Prognostic Implications The prognosis of PAH is relatively poor and directly related to the severity of right-heart dysfunction.1, 2, 27 44 Together with a number of hemodynamic and noninvasive parameters, the echocardiographic indicators of right-heart impairment Table 4 ; , which include indexed right atrial area, the degree of septal shift in diastole, a high Doppler RV performance index, and the severity of PE, have been associated with unfavorable outcomes death or lung transplantation ; .6, 49 61 Doppler echocardiography has also been used to monitor the efficacy of specific therapeutic interventions.8, 11 In a double-blind, randomized, placebocontrolled trial, Galie et al10, 11 evaluated the effects ` of the oral endothelin-receptor antagonist bosentan on the echocardiographic and Doppler parameters associated with RV and LV structure and function. In comparison with the placebo group, the patients treated with bosentan for 16 weeks had less RV dilatation, a larger LV, greater stroke volume, and a higher cardiac index. There was also an improvement in RV ejection and LV early diastolic filling, and beneficial effects on the diameter of the inferior vena cava and PE.10, 11.
What is the stage of development of this medicinal product? The effects of bosentan were evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension were completed. Bosentan was not marketed anywhere worldwide for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, at the time of submission. Orphan designation of bosentan was granted in the United States for the same condition. According to Regulation EC ; No 141 2000 of 16 December 1999, the Committee for Orphan Medicinal Products COMP ; adopted on 19 December 2000 a positive opinion recommending the grant of the above-mentioned designation. Update: Bosentan Tracleer ; is authorised in the European Union as of 15 May 2002 for the treatment of pulmonary arterial hypertension PAH ; to improve exercise capacity and symptoms in patients with grade III functional status. Efficacy has been shown in: - Primary PAH, - PAH secondary to scleroderma without significant interstitial pulmonary disease. For more information please see emea .int. Opinions on orphan medicinal products designations are based on the following cumulative criteria: i ; the seriousness of the condition, ii ; the existence or not of alternative methods of diagnosis, prevention or treatment and iii ; either the rarity of the condition considered to affect not more than five in ten thousand persons in the Community ; or the insufficient return of development investments. Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.

SMC recommendation Advice: following a full submission Iloprost trometamol nebuliser solution Ventavis ; is accepted for restricted use within NHS Scotland for the treatment of patients with New York Heart Association Class III primary pulmonary hypertension as a second-line treatment where bosentan is ineffective or is not tolerated. It is an orphan product and efficacy data are very limited. Iloprost should also be restricted to use only as an alternative in patients receiving other forms of prostacyclin treatment. It is not recommended for patients who would not otherwise have received prostacyclin treatment because it is not cost effective in this situation. It is further restricted only to use by Specialists working in the Scottish Pulmonary Vascular Unit. Click here for SMC link Tayside recommendation Restricted to the Scottish Pulmonary Vascular Unit Points for consideration: Iloprost is a stable analogue of prostacyclin with a pharmokinetic profile allowing nebulised administration. Clinical trial data on iloprost are limited. Epoprostenol infusion is the only treatment for primary pulmonary hypertension to show survival benefit in clinical studies. Iloprost offers an alternative to IV epoprostenol, which has problems with central venous access and associated infections. Nebulised iloprost is not stocked by the hospital pharmacy Nausea and Vomiting of Pregnancy NVP ; versus Hyperemesis Gravidarum NVP occurs in the majority of pregnant women, is commonly limited in duration, and does not adversely affect pregnancy outcomes. Non-pharmacological treatment of NVP is preferred over pharmacological therapies and includes dietary modifications such as eating small, bland, frequent, low fat, high carbohydrate meals; avoiding emetogenic odors; avoiding iron supplements; and relaxation. Hyperemesis gravidarum, which is more rare than uncomplicated NVP, is severe, persistent, uncontrollable nausea and vomiting during pregnancy resulting in dehydration and weight loss. Electrolyte and metabolic disturbances, nutritional deficiency, and ketosis may also occur. Treatment of hyperemesis gravidarum may include non-pharmacological therapies and parenteral hydration with glucose, electrolytes, and vitamins, often in an inpatient setting. Antiemetics, corticosteroids, and sedatives are used for the acute vomiting and botox.