Consumer medicine information

APO-Cefaclor CD Tablets

Cefaclor

BRAND INFORMATION

Brand name

APO-Cefaclor CD

Active ingredient

Cefaclor

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Cefaclor CD Tablets.

What is in this leaflet

This leaflet answers some common questions about cefaclor. 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 using this medicine against the benefits they expect it will have for you.

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

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

What this medicine is used for

Cefaclor is used to treat infections caused by bacteria in different parts of the body, including:

  • chest and lungs (lower respiratory tract)
  • nose, throat, sinuses and tonsils (upper respiratory tract)
  • bladder (lower urinary tract)
  • skin

Cefaclor belongs to a group of medicines called cephalosporin antibiotics. These are closely related to penicillin antibiotics.

It works by killing the bacteria causing your infection or by stopping its growth.

It will not work against infections caused by viruses such as colds or the flu.

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

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

This medicine is not addictive.

There is not enough information to recommend the use of this medicine in children under 12 years of age.

Before you take this medicine

When you must not take it

Do not take this medicine if you have an allergy to:

  • cefaclor
  • other cephalosporins
  • any of the ingredients listed at the end of this leaflet.

Do not take cefaclor if you have had a serious allergic reaction to penicillin.

Some of the symptoms of an allergic reaction may include:

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

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, talk to your doctor.

Before you start to take it

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:

  • kidney disease
  • liver disease
  • bowel conditions or diseases such as colitis
  • bleeding problems.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Do not take this medicine until you and your doctor have discussed the risks and benefits involved.

If you have not told your doctor about any of the above, tell them before you start taking this medicine.

Taking other medicines

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

Some medicines and cefaclor may interfere with each other. These include:

  • probenecid, used to treat gout or to prolong the action of certain antibiotics
  • antacids containing magnesium or aluminium – if you need to take an antacid do not take it within 1 hour of taking cefaclor
  • medicines used to prevent blood clots (e.g. warfarin, heparin)
  • aspirin and non-steroidal anti-inflammatory medicines (NSAIDs), used for pain and inflammation.

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

Talk to your doctor about the need for an additional method of contraception while taking cefaclor. Some antibiotics may decrease the effectiveness of some birth control pills, although this has not been shown with cefaclor.

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

Other medicines not listed above may also interact with cefaclor.

How to take this medicine

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

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

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

For most infections, the usual dose is one 375 mg tablet taken twice a day. This may be increased to two 375 mg tablets taken twice a day for certain types of infections.

If you have severe kidney problems your doctor may tell you to take a lower dose (using a different brand) or space the doses further apart.

How to take it

Swallow the tablets whole with a full glass of water. Do not cut, crush or chew the tablets.

When to take it

This medicine is usually taken twice a day, 12 hours apart.

Take this medicine at 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.

It does not matter if you take it with or without food. However, this medicine will be better absorbed into the body if you take it with food.

How long to take it for

Continue taking this medicine for as long as your doctor tells you, or until you finish the pack, even if you begin to feel better after a few days. If you do not complete the full course as prescribed by your doctor, the infection may not clear completely or your symptoms may return.

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If it is almost time to take 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 dose you missed. This may increase the chance of you experiencing side effects.

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 (telephone 13 11 26) for advice or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much of this medicine. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include nausea, vomiting, severe heartburn and diarrhoea.

While you are taking this medicine

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking this medicine.

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you are about to have any blood or urine tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

If you are diabetic, check with your doctor or pharmacist before using urine sugar tests. Cefaclor may cause false test results with some urine sugar tests.

If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.

If you get severe diarrhoea, tell your doctor, pharmacist or nurse immediately. Do this even if it occurs several weeks after you have stopped taking this medicine. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any diarrhoea medicine without first checking with your doctor.

If you get a sore white mouth or tongue while taking or soon after stopping this medicine, tell your doctor. Also tell your doctor if you get vaginal itching or discharge. This may mean you have a fungal infection called thrush. Sometimes the use of this medicine allows fungi to grow and the above symptoms to occur.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may occasionally do tests to make sure the medicine is working and to prevent side effects.

Things you must not do

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

Do not take your medicine to treat any other complaints unless your doctor tells you to.

Do not stop taking your medicine or change the dosage without first checking with your doctor.

Things to be careful of

Be careful when driving or operating machinery until you know how cefaclor affects you. Cefaclor generally does not cause any problems with your ability to drive a car or operate machinery. However, cefaclor may cause dizziness or tiredness 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 as soon as possible if you do not feel well while you are taking cefaclor.

This medicine helps most people with bacterial infections, 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 lists 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 or pharmacist if you notice any of the following and they worry you:

  • mild stomach complaints, including indigestion, nausea or vomiting, mild diarrhoea or headache
  • dizziness, tiredness, looking pale
  • nosebleed
  • hyperactivity, nervousness, insomnia, confusion, dizziness, hallucinations

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

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

  • oral thrush - white, furry, sore tongue and mouth
  • itching in the genital area
  • vaginal thrush - sore and itchy vagina and/or discharge
  • unusual muscle stiffness
  • pain in the stomach or elsewhere in your body, weakness
  • confusion

The above list includes serious side effects and you may need medical attention.

If any of the following happen, stop taking your medicine and contact your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • kidney pain, blood in the urine, passing more or less urine than is normal for you, cloudy urine
  • yellowing of the skin or eyes, and/or pale stools, dark urine (jaundice)
  • hallucinations
  • signs of frequent infections such as fever, chills, sore throat or mouth ulcers, or other changes in your blood which you may notice as feeling tired, weak, thirsty, or easily bruised
  • watery and severe diarrhoea, which may be bloody or contain mucous
  • swelling or pain in the joints, with or without fever, and sometimes with a rash
  • seizures (fits)
  • skin rashes (including a rash which looks like measles) or hives which may be itchy
  • feeling out of sorts, with fever, headache and cough, then suddenly getting spots or blisters which quickly develop into large amounts of blistering or peeling skin
  • shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body rash, itching or hives on the skin

The above list includes very serious side effects and you may need urgent medical attention or hospitalisation. Serious side effects are usually 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.

Some of these side effects can only be found when your doctor does tests from time to time to check your progress. These include:

  • swelling of the liver
  • inflammation of the kidney

After finishing it

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after you have finished taking this medicine:

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • fever, in combination with one or both of the above.

These are rare but serious side effects. You may have a serious condition affecting your bowel. Cefaclor can change bacteria (which are normally present in the bowel and normally harmless), so that they multiply and cause the above symptoms. You may need urgent medical attention. However, this side effect is rare.

Do not take any diarrhoea medicine without first checking with your doctor.

Storage and disposal

Storage

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

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

Do not store your medicine or any other medicine 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 this medicine 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 medicine left over.

Product description

What it looks like

Capsule shaped, biconvex, unscored, blue film-coated tablet, imprinted with "Cefaclor CD 375mg" in black. AUST R 76226.

Available in blister packs of 10 tablets.

Ingredients

Each tablet contains 375 mg of cefaclor monohydrate as the active ingredient.

It also contains the following:

  • hypromellose
  • hyprolose
  • lactose monohydrate
  • silica-colloidal anhydrous
  • magnesium stearate
  • talc-purified
  • titanium dioxide
  • macrogol 400
  • indigo carmine
  • iron oxide black
  • propylene glycol
  • methanol
  • isopropyl alcohol.

This medicine does not contain gluten, sucrose, tartrazine or any other azo dyes.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113
Tel: (02) 8877 8333
Web: http://www1.apotex.com/au

APO and APOTEX are registered trademarks of Apotex Inc.

This leaflet was prepared in December 2019.

Published by MIMS March 2020

BRAND INFORMATION

Brand name

APO-Cefaclor CD

Active ingredient

Cefaclor

Schedule

S4

 

1 Name of Medicine

Cefaclor monohydrate.

6.7 Physicochemical Properties

Cefaclor (monohydrate) is a white to off-white crystalline powder, slightly soluble in water, but is insoluble in alcohol and chloroform.
Chemical Name: 3-chloro-7-D-(2-phenylglycinamido)-3-cephem-4-carboxylic acid monohydrate.

Chemical structure.


CAS number.

70356-03-5.

Molecular formula.

C15H14ClN3O4S.H2O.

Molecular weight.

385.83.

2 Qualitative and Quantitative Composition

Each modified release tablet contains cefaclor monohydrate equivalent to 375 mg cefaclor.

Excipient with known effect.

Lactose monohydrate.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

375 mg modified release tablet.

Biconvex, capsule shape and coloured blue.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

The in vitro bactericidal activity of Cefaclor CD is due to cefaclor. In vitro tests demonstrate that the bactericidal action of the cephalosporins results from inhibition of cell wall synthesis. Cefaclor is stable in the presence of bacterial β-lactamases; consequently, β-lactamase producing organisms resistant to penicillins and some cephalosporins may be susceptible to cefaclor. Cefaclor have been shown to be active against most strains of the following organisms both in vitro and in clinical infections.

Gram-positive organisms.

Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes (group A Streptococci).

Note.

Cefaclor is not active against methicillin resistant Staphylococci.

Gram-negative organisms.

Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis.

Note.

Pseudomonas sp., Acinetobacter calcoaceticus, Enterococci, Enterobacter sp., indole positive Proteus, and Serratia sp. are resistant to cefaclor. Methicillin resistant strains are also resistant to cefaclor.

Susceptibility testing.

Dilution or diffusion techniques.

Either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of "intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small, uncontrolled technical factors from causing major discrepancies in interpretation. A report of "resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Cefaclor CD is well absorbed from the gastrointestinal tract after oral administration. Although Cefaclor CD can be taken with or without food, total absorption is enhanced with food. When it was given within one hour after a meal, the bioavailability of sustained release cefaclor was greater than 90%, using cefaclor taken fasting as a reference. When taken in the fasting state, the bioavailability of sustained release cefaclor was 77% that of cefaclor. Compared to cefaclor (fasted state), mean peak plasma concentrations of sustained release cefaclor (both fed and fasted states) were delayed 40 to 90 minutes and were lower. Concomitant administration of cimetidine does not affect the rate or extent of absorption. Administration of magnesium or aluminium hydroxide containing antacids one hour after sustained release preparations of cefaclor had no effect on the rate of absorption, but resulted in a 17% decrease in the extent of absorption. The effect of antacids taken at other times is uncertain.
Following administration of 375 mg, 500 mg and 750 mg tablets to fed subjects, average peak serum concentrations of 4, 8, and 11 microgram/mL, respectively, were obtained within 2.5 to 3 hours. No drug accumulation was noted when it was given twice daily for 2½ days.
The plasma half-life in healthy subjects is approximately independent of dosage form and averages 40-60 minutes.
In elderly subjects (> 65 years) with normal serum creatinine values, a higher peak plasma concentration and area under the curve (AUC) are effects resulting from mildly diminished renal function and are not expected to have clinical significance. Therefore, dosage changes are not necessary in elderly subjects with normal renal function.

Metabolism.

There is no evidence of metabolism of cefaclor in humans.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of the following infections caused by susceptible organisms, in adults and children 12 years and older.
Community acquired pneumonia of mild to moderate severity (excluding atypical pneumonia).
Acute bronchitis and acute exacerbations of chronic bronchitis.
Upper respiratory infections, including pharyngitis, tonsillitis and acute bacterial sinusitis.
Symptomatic lower urinary tract infections, including cystitis.
Skin and skin structure infections.

Note.

1. Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cefaclor CD is generally effective in the eradication of Streptococci from the oropharynx; however, substantial data establishing the efficacy of Cefaclor CD in the subsequent prevention of rheumatic fever are not available.
2. Bacteriological studies to determine the causative organism and its susceptibility to cefaclor should be performed. Therapy may be started while awaiting the results of these studies. Once these results become available, antimicrobial therapy should be adjusted accordingly.

4.3 Contraindications

Known allergy to cephalosporins or previous experience of a major allergy to penicillin (see Section 4.4 Special Warnings and Precautions for Use) or any of the excipients listed (see Section 6.1 List of Excipients).

4.4 Special Warnings and Precautions for Use

Except under special circumstances, this medication should not be used when the following medical problem exists.

Penicillin sensitive patients or those with hypersensitivity to other allergens.

Cephalosporin antibiotics should be administered cautiously in this patient group. There is clinical and laboratory evidence of partial cross allergenicity of the penicillins and the cephalosporins and there are instances in which patients have had reactions, including anaphylaxis, to both drug classes. Serious and occasionally fatal hypersensitivity (anaphylactic/ anaphylactoid) reactions have been reported in patients on penicillin/ cephalosporin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins/ cephalosporins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin/ cephalosporin hypersensitivity who have experienced severe reactions when treated with a penicillin/ cephalosporin.

Severe allergic reaction to penicillin or cephalosporin class of drugs, or other allergens.

Past history of a severe allergic reaction to drug from the penicillin or cephalosporin group of drugs is a contraindication to the use of cefaclor. Before initiating therapy with any cephalosporin careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, cefaclor should be discontinued and the appropriate therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated.

History of colitis or gastrointestinal disease.

Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastrointestinal disease, especially ulcerative colitis, regional enteritis, or antibiotic-associated colitis.

Risk-benefit should be considered when the following medical problems exist.

Pseudomembranous colitis.

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including cefaclor. A toxin produced by Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patient who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases appropriate therapy such as suitable oral antibacterial agents effective against Cl. difficile should be considered. Fluids, electrolytes and protein replacement therapy should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil), may prolong and/or worsen the condition and should not be used.

History of bleeding disorders.

All cephalosporins may cause hypoprothrombinaemia and, potentially, bleeding.

Adequate treatment period.

As with antibiotic therapy in general, administration of cefaclor should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained. A minimum of 10 days of treatment is recommended in infections caused by group A β-haemolytic Streptococci in order to guard against the risk of rheumatic fever or glomerulonephritis.

Prolonged use of cefaclor.

This may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in patients taking beta-lactam antibiotics. When SCAR is suspected, cefaclor should be discontinued immediately and an alternative treatment should be considered.

Use in hepatic impairment.

Cefaclor should be used with caution in patients with hepatic disease, as documented clinical experience in this group of patients is lacking.

Use in renal impairment.

Many cephalosporins are excreted renally. Cefaclor should be administered with caution in the presence of markedly impaired renal function. Since the half-life of cefaclor in anuria is 2.3 to 2.8 hours, dosage adjustments for patients with moderate or severe renal impairment are usually not required. Clinical experience with cefaclor under such conditions is limited; therefore, careful clinical observation and laboratory studies should be made.

Drug interactions.

The extent of absorption of Cefaclor CD is diminished if magnesium- or aluminium hydroxide-containing antacids are taken within 1 hour of administration; cimetidine did not alter either the rate or the extent of absorption of Cefaclor CD. As with other β-lactam antibiotics, the renal excretion of Cefaclor (and presumably Cefaclor CD) is inhibited by probenecid. No other significant drug interactions were noted during clinical trials.

Use in the elderly.

Cephalosporins have been used in the geriatric population, and no geriatrics-specific problems have been documented to date. However, elderly patients are more likely to have an age-related decrease in renal function, which may require and adjustment in dosage and/or dosing interval in patients receiving cephalosporins.

Paediatric use.

Safety and effectiveness of this product has not been studied in children. Serum sickness-like reactions including arthritis and arthralgia have been reported more frequently in children than in adults with the use of cefaclor.

Effects on laboratory tests.

Administration of Cefaclor CD may result in a false-positive reaction for glucose in the urine. This phenomenon has been seen in patients taking cephalosporin antibiotics when the test is performed using Benedict's and Fehling's solutions and also with Clinitest tablets but not with Tes-Tape (Glucose Enzymatic Test Strip, USP).
Positive direct Coombs' tests have been reported during treatment with cefaclor. In haematologic studies or in transfusion cross-matching procedures when anti-globulin tests are performed on the minor side, or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognised that a positive Coombs' test may be due to the drug.

Dental.

Long-term therapy with cephalosporins may allow for the overgrowth of Candida albicans, resulting in oral candidiasis.

Prothrombin time (PT).

May be prolonged.

Creatinine, serum.

Concentrations may be increased.

Carnitine or haematocrit.

Values may decrease during therapy.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticoagulants, coumarin- or indandione-derivatives, or heparin or thrombolytic agents.

Because all cephalosporins can inhibit vitamin K synthesis by suppressing gut flora, prophylactic vitamin K therapy is recommended when any of these medications is used for prolonged periods in malnourished or seriously ill patients.

Platelet aggregation inhibitors.

Hypoprothrombinaemia induced by large doses of salicylates and/or cephalosporins, and the gastrointestinal ulcerative or hemorrhagic potential of nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, or sulfinpyrazone may increase the risk of haemorrhage.

Probenecid.

Probenecid decreases renal tubular secretion of those cephalosporins excreted by this mechanism, resulting in increased and prolonged cephalosporin serum concentrations, prolonged elimination half-life, and increased risk of toxicity.
No other significant drug interactions were noted during clinical trials.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Reproduction studies have revealed no evidence of impaired fertility.
(Category B1)
The oral administration of high dose cefaclor (500 mg/kg) in pregnant rats and mice has resulted in a slight increase of minor skeletal malformation. Safety of this product for use during pregnancy has not been established. Cefaclor should not be used in women of childbearing potential unless, in the judgement of the treating clinician, its use is considered essential to the welfare of the patient and the expected benefits outweigh potential risks.
 No studies have been done with Cefaclor CD. Small amounts of cefaclor have been detected in breast milk following administration of single 500 mg doses of cefaclor. Average levels were 0.18, 0.20, 0.21 and 0.16 microgram/mL at 2, 3, 4 and 5 hours respectively. Trace amounts were detected at 1 hour. The effect on breastfed infants is not known. Caution should be exercised when cefaclor is administered to a breastfeeding woman.

Labour and delivery.

Cefaclor has not been studied for use during labour and delivery. Treatment should be given only if clearly needed.

4.8 Adverse Effects (Undesirable Effects)

The majority of adverse reactions observed in clinical trials of Cefaclor CD were mild and transient. Drug related adverse reactions requiring discontinuation of therapy occurred in 1.7% of patients. The following adverse reactions have been reported following use of Cefaclor CD in clinical trials. Incidence rates were less than 1% except where otherwise noted.

Gastrointestinal.

Diarrhoea (3.4%), nausea (2.5%), vomiting and dyspepsia.

Hypersensitivity.

Rash, urticaria or pruritus occurred in approximately 1.7% of patients.
One serum sickness-like reaction (0.03%) was reported among the 3,272 patients treated with the sustained release preparation of cefaclor during the controlled clinical trials.

Blood and lymphatic system disorders.

Eosinophilia.

Superinfection.

Vaginal moniliasis (2.5%) and vaginitis (1.7%).
Adverse events reported during a clinical trial of sustained release cefaclor (750 mg bid) vs. cefaclor capsules (500 mg tid) in patients with acute bacterial sinusitis are shown in . All adverse events occurring at an incidence of 2% or greater are included.

Causal relationship uncertain.

The following adverse effects have been reported in patients treated with sustained release preparations of cefaclor; the causal relationship is uncertain; incidence rates were less than 1% except where otherwise noted.

Central nervous system.

Headache (3.2%), dizziness and somnolence.

Hepatic.

Transient elevations in AST, ALT and alkaline phosphatase.

Renal.

Transient increase in serum urea or creatinine and abnormal urinalysis.

Blood and lymphatic system disorders.

Transient thrombocytopenia, leucopoenia, lymphocytosis, neutropenia and abnormal urinalysis.

Patients treated with cefaclor.

In addition, the following adverse reactions and altered laboratory tests have been reported in patients treated with the regular (not sustained-release) cefaclor preparations.

Gastrointestinal.

The most frequent side effect has been diarrhoea. Nausea and vomiting have been reported rarely. Colitis, including rare instances of pseudomembranous colitis, has been reported in conjunction with therapy with cefaclor (see Section 4.4 Special Warnings and Precautions for Use). Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment.

Immune system disorders.

Allergic reactions, such as urticaria and morbilliform eruptions, have been observed. These reactions usually subsided upon discontinuation of the drug.
Fever and angioedema have been reported rarely.
Cases of serum sickness-like reactions have been reported with the use of cefaclor. These have been reported more frequently in children than in adults, with an overall occurrence ranging from 0.5% (1 in 200) in one trial, to 0.024% (2 in 8,346) in overall clinical trials (with an incidence in children in clinical trials of 0.055%). The worldwide reporting rate for serum sickness-like reactions in adults is very rare (< 0.01%). Serum sickness-like reactions are characterised by findings of erythema multiforme, rashes and other skin manifestations accompanied by arthritis/ arthralgia, with or without fever, and differ from classic serum sickness in that there is infrequently associated lymphadenopathy and proteinuria, no circulating immune complexes and no evidence to date of sequelae of the reaction. While further investigation is ongoing, serum sickness-like reactions appear to be due to hypersensitivity and more often occur during or following a second (or subsequent) course of therapy with cefaclor. Such reactions have been reported more frequently in children than in adults. Signs and symptoms usually occur a few days after initiation of therapy and subside within a few days after cessation of therapy; occasionally these reactions have resulted in hospitalisation, usually of short duration (median hospitalisation: 2 to 3 days, based on post-marketing surveillance studies). In those requiring hospitalisation, the symptoms have ranged from mild to severe at the time of admission with more of the severe reactions occurring in children. Antihistamines and glucocorticoids appear to enhance resolution of the signs and symptoms. No serious sequelae have been reported.
More severe hypersensitivity reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely. Anaphylaxis may be more common in patients with a history of penicillin allergy. The worldwide reporting rate for anaphylaxis in the total population is very rare (< 0.01%).
Anaphylactoid events may present as solitary symptoms, including angioedema, asthenia, oedema (including face and limbs), dyspnoea, paraesthesias, syncope, or vasodilatation.
Rarely, hypersensitivity symptoms may persist for several months.
Positive direct Coombs' test and genital pruritus have been reported. Symptoms of pseudomembranous colitis may appear either during or after antibiotic treatment.
The following reactions have been reported in patients treated with cefaclor.

Renal and urinary disorders.

Reversible interstitial nephritis.

Hepatobiliary disorders.

Hepatic dysfunction, including transient hepatitis and cholestatic jaundice have been reported rarely.

Blood and lymphatic system disorders.

Eosinophilia, transient lymphocytosis leucopoenia, and rarely, thrombocytopenia, thrombocytosis, increased prothrombin time, with or without clinical bleeding, in patients receiving cefaclor and warfarin concomitantly; haemolytic anaemia, aplastic anaemia, agranulocytosis, reversible neutropenia of possible clinical significance. There have been rare reports of increased prothrombin time with or without clinical bleeding in patients receiving cefaclor and warfarin concomitantly.
There have also been reports of transient fluctuations in leucocyte count, predominantly lymphocytosis in infants and young children.

Superinfection.

Genital pruritus, moniliasis or vaginitis.

Nervous system disorders.

Rarely, reversible hyperactivity, hypertonia, nervousness, insomnia, confusion, dizziness, headache, somnolence and hallucinations.

Immune system disorders.

Angioedema and fever have been reported rarely.

Other.

Transitory abnormalities in clinical laboratory test results have been reported, but their clinical significance is uncertain. These include slight elevations in AST, ALT or alkaline phosphatase values; and slight elevations in serum urea or serum creatinine or abnormalities of urinalysis (haematuria, pyuria).
The following adverse reactions have been reported in patients treated with other beta-lactam antibiotics.

Renal dysfunction, and toxic nephropathy.

Several beta-lactam antibiotics have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy should occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Severe and other subcutaneous tissue disorders.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP) have been reported in beta-lactam antibiotics.

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 and contact Apotex Medical Information enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.2 Dose and Method of Administration

APO-Cefaclor CD modified release tablets are intended for oral administration.
Cefaclor CD can be taken with or without food; however absorption is enhanced when Cefaclor CD is administered with food (see Section 5.2 Pharmacokinetic Properties).
The tablets should not be cut, crushed or chewed.

Adults.

The usual adult dosage is 375 mg twice daily.
For pneumonia, and acute bacterial sinusitis the recommended dosage is 750 mg twice daily. For acute bacterial sinusitis Cefaclor CD should be taken for 10 days.
For infections involving S. pyogenes (group A Streptococci), a therapeutic dosage of Cefaclor CD should be administered for at least ten days.

Renal impairment.

For patients with markedly impaired renal function, see Section 4.4 Special Warnings and Precautions for Use.

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.

4.9 Overdose

Symptoms.

The toxic symptoms following an overdose of cefaclor may include nausea, vomiting, epigastric distress and diarrhoea. The severity of the epigastric distress and the diarrhoea are dose related. If other symptoms are present, it is probable that they are secondary to an underlying disease state, an allergic reaction, or the effects of other intoxication.

Treatment.

In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient.
Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal.
Forced diuresis, peritoneal dialysis, haemodialysis or charcoal haemoperfusion have not been established as beneficial for an overdose of cefaclor.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hypromellose, hyprolose, lactose monohydrate, silica-colloidal anhydrous, magnesium stearate, talc-purified, titanium dioxide, macrogol 400, indigo carmine, iron oxide black, propylene glycol, methanol and isopropyl alcohol.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of the 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 moisture and light.

6.5 Nature and Contents of Container

Blister packs (PVC/PVDC/Al) of 10. AUST R 76226.
APO- is a registered trademark of Apotex Inc.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes