Oxandrolone for hereditary angioedema

Last updated March 4, 2024, by Margarida Maia, PhD
Fact-checked by Joana Carvalho, PhD

 

What is oxandrolone for hereditary angioedema?

Oxandrolone, now discontinued in the U.S., was an oral synthetic (lab-made) anabolic steroid that was used off-label to prevent swelling attacks in hereditary angioedema (HAE). An off-label medication is one used to treat a condition different from that for which it was approved.

The drug’s regulatory approval has since been withdrawn in the U.S., meaning it can no longer be sold in any form.

Brand names and formulations

Oxandrolone was sold in the form of oral tablets under the brand name Oxandrin by Savient Pharmaceuticals. The medication also was available as generics.

The U.S. Food and Drug Administration (FDA) initially approved Oxandrin in July 1964. It was indicated for use as an add-on treatment to promote weight gain after weight loss following extensive surgery, chronic infection, or severe trauma, and for some people who failed to gain or to maintain normal weight for unknown reasons. The therapy also was indicated to offset protein breakdown associated with prolonged use of corticosteroids, and to relieve bone pain frequently accompanying osteoporosis, a disease that causes bones to become brittle and more prone to fracture.

However, multiple safety warnings and precautions were linked to oxandrolone tablets, as per the product’s label.

In March 2019, Gemini Laboratories, which held the rights to Oxandrin at that time, requested the FDA withdraw its approval of the therapy’s new drug application on the grounds that the medication was no longer on the market. In June 2023, the FDA withdrew approval of Oxandrin. Four abbreviated new drug applications for generic versions of the therapy also were withdrawn by the regulatory agency.

Therapy snapshot

Treatment name:	Oxandrolone
Administration:	Oral tablets
Clinical testing:	Not tested in clinical trials for hereditary angioedema; formerly used off-label, now discontinued

 

How does oxandrolone work in hereditary angioedema?

Angioedema occurs when blood vessels leak fluid into the deep layers of the skin or the mucous membranes lining the surface of internal organs and cavities in the body, resulting in repeated attacks of swelling.

In most cases of HAE, this is due to mutations in the gene that provides instructions for making a protein called C1 inhibitor, which normally stops the activity of an enzyme called kallikrein. When C1 inhibitor protein is faulty or missing, kallikrein becomes overactive and triggers the excessive production and release of another signaling molecule called bradykinin. Too much bradykinin, in turn, causes blood vessels to become more permeable and leak fluid into nearby tissues, leading to swelling.

Oxandrolone is an anabolic steroid that works in a way similar to testosterone, the main sex hormone in men. Like other anabolic steroids, oxandrolone is thought to increase the production of C1 inhibitor in the liver. In so doing, it’s expected to keep kallikrein’s activity under control, thereby helping to prevent swelling attacks.

How was oxandrolone administered in hereditary angioedema?

Oxandrolone was available as oral tablets containing 2.5 or 10 milligrams (mg) of the anabolic steroid. It was used off-label in HAE to prevent swelling attacks, given at a dose of 10 mg or less per day in adults, and at a dose of 0.1 mg per kilogram of body weight or less in children.

It also was recommended that patients, particularly young children, be placed on the lowest possible effective dose, given the therapy’s potential virilization effects.

Oxandrolone in hereditary angioedema clinical trials

No clinical trials were done to assess the effects of oxandrolone in people with HAE. However, a number of case reports, including some in the early 2000s, indicated the therapy could successfully prevent swelling attacks and raise C1 inhibitor levels in children and adolescents with HAE.

The medication was suggested to possibly be one of the safer anabolic steroids for use in pediatric patients due to its milder side effects and androgenic potential. But at least one report, involving the therapy’s use in a 6-year-old boy with angioedema, described the occurrence of virilization side effects at a dose of 0.1 mg/kg.

Common side effects of oxandrolone

Common side effects reported with oxandrolone included:

• cholestasis, or slowing or stalling of bile flow from the liver
• jaundice, which is a yellowing of the skin and mucous membranes
• frequent or persistent erections in male patients
• hoarseness, facial hair, and menstrual changes in female patients
• nausea and vomiting
• changes in skin color
• ankle swelling.

Liver problems

The use of an anabolic steroid like oxandrolone can lead to peliosis hepatis, which occurs when tissue in the liver, and sometimes the spleen, is replaced with cysts, or small sacs, filled with blood. Peliosis hepatis is usually asymptomatic, so it may go unrecognized until any blood-filled cysts rupture, causing bleeding into the abdominal cavity, or unless the liver starts failing. Blood-filled cysts normally disappear once the anabolic steroid is discontinued.

There also have been reports of liver tumors with the use of such steroid medications. Most times, these tumors are benign and their growth depends on the presence of male hormones. Stopping treatment with the anabolic steroid can cause the tumors to shrink or stop growing. However, some liver tumors can be cancerous and grow silently until life-threatening bleeding into the abdominal cavity occurs.

Even low doses of an anabolic steroid can lead to jaundice or cholestatic hepatitis, which is inflammation of the liver caused by a slowed or blocked flow of bile. If the liver stops working well, patients should be monitored closely and the anabolic steroid discontinued. If symptoms are mild, doses of the anabolic steroid could be lowered instead.

Due to the potential of liver toxicity associated with the use of anabolic steroids, it’s also recommended that liver function tests be performed periodically.

Changes in blood cholesterol

The use of an anabolic steroid can cause levels of high-density lipoprotein — so-called good cholesterol — to decrease and those of low-density lipoprotein, known as bad cholesterol, to increase. That, in turn, may increase the risk of heart disease. For this reason, it was recommended that blood cholesterol levels be periodically checked in patients given oxandrolone. Additionally, it was recommended that the therapy be used with caution in individuals with a history of cardiovascular disorders, or at risk of developing them.

Short stature

In youth, the use of an anabolic steroid may make bones mature faster but the children not grow taller, resulting in short stature as adults. The younger the child, the greater the chance of him or her not growing to full height. Children taking such medications should have their wrists and hands monitored every six months for bone age to watch for changes in bone maturation; these specific bones can indicate growth.

Use with anticoagulants

Oxandrolone might increase sensitivity to blood thinners, known as anticoagulants. Thus, anticoagulant dosing may have needed to be reduced to prevent bleeding in patients given the anabolic steroid.

Use in pregnancy and breastfeeding

Oxandrolone could cause birth defects in a fetus, so it was contraindicated in women who were or might become pregnant. It was not known whether oxandrolone could pass into breast milk, so women who were breastfeeding were advised to consult their doctor before taking oxandrolone.

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