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New drugs
(Aust Prescr 1997;20:45-51)
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 receptor
and modulates keratinisation and the differentiation of cells.
The gel can be used by patients with comedonal, papular or pustular 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 strength of tretinoin gel is not marketed in Australia, it is not clear how adapalene compares with the available 0.05% tretinoin creams.
The gel can irritate the skin causing the patients to complain of pruritis, stinging and scaling. No systemic reactions have occurred, but phototoxicity is a potential problem. Adapalene should not be used by patients with eczema. As the drug could
affect fetal development, it should not be used by women who are pregnant or are likely to become pregnant during treatment.
R E F E R E N C E
1. Verschoore M, Langner A, Wolska H, Jablonska S, Czernielewski J, Schaefer
H. Efficacy and safety of CD 271 alcoholic gels in the topical treatment
of 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 before
intubation to induce anaesthesia or to supplement analgesia.
After the drug is given intravenously, its maximum analgesic and respiratory depressant effects occur within two minutes.This onset of action is more rapid than an equianalgesic dose of fentanyl. A bolus dose is suitable for procedures lasting less than 10 minutes, but the drug can be given by infusion for longer procedures. The drug is metabolised by the liver with a terminal elimination half-life of 1-2 hours.
The duration of analgesia may be less than the respiratory
depressant effect. As respiratory depression can occur up to several hours
after 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 effects
on heart rate, blood pressure and muscle rigidity. The most common adverse
effects 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 oestradiol
in the peripheral tissues of postmenopausal women. A reduction in circulating
oestradiol can be beneficial in the treatment of advanced breast cancer.
Anastrozole has been approved for use by postmenopausal women with breast cancer that has progressed following therapy with tamoxifen. In clinical trials for this indication, anastrozole has similar efficacy to megestrol acetate. Approximately one-third of patients treated with either drug will respond or have stabilisation of their disease for more than 6 months. The cancer will progress in approximately half the patients. Women rarely respond to anastrozole if they did not respond to tamoxifen or if their cancer is oestrogen-receptor negative.
The recommended daily dose is 1 mg. This is rapidly absorbed, but is eliminated slowly (half-life 50 hours). The drug is extensively metabolised with most metabolites excreted in the urine; however, no dose reduction is advised for patients with liver or kidney disease. Although anastrozole can inhibit the cytochrome P450 system, this effect occurs at higher concentrations than would be expected to occur in patients.
Adverse events during treatment are common, but many can be
related 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 be
competing in the antihypertensive drug market; a market worth over $250 million
in 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 unchanged by the kidneys. Some patients may need a twice daily dose to control their blood pressure for 24 hours. Reduced doses are recommended for the elderly and patients with renal impairment.
A quality of life study compared cilazapril, atenolol and nifedipine in patients with mild to moderate essential hypertension. After 6 months' therapy, all 3 drugs had reduced diastolic blood pressure, but significantly more
patients taking cilazapril needed to have a diuretic added to their treatment. Atenolol and cilazapril had similar effects on the quality of life.1
Treatment begins at a low dose for the first two days and with the same precautions as for other ACE inhibitors. The adverse effects are also similar and include headache, dizziness and cough. Neutropenia, which can also occur in patients taking captopril, has been reported.
Cilazapril has only been approved for the treatment of mild to moderate hypertension. It has no apparent advantages over its competitors.
R E F E R E N C E
1. Fletcher AE, Bulpitt CJ, Chase DM, Collins WC, Furberg CD, Goggin TK, et
al. 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 several
isomers, one of which is cisatracurium. This isomer also causes neuromuscular
blockade, 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 bolus injection. During surgery or mechanical ventilation, neuromuscular blockade can 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 shorten the time to onset of neuromuscular block, but this increases the time to spontaneous recovery. In general, cisatracurium has an intermediate duration. Depending on the dose given, spontaneous recovery is complete within an hour. Recovery can be speeded by giving an anticholinesterase.
As cisatracurium degrades in the body, its elimination is largely organ independent. No dose alterations are required in hepatic or renal failure.
Cisatracurium appears to be as safe as atracurium. Adverse effects 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 commonly used drugs.
At present, it is uncertain if cisatracurium will have any significant clinical advantages over atracurium.
Diphtheria, tetanus and pertussis
Infanrix (SmithKline Beecham)
0.5 mL glass vials
Indication: immunisation
Despite the availability of triple antigen, there has been an epidemic of whooping
cough in Australia. Concern about the safety of the pertussis component of
the vaccine may be contributing to the inadequate immunisation of Australian
children.
The current pertussis component of triple antigen is a whole-cell vaccine. This is thought to be responsible for the frequent adverse effects such as irritability, crying, fever and injection-site reactions. The new product aims to stimulate immunity while reducing the incidence of adverse reactions.
The pertussis component of this product contains 3 purified
antigens 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 involving
over 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 containing
one of two brands of acellular pertussis vaccines. The acellular vaccines had
a much higher immunogenicity than the whole-cell vaccine and appeared to be
more effective. After a mean follow-up of 17 months, 37 cases of pertussis
occurred in the 4481 children who had received this product compared with 141
cases in the 4348 who had received whole-cell vaccine. The children who had
received whole-cell vaccine were also significantly more likely to have adverse
effects. The frequency of adverse events in children given the acellular vaccines
was similar to those given diphtheria and tetanus toxoids.
In addition to primary courses of immunisation, this product has also been
successfully used as a booster at 18 months or 4-6 years. It is effective and
has been approved for this indication, including children who were originally
immunised with the whole-cell vaccine.
The new vaccine is likely to be effective against the serotypes of Bordetella
pertussis currently found in Australia. On the available data, it appears
to be safe in the short term and has advantages over whole-cell vaccine. The
health economists will have to calculate if these advantages outweigh the cost
of the new vaccine.
R E F E R E N C E
1. Greco D, Salmaso S, Mastrantonio P, Giuliano M, Tozzi AE, Anemona A, et
al. A controlled trial of two acellular vaccines and one whole-cell vaccine
against 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). They
act on the ciliary processes to reduce the secretion of aqueous humor and
therefore intraocular pressure. Dorzolamide is a carbonic anhydrase inhibitor
which can be used topically for ocular hypertension or open angle glaucoma.
Eye drops should avoid the adverse effects, such as acidosis and electrolyte
disturbances, associated with systemic carbonic anhydrase inhibitors.
One drop of dorzolamide is given 3 times a day. This lowers the intraocular pressure by 3-5 mmHg. Most of the drug which reaches the systemic circulation is excreted unchanged in the urine. The drug accumulates in red blood cells during chronic dosing.
In clinical trials, approximately 7% of patients developed possible allergic reactions such as conjunctivitis. The most common ocular symptoms were burning, itching, stinging and blurred vision. Dorzolamide is a sulfonamide, so it may be inappropriate for patients who are hypersensitive to sulfa drugs.
Although dorzolamide can be used as monotherapy, it will probably
be a second-line therapy. If used as an adjunct to an ophthalmic beta blocker,
dorzolamide should only be given twice a day.
Eformoterol fumarate dihydrate
Foradile (Novartis Pharmaceuticals)
capsules containing 12 micrograms for inhalation
Indication: asthma
Patients with frequent nocturnal asthma who are already taking corticosteroids
may benefit from taking a long-acting beta2 adrenoceptor
agonist. Eformoterol will be competing with salmeterol which has been available
for this indication since 1993.
After inhalation of eformoterol powder, bronchodilatation begins within 3 minutes. This effect lasts for 12 hours with a peak effect within two hours of inhalation. These properties make eformoterol suitable for twice daily inhalation in patients who require regular, long-term treatment of reversible airways obstruction. It is not recommended for use in acute asthma. Patients should have a short-acting agonist, such as salbutamol, available to help deal with acute attacks.
Inhaled eformoterol is absorbed through the lungs into the circulation. Most of the dose is metabolised with less than 10% being excreted unchanged in the urine.
Common adverse effects include tremor, palpitations, headache, dizziness and pharyngitis. There is a potential for eformoterol to cause paradoxical bronchospasm. The beta2 agonists can also alter concentrations of glucose and potassium. Extra caution is needed when 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, steroids or theophylline can increase the risk of hypokalaemia. This may increase the risk of arrhythmia in patients taking digoxin.
Eformoterol is effective, but more information will be needed
to confirm its safety in long-term use. Salmeterol costs approximately $45
for a month's supply, so the uptake of eformoterol may be determined by its
relative cost.
Telfast (Hoechst Marion Roussel)
60 mg capsules
Indication: seasonal allergic rhinitis
There have been concerns about potentially fatal interactions between terfenadine
and drugs such as erythromycin. While there has been debate about the mechanism
of the interaction1, this
new product aims to overcome the concerns.
Fexofenadine is a metabolite of terfenadine which is being marketed 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 food appears not to be clinically significant. Most of the drug is excreted unchanged in the urine with a terminal elimination half-life of 11-16 hours. The pharmacokinetics are significantly affected by interactions with erythromycin and ketoconazole; however, these changes are not believed to increase the incidence of adverse effects.
The adverse effects of fexofenadine include headache, nausea, drowsiness and fatigue. Although fexofenadine seems to be well tolerated, health professionals should be aware that its approval was based on studies of two weeks' duration.
Fexofenadine will reduce the symptoms of seasonal allergic rhinitis. The antihistamine effect begins within an hour of taking the tablet and peaks after 6 hours. The effectiveness of fexofenadine relative to other antihistamines is unknown.
R E F E R E N C E
1. Moulds RF. Erythromycin and terfenadine should not be used together [see
comments]. Aust
Prescr 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 Australian
Prescriber in 19921, has
now been approved for use after surgical resection of cancer of the colon.
Levamisole is active against helminths, but also modulates the immune system, particularly when the immune response is impaired. Although the drug has little effect on its own, adjuvant treatment with fluorouracil improves survival in patients with advanced colonic cancer. Patients with stage III colon cancer were entered into a randomised controlled trial within 5 weeks of surgery. After 5 years, 119 of the 304 patients given the combination developed a recurrence, compared with 177 of the 315 given no additional treatment. In addition to this significant reduction in recurrence rate, deaths were also significantly reduced.2
Levamisole is given orally 3 times a day for 3 consecutive days in each fortnight. The combined schedule with fluorouracil is followed for a year.
The combination treatment is associated with frequent adverse effects which are more common than with levamisole alone. The common adverse effects of levamisole include nausea, dysgeusia, arthralgia, fatigue and rashes. Although a flu-like illness may occur during treatment, it may be a sign of agranulocytosis. As fatalities have occurred, it is essential that the blood count is routinely monitored during therapy. Other serious adverse effects include pancreatitis and neurological changes associated with demyelination.
Patients should be warned that levamisole can produce a disulfiram-like reaction with alcohol. The drug is metabolised in the liver and may interact with anticoagulants and phenytoin.
Although most patients will have some adverse effects, the combination of levamisole and fluorouracil is likely to become the standard treatment after surgery for (Dukes' stage C) colon cancer.
R E F E R E N C E S
1. Grygiel JJ. Adjuvant therapy in colorectal cancer. Aust Prescr 1992;15:54-6.
2. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie
JA, Tangen CM, et al. Fluorouracil plus levamisole as effective adjuvant therapy
after resection of stage III colon carcinoma: a final report. Ann Intern Med
1995;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 angiotensin
I 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 only 33% as it undergoes first pass metabolism. While the peak plasma concentration of 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 of 6-9 hours. Only 4% of a dose is excreted unchanged in the urine.
The usual starting dose is 50 mg once a day. Although symptomatic hypotension can occur early, particularly in volume-depleted patients, the maximal antihypertensive effect occurs up to 6 weeks after starting treatment. If 50 mg a day does not control the blood pressure, the manufacturers suggest giving 25 mg twice a day before increasing the dose. Increasing the dose may not produce much change in blood pressure and the maximum dose should not exceed 100 mg a day.
The company claims that the drug has a similar efficacy to daily doses of enalapril 20 mg, atenolol 50 mg and felodipine 5 mg. The long-term effectiveness of losartan is unknown.
Like ACE inhibitors, losartan is contraindicated in pregnancy. As the clinical studies of losartan have been relatively short, there are no data on how safe the drug will be if it is taken for several years. In the clinical trials, dizziness was the only symptom that occurred much more frequently with losartan than with placebo (4.1% vs. 2.4%). Hyperkalaemia can occur and serum concentrations of uric acid are reduced.
Losartan is not more effective than ACE inhibitors, but it
causes less cough. As mild to moderate hypertension usually requires long-term
treatment, 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 was
the first drug of the class, but as it was inactivated by renal dipeptidase,
it had to be formulated with cilastatin, a dipeptidase inhibitor. Meropenem
is a carbapenem which is not affected by renal dipeptidase.
Organisms which are sensitive to meropenem include streptococci and staphylococci, Escherichia coli, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae and Bacteroides fragilis. Some strains of Pseudomonas aeruginosa are susceptible to meropenem. In view of its bactericidal activity against many aerobic and anaerobic bacteria, the drug has been approved for several indications. It can be used to treat severe infections of the lower respiratory tract, urinary tract, skin and skin structures, meningitis, septicaemia, febrile neutropenia, intra-abdominal and gynaecological infections.
Meropenem is given intravenously by infusion or slow injection every 8 hours. Most of the dose is excreted unchanged in the urine within 12 hours. The half-life is approximately one hour.
Patients who are hypersensitive to penicillins may also be hypersensitive to meropenem. The drug is generally well tolerated, but children may 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. Meropenem
should be restricted to serious infections where other antibiotics are contraindicated
or 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% of
patients. As this can reduce the survival of the allograft, there is a need
to try to prevent acute rejection. Mycophenolate mofetil has been studied
because it inhibits guanosine nucleotide synthesis and hence the proliferation
of T and B lymphocytes.
A study of 491 patients compared mycophenolate with placebo in patients who were also given cyclosporin and corticosteroids to prevent rejection. In the first 6 months after surgery, significantly fewer rejections occurred in the patients receiving mycophenolate. Whereas 46% of patients given placebo developed biopsy-proven rejections, only 17% of those given 2 g of mycophenolate had a rejection. A 3 g dose gave a better response rate, but was less well tolerated.1
Mycophenolate has been compared with azathioprine in patients also given cyclosporin and corticosteroids. The combination containing mycophenolate was more effective in preventing rejection.
Treatment is taken twice a day starting within 72 hours of the transplant. Plasma level monitoring is not required in the prevention of toxicity. The drug is completely converted to an active metabolite. This metabolite is further metabolised and then excreted mainly in the urine. Extra caution is needed if there is severe renal impairment.
The patients need regular blood tests during the first year of treatment as anaemia and leucopenia can develop. Other adverse effects include vomiting, diarrhoea and infections. Opportunistic infections include Herpes simplex, Herpes zoster, cytomegalovirus and, rarely, candida and Pneumocystis carinii. The treatment of Pneumocystis carinii may be complicated by the possibility, suggested by animal studies, that there is an interaction with trimethoprim/sulfamethoxazole. Other potential interactions include acyclovir, antacids and cholestyramine.
Although mycophenolate has a proven benefit in the first 6 months after transplantation, its long-term safety and effectiveness will need to be confirmed. The studies of mycophenolate have revealed an increased incidence of skin carcinoma and lymphoma/lymphoproliferative disease compared to placebo.
R E F E R E N C E
1. European Mycophenolate Mofetil Co-operative Study Group. Placebo-controlled
study of mycophenolate mofetil combined with cyclosporin and corticosteroids
for 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, particularly
for metastatic disease. They can reduce the `flare' of the disease which
may occur when a patient starts treatment with a luteinising hormone releasing
hormone (LHRH) agonist.1
Flutamide has been available for several years for use in previously untreated patients with metastatic prostate cancer in combination with a LHRH agonist. Nilutamide, another non-steroidal antiandrogen, has been approved for the same indication. In addition, nilutamide has also been approved for treatment in conjunction with surgical castration.
A company meta-analysis2 reviewed 1056 patients given nilutamide or a placebo after orchidectomy. Complete or partial regression of the disease occurred in 50% of the treatment group and 33% of the placebo group. There were also significant differences in bone pain and the odds of disease progression. There was no significant improvement in survival. This accords with other studies which show that maximum androgen blockade does not result in longer survival than castration.3
Patients commence treatment when they have their orchidectomy or 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 adaptation to darkness. Other adverse reactions include altered liver function, interstitial pneumonitis, nausea and vomiting.
R E F E R E N C E S
1. Boyer M. The management of prostate cancer. Aust
Prescr 1996;19:22-4.
2. Bertagna C, De Gery A, Hucher M, Francois JP, Zanirato J. Efficacy of the combination of nilutamide plus orchidectomy in patients with metastatic prostatic cancer. A meta-analysis of seven randomized double-blind trials (1056 patients). Br J Urol 1994;73:396-402.
3. Prostate Cancer Trialists' Collaborative Group. Maximum
androgen blockade in advanced prostate cancer: an overview of 22 randomised
trials 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 bone
or by affecting bone metabolism. Hypercalcaemia can cause a variety of problems
ranging from fatigue to renal insufficiency and cardiac arrhythmias. Patients
with hypercalcaemia of malignancy often die within a few months. Bisphosphonates
such as clodronate can control the hypercalcaemia by reducing bone resorption.
Although oral formulations of clodronate are available, they have a low bioavailability (1-2%) and absorption is negligible if the dose is taken with food. Most patients will be given clodronate intravenously. This requires a daily infusion, over at least two hours, repeated until the serum calcium is normal. Usually normocalcaemia is achieved in 2-5 days.
Clodronate is not metabolised and most of the dose appears in the urine within a few days. Patients must be adequately hydrated before treatment and renal function must be monitored. The terminal elimination half-life may 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 bisphosphonate also approved for treating the hypercalcaemia of malignancy. Both drugs are effective, but the duration of normocalcaemia was 14 days for clodronate and 28 days for pamidronate.1
R E F E R E N C E
1. Purohit OP, Radstone CR, Anthony C, Kanis JA, Coleman RE. A randomised double-blind
comparison of intravenous pamidronate and clodronate in the hypercalcaemia
of 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. Those
who survive the subarachnoid haemorrhage are likely to be left with a neurological
deficit. One cause of the tissue damage may be the production of toxic superoxide
radicals. This can contribute to the cerebral vasospasm which occurs after
the acute haemorrhage. Tirilazad is thought to promote tissue survival by
inhibiting lipid peroxidation.
The drug is a new chemical entity. It is a nonhormonal 21-aminosteroid and 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 infused over 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 trials of tirilazad have also been given nimodipine to prevent cerebral vasospasm.
Although animal studies show that tirilazad improves the functional outcome, a significant benefit has not been confirmed in all clinical trials. Of the two studies included in the product information, only one showed a significant improvement in survival. Closer examination reveals that only male patients get a significant benefit from treatment. The drug is therefore only approved for men.
The common adverse effects are reactions at the site of infusion and changes in liver function. Tirilazad is metabolised in the liver and its clearance is increased 50% by phenytoin.
