SIPHENE®: White uncoated scored tablets each
containing 50 mg of Clomiphene Citrate IP.
SIPHENE® -100: White uncoated tablets each containing
100 mg of Clomiphene Citrate IP.
SIPHENE® -M: White uncoated tablets containing
25 mg of Clomiphene Citrate IP.
SIPHENE® is indicated for the treatment of
anovulation and infertility due to impaired hypothalamic pituitary
The best response to SIPHENE® is generally obtained in
women with evidence of follicular function and endogenous
oestrogen production. These patients lack adequate cyclic
stimulation of pituitary gonadotrophic function. SIPHENE®
may also be of benefit in patients with limited oestrogen
SIPHENE® 100 is indicated for patients requiring higher
doses of 100 mg, generally after the initial treatment
of 50 mg in earlier cycles.
SIPHENE® -M is indicated for the treatment
of male infertility. Endogenous gonadotrophin stimulation
is achieved with the administration of SIPHENE SIPHENE®
-M to subfertile male with oligospermia and asthenospermia
showing normal or low gonadotrophin levels and testes biopsy
showing mild germinal cell hypoplasia.
DOSAGE AND ADMINISTRATION
The recommended dose for the first treatment course of SIPHENE®
is 5Omg (one SIPHENE® tablet) daily for five
consecutive days starting within the first five days of spontaneous
or induced menstrual bleeding. The commencement date of SIPHENE®
therapy is arbitrary in women who have not experienced recent
uterine bleedings. Response to SIPHENE® , suggestive
of ovulation is indicated by a biphasic basal body temperature,
a mid-cycle rise in LH output, an increase in serum progesterone
during the presumptive mid-luteal phase or by menstrual bleeding
in an amenorrhoeic patient. If ovulation occurs, but pregnancy
does not result, the same dose of SIPHENE®
should be repeated in the next treatment course. If presumptive
evidence of ovulation is not followed by menstrual bleeding,
the possibility of pregnancy should be considered and excluded
before SIPHENE® treatment is restarted.
In the absence of ovulation, the daily dose of SIPHENE®
may be increased by increments of 50 mg each successive month
to a maximum of 200 mg given as a single daily dose for five
days. This dose level of SIPHENE® should not
be exceeded. If ovulation does not occur, a single i.m./s.c.
injection of up to 10,000 I.U. Human Chorionic Gonadotrophin
(HCG PROFASI® ) may be given 7 to 10 days after
the last SIPHENE® tablet, in order to reinforce
the LH surge. If the patient wishes to conceive, coitus particularly
around the expected time of ovulation is advised. A maximum
of six apparently ovulatory treatment courses with the lowest
effective dose of SIPHENE® is suggested. If
at this stage pregnancy has not occurred, then patients should
be reinvestigated and sequential METRODIN®
HP / PROFASI® therapy may be considered.
One tablet of SIPHENE® -M per day for 25
days continued with a rest period of 5 days for 6 to 9 months
or till conception occurs.
CONTRA-INDICATIONS, WARNINGS ETC
SIPHENE® should not be administered, to
patients with active liver disease or with hereditary defect
in bilirubin metabolism. SIPHENE® therapy is
precluded when an effective response cannot be obtained e.g.
ovarian dysgenesis or premature menopause. Appropriate treatment
should first be given for hypothyroidism, adrenocortical deficiency,
hyperprolactinaemia or pituitary tumor. Other possible causes
or infertility in either partner should first be excluded.
Patients with very low baseline levels of endogenous gonadotrophins
and oestrogens are usually less responsive to SIPHENE®
treatment and consideration should be given to gonadotrophin
METRODIN® HP / PROFASI® therapy.
Patients receiving SIPHENE® should be instructed
to report any abdominal discomfort immediately and a pelvic
examination should be performed to determine whether ovarian
enlargement has occurred or not. While the incidence of clinically
significant hyperstimulation is low with the recommended SlPHENE
dosage scheme, the presence of excessive ovarian enlargement
may require the dosage scheme to be modified. Rare occurrences
of lutein cyst rupture with intraperitoneal haemorrhage have
been reported. Vasomotor symptoms resembling "hot flushes"
may occur with SIPHENE®. Other side effects
of SIPHENE® are generally mild, not dose-related
and readily reversible on drug withdrawal. These include vomiting,
breast discomfort, skin reactions (dermatitis or urticaria),
dizziness and hair loss. SIPHENE® should be
withdrawn if visual disturbances occur e.g. blurring, spots
or flashes (in rare cases scotomata).
The multiple pregnancy rate is approximately 8%, twins representing
90% of this figure.
Although a higher abortion rate than in a normal population
has been reported, this is comparable with that in women with
other fertility problems. There is no evidence that this is
Care should be taken to avoid administration of SIPHENE®
if pregnancy is suspected. Although SIPHENE®
has been shown to be embryotoxic in animals at high doses,
there is no evidence to suggest that it increases the incidence
of congenital malformations in humans at therapeutic levels.
The incidence of congenital malformations following SIPHENE®
treatment is similar to that observed in women with other
There is evidence that some women ovulate spontaneously for
some cycles after cessation of SIPHENE® treatment.
There is no experience of acute poisoning with SIPHENE®
Should be stored below 25° C and protected from light
is packed in a box containing ten strips of 5 tablets each.
SIPHENE® -100 is packed in a box containing
ten strips of 5 tablets each.
SIPHENE® -M is packed in a box containing ten
strips of 10 tablets each.
The mode of action of SIPHENE®
at the recommended dose appears to be through competition
for available oestrogen receptor sites in the hypothalamus.
Oestrogen is thus displaced from sites which were responsible
for the suppression of gonadotrophin releasing hormone,
pituitary sacretion of FSH-and LH follows, which initiates
the normal menstrual cycle.