tumors.26 No cases of breast cancer linked to the use of spironolactone
have been reported.27 However, caution should be used
when prescribing the medication to women with a personal or
family history of breast cancer.21,26
Drug Interactions
Drug interactions with spironolactone center around its actions
on its P-glycoprotein inhibition properties and its actions
on the kidney as a potassium sparing/sodium wasting diuretic.
As a P-glycoprotein modulator, it alters serum concentrations of
medications that rely on these proteins for bioavailability such
as digoxin.28 Any drug that has a tendency to increase serum potassium
such as heparin or trimethoprim, potassium containing
medications such as penicillin G, or repeated transfusions with
blood products containing potassium salts have been cautioned
for use when on spironolactone.29 In addition, medications that
are dosed based on serum electrolytes can reach toxic levels, such
as lithium, due to increased excretion of sodium. Medications that
depend on the serum concentration of potassium, such as warfarin,
may be altered when co-administered with spironolactone.
When taken with other anti-hypertensives, spironolactone may
cause hypotension. Caution must be taken when prescribing spironolactone
to patients with renal insufficiency.
Dosing
Initially, recommendations for spironolactone dosing for acne
were similar to the higher doses recommended for hair loss
and hirsutism at 150- 200 mg/day.30 Current data suggests
that doses of 50mg-100mg/day result in significant improvement
comparable to results seen in higher doses; in a recent
study, 66% of patients dosed at 50-100mg/day of spironolactone
showed marked improvement to complete resolution of
acne lesions when compared to the previous studies of higher
doses.16 Anti-androgen activity may be augmented without
increasing the dose of spironolactone by adding Ethinyl estradiol/
drospirenone (EE/DRSP). Drospirenone is a derivative of 17
alpha spironolactone, which acts as an antagonist at androgen
and aldosterone sites. The equivalent to approximately 20-
25mg of spironolactone is 3mg of drospirenone.20,31
Drug Monitoring
Spironolactone does not appear to cause clinically significant
elevations in serum potassium levels in healthy patients at acne
doses (50-100mg). A study of 35 patients dosed at 100mg/day
were monitored for 3 months, serum potassium levels showed
no significant deviation from normal range during treatment.32
A recent study evaluating low dose spironolactone (50-100mg)
monitored potassium levels in 73 patients, and 13.7% showed
mild hyperkalemia ranging from 4.8-5.3; however, these mild
elevations were not considered to be clinically significant.16
A study evaluating serum potassium levels in patients on spironolactone
and EE/DRSP showed post therapy levels to be on
average 4.35 with a range of 3.5-5.3.20
DISCUSSION
We conducted a retrospective chart review on 41 female adult
patients with cyclical acne. Data was collected on 58 patients,
however 17 were lost to follow up. The 41 female patients in
this study were age 19-57. They were examined over the course
of 2 to 102 months while taking 50 to 200mg of spironolactone
and topical tretinoin 0.025% cream or adapalene 0.1% cream.
The majority of patients had been on their topical retinoid prior
to initiation of spironolactone treatment. All patients were prescribed
50-100mg of spironolactone with one patient with acne
and alopecia on 200mg daily. All were diagnosed with acne
rated mild to severe, prior to treatment, and were started on
an initial dose of 50mg po daily. If significant improvement was
not seen within the first 3-6 months, the dose was either held or
increased in 25mg increments every 3 months. Eleven patients
were increased to 75mg, and four patients were increased from
75mg to 100mg. The majority of patients were concurrently
treated with tretinoin 0.025% or adapalene 0.1% cream and instructed
to apply a thin layer to the face at bedtime. Patients
on oral and topical antibiotics, as well as patients on photodynamic
therapy were excluded from our study. The response to
treatment was rated on a 0-4 scale with 0 being no response
and 4 corresponding to clear skin. As shown in graph 1, only
one patient (2.4%) had no response to treatment. This patient
was only on 50mg po daily and only treated for 2 months. Only
5 (12.2%) patients had minimal response to treatment and 9
(22.0%), 12 (29.3%), and 14 (34.1%) had a good, excellent or
clear response respectively. The study showed that 26 (63.4%)
of women on treatment with spironolactone and topical retinoids
had an excellent or clear outcome, and 35 (85.4%) were
considered to have a good, excellent, or clear response. As the
majority of patients in our study had been on retinoids prior to
the initiation of spironolactone with minimal response, the addition
of spironolactone to topical retinoid treatment suggests
a superior response to retinoids alone in clearance of female
adult cyclical acne.
In our review, there were minimal side effects noted as a result
of spironolactone therapy. There was no change in tolerance to
topical retinoids in any of the patients as a result of spironolactone
treatment. Lightheadedness was reported in one patient
(2.4%) on a 50 mg dose that subsided with continuation of treatment.
Irregular periods were reported in two patients (4.9%),
which occurred with dosages of 200 mg and 50 mg. Orthostatic
hypotension was recorded in one patient (2.4%) taking a 50 mg
dose. Only one flare (2.4%) was reported in a patient taking 50
mg. There were no severe adverse events in the women on
treatment. None of our patients were elderly or had cardiac or
renal abnormalities warranting electively following laboratory
studies. There were no reports of malignancy in the patients
taking spironolactone. This coincides with the lack of reported
human malignancy cases to the FDA in the over 50 years spironolactone
has been approved for medical use.
