Some of the views expressed in the following notes on newly approved products should be regarded as tentative, as there may have been limited published data and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. As a result of fuller experience, initial comments may need to be modified. The Committee is prepared to do this. Before new drugs are prescribed, the Committee believes it is important that full information is obtained either from the manufacturer's approved product information, a drug information centre or some other appropriate source.
JE-VAX (CSL)
1 mL vials
Approved indication: Japanese encephalitis prophylaxis
Australian Medicines Handbook Section 20.1
Japanese encephalitis is a flavivirus infection transmitted by mosquitoes.In epidemics, the immediate mortality rate can reach 50% and many survivorshave neurological sequelae.1 The disease hasbeen reported in many Asian countries and the vaccine is recommended for
– persons who will be resident in endemic areas for more than one monthduring the transmission season
– travellers who visit rural areas during epidemics
– tourists travelling extensively in rural areas known to have endemicdisease.
This vaccine is an inactive vaccine produced from the brains of infectedmice. Studies of mass immunisation in endemic countries show seroconversionin over 80% of vaccinees. The efficacy of preventing disease is 91% (95%, confidenceinterval 54-98%), but the duration of protection in unknown.
To protect at-risk travellers over the age of 12 months, 3 injections areneeded. These injections are given subcutaneously over 30 days, with the lastdose being given at least 10 days before travel. The vaccine is not recommendedfor everyone travelling to Asia, but it is appropriate to encourage all travellersto take precautions against mosquito bites.
Patients should be observed for 30 minutes after vaccination as angioedemaor urticaria can occur within minutes. The risk of hypersensitivity is increasedin patients with a history of allergy. As delayed reactions can occur, vaccineesshould remain in an area with easy access to medical care for 10 days. Therate of serious allergic reactions ranges from 1-104 per 10 000 vaccinees.These adverse reactions are less common than local and systemic adverse effectswhich occur in 20% and 10% of vaccinees.
Reference
1. Bucens M, O'Connor L. Japanese encephalitisand the traveller. Aust Fam Physician 1990;19:163-5.
Primacin (Boucher & Muir)
7.5 mg tablets
Approved indication: malaria
Australian Medicines Handbook Section 5.4.1
Primaquine has been used in the treatment of malaria for over 50 years; however,it has not been available in Australia for several years. Each year there areapproximately 500 requests to use the drug under the Special Access Scheme.
Primaquine acts against the liver (hypnozoite) stage of Plasmodium vivax and Plasmodiumovale. It is therefore indicated for the prevention of relapse (radicalcure) of these infections. Primaquine can also be used as adjunctive therapyin the treatment of Plasmodium falciparum as it is effective againstgametocytes.
Usually, primaquine is well tolerated, but all patients should be tested forglucose-6-phosphate dehydrogenase deficiency. This is because of the risk ofhaemolytic anaemia. Leucocytosis, methaemoglobinaemia and haemolytic anaemiacan all occur at therapeutic doses. Gastrointestinal adverse effects are morecommon, but can be reduced by taking primaquine with food.
Relenza (Glaxo Wellcome)
blister packs containing 5 mg powder for inhalation
Approved indication: influenza
Australian Medicines Handbook Section 5.3
Zanamivir was developed in Australia by Biota Holdings as a treatment forinfluenza. The celebration which followed its approval by the Australian DrugEvaluation Committee in February 1999 was short-lived. Within a few days, theshare price of Biota Holdings slumped when the Antiviral Advisory Committeeof the Food and Drug Administration (FDA) in the U.S.A. voted against recommendingthe drug for approval by the FDA.
That Committee's decision may have been influenced by an unpublished studywhich did not show the benefit seen in other trials. Two multicentre studies,in North America and Europe, found that zanamivir reduced the symptoms of influenzaif treatment began early enough in the illness. Patients with fever got better3 days sooner if they were treated with zanamivir rather than a placebo.1
Zanamivir acts by inhibiting the neuraminidase of the influenza virus. Thissurface enzyme normally allows the release of the virus from infected cells,so inhibition reduces viral propagation. When volunteers were given zanamivirand then inoculated with the virus, only 13% developed influenza, comparedwith 70-83% of those given a placebo. Viral shedding was also significantlyreduced.2
The powdered drug is inhaled using the Diskhaler device. Patients inhale 10mg twice daily for 5 days. Most of the dose is deposited in the oropharynxand lungs. The 10-20% of the dose which is absorbed into the systemic circulationis excreted unchanged in the urine.
Zanamivir was well tolerated by patients in the clinical trials. No dose adjustmentsare recommended for the elderly or patients with liver or kidney disease. Cautionis required when prescribing for patients with severe asthma in case inhalingzanamivir affects lung function.
While epidemics of influenza can increase morbidity and mortality, high-riskgroups, such as the elderly, can be protected by immunisation. Amantadine isalready available for people who have been exposed to influenza, so what isthe role of zanamivir? An advantage of zanamivir is that, unlike amantadine,it is effective against the less common influenza B.
When a patient presents, the doctor does not know if the patient has influenzaor another infection. Even if the infection is confirmed as influenza, zanamivirwill only alleviate the symptoms one day faster than a placebo.1 Asinfluenza is a self-limiting condition for most otherwise healthy people, zanamiviris more likely to be a niche drug than a treatment for everyone with flu-likesymptoms.
References
1. GG167 Influenza Study Group. Efficacyand safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirusinfections. N Engl J Med 1997;337:874-80.
2. Hayden FG, Treanor JJ, Betts RF, Lobo M, Esinhart JD,Hussey EK. Safety and efficacy of the neuraminidase inhibitor GG167 in experimentalhuman influenza. JAMA 1996;275:295-9.
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