Riociguat: a novel new drug for treatment of pulmonary hypertension.

Riociguat is the first approved medication from the novel class of soluble guanylate cyclase (sGC) stimulators and the only agent approved for treating both chronic thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH). The novel mechanism of riociguat lies in its ability to restore the homeostatic and therapeutic effects of nitric oxide that are diminished as a result of phenotypic alterations associated with pulmonary hypertension (PH). Improvements in 6-minute walk distance (6MWD) in patients with PAH during the phase 3 PATENT-1 trial were comparable to other oral agents approved for the treatment of PAH. Improvements in 6MWD in patients with CTEPH during the phase 3 CHEST-1 trial were greater than those previously observed with other oral PAH-directed therapies. Hypotension is the dose-limiting adverse effect of riociguat and dose titration is performed gradually according to systolic blood pressure. Riociguat was tolerated at maximal doses by most patients during PATENT-1 and CHEST-1 and was well tolerated during long-term extension studies. Key factors to consider with riociguat are a patient's systolic blood pressure, drug interactions mediated by CYP1A1, CYP3A4, and P-glycoprotein, cost, and teratogenicity requiring enrollment in a Risk Evaluation and Mitigation Strategy program. Recently published guidelines recommend riociguat monotherapy as an option for treatment-naïve patients with World Health Organization Functional Class (WHO FC) II or III symptoms or as add-on therapy for patients with persistent WHO FC III or IV symptoms being treated with an ERA or inhaled prostanoid. Postmarketing experience and ongoing clinical investigations will further define the safety and role of riociguat in patients with PAH and other types of PH.

Reproducibility of the 6-minute walk test for ambulatory oxygen prescription.

BACKGROUND: Ambulatory oxygen is frequently prescribed for patients with chronic obstructive pulmonary disease (COPD) who have oxygen desaturation

Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review.

BACKGROUND: Telithromycin is a ketolide antibiotic approved by the U.S. Food and Drug Administration for acute bacterial infections causing sinusitis, bronchitis, and community-acquired pneumonia. OBJECTIVE: To describe 3 cases of severe hepatotoxicity in patients receiving telithromycin. DESIGN: Case reports. SETTING: A tertiary care medical center. PATIENTS: 3 previously healthy patients who had recently taken telithromycin and took no other prescription medications. MEASUREMENTS: Serologic, histologic, and liver function tests. RESULTS: Within a few days of receiving telithromycin, the patients presented with acute hepatitis. All had jaundice and markedly abnormal results on liver function tests. Results of viral serologic tests were negative. One patient spontaneously recovered, 1 required orthotopic liver transplantation, and 1 died. Histologic examination in the latter 2 patients showed massive hepatic necrosis. LIMITATIONS: Two patients had some history of alcohol use. The frequency of severe telithromycin-related hepatotoxicity cannot be established with case reports. CONCLUSIONS: Telithromycin can cause severe hepatotoxicity. Caution is advised in prescribing this drug pending additional postmarketing surveillance data.