(Aust Prescr 1999;22:70-1)
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.
Inactivated Japanese encephalitis vaccine
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 survivors have neurological sequelae.1 The disease has been reported in many Asian countries and the vaccine is recommended for
• persons who will be resident in endemic areas for more than one month during the transmission season
• travellers who visit rural areas during epidemics
• tourists travelling extensively in rural areas known to have endemic disease.
This vaccine is an inactive vaccine produced from the brains of infected mice. Studies of mass immunisation in endemic countries show seroconversion in over 80% of vaccinees. The efficacy of preventing disease is 91% (95%, confidence interval 54-98%), but the duration of protection in unknown.
To protect at-risk travellers over the age of 12 months, 3 injections are needed. These injections are given subcutaneously over 30 days, with the last dose being given at least 10 days before travel. The vaccine is not recommended for everyone travelling to Asia, but it is appropriate to encourage all travellers to take precautions against mosquito bites.
Patients should be observed for 30 minutes after vaccination as angioedema or urticaria can occur within minutes. The risk of hypersensitivity is increased in patients with a history of allergy. As delayed reactions can occur, vaccinees should remain in an area with easy access to medical care for 10 days. The rate of serious allergic reactions ranges from 1-104 per 10 000 vaccinees. These adverse reactions are less common than local and systemic adverse effects which occur in 20% and 10% of vaccinees.
Reference
1. Bucens M, O'Connor L. Japanese encephalitis and 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 are approximately 500 requests to use the drug under the Special Access Scheme.
Primaquine acts against the liver (hypnozoite) stage of Plasmodium vivax and Plasmodium ovale. It is therefore indicated for the prevention of relapse (radical cure) of these infections. Primaquine can also be used as adjunctive therapy in the treatment of Plasmodium falciparum as it is effective against gametocytes.
Usually, primaquine is well tolerated, but all patients should be tested for glucose-6-phosphate dehydrogenase deficiency. This is because of the risk of haemolytic anaemia. Leucocytosis, methaemoglobinaemia and haemolytic anaemia can all occur at therapeutic doses. Gastrointestinal adverse effects are more common, 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 for influenza. The celebration which followed its approval by the Australian Drug Evaluation Committee in February 1999 was short-lived. Within a few days, the share price of Biota Holdings slumped when the Antiviral Advisory Committee of the Food and Drug Administration (FDA) in the U.S.A. voted against recommending the drug for approval by the FDA.
That Committee's decision may have been influenced by an unpublished study which did not show the benefit seen in other trials. Two multicentre studies, in North America and Europe, found that zanamivir reduced the symptoms of influenza if treatment began early enough in the illness. Patients with fever got better 3 days sooner if they were treated with zanamivir rather than a placebo.1
Zanamivir acts by inhibiting the neuraminidase of the influenza virus. This surface enzyme normally allows the release of the virus from infected cells, so inhibition reduces viral propagation. When volunteers were given zanamivir and then inoculated with the virus, only 13% developed influenza, compared with 70-83% of those given a placebo. Viral shedding was also significantly reduced.2
The powdered drug is inhaled using the Diskhaler device. Patients inhale 10 mg twice daily for 5 days. Most of the dose is deposited in the oropharynx and lungs. The 10-20% of the dose which is absorbed into the systemic circulation is excreted unchanged in the urine.
Zanamivir was well tolerated by patients in the clinical trials. No dose adjustments are recommended for the elderly or patients with liver or kidney disease. Caution is required when prescribing for patients with severe asthma in case inhaling zanamivir affects lung function.
While epidemics of influenza can increase morbidity and mortality, high-risk groups, such as the elderly, can be protected by immunisation. Amantadine is already available for people who have been exposed to influenza, so what is the 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 influenza or another infection. Even if the infection is confirmed as influenza, zanamivir will only alleviate the symptoms one day faster than a placebo.1 As influenza is a self-limiting condition for most otherwise healthy people, zanamivir is more likely to be a niche drug than a treatment for everyone with flu-like symptoms.
References
1. GG167 Influenza Study Group. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. 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 experimental human influenza. JAMA 1996;275:295-9.
| Answers to self-test questions | ||
| 1. True | 2. False | 3. False |
| 4. False | 5. True | 6. True |
| 7. False | 8. True | 9. True |
| 10. False | ||
