Consumer medicine information

ROXITHROMYCIN SCP

Roxithromycin

BRAND INFORMATION

Brand name

Roxithromycin SCP

Active ingredient

Roxithromycin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using ROXITHROMYCIN SCP.

What is in this leaflet

This leaflet answers some common questions about this medicine.

It does not contain all the available information. It does not take the place of talking to your doctor and pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking roxithromycin 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 ROXITHROMYCIN is used for

Roxithromycin is used to treat infections in different parts of the body caused by bacteria. For example:

  • acute pharyngitis (sore throat and discomfort when swallowing)
  • tonsillitis
  • sinusitis
  • acute bronchitis (infection of the bronchi causing coughing)
  • pneumonia (lung infection characterised by fever, malaise, headache)
  • skin and soft tissue infections
  • non gonoccocal urethritis
  • impetigo (bacterial infection causing sores on the skin)

Roxithromycin is an antibiotic that belongs to a group of medicines called macrolides.

These antibiotics work by killing or stopping the growth of the bacteria that are causing your infection.

Roxithromycin, like other antibiotics, does not work against viral infections such as the flu.

Your doctor may have prescribed roxithromycin for another reason. Ask your doctor if you have any questions about why it has been prescribed for you. This medicine is available only with a doctor's prescription.

Roxithromycin is not addictive.

Before you take ROXITHROMYCIN

When you must not take it

Do not take roxithromycin if:

  1. you have an allergy to:
    - roxithromycin or any other macrolide antibiotic eg., azithromycin, clarithromycin or erythromycin.
    - any of the ingredients listed at the end of this leaflet (see Product description).
    Some of the symptoms of an allergic reaction may include 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.
  2. you have severe liver problems
  3. you are taking certain medicines for migraine headache called ergot alkaloids (eg., Migral, Cafergot, Ergodryl, Dihydergot; [not all brands listed])
    Ask your doctor if you are not sure if you are taking one of these medicines.
  4. the packaging is torn or shows signs of tampering
  5. the expiry date on the pack has passed.
    If you take this medicine after the expiry date has passed, it may not work as well.

If you are not sure whether you should start taking roxithromycin, talk to your doctor.

Before you start to take it

Tell your doctor if:

  1. you are pregnant or intend to become pregnant
    Your doctor will discuss the risks and benefits of using roxithromycin during pregnancy.
  2. you are breast-feeding or plan to breast-feed
    Roxithromycin passes into the breast milk. Your doctor will discuss the risks and benefits of using roxithromycin while breast-feeding.
  3. you have or have ever had any other health problems/medical conditions, including:
    - kidney problems (impaired function)
    - liver problems (hepatic cirrhosis with jaundice and/or ascites)
  4. you have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.

If you have not told your doctor about any of the above, tell him/her before you take roxithromycin.

Use in the elderly

Roxithromycin can be used in the elderly with no dosage adjustment required.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy, supermarket or health food shop. There may be interference between roxithromycin and some other medicines, including:

  • theophylline (Neulin, Austyn, Theo-dur), a medicine used to treat asthma
  • some medicines for migraine headache such as ergotamine (Migral, Ergodryl, Cafergot)or dihydroergotamine (Dihydroergot tablets)
  • disopyramide (Rythmodan), a medicine to treat irregular heart rhythms
  • terfenadine (Teldane) and astemizole (Hismanal), over the counter medicines used to treat allergies
  • warfarin (Coumadin, Marevan), a medicine used to prevent blood clots
  • digoxin (Lanoxin), a medicine used to treat heart failure
  • midazolam (Hypnovel), used to induce sleep before operations
  • cyclosporin (Neoral, Sandimmun), a medicine used to prevent organ transplant rejection or to treat certain problems with the immune system
  • cisapride (Prepulsid), a medicine used to treat gastrointestinal problems
  • pimozide (Orap), an antipsychotic medicine

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

Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking roxithromycin.

How to take ROXITHROMYCIN

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from 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

The recommended adult dosage is 300 mg per day which may be taken according to one of the following alternative dosage regimens:

  • one 300 mg tablet once a day, or
  • one 150 mg tablet twice a day, or
  • two 150 mg tablets once a day

However, depending on your condition and how you react to the medicine, your doctor may ask you to take a different dose.

The recommended dosage for children more than 40 kg, is one 150 mg tablet twice daily.

The dosage of roxithromycin given to children is dependant on the child's weight.

Roxithromycin is not recommended for children less than 40 kg in weight.

How to take it

Swallow roxithromycin tablets whole with a glass of water.

When to take it

Roxithromycin should be taken at least 15 minutes before food or on an empty stomach (that is, more than 3 hours after a meal). Roxithromycin works best if you take it on an empty stomach.

Take your 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.

How long to take it

For treating infections, roxithromycin is usually taken for 5 to 10 days. However, your doctor may prescribe roxithromycin for longer periods.

Check with your doctor if you are not sure how long you should be taking it.

Continue taking roxithromycin until you finish the pack or until your doctor recommends.

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 tablets as you would normally.

If you are not sure whether to skip the dose, talk to your doctor or pharmacist.

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

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (13 11 26), or go to casualty at your nearest hospital, if you think that you or anyone else may have taken too much roxithromycin. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are using ROXITHROMYCIN

Things you must do

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 roxithromycin has been stopped. 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 roxithromycin, tell your doctor or pharmacist.

Also tell your doctor or pharmacist if you get vaginal itching or discharge. This may mean you have a fungal/yeast infection called thrush. Sometimes the use of roxithromycin allows fungi/yeast to grow and the above symptoms to occur. Roxithromycin does not work against fungi/yeast.

If you become pregnant while you are taking roxithromycin, tell your doctor.

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are taking roxithromycin.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking roxithromycin.

Things you must not do

Do not stop taking your tablets because you are feeling better, unless advised by your doctor. If you do not complete the full course prescribed by your doctor, all of the bacteria causing your infection may not be killed. These bacteria may continue to grow and multiply so that your infection may not clear completely or it may return.

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

Do not use roxithromycin to treat any other complaints unless your doctor tells you to.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking roxithromycin. Roxithromycin helps many people with bacterial infections, but it may have unwanted side effects in some people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. Medical treatment may be required for some of the side effects.

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

While taking it

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

  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina and/or discharge
  • nausea, vomiting, stomach pain, diarrhoea, flatulence
  • loss of appetite
  • red and/or itchy skin
  • headache, dizziness, ringing in the ears
  • tiredness
  • altered taste

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

  • swelling of the face, lips, mouth and tongue; difficulty breathing or asthma
  • an allergic reaction (for example, itchy skin, rash, swelling, asthma)
  • severe persistent diarrhoea

These may be signs of a serious allergic reaction.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice any other effects.

After finishing it

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with roxithromycin:

  • 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.

Therefore, you may need urgent medical attention. However, this side effect is rare.

Do not take any diarrhoea medicine without first checking with your doctor. Some people may get other side effects while taking roxithromycin.

Do not be alarmed by this list of possible side effects. Most people do not experience any of them.

After taking ROXITHROMYCIN

Storage

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

Keep roxithromycin 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. Do not leave it in the car or on window sills. 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 the tablets or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets that are left over.

Where to go for further information

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your doctor or pharmacist is the best person to give you advice on the treatment of your condition.

Product description

What it looks like

ROXITHROMYCIN SCP 150 mg and 300 mg tablets are white to off-white round convex and film coated. Each blister pack contains either 5 tablets (300 mg strength) or 10 tablets (150 mg strength).

Ingredients

Each ROXITHROMYCIN SCP tablet contains either 150 mg or 300 mg of the active ingredient roxithromycin.

The tablets also contain the following inactive ingredients:

  • maize starch,
  • hydroxypropylcellulose,
  • silica - colloidal anhydrous,
  • sodium starch glycollate,
  • poloxamer,
  • povidone,
  • magnesium stearate,
  • talc - purified,
  • propylene glycol,
  • glucose,
  • titanium dioxide, and
  • hypromellose.

ROXITHROMYCIN SCP does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Manufacturer/Distributor

ROXITHROMYCIN SCP tablets are manufactured for:
Southern Cross Pharma Pty Ltd
56 Illabunda Drive
Malua Bay
NSW 2536
Australia

Date of preparation:
17 February 2012

Australian Registration Numbers:
ROXITHROMYCIN SCP 150 mg 133756
ROXITHROMYCIN SCP 300 mg 133757

Published by MIMS April 2015

BRAND INFORMATION

Brand name

Roxithromycin SCP

Active ingredient

Roxithromycin

Schedule

S4

 

Name of the medicine

Roxithromycin.

Excipients.

Maize starch, hydroxypropylcellulose, silica - colloidal anhydrous, sodium starch glycollate, poloxamer, povidone, magnesium stearate, talc - purified, propylene glycol, glucose, titanium dioxide and hypromellose.

Description

Chemical names: (3R, 4S, 5S, 6R, 7R, 9R, 11S, 12R, 13S, 14R)-4- [(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribo-hexopyranosyl)oxy] -14-ethyl-7,12,13-trihydroxy-10-[(E)- [(2-methoxyethoxy)-methoxy]imino] -3,5,7,9,11,13,-hexamethyl-6-[(3,4,6-trideoxy-3- (dimethylamino) -β-D-xylo-hexopyranosyl)oxy] -oxacyclotetradecan-2-one. Molecular formula: C41H76N2O15. Molecular weight: 837.07. CAS Registry Number: 80214-83-1.
Roxithromycin is a semi-synthetic macrolide antibiotic. Each Roxithromycin filmcoated tablet contains either 150 mg or 300 mg of roxithromycin as the active ingredient.
Roxythromycin SCP tablets also contain the following inactive ingredients: maize starch, hydroxypropylcellulose, silica - colloidal anhydrous, sodium starch glycollate, poloxamer, povidone, magnesium stearate, talc - purified, propylene glycol, glucose, titanium dioxide and hypromellose.

Pharmacology

Microbiology.

Roxithromycin is bacteriostatic at low concentrations and bactericidal at high concentrations. It binds to the 50S subunit of the 70S ribosome, thereby disrupting bacterial protein synthesis.
A prolonged postantibiotic effect has been observed with roxithromycin. Whilst the clinical significance of this remains uncertain, it supports the rationale for once daily dosing. Although clinical data have demonstrated the efficacy and safety of once daily dosing in adults, these have not been demonstrated in children.
At plasma concentrations achieved with the recommended therapeutic doses, roxithromycin has been demonstrated to have in vitro and clinical activity against the following microorganisms: Streptococcus pneumoniae, Strep. pyogenes, Mycoplasma pneumoniae, Moraxella catarrhalis, Ureaplasma urealyticum and Chlamydia sp. Roxithromycin has been demonstrated to have clinical activity against the following microorganisms which are partially sensitive in vitro to roxithromycin: Haemophilus influenzae and Staphylococcus aureus, except methicillin resistant Staph. aureus (MRSA). The following strains of microorganisms are resistant: multiresistant Staph. aureus, Enterobacteriaceae, Pseudomonas sp. and Acinetobacter sp.

Susceptibility tests.

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint should be used following a regularly updated, recognized and standardized 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.
Using the National Committee for Clinical Laboratory Standards (NCCLS) method of susceptibility testing with a 15 microgram roxithromycin disc, susceptible organisms other than Haemophilus influenzae produce zones of inhibition of diameter 21 mm or greater. A zone diameter of 10 to 20 mm should be considered intermediate and a zone diameter of 9 mm or less indicates resistance. A bacterial isolate may be considered susceptible if the minimal inhibitory concentration (MIC) value for roxithromycin is less than or equal to 1 mg/L. Organisms are considered resistant if the MIC value is greater than 8 mg/L.
For H. influenzae, zones of inhibition of diameter 10 mm or greater indicate susceptibility when CO2 incubation and the HTM agar is used with a 15 microgram roxithromycin disc. An isolate may be considered susceptible if the MIC value for roxithromycin is less than or equal to 8 mg/L.

Pharmacokinetics.

Absorption.

Roxithromycin is absorbed after oral administration with an absolute bioavailability of approximately 50%. Peak plasma concentrations following administration of 150 and 300 mg film coated tablets are achieved in young and elderly adult patients approximately one to two hours post-dose. As food intake delays absorption, roxithromycin should be administered at least 15 minutes before food or, alternatively, on an empty stomach (i.e. more than three hours after a meal).
Absorption is not linear; with increasing doses in the range 150 to 300 mg, peak plasma levels and area under the curve (AUC) do not increase in proportion to the dose.
After repeated administration of 2.5 mg/kg every twelve hours to children, the average peak plasma concentration at steady state was 9 mg/L and the AUC was 61 mg.hour/L.
Following administration of a single oral dose of roxithromycin 150 mg to healthy young adults, the mean peak plasma concentration was 6.6 mg/L and the AUC was 69 mg.hour/L. At steady state following doses of 150 mg twice daily, the mean peak plasma concentration was 9.3 mg/L and the AUC was 71 mg.hour/L.
In elderly patients the mean peak plasma concentration following a single 150 mg dose was 9.1 mg/L and the AUC was 148 mg.hour/L. At steady state, a dosage regimen of 150 mg twice daily produced a mean peak plasma concentration of 11.3 mg/L and an AUC of 83 mg.hour/L.
Following administration of a single oral dose of roxithromycin 300 mg tablets to healthy young adults, the mean peak plasma concentration was 9.7 mg/L and the AUC was 98 mg.hour/L. At steady state following doses of 300 mg once daily, the mean peak plasma concentration was 10.9 mg/L and the AUC was 77 mg.hour/L.
In elderly patients, the mean peak plasma concentration following a single 300 mg dose was 10.8 mg/L and the AUC was 197 mg.hour/L.

Distribution.

Roxithromycin is 92 to 96% bound to plasma proteins (principally alpha-1-acid glycoprotein, but also albumin) at concentrations less than 4.2 mg/L. The binding is saturable; in subjects with normal plasma levels of alpha-1-acid glycoprotein, the extent of binding decreases when plasma concentrations of roxithromycin exceed 4.2 mg/L. At a plasma concentration of 8.4 mg/L approximately 87% of the drug is protein bound.
Roxithromycin is highly concentrated in polymorphonuclear leucocytes and macrophages, where levels 30 times those in serum have been reported.

Metabolism.

The mean half-life of roxithromycin is approximately 12 hours in young adults and 20 hours in children. The apparently longer half-life in children does not cause excessive accumulation; minimum concentration (Cmin) and AUC values are comparable for adults and children.
The half-life is prolonged to 25 hours in patients with impaired hepatic function and 18 hours in patients with renal insufficiency.
The mean half-life in elderly patients is approximately 27 hours.
Roxithromycin undergoes limited metabolism in the body, presumably in the liver. The major metabolite is descladinose roxithromycin. Two minor metabolites have also been identified. Plasma levels of roxithromycin are approximately twice those of all metabolites; a similar ratio is seen in the urine and faeces.

Excretion.

Approximately 7% of a dose is excreted in the urine and 13% is eliminated via the lungs. Faecal excretion, which represents the unabsorbed fraction and the small proportion excreted by the liver, accounts for approximately 53% of the dose. The fate of the remainder is unknown.
When roxithromycin plasma levels are above 4.2 mg/L, renal clearance increases because reduced plasma protein binding (see Distribution) causes increased levels of unbound roxithromycin which may be excreted by the kidneys.

Indications

Adults.

Roxithromycin is indicated for the treatment of the following types of mild to moderately severe infections caused by or likely to be caused by susceptible microorganisms:
Upper respiratory tract infection: acute pharyngitis, tonsillitis and sinusitis.
Lower respiratory tract infection: acute bronchitis and acute exacerbations of chronic bronchitis; community acquired pneumonia.
Skin and skin structure infections.
Nongonococcal urethritis.

Children.

Roxithromycin 150 mg tablets are indicated for the treatment of the following mild to moderately severe infections in children caused by or likely to be caused by susceptible microoganisms:
Acute pharyngitis.
Acute tonsillitis.
Impetigo.
Appropriate culture and sensitivity tests should be performed when necessary to determine organism susceptibility and thus treatment suitability. Therapy with roxithromycin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

Contraindications

Known hypersensitivity to macrolides, including erythromycin.
Severely impaired hepatic function (see Precautions).
Concomitant therapy with vasoconstrictive ergot alkaloids (see Interactions with Other Medicines).

Precautions

Prolonged or repeated use of antibiotics including roxithromycin may result in superinfection by resistant organisms. In the event of superinfection, roxithromycin should be discontinued and appropriate therapy instituted.
When indicated, incision, drainage or other appropriate surgical procedures should be performed in conjunction with antibiotic therapy.

Pseudomembranous colitis.

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics. 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 patients 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 with a suitable oral antibacterial agent effective against Cl. difficile should be considered. Fluids, electrolytes and protein replacement therapy should be provided when indicated.
Drugs that delay peristalsis, e.g. opiates and diphenoxylate with atropine (e.g. Lomotil), may prolong and/or worsen the condition and should not be used.
Roxithromycin, like erythromycin, has been shown in vitro to elicit a concentration-dependent lengthening in cardiac action potential duration. Such an effect is manifested only at supratherapeutic concentrations. Accordingly, the recommended doses should not be exceeded.

Impaired renal function.

The safety of roxithromycin has not been demonstrated in patients with impaired renal function. Caution should be exercised if roxithromycin is administered to patients with impaired renal function.

Impaired hepatic function.

The safety of roxithromycin has not been demonstrated in patients with impaired hepatic function. Caution should be exercised if roxithromycin is administered to patients with impaired hepatic function. If administered to patients with severely impaired hepatic function (e.g. hepatic cirrhosis with jaundice and/or ascites), consideration should be given to reducing the daily dosage to half the usual dosage.

Use in children.

In young animal studies, high oral doses of roxithromycin were associated with bone growth plate abnormalities. However no abnormalities were observed in the animals at doses resulting in unbound plasma roxithromycin concentrations that were 10 to 15 times higher than the unbound concentration measured in children receiving the therapeutic dose. The maintenance of such safety margins is primarily dependent on high affinity binding of roxithromycin to plasma alpha-1-acid glycoprotein and will be compromised by any circumstances attenuating the extent of this binding. It is recommended that the approved paediatric dosage regimen (i.e. 5 to 8 mg/kg/day for a maximum of ten days) be adhered to strictly.
Neutropenia was observed in children treated with roxithromycin. 31.6% of 402 children in clinical trials had a neutrophil count below the lower limit of the normal range (3,500/mm3) at the conclusion of therapy with roxithromycin. Of these, 4% had a neutrophil count of less than 1,500/mm3 and 1.2% had a count of less than 1,000/mm3. It is not known whether this is an effect of the drug, or whether it reflects a normal fluctuation of the neutrophil count or a response to infection in children.

Use in pregnancy.

(Category B1)
Reproductive studies in rats, mice and rabbits at doses of 100, 400 and 135 mg/kg/day, respectively, did not demonstrate evidence of developmental abnormalities. In rats, at doses above 180 mg/kg/day, there was evidence of embryotoxicity and maternotoxicity. The safety of roxithromycin for the human foetus has not been established.
Australian categorisation definition of B1: Drugs which have been taken by only a limited number of pregnant women and women of child bearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have not shown evidence of an increased occurrence of foetal damage.

Use in lactation.

Small amounts of roxithromycin are excreted in the breast milk. Breastfeeding or treatment of the mother should be discontinued as necessary.

Use in the elderly.

No dosage adjustment is required in elderly patients.

Carcinogenesis, mutagenesis and effects on fertility.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of roxithromycin. Roxithromycin has shown no mutagenic potential in standard laboratory tests for gene mutation and chromosomal damage.
There was no effect on the fertility of rats treated with roxithromycin at oral doses up to 180 mg/kg/day.

Interactions

Roxithromycin has a much lower affinity for cytochrome P450 than erythromycin, and consequently has fewer interactions. Interactions may be observed, however, with drugs that bind to alpha-1-acid glycoprotein, such as disopyramide.
Roxithromycin does not appear to interact with oral contraceptives, prednisolone, carbamazepine, ranitidine or antacids.

Theophylline.

A study in normal subjects concurrently administered roxithromycin and theophylline has shown some increase in the plasma concentration of the latter. While a change in dosage is usually not required, patients with high levels of theophylline at commencement of treatment should have levels monitored.

Ergot alkaloids.

Reactions of ergotism with possible peripheral necrosis have been reported after concomitant therapy of macrolides with vasoconstrictive ergot alkaloids, particularly ergotamine and dihydroergotamine. Because a clinical interaction with roxithromycin cannot be excluded, administration of roxithromycin to patients taking ergot alkaloids is contraindicated.

Disopyramide.

An in vitro study has shown that roxithromycin can displace protein bound disopyramide; such an effect in vivo could result in increased serum levels of disopyramide. Consequently ECG and, if possible, disopyramide serum levels should be monitored.

Terfenadine.

Some macrolide antibiotics (e.g. erythromycin) may increase serum levels of terfenadine. This can result in severe cardiovascular adverse events, including QT prolongation, Torsades de Pointes and other ventricular arrhythmias. Such a reaction has not been documented with roxithromycin, which has a much lower affinity for cytochrome P450 than erythromycin. However, in the absence of a systematic interaction study, concomitant administration of roxithromycin and terfenadine is not recommended.

Astemizole, cisapride, pimozide.

Other drugs, such as astemizole, cisapride or pimozide, which are metabolised by the hepatic isozyme CYP3A4, have been associated with QT interval prolongation and/or cardiac arrhythmias (typically Torsades de Pointes) as a result of an increase in their serum level subsequent to interaction with significant inhibitors of this isozyme, including some macrolide antibacterials. Although roxithromycin has no or limited ability to complex CYP3A4 and therefore to inhibit the metabolism of other drugs processed by this isozyme, a potential for clinical interaction of roxithromycin with the above mentioned drugs cannot be either ascertained or ruled out in confidence; therefore, concomitant administration of roxithromycin and such drugs is not recommended.

Warfarin.

While no interaction was observed in volunteer studies, roxithromycin appears to interact with warfarin. Increases in prothrombin time (international normalised ratio (INR)) have been reported in patients treated concomitantly with roxithromycin and warfarin or the related vitamin K antagonist phenprocoumon, and severe bleeding episodes have occurred as a consequence.

Digoxin and other cardiac glycosides.

A study in healthy volunteers has shown that roxithromycin may increase the absorption of digoxin. This effect, common to other macrolides, may very rarely result in cardiac glycoside toxicity. This may be manifested by symptoms such as nausea, vomiting, diarrhoea, headache or dizziness; cardiac glycoside toxicity may also elicit heart conduction and/or rhythm disorders. Consequently, in patients treated with roxithromycin and digoxin or another cardiac glycoside, ECG and, if possible, the serum level of the cardiac glycoside should be monitored; this is mandatory if symptoms which may suggest cardiac glycoside overdosage occur.

Midazolam.

Roxithromycin, like other macrolides, may increase the area under the midazolam concentration-time curve and the midazolam half-life, therefore the effects of midazolam may be enhanced and prolonged in patients treated with roxithromycin. There is no conclusive evidence for an interaction between roxithromycin and triazolam.

Cyclosporin.

A slight increase in plasma concentrations of cyclosporin A has been observed. This does not generally necessitate altering the usual dosage.

Adverse Effects

Roxithromycin is generally well tolerated. In clinical trials, treatment discontinuation due to adverse reactions occurred in only 1.2% of adult patients and 1.0% of children. The following side effects or serious adverse events possibly associated with roxithromycin have been reported.

Gastrointestinal.

Nausea, vomiting, epigastric pain, diarrhoea (very rarely containing blood), anorexia, flatulence. In clinical studies, the incidence of gastrointestinal events was higher with the 300 mg once daily dosage regimen than with 150 mg twice daily.

Hypersensitivity.

Urticaria, rash, pruritus, angioedema. Rarely, serious allergic reactions may occur, e.g. asthma, bronchospasm, anaphylactic like reactions, purpura, glottic oedema, generalised oedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome.

Hepatic.

Moderate increases in serum transaminases (AST and ALT) and/or alkaline phosphatase levels have been observed and are somewhat more likely to occur in the elderly (> 65 years). Acute cholestatic hepatitis and acute hepatocellular injury are rarely reported.

Hematological effects.

Transient eosinophilia and thrombocytosis have been reported in patients receiving roxithromycin 150 mg twice a day for 10 days.

Dermatological.

Mild itching (1 to 5%), nail discoloration.

Other.

Headache, dizziness, paraesthesia, tinnitus, malaise, moniliasis (candidiasis), pancreatitis, disorders of taste and/or smell.

Dosage and Administration

Adults.

Roxithromycin should be taken at least 15 minutes before food or on an empty stomach (i.e. more than three hours after a meal).
The recommended dosage is 300 mg per day which may be taken according to one of the following dosage regimens (see Table 1).

Atypical pneumonia.

For atypical pneumonia, the recommended dosage is 150 mg twice daily.
Roxithromycin 150 and 300 mg film coated tablets must be swallowed whole with a drink.
The usual duration of treatment is five to ten days depending on the indication and clinical response. Streptococcal throat infections require at least ten days of therapy. A small proportion of patients with nongonococcal genital infections may require 20 days for complete cure.

Children.

The recommended dose and duration of treatment should not be exceeded in children (see Precautions).
Roxithromycin should be taken at least 15 minutes before food or on an empty stomach (i.e. more than three hours after a meal).
Roxithromycin is administered twice daily at a dose of 5 to 8 mg/kg/day.
Recommended dosage regimens are as follows.

40 kg and over.

One roxithromycin 150 mg tablet morning and evening.
Roxithromycin tablets are not recommended for children weighing less than 40 kg.
The usual duration of treatment is five to ten days depending on the indication and clinical response. Streptococcal throat infections require ten days of therapy. The duration of treatment should not exceed ten days.

Overdosage

In case of overdosage, gastric lavage may remove residual drug in the stomach. Symptomatic treatment should be provided as required. There is no specific antidote.
Contact the Poisons Information Centre on 131 126 regarding overdose management.

Presentation

Roxithromycin SCP 150 mg tablets are white to off-white, round, convex and film-coated tablets. Blister packs of 10.
Roxithromycin SCP 300 mg tablets are white to off-white, round, convex and film-coated tablets. Blister packs of 5.

Storage

Store below 25°C.
Protect from heat and moisture.

Poison Schedule

S4.