Tracleer and PPH News FDA Safety Labeling Changes: Depo-Provera, Tracleer, Tabloid Yael Waknine
Feb. 2, 2005 — The U.S. Food and Drug Administration (FDA) approved revisions to drug safety labeling last November, advising healthcare professionals of the following changes: use of medroxyprogesterone acetate (MPA) injection is contraindicated in patients with significant liver disease, and use of MPA injection may result in significant bone loss that increases with duration of use and may not be completely reversible; bosentan may reduce the efficacy of concurrently administered hormonal contraceptives; long-term use of thioguanine is not recommended due to a high risk of hepatotoxicity. Medroxyprogesterone Acetate (Depo-Provera) Linked to Bone Loss On Nov. 17, the FDA approved revisions to the safety labeling for medroxyprogesterone acetate (MPA) injectable suspension (Depo-Provera Contraceptive Injection, made by Pfizer, Inc.), advising of contraindications and warnings associated with its use. Use of MPA is contraindicated in patients with significant liver disease. In addition, the FDA warns that use of MPA may result in a significant loss of bone mineral density (BMD) that increases with duration of use and may not be completely reversible. The FDA notes that it is unknown whether use during adolescence or early adulthood (a critical period of bone accretion) will result in reduced peak bone mass and increased risk of future osteoporotic fracture. Other contraceptive options should be considered in women with risk factors for osteoporosis because the use of MPA may pose additional risk in those with a history of metabolic bone disease; chronic alcohol and/or tobacco use; anorexia nervosa; chronic use of anticonvulsants, corticosteroids, or other drugs that may reduce bone mass; or a strong family history of osteoporosis. Use of MPA should exceed two years' duration only in those women for whom other methods of birth control are inadequate. The FDA recommends that BMD be evaluated in long-term users (> two years) and that age and skeletal maturity be considered when interpreting results in adolescents. An adequate intake of calcium and vitamin D is recommended in all women using MPA, although no studies have addressed the effect of such intake on reducing bone loss in these patients. The FDA advises that factors such as BMD loss in women of all ages, the effect on peak bone mass in adolescents, and decreases in BMD due to pregnancy and/or lactation be considered in a risk-benefit analysis prior to long-term use of MPA. Particular caution is recommended in prescribing for young adults and adolescents. MPA is indicated for the prevention of pregnancy in women of child-bearing potential. Bosentan (Tracleer) Decreases Efficacy of Hormonal Contraceptives On Nov. 24, the FDA approved revisions to the safety labeling for bosentan (Tracleer tablets, made by Actelion, Inc.), warning that concurrent use of transdermal hormonal contraceptives (in addition to oral, injectable, and implantable formulations) may decrease the contraceptives' efficacy and that they should not be relied on as a sole means of contraception. The labeling has been updated with data from an interaction study showing that concurrent administration of bosentan and the oral hormonal contraceptive Ortho-Novum (made by Ortho-McNeil Pharmaceuticals, Inc.) resulted in mean decreases of norethindrone (14%) and ethinyl estradiol (31%) levels, with individual exposures decreasing by as much as 56% and 66%, respectively. The FDA recommends that women practice additional methods of contraception and not rely on hormonal contraception alone when taking bosentan. Bosentan is indicated for the treatment of pulmonary arterial hypertension in patients with World Health Organization class III or IV symptoms to improve exercise ability and decrease the rate of clinical worsening. Thioguanine (Tabloid) Not for Long-term Use Due to High Risk of Hepatotoxicity On Nov. 15, the FDA approved revisions to the safety labeling for thioguanine (Tabloid tablets, made by GlaxoSmithKline), warning that thioguanine is not recommended for maintenance or long-term continuous therapy due to a high risk of hepatotoxicity associated with vascular endothelial damage. Hepatotoxicity has been observed in a high proportion of pediatric patients (particularly in boys) receiving thioguanine as part of maintenance therapy for acute lymphoblastic leukemia and other conditions. The toxicity presents clinically as a syndrome of hepatic veno-occlusive disease (hyperbilirubinemia, tender hepatomegaly, weight gain due to fluid retention, and ascites) or with signs of portal hypertension (splenomegaly, thrombocytopenia, and esophageal varices). Histopathologic features include hepatoportal sclerosis, nodular regenerative hyperplasia, peliosis hepatis, and periportal fibrosis. Patients receiving thioguanine should be carefully monitored for early indications of portal hypertension, such as thrombocytopenia out of proportion with neutropenia and splenomegaly. Elevated liver enzyme levels have been associated with liver toxicity but do not always occur. The FDA recommends that thioguanine therapy be discontinued in patients with evidence of hepatotoxicity; signs and symptoms of the condition may reverse upon withdrawal. Thioguanine is indicated for remission induction and consolidation treatment of acute nonlymphocytic leukemias. Reviewed by Gary D. Vogin, MD Related Links
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Transition From Epoprostenol and Treprostinil to the Oral Endothelin Receptor Antagonist Bosentan in Patients With Pulmonary Hypertension
Online CME
Acute Myeloid Leukemia: Review of Current Treatment Strategies
News
Depo-Provera May Be Associated With Significant Bone Loss
FDA Approvals: Eloxatin, Orphan Drugs for Leukemia and Renal Cell Carcinoma, and More External Links
Medscape News CME: Depot Medroxyprogesterone May Cause Loss of Bone Mineral Density ---------------------------------------------------- Yael Waknine is a freelance writer for Medscape.
Medscape Medical News is edited by Deborah Flapan, assistant managing editor of news at Medscape. Send press releases and comments to news@webmd.net.
Life goes on despite disease
Lorenzo Washington can do almost everything a typical 11-year-old can do.
Lorenzo Washington, 11, suffers from a life-threatening illness, but he doesn't let it keep him from living.
By Melissa J. Brachfeld
As Lorenzo Washington rides his bike up and down the street in front of his Fort Washington home with his friends, he looks to all the world like a normal, healthy 11-year-old boy.
However, upon closer examination, a clear, plastic tube wraps around his neck, disappearing underneath his white T-shirt. This is because Lorenzo, a fifth grader at Apple Grove Elementary, suffers from a little-known, life threatening lung disease known as Pulmonary Arterial Hypertension. The condition affects the pulmonary arteries connecting the right side of the heart to the lungs, leading to extra stress on the heart and lungs, which could result in heart failure if not treated. It is estimated to afflict an estimated 100,000 to 200,000 people worldwide and is sometimes misdiagnosed as asthma, allergies or a variety of other conditions.
The plastic tube Lorenzo wears supplies a medicine called epoprostenol to the young boy's heart 24 hours a day and he also receives supplemental oxygen at night. But when chatting with the fifth grader, he would rather talk about his favorite rapper T.I. or how he wants an iPod for his 12th birthday on June 30.
As Peter Washington, Lorenzo's father, settles himself into a living room chair, he speaks of how he considers his youngest son a born fighter. He says that Lorenzo has been since birth, having been born without a gallbladder and then being diagnosed with PAH at 7 years old.
But thanks to the combination of a carefully monitored diet and his medications, Peter Washington said Lorenzo is able to lead the life typical of an 11-year-old boy. When Lorenzo is not playing practical jokes on his sister Teresa, 19, or playing basketball with his brother Peter, Jr., 14, he enjoys riding his bike, skateboarding or challenging his friends to video games. Lorenzo says he would like to be a professional basketball player for his favorite team the Houston Rockets, but he and his parents know that is not in the cards for him.
"The one thing we stress to him is not to let it [the PAH] limit what he can do," Peter Washington says. "We say he can't play pro ball, but what's to stop him from coaching or owning a team."
It is this sort of family attitude that keeps Lorenzo grounded. Peter Washington says Lorenzo is not allowed to let his conditions act as a crutch. He is expected to do the same chores as his brother and sister and if he steps out of line, he is punished like any other child.
"I don't want this disease to cripple his mind," Peter Washington says. "It may slow his body some, but his mind is still as sharp as a tack."
Having been mostly quiet while his father talks, Lorenzo chimes in to add that if someone were to tell him he was incapable of a task, they would be dead wrong.
"I would say to them, 'I can do it,'" he says. "There's nothing I can't do."
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