NATIONALLY CIRCULATED INFORMATION
Australia
ADRAC Bulletin, Vol 16, No 4, November 1997
SSRIs and neonatal disorders
The selective serotonin reuptake inhibitors (SSRIs)
1- Fluoxetine (Erocap, Lovan, Prozac, Zactin)
2- Fluvoxamine (Luvox)
3- Paroxetine (Aropax) and
4- Sertraline (Zoloft)
is now the most widely used class of antidepressants in
Australia.
ADRAC has received a relatively large number of reports
(fluoxetine, 803; fluvoxamine, 5; paroxetine, 887; sertraline, 1243) including
reports of effects on the neonate.
ADRAC has received four reports describing withdrawal
reactions in neonates whose mothers had taken SSRIs throughout their pregnancies.
The effects in all four cases appeared to resolve spontaneously.
ADRAC has also received a further four reports related
to probable breast milk transfer.
These reports suggest that adverse reactions to SSRIs
can occur in neonates, through either placental or breast milk transfer.
Practitioners should consider this possibility when prescribing to depressed
patients who are pregnant or breastfeeding.
:
Fatal outcome after sumatriptan
In 1993, ADRAC drew attention to the problem of chest
pain associated with the use of sumatriptan.
ADRAC has received 3 reports documenting a fatal outcome.
Although there were significant confounding features,
these 3 reports describe fatal outcomes following the onset of chest pain
in women who had taken sumatriptan orally some hours earlier.
Non had complained of chest pain previously and in two
cases there was evidence of myocardial ischaemia/infarction. The product
information states that serious coronary events, hypotension and arrhythmias
have been reported in connection with the use of sumatriptan. Prescribers
should be aware that sumatriptan is contraindicated in any patient with
heart disease or uncontrolled hypertension.
Reference:
ADRAC. Sumatriptan and chest pain. Aust.Adv. Drug Reaction
Bull; 1993: 12: 3
Laboratory monitoring with calcitriol
The product information has now been changed so that laboratory
monitoring is specified according to the indication for use. For osteoporosis,
the indication for which ADRAC has received most reports, the current recommendation
for serum calcium monitoring is as follows:
at the commencement of therapy, at 2-4 weeks, and thereafter
at 2 to 3 monthly intervals.
Reference:
ADRAC: Calcitriol and hypercalcaemia.Aust Adv Drug React
Bull 1997; 16:2
Netherlands
Adverse Drug Reaction Bulletin, No. 186, October 1997
Adverse effects of drugs on the function of the
inner ear
Drug-induced hearing loss is characteristically associated
with tinnitus and vertigo. It results from damage to the sound-sensitive
hair cells of the inner ear, and leads to degeneration of the nerves that
supply them.
Important causes include: aminoglycoside antibiotics such
as streptomycin, and cisplatin and certain other antineoplastic agents.
Loop diuretics, quinine and its derivatives, and salicylates are also well-known
causes of hearing loss.
United Kingdom
Current Problem in Pharmacovigilance, Vol 23, December
1997.
Drug interactions of rifabutin
Rifabutin is indicated for:
1 The prophylaxis of Mycobacterium avium intracellutare
complex (MAC) infections in patients with HIV disease with CD4 counts lower
than 75 cells/ul.
2 The treatment of non-tuberculous mycobacterial disease
(such as that caused by MAC and M. xenopi) or pulmonary tuberculosis in
combination regimens.
Example of frequently prescribed drugs whose metabolism
and efficacy may be affected by rifabutin are:
1 Oral contraceptives (alternative method of contraception
advised).
2 HIV protease inhibitors (in particular rifabutin should
not be used with ritonavir).
3 Anticoagulants.
4 Cyclosporin.
5 Oral hypoglycaemics.
6 Anticonvulsants such as phenytoin and carbamazepine.
Uveitis has been associated with rifabutin treatment.
The risk of uveitis with rifabutin occurs mainly when it is used in combination
with clarithromycin for treatment MAC infection.
It has been advised to the prescribers to reduce the dose
of rifabutin to 300mg/day when it is used with macrolides or triazole antifungals
because of increased plasma levels of rifabutin resulting from these combinations.
This dosage reduction of rifabutin, when prescribed with either clarithromycin
or fluconazole, has reduced the frequency of uveitis while maintaining
satisfactory efficacy in the treatment of MAC infection.
Reference:
1. Shafran SD, et al. AIDS 1995; 9:1337-1342.
2. USPHS/IDSA Prevention of Opportunistic Infection Working
Group.Amm.Int. Med.1996; 124(3): 348-368.
3. CSM/MCA Current Problems in Pharmacovigilance 1994;
20:4.
4. Moore RD, et al. New Eng.J Med. 1996; 335:377-383.
Ototoxicity with aminoglycoside eardrops
Ototoxicity is a well-recognised adverse reaction to aminoglycoside
antibiotics.
In 1981 the Committee on Safety of Medicines (CSM) issued
a warning about the increased risk of deafness associated with topical
aminoglycosides for the treatment of otitis externa complicated by a perforated
tympanic membrane.
A recent review revealed 34 literature reports and 7 spontaneous
reports of ototoxicity in patients with a perforation. The topical treatment
with aminoglycosides is contra-indicated in patients with a tympanic perforation.
Reference: CSM Current Problems No. 5, 1981
Confusions between lamictal & lamisil
Lamictal (lamotrigine): anti-epileptic
Lamisil (terbinafine): anti-fungal
These product names have similar spelling and pronunciation.
Recently, information has been received suggesting that a small number
of patients have been prescribed, or have received, the wrong drug.
Prescribing with the approved name will avoid confusion.
Cephalosporins and haemolytic anaemia
Cephalosporins can bind to red blood cell membranes in
such a way as to combine with specific IgG antibodies. This may result
in a positive direct antiglobulin test (Coomb´s test), and can be
sufficient to cause haemolytic anaemia. By different mechanism, immune
complexes containing the antigen derived from cephalosporins, can activate
complement and cause non-specific damage to red blood cells. Very rarely,
acute intravascular haemolytic anaemia can result.
Reference:
1 Shulman IA, et al. Transfusion 1990; 30: 263-266.
2 Chambers LA, et al. Am. J. Clin.Pathol. 1991; 95: 393-396.
3 Garratty G. Lancet 1991; 338: 119-120.
4 Bernini JC, et al. J. Paed. 1995; 126: 813.815.
Terfenadine: additional drug interactions
The interacting agents already indentified include the
azole antifungals, macrolide antibiotics, and grapefruit juice. Because
of similar interactions, it is now recommended that the following drugs
should not be used with terfenadine:
1 mibefradil dihydrocloride (Posicor)
2 serotonin reuptake inhibitors (fluvoxamine, nefazodone,
sertraline)
3 HIV protease inhibitors (indinavir, ritonavir, saquinavir)
4 cisapride
USA
FDA talk paper, 11 November 1997
Troglitazone labelling changes
Troglitazone (Rezulin ) is used in combination with insulin
or sulfonylurea in patients with type II diabetes (adult-onset diabetes
mellitus) whose blood glucose levels are not adequately controlled by these
other therapies alone.
Several hundred thousand patients in the USA have been
treated with troglitazone. FDA has received 35 post-marketing reports of
liver injury of various degree. These reports ranged from mildly elevated
blood levels of the liver transaminase enzymes to liver failure leading
to one liver transplant and one death.
FDA and the manufacturer are recommending that serum transaminase
levels in patients be checked routinely within the first one to two months
of troglitazone therapy, every three months thereafter during the first
year of treatment, and periodically thereafter. In addition, liver function
tests should be performed on any patient on troglitazone who develops symptoms
of liver dysfunction, such as nausea, vomiting, abdominal pain, fatigue,
loss of appetite, or dark urine.
Patients on troglitazone who develop jaundice or whose
laboratory results indicate liver injury should stop taking the drug.
Herbal Fen-Phen
FDA has issued a warning to consumers about products being
marketed as herbal alternatives to fen-phen, drugs used to aid weight loss
prior to the withdrawal of fenfluramine and phentermine from the market
due to safety concerns.
So-called "herbal fen-phen" products are being marketed
over the Internet and through weight loss centers. Many of these advertisements
promote the idea that these products are "natural alternatives" to fen-phen
prescription drugs. FDA considers these products to be unapproved drugs
because their names reflect that they are intended for the same use as
the anti-obesity drugs, fenfluramine and phentermine.
The main ingredient of most herbal fen-phen products is
ephedra, known as Ma Huang (Ephedra sinica). Many ephedra-containing herbal
fen-phen products also contain Hypericum perforatum, an herb commonly known
as St. John´s Wort and sometimes referred to as "herbal Prozac".
Other herbal fen-phen products contain 5-hydroxy-tryptophan
used primarily as a sleep aid, L-tryptophan was pulled from the market
after it was found to be linked to more than 1500 cases, including about
38 deaths, of a rare blood disorders known as eosinophilia myalgia syndrome.
DRUG WITHDRAWALS
Germany
Deutschen Ärzteblatt 94, No. 42, 17 October 1997
(90), A-2770
Recall of fenfluramine (Ponderax) and dexfenfluramine
(Isomeride)
The Adverse Drug Reactions Committee of the Drug Commission
of the German Medical Profession (ÄkdÄ), the rare, but serious
risk of pulmonary hypertension following intake of the serotonine agonist
dexfenfluramine was discussed and a critical risk/benefit analysis conducted.
Laboratoires Servier decided to recall fenfluramine and
dexfenfluramine from the market, even though a causal relationship between
the occurrence of serious changes in the mitral, aortic and/or tricuspid
valves and the intake of fenfluramine, phentermine or dexfenfluramine has
not been confermed.
The Federal Institute of drugs and Medical Divices (BfArM)
issued a notification on 23 September 1997 ordering the suspension of the
registration proceedings for these drugs and the recall of all circulating
batches of the following preparations:
Commercial drugs: Ponderax, Ponderax retard, Isomeride.
United Kingdom
Current Problem in Pharmacovigilance, Vol 23, December
1997.
Troglitazone - serious hepatic reactions
Troglitazone (Romozin) is the first of a new class of
orally active anti-diabetic agents. It was launched in the USA and Japan
in March, and in the UK in October 1997.
By early November, 40 cases of serious hepatic reactions
occurring during treatment with troglitazone had been reported worldwide.
Reactions included severe hepatocellular damage, hepatic necrosis and hepatic
failure. One patient had died and another required liver transplantation.
GlaxoWellcome and Sankyo Pharma, the companies marketing
troglitazone in the UK, have voluntarily withdrawn from the market as from
1 December 1997, and have informed doctors and pharmacists by letter.
Fenfluramine and dexfenfluramine
In the previous Current Problems in Pharmacovigilance
the CSM/MCA reported on the occurrence of valvular heart disease associated
with the combination of fenfluramine (Ponderax Pacaps) and phentermine
(Ionamine and Duromine).
According to Connolly HM, et al, New Eng.J. Med. 1997,
337: 581, the number of cases reported in the USA increased to more than
100.
Some of these reports were associated with dexfenfluramine
(Adifax) or fenfluramine treatment alone but none with phentermine alone.
Patients developed mitral, aortic, tricuspid or mixed valve disease.
The manufactures have voluntarily withdrawn fenfluramine
and dexfenfluramine worldwide.
LITERATURE REFERENCES
Netherlands
Antoine C.G. Ebgerts, Ronald H. B. Meybroom, Fred H.P.
De Koning,Albert Bakker and Hubert G. M. Leufkens. British Journal of Clinical
Pharmacology 1997; 44: 277-281
Non-puerperal lactation associated with antidepressant
drug use.
Serotonergic antidepressants are associated with an approximately
eight times higher risk of non-puerperal lactation compared with other
antidepressants. This effect is probably mediated by an indirect inhibition
effect of serotonin on the dopaminergic transmission. This finding is in
line with the occurrence of other antidopaminergic effects, such as extrapyramidal
symptoms, in patients using serotonergic antidepressants.
RHB Meyboom, EP van Puijenbroek, MHAM Vinks, CJ Lastdrager
New Zealand Medical Journal 8 August 1997, page 300
Disturbance of withdrawal bleeding during concomitant
use of itraconazole and oral contraceptives.
The antifungal drug itraconazole was approved for marketing
in the Netherlands 1991.
Although the SPC of itraconazole mentions the occurrence
of menstrual disorders and impotence as possible side effects, hormonal
effects have not been established. It is known that itraconazole may interact
with a variety of drugs, but not with oral contraceptives.
In this journal one case has been reported of pill failure,
occurring in possible relationship with the concomitant use of itraconazole
and oral contraception.