William R. Bowie, MD.

Urethral Discharge in the Male

SUMMARY
Urethritis in the male is frequent, and is
ahmost always sexually transmitted. It is
classically divided into gonorrhea, and
nongonococcal urethritis. By definition, men
with gonorrhea have Neisseria gonorrhoeae
present, but approximately 20% also have
Chlamydia trachomatis. C. trachomatis is
present in 30%-50% of men with acute
nongonococcal urethritis. The specific etiologic
diagnosis requiires laboratory evaluation.
Recommended treatment for urethritis
includes a one-week regimen of a tetracycline
for all men, plus a single-dose regimen active
again.st N. gonorrhoeae in men in whom
gonorrhea is proven or has not been
excluded. Partners should be investigated and
should receive similar treatment. Recurrence
of nongonococcal urethritis is frequent after
treatment, but the condition is only rarely the
result of persistent C. trachomatis infection.
Men with recurrent urethritis require
re-evaluation. If no cause is found or if
Ureaplasma urealyticum is isolated, the men
are treated with a two-week course of
erythromycin. If there are subsequent
recurrences, they are usually left untreated.
(Can Fam Physician 1987; 33:1863-1868.)
Key words: urethritis, males, sexually transmitted diseases
RESUME
Le probleme d'uretrite chez l'homme est frequent et
presque toujours transmis sexuellement. II existe
deux categories d'uretrite: la gonorrhee et l'uretrite
non gonococcique. Par definition, il y a presence de
Neisseria gonorrheae chez les hommes souffrant de
gonorrhee mais, dans environ 20% des cas, il y a
aussi presence de Chlamydia trachomatis. Le C.
trachomatis est present chez environ 30% a 50% des
hommes souffrant d'une uretrite aigue non
gonococcique. Le diagnostic etiologique specifique
requiert une evaluation biologique. Le traitement
recommande pour l'uretrite inclut la tetracycline
pendant une semaine dans tous les cas, plus une
dose unique d'un medicament actif contre le N.
gonorrheae chez les hommes dont la gonorrhee est
prouvee ou n'a pas ete exclue. Les partenaires
devraient faire l'objet d'une investigation et recevoir
un traitement semblable. La recidive de l'uretrite
non gonococcique est frequente apres le traitement
mais cette condition n'est que rarement le resultat
d'une infection a C. trachomatis persistante. II est
necessaire de reevaluer les hommes dont l'uretrite
recidive. Lorsqu'aucune cause n'est identifiee ou que
Ureaplasma urealyticum est isole, il faut traiter avec
erythrorrycine pendant deux semaines. Les cas de
recidives subsequentes sont hatituellement non
traitees.

Dr. Bowie is a professor in the
Division of Infectious Diseases in.
the Department of Medicine at
U.B.C. His major research interests
have been related to sexually
transmitted diseases. He is a
member of the Health and Welfare
Canada Expert Interdisciplinary
Advisory Committee on Sexually
Transmitted Diseases in Children
and Youth. Requests for reprints
to: Dr. William R. Bowie, Division
CAN. FAM. PHYSICIAN Vol. 33: AUGUST 1987
of Infectious Diseases, G.F. Strong
Research Laboratory, Vancouver
General Hospital, 2733 Heather
Street, Vancouver, B.C. V5Z 1M9
I RRITATION of the male urethra
caused by any stimulus can result in
urethral discharge, buming with urina-
tion, and urethral itch or irritation.'
Although the list of potential causes is
long, including congenital abnormali-
ties, chemical irritation, tumours, or
mechanical causes, the vast majority
of cases of urethritis result from infec-
tions, of which by far the most are sex-
ually transmitted. Unless another
cause is obvious, it should always be
considered that urethritis of recent
onset is caused by a sexually transmit-
ted pathogen. Verification of a diag-
nosis of urethritis requires demonstra-
tion of a polymorphonuclear leukocyte
response in urethral material. How-
ever, infection of the male urethra with
1863
even the most clinically important
urethral pathogens like Neisseria gon-
orrhoeae and Chlamydia trachomatis,
can occur without symptoms, signs, or
a polymorphonuclear leukocyte re-
sponse and will be recognized only be-
cause infection is recognized in a
partner or because of a positive screen-
ing test.
Epidemiology
The peak period of onset of
urethritis in men is from age 20 to 24
years, but urethritis occurs in postpu-
bertal men of all ages.2 The major risk
factor for development of urethritis is
sexual activity, especially in non-mo-
nogamous relationships with potential
exposure to new genital pathogens.
Gonorrhea remains the best-known ex-
ample of urethritis, but non-gonococ-
cal urethritis is more frequent, espe-
cially among heterosexual men. This
is true in most sexually transmitted
disease (STD) clinics, but is especially
true in student health services and pri-
vate practice, where 80%- 90% of
urethritis in heterosexual men is non-
gonococcal.
The incidence of both gonorrhea
and non-gonococcal urethritis rose
steadily through the 1950s, 1960s, and
1970s. Canadian rates of gonococcal
urethritis in men have since fallen. In-
deed, probably in response to AIDS-
related preventive measures, the rate
of decline in the last one to two years
has been pronounced, although it has
been more pronounced in homosexual
than in heterosexual men. From the
mid-1960s on, the rate of non-gono-
coccal infection rose much faster than
that of gonococcal infections, and it
continued to rise at least to the late
'70s and early '80s. Data are too in-
complete to know whether the rate has
fallen recently as well.
The relative proportion of non-gon-
ococcal cases of urethritis in a given
practice or a given person will depend
upon the sexual preference of the per-
son, whether that person has come to
an STD clinic or is being seen else-
where, and what disease has been re-
cognized in his or her partner.
Etiology
From the clinician's point of view,
the usual differential in a man with
proven urethritis is between gonorrhea
and non-gonococcal urethritis, where
gonorrhea is diagnosed if a smear of
1864
urethral material shows gram-negative
diplococci or a diagnostic test is posi-
tive for N. gonorrhoeae. When neither
is positive, non-gonococcal urethritis
is diagnosed. Although the distinction
should still be made and may have
treatment significance because of the
increase in penicillin- and tetracycline-
resistant strains of N. gonorrhoeae,
from the management point of view
the distinction is less critical because
of current recommendations to treat all
men with urethritis, including those
with gonorrhea, with a regimen that as
a minimum is active against C. tracho-
matis. Presentation with gonorrhea
carries with it a significant likelihood
of concurrent C. trachomatis infection.
Among persons with gonorrhea, C.
trachomatis is present in 20% of he-
terosexual men, 10%- 15% of homo-
sexual men, and 40%- 50% of
women.4
The etiology of non-gonococcal
urethritis varies, depending on
whether the patient has acute, persis-
tent, or recurrent non-gonococcal
urethritis.5 Acute non-gonococcal
urethritis is defined as 'a new and pre-
viously untreated episode'. It is impor-
tant that there be a high index of suspi-
cion for diagnosis of acute
non-gonococcal urethritis because C.
trachomatis is isolated from
30%- 50% of such men. Most men
with C. trachomatis (or N. gonorr-
hoeae) urethritis are unlikely to de-
velop severe sequelae even if left un-
treated for a long time. By contrast,
and representing a major reason why
early recognition of the problem is re-
quired, is the considerable risk for fe-
male partners of developing rapid as-
cending infection of the uterus and
fallopian tubes (endometritis or pelvic
inflammatory disease), with its atten-
dant risks of infertility, tubal preg-
nancy, and chronic pelvic pain.4 A
second cause of approximately
30%-40% of cases of acute non-gon-
ococcal urethritis is the genital myco-
plasma, Ureaplasma urealyticum. 1 6
In 20%- 30% of cases of acute non-
gonococcal urethritis, however, nei-
ther organism is identified. In these
men, the etiology is rarely ascertained.
A very small proportion (1%-2%) of
cases are caused by unrecognized
Herpes simplex virus infection or Tri-
chomonas vaginalis. Evidence linking
other putative causes is meager, al-
though sporadic cases may be caused
by adenoviruses or organisms such as
Haemophilus parainfluenzae or H. in-
fluenzae.
Men with acute non-gonococcal
urethritis are treated with a one-week
course of a tetracycline or erythromy-
cin.33 5 7 On these regimens, at least
95% of men show a significant-often
a total-clinical response. In 5% of
men, urethritis persists with minimal
or no improvement. Among the men
with persistent urethritis who have
taken their medications C. trachomatis
is virtually never re-isolated at the end
of therapy. About one-half have tetra-
cycline-resistant U. urealyticum, and
some have T. vaginalis or herpes.
Herpes should be considered espe-
cially if the dysuria is very severe,
there is point tenderness on palpation
of the urethra, or there is tender in-
guinal lymphadenopathy.
Of the 95% of men who initially re-
spond, 30%- 40% will have recur-
rence or exacerbation of the urethral
polymorphonuclear leukocyte re-
sponse within six weeks of the end of
treatment.7 Approximately half will by
symptomatic. In compliant men not
exposed to new or untreated partners,
C. trachomatis is rarely re-isolated so
that this type of failure is not caused by
persistence of C. trachomatis infec-
tion. In approximately 10%- 20% U.
urealyticum will be re-isolated, but the
etiology in the rest is usually un-
known.
Post-gonococcal urethritis is similar
to non-gonococcal urethritis, but
occurs after treatment of gonorrhea
with a penicillin, cephalosporin, or
aminoglycoside regimen that only
rarely eradicates C. trachomatis. In ap-
proximately 50% of these men C. tra-
chomatis will be isolated at the time
of diagnosis of post-gonococcal
urethritis.4
Diagnosis
Urethritis may be suspected if cer-
tain symptoms and clinical findings
are present, but the specific etiologic
diagnosis requires laboratory evalua-
tion to document a polymorphonuclear
leukocyte response and to demonstrate
the presence of N. gonorrhoeae. Clini-
cal manifestations tend to be more
acute and more profuse for gonorrhea,
but on rare occasions non-gonococcal
urethritis presents with a profuse and
purulent discharge. Men with less pro-
fuse and less purulent discharge more
often have non-gonococcal urethritis,
but may have either infection. There
CAN. FAM. PHYSICIAN Vol. 33: AUGUST 1987
are no useful clinical clues to distin-
guish men with C. trachomatis or U.
urealyticum, although men with multi-
ple prior episodes of urethritis are less
likely to have C. trachomatis or U.
urealyticum isolated.
Typical symptoms of urethritis in-
clude discharge, dysuria, and itch.
Symptoms of hematuria, fever, fre-
quency, nocturia, urgency, a problem
with initiating the urinary stream or
with post-void dribbling, and genital
pain other than dysuria are not typical
symptoms and suggest the presence of
other genital problems. In addition, a
diagnosis of urethritis can be suspected
if a partner has cervicitis or a pelvic in-
flammatory disease, has delivered an
infant with a sexually transmitted in-
Figure 1
Urethral Infection: A Protocol
Present
Swabs of exudate
Test for
C. trachomatis
Gram stain for Gram negative diplococci
Negative
-*o
I
RX for NGU RX for GC and NGU
Examine and treat
sexpartners for NGU
CAN. FAM. PHYSICIAN vol.
Vol. 33: AUGUST 1987
1987
fection, has a positive diagnostic test
for C. trachomatis or N. gonorrhoeae,
or if the patient has had one or more
new sex partners recently. The incuba-
tion period of gonorrhea tends to be
shorter, with a typical range of two to
seven days, whereas that of non-gono-
coccal urethritis tends to be two to
three weeks. It can, however, be
longer for both infections, and asymp-
tomatic disease is frequent with both
infections.
Genital examination must be thor-
ough and should include careful ob-
servation for skin lesions, inguinal
lymphadenopathy, and scrotal abnor-
malities, in addition to detection of a
discharge. Discharge may be sponta-
neous, but if it is not, the urethra must
Urethral infection suspected
Examine for urethral discharge
Endourethral swabs Endourethral swab
Gram stain
PMN present
Equivocal or not Positive
available
RX for GC and CT
Examine and treat sex partners
for GC and CT
be milked three or four times from the
base to the meatus to attempt to ex-
press discharge. (See Figure 1.) For
many men, examination during a typi-
cal afternoon office visit will not allow
the physician to detect discharge.
Symptomatic men without apparent
discharge should be re-evaluated after
a longer interval without voiding. Pre-
ferably, this should be done in the
morning prior to their voiding. The
next step is to document a polymor-
phonuclear leukocyte response. If
purulent urethral exudate is present, it
should be swabbed to prepare a gram
stain and for culture for N. gonorr-
hoeae. If a purulent discharge is not
detected, an endourethral swab is re-
quired to obtain material for gram stain
Absent
Culture for
N. gonorrhoeae
Few or no PMN
Examine for first
glass pyuria (NGU)
or other causes
of symptoms
410
1 865
1885
and culture for N. gonorrhoeae. A cul-
ture for N. gonorrhoeae is desirable in
all men with suspected urethritis both
for diagnosis and to evaluate the sus-
ceptibility of N. gonorrhoeae to peni-
cillin and tetracycline. If there is a
problem with maintenance of N. gon-
orrhoeae bacteria in transit, a non-cul-
ture test may be useful. A chlamydial
diagnostic test is not mandatory in a
patient with suspected or proven
urethritis if he is going to be treated
with a regimen that will eradicate C.
trachomatis; it is indicated, however,
if urethritis is not diagnosed, or if
treatment is withheld. Nevertheless,
whether a discharge is present or not,
if a diagnostic test is performed for C.
trachomatis, the correct specimen is
obtained by inserting an endourethral
swab 3-4cm into the anterior urethra.
The patient should be warned that the
procedure is painful, and that the next
urination will be painful. This type of
assessment is required because the
diagnostic yield from discharge at the
meatus is only half the yield from an
appropriately taken endourethral
swab. Symptomatic men in whom no
polymorphonuclear leukocyte re-
sponse is detected should be re-exam-
ined in the morning prior to their void-
ing. After cultures are taken, the first
lOml- 15ml of urine should be ob-
tained to detect pyuria.
The presence of a mean of four or
more polymorphonuclear leukocytes
x 1,000 field on gram stain is indica-
tive of urethritis. The presence of 15 or
more polymorphonuclear leukocytes
in two or more of five x 400 fields of
the sediment of the first-voided urine
(pyuria) also indicates urethritis.5
While the smear is being evaluated for
a polymorphonuclear leukocyte re-
sponse, it is also examined for gram-
negative diplococci. The presence of
gram-negative intracellular diplococci
is virtually diagnostic of N. gonorr-
hoeae infection, but provides no infor-
mation about the presence or absence
of C. trachomatis. The presence of
typical gram-negative extracellular di-
plococci correlates with a positive
culture for N. gonorrhoeae in approxi-
mately 25% of cases. A gram stain
showing polymorphonuclear leuko-
cytes but no gram-negative intracellu-
lar or extracellular diplococci is only
rarely associated with a positive cul-
ture for N. gonorrhoeae.
Independent of demonstration of a
polymorphonuclear leukocyte re-
1866
sponse, a positive diagnostic test for
N. gonorrhoeae or C. trachomatis that
seems to be a true positive result is an
indication for treatment. If U. urealyti-
cum is sought and is diagnosed by cul-
ture, it does not necessarily follow that
it is the cause of urethritis, and is not
by itself an indication for treatment.6
Complaints of frequency and ur-
gency of uriflation, nocturia of recent
onset, hematuria, a problem with urin-
ary flow, perineal pain, scrotal
masses, or chills and fever should
prompt consideration of classic urinary
tract infections, acute prostatitis, a
flare-up of chronic prostatitis, or acute
epididymitis or orchitis. The presence
of inguinal lymphadenopathy with or
without pain, or of a genital rash
should prompt consideration of dis-
eases like herpes, syphilis, or chan-
croid. A history of conjunctivitis, or
arthralgias and arthritis, or prior diar-
rhea suggest the possibility of Reiter's
syndrome.
Treatment
All men with urethritis (and their
partners) should receive at least a one-
week regimen of medication active
against C. trachomatis and U. urealyti-
cum.3 Those with suspected or proven
N. gonorrhoeae, or in whom the pres-
ence of N. gonorrhoeae infection has
not been investigated, should receive,
in addition, a single-dose regimen of
medication active against N. gonorr-
hoeae. Single-dose regimens include
amoxicillin 3.Og orally, ampicillin
3.5g orally, or aqueous procaine peni-
cillin G 4.8 million units intramuscu-
larly, all with probenecid 1.Og orally;
cefoxitin 2.0g intramuscularly with
l1Og probenecid orally; spectinomycin
2.0g intramuscularly; or ceftriaxone
250mg intramuscularly. Ceftriaxone is
a new cephalosporin with close to
100% efficacy against all strains of N.
gonorrhoeae at all sites of uncompli-
cated infection.8 Penicillins are con-
traindicated if penicillinase-producing
N. gonorrhoeae (PPNG) or chromoso-
mally-mediated resistant N. gonorr-
hoeae (CMRNG, those strains with de-
creased penicillin susceptibility not on
the basis of plasmid-mediated resis-
tance) are suspected because of labora-
tory documentation in the patient or
partner, treatment failure, or acquisi-
tion of the gonorrhoea in Southeast
Asia or Africa. In a recent study in
Vancouver, 1.5% of consecutive iso-
lates of N. gonorrhoeae were PPNG,
and approximately 6% were CMRNG.9
In addition, we have since recognized
isolates with high-level tetracycline re-
sistance. None of the single-dose regi-
mens are adequate for eradication of
C. trachomatis, and hence single-dose
treatment should be followed by a
weak of treatment with a tetracycline
or erythromycin.
The recommendation for treatment
of gonococcal urethritis with a combi-
nation of a single-dose regimen of
medication active against N. gonorr-
hoeae, and a multiple-dose regimen
active against C. trachomatis appears
desirable, but is contentious for some.
Canadian guidelines which should be
published in late 1987 will recommend
the combination approach. The advan-
tages of this approach are as follows.
A combined approach:
1) maintains the traditional single-
dose treatment for gonorrhea given to
the patient when the diagnosis is first
made;
2) regimen is effective against chla-
mydial infections;
3) is effective for pharyngeal N. gon-
orrhoeae infection and usually for rec-
tal N. gonorrhoeae infection; and
4) means that tetracycline-resistant N.
gonorrhoeae are likely to be covered
by the single-dose components of the
regimen.
Potentially, this combined approach
could also decrease the spread of resis-
tant isolates of N. gonorrhoeae. The
disadvantages of the combined ap-
proach are that:
1) although the approach has been
shown to be effective in treatment of
individuals with gonorrhea, it has
never been shown to be effective on a
community-wide basis;
2) approximately 80% of men and
50% of women with N. gonorrhoeae
are given a multiple-day, multiple-
dose regimen for C. trachomatis infec-
tion that they do not have;
3) the risk of secondary vulvovaginal
candidiasis in women is increased;
4) since test-of-cure cultures for N.
gonorrhoeae must be delayed for at
least three to four days after comple-
tion of the therapy, the time to test of
cure cultures is prolonged;
5) there is an unknown potential for
selection of resistant isolates of C. tra-
chomatis if compliance is poor;
6) there is an unknown potential for
masking C. trachomatis infections if
compliance is poor;
CAN. FAM. PHYSICIAN Vol. 33: AUGUST 1987
7) there is an increased likelihood of should be re-evaluated, preferably prolonged and no cause is determined,
giving tetracycline to pregnant when they have not voided for at least treatment is often a four- to six-week
women; and four hours. They should be carefully course of a regimen such as tetracy-
8) the use of tetracycline in conditions
questioned about compliance and re- cline 500mg four times daily or doxy-
where it is not needed will likely con-exposure, and examined to detect a cycline 100mg twice daily. Most men
tribute further to the rapid spread of te-
urethral discharge and to check for will improve on this regimen, but a
tracycline resistance in other genital other genital abnormalities, and to proportion will have recurring symp-
pathogens. have urethritis documented by a poly- toms. It is not known whether the pro-
The treatment of choice for non- morphonuclear leukocyte response. If, longed course of therapy improves the
gonococcal urethritis and adjunctive in men who initially received a tetracy- ultimate outcome. If there are atypical
treatment of gonorrhea is a tetracy- cline regimen, urethritis persists and features or disease remains florid, fur-
cline. Either tetracycline 500mg four no other cause is found, erythromycin ther investigations may be warranted.
times daily orally for seven days or 500mg orally four times daily for 14 Evaluation for prostatitis is usually
doxycycline 100mg twice daily orally days should be given to the patient, but negative in these men. Occasionally,
for seven days is effective against C. not the partner if both have taken their urethroscopy will show meatal warts
trachomatis. In compliant patients initial course of medication appro- or strictures. This procedure should be
these regimens produce no difference priately. performed if there is any suspicion
in outcome. Prolonging initial treat- Most men will improve again on the whatsoever of an intraurethral abnor-
ment beyond seven days does not en- second course of therapy, but approxi- mality or a history of concurrent or
hance the outcome.7 Doxycycline has mately 30% will have recurrence of past genital warts.
an advantage over tetracycline in that symptoms. At that stage, unless
it may be taken with food, and its longurethritis is florid, there are some Management
half-life may be beneficial in less com-
atypical features, or the man has been of Female Partners
pliant individuals, but doxycyline has re-exposed to a new or untreated
the distinct disadvantage of increased partner, further antimicrobial therapy As I have mentioned earlier, a major
cost. When tetracyclines are contrain- should be avoided. The following reason for diagnosis of acute urethritis
dicated or not tolerated, erythromycin issues should be discussed with the in the male is suspicion of disease in
500mg orally four times daily for male: partners; such a suspicion is an indica-
seven days, or an equivalent erythro- tion for initiation of treatment in the
1) the likelihood of long-term seque- partner without delay. The major se-
mycin regimen, is recommended. All lae such as infertility or cancer appears
of these regimens will virtually always quelae of most STDS occur in women,
to be exceedingly low even in men and this is especially true of C. tracho-
eradicate C. trachomatis, but they willwho have recurrent urethritis after both
not necessarily always eradicate U. matis and N. gonorrhoeae. Both infec-
urealyticum. therapies; tions are major causes of pelvic in-
Men with N. gonorrhoeae should 2) the risk of transmission of disease flammatory disease and are the major
have a test-of-cure culture performed to partners is exceedingly low because cause of infertility resulting from bilat-
four or more days post treatment. these men do not have ongoing C. tra- eral tubal inflammation. Female
Since C. trachomatis is virtually chomatis infection, and other patho- partners of men with urethritis should
always eradicated in men who take a gens are usually not identified or are be thoroughly evaluated for the pres-
one-week course of a tetracycline and not important causes of sequelae in ence of sexually transmitted patho-
women;
are not re-exposed to the infection, the gens. Intially, almost all should re-
need for follow-up of men who remain 3) even if no treatment were given, ceive treatment with a regimen similar
asymptomatic is arguable. If C. tra- symptoms would likely disappear over to that used in the male, even if diag-
chomatis was initially diagnosed and time in most of these men; nostic tests are negative for C. tracho-
follow-up is performed, the physician 4) if the man has an ongoing monoga- matis or N. gonorrhoeae. If pelvic in-
must be aware of two important fac- mous sexual relationship, there is no flammatory disease is suspected,
tors. First, because C. trachomatis re-need for further treatment of the therapy should be prolonged, and con-
plicates slowly and often requires partners if both have received an initial sideration should be given, in certain
course of therapy active against C. tra-
weeks to replicate to levels that current circumstances, to hospitalization of
tests will detect, a negative follow-upchomatis; the woman.3 In pregnant women or
culture taken soon after treatment does5) most of these recurrences will arise those for whom tetracyclines are con-
not exclude C. trachomatis infection. independent of resumption of sexual traindicated, erythromycin should be
Rather, tests should be performed activity, and these recurrences do not used in place of tetracycline. Although
three or more weeks after the end of mean that the partner has been "un- 500mg orally four times daily for
treatment. The second point is that a faithful"; seven days is often recommended, this
non-culture technique for detection of 6) finally, as part of a general discus- regimen is often poorly tolerated, and
C. trachomatis may have a high rate of sion with patients who have a sexually so 250mg orally four times daily for 14
false positivity (i.e., a low predictive
transmitted disease, men should be days is likely preferable. Usually the
value of a positive) in test-of-cure set-
warned that one episode of urethritis woman is not treated repeatedly if the
tings of compliant asymptomatic men. does not provide immunity to subse- male has recurrent non-gonococcal
Use of the test in these circumstances quent episodes. urethritis because in the absence of
is likely inappropriate. non-compliance or of other partners,
Men with persistent or symptomatic If the man has florid urethral dis- the woman is not a significant contrib-
recurrent non-gonococcal urethritis charge, or if symptomatic disease is utor to these recurrences, and C. tra-
CAN. FAM. PHYSICIAN Vol. 33: AUGUST 1987 1867
chomatis should have been eradicated sure to pathogens, either by avoiding al., eds. Sexually transmitted diseases.
from the couple. U. urealyticum is non-monogamous relationships or by New York: McGraw-Hill Book Company,
highly prevalent in women, is hard to use of a condom, taking care that the 1984:638- 50.
eradicate from women, and is only condom is applied prior to any genital 2. McCutchan JA. Epidemiology of ven-
rarely clinically significant to the contact. Post-exposure prophylaxis ereal urethritis: comparison of gonorrhea
and nongonococcal urethritis. Rev Inf Dis
woman; thus attempts to eradicate U. with a tetracycline has significant effi- 1984; 6:669- 88.
urealyticum in women are usually in- cacy in decreasing development of
non-gonococcal urethritis, but is not 3. Centers for Disease Control. 1985 Sex-
appropriate.6 ually transmitted diseases treatment guide-
an appropriate preventive measure. lines. MMWR 1985; 34(5):75S- 108S.
Complications Public health measures include in-
Complications of urethritis in the creased public and physician aware- 4. Schacter J. Chlamydial infections. N
Engl J Med 1978; 298:423-35, 490-5,
male are very infrequent. A very small ness of sexually transmitted diseases-; a 540-9.
proportion of these patients will de- high index of suspicion of the possibil-
velop acute epididymitis. Similarly, a ity that a sexually transmitted patho- 5. Bowie WR. Nongonococcal urethritis.
very small proportion will develop gen may be present in sexually active Urol Clin North Amer 1984; 1 1:55-64.
reactive arthritis, of which Reiter's persons, especially those who are 6. Taylor-Robinson D, McCormack WM.
syndrome is the classical example. Of young or who have more than one The genital mycoplasmas. N Engl J Med
men with gonorrhea, a small propor- partner; knowledge of the sexual pref- 1980; 302:1003-10, 1063-7.
tion will develop disseminated gono- erence and sexual activity of patients 7. Bowie WR, Alexander ER, Stimson JB,
coccal infection. Development of seen by physicians for other reasons; et al. Therapy for nongonococcal urethritis:
urethral strictures in men who have aggressive disease diagnosis; aggres- double-blind randomized comparison of
two doses and two durations of minocy-
been adequately treated is exceedingly sive treatment of partners; and in- cline. Ann Intern Med 1981; 95:306-1 1.
rare in North America and Europe. creased access to diagnostic tests for
screening purposes to try to decrease 8. Judson FN. Treatment of uncomplicated
Prevention the pool of pathogens in the commu-
gonorrhea with ceftriaxone: a review. Sex
Transm Dis 1986; 13:119-202.
Prevention of urethritis requires nity.
both a personal and a public health ef- 9. Bowie WR, Shaw CE, Chan DGW, et
fort. Since most urethritis is sexually References al. In vitro susceptibility of 400 isolates of
Neisseria gonorrhoeae in Vancouver,
transmitted, personal preventive mea- 1. Bowie WR. Urethritis in males. In: 1982-84. Can Med Assoc J 1986;
sures include decreasing risk of expo- Holmes KK, Mardh PA, Sparling PF, et 135:489- 93.

(ranitidine HCI)

Prescribing Information
Zantac Tablets (ranitidine hydrochloride)
Pharmacological Classification Histamine H -receptor antagonist
Indications and Clinical use-Zantac Tablets are indicated for the treatment of all
conditions where a controlled reduction of gastric secretion is required for the rapid relief of
pain and/or ulcer healing. These include duodenal ulcer, benign gastric ulcer and reflux
oesophagitis.
Contraindications -Zantac is contraindicated for patients known to have hypersensitivity to
the drug.
Warnings-Gastric ulcer -Treatment with a histamine H -antagonist may mask symp-
toms associated with carcinoma of the stomach and therefore may delay diagnosis of the
condition. Accordingly, where gastric ulcer is suspected the possibility of malignancy should
be excluded before therapy with Zantac Tablets is instituted.
Precautions - Use in pregnancy and nursing mothers - The safety of Zantac in the
treatment of conditions where a controlled reduction of gastric secretion is required during
pregnancy has not been established. Reproduction studies performed in rats and rabbits have
revealed no evidence of impaired fertility or harm to the foetus due to Zantac. If the
administration of Zantac is considered to be necessary, its use requires that the potential
benefits be weighed against possible hazards to the patient and to the foetus. Ranitidine is
secreted in breast milk in lactating mothers but the clinical significance of this has not been
fully evaluated.
Use in impaired renal function - Ranitidine is excreted via the kidney and in the presence
of severe renal impairment, plasma levels of ranitidine are increased and prolonged.
Accordingly, in the presence of severe renal impairment, clinicians may wish to reduce the
dose to a half of the usual dose taken twice daily.
Children -- Experience with Zantac Tablets in children is limited and such use has not been
fully evaluated in clinical studies. It has however been used successfully in children aged 8-18
years in doses up to 150 mg twice daily without adverse effect.
Interactions with other drugs -Although ranitidine has been reported to bind weakly to
cytochrome P450 in vitro, recommended doses of the drug do not inhibit the action of the
cytochrome P450-linked oxygenase in the liver. There are conflicting reports in the literature
about possible interactions between ranitidine and several drugs; the clinical significance of
these reports has not been substantiated. Amongst the drugs studied were warfarin,
diazepam, metoprolol and nifedipine.
Adverse Reactions -Headache, rash, dizziness, constipation, diarrhoea and nausea have
been reported in a very small proportion of drug-treated patients but these also occurred in
patients receiving placebo. A few patients on re-challenge with Zantac have had a recurrence
of skin rash, headache or dizziness. Some increases in serum transaminases and gamma-glu-
tamyl transpeptidase have been reported which have returned to normal either on continued
treatment or on stopping Zantac. In placebo controlled studies involving nearly 2,500
patients, there was no difference between the incidence of elevations of SGOT and/or SGPT
values in the Zantac-treated or placebo-treated groups. Rare cases of hepatitis have been
reported but have been transient and no causal relationship has been established.
Anaphylactoid reactions (anaphylaxis, urticaria, angioneurotic oedema, bronchospasm)
have been seen rarely following the parenteral and oral administration of Zantac. These
reactions have occasionally occurred after a single dose.
Decreases in white blood cell count and platelet count have occurred in a few patients.
Other haematological and renal laboratory tests have not revealed any drug related abnormalities.
No clinically significant interterence with endocrine or gonadal function has been reported.
Symptoms and Treatment of Overdosage - No particular problems are expected
following overdosage with Zantac. Symptomatic and supportive therapy should be given as
appropriate. If need be, the drug may be removed from the plasma by haemodialysis.
Dosage and Administration -Adults: Duodenal ulcer and benign gastric ulcer: 300 mg
once daily, at bedtime. It is not necessary to time the dose in relation to meals. In most cases
of duodenal ulcer and benign gastric ulcer, healing will occur in four weeks. In the small
number of patients whose ulcers may not have fully healed, these are likely to respond to a
further course of treatment.
Patients who have responded to this short term therapy, particularly those with a history
of recurrent ulcer, may usefully have extended maintenance treatment at a reduced dosage of
one 150 mg tablet at bedtime.
To help in the management of reflux oesophagitis, the recommended course of
treatment is one 150 mg tablet twice daily for up to 8 weeks.
Experience with Zantac in children is limited and it has not been fully evaluated in clinical
studies-see Precautions.
Availability - Zantac Tablets are available as white film-coated tablets engraved
ZANTAC 150 on one face and GLAXO on the other, containing 150 mg ranitidine (as the
hydrochloride), in packs of 28 and 56 tablets.
Zantac Tablets are also available as white, capsule shaped, film-coated tablets engraved
ZANTAC 300 on one face and GLAXO on the other, containing 300 mg ranitidine (as the
hydrochloride) packed in cartons containing 28 tablets.
Zantac Injection is available as 2 mL ampoules each containing 50 mg ranitidine (as the
hydrochloride) in 2 mL solution for intravenous or intramuscular administration. Packages of
10 ampoules.
References:
1. Ireland etal: The Lancet, August 4, 1984; 274-275. 2. Barbara eta!: Interniational J. of
Clinical Pharmacology, Therapy and Toxicology 1986; 24 (2) 104-107. 3. Product
Monograph. 4. Silvis et al: J. of Clinical Gastroenterology 1985; 7 (6): 424-487. 5. Gough
etal: The Lancet, September 22, 1984; 659-662.
Glaxo
Glaxo Laboratories
A Glaxo Canada Limited Company IPAAB
Toronto, Ontario Montreal, Quebec LCCPP