Consumer medicine information

Roxithromycin Sandoz

Roxithromycin

BRAND INFORMATION

Brand name

Roxithromycin Sandoz

Active ingredient

Roxithromycin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Roxithromycin Sandoz.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Roxithromycin Sandoz.

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 risk of you taking this medicine 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 SANDOZ IS USED FOR

This medicine is used to treat various infections caused by bacteria such as:

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

It contains the active ingredient roxithromycin. Roxithromycin belongs to a group of medicines called macrolides.

It works by killing or stopping the growth of the bacteria that are causing the infection.

However, Roxithromycin Sandoz does not have any effect on viral infections such as the flu.

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.

This medicine is not addictive.

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

BEFORE YOU TAKE ROXITHROMYCIN SANDOZ

When you must not take it

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

  • roxithromycin, the active ingredient, or to any of the other ingredients listed at the end of this leaflet under Product Description.
  • any other macrolide antibiotic (such as azithromycin, clarithromycin or erythromycin).

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.

Do not take this medicine if you have severe problems with your liver.

Do not take this medicine if you are also taking certain medicines for migraine headache of the group of ergot alkaloids (such as Migral®, Cafergot®, Ergodryl®, Dihydergot®).

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:

  • impaired kidney function
  • problems with your liver (hepatic cirrhosis with jaundice and/or ascites).

Tell your doctor if you are pregnant or plan to become pregnant. This medicine is not recommended for use during pregnancy.

Your doctor or pharmacist can discuss with you the risks and benefits involved.

Tell your doctor if you are breastfeeding or planning to breastfeed.

Roxithromycin passes into breast milk

Your doctor or pharmacist can discuss with you the risks and benefits involved.

Tell your doctor or pharmacist if you plan to have surgery.

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

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 Roxithromycin Sandoz may interfere with each other. These include:

  • theophylline, a medicine used to treat asthma
  • some medicines for migraine headache such as ergotamine or dihydroergotamine
  • disopyramide, a medicine used to treat irregular heart rhythms
  • terfenadine and astemizole, medicines used to treat allergies
  • warfarin, a medicine used to prevent blood clots
  • digoxin, a medicine used to treat heart failure
  • midazolam, a medicine used to induce sleep before operations
  • cyclosporin, a medicine used to prevent organ transplant rejection or to treat certain problems with the immune system
  • cisapride, a medicine used to treat gastrointestinal problems
  • pimozide, an antipsychotic medicine.

These medicines may be affected by Roxithromycin Sandoz, 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 ROXITHROMYCIN SANDOZ

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

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

How much to take

The recommended dosage for adults is 300mg per day.

You may take this according to one of the following dosage regimens:

  • one 300mg tablet once a day, or
  • one 150mg 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 dose for a child will depend on the child's weight.

The recommended dose for children weighing 40kg and more is 150mg twice a day.

Roxithromycin Sandoz should not be used for children less than 40kg in weight.

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, Roxithromycin Sandoz may not work as well and your problem may not improve.

How to take it

Roxithromycin Sandoz tablets should be swallowed whole with a glass of water.

If you need to break Roxithromycin Sandoz, hold the tablet with both hands and snap along the break line.

When to take Roxithromycin Sandoz

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.

Take your medicine on an empty stomach, for example, at least 15 minutes before food or at least 3 hours after food. Food can interfere with the absorption of this medicine.

How long to take Roxithromycin Sandoz

Roxithromycin Sandoz is usually taken for 5 to 10 days for treating infections. Your doctor may want you to take Roxithromycin Sandoz for a longer period.

Continue taking your medicine for as long as your doctor tells you.

It is important to keep taking your medicine even if you feel well.

If you forget to take it

Take your dose as soon as you remember, and continue to take it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose that you missed. 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 (telephone 13 11 26 or New Zealand 0800 POISON or 0800 764766) 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 Roxithromycin Sandoz. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

WHILE YOU ARE TAKING ROXITHROMYCIN SANDOZ

Things you must do

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

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

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

Tell your doctor immediately if you get severe diarrhoea. Do this even if it occurs several weeks after Roxithromycin Sandoz has been stopped. Diarrhoea may be a sign for a serious condition affecting your bowel. You may need urgent medical attention. Check with your doctor before taking any diarrhoea medication.

Tell your doctor or pharmacist if you get vaginal itching or discharge.

Tell your doctor or pharmacist if you get a sore, white mouth or tongue while or shortly after taking Roxithromycin Sandoz. These could be the symptoms of a fungal/yeast infection called thrush. The use of Roxithromycin Sandoz can allow fungi/yeast to grow and cause the above symptoms. Roxithromycin Sandoz is not effective against fungi/yeast.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

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

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

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

If you stop taking Roxithromycin Sandoz too early, not all of the bacteria might be killed. The remaining could start to grow again and prevent your infection from clearing completely or even cause it to return.

SIDE EFFECTS

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

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:

  • oral thrush with a white, furry, sore tongue and mouth
  • vaginal thrush with a sore and itchy vagina and/or discharge
  • nausea, vomiting, stomach pain, diarrhoea, flatulence, loss of appetite
  • red and/or itchy skin, skin rash
  • headache, tiredness, dizziness, pins and needles, ringing in the ears
  • hallucinations
  • altered taste and/or smell.
  • Blurred vision and /or visual impairment

These are mild side effects of the medicine, and are short-lived.

Tell your doctor as soon as possible if you notice any of the following, in particular if they occur several weeks after you finished taking Roxithromycin Sandoz:

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

The above list includes serious side effects of Roxithromycin Sandoz. These side effects are rare. You may suffer from a serious condition affecting your bowel requiring medical attention.

Check with your doctor before taking any diarrhoea medication.

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

  • severe persistent diarrhoea
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • swelling of the face, lips, mouth and tongue
  • difficulty in swallowing or breathing
  • an allergic reaction (for example, itchy skin, rash, swelling, asthma or wheezing)
  • severe skin rash.
  • Sever blisters and bleeding in the lips, eyes, mouth, nose and genitals

The above list includes very serious side effects. If you have them, you may have had a serious allergic reaction to Roxithromycin Sandoz. You may need urgent medical attention or hospitalisation. These side effects are very rare.

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

AFTER TAKING ROXITHROMYCIN SANDOZ

Storage

Keep your medicine in the original container.

If you take it out of its original container it may not keep well.

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

Do not store Roxithromycin Sandoz 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 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 medicine that is left over.

PRODUCT DESCRIPTION

What it looks like

Roxithromycin Sandoz comes in two types of tablets:

Roxithromycin Sandoz 150mg - white, round, convex film-coated tablets, scored on one side, embossment R150 on the other side.

Available in blister packs of 10 tablets.

Roxithromycin Sandoz 300mg - white, round, convex film-coated tablets, scored on one side, embossment R300 on the other side.

Available in blister packs of 5 tablets.

Ingredients

Active ingredient:

  • Roxithromycin Sandoz 150mg - 150mg roxithromycin
  • Roxithromycin Sandoz 300mg - 300mg roxithromycin

Inactive ingredients:

  • microcrystalline cellulose
  • povidone K30
  • croscarmellose sodium
  • precipitated silica
  • lactose
  • hypromellose
  • titanium dioxide
  • magnesium stearate
  • macrogol 4000
  • poloxamer 188.

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

Supplier

Roxithromycin Sandoz is supplied in Australia by:

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park NSW 2113
Australia
Tel: 1800 726 369

Novartis New Zealand Limited
PO Box 99102
Newmarket Auckland 1149
New Zealand
Tel: 0800 354 335

This leaflet was revised in February 2019.

Australian Register Numbers:

Roxithromycin Sandoz 150mg film-coated tablets: AUST R 100989

Roxithromycin Sandoz 300mg film-coated tablets: AUST R 101028

Published by MIMS March 2019

BRAND INFORMATION

Brand name

Roxithromycin Sandoz

Active ingredient

Roxithromycin

Schedule

S4

 

1 Name of Medicine

Roxithromycin.

2 Qualitative and Quantitative Composition

Each Roxithromycin Sandoz 150 mg film-coated tablets contains 150 mg roxithromycin.
Each Roxithromycin Sandoz 300 mg film-coated tablets contains 300 mg roxithromycin.
It is a white crystalline powder.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Roxithromycin Sandoz 150 mg film-coated tablets: White, round, convex film-coated tablets, scored on one face, embossment R 150.
Roxithromycin Sandoz 300 mg film-coated tablets: White, round, convex film-coated tablets, scored on one face, embossment R 300.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults.

Roxithromycin Sandoz is indicated for the treatment of the following types of mild to moderately severe infections in adults 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 Sandoz 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.

4.2 Dose and Method of Administration

Dosage.

Adults. The recommended dosage is 300 mg per day which may be taken according to one of the following dosage regimens.

Usual dosage.

Roxithromycin Sandoz 300 mg tablets: one tablet daily.
Roxithromycin Sandoz 150 mg tablets: one tablet twice daily, or two tablets once daily.
For atypical pneumonia, the recommended dosage is 150 mg twice daily.
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 Section 4.4 Special Warnings and Precautions for Use).
Roxithromycin Sandoz 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 Sandoz 150 mg tablet morning and evening. Roxithromycin Sandoz is not recommended for children of under 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.

Method of administration.

Roxithromycin Sandoz should be taken at least 15 minutes before food or on an empty stomach (i.e. more than three hours after a meal).
Roxithromycin Sandoz 150 mg and 300 mg film-coated tablets must be swallowed whole with a drink.

Dosage adjustment.

Renal impairment.

Roxithromycin Sandoz 300 mg tablets: one tablet daily.
Roxithromycin Sandoz 150 mg tablets: one tablet twice daily or two tablets once daily.

Elderly.

Roxithromycin Sandoz 300 mg tablets: one tablet daily.
Roxithromycin Sandoz 150 mg tablets: one tablet twice daily or two tablets once daily.

4.3 Contraindications

Hypersensitivity to roxithromycin, macrolides, including erythromycin or to any of the excipients.
Severely impaired hepatic function (see Section 4.4 Special Warnings and Precautions for Use).
Concomitant therapy with vasoconstrictive ergot alkaloids (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Coadministration with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4 (e.g. astemizole, cisapride, pimozide and terfenadine) (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

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.
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.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics. A toxin produced by Clostridium difficile appears to be the primary cause.
If pseudomembranous colitis is suspected, roxithromycin must be stopped immediately.
The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea particularly if severe, persistent and/or bloody, or colitis in association with antibiotic use (this may occur during treatment and 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 Clostridium 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.
In certain conditions macrolides, including roxithromycin, have the potential to prolong the QT interval. Therefore roxithromycin should be used with caution in patients with congenital prolongation of the QT interval, with ongoing proarrhythmic conditions (i.e. uncorrected hypokalemia or hypomagnesaemia, clinically significant bradycardia), and in patients receiving class IA (e.g. quinidine, procainamide, disopyramide) and class III (e.g. dofetilide, amiodarone) antiarrhythmic agents, citalopram, tricyclic antidepressants, methadone, some antipsychotics (e.g. phenothiazines), fluoroquinolones (e.g. moxifloxacin), some antifungals (e.g. fluconazole, pentamidine), and some antiviral drugs (e.g. telaprevir) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
As with other macrolides, roxithromycin may have the potential to aggravate myasthenia gravis.
Cases of severe bullous skin reactions such as Stevens Johnson Syndrome or Toxic Epidermal Necrosis have been reported with roxithromycin (see Section 4.8 Adverse Effects (Undesirable Effects)). If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, roxithromycin treatment should be discontinued.
Severe vasoconstriction ("ergotism") with possibly necrosis of the extremities has been reported when macrolides antibiotics have been associated with vasoconstrictive ergot alkaloids. Absence of treatment by these alkaloids must always be checked before prescribing roxithromycin.
Monitoring of the liver and kidney function and the blood counts is recommended especially during long-term treatment.

Use in hepatic impairment.

The safety of roxithromycin has not been demonstrated in patients with impaired hepatic function. Caution should be exercised if Roxithromycin Sandoz is administered to patients with impaired hepatic function, in severe cases, use of roxithromycin is not recommended. 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 renal impairment.

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.
Renal excretion of roxithromycin and its metabolites accounts for a small amount of an oral dose. The dosage should be kept unchanged in renal insufficiency.

Use in the elderly.

No dosage adjustment is required in elderly patients.

Paediatric use.

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.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of 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, e.g. disopyramide.

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. Absence of treatment with these alkaloids must always be checked before prescribing roxithromycin.

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.

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. INR should be monitored during combined treatment with roxithromycin and vitamin K antagonists.

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. Roxithromycin, like other macrolides, should be used with caution in patients receiving class IA and class III antiarrhythmic agents (see Section 4.4 Special Warnings and Precautions for Use).

HMG-CoA reductase inhibitors.

When roxithromycin and an HMG-CoA reductase inhibitor (statin) are combined, there is a potential risk of muscle related adverse events, such as rhabdomyolysis due to a possible increase of the statin exposure.
Caution should be exercised when a statin is combined with roxithromycin and patients should be monitored for signs and symptoms of myopathy.

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.

Bromocriptine.

Roxithromycin may increase the AUC and plasma concentrations of bromocriptine, which could lead to an increased risk for adverse effects of the compound.

Rifabutin.

Roxithromycin can increase the plasma concentration of rifabutin.

Theophylline and cyclosporin.

A slight increase in plasma concentrations of theophylline or cyclosporin A has been observed. This does not generally necessitate altering the usual dosage.
Roxithromycin does not appear to interact with oral contraceptives containing oestrogens and progestogens, prednisolone, carbamazepine, ranitidine or antacids.

CYP3A.

Roxithromycin is a weak CYP3A inhibitor. The effect of roxithromycin on exposure to drugs predominantly cleared by CYP3A metabolism would be expected to be 2-fold or less. Caution should be exercised when roxithromycin is concomitantly prescribed with drugs metabolised by CYP3A (such as rifabutin and bromocriptine).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There was no effect on the fertility of rats treated with roxithromycin at oral doses up to 180 mg/kg/day.
(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 fetus has not been established.
Small amounts of roxithromycin are excreted in the breast milk. Breastfeeding or treatment of the mother should be discontinued as necessary.

4.7 Effects on Ability to Drive and Use Machines

Attention should be drawn to the possibility of dizziness, visual impairment and blurred vision.

4.8 Adverse Effects (Undesirable 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 (dyspepsia), diarrhoea (sometimes containing blood), anorexia, flatulence, pseudomembranous colitis. In clinical studies, the incidence of gastrointestinal events was higher with the 300 mg once daily dosage regimen than with 150 mg twice daily. Symptoms of pancreatitis have been observed; most patients had received other drugs for which pancreatitis is a known adverse reaction.

Hypersensitivity.

Urticaria, rash, pruritus, angioedema. Rarely, serious allergic reactions may occur, e.g. asthma, bronchospasm, anaphylactic like reactions, anaphylactic shock, purpura, glottic oedema, generalised oedema, erythema multiforme, exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, and Toxic Epidermal Necrosis (TEN) (see Section 4.4 Special Warnings and Precautions for Use).

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 (sometimes with jaundice) are rarely reported.

Infections and infestations.

Superinfection (on prolonged use), Clostridium difficile colitis (pseudomembranous colitis).

Blood and lymphatic system disorders.

Eosinophilia, agranulocytosis, neutropenia, thrombocytopenia.

Immune system disorders.

Anaphylactic shock.

Cardiac disorders.

QT interval prolongation, ventricular tachycardia, Torsade de pointes.

Other.

Eosinophilia, bronchospasm, hallucination, headache, dizziness, paraesthesia, tinnitus, malaise, moniliasis (candidiasis), pancreatitis, disorders of taste and/or smell, visual impairment, blurred vision, temporary deafness, hypoacusis and vertigo.
Prolonged use of antibiotics including roxithromycin may result in superinfection; overgrowth of non-susceptible organisms. Repeated evaluation of the patient's condition is essential. In the event of superinfection, appropriate measures should be taken.

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

Symptomatic treatment should be provided as required. There is no specific antidote.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Roxithromycin is a semisynthetic macrolide antibiotic.

Mechanism of action.

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 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 a 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 Standard (NCCLS) method of susceptibility testing with a 15 microgram roxithromycin disc, susceptible organisms other than Haemophilus influenzae produce zones of inhibition 21 mm or greater. A zone size of 10 to 20 mm should be considered intermediate and a zone size of 9 mm or less indicates resistance. A bacterial isolate may be considered susceptible if the 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 Haemophilus influenzae, zones of inhibition 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

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 postdose.
As food intake delays absorption, Roxithromycin Sandoz 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 12 hours to children, the average peak plasma concentration at steady state was 9 mg/L and the AUC was 61 mg.h/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.h/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.h/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.h/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.h/L.
Following administration of a single oral dose of roxithromycin 300 mg to healthy young adults, the mean peak plasma concentration was 9.7 mg/L and the AUC was 98 mg.h/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.h/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.h/L.
After administration of a single oral dose of Roxithromycin Sandoz 150 mg to healthy male and female adults, the mean peak plasma concentration was 6.58 mg/L and the AUC was 94.98 mg.hour/L.
After administration of a single oral dose of Roxithromycin Sandoz 300 mg to healthy male and female adults, the mean peak plasma concentration was 10.10 mg/L and the AUC was 143.48 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.

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.
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.

Excretion.

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.

5.3 Preclinical Safety Data

Genotoxicity.

Roxithromycin has shown no mutagenic potential in standard laboratory tests for gene mutation and chromosomal damage.

Carcinogenicity.

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of roxithromycin.

6 Pharmaceutical Particulars

6.1 List of Excipients

Roxithromycin Sandoz tablets also contain inactive (excipients) ingredients: microcrystalline cellulose, povidone, croscarmellose sodium, silicon dioxide, lactose monohydrate, hypromellose, titanium dioxide, magnesium stearate, macrogol 4000, poloxamer.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5.

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.

6.5 Nature and Contents of Container

Roxithromycin Sandoz 150 mg film-coated tablets.

Available in PVC/Al blister packs of 10 tablets.

Roxithromycin Sandoz 300 mg film-coated tablets.

Available in PVC/Al blister packs of 5 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

The chemical name of roxithromycin is erythromycin- [O-[(2-methoxyethoxy)- methyl]oxime]. Its molecular formula is C41H76N2O15 (MW: 837.1).

Chemical structure.


CAS number.

80214-83-1.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes