Consumer medicine information

Roxar

Roxithromycin

BRAND INFORMATION

Brand name

Roxar

Active ingredient

Roxithromycin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Roxar.

SUMMARY CMI

ROXAR TABLETS

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using ROXAR?

ROXAR contains the active ingredient roxithromycin. ROXAR is used to treat infections in different parts of the body caused by bacteria. For more information, see Section 1. Why am I using ROXAR? in the full CMI.

2. What should I know before I use ROXAR?

Do not use if you have ever had an allergic reaction to roxithromycin or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I use ROXAR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ROXAR and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ROXAR?

  • The recommended adult dosage is 300 mg per day
  • The recommended dosage for children more than 40 kg is one 150 mg tablet twice daily.

More instructions can be found in Section 4. How do I use ROXAR? in the full CMI.

5. What should I know while using ROXAR?

Things you should do
  • Remind any doctor or dentist you visit that you are using ROXAR.
  • 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 ROXAR has been stopped.
  • If you get a sore, white mouth or tongue while taking, or soon after stopping ROXAR, tell your doctor or pharmacist.
  • Tell your doctor or pharmacist if you get vaginal itching or discharge.
  • If you are about to start taking any new medicine, tell your doctor and pharmacist that you are taking ROXAR.
Things you should not do
  • Do not take more than the recommended dose unless your doctor or pharmacist tells you to.
  • Do not give this medicine to anyone else, even if they have the same condition as you.
  • Do not use this medicine to treat any other complaints unless your doctor tells you to.
  • Do not stop taking your tablets because you are feeling better, unless advised by your doctor or pharmacist.
Driving or using machines
  • Make sure you know how ROXAR affects you before driving or operating machinery.
Drinking alcohol
  • Tell your doctor if you drink alcohol
Looking after your medicine
  • Keep the medicine in a cool dry place where the temperature stays below 25°C.
  • Keep the tablets in the blister until it is time to take them

For more information, see Section 5. What should I know while using ROXAR? in the full CMI.

6. Are there any side effects?

Common side effects include: rash; loss of appetite. Refer to the CMI for all side effects.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ROXAR TABLETS

Active ingredient(s): Roxithromycin

Consumer Medicine Information (CMI)

This leaflet provides important information about using ROXAR. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using ROXAR.

Where to find information in this leaflet:

1. Why am I using ROXAR?
2. What should I know before I use ROXAR?
3. What if I am taking other medicines?
4. How do I use ROXAR?
5. What should I know while using ROCAR?
6. Are there any side effects?
7. Product details

1. Why am I using ROXAR?

ROXAR contains the active ingredient roxithromycin. ROXAR 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.

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

ROXAR 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)
  • 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).

2. What should I know before I use ROXAR?

Warnings

Do not use ROXAR if:

  • you are allergic to roxithromycin, or any other macrolide antibiotic e.g. azithromycin, clarithromycin or erythromycin, any of the ingredients listed at the end of this leaflet. Symptoms of an allergic reaction may include skin rash, itching, shortness of breath or swelling of the face, lips or tongue which cause difficulty in swallowing or breathing. Always check the ingredients to make sure you can use this medicine.
  • you have severe liver problems
  • if you are taking certain medicines migraine headache called ergot alkaloids e.g. Cafergot, Dihydergot; (not all brands listed)
  • the product has expired or the packaging appears tampered with.

Check with your doctor or pharmacist if you:

  • have allergies to any other substances, such as foods, preservatives or dyes
  • are pregnant or intend to become pregnant
  • are breastfeeding or plan to breastfeed
  • have or have had the following medical conditions:
    - kidney problems (impaired function)
    - liver problems (hepatic cirrhosis with jaundice and /or ascites)
  • have any other medical conditions
  • take any medicines for any other condition
  • plan to have surgery.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Tell your doctor or pharmacist if you are pregnant or intend to become pregnant. Like most medicines of this kind, ROXAR is not recommended for use during pregnancy. Your doctor or pharmacist will discuss the risks and benefits of taking it if you are pregnant.

Tell your doctor or pharmacist if you are breastfeeding or plan to breastfeed. ROXAR passes into breast milk. Your doctor or pharmacist will discuss the risks and benefits of taking it if you are breastfeeding or planning to breastfeed.

Use in the Elderly

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

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop. Some medicines may be affected by ROXAR, or may affect how well ROXAR works. These include:

  • theophylline (Neulin), a medicine used to treat asthma
  • some medicines for migraine headache such as ergotamine (Cafergot)or dihydroergotamine (Dihydergot tablets)
  • terfenadine and astemizole, over the counter medicines used to treat allergies
  • warfarin (Coumadin, Marevan), a medicine used to prevent blood clots
  • digoxin (Lanoxin, Sigmaxin), a medicine used to treat heart failure
  • midazolam (Hypnovel, Midazolam Sandoz), used to induce sleep before operations
  • ciclosporin (Neoral, Cicoral, Cysporin, Sandimmun), 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 (Orap), an antipsychotic medicine
  • hydroxychloroquine or chloroquine, used to treat conditions including rheumatoid arthritis, or to treat or prevent malaria. Taking these medicines at the same time as ROXAR D may increase the chance of you getting side effects that affect your heart.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ROXAR.

4. How do I use ROXAR?

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 ROXAR given to children is dependent on the child's weight.
  • Your doctor will tell you exactly how much to take.
  • Follow the instructions provided and use ROXAR until your doctor tells you to stop.

When to take / use ROXAR

  • ROXAR should be taken at least 15 minutes before food or on an empty stomach (i.e. more than 3 hours after a meal).
  • ROXAR works best if you take it on an empty stomach.

How to take ROXAR?

  • Swallow the tablets whole with a glass of water.

How long to take it

  • For treating infections, ROXAR is usually taken for 5 to 10 days. However, your doctor may prescribe ROXAR for longer periods.
  • Continue taking the tablets until you finish the pack or until your doctor or pharmacist tells you to stop.

If you forget to use ROXAR

ROXAR should be used regularly at the same time each day.

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 you missed.

If you use too much ROXAR

If you think that you have used too much ROXAR, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using ROXAR?

Things you should 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 ROXAR 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 ROXAR, 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 ROXAR allows fungi/yeast to grow and the above symptoms to occur. ROXAR does not work against fungi/yeast.
  • Tell all the doctors, dentists and pharmacists who are treating you that you are taking ROXAR.
  • If you are about to start taking any new medicine, tell your doctor and pharmacist that you are taking ROXAR.
  • If you plan to have surgery that needs a general anaesthetic tell your doctor or dentist that you are taking this medicine.

Call your doctor straight away if you:

  • If you become pregnant while you are taking ROXAR, tell your doctor or pharmacist immediately.

Things you should not do

  • Do not take more than the recommended dose unless your doctor or pharmacist tells you to.
  • Do not give this medicine to anyone else, even if they have the same condition as you. •
  • Do not use this medicine to treat any other complaints unless your doctor tells you to.
  • Do not stop taking your tablets because you are feeling better, unless advised by your doctor or pharmacist.

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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ROXAR affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep the medicine in a cool dry place where the temperature stays below 25°C.
  • Keep your tablets in the blister pack until it is time to take them.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Do not use this medicine after the expiry date.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions.

Less serious side effects

Less serious side effectsWhat to do
  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina and/or discharge
  • nausea, vomiting, stomach pain, indigestion, diarrhoea, flatulence
  • loss of appetite
  • red and/or itchy skin
  • headache, dizziness, ringing in the ears
  • hallucinations
  • confusion
  • tiredness
  • altered taste
  • rash
  • blurred vision and/or visual impairment
Speak to your doctor if you have any of these less serious side effects and they worry you.
These side effects are usually mild and short-lived.

Serious side effects

Serious side effectsWhat to do
  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may sometimes be bloody
  • fever, in combination with one or both of the above
Tell your doctor or pharmacist immediately if you notice any of the following, particularly if they occur several weeks after stopping treatment with ROXAR.
These are rare but serious side effects. You may have a serious condition affecting your bowel.
Therefore, you may need urgent medical attention Do not take any diarrhoea medicine without first checking with your doctor
  • frequent infections such as fever, severe chills, sore throat or mouth ulcers
  • severe persistent diarrhoea
  • swelling of the face, lips, mouth and tongue
  • difficulty in swallowing or breathing
  • an allergic reaction (for example, itchy skin, rash, swelling, asthma)
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • severe skin rash.
Stop taking this medicine and call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
These are very serious side effects. If you have them, you may have had a serious allergic reaction to ROXAR. You may need urgent medical attention or hospitalisation

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is available with a doctor's prescription.

What ROXAR contains

Active ingredient
(main ingredient)		Each tablet contains either 150 mg or 300 mg of roxithromycin
Other ingredients
(inactive ingredients)		ROXAR tablets:
  • hyprolose
  • colloidal anhydrous silica
  • purified talc
  • povidone
  • maize starch
  • magnesium stearate
  • hypromellose
  • anhydrous glucose
  • titanium dioxide
  • propylene glycol.

Do not take this medicine if you are allergic to any of these ingredients.

The tablets do not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

What ROXAR looks like

ROXAR comes in 2 strengths of tablets:

  • ROXAR 150 - round white tablet. Each pack contains 10 tablets (AUST R 114040).
  • ROXAR 300 - round white tablet. Each pack contains 5 tablets (AUST R 114041).

Who distributes ROXAR

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel St
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in February 2024

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Roxar

Active ingredient

Roxithromycin

Schedule

S4

 

1 Name of Medicine

Roxithromycin.

2 Qualitative and Quantitative Composition

Roxar 150 tablets contain 150 mg of roxithromycin.
Roxar 300 tablets contain 300 mg of roxithromycin.

Physical and chemical characteristics.

Roxithromycin is a white, crystalline powder. It is very slightly soluble in water and freely soluble in acetone, alcohol and methylene chloride.

Excipients.

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

3 Pharmaceutical Form

Roxar 150 tablets are white to off white round biconvex film-coated tablet plain on both sides.
Roxar 300 tablets are white to off white round biconvex film-coated tablet plain on both sides.

4 Clinical Particulars

4.1 Therapeutic 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 microorganisms: 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

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.

Usual dosage.

Roxar 300 mg tablets: one tablet daily; Roxar 150 mg tablets: one tablet twice daily or two tablets once daily.

Elderly.

Roxar 300 mg tablets: one tablet daily; Roxar 150 mg tablets: one tablet twice daily or two tablets once daily.

Impaired renal function.

Roxar 300 mg tablets: one tablet daily; Roxar 150 mg tablets: one tablet twice daily or two tablets once daily.
For atypical pneumonia, the recommended dosage is 150 mg twice daily.
Roxar 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 Section 4.4 Special Warnings and Precautions for Use).
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.
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.

4.3 Contraindications

Known hypersensitivity to macrolides, including erythromycin.
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).

4.4 Special Warnings and Precautions for Use

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. 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.
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 hypokalaemia or hypomagnesaemia, clinically significant bradycardia), and in patients receiving Class IA and III antiarrhythmic agents and drugs such as astemizole, cisapride or pimozide, and hydroxychloroquine or chloroquine (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.

Clostridium difficile-associated disease.

Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with roxithromycin, may be symptomatic of pseudomembranous colitis (see Section 4.8 Adverse Effects (Undesirable Effects)). If pseudomembranous colitis is suspected, roxithromycin must be stopped immediately.
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.
Carefully consider the balance of benefits and risks before prescribing roxithromycin or other macrolides for any patients taking hydroxychloroquine or chloroquine, because of the potential for an increased risk of cardiovascular events and cardiovascular mortality (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use in hepatic impairment.

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 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 percentage 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.
Roxithromycin does not appear to interact with oral contraceptives containing oestrogens and progestogens, 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. Absence of treatment with these alkaloids must always be checked before prescribing roxithromycin.

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

Vitamin K antagonists.

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.

Hydroxychloroquine or chloroquine.

Observational data have shown that co-administration of azithromycin with hydroxychloroquine in patients with rheumatoid arthritis is associated with an increased risk of cardiovascular events and cardiovascular mortality. Because of the potential for similar risk with other macrolides when used in combination with hydroxychloroquine or chloroquine, careful consideration should be given to the balance of benefits and risks before prescribing roxithromycin for any patients taking hydroxychloroquine or chloroquine.

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.

Theophylline and cyclosporin.

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

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 foetus 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 effect.

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.

Other.

Eosinophilia, agranulocytosis, neutropenia, thrombocytopenia, bronchospasm, hallucination, confusion, headache, dizziness, paraesthesia, tinnitus, malaise, moniliasis, pancreatitis, QT prolongation, 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 www.tga.gov.au/reporting-problems.

4.9 Overdose

In case of overdosage, 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 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Roxithromycin is a semisynthetic macrolide antibiotic.
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, 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.

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 to healthy young adults, the mean peak plasma concentration was 10.7 mg/L and the AUC was 146.0 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 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.

Elimination.

The mean half-life of roxithromycin is approximately 13 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.

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.

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.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Mutagenesis.

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

Roxar tablets contain the following excipients: low substituted hyprolose, colloidal anhydrous silica, povidone, purified talc, maize starch, magnesium stearate, hypromellose, anhydrous glucose, titanium dioxide and propylene glycol.
The tablets are gluten free.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

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

6.5 Nature and Contents of Container

Roxar 150 tablets is available in blister pack (PVC/PVDC/Al) of 10 tablets.
Roxar 300 tablets is available in blister pack (PVC/PVDC/Al) of 5 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

The chemical name for roxithromycin is (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-(dimethyl amino)-β-d-xylo- hexopyranosyl] oxy]oxacyclotetradecan-2-one. The structural formula of roxithromycin is:
C41H76N2O15. Molecular weight: 837.

CAS number.

CAS No.: 80214-83-1.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription only Medicine.

Summary Table of Changes