(Aust Prescr 1997;20:22-3)
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.
Ethyol (Schering-Plough)
vials containing 500 mg as lyophilised powder
Indication: chemoprotection
As the drugs used in chemotherapy damage normal tissues as well as cancer cells,
their dose may be limited by toxicity. Amifostine has been developed to protect
the kidney from nephrotoxic effects and to prevent the complications of haematological
toxicity.
The drug is given by a 15 minute infusion starting half an hour before chemotherapy.
Amifostine is rapidly converted to its active metabolite by alkaline phosphatase.
As the concentration of this enzyme is higher in normal cells, only small amounts
of the metabolite occur in tumour cells. The metabolite may protect normal
cells by scavenging the free radicals produced during chemotherapy.
Amifostine has been approved for decreasing the incidence of the acute and
cumulative nephrotoxicity associated with platinum-based therapy. It is also
indicated to decrease the incidence of neutropenia-related fever and infection
induced by DNA-binding agents (classical alkylating agents such as cyclophosphamide
and non-classical alkylating agents such as mitomycin-C and platinum-containing
drugs).
As most of the drug and its metabolites are taken into the tissues, very little
is excreted. The active metabolite can be found in bone marrow within 10 minutes
of the infusion.
In advanced ovarian cancer, amifostine, compared to chemotherapy alone, reduces
the incidence of myelotoxicity. The patients given amifostine also spent fewer
days in hospital for the treatment of complications of neutropenia.
Although amifostine appears to have some benefit in preventing adverse effects, it has its own adverse reactions. Hypotension commonly occurs towards the end of the infusion. Although the hypotension is transient, some patients may become unconscious or require the infusion to be stopped. Nausea and vomiting also occur frequently. Giving the infusion more slowly increases the adverse effects. Calcium concentrations should be measured as they can be reduced by amifostine.
Norvir (Abbott Australasia)
100 mg capsules
Indication: HIV infection
The approval of ritonavir adds to the choice of HIV protease inhibitors in
Australia. While most of the efficacy data for this class of drugs are based
on surrogate markers, there is some evidence that ritonavir reduces mortality.
The drug acts by inhibiting the HIV-1 protease. This results in the formation
of non-infectious HIV particles. The drug is metabolised with most of each
dose being excreted in the faeces. Only 4% is excreted unchanged in the urine.
Several studies, including an Australian study1,
show that treatment with ritonavir increases the number of lymphocytes. In
patients who have not previously taken antiretroviral drugs, ritonavir has
a greater effect than zidovudine. Ritonavir alone also appears to be more effective
than a combination with zidovudine. For patients with advanced disease, one
study, with a median duration of 6 months, has found a reduction in mortality
and clinical progression of HIV disease. During the study, 26 (4.8%) of the
543 patients who had ritonavir added to their therapy died, compared with 46
(8.4%) of the 547 who had a placebo added.
One of the problems with treating HIV is the development of resistant strains. While ritonavir and other HIV protease inhibitors are unlikely to develop cross-resistance with reverse transcriptase inhibitors, it is not known if cross-resistance will develop between the protease inhibitors. Viral clones with reduced susceptibility to ritonavir have already been isolated.
The long-term effects of ritonavir are not known, but several adverse effects are associated with treatment. Common adverse effects are vomiting, diarrhoea, asthenia and paraesthesia. Nausea is the most frequent adverse reaction and is moderate or severe in at least 25% of patients. Ritonavir increases the concentrations of triglycerides and liver enzymes. The metabolism of ritonavir by the cytochrome P450 system creates a potential for many drug interactions. Commonly used drugs which may interact include macrolide antibiotics, calcium channel blockers, oral contraceptives containing ethinyloestradiol, warfarin and many antidepressants.
Reference
1. Kelleher AD, Carr A, Zaunders J, Cooper DA. Alterations
in the immune response of human immunodeficiency virus (HIV) - infected subjects
treated with an HIV-specific protease inhibitor, ritonavir. J Infect Dis 1996;173:321-9.
NEW COMBINATIONS
Loratidine/pseudoephedrine sulfate
Clarinase Repetabs (Schering-Plough)
tablets containing 5 mg loratidine and 120 mg pseudoephedrine sulfate
Correction
Loratadine
Spelling corrected Jan 2008
NEW FORMULATIONS
Zovirax Cold Sore Cream (Warner Lambert)
5% cream
Uromitexan (Asta Medica)
4 00 mg and 600 mg tablets
NEW STRENGTHS
Xanax (Pharmacia & Upjohn)
2 mg tablets
MS Contin (Pharmacia & Upjohn)
200 mg controlled-release tablets
NEW PROPRIETARY BRANDS
Cephazolin (David Bull Laboratories)
vials containing 500 mg and 1 g for injection
Paxam 0.5 and 2 (Alphapharm)
0.5 mg and 2 mg tablets
Cyproterone acetate/ethinyloestradiol
Brenda-35 ED (Alphapharm)
tablets containing 2 mg cyproterone acetate and 35 micrograms ethinyloestradiol
Doxy-100 (Douglas Pharmaceuticals)
100 mg tablets
