sildenafil-citrate and Hemoglobinopathies

New approaches to the treatment of pulmonary arterial hypertension (PH) have increased symptomatic relief and prolonged survival. PH is a common sequela of the hemoglobinopathies, but the use of standard oral treatment options is limited because of toxicity and poor effectiveness. Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5), which promotes selective smooth muscle relaxation in lung vasculature and has been used successfully in the treatment of PH. Hemoglobinopathic patients suffering from severe PH who were treated with sildenafil citrate (50 mg b.i.d.) for periods ranging from 4 to 48 months showed a significant decrease in pulmonary pressure and improvement in exercise capacity and functional class. No significant adverse events were reported. These data, described in a small group of patients, indicate that sildenafil citrate is effective in the treatment of PH in hemoglobinopathies and is well tolerated long-term at a daily dose of 100 mg.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Evaluation; Exercise Tolerance; Hemoglobinopathies; Humans; Hypertension, Pulmonary; Hypoxia; Muscle, Smooth, Vascular; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Topics: Hemoglobinopathies; Humans; Hypertension, Pulmonary; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Adult; Hemoglobinopathies; Humans; Hypertension, Pulmonary; Piperazines; Prognosis; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

During the last decade new approaches to the treatment of pulmonary arterial hypertension (PH) have increased symptomatic relief and prolonged survival. PH is a common sequel of the hemoglobinopathies, thalassemia and sickle cell anemia, but the use of standard oral treatment options, such as calcium channel blockers, endothelin receptor antagonists, and long-term anticoagulation therapy, is limited because of toxicity and poor effectiveness. Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5) which promotes selective smooth muscle relaxation in lung vasculature and has been utilized successfully in the treatment of PH. The primary objective of this study was to evaluate the efficacy of sildenafil treatment in the control of PH in patients with hemoglobinopathies.. In this study patients with hemoglobinopathies (thalassemia intermedia n=4; thalassemia major n=2; sickle thalassemia n=1) suffering from severe PH were treated with sildenafil citrate (50 mg b.i.d.) for periods ranging from 4 to 48 months.. A significant decrease in pulmonary pressure and improvement in exercise capacity and functional class were observed in all patients. No significant adverse events were reported.. These data, in a small group of patients, indicate that sildenafil citrate is effective in the treatment of PH in hemoglobinopathies that cannot be treated with alternative oral drugs and is well tolerated long-term at a daily dose of 100 mg, though studies including more patients may uncover toxicities and limitations of efficacy.

Topics: Administration, Oral; Adult; Blood Transfusion; Clinical Trials as Topic; Dose-Response Relationship, Drug; Echocardiography, Doppler; Female; Hemoglobinopathies; Humans; Hypertension, Pulmonary; Male; Piperazines; Priapism; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Vasodilator Agents