NEW ZEALAND DATA SHEET

1. PRODUCT NAME
Arrow – Roxithromycin 150, 150 mg, coated tablets
Arrow – Roxithromycin 300, 300 mg, coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 150 mg or 300 mg of roxithromycin.
For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM
White, round, coated tablets.

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 micro-organisms:

• upper respiratory tract infection - acute pharyngitis, tonsillitis and sinusitis

• dental infections
• lower respiratory tract infection - acute bronchitis; acute exacerbations of chronic bronchitis and
community acquired pneumonia
• skin and skin structure infections
• non-gonococcal 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 micro-organisms: acute
pharyngitis, acute tonsillitis and 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
This product may not be interchangeable with other products containing this ingredient in the New
Zealand's market. The bioequivalence with Rulide® marketed in Australia has been demonstrated.
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 film coated tablets must be swallowed whole with a drink.
Adults
The recommended dosage is 300 mg per day, which may be taken according to one of the following
dosage regimens.
Usual dosage: Roxithromycin 300 mg tablets: one tablet daily. Roxithromycin 150 mg tablets: one
tablet twice daily or two tablets once daily.

Version 1.0 1
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
non-gonococcal genital infections may require twenty days for complete cure.
Special populations
Elderly
Roxithromycin 300 mg tablets: one tablet daily. Roxithromycin 150 mg tablets: one tablet twice daily
or two tablets once daily.
Impaired renal function
Roxithromycin 300 mg tablets: one tablet daily. Roxithromycin 150 mg tablets: one tablet twice daily
or two tablets once daily.
Impaired hepatic function
One roxithromycin 150 mg tablet once daily for patients with documented cirrhotic liver disease.
Paediatric population
Roxithromycin is administered twice daily at a dose of 5 to 8 mg/kg/day (see Special warnings and
precautions for use).
For children 40 kg and over
One roxithromycin 150 mg tablet morning and evening.
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
Arrow - Roxithromycin is contraindicated in the following conditions:

• known hypersensitivity to macrolides, including erythromycin

• severely impaired hepatic function (see Special warnings and precautions for use)
• concomitant therapy with vasoconstrictive ergot alkaloids (see Interaction with other medicines
and other forms of interaction).

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.
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.
As with other macrolides, roxithromycin may have the potential to aggravate myasthenia gravis.

Version 1.0 2
Cases of severe bullous skin reactions such as Stevens Johnson Syndrome or Toxic Epidermal
Necrosis have been reported with roxithromycin (see Undesirable effects). If symptoms or signs of
SJS or TEN (eg. 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
macrolide antibiotics have been associated with vasoconstrictive ergot alkaloids. Absence of
treatment by these alkaloids must always be checked before prescribing roxithromycin.
Increased INR levels have been reported in patients when Arrow - Roxithromycin and coumarin
anticoagulants are used concomitantly. Patients using Arrow - Roxithromycin and coumarin
anticoagulants should be closely monitored (see Interaction with other medicines and other forms of
interaction).
Prolongation of the QT Interval
Ventricular arrhythmias associated with prolonged QT interval, including ventricular tachycardia and
torsades de pointes have been reported with macrolide antibiotics including roxithromycin.
Prescribers should consider the risk of QT prolongation (which can be fatal) when weighing the risks
and benefits of roxithromycin for at-risk groups including:

• Patients predisposed to QT interval prolongation such as those with a history of torsades de

pointes or congenital long QT syndrome.
• Patients taking other medication known to prolong the QT interval such as antiarrhythmics of
classes IA and III; antipsychotic agents; antidepressants; and fluoroquinolones.
• Patients with electrolyte disturbance, particularly in cases of hypokalaemia and
hypomagnesaemia.
• Patients with clinically relevant bradycardia, cardiac arrhythmia or cardiac insufficiency.

Impaired hepatic function

Caution should be exercised if roxithromycin is administered to patients with impaired hepatic
function, as its serum half life is increased in patients with hepatic failure. If administered to patients
with severe hepatic insufficiency (e.g. hepatic cirrhosis with jaundice and/or ascites), the dose should
be reduced by half to 150 mg once daily.
Impaired renal function
In the elderly and those with renal failure, dosage reduction is not required for the normally short
course of treatment.
Use in children
In young animal studies, high oral doses of roxithromycin were associated with bone growth plate
abnormalities. However, no abnormalities were observed in the animals at doses resulting in unbound
plasma roxithromycin concentrations that were 10 to 15 times higher than the unbound concentration
measured in children receiving the therapeutic dose. The maintenance of such safety margins is
primarily dependent on high affinity binding of roxithromycin to plasma alpha-1-acid glycoprotein
and will be compromised by any circumstances attenuating the extent of this binding. It is
recommended that the approved paediatric dosage regimen (i.e. 5 to 8 mg/kg/day for a maximum of
ten days) be adhered to strictly.
Neutropenia was observed in children treated with roxithromycin. 31.6% of 402 children in clinical
trials had a neutrophil count below the lower limit of the normal range (3,500/mm3) at the conclusion
of therapy with roxithromycin. Of these, 4% had a neutrophil count of less than 1,500/mm3 and 1.2%
had a count of less than 1,000/mm3. It is not known whether this is an effect of the drug, or whether it
reflects a normal fluctuation of the neutrophil count or a response to infection in children.

Version 1.0 3
Use in the elderly
No dosage adjustment is required in elderly patients.
4.5 Interaction with other medicines and other forms of interaction
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, 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 hence 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. Thus, 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 Special warnings and precautions for use).
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

Version 1.0 4
phenprocoumon, and severe bleeding episodes have occurred as a consequence. INR should be
monitored during combined treatment with roxithromycin and warfarin.
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 suggesting cardiac
glycoside overdosage have occurred.
Midazolam
Roxithromycin, like other macrolides, may increase the area under the midazolam concentration-time
curve and the midazolam half-life. Thus, 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 theophylline and 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
Use in pregnancy (Category B1)
Reproductive studies in rats, mice and rabbits at doses of 100, 400 and 135 mg/kg/day, respectively,
did not demonstrate evidence of developmental abnormalities. In rats, at doses above 180 mg/kg/day,
there was evidence of embryotoxicity and maternotoxicity. The safety of roxithromycin for the human
fetus has not been established.
Use in lactation
Small amounts of roxithromycin are excreted in the breast milk. Breastfeeding or treatment of the
mother should be discontinued as necessary.
Carcinogenicity, mutagenicity, impairment of fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of
roxithromycin. Roxithromycin has shown no mutagenic potential in standard laboratory tests for gene
mutation and chromosomal damage.
There was no effect on the fertility of rats treated with roxithromycin at oral doses up to 180
mg/kg/day.
4.7 Effects on ability to drive and use machines
Attention should be drawn to the possibility of dizzy sensations.
4.8 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.

Version 1.0 5
Gastrointestinal
Nausea, vomiting, epigastric pain, diarrhoea (very rarely 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 have 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, purpura, glottic oedema, generalised oedema, erythema
multiforme, exfoliative dermatitis, Stevens-Johnson syndrome and Toxic Epidermal Necrosis (TEN)
(see 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 are rarely reported.
Other
Eosinophilia, bronchospasm, hallucination, confusion, headache, dizziness, paraesthesia, tinnitus,
malaise, moniliasis (candidiasis), pancreatitis, QT prolongation, disorders of taste and/or smell,
temporary deafness, hypoacusis and vertigo.
4.9 Overdose
In case of overdosage, gastric lavage may remove residual drug in the stomach. Clinical monitoring
should be considered along with symptomatic and supportive treatment as required. There is no
specific antidote.
LD50 dosage was high in mice and rats at 0.75 g/kg and 1 - 1.7 g/kg, respectively. In dogs, a dose of 2
g/kg did not result in toxicity.
For advice on the management of overdose please contact the National Poisons Centre on 0800
POISON (0800 764766).

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Macrolides, ATC code: J01FA06
Microbiology
Roxithromycin is a semi-synthetic 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 micro-organisms:
Streptococcus pneumoniae, Strep. pyogenes, Mycoplasma pneumoniae, Moraxella catarrhalis,
Ureaplasma urealyticum and Chlamydia sp.

Version 1.0 6
Roxithromycin has been demonstrated to have clinical activity against the following micro-organisms
which are partially sensitive in vitro to roxithromycin: Haemophilus influenzae and Staphylococcus
aureus, except methicillin resistant Staph. aureus (MRSA).
The following strains of micro-organisms are resistant: multi-resistant Staph. aureus,
Enterobacteriaceae, Pseudomonas sp. and Acinetobacter sp.
Susceptibility tests
Using the National Committee for Clinical Laboratory Standards (NCCLS), method of susceptibility
testing with a 15 microgram roxithromycin disc, susceptible organisms other than Haemophilus
influenzae produce zones of inhibition of diameter 21 mm or greater. A zone diameter of 10 to 20 mm
should be considered intermediate and a zone diameter of 9 mm or less indicates resistance. A
bacterial isolate may be considered susceptible if the minimal inhibitory concentration (MIC) value
for roxithromycin is less than or equal to 1 mg/L. Organisms are considered resistant if the MIC value
is greater than 8 mg/L.
For H. influenzae, zones of inhibition of diameter 10 mm or greater indicate susceptibility when CO2
incubation and the HTM agar is used with a 15 microgram roxithromycin disc. An isolate may be
considered susceptible if the MIC value for roxithromycin is less than or equal to 8 mg/L.
Note: The prevalence of resistance may vary geographically for selected species and local information
on resistance is desirable, particularly when treating severe infections.
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.

Version 1.0 7
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.
After a single oral dose of 150 mg roxithromycin, good concentrations are reached in respiratory tract
tissues and secretions, male and female genital tracts, tonsils and paranasal sinuses, synovial fluid and
the skin. Roxithromycin is not detected in saliva.
Metabolism
The mean half-life of roxithromycin is approximately 12 hours in young adults and 20 hours in
children. The apparently longer half-life in children does not cause excessive accumulation; minimum
concentration (Cmin) and AUC values are comparable for adults and children.
The half-life is prolonged to 25 hours in patients with impaired hepatic function and 18 hours in
patients with renal insufficiency. The mean half-life in elderly patients is approximately 27 hours.
Roxithromycin undergoes limited metabolism in the body, presumably in the liver. The major
metabolite is descladinose roxithromycin. Two minor metabolites have also been identified. Plasma
levels of roxithromycin are approximately twice those of all metabolites; a similar ratio is seen in the
urine and faeces.
Excretion
Approximately 7% of a dose is excreted in the urine and 13% is eliminated via the lungs. Faecal
excretion, which represents the unabsorbed fraction and the small proportion excreted by the liver,
accounts for approximately 53% of the dose. The fate of the remainder is unknown.
When roxithromycin plasma levels are above 4.2 mg/L, renal clearance increases because reduced
plasma protein binding (see Distribution) causes increased levels of unbound roxithromycin which
may be excreted by the kidneys.
5.3 Preclinical safety data
None.

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Low substituted hydroxypropyl cellulose (hyprolose), colloidal anhydrous silica, povidone, purified
talc, maize starch, magnesium stearate, hypromellose, anhydrous glucose, titanium dioxide and
propylene glycol.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
24 months
6.4 Special precautions for storage
Store in a cool, dry place where it stays below 25°C, and protect from light and moisture.
6.5 Nature and contents of container
PVC/PVdC/Aluminium foil blister strips. Pack size of 10 tablets (150 mg) and 5 tablets (300 mg).

Version 1.0 8
6.6 Special precautions for disposal
No special requirements for disposal.

7. MEDICINE SCHEDULE
Prescription Medicine

8. SPONSOR
Teva Pharma (New Zealand) Limited
PO Box 128 244
Remuera
Auckland 1541
Telephone: 0800 800 097

9. DATE OF FIRST APPROVAL

28 September 2006

10. DATE OF REVISION OF THE TEXT

10 February 2017

SUMMARY TABLE OF CHANGES

Section changed Summary of new information

Update to the SPC-style format
4.4 Warning regarding potential interaction between
roxithromycin and warfarin as per MARC recommendation
4.4, 4.5 & 4.8 Updated
8. Sponsor company name and address details updated

Version 1.0 9