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.
Differin (Galderma Australia)
0.1% gel in 30 g tubes
Indication: acne
Adapalene is similar to the retinoids. It binds to a retinoic acid receptorand modulates keratinisation and the differentiation of cells.
The gel can be used by patients with comedonal, papular orpustular acne. It is applied once daily, at bedtime, after the skin is washed.Clinical improvement is evident in one to two months.
Adapalene 0.1% gel is reported to be as effective as 0.025%tretinoin gel.1 As this strengthof tretinoin gel is not marketed in Australia, it is not clear how adapalenecompares with the available 0.05% tretinoin creams.
The gel can irritate the skin causing the patients to complainof pruritis, stinging and scaling. No systemic reactions have occurred, butphototoxicity is a potential problem. Adapalene should not be used by patientswith eczema. As the drug could
affect fetal development, it should not be used by women whoare pregnant or are likely to become pregnant during treatment.
Reference
1. Verschoore M, Langner A, Wolska H, Jablonska S, Czernielewski J, SchaeferH. Efficacy and safety of CD 271 alcoholic gels in the topical treatmentof acne vulgaris. Br J Dermatol 1991;124:368-71.
Rapifen (ICI Australia Operations)
0.5 mg/mL in 2 mL and 10 mL ampoules
Indication: anaesthesia
Alfentanil is an opioid analgesic related to fentanyl. It can be used beforeintubation to induce anaesthesia or to supplement analgesia.
After the drug is given intravenously, its maximum analgesicand respiratory depressant effects occur within two minutes.This onset of actionis more rapid than an equianalgesic dose of fentanyl. A bolus dose is suitablefor procedures lasting less than 10 minutes, but the drug can be given by infusionfor longer procedures. The drug is metabolised by the liver with a terminalelimination half-life of 1-2 hours.
The duration of analgesia may be less than the respiratorydepressant effect. As respiratory depression can occur up to several hoursafter a dose of alfentanil, the patient must be monitored in the recovery area.Naloxone should be available.
Apart from respiratory depression and apnoea, there are other adverse effectson heart rate, blood pressure and muscle rigidity. The most common adverseeffects are nausea and vomiting.
Arimidex (ICI Australia Operations)
1 mg tablets
Indication: breast cancer
Aromatase is an enzyme involved in the synthesis of oestradiol and oestrone.By inhibiting this enzyme, anastrozole reduces the production of oestradiolin the peripheral tissues of postmenopausal women. A reduction in circulatingoestradiol can be beneficial in the treatment of advanced breast cancer.
Anastrozole has been approved for use by postmenopausal womenwith breast cancer that has progressed following therapy with tamoxifen. Inclinical trials for this indication, anastrozole has similar efficacy to megestrolacetate. Approximately one-third of patients treated with either drug willrespond or have stabilisation of their disease for more than 6 months. Thecancer will progress in approximately half the patients. Women rarely respondto anastrozole if they did not respond to tamoxifen or if their cancer is oestrogen-receptornegative.
The recommended daily dose is 1 mg. This is rapidly absorbed,but is eliminated slowly (half-life 50 hours). The drug is extensively metabolisedwith most metabolites excreted in the urine; however, no dose reduction isadvised for patients with liver or kidney disease. Although anastrozole caninhibit the cytochrome P450 system, this effect occurs at higher concentrationsthan would be expected to occur in patients.
Adverse events during treatment are common, but many can berelated to the cancer. Adverse reactions seen in trials include asthenia, nausea,headache and hot flushes.
Inhibace (Bayer Australia)
1 mg, 2.5 mg and 5 mg tablets
Indication: hypertension
This is another angiotensin converting enzyme (ACE) inhibitor which will becompeting in the antihypertensive drug market; a market worth over $250 millionin 1992/93.
Cilazapril is a prodrug which is converted to active cilazaprilat.The half-life of cilazaprilat is approximately 9 hours and it is excreted unchangedby the kidneys. Some patients may need a twice daily dose to control theirblood pressure for 24 hours. Reduced doses are recommended for the elderlyand patients with renal impairment.
A quality of life study compared cilazapril, atenolol andnifedipine in patients with mild to moderate essential hypertension. After6 months' therapy, all 3 drugs had reduced diastolic blood pressure, but significantlymore
patients taking cilazapril needed to have a diuretic addedto their treatment. Atenolol and cilazapril had similar effects on the qualityof life.1
Treatment begins at a low dose for the first two days andwith the same precautions as for other ACE inhibitors. The adverse effectsare also similar and include headache, dizziness and cough. Neutropenia, whichcan also occur in patients taking captopril, has been reported.
Cilazapril has only been approved for the treatment of mildto moderate hypertension. It has no apparent advantages over its competitors.
Reference
1. Fletcher AE, Bulpitt CJ, Chase DM, Collins WC, Furberg CD, Goggin TK, etal. Quality of life with three antihypertensive treatments: cilazapril, atenolol,nifedipine. Hypertension 1992;19:499-507.
Nimbex (Glaxo Wellcome)
2 mg/mL in 2.5 mL and 5 mL ampoules
5 mg/mL in 30 mL vials
Indication: muscle relaxation
Atracurium is a non-depolarising neuromuscular blocker. The molecule has severalisomers, one of which is cisatracurium. This isomer also causes neuromuscularblockade, probably by competing for cholinergic receptors on the motor end-plate.It is probably more potent than atracurium.
For tracheal intubation, cisatracurium is given as a bolusinjection. During surgery or mechanical ventilation, neuromuscular blockadecan be maintained by repeat injections or an infusion. After a bolus dose,the patient will be ready for intubation in 2-3 minutes. Higher doses shortenthe time to onset of neuromuscular block, but this increases the time to spontaneousrecovery. In general, cisatracurium has an intermediate duration. Dependingon the dose given, spontaneous recovery is complete within an hour. Recoverycan be speeded by giving an anticholinesterase.
As cisatracurium degrades in the body, its elimination islargely organ independent. No dose alterations are required in hepatic or renalfailure.
Cisatracurium appears to be as safe as atracurium. Adverseeffects include bronchospasm, bradycardia, hypotension, rashes and flushing.The risk of histamine release is unlikely to be greater than that of atracurium.The effect of cisatracurium is influenced by interactions with many commonlyused drugs.
At present, it is uncertain if cisatracurium will have anysignificant clinical advantages over atracurium.
Infanrix (SmithKline Beecham)
0.5 mL glass vials
Indication: immunisation
Despite the availability of triple antigen, there has been an epidemic of whoopingcough in Australia. Concern about the safety of the pertussis component ofthe vaccine may be contributing to the inadequate immunisation of Australianchildren.
The current pertussis component of triple antigen is a whole-cellvaccine. This is thought to be responsible for the frequent adverse effectssuch as irritability, crying, fever and injection-site reactions. The new productaims to stimulate immunity while reducing the incidence of adverse reactions.
The pertussis component of this product contains 3 purifiedantigens of Bordetella pertussis. Although it is not a whole-cell vaccine,it induces antibodies in over 95% of children given a 3-dose course.
Two types of acellular vaccine have been tested in a double-blind trial involvingover 14 000 children.1 At 2,4 and 6 months of age, they were given either diphtheria and tetanus toxoid,triple antigen including whole-cell pertussis, or triple antigen containingone of two brands of acellular pertussis vaccines. The acellular vaccines hada much higher immunogenicity than the whole-cell vaccine and appeared to bemore effective. After a mean follow-up of 17 months, 37 cases of pertussisoccurred in the 4481 children who had received this product compared with 141cases in the 4348 who had received whole-cell vaccine. The children who hadreceived whole-cell vaccine were also significantly more likely to have adverseeffects. The frequency of adverse events in children given the acellular vaccineswas similar to those given diphtheria and tetanus toxoids.
In addition to primary courses of immunisation, this product has also beensuccessfully used as a booster at 18 months or 4-6 years. It is effective andhas been approved for this indication, including children who were originallyimmunised with the whole-cell vaccine.
The new vaccine is likely to be effective against the serotypes of Bordetellapertussis currently found in Australia. On the available data, it appearsto be safe in the short term and has advantages over whole-cell vaccine. Thehealth economists will have to calculate if these advantages outweigh the costof the new vaccine.
Reference
1. Greco D, Salmaso S, Mastrantonio P, Giuliano M, Tozzi AE, Anemona A, etal. A controlled trial of two acellular vaccines and one whole-cell vaccineagainst pertussis. N Engl J Med 1996;334:341-8.
Trusopt Eye Drops (Merck Sharp & Dohme)
20 mg/mL in 5 mL bottles
Indication: high intraocular pressure
Systemic carbonic anhydrase inhibitors can be used in the treatment of glaucoma(see `The medical treatment of glaucoma' Aust Prescr 1993;16:34-7). Theyact on the ciliary processes to reduce the secretion of aqueous humor andtherefore intraocular pressure. Dorzolamide is a carbonic anhydrase inhibitorwhich can be used topically for ocular hypertension or open angle glaucoma.Eye drops should avoid the adverse effects, such as acidosis and electrolytedisturbances, associated with systemic carbonic anhydrase inhibitors.
One drop of dorzolamide is given 3 times a day. This lowersthe intraocular pressure by 3-5 mmHg. Most of the drug which reaches the systemiccirculation is excreted unchanged in the urine. The drug accumulates in redblood cells during chronic dosing.
In clinical trials, approximately 7% of patients developedpossible allergic reactions such as conjunctivitis. The most common ocularsymptoms were burning, itching, stinging and blurred vision. Dorzolamide isa sulfonamide, so it may be inappropriate for patients who are hypersensitiveto sulfa drugs.
Although dorzolamide can be used as monotherapy, it will probablybe a second-line therapy. If used as an adjunct to an ophthalmic beta blocker,dorzolamide should only be given twice a day.
Foradile (Novartis Pharmaceuticals)
capsules containing 12 micrograms for inhalation
Indication: asthma
Patients with frequent nocturnal asthma who are already taking corticosteroidsmay benefit from taking a long-acting beta2 adrenoceptoragonist. Eformoterol will be competing with salmeterol which has been availablefor this indication since 1993.
After inhalation of eformoterol powder, bronchodilatationbegins within 3 minutes. This effect lasts for 12 hours with a peak effectwithin two hours of inhalation. These properties make eformoterol suitablefor twice daily inhalation in patients who require regular, long-term treatmentof reversible airways obstruction. It is not recommended for use in acute asthma.Patients should have a short-acting agonist, such as salbutamol, availableto help deal with acute attacks.
Inhaled eformoterol is absorbed through the lungs into thecirculation. Most of the dose is metabolised with less than 10% being excretedunchanged in the urine.
Common adverse effects include tremor, palpitations, headache,dizziness and pharyngitis. There is a potential for eformoterol to cause paradoxicalbronchospasm. The beta2 agonistscan also alter concentrations of glucose and potassium. Extra caution is neededwhen prescribing eformoterol for patients with diabetes, heart disease or thyrotoxicosis.The cardiac effects may be potentiated by other drugs such as antidepressants,antihistamines and phenothiazines. Concomitant treatment with diuretics, steroidsor theophylline can increase the risk of hypokalaemia. This may increase therisk of arrhythmia in patients taking digoxin.
Eformoterol is effective, but more information will be neededto confirm its safety in long-term use. Salmeterol costs approximately $45for a month's supply, so the uptake of eformoterol may be determined by itsrelative cost.
Telfast (Hoechst Marion Roussel)
60 mg capsules
Indication: seasonal allergic rhinitis
There have been concerns about potentially fatal interactions between terfenadineand drugs such as erythromycin. While there has been debate about the mechanismof the interaction1, thisnew product aims to overcome the concerns.
Fexofenadine is a metabolite of terfenadine which is beingmarketed as a non-sedating antihistamine without the risks of the parent compound.One capsule can be taken up to twice a day for the relief of symptoms.
The drug has a bioavailability of 33%, but the effect of foodappears not to be clinically significant. Most of the drug is excreted unchangedin the urine with a terminal elimination half-life of 11-16 hours. The pharmacokineticsare significantly affected by interactions with erythromycin and ketoconazole;however, these changes are not believed to increase the incidence of adverseeffects.
The adverse effects of fexofenadine include headache, nausea,drowsiness and fatigue. Although fexofenadine seems to be well tolerated, healthprofessionals should be aware that its approval was based on studies of twoweeks' duration.
Fexofenadine will reduce the symptoms of seasonal allergicrhinitis. The antihistamine effect begins within an hour of taking the tabletand peaks after 6 hours. The effectiveness of fexofenadine relative to otherantihistamines is unknown.
Reference
1. Moulds RF. Erythromycin and terfenadine should not be used together [seecomments]. AustPrescr 1995;18:18. Comment in: Aust Prescr 1995;18:29.
Ergamisol (Janssen-Cilag)
50 mg tablets
Indication: colonic cancer
The combination of levamisole and fluorouracil, which was discussed in AustralianPrescriber in 19921, hasnow been approved for use after surgical resection of cancer of the colon.
Levamisole is active against helminths, but also modulatesthe immune system, particularly when the immune response is impaired. Althoughthe drug has little effect on its own, adjuvant treatment with fluorouracilimproves survival in patients with advanced colonic cancer. Patients with stageIII colon cancer were entered into a randomised controlled trial within 5 weeksof surgery. After 5 years, 119 of the 304 patients given the combination developeda recurrence, compared with 177 of the 315 given no additional treatment. Inaddition to this significant reduction in recurrence rate, deaths were alsosignificantly reduced.2
Levamisole is given orally 3 times a day for 3 consecutivedays in each fortnight. The combined schedule with fluorouracil is followedfor a year.
The combination treatment is associated with frequent adverseeffects which are more common than with levamisole alone. The common adverseeffects of levamisole include nausea, dysgeusia, arthralgia, fatigue and rashes.Although a flu-like illness may occur during treatment, it may be a sign ofagranulocytosis. As fatalities have occurred, it is essential that the bloodcount is routinely monitored during therapy. Other serious adverse effectsinclude pancreatitis and neurological changes associated with demyelination.
Patients should be warned that levamisole can produce a disulfiram-likereaction with alcohol. The drug is metabolised in the liver and may interactwith anticoagulants and phenytoin.
Although most patients will have some adverse effects, thecombination of levamisole and fluorouracil is likely to become the standardtreatment after surgery for (Dukes' stage C) colon cancer.
References
1. Grygiel JJ. Adjuvant therapy in colorectal cancer. Aust Prescr 1992;15:54-6.
2. Moertel CG, Fleming TR, Macdonald JS, Haller DG, LaurieJA, Tangen CM, et al. Fluorouracil plus levamisole as effective adjuvant therapyafter resection of stage III colon carcinoma: a final report. Ann Intern Med1995;122:321-6.
Cozaar (Merck Sharp & Dohme)
50 mg tablets
Indication: hypertension
The renin-angiotensin system (RAS) is involved in the control of blood pressure.In patients with hypertension, ACE inhibitors block the conversion of angiotensinI to angiotensin II, a potent vasoconstrictor. Losartan also affects the RAS,but reduces blood pressure by antagonising angiotensin II at its receptor.
The drug is well absorbed, but the bioavailability is only33% as it undergoes first pass metabolism. While the peak plasma concentrationof losartan is reached after one hour, the active metabolite peaks at 4 hours.The drug has a half-life of two hours and the metabolite has a half-life of6-9 hours. Only 4% of a dose is excreted unchanged in the urine.
The usual starting dose is 50 mg once a day. Although symptomatichypotension can occur early, particularly in volume-depleted patients, themaximal antihypertensive effect occurs up to 6 weeks after starting treatment.If 50 mg a day does not control the blood pressure, the manufacturers suggestgiving 25 mg twice a day before increasing the dose. Increasing the dose maynot produce much change in blood pressure and the maximum dose should not exceed100 mg a day.
The company claims that the drug has a similar efficacy todaily doses of enalapril 20 mg, atenolol 50 mg and felodipine 5 mg. The long-termeffectiveness of losartan is unknown.
Like ACE inhibitors, losartan is contraindicated in pregnancy.As the clinical studies of losartan have been relatively short, there are nodata on how safe the drug will be if it is taken for several years. In theclinical trials, dizziness was the only symptom that occurred much more frequentlywith losartan than with placebo (4.1% vs. 2.4%). Hyperkalaemia can occur andserum concentrations of uric acid are reduced.
Losartan is not more effective than ACE inhibitors, but itcauses less cough. As mild to moderate hypertension usually requires long-termtreatment, this drug will have a limited role until more data become available.
Merrem IV (ICI Australia Operations)
v ials containing 250 mg, 500 mg and 1 g
Indication: specified infections
The carbapenems are antibiotics with a beta lactam structure. Imipenem wasthe first drug of the class, but as it was inactivated by renal dipeptidase,it had to be formulated with cilastatin, a dipeptidase inhibitor. Meropenemis a carbapenem which is not affected by renal dipeptidase.
Organisms which are sensitive to meropenem include streptococciand staphylococci, Escherichia coli, Haemophilus influenzae, Moraxella catarrhalis,Klebsiella pneumoniae and Bacteroides fragilis. Some strains of Pseudomonasaeruginosa are susceptible to meropenem. In view of its bactericidal activityagainst many aerobic and anaerobic bacteria, the drug has been approved forseveral indications. It can be used to treat severe infections of the lowerrespiratory tract, urinary tract, skin and skin structures, meningitis, septicaemia,febrile neutropenia, intra-abdominal and gynaecological infections.
Meropenem is given intravenously by infusion or slow injectionevery 8 hours. Most of the dose is excreted unchanged in the urine within 12hours. The half-life is approximately one hour.
Patients who are hypersensitive to penicillins may also behypersensitive to meropenem. The drug is generally well tolerated, but childrenmay be more prone to adverse effects. The adverse reactions include rashes,headache, thrombocytopenia, altered liver function, nausea and vomiting.
Most hospitals control the prescription of carbapenems. Meropenemshould be restricted to serious infections where other antibiotics are contraindicatedor ineffective.
CellCept (Roche Products)
250 mg capsules
500 mg tablets
Indication: renal transplantation
Acute rejection of an allogeneic renal transplant can occur in up to 60% ofpatients. As this can reduce the survival of the allograft, there is a needto try to prevent acute rejection. Mycophenolate mofetil has been studiedbecause it inhibits guanosine nucleotide synthesis and hence the proliferationof T and B lymphocytes.
A study of 491 patients compared mycophenolate with placeboin patients who were also given cyclosporin and corticosteroids to preventrejection. In the first 6 months after surgery, significantly fewer rejectionsoccurred in the patients receiving mycophenolate. Whereas 46% of patients givenplacebo developed biopsy-proven rejections, only 17% of those given 2 g ofmycophenolate had a rejection. A 3 g dose gave a better response rate, butwas less well tolerated.1
Mycophenolate has been compared with azathioprine in patientsalso given cyclosporin and corticosteroids. The combination containing mycophenolatewas more effective in preventing rejection.
Treatment is taken twice a day starting within 72 hours ofthe transplant. Plasma level monitoring is not required in the prevention oftoxicity. The drug is completely converted to an active metabolite. This metaboliteis further metabolised and then excreted mainly in the urine. Extra cautionis needed if there is severe renal impairment.
The patients need regular blood tests during the first yearof treatment as anaemia and leucopenia can develop. Other adverse effects includevomiting, diarrhoea and infections. Opportunistic infections include Herpessimplex, Herpes zoster, cytomegalovirus and, rarely, candida and Pneumocystiscarinii. The treatment of Pneumocystis carinii may be complicatedby the possibility, suggested by animal studies, that there is an interactionwith trimethoprim/sulfamethoxazole. Other potential interactions include acyclovir,antacids and cholestyramine.
Although mycophenolate has a proven benefit in the first 6months after transplantation, its long-term safety and effectiveness will needto be confirmed. The studies of mycophenolate have revealed an increased incidenceof skin carcinoma and lymphoma/lymphoproliferative disease compared to placebo.
Reference
1. European Mycophenolate Mofetil Co-operative Study Group. Placebo-controlledstudy of mycophenolate mofetil combined with cyclosporin and corticosteroidsfor prevention of acute rejection. Lancet 1995;345:1321-5.
Anandron (Hoechst Marion Roussel)
150 mg tablets
Indication: prostate cancer
Antiandrogens can be used in the treatment of prostrate cancer, particularlyfor metastatic disease. They can reduce the `flare' of the disease whichmay occur when a patient starts treatment with a luteinising hormone releasinghormone (LHRH) agonist.1
Flutamide has been available for several years for use inpreviously untreated patients with metastatic prostate cancer in combinationwith a LHRH agonist. Nilutamide, another non-steroidal antiandrogen, has beenapproved for the same indication. In addition, nilutamide has also been approvedfor treatment in conjunction with surgical castration.
A company meta-analysis2 reviewed1056 patients given nilutamide or a placebo after orchidectomy. Complete orpartial regression of the disease occurred in 50% of the treatment group and33% of the placebo group. There were also significant differences in bone painand the odds of disease progression. There was no significant improvement insurvival. This accords with other studies which show that maximum androgenblockade does not result in longer survival than castration.3
Patients commence treatment when they have their orchidectomyor start taking a LHRH agonist. The dose of nilutamide is reduced after 4 weeks,or earlier if adverse effects occur.
The most frequent adverse effect is impaired visual adaptationto darkness. Other adverse reactions include altered liver function, interstitialpneumonitis, nausea and vomiting.
References
1. Boyer M. The management of prostate cancer. AustPrescr 1996;19:22-4.
2. Bertagna C, De Gery A, Hucher M, Francois JP, ZaniratoJ. Efficacy of the combination of nilutamide plus orchidectomy in patientswith metastatic prostatic cancer. A meta-analysis of seven randomized double-blindtrials (1056 patients). Br J Urol 1994;73:396-402.
3. Prostate Cancer Trialists' Collaborative Group. Maximumandrogen blockade in advanced prostate cancer: an overview of 22 randomisedtrials with 3283 deaths in 5710 patients. Lancet 1995;346:265-9.
Bonefos (Rhone-Poulenc Rorer)
400 mg capsules
ampoules containing 300 mg/5 mL
Indication: hypercalcaemia of malignancy
Malignant tumours can cause hypercalcaemia either by a direct effect on boneor by affecting bone metabolism. Hypercalcaemia can cause a variety of problemsranging from fatigue to renal insufficiency and cardiac arrhythmias. Patientswith hypercalcaemia of malignancy often die within a few months. Bisphosphonatessuch as clodronate can control the hypercalcaemia by reducing bone resorption.
Although oral formulations of clodronate are available, theyhave a low bioavailability (1-2%) and absorption is negligible if the doseis taken with food. Most patients will be given clodronate intravenously. Thisrequires a daily infusion, over at least two hours, repeated until the serumcalcium is normal. Usually normocalcaemia is achieved in 2-5 days.
Clodronate is not metabolised and most of the dose appearsin the urine within a few days. Patients must be adequately hydrated beforetreatment and renal function must be monitored. The terminal elimination half-lifemay exceed a year as clodronate bound to bone is slowly released.
Adverse reactions include renal insufficiency and hypocalcaemia.The oral formulations can also have adverse effects on the gut.
Clodronate has been compared with pamidronate, a bisphosphonatealso approved for treating the hypercalcaemia of malignancy. Both drugs areeffective, but the duration of normocalcaemia was 14 days for clodronate and28 days for pamidronate.1
Reference
1. Purohit OP, Radstone CR, Anthony C, Kanis JA, Coleman RE. A randomised double-blindcomparison of intravenous pamidronate and clodronate in the hypercalcaemiaof malignancy. Br J Cancer 1995;72:1289-93.
Freedox (Pharmacia & Upjohn)
1.5 mg/mL in 100 mL vials
Indication: aneurysmal subarachnoid haemorrhage
Patients who rupture an intracranial aneurysm have a high mortality. Thosewho survive the subarachnoid haemorrhage are likely to be left with a neurologicaldeficit. One cause of the tissue damage may be the production of toxic superoxideradicals. This can contribute to the cerebral vasospasm which occurs afterthe acute haemorrhage. Tirilazad is thought to promote tissue survival byinhibiting lipid peroxidation.
The drug is a new chemical entity. It is a nonhormonal 21-aminosteroidand is lipid soluble. The vials of tirilazad have to be kept in a refrigerator(2-8oC) and protected from light. The solution is diluted and infusedover 10-30 minutes every 6 hours starting within 48 hours of the haemorrhage.Treatment continues for 8-10 days. Most of the patients in clinical trialsof tirilazad have also been given nimodipine to prevent cerebral vasospasm.
Although animal studies show that tirilazad improves the functionaloutcome, a significant benefit has not been confirmed in all clinical trials.Of the two studies included in the product information, only one showed a significantimprovement in survival. Closer examination reveals that only male patientsget a significant benefit from treatment. The drug is therefore only approvedfor men.
The common adverse effects are reactions at the site of infusionand changes in liver function. Tirilazad is metabolised in the liver and itsclearance is increased 50% by phenytoin.
The T-score (
) is explained in 'New drugs: transparency', Vol 30 No 1, Aust Prescr 2007;30:26-7.
