New drugs

(Aust Prescr 1995;18:7-9)

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.

Alglucerase

Ceredase (Arrow Scientific/Genzyme)
vials containing 10 IU/mL and 80 IU/mL for intravenous infusion

Indication: Gaucher's disease type I
Gaucher's disease is an autosomal recessive lysosomal storage disease. There is a deficiency of glucocerebrosidase which can lead to an accumulation of the enzyme's substrate. Some patients may have a normal life, but others can develop problems which require longterm enzyme replacement therapy. This product has approval for use in patients with significant hepatomegaly or splenomegaly, moderate to severe anaemia, thrombocytopenia with a bleeding tendency, and bone disease.

Alglucerase is a modified form of glucocerebrosidase derived from human placental tissue. The product contains some human chorionic gonadotrophin and there is the potential risk of a virus surviving the manufacturing process. Alglucerase is supplied in a solution containing human serum albumin. It is diluted before being infused over one or two hours.

Although the optimum use of the product is still being determined, it is effective when used for the recommended indications.

Enoxacin

Enoxin (Faulding Pharmaceuticals)
200 mg and 400 mg tablets

Indication: specified infections
Enoxacin is a 4quinolone antibiotic related to norfloxacin.

The drug is rapidly absorbed after oral administration to produce peak plasma levels within 2 hours. The halflife is 4-6 hours, so with twice daily dosing, steady state is reached within 2-3 days.

Most of the drug is excreted unchanged in the urine, but there are some active metabolites. The dose should be adjusted in patients with reduced renal function and in the elderly.

Although enoxacin has in vitro activity against many organisms, the anaerobes and some streptococci are less susceptible. Enoxacin has been approved for the treatment of skin and skin structure infections, but not as first-line treatment as there are more effective antibiotics. The drug has been approved for use in urinary tract infections, chancroid and simple urethral or endocervical gonorrhoea. It should not be prescribed for children or pregnant women.

In clinical trials, approximately 5% of patients had to discontinue treatment due to adverse effects. Most adverse effects involve the gastrointestinal system, but central nervous system stimulation can occur. As this may result in seizures, enoxacin should be used with great caution in patients with epilepsy, cerebral arteriosclerosis and other neurological disturbances.

Enoxacin interacts with several commonly used drugs including theophylline, antacids and H2 antagonists.

This drug increases the number of conditions which may be treated with a quinolone antibiotic.

Gestodene with ethinyloestradiol

Femoden ED and Trioden ED (Schering)

Minulet ED and Triminulet ED (Wyeth Australia)

Femoden ED and Minulet ED tablets contain

gestodene 75 micrograms/ethinyloestradiol 30 micrograms

(21 tablets)

Trioden ED and Triminulet ED contain

gestodene 50 micrograms/ethinyloestradiol 30 micrograms

(6yellow or light beige tablets)

gestodene 70 micrograms/ethinyloestradiol 40 micrograms

(5 dark brown tablets)

gestodene 100 micrograms/ethinyloestradiol 30 micrograms (10white tablets)

All products are available as 28 day packs and include 7 inert tablets

Indication: contraception
Gestodene is a relatively new synthetic progestogen with a structure related to levonorgestrel. The combination of gestodene with ethinyloestradiol is contraceptive and these products are the monophasic and triphasic formulations.

Taken orally, gestodene is completely bioavailable. It binds to sex hormone binding globulin and is eliminated by metabolism. Most of the metabolites are excreted in the urine.

If gestodene/ethinyloestradiol tablets are taken correctly, pregnancy is unlikely to occur. Cycle control may be better than with monophasic pills containing levonorgestrel, although there have not been any comparative studies.1 Spotting occurs in 3-6% and breakthrough bleeding in approximately 1% of patients.

The metabolic effects of these products are similar to those of other combined oral contraceptives e.g. elevated triglyceride concentrations. The range of adverse effects also appears similar.

These products should be prescribed in the same way as currently available combined oral contraceptives. What practitioners need to know is whether or not gestodene has any advantage over other progestogens. Overseas information suggests that these products will be more expensive than their established competitors. Therefore, gestodenecontaining products may be of benefit in patients who have problems while taking other oral contraceptives.

R E F E R E N C E
1. Chez RA. Clinical aspects of three new progestogens: desogestrel, gestodene and norgestimate. Am J Obstet Gynecol 1989;160:1296-300.

Modified bovine lung extract (beractant)

Survanta (Abbott Australasia)
vials containing 200 mg/8 mL suspended in 0.9% sodium chloride solution

Indication: respiratory distress syndrome
The lack of surfactant in the lungs of premature neonates can cause respiratory distress syndrome (RDS). An artificial surfactant is available for treatment (see 'New drugs' Aust Prescr 1992;15:58), but this new product is also approved for preventive use.

Beractant is produced by adding substances such as colfosceril palmitate to an extract of bovine lungs to mimic natural surfactant. By lowering the alveolar surface tension, beractant can prevent the alveoli from collapsing during respiration.

The modified extract is given into the trachea and there are detailed instructions how to do this. While many babies who develop RDS will be intubated, elective intubation is needed when beractant is used to prevent RDS. If prevention is required, the first dose must be given within 15 minutes of birth.

In the treatment of RDS, beractant is as effective as colfosceril palmitate in reducing death and bronchopulmonary dysplasia.1 The outcome of prevention or treatment may be influenced by birth weight and the use of steroids before delivery.

Many of the adverse effects of beractant are related to the dosing procedure. Disconnecting the ventilator to give beractant can result in bradycardia or a fall in oxygen saturation. In some studies, the rate of intracranial haemorrhage has been higher in patients treated with beractant than in the control groups. This effect is not seen when the results of all controlled trials are pooled.

R E F E R E N C E
1. Horbar JD, Wright LL, Soll RF, Wright EC, Fanaroff AA, Korones SB, et al. A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. J Pediatr 1993;123:757-66.

Teicoplanin

Targocid (Marion Merrell Dow Australia)
20 mg/mL as lyophilised powder in 20 mL vials

Indication: specified infections
Teicoplanin is a glycopeptide antibiotic with similarities to vancomycin. The drug acts by inhibiting cell wall synthesis in dividing organisms. As this mechanism is different to the action of beta-lactam antibiotics, teicoplanin has no crossresistance with these drugs. Only Grampositive organisms are susceptible; all Gramnegative organisms are resistant.

The drug should be reconstituted with water precisely in accordance with the manufacturer's directions. After teicoplanin is given intravenously, there is a biphasic distribution, followed by a prolonged elimination period. The elimination halflife is 70-100 hours with most of the dose being excreted unchanged in the urine. Twice daily dosing is advised with reduced doses for patients with renal impairment.

Teicoplanin has been approved for the treatment of serious staphylococcal or streptococcal infections which cannot be treated satisfactorily with less toxic antibiotics. Therefore, teicoplanin can be used in cases of osteomyelitis, septic arthritis and septicaemia. Endocarditis is not an approved indication. Practitioners should be aware that teicoplanin may be less active than vancomycin against some staphylococci e.g. Staphylococcus haemolyticus.

Common adverse effects include rashes, fever, pruritus, diarrhoea, nausea and vomiting. Ototoxicity has been reported so auditory function should be monitored if other neurotoxic drugs, e.g. aminoglycosides, are being given or treatment is prolonged in a patient with renal insufficiency. Other adverse effects include altered liver function, leucopenia, thrombocytopenia, hypersensitivity and impaired renal function.

Although teicoplanin may have fewer adverse effects, this advantage is said to be insufficient to recommend that it is used instead of vancomycin.1

R E F E R E N C E
1. Phillips G, Golledge CL. Vancomycin and teicoplanin: something old, something new. Med J Aust 1992;156:53-7.

Terazosin hydrochloride

Hytrin (Abbott Australasia)
1 mg, 2 mg, 5 mg and 10 mg tablets

Indication: hypertension, benign prostatic hypertrophy
Terazosin is an alpha1 adrenergic receptor antagonist with a structure similar to prazosin. It lowers blood pressure by decreasing vascular resistance and can relieve the symptoms of benign prostatic hypertrophy by reducing the smooth muscle tone of the bladder outlet.

For both indications, treatment should begin with a low dose and be increased according to the response. Giving the dose at bedtime also helps to reduce the risks of hypotension and syncope.

Terazosin is rapidly absorbed from the gut. Its effects begin within 15 minutes and can last for up to 24 hours so only one dose per day is needed. The drug is mainly metabolised and has a halflife of 12 hours.

For benign prostatic hypertrophy, the maximum benefit occurs after 3-6 months of treatment. While terazosin improves urinary flow rates significantly more than placebo, the clinical improvement may be modest. If there has been no response after 6 months, continuing treatment has no advantage.

In hypertension, the company recommends that the blood pressure is checked at the end of a dose interval. If the blood pressure has not been controlled by a single daily dose, the dose can be increased or the drug may be given twice a day. There is probably no benefit in giving higher doses to patients who are not controlled on 20 mg per day.

The adverse reactions profile varies slightly between the treatment groups. Patients taking terazosin for prostatic symptoms are more likely to develop postural hypotension, while hypertensive patients are more likely to experience palpitations and peripheral oedema. Common adverse effects associated with each indication include headache, dizziness and asthenia.

NEW PROPRIETARY BRANDS

Acyclovir

Zyclir (AMRAD Pharmaceuticals)
200 mg and 800 mg tablets and 250 mg intravenous infusion

Allopurinol

Allorin (Douglas Pharmaceuticals)
100 mg and 300 mg tablets

Atenolol

Anselol (Douglas Pharmaceuticals)
50 mg tablets

Diltiazem hydrochloride

Dilzem (Douglas Pharmaceuticals)
60 mg tablets

Mianserin hydrochloride

Lerivon (Organon Pharmaceuticals)
10 mg and 20 mg tablets

Nifedipine

Nifecard (Sigma Pharmaceuticals)
20 mg tablets

Piroxicam

Candyl (Douglas Pharmaceuticals)
10 mg and 20 mg capsules

Spironolactone

Spiractin 25 and Spiractin 100 (Alphapharm)
25 mg and 100 mg tablets