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.
Zithromax (Pfizer)
250 mg capsules
Indication: specified infections
Azithromycin is structurally related to erythromycin. Although its antibiotic properties are similar to erythromycin, the structural differences give azithromycin different pharmacokinetics.
The oral bioavailability of azithromycin is 37%. Absorption is reduced if the drug is taken with food. There is a large volume of distribution with azithromycin being concentrated in the tissues. This tissue concentration results in a half life of 68 hours and excretion over several days. Most indications require only a 3-day course given as a single daily dose. Genital infections with Chlamydia trachomatis can be treated with one dose. Azithromycin inhibits bacterial protein synthesis. In vitro, it is less effective than erythromycin against Gram positive organisms, e.g. streptococci and staphylococci, but it has greater activity against some Gram negative organisms e.g. Moraxella catarrhalis, Haemophilus influenzae and parainfluenzae.
In addition to chlamydial infections, azithromycin has also been studied in respiratory tract infections. It has been approved for use in sinusitis and community acquired pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae and acute bronchitis due to these organisms or Moraxella catarrhalis. Azithromycin can also be used to treat acute streptococcal pharyngitis.
Uncomplicated skin infections due to Staphylococcus aureus, Streptococcus pyogenes or Streptococcus agalactiae are also approved indications for azithromycin.
In clinical trials, adverse effects occurred in approximately 13% of patients, but less than 1% had to discontinue treatment. The most frequent adverse reactions affected the gastrointestinal system. Rare adverse effects include angioedema and cholestatic jaundice.
Azithromycin offers a more convenient treatment regimen than erythromycin and may have fewer adverse effects, but it is likely to cost much more. It is not approved for use in children.
Daivonex (CSL)
ointment containing 50 micrograms/g in 30 g and 100 g tubes
Indication: psoriasis
Psoriasis is a common skin condition which affects at least 1% of the population. The majority of patients have a chronic plaque psoriasis which is amenable to topical therapy.
The pathophysiology of psoriasis involves a proliferation of keratinocytes. This cell proliferation can be suppressed by vitamin D, but the vitamin can also affect calcium metabolism (hypervitaminosis D causes hypercalcaemia). Calcipotriol is a vitamin D derivative which suppresses cell proliferation, but has less effect on calcium metabolism.
Calcipotriol ointment is more effective than placebo. In a 6-week double blind comparison with betamethasone valerate ointment, calcipotriol was more effective at reducing erythema, thickness and scaling.1 Some data exist to suggest that calcipotriol is more effective than short contact dithranol regimens. Calcipotriol is likely to be more cosmetically acceptable than dithranol.
Most of the improvement with calcipotriol treatment occurs in the first two weeks. Some patients who have a good response will relapse, but it is unknown for how long the treatment can be repeated. There is little experience in the use of calcipotriol for more than one year.
It is uncertain how much topical calcipotriol is absorbed through the skin. Although hypercalcaemia has occurred with the recommended twice daily application (up to 100 g a week), most adverse effects occur on the skin. In clinical trials, 23% of patients reported an adverse reaction and 2% had to discontinue therapy. Local reactions include irritation, contact dermatitis, blisters and photosensitivity.
R E F E R E N C E
1. Kragballe K, Gjertsen BT, de Hoop D, Karlsmark T, van de Kerkhof PC, Larko O, et al. Doubleblind, right/left comparison of calcipotriol and bethamethasone valerate in treatment of psoriasis vulgaris. Lancet 1991;337:1936.
Orelox (Roussel Uclaf Australia)
100 mg film coated tablets
Indication: respiratory infections
If a cephalosporin is used to treat a resistant infection, it often has to be given by injection.1 Cefpodoxime now offers the possibility of oral therapy for adults with infections resistant to commonly used antibiotics.
This drug is given twice a day with food to increase absorption. The cefpodoxime proxetil ester is rapidly hydrolysed to active cefpodoxime. The active drug is bactericidal and is not hydrolysed by most beta-lactamases.
Cefpodoxime is active against staphylococci, streptococci, Haemophilus influenzae and parainfluenzae, Moraxella catarrhalis and Klebsiella pneumoniae. Pseudomonas aeruginosa is resistant. The drug has been successful in the treatment of bronchitis, community acquired pneumonia, sinusitis and streptococcal pharyngitis/tonsillitis.
Cefpodoxime is mainly excreted in the urine, with a mean elimination half life of 2-4 hours. The dose should be reduced if renal function is impaired.
Adverse reactions were reported in approximately 10% of patients involved in clinical trials. Common adverse effects are diarrhoea and nausea, but anaphylactic shock and pseudomembranous colitis have been reported. As haematological problems, e.g. neutropenia, can occur, the company recommends a blood count if treatment exceeds 10 days.
R E F E R E N C E
1. Turnidge J. The choice of cephalosporins. Aust Prescr 1992;15:268.
Orgaran (Organon)
750 anti-Xa units in 0.6 mL ampoules
Indication: prevention of venous thromboembolism
Flixotide (Glaxo)
metered dose inhalers delivering 50 and 250 micrograms per inhalation
disks of blisters delivering 100 and 500 micrograms per inhalation
Indication: asthma prophylaxis
Anti inflammatory drugs have an important role in asthma management (see `The changing approach to the pharmacotherapy of asthma' Aust Prescr 1991;14:71-3). Fluticasone adds to the choice of available inhaled steroids.
There has been recent concern about the effect of inhaled steroids on the growth of children. Fluticasone can affect the hypothalamicpituitary axis, particularly with prolonged treatment or at high doses. However, no stunting of growth has yet been observed. If some of the dose is swallowed rather than inhaled, it is unlikely to cause any systemic effect as the biovailability of oral fluticasone is low.
The product is available in a variety of strengths, either as a metered dose inhaler or as dry powder contained in blisters for use in the Flixotide Diskhaler. Fluticasone is inhaled twice a day with the dose being tailored to each patient's requirements. Caution is advised when changing from the dry powder to the aerosol form of fluticasone and patients transferring from beclomethasone therapy are recommended to begin fluticasone at half the total daily dose of beclomethasone.
While fluticasone may be more potent than beclomethasone at the same dose, both drugs are effective and it is unclear if better control, e.g. reduced frequency of exacerbations, is achieved with fluticasone.
Neurontin (Parke-Davis)
300 mg and 400 mg capsules
Indication: epilepsy
Gammaaminobutyric acid (GABA) has anticonvulsant effects in animals. Although the precise mechanism of action is unclear, gabapentin, an analogue of GABA, can reduce the frequency of seizures in patients whose partial seizures are incompletely controlled by other drugs.
The bioavailability of gabapentin decreases as the dose is increased. Food does not significantly affect absorption. The drug penetrates the blood brain barrier and concentrations in the cerebrospinal fluid are approximately 20% of the plasma concentration. Gabapentin is not metabolised. It is mainly excreted in the urine and the dose should be adjusted in patients with renal impairment. The elimination hal flife is 5-7 hours. It is not necessary to monitor the plasma concentration.
A multi centre, double blind study of gabapentin as an adjunctive therapy found that a dose of 1200 mg/day reduced the number of partial seizures more than placebo.1 In other trials, the effective dose range was 900-1800 mg/day. The drug is given in divided doses and is introduced gradually over a few days.
As gabapentin is only approved for use in combination with other antiepileptic drugs, attributing drug related adverse reactions can be problematic. In clinical studies, approximately 7% of the trial population withdrew due to adverse effects. Many of the adverse effects involved the nervous system, the most common effects being somnolence, dizziness, ataxia and fatigue. Pancreatic tumours have occurred in rodents given gabapentin, but the relevance of this finding to clinical practice is unclear.
Reference
1. U.K. gabapentin study group. Gabapentin in partial epilepsy. Lancet 1990;335:1114-7.
Ismelin (CibaGeigy)
10 mg/mL in 1 mL ampoules
Indication: regional sympathetic block
Zoton (Lederle Laboratories)
30 mg capsules
Indication: peptic ulcer, reflux oesophagitis
#N8_v17n3LansoprazoleZoton (Lederle Laboratories)30 mg capsules Indication: peptic ulcer, reflux oesophagitis
Elmiron (Arthropharm)
100 mg capsules
Indication: interstitial cystitis
Interstitial cystitis develops when the bladder epithelium loses its protective layer of glycosaminoglycans and becomes irritated by urine. Pentosan polysulphate sodium resembles the glycosaminoglycans and restores the bladder's protection by binding to the transitional epithelium.
The product is a heparinoid. In addition to its anticoagulant effect, it also has fibrinolytic and anti inflammatory activity.
Approximately half the oral dose is absorbed and most of it is excreted in the faeces. Only about 11% of a radio labelled dose is excreted by the kidneys and only 3% is unchanged when it reaches the bladder. The half-life is about one hour and a 3 times daily regimen is recommended.
Pentosan polysulphate sodium will relieve symptoms such as frequency and urgency in some patients, however, relief may take 6-8 weeks of treatment. Patients are likely to gradually relapse when treatment is discontinued.
Few adverse reactions have been reported. Although the anticoagulant properties of the molecule are weak, caution is advised if the patient has a bleeding tendency or is taking other anticoagulants.
azocin (Lederle Laboratories)
vials containing 2 g piperacillin sodium with 250 mg tazobactam sodium, and 4 g piperacillin sodium with 500 mg tazobactam sodium as lyophilised powder for reconstitution
Indication: specified infections
Zoloft (Pfizer)
50 mg and 100 mg film coated tablets
Indication: depression
Sertraline is a serotonin (5-hydroxytryptamine, 5-HT) reuptake blocker. After absorption, it undergoes first pass hepatic metabolism before being extensively distributed. Metabolism also accounts for most of the elimination of sertraline, so a dose reduction is advised in patients with hepatic impairment. The cytochrome P450 system is involved in sertraline metabolism. The main metabolite has a longer half life than the parent compound (26 hours), but is inactive.
There are few published efficacy studies which compare sertraline to other antidepressants. Its efficacy may be similar to that of amitriptyline, but safety and efficacy have not been evaluated beyond 24 weeks' therapy.
The more common adverse effects are similar to those seen with other serotonin reuptake blockers and include gastrointestinal upset, somnolence and sweating. In pre marketing studies, 15% of patients discontinued treatment due to adverse effects.
There is little information on the use of sertraline in patients taking other psychiatric drugs. The clinical significance of recognised interactions is uncertain. Sertraline interacts with cimetidine, tolbutamide and warfarin. It should not be prescribed within two weeks of monoamine oxidase inhibitor therapy.
| Answers to self-test questions | ||
| 1. True | 2. True | 3. False |
| 4. True | 5. True | 6. False |
The T-score (
) is explained in 'New drugs: transparency', Vol 32 No 3, Aust Prescr 2009;32:80-1.
