MEDICAL
ALTERNATIVES TO ORAL BROMOCRIPTINE IN HYPERPROLACTINEMIA
Oral bromocriptine
in the treatment of hyperprolactinemia is plagued with the side
effects of nausea and vomiting which are quite troublesome, and
sometimes responsible for patient non-compliance. Hence alternatives
have been adopted so as to ensure adequate medical treatment in
a case of hyperprolactinemia. These are administering bromocriptine
as a depot preparation or vaginally, and use of other dopamine
agonists.
Injectable
bromocriptine
This is given as a singly monthly injection of 50 mg. It is as
effective as oral bromocriptine and, with similar but milder and
transient side effects. However it ensures patient compliance.
It is marketed as long acting repetitive (LAR) bromocriptine.
Maximum dose is 100 mg/month.
Vaginal
route
At BACC this forms the first line of therapy with bromocriptine,
for the simple reason that it is better tolerated due to the absence
of gastrointestinal side effects. It is as effective as the oral
route. The dose is 2.5 - 5 mg twice daily i.e. the tablet is inserted
into the vagina.
Other dopamine agonists
These are used for patients who do not tolerate bromocriptine
or are resistant to it. The drugs decrease prolactin levels by
binding more effectively with dopamine D2 receptors. They include
cabergoline, pergolide, quinagolide and hydergine. They have long
half-life's.
Cabergoline
Cabergoline has a high affinity and specificity for the dopamine
D2 receptor. It is long acting, potent and lowers prolactin levels
rapidly. Studies have shown that after a single dose, low levels
of prolactin were evident at the end of 14 days in patients with
hyperprolactinemia and 21 days in puerperal women.
Superiority over bromocriptine was established through the following
data.
The starting
dose is 0.5 mg/week. It is increased at monthly intervals in increments
of 0.5 mg/week. The optimal therapeutic dose is usually 1 mg weekly;
range is 0.25 - 2 mg weekly. A maximum of 4.5 mg weekly has been
used. Serum prolactin levels are monitored monthly. Once prolactin
secretion is adequately controlled, the dose of cabergoline could
often be significantly decreased, with reductions in cost to the
patient.
However the
teratogenecity of cabergoline needs to be kept in mind. Although
not extensively studied in humans, one study showed the presence
of congenital abnormalities in 10 out of 199 cabergoline-associated
pregnancies. Although these abnormalities did not fall into a
set pattern, it means that cabergoline cannot be considered as
a first choice in infertility cases. Cabergoline has its use in
the prevention of puerperal lactation. A single dose of cabergoline
1.0mg is effective. Data suggest cabergoline 0.25mg twice daily
for 2 days also to be effective in suppressing established puerperal
lactation. The incidence of rebound lactation in the third postpartum
week was far less compared to bromocriptine. It also mitigates
the increased risk of serious thromboembolic events associated
with bromocriptine.
Cabergoline is marketed in 40 countries.
Pergolide
This is a synthetic ergolide where the peptide side chain of bromocriptine
is absent. It is given orally. The initial dose is 25 mcg once
daily and then increased slowly after 3 days to 50 mcg, in the
absence of adverse effects. The daily maximum dose should not
exceed 500 mcg. It is as effective as bromocriptine. Side effects
include nausea, vasodilatation and flu like syndrome.
Quinagolide
This is not an ergot derivative. The dose ranges from 50 mcg -
75 mcg per day. Nausea is the most common side effect.
Hydergine
The dose is 6 - 12 mg per day in divided doses. It reduces prolactin
levels but only if the levels are less than 100 ng/ml. It is well
tolerated and no side effects have been reported.
