative and Quantitative Composition

See Table 1.

3 Pharmaceutical Form

Colazide capsules are size 00 hard gelatine capsules (beige body and cap), containing an orange/yellow powder with "CZ" printed in black on the cap.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of mild to moderate active ulcerative colitis and maintenance of remission, in patients who are intolerant to sulfasalazine.

4.2 Dose and Method of Administration

Colazide capsules should be swallowed whole with food.

Adults.

Treatment of active disease.

3 capsules three times daily until remission or for 12 weeks maximum.

Maintenance treatment.

2 capsules twice daily. The dose can be adjusted based on each patient's response. An additional benefit has been shown with a dose of 8 capsules daily.
Rectal or oral steroids can be given concomitantly if necessary.

4.3 Contraindications

Hypersensitivity to any component of the product or its metabolites, including mesalazine. History of hypersensitivity to salicylates. Severe hepatic impairment, moderate-severe renal impairment. Last weeks of pregnancy. Patients with a pathological tendency to bleeding, those on concomitant anticoagulants and those with active peptic ulceration.

4.4 Special Warnings and Precautions for Use

General.

Balsalazide should be used with caution in patients with asthma.

Blood dyscrasias.

During treatment with Colazide, blood counts, BUN/ creatinine and urine analysis should be performed. Blood dyscrasias have been reported rarely with other mesalazine releasing products. Patients receiving balsalazide should be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or malaise that occurs during treatment. A blood count should be performed and the drug stopped immediately if there is suspicion of a blood dyscrasia.

Use in hepatic impairment.

Balsalazide should be used with caution in patients with mild to moderate hepatic impairment.

Use in renal impairment.

Renal toxicity has been observed in animals and in patients given other mesalazine products. Balsalazide is therefore contraindicated in patients with moderate to severe renal impairment. Caution should be exercised when administering balsalazide to patients with mild renal impairment or a history of renal disease.

Use in the elderly.

No dose adjustment is required in elderly patients.

Paediatric use.

Balsalazide is not recommended for use in children < 18 years old.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No formal drug interaction studies have been conducted with balsalazide.
The acetylated metabolites of balsalazide are actively secreted in the renal tubule to a high degree. Therefore, plasma levels of co-prescribed drugs also eliminated by this route may be raised and this should be noted in the case of those with a narrow therapeutic range, such as methotrexate.
Pharmacodynamic interactions have not been studied. However, while balsalazide, mesalazine and N-acetylmesalazine are salicylates chemically, their properties and kinetics make classical salicylate interactions such as those found with acetylsalicylic acid very unlikely.
The uptake of digoxin has been impaired in some individuals by concomitant treatment with sulfasalazine. Even if it is not known whether this would occur also during treatment with balsalazide, it is recommended that plasma levels of digoxin should be monitored in digitalised patients starting Colazide.
The use of orally administered antibiotics could, theoretically, interfere with the release of mesalazine in the colon.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies in rats showed no adverse effects of balsalazide on fertility or general reproductive performance at oral doses up to 2 g/kg/day (about 2.4 times the maximum recommended clinical dose of 6.75 g/kg, based on body surface area).
(Category C)
Studies in rats and rabbits revealed no evidence for fetotoxicity of balsalazide at oral doses up to 2 and 1.2 g/kg/day, respectively (approximately 3 times the maximum recommended clinical dose of 6.75 g/kg, based on body surface area). Adequate human data on use during pregnancy are not available. In common with other anti-inflammatory agents, mesalazine (released from Colazide) may produce premature closure of the ductus arteriosus and may, if given at term, prolong labour and delay parturition. Mesalazine is a salicylate and salicylates (for example aspirin (acetylsalicylic acid)) may increase bleeding tendency both in the newborn child and the mother. Colazide is therefore contraindicated in the last weeks of pregnancy. Colazide should only be given during pregnancy if the benefits clearly outweigh the risks.
 Balsalazide should not be given to breastfeeding women as the active metabolite mesalazine has produced adverse effects in nursing infants. It is not known whether balsalazide is excreted into human or animal milk.

4.7 Effects on Ability to Drive and Use Machines

Balsalazide does not affect the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

In clinical trials with balsalazide in ulcerative colitis, the most commonly reported adverse effects were headache and gastrointestinal symptoms such as abdominal pain, diarrhoea, nausea and vomiting.
Adverse events reported by 1% or more of patients treated with balsalazide 6.75 g/day in three controlled clinical studies are presented by treatment group in Table 2.
Generally, adverse effects are expected to be those of mesalazine. Reactions reported during treatment with oral mesalazine are listed below.

Blood and lymphatic system disorders.

Blood dyscrasias, aplastic anaemia, leucopenia, neutropenia, agranulocytosis, thrombocytopenia.

Nervous system disorders.

Headache, neuropathy.

Cardiac disorders.

Myocarditis, pericarditis.

Respiratory, thoracic and mediastinal disorders.

Bronchospasm, allergic alveolitis.

Gastrointestinal disorders.

Abdominal pain, diarrhoea, nausea, vomiting, aggravation of ulcerative colitis, acute pancreatitis.

Hepatobiliary disorders.

Hepatitis, cholelithiasis, increased liver enzymes.

Skin and subcutaneous tissue disorders.

Alopecia, rash, angioedema.

Musculoskeletal and connective tissue disorders.

Systemic lupus erythematosus-like syndrome, arthralgia, myalgia.

Renal and urinary disorders.

Interstitial nephritis.

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

There is limited experience with overdosing. Possible symptoms include nausea, vomiting, diarrhoea as well as intensification of the described adverse effects. In the event of an overdose the mainstay of treatment is supportive and symptomatic care. For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Balsalazide is a prodrug of the active metabolite, mesalazine, which is linked to a carrier molecule (4-aminobenzoyl-β-alanine) via an azo bond. It is believed that mesalazine is released in the colon by bacterial azo reduction. Mesalazine is an intestinal anti-inflammatory agent acting locally on the colonic mucosa. Its precise mechanism of action is unknown. Balsalazide and the carrier molecule are not thought to contribute to the pharmacological action of the drug.

Clinical trials.

Two randomized, double blind studies demonstrated the efficacy and safety of Colazide compared to mesalazine in patients with mildly to moderately active ulcerative colitis. Efficacy measurements included clinical symptoms and endoscopic findings.
In the first trial, 154 patients were randomized and treated with daily doses of Colazide 6.75 g (equivalent to 2.4 g of mesalazine), Colazide 2.25 g (equivalent to 0.8 g of mesalazine) or mesalazine 2.4 g. After 8 weeks of treatment, Colazide 6.75 g was shown to be significantly superior to Colazide 2.25 g in improving stool blood, stool frequency and/or sigmoidoscopic score and Physician's Global Assessment (PGA) (see Figure 1).
A greater percentage of patients treated with Colazide reported improvement in clinical symptoms than patients treated with mesalazine, however, these differences did not reach statistical significance.
Colazide 6.75 g was shown to be significantly better than mesalazine 2.4 g in improving sigmoidoscopic results at weeks 2 (p = 0.006) and 8 (p = 0.032), but not at week 4 (p = 0.074) (see Figure 2). At all time points, a greater percentage of patients treated with Colazide 6.75 g showed sigmoidoscopic improvement than patients treated with either mesalazine 2.4 g or Colazide 2.25 g.
In a second study, 101 patients were randomized to receive daily doses of Colazide 6.75 g or mesalazine 2.4 g for up to 12 weeks. Colazide was shown to be comparable to mesalazine in achieving symptomatic improvement of acute ulcerative colitis. The median time to complete symptom relief was 10 days for patients treated with Colazide 6.75 g, compared to 25 days for patients treated with mesalazine 2.4 g (see Figure 3).

5.2 Pharmacokinetic Properties

Absorption.

Balsalazide is believed to achieve its action through the topical effects of mesalazine on the colonic mucosa. Systemic absorption is therefore not necessary for efficacy. However, following oral administration an undetermined proportion of the dose is absorbed. Less than 1% of this proportion appears as intact balsalazide in the systemic circulation. Most of the absorbed material is in the form of mesalazine (5-ASA) or N-acetyl 5-ASA. The absolute bioavailability of balsalazide has not been determined.
The Tmax for intact balsalazide is 1-2 hours. The Tmax for 5-ASA and N-acetyl 5-ASA is approximately 9-10 hours, suggesting that release of the active drug mesalazine occurs in the colon.
Administration with food results in decreased absorption of intact balsalazide, but no change in the absorption of 5-ASA or N-acetyl 5-ASA.

Distribution.

The protein binding of intact balsalazide is approximately 99%.

Metabolism.

Balsalazide is believed to be broken down in the colon into the active molecule 5-ASA and the carrier molecule 4-aminobenzoyl-β-alanine (4-ABA). On systemic absorption, both the carrier molecule and 5-ASA are rapidly N-acetylated.

Excretion.

Approximately 25% of an orally administered dose is eliminated in the urine, in the form of the N-acetyl metabolites. The remainder is eliminated in the faeces.

Special populations.

No information is available on the effects of age, gender, hepatic impairment or renal insufficiency on the pharmacokinetics of balsalazide or its metabolites.

5.3 Preclinical Safety Data

Genotoxicity.

Balsalazide was not genotoxic in assays for chromosomal damage (including the in vivo mouse micronucleus test). In assays for gene mutations, balsalazide was negative in the Ames test and mouse lymphoma cell forward gene mutation test, but gave equivocal results in the Chinese hamster lung cell forward gene mutation test.
4-aminobenzoyl-β-alanine, a metabolite of balsalazide, was not genotoxic in assays for gene mutations (Ames test and the mouse lymphoma cell forward gene mutation test) but gave equivocal results in an assay for chromosomal damage (in vitro human lymphocyte chromosomal aberration test). N-acetyl-4-aminobenzoyl-β-alanine, a conjugated metabolite of balsalazide, was not genotoxic in gene mutation assays (Ames test and the mouse lymphoma cell forward mutation tests) or an assay for chromosomal damage (in vitro human lymphocyte chromosomal aberration test).

Carcinogenicity.

When balsalazide was given to rats at dietary doses up to 2 g/kg/day for 104 weeks, an increased incidence of benign adrenal phaeochromocytoma was noted in male rats at the highest dose tested (representing a systemic exposure of about 2.4 times the maximum anticipated patient exposure on a mg/m2 basis).

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

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

6.3 Shelf Life

Approved shelf life as packaged for sale: 2 years.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

AUST R 77358.
Colazide is registered in bottles of 130, 180, 280 capsules (not all pack sizes are available).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical Name: 5-[4-(2-carboxyethylcarbamoyl)-phenylazo]-salicylic acid disodium salt dihydrate.
Empirical Formula: C17H13N3O6Na2.2H2O.
Molecular Weight: 401.32 (437.32 for the dihydrate).

Chemical structure.


CAS number.

Active substance: balsalazide sodium.
CAS number: 80573-04-2.

7 Medicine Schedule (Poisons Standard)

Australia: Schedule 4 - Prescription Only Medicine.

Summary Table of Changes