Relenza Rotadisks
(zanamivir)
5mg/blister
PRESCRIPTION MEDICINE
RELENZA is indicated for treatment of both influenza A and B in adults and children (¡Ý 5 years) who present with symptoms typical of influenza when influenza is circulating in the community.
RELENZA is for administration to the respiratory tract by oral inhalation only, using the Diskhaler device provided.
INFLUENZAInfluenza is a viral infection more commonly known as 'the flu'. It can be a serious illness, especially in frail and elderly people. The types of flu vary from year to year but the strains of flu this year seem particular nasty with many people being affected for a week or more. As it is viral infection antibiotics are of no value in treatment unless the flu is accompanied by a bacterial infection. Until recently there have been no effective products to treat the underlying infection. Treatment has been focussed on the symptoms, leaving the body to deal with the infection. Relenza is a new product from Glaxo Wellcome which has been clinically proven to shorten the length of time flu symptoms last. It needs to be taken as soon as possible after the symptoms are noticed to get the best results (within 48hrs). It is only available on the prescription of a doctor.
(For the technically minded here's just how Relenza works¡¡..)
Zanamivir inhibits the flu virus neuraminidase enzyme which normally cleaves the bond holding new virus particles to infected cells. Inhibiting the cleavage process stops the release of new virus particles, which lessens the spread of flu in the body. Zanamivir is effective against influenza A and B viruses. It is given as a powder inhaled via a special device and deposited on to the surface of the lungs where the flu virus replicates.
Another product in the same family as Relenza, but in tablet form has been developed by Roche and could be on the market next year.
Flu symptoms are quite different from the common cold.
A person suffering from the flu is likely to have:
A high fever (39 - 40oC). (rare with the common cold) Muscle and joint aches and pains (rare with the common cold) Extreme tiredness and weakness to the point of having difficulty moving or getting out of bed. (more severe than with the common cold) Headache. (more severe than with the common cold) Pain on eye movement (A cold usually causes watery eyes) Cough, usually dry and often irritating. (may also occur with the common cold) Sore throat. (may also occur with the common cold) The flu can be more serious and you should see a doctor if:
Secondary infections such as bronchitis or pneumonia develop. The patient is a child or elderly. Serious fever or high temperatures develop. A severe headache, sensitivity to light, a stiff neck or a rash are present. Confusion or impaired mental functioning or alertness. There is vomiting or diarrhoea associated with other symptoms. Loss of appetite Symptoms don't improve over a 48hour period or last longer than 7 days If the cough produces flem and especially if it is coloured and unpleasant. Treatment Options
The following treatment options help to reduce the uncomfortable and distressing symptoms associated with the flu. They will not lessen the length of the infection but will help make it more bearable.
Aspirin (Aspro, Disprin), and Paracetamol (Disprol, Pamol, Panadol)
These medicines should be taken regularly (usually every four hours) to help lower the temperature and to relieve the muscle aches and headache. Aspirin should be stopped if indigestion occurs or if increased bruising or prolonged bleeding occurs. Aspirin should not be used in children under 12 years old unless advised by a doctor. Cough Mixtures
There are a number of cough mixtures available but essentially they contain one or more of these common ingredients (Pholcodine, Dextromethorphan - can cause mild sedation in some people). A dry cough is often treated with something to stop the cough. A cough that produces flem and is clearing the lungs should not be stopped as a more serious infection can develop. If in doubt then you must consult a pharmacist or doctor.
Supportive measures
Best rest and a high intake of fluids are important supportive measures for getting over the flu.
Supplements that may help include
Pine bark extract
Vitamin C plus bioflavinoids
Echinacea with vitamin C and bioflavinoids
Garlic and echinacea.
Preventative measures
Vaccines
A flu vaccination should be considered if the person gets influenza regularly or for those at risk. It is available from your doctor and free for people over 65 or for people with conditions such as Asthma. Buccaline Berna
These tablets contain very small inactivated amounts of bacteria which can cause the other infections associated with colds and flu. A three day course can help the body build an immunity towards these bugs, the course can be repeated every 4 weeks if required. Protection may last for up to three months. Flu tests
ZstatFlu, positively identifies type A and type B flu viruses. Previous tests have taken up to two weeks to show a negative test.
The flu test, distributed by New Zealand Diagnostics, is of special interest for nursing homes, institutions, the military and workplaces where flu infection spreads easily. Data Sheet
RELENZA Rotadisks
Zanamivir 5mg/blister
Qualitative and Quantitative Composition
Each RELENZA Rotadisk consists of four regularly spaced double foil blisters each containing a powder mixture of zanamivir (5mg) and lactose (20mg).
Pharmaceutical Form
Inhalation powder.
Therapeutic Indications
Treatment of Influenza:
RELENZA is indicated for treatment of both influenza A and B in adults and children (¡Ý 5 years) who present with symptoms typical of influenza when influenza is circulating in the community.
Posology and Method of Administration
RELENZA is for administration to the respiratory tract by oral inhalation only, using the Diskhaler device provided.
Treatment of Influenza:
The recommended dose of RELENZA is two inhalations (2 x 5mg) twice daily for five days, providing a total daily inhaled dose of 20mg.
For maximum benefit, treatment should begin as soon as possible (preferably within two days) after onset of symptoms.
Impaired Renal or Hepatic Function:
No dose modification is required (see Pharmacokinetic properties).
Elderly patients:
No dose modification is required (see Pharmacokinetic properties).
Paediatric patients:
No dose modification is required (see Pharmacokinetic Properties).
Patients on asthma medication
Patients scheduled to take inhaled medicines, e.g. fast acting bronchodilators, at the same time as RELENZA, should be advised to administer that medicine prior to administration of RELENZA.
Zanamivir has not been evaluated in immunocompromised patients.
Contraindications
Hypersensitivity to any ingredient of the preparation.
Special Warnings and Special Precautions for Use
Influenza infection can be associated with increased airways hyper-responsiveness. There have been very rare reports of patients being treated for influenza who have experienced bronchospasm and/or decline in respiratory function after the use of zanamivir, some of whom did not have any previous history of respiratory disease. Any such patients should discontinue zanamivir and seek medical evaluation. Patients with underlying respiratory disease should have a fast acting bronchodilator available when taking zanamivir (see Posology and Method of Administration).
Due to the limited number of patients evaluated, it has not been possible to demonstrate efficacy in high risk populations, with the exception of patients with underlying respiratory disease.
Use During Pregnancy and Lactation
Pregnancy
The safe use of RELENZA during pregnancy has not been established.
Reproductive studies performed in rats and rabbits indicated that placental transfer of zanamivir occurs. Studies in rats did not show any evidence of teratogenicity, impairment of fertility or clinically significant impairment of peri or post-natal development of offspring following administration of zanamivir. However, there is no information on placental transfer in humans.
RELENZA should not be used in pregnancy, especially during the first trimester, unless the possible benefit to the patient is thought to outweigh any possible risk to the foetus.
Lactation
In rats zanamivir has been shown to be secreted into milk. However, there is no information on secretion into breast milk in humans.
As experience is limited, the use of zanamivir in nursing mothers should be considered only if the possible benefit to the mother is thought to outweigh any possible risk to the infant.
Effects on Ability to Drive and Use Machines
None known.
Interaction with Other Medicinal Products and Other Forms of Interaction
Zanamivir is not protein bound and not hepatically metabolised or modified. Clinically significant drug interactions are unlikely.
Undesirable Effects
Clinical trial data
RELENZA is well tolerated by the oral inhaled route of administration. In clinical studies, including those studies with high risk patients (the elderly, and patients with certain chronic medical conditions), the adverse events reported were similar in the RELENZA and placebo groups.
Post-marketing data
Very common | 1/10 |
Common | 1/100 and <1/10 |
Uncommon | 1/1000 and <1/100 |
Rare | 1/10,000 and <1/1000 |
Very rare | <1/10,000 |
The following events have been identified during post-approval use of zanamivir (RELENZA) for the treatment of influenza.
General:
Very rare: | Allergic-type reaction, including facial and oropharyngeal oedema |
Respiratory
Very rare: | bronchospasm, dyspnoea |
Skin
Very rare: | rash, urticaria |
Overdose
Accidental overdose is unlikely due to the physical limitations of the presentation, the route of administration and the poor oral bioavailability (2 to 3%) of zanamivir. Doses of zanamivir up to 64mg/day (approximately 3 times the maximum daily recommended dose) have been administered by oral inhalation (by nebuliser) without adverse effects. Additionally, systemic exposure by intravenous administration of up to 1200mg/day for five days showed no adverse effect.
Pharmacological Properties
Pharmacodynamic Properties
Mechanism of action.
Zanamivir is a potent and highly selective inhibitor of neuraminidase, the influenza virus surface enzyme. Viral neuraminidase aids the release of newly formed virus particles from infected cells, and may facilitate access of virus through mucus to epithelial cell surfaces, to allow viral infection of other cells. The inhibition of this enzyme is reflected in both in vitro and in vivo activity against influenza A and B virus replication, and encompasses all of the known neuraminidase subtypes of influenza A viruses.
The activity of zanamivir is extracellular. It reduces the propagation of both influenza A and B viruses by inhibiting the release of infectious influenza virions from the epithelial cells of the respiratory tract. Influenza viral replication is confined to the superficial epithelium of the respiratory tract. The efficacy of topical administration of zanamivir to this site has been confirmed in clinical studies. Clinical trial data have shown that treatment of acute influenza infections with zanamivir produces reductions in virus shedding from the respiratory tract compared to placebo without any detectable emergence of virus with reduced susceptibility to zanamivir.
Clinical experience
RELENZA, when taken as recommended for treatment of influenza in otherwise healthy and high risk patients, alleviates the symptoms and reduces their duration. In a pooled analysis of the principle phase III treatment studies (NAIB3001, NAIA3002, NAIB3002 and NAI30008) the median time to alleviation of influenza symptoms was reduced by 1.5 days for patients taking Relenza as compared to placebo (p<0.001). Complications were reduced from 208/711 (29%) of placebo patients to 171/769 (22%) of zanamivir patients (relative risk: 0.77; 95% CI: 0.65 to 0.92; p=0.004). Use of antibiotics for treatment of complications was reduced from 136/711 (19%) of placebo patients to 110/769 (14%) of zanamivir patients (relative risk: 0.76; 95% CI: 0.60 to 0.95; p=0.021).
The efficacy of RELENZA has been shown to be optimal if treatment is initiated as soon as possible after the onset of symptoms.
Pharmacokinetic Properties
Absorption:
Pharmacokinetic studies in humans have shown that the absolute oral bioavailability of the drug is low (mean 2%). Similar studies of orally inhaled zanamivir indicate that approximately 10-20% of the dose is systemically absorbed, with serum concentrations generally peaking within 1-2 hours. The poor absorption of the drug results in low systemic concentrations and therefore there is no significant systemic exposure to zanamivir after oral inhalation. There is no evidence of modification in the kinetics after repeated dosing with oral inhaled administration.
Distribution:
After oral inhalation, zanamivir is widely deposited at high concentrations throughout the respiratory tract, thus delivering the drug to the site of influenza infection. Following a single 10mg dose the concentrations of zanamivir were measured at the epithelial layer of the airways, the major sites of influenza viral replication. Zanamivir concentrations of approximately 340 and 52 fold above the median viral neuraminidase IC50 were measured at 12h and 24h respectively. The high concentrations of zanamivir in the respiratory tract will result in the rapid onset of inhibition of the viral neuraminidase. The two major sites of deposition are the oropharynx and the lungs (mean 77.6% and 13.2%, respectively).
Metabolism:
Zanamivir has been shown to be renally excreted as unchanged drug, and does not undergo metabolism.
Elimination:
The serum half-life of zanamivir following administration by oral inhalation ranges from 2.6 to 5.05 hours. It is entirely excreted unchanged in the urine. Total clearance ranges from 2.5 to 10.9L/h as approximated by urinary clearance. Renal elimination is completed within 24 hours.
Patients with renal impairment:
At the therapeutic daily dose of 20mg, bioavailabilty is low (10-20%), and as a result there is no significant systemic exposure of patients to zanamivir. Given the wide safety margin of zanamivir the possible increased exposure in patients with severe renal failure is not considered problematic and no dose adjustment is required.
Patients with hepatic impairment:
Zanamivir is not metabolised, therefore dose adjustment in patients with hepatic impairment is not required.
Elderly patients:
At the therapeutic daily dose of 20mg, bioavailabilty is low (10-20%), and as a result there is no significant systemic exposure of patients to zanamivir. Any alteration of pharmacokinetics that may occur with age is unlikely to be of clinical consequence and no dose modification is recommended.
Paediatric patients:
In an open-label single-dose study the pharmacokinetics of zanamivir have been evaluated in 24 paediatric subjects ages 3 months to 12 years using nebulised (10mg) and dry powder (10mg) inhalation formulations. The systemic exposure in children was similar to 10mg of inhaled powder in adults.
Preclinical Safety Data
Administration of Zanamivir in animal toxicity studies was not associated with any clinically relevant effects. Zanamivir was not genotoxic and showed no evidence of carcinogenic potential in long term carcinogenicity studies in rats and mice.
Pharmaceutical Particulars
List of Excipients
RELENZA is a white to off-white powder blend of micronised zanamivir and lactose.
Incompatibilities
None known
Shelf Life
36 months
Special Precautions for Storage
RELENZA Rotadisks should not be stored above 30¡ãC.
Nature and Contents of Container
RELENZA Rotadisks consists of a circular foil disk (a Rotadisk) with four regularly distributed blisters each containing 5mg of zanamivir and 20mg of lactose. A Diskhaler is provided to administer the medication.
Instructions for Use/Handling
The powdered medicine is inhaled through the mouth into the lungs. The Diskhaler device is loaded with a disk that contains the medicine in individual blisters which are opened as the device is manipulated.
For detailed instructions for use refer to the Patient Instruction Leaflet in every pack.
Instructions for Use:
A RELENZA Rotadisk may be kept in the Diskhaler at all times but a blister should only be pierced immediately prior to use. Failure to observe this instruction will affect operation of the Diskhaler.
The Diskhaler is a device which is used together with a Rotadisk for inhaling medication.
The Diskhaler consists of:-
an outer coloured body with a hinged lid and piercing needle
a dark mouthpiece cover
a white sliding tray with mouthpiece
a dark wheel to support the Rotadisk
The Rotadisk consists of 4 blisters. Each blister contains a measured dose of dry powder medication.
WARNING:-
Do not puncture any Rotadisk blister until loaded into the Diskhaler.
TO LOAD THE ROTADISK INTO THE DISKHALER
Remove the mouthpiece cover and check inside and outside to ensure that the mouthpiece is clean.
Hold the corners of the white tray and pull out gently until you can see all the plastic ridges on the sides of the tray.
Put your finger and thumb on the ridges, squeeze inwards and gently pull the tray out of the Diskhaler body.
Place the Rotadisk on the dark wheel with the blisters facing down. Then slide the tray back fully into the Diskhaler body.
TO PIERCE THE BLISTER IN THE ROTADISK
Raise the lid as far as it will go into the fully upright position. Both surfaces of the blister must be pierced. Some resistance will be felt as the upper and especially the lower surfaces of the blister are pierced. Then close the lid.
WARNING:-
Do not try to lift the lid unless the tray is positioned fully within the body of the Diskhaler or is completely removed.
TO INHALE FROM THE DISKHALER
Breathe out as far as is comfortable. Keeping the Diskhaler level, raise the Diskhaler to your mouth and gently place the mouthpiece between your teeth and lips but do not bite the mouthpiece. Do not cover the air holes on either side of the mouthpiece. Breathe in through your mouth steadily and as deeply as you can. Hold this breath in for several seconds and remove the Diskhaler from your mouth. Continue to hold your breath for as long as is comfortable.
TO PREPARE FOR THE NEXT INHALATION
Rotate the Rotadisk to the next blister by gently pulling the tray once out and in. Do not pierce the blister until immediately before inhalation. When you take another inhalation pierce the blister and inhale as shown in steps 5 and 6.
Always replace the mouthpiece cover after use.
TO REPLACE THE ROTADISK
Each Rotadisk consists of 4 blisters containing medication. When the Rotadisk is empty, it should be replaced with a new Rotadisk by repeating steps 2 to 4.
WARNING:-
Do not throw the wheel away with the empty Rotadisk.
Medicines Classification
Prescription Only Medicine
Company Name and Address
Glaxo Wellcome New Zealand Limited
Quay Tower
Cnr Albert & Customs Streets
Private Bag 106600
Downtown
Auckland
NEW ZEALAND
