The safety of the
broad-spectrum antibiotic co-trimoxazole, prescribed most frequently as Septrin
(Septra in the US) or Bactrim, has been suspect for many years. This drug
usually consists of five parts sulphamethoxazole, a sulphonamide component, and
one part trimethoprim.|
Even a decade ago doctors
were being advised to use the single-drug trimethoprim for chronic bronchitis
and urinary infections in preference to the combination drug (Drugs & Ther Bull,
1986, Vo1.24 No.5).
Major medical textbooks have
detailed serious adverse reactions to co-trimoxazole, including
Stevens Johnson's Syndrome (SJS), a severe skin condition, which is fatal in
about 10 per cent of cases, and Lyell Syndrome, causing death to the top layer
of the skin, with a high mortality rate (See also WDDTY vol 4 no 10 and vol 5 no
4). Nevertheless, this drug was widely publicized in the 1970s and early 1980s
and continued to be prescribed, even for children.
Then, last year, several
newspaper articles and a BBC television programme brought attention to the fact
that many people who had been treated with it had become very ill. Thus far,
about 136 people allegedly have died as a result of taking Septrin and over 6000
were injured in the UK alone; the true figures could be far higher. Severe
reactions were thought to be attributable almost entirely to the sulphonamide
component of the drug.
Following a petition plus 200
selected case histories sent to the Committee on Safety of Medicines, MPs in the
UK House of Commons debated the safety of co-trimoxazole this summer, and the UK
government decided to severely restrict its future use (The Lancet, 1995; 346:
175), in favour of the supposedly safer one of its components, trimethoprim.
This antibiotic is available,
under several brand names and as one ingredient in many drugs. Trimethoprim has
been touted as a drug that is cheaper, and more effective with fewer side
But how safe, actually, is
Recently published data
comparing trimethoprim with co-trimoxazole and. the antibiotic cephalexin shows
that the risk of liver disease was similar for persons prescribed co-trimoxazole
and trimethoprim alone, even though there was an increased risk of erythema
multiforme (a rash resulting from an allergic reaction), SJS and Lyell's
Syndrome for the combination drug (Pharmacotherapy, 1995, 15; 4: 428-32; Lancet
1995, 345: 1118-9).
There also have been records
of severe reactions to the trimethoprim alone, such as a case of aseptic
meningitis (JAMA, 1984; 20:2865-66). Interestingly, this patient first
experienced such a reaction after co-trimoxazole, which suggests that once a
person is sensitized to co-trimoxazole, he may also react to trimethoprim alone
(Martindale's Extra Pharmacop, 1993).
Doctors have also observed
adverse effects on kidney function in renal transplant patients (The Lancet,
An elderly male patient
developed pseudo-membranous colitis following the administration of trimethoprim
after an operation and died (BMJ, 1985; 290:1112). Another case of erythema
multiforme followed use of trimethoprim in a patient known to be allergic to
co-trimoxazole (BMJ, 1987; 295:56).
In another case, a patient
given trimethoprim for chronic sinusitis experienced nausea and skin eruptions,
similar to those that had been attributed to co-trimoxazole six years before.
Other reports have also linked trimethoprim with rashes, including erytheme
multiforme (Ladartidningen, 1982; 79: 124) and other skin reactions (lnd J
Dermatol 1982; 48: 207-8; BMJ, 1982; 284: 1529-30; Dermatologica, 1986; 172:
230-1; Br J Dermatol, 1987; 116: 241-2).
Serious side effects with
trimethoprim, such as sore throat, fever, pallor or purpura, may be early
indications of serious blood disorders, requiring complete blood counts (Drug
Facts & Comparisons, 1995, 2213).
In the past, proponents of
co-trimoxazole have argued that use of the combination drug would delay
bacterial resistance to trimethoprim. But the evidence shows that resistance to
both drugs has simply grown in tandem. In one British study, overall resistance
to TMP increased from 12 per cent in 1981 to 19 per cent in 1982, and
resistance in general practice doubled (BMJ, 1983; 286: 1182-3).
The other worry is that
trimethoprim can have the same effect on metabolism of folic acid that the
combination drug has. At a major conference on co-trimoxazole in 1972, early
investigators disclosed that 1g of trimethoprim daily for four weeks given to 10
normal subjects produced mild evidence of interference with folate metabolism in
all, including thrombocytopenia (reduced number of platelets) in one case and
anaemia in another (Clin Pharmacol Ther, 1968; 9:550-60).
This could effect blood
cells, particularly those that line the small bowel (V Herbert: In:
Trimethoprim-Sulphamethlwxazole, M Finland, EH Kass, eds, Univ of Chicago
Considering these studies,
only one thing can be said with certainty: There may be a big question mark over
the safety of trimethoprim.
There also may be some
question marks over its effectiveness. One study demonstrated that there was
weak evidence that trimethoprim, in combination with another drug, had any
benefit in treating acute sinusitis (one of its big indications), compared with
a decongestant which helped nearly three-quarters of patients.
As a group of doctors
concluded: in treating sinusitis, "we may be using the antibiotics as a placebo"
or just using it to keep themselves happy (JAMA, November 1, 1995).
Republished with permission of What Doctors
Don't Tell You, a monthly newsletter which reviews conventional medicine and
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