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ISSUE 3 JUNE
New drug

Ranibizumab

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, 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. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Lucentis (Novartis)
1.8 mg/0.3 mL or 3.0 mg/0.3 mL in single-dose vials
Approved indication: neovascular age-related macular degeneration
Australian Medicines Handbook section 11.7

Age-related macular degeneration is the leading cause of irreversible blindness in Australia. It is a progressive disease that causes loss of 'straight ahead' vision. Approximately 10% of people with this condition have the neovascular or 'wet' form. This is caused by abnormal blood vessels under the macula leaking fluid and bleeding, which eventually leads to scarring. Using fluorescein angiography, these lesions can be classified as 'classic' or 'occult'.1One current treatment for this disease in Australia is verteporfin, which is given intravenously and then followed by photodynamic therapy (see New drugs, Aust Prescr 2000;23:137–9).

Ranibizumab is a humanised monoclonal antibody fragment which blocks vascular endothelial growth factor A (VEGF-A), a key mediator in neovascular age-related macular degeneration.

Following intravitreal injection very little ranibizumab is absorbed systemically and any that is, is rapidly cleared. The terminal half-life of ranibizumab in the vitreous humour is approximately 10 days.

Most of the published efficacy data for ranibizumab comes from two randomised controlled trials. One trial compared monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) with sham injections (pressing a needleless syringe against the conjunctiva) in 716 patients with age-related macular degeneration. Patients had either occult or minimally classic choroidal neovascularisation. After 12 months of treatment, around 94% of patients given ranibizumab and 62% of patients receiving a sham injection maintained their vision. This was defined as losing less than 15 letters of visual acuity on the chart used in the Early Treatment Diabetic Retinopathy Study. The chart consists of 14 rows of 5 letters each. For patients in the ranibizumab groups, visual acuity increased by an average of 6.5 letters for the 0.3 mg dose and 7.2 letters for the 0.5 mg dose and decreased by an average of 10.4 letters in the sham injection group. After 24 months of treatment visual improvements were largely maintained in the patients receiving ranibizumab, whereas vision continued to decline in patients receiving sham injections.2

In the other efficacy trial, monthly injections of ranibizumab (0.3 mg or 0.5 mg) were compared with an active treatment, verteporfin photodynamic therapy, in 423 patients with (predominantly classic) neovascular age-related macular degeneration. After 12 months of treatment, around 95% of patients given ranibizumab and 64% of patients receiving verteporfin therapy maintained their vision. On average, visual acuity in patients receiving ranibizumab increased by 8.5 letters in the 0.3 mg group and 11.3 in the 0.5 mg group and decreased by 9.5 letters in the verteporfin group.3

Within both of these trials, the difference between the efficacy of ranibizumab and the sham injection or verteporfin therapy was statistically significant, whereas the difference between the two ranibizumab doses was not.2,3

In the larger efficacy trial, serious uveitis, endophthalmitis and retinal tear occurred in the ranibizumab groups but not in the sham group. Increases in intraocular pressure (of 30 mmHg or more) occurred more often after ranibizumab injections than sham injections.1In both trials, non-ocular haemorrhage was more common in patients treated with ranibizumab compared to control patients.2,3Some trials have reported an increase in arterial thromboembolism in patients given intravitreal ranibizumab.

After two years of treatment, 4.4% of patients given 0.3 mg of ranibizumab and 6.3% of those given the 0.5 mg dose tested positive for circulating antibodies to ranibizumab. This did not seem to affect the efficacy of ranibizumab.2

Doctors should be aware that only one eye should be injected at each visit. As ranibizumab is injected into the vitreous cavity, aseptic technique is important and patients should be monitored during the week following treatment in case infection occurs. Advise patients to administer antimicrobial eye drops for three days before and after the injection.

Increases in intraocular pressure and changes in perfusion of the optic nerve head may occur within 60 minutes of the injection and so these should be monitored. Ranibizumab can temporarily affect vision and patients should be warned not to operate machinery if this occurs.

Ranibizumab seems to offer a promising alternative to current therapy for neovascular age-related macular degeneration. Ongoing trials are investigating whether patients can have the same benefit from less frequent injections of ranibizumab.4

manufacturer provided the product information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

 

Withdrawal of thioridazine

Thioridazine is an old antipsychotic drug. Its use has declined partly because of concerns about it causing serious cardiac arrhythmias.

The current manufacturer is ceasing production of thioridazine in Australia. It is expected that stocks will be exhausted in August 2007.

No protocol has been published to assist prescribers switch patients to other therapy. Some information was made available to Canadian prescribers when thioridazine sales ceased in Canada during 2005 (see www.hc-sc.gc.ca).Thioridazine is an old antipsychotic drug. Its use has declined partly because of concerns about it causing serious cardiac arrhythmias. The current manufacturer is ceasing production of thioridazine in Australia. It is expected that stocks will be exhausted in August 2007. No protocol has been published to assist prescribers switch patients to other therapy. Some information was made available to Canadian prescribers when thioridazine sales ceased in Canada during 2005 (see www.hc-sc.gc.ca).
 

References

  1. Guymer R. Drug treatment of macular degeneration. Aust Prescr 2002;25:116-9.
  2. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419-31.
  3. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44.
  4. Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: phase III clinical trial results. Ophthalmol Clin N Am 2006;19:361-72.