Consumer medicine information

Pro-Cid

Probenecid

BRAND INFORMATION

Brand name

Pro-Cid

Active ingredient

Probenecid

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Pro-Cid.

What is in this leaflet

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

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

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

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

What PRO-CID is used for

PRO-CID is used to prevent gout or gouty arthritis. It is not used to treat an acute attack of gout.

PRO-CID helps remove excess uric acid from the body which helps prevent uric acid crystals forming deposits in some joints. This will help prevent joints becoming swollen and painful.

PRO-CID can also help increase the level of certain antibiotics in the blood which helps increase the effectiveness of the antibiotics to treat an infection.

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

Before you take PRO-CID

When you must not take it

Do not take PRO-CID if you have an allergy to:

  • any medicine containing probenecid
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction are:

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

Do not take this medicine if you have certain blood disorders. Your doctor will advise you.

Do not take this medicine if you currently have, or are prone to, kidney stones.

Do not take this medicine if you are taking aspirin or any medicines containing aspirin.

Do not start to take this medicine if you have an acute attack of gout. Other medication may be needed to relieve the symptoms of an acute attack of gout.

Do not give this medicine to children under the age of two years. Safety and effectiveness in children under the age of two has not been established.

You should 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, talk to your doctor.

Before you start to take PRO-CID

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

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

  • stomach ulcers
  • kidney disease.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor will discuss with you the possible risks and benefits involved.

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

Taking other medicines

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

Some medicines and PRO-CID may interfere with each other. These include:

  • aspirin or any medicine containing aspirin
  • pyrazinamide and rifampicin, medicines used to treat tuberculosis and other infections
  • methotrexate, a medicine used to treat cancer
  • allopurinol, medicines used to treat high levels of uric acid in the blood
  • some antibiotics known as sulphonamides
  • thiazide diuretics, medicines used to treat excess fluid
  • thiopental and ketamine, medicines used for general anaesthesia
  • medicines used to treat viral infections such as valaciclovir/aciclovir, ganciclovir, famciclovir/penciclovir.
  • zidovudine (AZT), a medicine used to treat HIV infection
  • lorazepam, a medicine used to treat anxiety
  • anti-inflammatories and antipyretic medicines used to reduce pain and fever such as paracetamol and naproxen
  • ciprofloxacin, a medicine used to treat antibacterial infections
  • anxiolytic, sedative, hypnotic and antipsychotic medicines such as midazolam and nitrazepam
  • medicines used to treat diabetes
  • famotidine, a medicine used to treat stomach ulcers.

These medicines may be affected by PRO-CID or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

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

How to take PRO-CID

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

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

How much to take

When taking PRO-CID to treat gout the standard starting dose for adults is half a tablet twice a day for a week, then one tablet twice a day thereafter.

Your doctor may have prescribed a different dose depending on the amount of uric acid in your blood or urine.

When taking PRO-CID to help antibiotics work better the dose will depend on the infection being treated and the type of antibiotic being used.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take.

Follow the instructions they give you. If you take the wrong dose, PRO-CID may not work as well and your problem may not improve.

How to take it

Swallow the tablets whole with a full glass of water.

When to take it

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

If you take the tablets twice a day take them about 12 hours apart.

If you take the tablets four times a day take them about every 6 hours.

How long to take it

Continue taking your medicine for as long as your doctor tells you. This medicine helps to control your condition but does not cure it. It is important to continue to take your medicine even if you feel well.

Continue taking your medicine if you have an acute attack of gout. Your doctor may prescribe other medicines to relieve the symptoms of the acute attack.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

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

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

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

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre on 13 11 26 (Australia) for advice, or go to the Emergency Department at your nearest hospital, if you think that you or anyone else may have taken too much PRO-CID, even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include:

  • stomach upset
  • fits or seizures
  • difficulty breathing

Refer to the Side effects section below for other side effects that may occur while taking PRO-CID.

While you are taking PRO-CID

Things you must do

Tell any other doctors, dentists, and pharmacists who are treating you that you are taking PRO-CID.

If you are about to be started on any new medicine, remind your doctor, or pharmacist that you are taking PRO-CID.

Check with your doctor before using urine sugar tests, which contain copper sulphate, for example Clinitest. PRO-CID may cause false test results with some urine sugar tests.

Always drink plenty of fluid, especially when you first start on PRO-CID. The amount of uric acid in the kidneys is increased and this can cause kidney problems in some people. Drinking plenty of water may help prevent this.

Follow your doctor’s advice on diet and alcohol consumption. Some foods are best avoided when suffering from gout.

Things you must not do

Do not give PRO-CID to anyone else, even if they have the same condition as you.

Do not use PRO-CID to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how PRO-CID affects you. This medicine may cause dizziness in some people. If you have any of these symptoms do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking PRO-CID. This medicine helps most people with gout, 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 attention if you get some of the side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

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
  • nausea or vomiting
  • loss of appetite
  • flushing or redness of the skin
  • looking pale
  • dizziness or light-headedness
  • frequent urge to pass water
  • sore gums
  • hair loss.

The above list includes the more common side effects of PRO-CID.

Tell your doctor as soon as possible if you notice any of the following:

  • blood in the urine or other kidney problems
  • severe or sharp pain in the side or lower back
  • tiredness
  • frequent or worrying infection such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than usual
  • nosebleeds
  • yellowing of the skin and/or eyes
  • unusual hair loss or thinning
  • painful swollen joints.

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

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

  • severe skin reaction which starts with large blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • swelling of the face lips, tongue or other parts of the body. This may cause difficulties swallowing or breathing
  • shortness of breath, wheezing or trouble breathing
  • rash, itching or hives on the skin
  • fainting.

These may be very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

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

After taking PRO-CID

Storage

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

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store PRO-CID 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.

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

Disposal

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

Product description

What it looks like

PRO-CID is a yellow capsule-shaped film coated tablet, bisected on one side, with no embossing.

PRO-CID is supplied in bottles of 100.

Ingredients

Each PRO-CID tablet contains 500 mg of probenecid as the active ingredient.

Each tablet also contains:

  • maize starch
  • microcrystalline cellulose
  • sodium starch glycolate
  • povidone
  • stearic acid
  • colloidal anhydrous silica
  • magnesium stearate
  • opadry yellow and opadry clear.

The medicine does not contain lactose, sucrose, gluten or tartrazine.

Supplier

PRO-CID™ is supplied in Australia by:

Phebra Pty Ltd
19 Orion Road,
Lane Cove West, NSW 2066,
Australia.

PRO-CID™ 500 mg probenecid per tablet 100 tablets

AUST R 74598

Phebra product code- TAB009

Date of most recent amendment: June 2018.

Phebra, PRO-CID and the Phi symbol are trademarks of Phebra Pty Ltd, 19 Orion Road, Lane Cove West, NSW 2066, Australia.

Published by MIMS November 2018

BRAND INFORMATION

Brand name

Pro-Cid

Active ingredient

Probenecid

Schedule

S4

 

1 Name of Medicine

Probenecid.

2 Qualitative and Quantitative Composition

Each Pro-Cid tablet contains 500 mg probenecid.
Probenecid is a white or nearly white, fine, crystalline powder. It is slightly bitter with a pleasant aftertaste.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Pro-Cid 500 mg tablets are a yellow capsule-shaped film coated tablet, bisected on one side, with no embossing.

4 Clinical Particulars

4.1 Therapeutic Indications

Pro-Cid is indicated for:

Gout.

Probenecid is a uricosuric agent for the treatment of hyperuricaemia in all stages of gout and gouty arthritis except an acute attack.
Asymptomatic hyperuricaemia seems to occur in a significant percentage of relatives of gouty patients. Probenecid may be given prophylactically to these people to forestall gouty attacks and urate deposition in tissues.
By virtue of its effective uricosuric activity, probenecid may be used to control the hyperuricaemia induced or aggravated by many diuretics employed for the treatment of oedema and hypertension (e.g. thiazides and similar diuretics).

β-Lactam antibiotic therapy.

Probenecid is indicated for the elevation and prolongation of plasma levels by whatever route the antibiotic is given. A two-to-fourfold increase in plasma levels has been demonstrated for benzylpenicillin, phenoxymethylpencillin, the synthetic penicillins, ampicillin, methicillin, oxacillin, cloxacillin, nafcillin, carbenicillin, and for the cephamycin, Mefoxin (cefoxitin sodium, MSD), and the cephalosporins, cephalothin, cephalexin and cephaloglycin.
Because of its mechanism of action, probenecid is not recommended in conjunction with a β-lactam antibiotic in the presence of known renal impairment.

Concurrent treatment with cidofovir for CMV retinitis in HIV patients.

Probenecid is recommended to be administered concomitantly with cidofovir, as the combination reduces the potential for nephrotoxicity associated with cidofovir.

4.2 Dose and Method of Administration

Tablet 500 mg probenecid, oral use.

Gout.

Probenecid therapy should not be initiated until an acute gouty attack has subsided. Should an acute attack be precipitated during therapy, the drug may be continued without changing the dosage, and therapeutic doses of colchicine, indomethacin, or other appropriate therapy may be administered to control the acute attack.

Adults.

The recommended dose for adults is 250 mg (½ tablet) twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter.
As some degree of renal impairment is common in patients with gout, a daily dosage of 1 g may be adequate for many patients. The daily dosage may be increased, if necessary, by increments of 500 mg every four weeks, but usually not beyond 2 g daily, if symptoms of gouty arthritis are not controlled or the 24-hour urate excretion is not above 700 mg.
In chronic renal insufficiency, particularly when the glomerular filtration rate is 30 mL/minute or less, probenecid may not be effective.
Gastric intolerance may be indicative of overdosage. This may be corrected by reducing the dose without losing the required therapeutic response.
To maintain an alkaline urine, sufficient sodium bicarbonate (3 g to 7.5 g daily) or potassium citrate (7.5 g daily) is recommended. When such quantities of alkali are administered, monitor the acid-base balance of the patient. Alkalisation of the urine is recommended until the serum uric acid level returns to normal and tophaceous deposits disappear, i.e. during the period when urinary excretion of urates is at a high level. Male normal upper limit is about 0.36 mmol/L. Female normal upper limit is about 0.30 mmol/L. Alkalisation of the urine probably is unnecessary after the miscible pool of uric acid decreases to normal (about 1 g) and deposited urates are resorbed and eliminated, since the urinary urate concentration is lower and less likely to cause crystallisation.
Probenecid should be continued long term at a dosage that will maintain a normal serum uric acid level. If acute attacks have been absent for six months or more and serum uric acid levels remain within normal limits, the daily dosage may be decreased by one tablet every six months to a minimum effective dose. The maintenance dosage should not be reduced to the point where serum uric acid levels tend to rise.

Therapy of uncomplicated gonorrhoea.

For this condition treatment in men or women, a single 1 g dose of Pro-Cid (2 tablets) should be given with adequate doses of oral ampicillin, intramuscularly injected aqueous procaine penicillin or cefoxitin. If oral ampicillin is used, probenecid should be administered simultaneously. If a parenteral antibiotic is administered, the dose of probenecid should be given preferably at least 30 minutes before the injection.

General beta-lactam antibiotic therapy.

The adult recommended dosage is 2 g Pro-Cid (4 tablets) daily in divided doses, reduced in older patients suspected of having renal impairment. Due to its mechanism of action, probenecid is not recommended for concurrent use with a β-lactam antibiotic in the presence of known renal impairment.

Therapy with cidofovir.

2 g Pro-Cid (4 x 500 mg tablets) should be administered three hours before each dose of cidofivir and 1 gram (2 x 500 mg tablets) two and eight hours after the completion of the one hour infusion period (4 grams altogether). Evidence for a nephroprotective effect of probenecid with cidofovir was shown in a 52 week study conducted in cynomolgus monkeys.

Children.

For two years of age or older the recommended dosage is 25 mg/kg (or 0.7 g/square metre body surface) of bodyweight initially, followed by 40 mg/kg (or 1.2 g/square metre body surface) daily in divided doses every six hours. For children weighing more than 50 kilograms the adult dose is recommended.

Note.

The phenolsulfonphthalein (PSP) excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. When the dose of probenecid is adequate the renal clearance of PSP is reduced to about one-fifth of the normal rate.

4.3 Contraindications

Pro-Cid is contraindicated in:
Hypersensitivity to any component of this product;
Blood dyscrasias;
Uric acid stones;
Children less than two years of age;
Coadministration with salicylates.

4.4 Special Warnings and Precautions for Use

Use with caution.

In patients with a history of peptic ulcer.
If given concurrently with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Haematuria, renal colic, costovertebral pain, and formation of urate stones associated with the use of probenecid in gouty patients may be prevented by alkalisation of the urine and a liberal fluid intake (see Section 4.2 Dose and Method of Administration). When alkali is administered, the acid-base balance should be watched.
Should exacerbation of gout occur during therapy with probenecid, a therapeutic dose of indomethacin, colchicine or other appropriate therapy should be added.
If hypersensitivity reactions appear cease therapy with probenecid preparations.

Use in renal impairment.

Probenecid may not be effective in chronic renal insufficiency, particularly when the glomerular filtration rate is 30 mL/min or less.

Use in the elderly.

No data available.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

Patients receiving probenecid may produce a false-positive Benedict's test leading to the possibility of a false diagnosis of glycosuria due to the presence of a reducing substance in the urine. This effect disappears when therapy is discontinued. Suspected glycosuria should be confirmed using a specific test for glucose, using enzymatic glucose oxidase reactions instead of copper reduction methods.
When therapeutic concentrations of theophylline and probenecid were added to human plasma in an in vitro study, falsely high readings for theophylline were reported using the Schack and Waxler technique.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Aspirin use in either small or large doses is contraindicated because it antagonises the uricosuric action of probenecid. In patients on probenecid who require a mild analgesic agent, the use of paracetamol rather than small doses of salicylates would be preferable.
Pyrazinamide also antagonises the uricosuric action of probenecid.
If methotrexate is given concurrently, its dosage should be reduced and serum levels may need to be monitored. Probenecid decreases the tubular secretion of methotrexate and may potentiate its toxicity.
Probenecid increases the mean plasma elimination half-life of paracetamol, naproxen, ciprofloxacin, indomethacin, ketoprofen, meclofenamate, rifampicin, valaciclovir/aciclovir, famiciclovir/penciclovir, ganciclovir, zidovudine, dapsone, ketorolac, lorazepam, midazolam, and nitrazepam (not temazepam). Increased plasma concentrations and adverse events may result, requiring an adjustment in the usual dosage of these drugs.
Allopurinol and probenecid used together may both have increased plasma concentrations.
Since probenecid decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when coadministration for prolonged periods occurs.
Probenecid may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycaemia. Probenecid may also potentiate the effects of thiazide diuretics.
Less thiopental for induction of anaesthesia may be required. Ketamine and thiopental anaesthesia may be prolonged.
Probenecid has also been reported to inhibit the renal transport of many other compounds including rho-aminohippuric acid (PAH), para-aminosalicylic acid (PAS), panthothenic acid, indomethacin, famotidine, sodium iodomethamate and related iodinated organic acids, sodium acetrizoate, erythromycin, 17-ketosteroids, pantothenic acid, phenolsulfonphthalein (PSP) and cephalosporins (excluding ceftazidime and ceftriaxone). It decreases both hepatic and renal secretion of sulfobromophthalein (BSP).
Probenecid does not influence plasma salicylate concentrations, nor does it affect the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline or neomycin. The effects on excretion of cephaloridine are not clinically significant.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There were no adverse effects on reproductive parameters in groups of male and female SD rats, given probenecid in the diet at dose levels of 10, 50, and 100 mg/kg/day from 10 weeks prior to breeding and through the breeding of two successive litters.
(Category B2)
Probenecid is Pregnancy Category B2 - 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 fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Probenecid crosses the placental barrier and appears in cord blood. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against possible hazards.
 It is not known whether this drug is excreted in human or animal milk. Because many drugs are excreted in human milk, caution should be exercised when probenecid is administered to a nursing mother.

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)

CNS.

Headache, dizziness.

Gastrointestinal.

Nausea, anorexia, vomiting, sore gums. Hepatic necrosis occurs rarely.

Genitourinary.

In gouty patients, uric acid stones with or without haematuria, renal colic or costovertebral pain has been observed. Nephrotic syndrome occurs rarely. Urinary frequency has been reported.

Hypersensitivity.

Anaphylaxis, fever, pruritus, urticaria, Stevens-Johnson syndrome.

Haematologic.

Anaemia, haemolytic anaemia which could be related to genetic deficiency of glucose-6-phosphate dehydrogenase in red blood cells. Aplastic anaemia, leucopenia and thrombocytopenia occur rarely.

Integumentary.

Alopecia, dermatitis, flushing. After combination therapy of colchicine and probenecid, toxic epidermal necrolysis has been reported rarely.

Musculoskeletal.

Exacerbation of gout.
Retinopathy has been reported once in conjunction with chloroquine.

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

In massive overdosage, probenecid causes stimulation of the central nervous system which may lead to convulsions and death from respiratory failure. Symptomatic and supportive measures should be employed in the event of overdosage. Use activated charcoal, ideally within one hour of ingestion. Should signs of central nervous system excitation be present, a short-acting barbiturate may be given parenterally.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Probenecid is a uricosuric and renal tubular blocking agent. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits.
Despite pronounced uricosuric activity, time is required to achieve clinical results. Acute attacks of gout may occur during the early phase of therapy in spite of the return to normal of the serum uric acid level. However, with continued use for some months, attacks of acute gout become less frequent and less intense.
As urate deposits in periarticular and articular structures are reabsorbed, joint pain is relieved, greater articular mobility is achieved, and further joint destruction may be averted. As urate deposits are mobilised from the gouty kidney, renal function may improve and further destructive changes may be prevented.
Probenecid inhibits the tubular reabsorption of phosphorus in hypoparathyroid but not in euparathyroid individuals.
Probenecid increases plasma concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Probenecid is completely absorbed after oral administration. Peak plasma levels are reached in two to four hours.

Distribution.

Between 85 and 95% of probenecid is bound to plasma albumin; the apparent volume of distribution of the drug is 11 litres.

Metabolism.

Metabolism involves oxidation of alkyl side chains and glucuronide conjugation. The major metabolite, probenecid acyl glucuronide, accounts for close to 50% of the dose. Approximately equal amounts (10 - 15%) of mono-n-propyl, secondary alcohol and carboxylic acid metabolites are excreted. The primary alcohol metabolite is not found in measurable amounts. The plasma half-life is between six and twelve hours, and increases with increasing dose (over the therapeutic dosage range) due to nonlinear disposition.

Excretion.

Probenecid is excreted both by glomerular filtration (unbound fraction only) and by active secretion by the proximal renal tubule. Following oral administration, 75 - 88% of the dose is found in the urine mainly as metabolites and as lesser amounts of unchanged drug. The urinary excretion of unchanged probenecid is dependent on both the pH and flow rate of urine.

5.3 Preclinical Safety Data

Genotoxicity.

No evidence of mutagenicity was observed in a microbial mutagenicity test using mutant strains of Salmonella typhimurium with or without rat or hamster liver metabolic activation. No genetic damage was noted in a chromosome aberration study in CHO cells. Variable results were obtained in a sister chromatid exchange (SCE) test in CHO cells. One trial caused a dose-related increase in SCE's, a second trial was negative, and a third trial had significant increases at the lowest and highest doses tested (but not in the intermediate doses).

Carcinogenicity.

In a 23-month carcinogenic study in mice, a significant increase in the incidence of hepatocellular carcinomas and adenomas was observed at a dose of 400 mg/kg/day in female mice. These changes were not observed in male mice or rats of either sex that received the same dose, or in mice of either sex at a dose of 100 mg/kg/day.

6 Pharmaceutical Particulars

6.1 List of Excipients

The excipients are cellulose microcrystalline, starch (maize), sodium starch glycollate, stearic acid, povidone, silica colloidal anhydrous, magnesium stearate and opadry yellow and opadry clear.

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)1. The expiry date can be found on the packaging.
1AUST R 74598.

6.4 Special Precautions for Storage

Store below 30°C in a dry place.

6.5 Nature and Contents of Container

Pro-Cid is supplied in a bottle of 100 tablets.
Phebra product code - TAB009.

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 Name: 4-(dipropylsulphamoyl) benzoic acid, calculated with reference to the dried substance.
The molecular weight of the compound is 285.4. The molecular formula is C13H19NO4S.

Chemical structure.


CAS number.

57-66-9.
Probenecid is soluble in chloroform, dilute alkali, alcohol, and acetone, and practically insoluble in water and dilute acids. It is soluble in dilute solutions of sodium hydroxide which can be buffered to pH 7.4 with monopotassium phosphate or other similar buffer.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes