(Aust Prescr 1994;17:6-8)
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.
Ocufen (Allergan Australia)
0.03% ophthalmic solution in 5 mL dropper bottles
Indication: inhibition of intra-operative miosis
Flurbiprofen is a derivative of the non-steroidal antiinflammatory drug ibuprofen. As it inhibits cyclo-oxygenase, it blocks the prostaglandin mediated pupillary constriction which can occur during ophthalmic surgery.
The eye drops are instilled before surgery. Patients may complain of burning or stinging, with 3% reporting severe discomfort. Although the drug is generally effective and safe, persistent mydriasis and increased bleeding, e.g. hyphaema, have been reported.
Skinoren (Schering)
cream containing 0.2 g/g in 30 g tubes
Indication: acne
The precise mechanism of action of azelaic acid in patients with acne is unclear. There is an antibacterial action on Propionibacterium acnes and a possible effect on follicular plugging.
Azelaic acid cream is applied twice a day. Part of the dose is absorbed through the skin and azelaic acid can be detected in breast milk. The drug is not approved for patients under 17 years old.
In comparative studies, azelaic acid has been more effective than placebo, but has no significant advantage over other treatments e.g. benzoyl peroxide, oral tetracycline.
Most adverse effects are due to irritation of the skin and often occur in the first few weeks of treatment. Some patients will stop using the cream before a clinical improvement in their acne becomes apparent after approximately one month of treatment. While burning, itching, erythema and scaling are the common adverse reactions, photosensitivity can occur.
The maximum improvement may require 4 months of treatment. However, a 30 g tube will only last about two weeks if used on the face alone. Treatment should not exceed 6 months' duration.
Voltaren Rapid (Ciba-Geigy)
25 mg and 50 mg tablets
Indication: analgesia
Diclofenac has been available as a sodium salt for many years. The substitution of a potassium salt results in an earlier onset of action. After oral administration of a 50 mg tablet, the peak plasma concentration is reached in 20-60 minutes compared with an average of 120 minutes for diclofenac sodium. This new formulation has therefore been approved as a short-term treatment for the relief of acute pain states in which there is an inflammatory component and in the symptomatic treatment of primary dysmenorrhoea.
The adverse effects of diclofenac potassium resemble those of the sodium salt.
Botox (Allergan Australia)
vials containing 100 units of toxin, 0.5 mg human albumin and 0.9 ing sodium chloride as lyophilised powder
Indication: blepharospasm
Clostridium botulinum produces a neurotoxin which blocks the release of acetylcholine in cholinergic nerves.
By blocking transmission at the neuromuscular junction, the toxin causes paralysis.
Small amounts of the toxin injected into muscles cause weakness and atrophy. The muscles only recover when new nerve terminals grow, a process which takes several months.
Botulinum toxin injections have been used clinically in several conditions characterised by muscle spasm. The treatment is particularly effective (>90%) in the treatment of blepharospasm. It has been approved for use by patients over the age of 12 years with blepharospasm associated with dystonia, including benign blepharospasm and VII cranial nerve disorders (hemifacial spasm). The treatment may be repeated when the muscle recovers, but the longterm effects of repeated injections are unknown.
The toxin must be injected by a practitioner with a detailed knowledge of the anatomy in the orbital region. Adverse effects can occur due to the spread of the toxin from the injection site. Ptosis is a common adverse effect.
Holoxan (Farmitalia Carlo Erba)
500
mg, 1 g and 2 g in single dose vials
Indication: tumour chemotherapy
Ifosfamide is an alkylating agent similar to cyclophosphamide. It has anti-tumour activity in sarcomas, lymphomas and germ cell tumours, and may have some activity in other tumours e.g. cervical carcinoma.
After the drug is given intravenously, it is activated in the liver. The active metabolite affects nucleic acids and protein synthesis and leads to the death of the cell. Most of the dose is excreted in the urine and urotoxicity can be a major problem.
As haemorrhagic cystitis occurs frequently, ifosfamide should be given with a uroprotective drug (see 'Mesna' below). If a uroprotector is used, myelosuppression becomes the dose-limiting toxicity. Leucopenia is observed commonly and has been used as a guide to treatment. Anaemia and thrombocytopenia can also occur.
Other adverse effects include alopecia, nausea, vomiting and a potentially fatal central nervous system toxicity.
Uromitexan (Farmitalia Carlo
Erba)
100 mg/mL in 2 mL, 4 mL and
10 mL single dose ampoules
Indication: prevention and reduction of urothelial toxicity
Alkylating agents such as cyclophosphamide and ifosfamide can cause haemorrhagic cystitis. Mesna can reduce this toxicity as it reacts with the metabolites which cause the adverse effects on the urothelium.
The drug is given intravenously at the same time as the alkylating agent and is then repeated after 4 and 8 hours. It is eliminated rapidly from the plasma and the majority of the dose is excreted renally within 4 hours.
As mesna is usually given with potent anticancer drugs, it is difficult to attribute adverse effects. Mesna may be associated with diarrhoea, headache and altered taste.
Lamictal (Wellcome)
25 mg, 50 mg, 100 mg and 200 ing
tablets
Indication: epilepsy
Lamotrigine is a phenyltriazine compound unrelated to other antiepileptic drugs. It is thought to act by inhibiting the release of excitatory neurotransmitters in the brain.
The drug is completely and rapidly absorbed from the gut. Although first pass metabolism is insignificant, the drug is extensively metabolised by the liver. The metabolites are mostly excreted in the urine. Lamotrigine has an elimination half-life of approximately 30 hours, but multiple administration may reduce the half-life by enzyme induction. Other antiepileptic drugs may affect the metabolism of lamotrigine.
Lamotrigine has been studied in patients whose seizures are not satisfactorily controlled on a single drug. Clinical trials suggest that the addition of lamotrigine will significantly reduce some patient's frequency of seizures. On the basis of these trials, the drug has been approved as an 'add-on' therapy for partial seizures. Further studies may reveal a role for lamotrigine in the treatment of other seizures.
Treatment should begin at a low dose and gradually be increased until an optimal response is obtained. The patient's other treatment may affect the dosage e.g. a lower dose is used in patients taking sodium valproate.
Most adverse effects occur during the first weeks of treatment with lamotrigine. Commonly observed adverse effects include skin rashes, dizziness, headache, diplopia, ataxia, somnolence and nausea.
Logiparin (CSL)
pre-filled syringes containing 11700
anti-Xa IU/mL, (2500 anti-Xa IU/0.2 mL, 3500 anti-Xa IU/0.3 mL and 4500
antiXa IU/0.4 mL)
multidose vials containing
10 000 anti-Xa IU/mL in 2 mL vials
Indication: prevention of postoperative thromboembolism
Tinzaparin is an addition to the choice of low molecular weight heparins. These products are fragments of heparin which differ in their method of production. Tinzaparin is produced by depolymerisation of heparin obtained from the intestine of pigs.
The low molecular weight heparins cannot be interchanged and the clinical effect may not be directly related to the antiXa activity. The efficacy of tinzaparin in orthopaedic surgery has only been evaluated in patients undergoing elective hip replacement.
The adverse effect profile is similar to that of conventional heparin. A reduced risk of bleeding with low molecular heparins has not been demonstrated. As tinzaparin comes in a variety of dose forms, great care should be taken to ensure the patient receives the recommended dose.
Meningococcal vaccine tetravalent
Mencevax ACWY (SmithKIine Beecham)
monodose and multidose vials containing lyophilised vaccine for reconstitution
Indication: meningitis prophylaxis
Meningococci are divided into serologic groups by the different antigens in their capsular polysaccharides. Serious disease is caused by groups A, B, C, W and Y. The previously available vaccine contained purified polysaccharides from groups A and C only.
The reformulated vaccine is approved for use in controlling epidemics or immunising the contacts of patients infected with A, C, W 135 or Y meningococci. Travellers to countries where the disease is endemic or highly epidemic can also be immunised.
Little data are available on the use of the vaccine in children under 14 years of age and there are no data on the protective efficacy of the antibody response to the added W 135 and Y polysaccharides. The vaccine offers no protection against infection by other groups.
Local reactions to the vaccine occur in a majority of patients and may be more frequent in children.
Elocon (Schering-Plough)
0.1 % cream and ointment in 15 g, 30 g, 50 g and 100 g tubes
Indication: inflammatory and pruritic dermatoses
Mometasone is a synthetic corticosteroid which has been approved for the topical treatment of steroid responsive dermatoses such as eczema and psoriasis. The drug is of intermediate potency compared to other topical steroids, but has the convenience of a once daily application.
Systemic absorption can occur, so mometasone should not be applied to large areas of skin, particularly in children. Adverse effects are similar to those of other topical steroids. Until long-term safety data are available, treatment should not exceed one month's duration.
Roxiam (Astra)75 mg, 150 mg and 300 mg capsules
100 mg/mL intramuscular injection in 2 mL ampoules
Indication: schizophrenia
The dopamine hypothesis of the pathophysiology of schizophrenia proposes that dopamine overactivity leads to schizophrenic symptoms. Antipsychotic drugs antagonise the actions of dopamine in sub-cortical pathways, but there are often extrapyramidal adverse effects. As remoxipride is a selective antagonist of central D 2 dopamine receptors, it has fewer extrapyramidal adverse effects.
Remoxipride is absorbed rapidly from the gut and is 70-80% bound to plasma proteins. The drug is metabolised by the liver and excreted by the kidney. In severe renal or hepatic disease, the plasma half-life of 4-7 hours may be doubled, so lower doses are required.
The drug is as effective as other antipsychotics such as haloperidol in the treatment of schizophrenia and schizophrenia-like psychoses. However, remoxipride binds specifically to the D 2 receptor and has little affinity for other central receptors e.g. adrenergic, muscarinic and 5-HT receptors. Therefore, the incidence of adverse effects is less than with other antipsychotics, but the range of adverse effects is similar.
In clinical trials, the common extrapyramidal effects have been tremor, akathisia and rigidity. Although the incidence of these adverse effects is 10-20%, this is significantly less than one would expect with haloperidol. However, there have been recent overseas reports of patients developing aplastic anaemia. The company now advises that all patients should have a normal blood count before starting treatment and it should be monitored during treatment. Patients need to be advised to report promptly any bruising, bleeding, fever or other signs of infection.
Proscar (Merck Sharp & Dohme)
5 mg film coated tablets
Indication: benign prostatic hypertrophy
The development of benign prostatic hypertrophy is related to the production of dihydrotestosterone. This potent androgen is produced by the action of 5 alpha reductase on testosterone. Finasteride blocks this metabolism by inhibiting the enzyme.
A daily dose of 5 mg finasteride can reduce the size of the prostate gland and improve the flow of urine. These benefits may take several months to appear, and when treatment ceases, the volume of the prostate increases again, approaching pre-treatment size.
The bioavailability of the tablets is approximately 80% and absorption is complete after 8 hours. Plasma clearance is approximately 165 mL/minute giving a half-life of 6 hours. Finasteride is metabolised with a greater proportion of the two metabolites being excreted in the faeces. The company does not recommend different doses for elderly patients or those with renal insufficiency.
Adverse effects associated with inhibition of 5 alpha reductase are decreased libido, impotence and ejaculatory disorders. Treatment with finasteride decreases prostate specific antigen levels, even in the presence of prostate cancer.
It is not known if finasteride can mask a prostate cancer. Although the rate of cancer detection was not altered in clinical trials, will everyday patients be subjected to the same intensity of monitoring?
There are few data on long-term safety and efficacy. The optimum use of this drug is not yet clearly defined. At present, its use will be restricted to patients with symptomatic benign prostatic hypertrophy who cannot undergo surgery.
