However, paradoxically, a case report of severe fluoxymesterone-induced gynecomastia exists, and gynecomastia associated with fluoxymesterone has also been reported in other publications, although this may not be due to estrogenic activity. Fluoxymesterone is thought to possess little or no progestogenic activity.Because of the presence of its 17α-methyl group, the metabolism of fluoxymesterone is impeded, resulting in it being orally active, although also hepatotoxic. 11β-HSD inhibition
Fluoxymesterone has been found to act as a potent inhibitor of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) (IC50 = 60–630 nM), with a potency comparable to that of the 11β-HSD2 inhibitor glycyrrhetinic acid. This action of fluoxymesterone is unique among AAS and is likely related to its 11β-hydroxyl group. 11β-HSD2 is responsible for the inactivation of the glucocorticoids cortisol and corticosterone (into cortisone and 11-dehydrocorticosterone, respectively). Inhibition of 11β-HSD2 by fluoxymesterone may result in mineralocorticoid receptor overactivation and associated side effects such as hypertension and fluid retention, and has been hypothesized to be involved in the cardiovascular and other adverse effects of fluoxymesterone. Glucocorticoid activity
Unlike other AAS, fluoxymesterone has structural features in common with corticosteroids, including its C9α fluoro and C11β hydroxyl groups. In relation to this, it has weak (micromolar) but potentially clinically significant affinity for the glucocorticoid receptor. Pharmacokinetics
Fluoxymesterone has approximately 80% oral bioavailability, unlike testosterone, as the C17α methyl group of fluoxymesterone inhibits first-pass metabolism. It has very low affinity for human serum sex hormone-binding globulin (SHBG), less than 5% of that of testosterone and less than 1% of that of DHT.
Contraindications
unstable angina; within 6 months of myocardial infarction; decompensated cardiac failure (unless under close medical supervision); severe arrhythmias; congenital or acquired heart-valve defects; within 3 months of cerebrovascular events; pulmonary veno-occlusive disease; conditions which increase risk of bleeding. Common side effects
In clinical studies, common adverse reactions due to inhaled iloprost included: vasodilation (flushing, 27%), cough (39%), headache (30%), flu syndrome (14%), nausea (13%), neck spasms (12%), hypotension (11%), insomnia (8%), and fainting (syncope) (8%); other serious adverse events reported with the use of Ventavis included congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, swelling of the limbs (especially around the ankles and feet), and kidney failure.Serious adverse events reported with the use of inhaled iloprost include congestive heart failure, chest pain, supraventricular tachycardia, shortness of breath, peripheral edema, and kidney failure. Warnings
Iloprost as Ventavis is intended for inhalation administration only via the I-Neb AAD or Prodose AAD Systems, pulmonary drug delivery devices. It has not been studied with any other nebulizers. Vital signs should be monitored while initiating inhaled iloprost therapy. Dose adjustments or a change in therapy should be considered if exertional syncope occurs. Inhaled iloprost should not be initiated in patients with systolic blood pressure lower than 85 mm Hg. Iloprost should be stopped immediately if signs of pulmonary edema occur. This may be a sign of pulmonary venous hypertension. Iloprost has not been evaluated in patients with chronic obstructive pulmonary disease (COPD), severe asthma, or with acute pulmonary infections.