http://www.australianprescriber.com/magazines/vol24no6/new_drugs.htm
Some of the views expressed in the following notes on newly approved
products should be regarded as tentative, as there may have been little
experience in
Cetrotide (Serono)
vials containing 250 microgram or 3 mg as powder for reconstitution
Approved indication: assisted reproduction
Australian Medicines Handbook Section 10.6.3
Luteinising hormone has an important role in the
menstrual cycle. In assisted reproduction programs a premature surge in luteinising hormone can cause ovulation, and therefore
disrupt the collection of oocytes. This surge can be
prevented by antagonising luteinising
hormone releasing hormone (LHRH).
Cetrorelix competes with LHRH for binding sites in
the pituitary gland. This reduces the secretion of luteinising
hormone and follicle stimulating hormone. A 250 microgram dose is injected
every day starting five or six days after ovarian stimulation is begun. These
injections continue until the day before ovulation is induced. A single large
dose (300 mg) can be used to suppress ovulation for at least four days.
Analogues of gonadotrophin-releasing hormones have
also been used to prevent surges of luteinising
hormone. (Prolonged administration of an analogue agonist eventually reduces gonadotrophin production.) Cetrorelix
has therefore been compared with the LHRH agonists such as triptorelin
and buserelin. While cetrorelix
was as efficacious as the agonists it has the advantage of a more immediate
action.
The most frequent adverse effects of cetrorelix
are injection site reactions. Ovarian hyperstimulation
can occur, but it is uncertain if this is caused by cetrorelix
rather than the hormones used to promote follicular development. Compared to
patients given LHRH agonists there are fewer cases of ovarian hyperstimulation.
While cetrorelix has been approved for use by
specialists in the management of female infertility, researchers are studying
other possible uses of LHRH antagonists.
Ganirelix
Orgalutran (Organon)
250 microgram/0.5 mL in pre-filled syringes
Approved indication: assisted reproduction
Australian Medicines Handbook Section 10.6.3
Ganirelix is the second member of its class to be
approved for use in
These drugs are given to prevent premature ovulation when controlled ovarian
hyperstimulation is used to assist conception. The
patients are given follicle stimulating hormone (FSH) starting on the second or
third day of their menstrual cycle. When they have their sixth dose of FSH they
start daily subcutaneous injections of ganirelix. By
binding to pituitary gonadotrophin receptors, ganirelix inhibits a surge in the concentration of luteinising hormone. By preventing this surge, the timing
of ovulation can be controlled. This enables an adequate number of follicles to
develop to the required size for collection.
Earlier attempts to create gonadotrophin antagonists
had problems because they triggered allergic reactions by releasing histamine.
Although this does not appear to occur with ganirelix,
it can cause reactions at the injection site in up to 15% of patients. Other
adverse effects include headache and nausea.
The efficacy of ganirelix is probably similar to
that of the gonadotrophin agonists which have also
been used to prevent surges of luteinising hormone. Ganirelix has the advantage of acting more quickly. There
is, however, a concern that implantation rates may be reduced for follicles
exposed to LHRH antagonists.1
R E F E R E N C E
Lercanidipine hydrochloride
Zanidip (Solvay)
10 mg film-coated tablets
Approved indication: hypertension
Australian Medicines Handbook Section 6.4.6
Lercanidipine is a dihydropyridine
calcium channel antagonist. Four other dihydropyridines
are already available in
Like other dihydropyridines, lercanidipine
relaxes vascular smooth muscle to lower peripheral resistance. This
vasodilatation occurs slowly so patients are less likely to develop acute
hypotension and reflex tachycardia.
Although lercanidipine is completely absorbed its
bioavailability is reduced to 10% by first-pass metabolism. The tablets should
be taken at least 30 minutes before a meal because food increases the
bioavailability. As the enzymes involved in the first-pass metabolism can
become saturated, doubling the dose causes the plasma concentrations to more
than double.
Lercanidipine is eliminated by liver metabolism.
It is completely metabolised with approximately half
the metabolites being excreted in the urine. This metabolism involves cytochrome P450 3A4 so the plasma concentration of lercanidipine may be increased by drugs, such as
erythromycin, fluoxetine and ketoconazole,
which inhibit the enzyme. The plasma concentration may be reduced by drugs,
such as phenytoin and carbamazepine,
which induce CYP 3A4. Lercanidipine is
contraindicated in patients with moderate or severe liver disease and in
patients with severe renal impairment. Although the half-life of lercanidipine is relatively short, its antihypertensive
effect is sustained for 24 hours.
Short-term studies show that lercanidipine reduces
diastolic blood pressure by 5-7 mmHg more than a placebo. During comparative
studies lasting 12-16 weeks no significant differences emerged between lercanidipine and slow-release nifedipine,
atenolol, hydrochlorothiazide or captopril.
In a double-blind crossover study of 16 patients, lercanidipine
reduced diastolic blood pressure by 13 mmHg while amlodipine
produced a 10 mmHg reduction.1
Many of the adverse effects of lercanidipine are
caused by vasodilatation. Headache, flushing and palpitations are the commonest
adverse reactions. As most studies have only lasted a few months, more
information is needed on the long-term safety of lercanidipine.
Given the concerns about the adverse effects of dihydropyridines2,
it is unlikely that lercanidipine will have a
prominent role in the treatment of hypertension.
Although it appears to be effective for mild to moderate hypertension it is
not indicated for severe hypertension.
R E F E R E N C E S
Lopinavir/ritonavir
Kaletra (Abbott
capsules containing 133.3 mg lopinavir/33.3 mg ritonavir
oral solution containing 400 mg lopinavir/100 mg ritonavir
in 5 mL
Approved indication: HIV
Australian Medicines Handbook Section 5.3
Combinations of antiviral drugs which include a protease inhibitor
effectively suppress HIV. By inhibiting viral proteases drugs, such as ritonavir, reduce replication of the virus.
Lopinavir is also a protease inhibitor. After
absorption it undergoes high first-pass metabolism and is rapidly cleared from
the circulation. Lopinavir is extensively metabolised by cytochrome P450
3A. This is one of the enzymes inhibited by ritonavir,
so giving ritonavir in combination with lopinavir increases the plasma concentrations of lopinavir.
The combination should not be prescribed with drugs such as triazolam, midazolam, simvastatin, lovastatin, ergot
derivatives, cisapride or rifampicin.
Other drugs with potentially significant interactions include atorvastatin, cerivastatin, dihydropyridines, oral contraceptives, sildenafil
and warfarin. Patients should not take
A randomised double-blind trial has studied lopinavir/ritonavir in combination with stavudine
and lamivudine in patients who have not been
previously treated with antiretroviral drugs. After 48 weeks of treatment the
concentration of HIV RNA had fallen below 400 copies/mL in most patients.1
In a comparison with nelfinavir, another protease
inhibitor, lopinavir/ritonavir was given to patients
who also took stavudine and lamivudine.
After 24 weeks the HIV RNA was below 400 copies/mL in 71% of the patients taking nelfinavir
and in 79% of those taking lopinavir/ritonavir.
This difference is statistically significant.
Lopinavir/ritonavir has also been studied in
patients previously treated with a protease inhibitor. It has been given in a
regimen with two nucleoside reverse transcriptase inhibitors and nevirapine (a non-nucleoside reverse transcriptase
inhibitor). After 72 weeks, 75% of the patients had less than
400 copies/mL.
Approximately 3% of the patients withdrew from clinical trials of lopinavir/ritonavir because of adverse reactions. Diarrhoea affects 14-22% of patients. Other adverse effects
include nausea, abdominal pain and asthenia. The combination alters liver
function and can also increase concentrations of total cholesterol and
triglycerides. Possibly related to the changes in triglycerides, are reports of
pancreatitis in patients taking lopinavir/ritonavir.
Although lopinavir/ritonavir can be used to treat
patients who have previously been treated with a protease inhibitor the extent
of cross-resistance is uncertain. Some viruses will develop a reduced
sensitivity to lopinavir/ritonavir during treatment.
Lopinavir/ritonavir may have a role in treating
patients who are infected with HIV that is resistant to other drugs. Its
precise role and the most suitable regimen will need further study as there are
no data about the clinical outcomes of treatment.
R E F E R E N C E
Meningococcal group C conjugate vaccine
Meningitec (Wyeth)
vials containing 0.5 mL
Approved indication: immunisation
Australian Medicines Handbook Section 20.1
Neisseria meningitidis
is a major cause of meningitis and infants are particularly at risk. Babies are
not currently immunised against the meningococcus because the available polysaccharide vaccines
are not very effective. Conjugating the meningococcal group C oligosaccharide
to diphtheria protein increases the immune response.1
Immunogenicity data enabled this conjugate vaccine to
be approved in the
A randomised controlled trial compared a conjugate
vaccine with a quadrivalent polysaccharide vaccine in
127 infants aged 15-23 months. Each child had two injections two months apart,
followed by a booster dose of polysaccharide vaccine a year later. After two
doses the IgG response in the children who received
conjugate vaccine was 10 times greater than the response to the polysaccharide
vaccine. Their titres were still twice as high one
year later. One month after the booster their titres
were 50 times greater than those of the children who had the polysaccharide
vaccine.2
Meningococcal group C conjugate vaccine is now part of the routine immunisation schedule in the
The injections are given intramuscularly. Meningococcal vaccine can be given
at the same time as routine childhood vaccines, but there is limited
information about giving it with inactivated polio vaccine or varicella vaccine.
Injection site reactions are common. Some children will develop a fever in
excess of 38°C and there may be signs of irritability. Convulsions have been
reported.
While the conjugate vaccine appears to be safe and effective in the short
term, it will not protect people against other causes of meningitis, for
example Neisseria meningitidis
group B which is more common in
R E F E R E N C E S
Moxifloxacin hydrochloride
Avelox (Bayer)
400 mg tablets
Approved indication: respiratory infections
Australian Medicines Handbook Section 5.1.12
Moxifloxacin is a fluoroquinolone
antibiotic. Like other fluoroquinolones it is active
against Gram-negative bacteria such as Haemophilus
influenzae. Compared to older members of the
class, such as ciprofloxacin, moxifloxacin has more
activity against Gram-positive bacteria such as Streptococcus pneumoniae.
Given its spectrum of antibacterial activity moxifloxacin
has been approved for the treatment of community-acquired pneumonia,
exacerbations of chronic bronchitis and sinusitis. In studies of patients with
community-acquired pneumonia, moxifloxacin has been
as effective as other drugs such as clarithromycin.
Moxifloxacin is as effective as cefuroxime in the treatment of acute maxillary sinusitis. Cefuroxime was also equivalent to moxifloxacin
in the treatment of exacerbations of chronic bronchitis. For this indication, a
five day course of moxifloxacin is as effective as a
seven day course of clarithromycin.
Moxifloxacin has a half-life of 12 hours, but can
be given once a day. It is eliminated by renal and hepatic clearance. The
metabolism of moxifloxacin does not involve the cytochrome P450 system. Although it has not been associated
with the severe liver problems associated with trovafloxacin,
moxifloxacin should not be given to patients with
significant hepatic impairment.
Like other oral antibiotics, nausea, vomiting and diarrhoea
are common adverse effects of moxifloxacin. It may
cause dizziness and lightheadedness so patients should know how they react to
this drug before they drive or operate machinery. Moxifloxacin
can also prolong the QT interval so there is a potential for arrhythmias.
Similar ECG changes led to the withdrawal of grepafloxacin.
Moxifloxacin should therefore not be given to
patients with a prolonged QTc interval, hypokalaemia, or those taking drugs which prolong the QTc interval. Although the photosensitivity
potential of moxifloxacin appears to be low,
hypersensitivity reactions can occur after the first dose.
Bacteria are becoming resistant to the fluoroquinolones
and there is cross-resistance to drugs within the class. To maintain the
usefulness of these drugs, moxifloxacin should
probably not be used as a first-line treatment for common infections such as
sinusitis.
Thyrotropin alfa-rch
Thyrogen (Genzyme)
0.9 mg/mL in 5 mL vials
Approved indication: thyroid cancer testing
Australian Medicines Handbook Section 10.3
This recombinant form of human thyroid stimulating hormone (TSH) can be used
in diagnostic tests of patients with thyroid cancers. One indication, in
conjunction with radioactive iodine imaging, is for the detection of remnant
thyroid tissue after total thyroidectomy. The
radioiodine is given 24 hours after the second of two intramuscular injections
of reconstituted thyrotropin (also given 24 hours
apart). A similar regimen is used for thyroglobulin
testing with a serum sample being taken 72 hours after the second injection. (Thyroglobulin should be undetectable after total thyroidectomy.)
The common adverse effects of thyrotropin are
nausea and headache.
NEW FORMULATIONS
Calcipotriol
Diavonex Scalp Solution (CSL)
50 microgram/mL solution
Gliclazide
Diamicron MR (Servier)
30 mg modified-release tablets
NEW STRENGTH
Conjugated oestrogens/medroxyprogesterone
acetate
Premia 10 (Wyeth)
packs of 14 tablets containing 0.625 mg conjugated oestrogens
and 14 tablets containing 0.625 mg conjugated oestrogens/10 mg medroxyprogesterone acetate
NEW COMBINATION
Abacavir/lamivudine/zidovudine
Trizvir (GlaxoSmithKline)
tablets containing 300 mg abacavir/150 mg lamivudine/300 mg zidovudine
NEW PROPRIETARY BRANDS
Cefotaxime sodium
DBL Cefotaxime Sodium for Injection (Faulding)
500 mg, 1 g and 2 g vials
Gliclazide
Nidem (Arrow)
80 mg tablets
ALL
INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR
GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE
KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED
AS PROVIDING MEDICAL OR LEGAL ADVICE. THE DECISION WHETHER OR NOT TO
VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU
ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.