Consumer medicine information

Rulide D

Roxithromycin

BRAND INFORMATION

Brand name

Rulide and Rulide D

Active ingredient

Roxithromycin

Schedule

SUMMARY CMI

Rulide^® D 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 Rulide D?

Rulide D contains the active ingredient roxithromycin. Rulide D is mainly used to treat respiratory tract infections, and skin and soft tissue infections. For more information, see Section 1. Why am I using Rulide D? in the full CMI.

2. What should I know before I use Rulide D?

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 Rulide D? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Rulide D 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 Rulide D?

For children weighing less than 40 kg, the dosage can range from one half a tablet, one tablet or two tablets twice a day.
Your doctor will tell you the correct number of tablets to give your child

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

5. What should I know while using Rulide D?

Things you should do	Remind any doctor or dentist you visit that your child is taking Rulide D. If symptoms of your child's infection do not improve with a few days, or if they become worse, tell your doctor. If your child is about to start taking any new medicine, tell your doctor or pharmacist that they are taking Rulide D
Things you should not do	Rulide D has been prescribed for your child. Do not give to anyone else, even if they have the same condition as your child. Do not use Rulide D to treat any other complaints unless your doctor tells you to
Looking after your medicine	Keep the tablets in a cool dry place where the temperature stays below 30°C Keep the tablets in the foil until its time to take them

For more information, see Section 5. What should I know while using Rulide D? 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

Rulide^® D Tablets (roo-lied)

Active ingredient: Roxithromycin (rocks-e-throw-my-sin)

Consumer Medicine Information (CMI)

This leaflet provides important information about using Rulide D. 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 Rulide D.

Where to find information in this leaflet:

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

1. Why am I using Rulide D?

Rulide D contains the active ingredient roxithromycin. Rulide 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 the infection.

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

Rulide D is used mainly to treat respiratory tract infections, and skin and soft tissue infections

2. What should I know before I use Rulide D?

Warnings

Do not use Rulide D if:

your child has an allergy 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.

your child has severe liver problems
your child is 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 if your child:

have allergies to any other substances, such as foods, preservatives or dyes
has or has had the following medical conditions:
- kidney problems (impaired function)
- liver problems (hepatic cirrhosis with jaundice and /or ascites)
has any other medical conditions
takes any medicines for any other condition
plans 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?

3. What if I am taking other medicines?

Tell your doctor or pharmacist if your child is 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 Rulide D, or may affect how well Rulide D 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, over the counter medicine 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

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

4. How do I use Rulide D?

How much to take

For children weighing less than 40 kg, the dosage can range from one half a tablet, one tablet or two tablets twice a day.
Your doctor will tell you the correct number of tablets to give your child

When to take Rulide

Rulide D works best on an empty stomach so it should be taken at least 15 minutes before food or at least 3 hours after a meal

How to take it

Follow the instructions below on how to give your child Rulide D.

The number of tablets your doctor has recommended should be added to water

Remove the correct number of tablets from the foil.

If your child is only taking half a tablet at a time, place the remaining half of the tablet back in the foil and cover it up

Add half, one or two tablets as directed by your doctor, to water and mix well. At least a spoonful of water should be used
Wait about 30 or 40 seconds for the tablet to break down into fine granules. (The tablets will not completely dissolve). Stir if necessary
Have a glass of water ready and give your child a drink immediately after taking the medicine to ensure all the Rulide D is swallowed

How long to take it

Rulide D is usually taken for 5 to 10 days. Children should not take Rulide D for more than 10 days
Ask your doctor if you are not sure how long your child should be taking it
Make sure your child takes Rulide D for the number of days your doctor has prescribed, even if they begin to feel better after a few days. If the full course is not finished, the infection may not clear completely or their symptoms may return

If you forget to use Rulide D

Rulide D 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 Rulide D

If you think that your child may have used too much Rulide, your child may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26),
or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).
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 Rulide D?

Things you should do

If symptoms of your child's infection do not improve with a few days, or if they become worse, tell your doctor
If your child is about to start taking any new medicine, tell your doctor or pharmacist that they are taking Rulide D

Things you should not do

Rulide D has been prescribed for your child. Do not give to anyone else, even if they have the same condition as your child.
Do not use Rulide D to treat any other complaints unless your doctor tells you to

Looking after your medicine

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

Inform your doctor as soon as possible if your child has any problems while taking Rulide D, even if you do not think the problems are connected with the medicine or they are not listed in this leaflet

Less serious side effects

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

Serious side effects

Serious side effects	What to do
frequent infections such as fever, severe chills, sore throat or mouth ulcers severe persistent diarrhoea an allergic reaction (for example, itchy skin, rash, swelling, asthma or wheezing) swelling of the face lips mouth and tongue which may cause difficulty in swallowing or breathing Severe blisters and bleeding in the lips, eyes, mouth, nose and genitals severe skin rash	Tell your doctor or pharmacist immediately or go to the Accident and Emergency Department at your nearest hospital. These may be serious side effects or signs of a serious allergic reaction
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 immediately if you notice any of the following symptoms, particularly if they occur within several weeks of stopping treatment with Rulide D. These are rare but serious side effects. Your child may have a serious condition affecting the bowel. Therefore, your child may need urgent medical attention

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

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

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 or medsafe at nzphvc.otago.ac.nz/reporting (New Zealand).

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 only available with a doctor's prescription.

What Rulide D contains

Active ingredient (main ingredient)	Each tablet contains either 50 mg of roxithromycin
Other ingredients (inactive ingredients)	cellulose - microcrystalline fumaric acid methacrylic acid copolymer type c crospovidone macrogol 6000 talc - purified saccharin sodium silica - colloidal anhydrous magnesium stearate triethyl citrate sodium lauryl sulfate sodium hydroxide Strawberry Flavour Dry 995/2L 1/1000 Essepi (PI 2338) Liquorice Flavour Atomized (PI 2341)

Do not take this medicine if your child is allergic to any of these ingredients.

What Rulide D looks like

Rulide D tablets are round, off-white, scored tablets. Each blister pack contains 10 tablets (Aust R 54811).

Who distributes Rulide D

Rulide D tablets are manufactured for:

sanofi aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113

This leaflet was prepared in September 2020.
rulide-d-ccdsv7-cmiv10-23sep20

Published by MIMS November 2020

BRAND INFORMATION

Brand name

Rulide and Rulide D

Active ingredient

Roxithromycin

Schedule

1 Name of Medicine

Roxithromycin.

2 Qualitative and Quantitative Composition

Rulide 300 mg and 150 mg tablets contain 300 mg and 150 mg of roxithromycin per tablet respectively.
Rulide D tablets contain 50 mg of roxithromycin per tablet.
Tablets also contain saccharin sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Rulide 300 mg tablets.

White, biconvex, cylindrical, 11 mm diameter, film-coated tablets, debossed on one side with 164J.

Rulide 150 mg tablets.

White, biconvex, cylindrical, 9 mm diameter, film-coated tablets, debossed on one side with 164.

Rulide D 50 mg tablets for suspension.

Practically white, scored, cylindrical tablets, 8 mm in diameter.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults.

Rulide 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 infections: acute pharyngitis, tonsillitis, sinusitis.
Lower respiratory tract infections: acute bronchitis and acute exacerbations of chronic bronchitis; community acquired pneumonia.
Skin and skin structure infections.
Nongonococcal urethritis.

Children.

Rulide D 50 mg tablets and Rulide 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 an organism's 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

Adults.

Rulide should be taken at least 15 minutes before food or on an empty stomach (i.e. more than 3 hours after a meal).
The recommended dosage is 300 mg per day which may be taken according to one of the following alternative dosage regimens (see Table 1):

For atypical pneumonia, the recommended dosage is one 150 mg tablet twice daily.
Rulide 150 mg and 300 mg film coated tablets must be swallowed whole with a drink.
The usual duration of treatment is 5 to 10 days depending on the indication and clinical response. Streptococcal throat infections require at least 10 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).
Rulide should be taken at least 15 minutes before food or on an empty stomach (i.e. more than 3 hours after a meal).
Rulide is administered twice daily at a dose of 5 to 8 mg/kg per day. Recommended dosage regimens are presented in Table 2

Rulide D 50 mg tablets are administered to children weighing less than 40 kg as an aqueous suspension that is made by adding either a half, one or two tablets to a spoonful of water. After waiting for 30 to 40 seconds for the tablet(s) to disintegrate into fine granules, the suspension is given to the child. A drink of water should follow the dose.

Note.

Only Rulide D 50 mg tablets are designed to be mixed with water. The 150 mg and 300 mg film coated tablets must be swallowed whole with a drink.
The usual duration of treatment is 5 to 10 days depending on the indication and clinical response. Streptococcal throat infections require 10 days of therapy. The duration of treatment should not exceed 10 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 Clostridium difficile should be considered. Fluids, electrolytes and protein replacement therapy should be provided when indicated.
Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil), may prolong and/or worsen the condition and should not be used.
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 supra-therapeutic 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 hypokalemia or hypomagnesaemia, clinically significant bradycardia), and in patients receiving Class IA and III antiarrhythmic agents and drugs such as astemizole, cisapride or pimozide (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.

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 severe impaired hepatic function (e.g. hepatic cirrhosis with jaundice and/or ascites), the dose should be reduced by half.

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 10 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 (3500/mm³) at the conclusion of therapy with roxithromycin. Of these, 4% had a neutrophil count of less than 1500/mm³ and 1.2% had a count of less than 1000/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.
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 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.

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 metabolized 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 abovementioned 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 normalized 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.

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 ciclosporin.

A slight increase in plasma concentrations of theophylline or ciclosporin 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. Breast feeding 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 effects 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 such as 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).

Liver.

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

Others.

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 http://www.tga.gov.au/reporting-problems or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

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) or the National Poisons Centre, 0800 POISON or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

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 has demonstrated the efficacy and safety of once daily dosing in adults, this has 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, Streptococcus pyogenes, Mycoplasma pneumoniae, Moraxella catarrhalis, Ureaplasma urealyticum, Chlamydia spp.
Roxithromycin has been demonstrated to have clinical activity against the following microorganisms which are partially sensitive in vitro to roxithromycin: Haemophilus influenzae, Staphylococcus aureus, (except MRSA).
The following strains of microorganisms are resistant:
Multiresistant Staphylococcus aureus, Enterobacteriaceae, Pseudomonas spp. Acinetobacter spp.

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.
Using the 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 mg and 300 mg film coated tablets are achieved in young and elderly adult patients approximately 1 to 2 hours postdose. However, Rulide D 50 mg tablets for suspension appear to be absorbed more slowly than the Rulide film coated tablets, with peak plasma concentrations achieved approximately 3 hours postdose.
As food intake decreases absorption, Rulide should be administered at least 15 minutes before food or, alternatively, on an empty stomach (i.e. more than 3 hours after a meal).
Absorption is not linear; with increasing doses in the range 150 mg to 300 mg, peak plasma levels and 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 Rulide 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 Rulide 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.

Distribution.

Roxithromycin is 92-96% bound to plasma proteins (principally α₁-acid glycoprotein, but also albumin) at concentrations less than 4.2 mg/L. The binding is saturable; in subjects with normal plasma levels of α₁-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.

Elimination.

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: C_min and AUC values are comparable for adults and children.
The half-life is prolonged to 25 hours in adults with impaired hepatic function and 18 hours in adults 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

Mutagenesis.

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

Genotoxicity.

No data available.

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

Excipients present in Rulide tablets are colloidal anhydrous silica, glucose, hyprolose, hypromellose, magnesium stearate, maize starch, poloxamer, povidone, propylene glycol, purified talc and titanium dioxide.
Excipients present in Rulide D tablets are colloidal anhydrous silica, crospovidone, fumaric acid, Liquorice Flavour Atomized (PI 2341), macrogol 6000, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, purified talc, saccharin sodium, sodium hydroxide, sodium lauryl sulfate, Strawberry Flavour Dry 995/2L 1/1000 Essepi (PI 2338) and triethyl citrate

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

Rulide 300 mg Tablets: store in a cool dry place below 30°C.
Rulide 150 mg Tablets: store in a cool dry place below 25°C.
Rulide D 50 mg Tablets: store in a cool place below 30°C.

6.5 Nature and Contents of Container

Rulide 300 mg Tablets: available in blister packs of 5 tablets.
Rulide 150 mg Tablets: available in blister packs of 10 tablets.
Rulide D 50 mg Tablets: available in aluminium blister packs of 10 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

Roxithromycin is a semi-synthetic macrolide antibiotic. It is a white crystalline powder. Roxithromycin is very slightly soluble in water, freely soluble in acetone, in alcohol and in methylene chloride. It is slightly soluble in dilute hydrochloric acid.

Chemical structure.

Roxithromycin has the following structural formula:

The empirical formula for roxithromycin is C₄₁H₇₆N₂O₁₅. Its molecular weight is 837.07.

CAS number.

80214-83-1.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

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Rulide D

Roxithromycin

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BRAND INFORMATION

Rulide D Tablets 50 mg