Colazide

Colazide 750 mg hard capsules

Each capsule contains 750 mg of balsalazide disodium corresponding to balsalazide 612.8 mg and to mesalazine 262.5 mg.

For the full list of excipients, see section 6.1.

Capsule, hard.

Size 00 beige gelatin capsules.

Colazide is indicated for the treatment of mild-to-moderate active ulcerative colitis and maintenance of remission.

Posology

Method of administration

To be swallowed whole with or after food.

Hypersensitivity to the active substance, to its metabolites, including mesalazine, or to any of the excipients listed in section 6.1.

History of hypersensitivity to salicylates.

Severe hepatic impairment, moderate-severe renal impairment.

Pregnant and breast feeding women.

Colazide should be used with caution in patients with asthma, bleeding disorders, active ulcer disease, mild renal impairment or those with established hepatic disease.

Renal function should be monitored before starting an oral aminosalicylate, at 3 months of treatment, and then annually during treatment (more frequently in renal impairment). Blood disorders can occur with aminosalicylates (see recommendation below).

Blood disorders

During treatment with Colazide blood counts, BUN/creatinine and urine analysis should be performed. Patients receiving aminosalicylates 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.

Formal interaction studies have not been performed with Colazide. Available data suggest that the systemically available amounts of balsalazide and its metabolites may be increased if Colazide is administered in the fasting as compared with the fed state. Therefore, Colazide should preferably be administered with food.

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 sulphasalazine. 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.

Mesalazine inhibits thiopurine methyltransferase. In patients receiving azathioprine or 6-mercaptopurine, caution is recommended for concurrent use of mesalazine as this can increase the potential for blood dyscrasias.

Pregnancy

Human experience with balsalazide is limited, therefore Colazide should not be given to pregnant women.

Breast-feeding

Colazide should not be given to breast feeding women as the active metabolite mesalazine has produced adverse effects in nursing infants.

Fertility

Animal studies on fertility and reproductive function did not reveal adverse effects of balsalazide.

Colazide has no or negligible influence on the ability to drive and use machines.

The adverse effects are expected to be those of mesalazine.

Reactions reported during treatment with oral mesalazine are listed in the table below.

See Section 4.4 Special warnings and precautions for use.

Reporting of suspected adverse reactions

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

To date, there are no reports of overdosage with mesalazine-releasing products. Overdose with large amounts of balsalazide may result in symptoms resembling mild salicylate intoxication. Treatment should be symptomatic.

Pharmacotherapeutic group: Aminosalicylic and similar agents, ATC code: A07EC.Balsalazide consists of mesalazine linked to a carrier molecule (4-aminobenzoyl-ß-alanine) via an azo bond.

Bacterial azo-reduction releases mesalazine as an active metabolite in the colon. Mesalazine is an intestinal anti-inflammatory agent acting locally on the colonic mucosa. Its precise mechanism of action is unknown. Balsalazide and the carrier do not contribute to the pharmacodynamic action.

The pharmacokinetics of balsalazide and its metabolites have been studied in healthy subjects and patients in remission. The systemic uptake of balsalazide itself is low (<1%) and the major part of the dose is split in the colon by bacterial azoreductase. This cleavage results in the primary metabolites 5-aminosalicylic acid (5-ASA), responsible for the anti-inflammatory action, and 4-aminobenzoyl-beta-alanine (4-ABA), considered to be an inert carrier.

Most of the dose is eliminated via the faeces but about 25% of the released 5-ASA appears systemically predominantly as the N-acetylated metabolite (NASA) after inactivation in the colonic mucosa and liver. The systemic uptake of 4-ABA is only 10-15% of that of 5-ASA and also this metabolite is grossly N-acetylated (to NABA) in the first pass.

In urine, virtually only NASA and NABA are recovered and their renal clearances are high: 0.2-0.3 L/min and 0.4-0.5 L/min, respectively. The half-life of NASA is in the order of 6-9 hours. The half-life of 5-ASA itself is very short: about 1 hour.

Because of the great importance of renal clearance for the elimination, Colazide should be used with caution in renal impairment. No studies have been performed in patients with hepatic disease.

Protein binding of 5-ASA is about 40% and that of NASA about 80%. Available data suggest that the pharmacokinetics of balsalazide is not affected by genetic polymorphism, nor does age seem to be an important factor. Fasting slightly increases the systemic uptake of balsalazide and its metabolites.

Preclinical data reveal no special hazard for humans based on conventional studies of genotoxicity, carcinogenic potential, toxicity to reproduction, safety pharmacology and validating kinetics and metabolism. In repeated dose toxicity studies, nephrotoxicity, an effect known to occur following mesalazine, was observed particularly in rats.

Magnesium stearate, colloidal anhydrous silica, gelatin, shellac, titanium dioxide (E 171), yellow, red and black iron oxide (E 172).

Not applicable

3 years.

No special precautions for storage.

High density polyethylene container fitted with tamper-evident, child-resistant, high density polyethylene screw caps.

Pack sizes are: 50, 54, 56, 100, 112, 130, 224 (2 x 112), 260 (2 x 130), 300 (3 x 100), 500 (10 x 50), 672 (6 x 112) and 780 (6 x 130) capsules.

Not all pack sizes may be marketed.

None.

Almirall, S.A.

Ronda General Mitre, 151

08022 Barcelona

Spain

PL 16973/0019

Date of first authorisation: 18 December 1997

Date of latest renewal: 11 August 2009

17 September 2018