(Aust Prescr 1995;18:58-9)
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.
Iopidine (Alcon Laboratories)
0.5% ophthalmic solution
Indication: glaucoma
Several drugs are available to reduce aqueous secretion or increase aqueous outflow (see 'The medical treatment of glaucoma' Aust Prescr 1993;16:34-7). Apraclonidine can be used to control the intraocular pressure of patients on maximally tolerated treatment for chronic glaucoma.
The drug is an alpha adrenergic agonist. Intraocular pressure falls within an hour of a single dose and the peak reduction occurs in 3-5 hours. The halflife is 8 hours and 3 times a day instillation is recommended. A 5minute interval should separate the instillation of apraclonidine and other eye drops.
After two months' treatment, the effectiveness of apraclonidine may decline. If treatment is continued for more than 3 months, patients should be more closely monitored, particularly for corneal changes.
In clinical studies, 15% of patients discontinued treatment due to adverse effects. The patients' complaints included hyperaemia, pruritis, discomfort and dry mouth. Systemic adverse reactions include headache, asthenia and chest pain. The drug is contraindicated in patients taking monoamine oxidase inhibitors, tricyclic antidepressants or sympathomimetics.
Wellvone (Wellcome Australia)
250 mg filmcoated tablets
Indication: Pneumocystis carinii pneumonia
Immunocompromised patients, including those with HIV infection, are at risk of developing Pneumocystis carinii pneumonia. The pneumonia is usually treated with trimethoprim/sulfamethoxazole and this combination can be used as prophylaxis against recurrent infections. However, many patients with AIDS cannot tolerate trimethoprim /sulfamethoxazole. Pentamidine is one alternative treatment, but the majority of patients develop adverse reactions. Patients who are intolerant of trimethoprim/sulfamethoxazole can now be treated with atovaquone.
Atovaquone is an antimalarial drug which also has activity against Pneumocystis carinii and Toxoplasma gondii . It acts by inhibiting electron transport in protozoal mitochondria.
The bioavailability of atovaquone is low, but absorption can be increased by taking the drug with food, especially high fat food. Atovaquone is mainly excreted unchanged in the faeces. The halflife is approximately 3 days.
A doubleblind trial has compared atovaquone with trimethoprim/sulfamethoxazole in patients with AIDS and Pneumocystis carinii pneumonia. After 21 days, significantly more patients taking atovaquone had failed to respond to treatment. One month after therapy, mortality was significantly higher in the atovaquone group. Although atovaquone was less effective, it produced fewer treatmentlimiting adverse effects.1
Atovaquone has also been compared with intravenous pentamidine. Although more patients taking atovaquone failed to respond, the group had fewer treatmentlimiting adverse effects and more patients were improved one month after treatment.2
The most common adverse effect is rash. Other adverse reactions include nausea,
vomiting, diarrhoea, headache, insomnia and fever. Information about drug interactions
is limited, but plasma concentrations of atovaquone are significantly decreased
by metoclopramide and rifampicin. Although zidovudine does not appear to affect
the pharmacokinetics of atovaquone, zidovudine metabolism may be decreased
by atovaquone.
References
1. Hughes W, Leoung G, Kramer F, Bozzette SA, Safrin S,
Frame P,
et al. Comparison of atovaquone (566C80) with trimethoprimsulfamethoxazole
to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl
J Med 1993;328:1521-7.
2. Dohn MN, Weinberg WG, Torres RA, Follansbee SE, Caldwell
PT, Scott JD, et al. Oral atovaquone compared with intravenous pentamidine
for Pneumocystis carinii pneumonia in patients with AIDS. Ann Intern
Med 1994;121:174-80.
Famvir (SmithKline Beecham)
250 mg film coated tablets
Indication: herpes zoster
Patients who present within 72 hours of developing herpes zoster can be treated with acyclovir tablets 5 times daily. Prescribers now have the option of treating adults with famciclovir tablets 3 times daily.
Famciclovir is rapidly absorbed from the gut, but absorption is delayed by food. The drug is quickly converted to penciclovir. This is converted to penciclovir triphosphate in infected cells and, subsequently, viral DNA synthesis is inhibited. Excretion is by the kidneys, but no unchanged famciclovir is found in the urine. The interval between doses should be increased in patients with renal impairment. The halflife of penciclovir is approximately 2 hours.
For the treatment of shingles, the efficacy of famciclovir is probably similar to that of acyclovir. However, the efficacy of famciclovir in ophthalmic herpes zoster and chicken pox has not been studied, and the drug is less efficacious in patients less than 50 years old. If treatment is started early enough, patients taking famciclovir will heal sooner than patients taking placebo. The duration of postherpetic neuralgia may also be reduced.
The adverse effects of famciclovir include headache and nausea. These effects are also associated with acyclovir, so at present the only advantage of famciclovir over acyclovir appears to be that it has to be taken less often.
Oestradiol valerate/medroxyprogesterone acetate
Divina (Organon Australia) oestradiol valerate 2 mg (11 white tablets) and oestradiol valerate 2 mg/medroxyprogesterone acetate 10 mg (10 blue tablets)
Indication: hormone replacement therapy
The drugs contained in this combination are already available as individual
formulations. If a woman requires hormone replacement therapy after a natural
or surgical menopause, a personal regimen should be devised. Women who use
a regimen containing oestradiol valerate and medroxyprogesterone acetate
may wish to change to this combination product. When making this change,
practitioners should consider if this fixed dose combination is bioequivalent
to the existing formulations of its components.
The advantage of this product is that it combines a natural oestrogen with
a nonandrogenic progestogen. Medroxyprogesterone acetate does not antagonise
the effects of the oestrogen on lipoproteins as much as the 19-nortestosterone
types of progestogens. However, continuous oestrogen replacement is preferred
to a 21-day regimen1, so the usefulness of this product
may be limited.
Reference
1. Palmer D. Regimens for hormone replacement therapy. Aust
Prescr 1994;17:13-6.
NEW STRENGTHS
Caverject (Upjohn)
ampoules containing 5 microgram/mL, 10 microgram/mL and 20 microgram/mL
Indication: erectile dysfunction
Alprostadil is prostaglandin E1. A continuous infusion of prostaglandin has been used to maintain the patency of the ductus arteriosus in neonates with congenital heart defects. As the drug causes vasodilatation, it has been studied in the investigation and treatment of erectile dysfunction.
After the drug is injected into the corpus cavernosa of the penis, most patients will develop an erection within 30 minutes. The dose may need to be adjusted to find the most effective dose for a patient's needs. After appropriate training, the patients can inject themselves with the drug. They should be instructed not to inject themselves with a dose which produces an erection which lasts for more than an hour. Alprostadil should only be used once a day and not more than 3 times a week.
The adverse effects of treatment include penile pain, priapism, haematoma
and penile fibrosis.
