(Aust Prescr 2000;23:137-9)
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.
Stemgen (Amgen Australia)
vials containing 1.875 mg as powder for reconstitution
Approved indication: stem cell transplant
Australian Medicines Handbook Section 14.2
Some cancer treatments require the patient to have an autologous stem cell
transplant after chemotherapy. The cells for transplant are collected before
treatment. Granulocyte colony stimulating factor (G-CSF) is often used to increase
the number of circulating haemopoietic precursor cells available for collection.
Ancestim has been developed for use with G-CSF to further increase the number
of cells which can be harvested for transplant. It is a recombinant form of
human stem cell factor, the protein which normally stimulates stem cell production.
Ancestim and G-CSF have been compared with G-CSF alone in 205 women with breast
cancer. The objective was to collect a target number (5 x 106/kg)
of CD34+ cells. Treatment continued until the target was reached
or aphoresis had been carried out five times. The proportion of the patients
given the combination who reached the target was 63% compared with only 47%
of the patients given G-CSF alone. Fewer collections were needed in the combination
group; a median of four aphoresis procedures was required.
Everyone prescribed ancestim must be given a bronchodilator and H1 and
H2 antagonists before each subcutaneous injection. There is a risk
that ancestim will stimulate mast cells and cause allergic reactions. Nearly
all patients will experience an injection site reaction. Other common adverse
effects include respiratory symptoms, paraesthesia and rashes.
The stimulant effect of ancestim may promote the growth of tumour cells. Particular
caution is needed if the drug is considered for use in patients with myeloid
malignancies, melanomas, or small cell lung cancers.
While ancestim has achieved its targets for efficacy, there is little information
on its benefits for the patients. Although the patients may be spared additional
aphoresis, it is unknown if adding ancestim to G-CSF will ultimately improve
end-points such as survival.
Revasc (Aventis Pharma)
vials containing 15 mg as lyophilised powder
Approved indication: prevention of thromboembolism
Australian Medicines Handbook Section 7.1
The influence of the leech on medical practice seems set to continue into the
next century following the approval of desirudin. This is a recombinant product
with a structure that is almost identical to hirudin, an anticoagulant found
in the saliva of Hirudo medicinalis. It has been approved for the prevention
of thromboembolism after hip replacement surgery.
Desirudin is reconstituted with mannitol and injected subcutaneously no more
than 30 minutes before elective hip replacement. Twice daily injections continue
for 9-12 days until the patient is walking. The injections should be rotated
through at least four different sites.
The maximum plasma concentrations occur within three hours of injection. Desirudin
is partly metabolised before excretion. Approximately half the dose is excreted
unchanged in the urine. The APTT should be monitored in patients with impaired
hepatic or renal function.
Desirudin acts by specifically inhibiting thrombin. As desirudin can inactivate
thrombin bound to fibrin, it has a potential advantage over heparin which also
has a less specific action.
A double-blind trial has compared subcutaneous heparin and desirudin in 1119
patients having hip surgery.1 Patients given the dose of desirudin
recommended for use in Australia (15 mg twice daily) were significantly less
likely to develop deep vein thrombosis than those given unfractionated heparin
(18.4% versus 34.2%). The respective frequencies of proximal thrombosis were
3.1% versus 19.6%. The frequency of bleeding complications was similar in both
groups.
Episodes of bleeding occurred in 13% of patients given desirudin in clinical
trials. There is no antidote. Other adverse effects include haematoma, injection
site masses and secretion from the wound.
While hirudin is more effective than subcutaneous unfractionated heparin, its
role in clinical practice is not yet clear. There needs to be a comparison
between hirudin and other approaches to preventing thrombosis such as adjusted
dose intravenous heparin or subcutaneous low molecular weight heparin.
Reference
1. Eriksson BI, Ekman S, Kalebo P, Zachrisson B, Bach D, Close
P. Prevention of deep-vein thrombosis after total hip replacement: direct thrombin
inhibition with recombinant hirudin, CGP 39393. Lancet 1996;347:635-9.
Vioxx (Merck Sharp & Dohme)
12.5 mg and 25 mg tablets
Approved indication: osteoarthritis
Australian Medicines Handbook Section 15.1
Rofecoxib is the second inhibitor of cyclo-oxygenase 2 (COX-2) to be marketed
in Australia. Unlike celecoxib (see ‘New drugs’ Aust
Prescr 1999;22:147-8), in Australia its approval is limited to osteoarthritis.
Compared to celecoxib, rofecoxib is more selective for COX-2. It therefore
has little effect on the synthesis of prostaglandins in the gut. Rofecoxib
has a half-life of 17 hours and can be taken once a day. Each dose is well
absorbed resulting in a bioavailability of 93%. The drug is metabolised in
the liver and most of the metabolites are excreted in the urine.
In clinical trials rofecoxib has reduced joint pain in osteoarthritis more
than placebo. It also improves stiffness and joint function. During a six-week
study the efficacy of 12.5 mg or 25 mg rofecoxib daily was similar to that
of 800 mg ibuprofen three times a day. In a year-long comparison, rofecoxib
was comparable to 50 mg diclofenac three times a day.
Studies which used endoscopy to look for gastroduodenal ulcers, found that
rofecoxib 25 mg or 50 mg/day caused significantly fewer ulcers than ibuprofen
2400 mg/day during 24 weeks of treatment. However, gastrointestinal bleeding
can still occur. Among the 3357 patients treated with rofecoxib in clinical
trials, three experienced a haemorrhage. This incidence is lower than that
seen with non-steroidal anti-inflammatory drugs, but a long-term study of comparative
safety has not been performed.
In the clinical trials of rofecoxib the most commonly reported adverse effects
were headache, diarrhoea and abdominal pain. Some patients will have increased
blood pressure or fluid retention so extra caution is required if a patient
has heart failure or reduced renal function. Approximately 1% of patients will
develop abnormal liver function tests. Rofecoxib interacts with several drugs
including warfarin and ACE inhibitors.
For patients with osteoarthritis, who cannot be managed with other analgesics,
prescribers now have a choice between celecoxib and rofecoxib. Although rofecoxib
is more selective it may not be safer. Until evidence of long-term safety and
efficacy is available the choice of treatment will be influenced by the cost
of the drugs.
Visudyne (CIBA Vision)
vials containing 15 mg as powder for reconstitution
Approved indication: macular degeneration
Australian Medicines Handbook Section 11.4
As people grow older they can develop macular degeneration. This is caused
by a failure to clear the products of retinal metabolism. In some patients
this prompts vessels to grow from the choroid into the retina. If these abnormal
vessels leak or bleed, the resulting scar reduces the patient’s central
vision. The only treatment is laser photocoagulation, but this has several
limitations.1
Verteporfin is a drug treatment which aims to destroy new blood vessels affecting
the retina. As verteporfin is not very soluble it has to be formulated in a
liposomal delivery system. This is diluted and given as an infusion over 10
minutes. Verteporfin is transported around the body by lipoproteins.
To activate the drug a non-thermal laser light is shone into the affected eye
15 minutes after the infusion begins. An exposure of 83 seconds generates reactive
oxygen radicals which may cause damage to vascular endothelium. This can lead
to the occlusion of the abnormal vessels.
In double-blind trials involving 609 patients, 402 eyes were given photodynamic
therapy with verteporfin and 207 eyes were treated with a placebo. The treatments
were repeated every three months if fluoroscein angiography revealed leaking
vessels. After one year the visual acuity and angiographic assessments were
significantly better in the eyes exposed to verteporfin. The loss of visual
acuity was particularly reduced in a sub-group of patients with classic choroidal
revascularisation. Only 33% of this group had a substantial loss of vision
compared with 61% of the placebo group.2 Verteporfin has
only been approved for use in patients with predominantly classic subfoveal
choroidal neovascularisation.
There were few serious adverse reactions to verteporfin. Compared to placebo,
there were more complaints about visual disturbance, injection site reactions
and nausea.2 Although verteporfin has a half-life of 5-6
hours, patients are advised to remain indoors for five days after treatment.
This is because they become photosensitive after treatment. Although verteporfin
may tend to accumulate in abnormal vessels it can also enter the retina. This
could result in retinal damage when the drug is activated.
The long-term effects of verteporfin are currently unknown. Although it can
help some patients with macular degeneration, future research is needed to
prevent this common cause of blindness.1
References
1. Fine SL, Berger JW, Maguire MG, Ho AC. Age-related macular
degeneration. N Engl J Med 2000;342:483-92.
2. TAP Study Group. Photodynamic therapy of subfoveal choroidal
neovascularization in age-related macular degeneration with verteporfin. Arch
Ophthalmol 1999;117:1329-45.
NEW FORMULATIONS
Nurofen Meltlets (Boots Healthcare)
200 mg tablets
NEW STRENGTHS
Desferrioxamine for injection BP (Faulding)
2 g vials
Fibro-vein (Australasian Medical and Scientific)
0.2%, 0.5% and 1% injections
Sotacor (Bristol-Myers Squibb)
80 mg tabletsNEW COMBINATIONS
Fosinopril sodium/hydrochlorothiazide
Monoplus (Bristol-Myers Squibb)
10 mg fosinopril sodium/12.5 mg hydrochlorothiazide and
20 mg fosinopril sodium/12.5 mg hydrochlorothiazide tablets
Irbesartan/hydrochlorothiazide
Avapro HCT (Bristol-Myers Squibb)
150 mg irbesartan/12.5 mg hydrochlorothiazide and 300 mg irbesartan/12.5 mg hydrochlorothiazide tablets
Karvezide (Sanofi-Synthelabo)
150 mg irbesartan/12.5 mg hydrochlorothiazide and 300 mg irbesartan/12.5 mg hydrochlorothiazide tablets
