Patient with scleroderma, referral to investigate pulmonary arterial hypertension*

Adapted from information provided by physicians at PH centers

Michelle T   47-year-old female   Married with 2 children   Employed (laboratory technician)	Weight: 181 lb   Nonsmoker, rare alcohol use, no IV drug abuse, no anorexigen use, no HIV risk factors
History   Diagnosed with systemic sclerosis 5 years ago   Referred by her rheumatologist —  Matted telangiectasia —  Raynaud's phenomenon —  Gastroesophageal reflux disease —  Dry, cracking skin on digits but without true ulcerations	Symptoms   Some dyspnea on exertion: —  Climbing 2 or 3 flights of stairs —  Walking up inclines —  Carrying heavy packages   Some fatigue after "hard day" at work   Occasional palpitations with exertion
Reasons to investigate PAH*   Long-standing limited SSc   Progressive exertional dyspnea and fatigue	Physical examination   Vital signs: BP 141/88 mm Hg; HR 83 bpm; RR 16 bpm; SaO2 98% (room air)   CV: RRR, S1S2 no murmur, rub, or gallop   Lungs: clear without rales, rhonchi, or wheeze   Neck: no JVD   Extremities: —  Multiple matted telangiectasia on face, arms, chest —  No clubbing, cyanosis, or edema
Chest x-ray findings   Normal pulmonary arteries
Laboratory findings   CBC unremarkable —  Hgb within normal limits —  Hct within normal limits —  WBC within normal limits   Chem-7 —  Cr: 0.6 mg/dL (normal 0.8 to 1.4 mg/dL1) —  BUN within normal limits —  Na+ within normal limits —  K+ within normal limits —  Cl– within normal limits   LFTs —  ALT: 14 IU/L (normal range varies)2 —  AST: 25 IU/L (normal 10 to 34 IU/L)3   ESR: 17 mm/hr (normal <30 mm/hr)4   HCO3-: 24 mEq/L (normal 20 to 29 mEq/L)5   ANA positive, 1:256   Scl-70 negative	Other findings   PFTs —  FEV1: 94% predicted —  LC: 80% predicted —  FVC: 85% predicted —  DLCO: 54% predicted —  FEV1/FVC: 0.85 —  % FVC/% DLCO: 1.6   6-minute walk test —  470 m —  Borg dyspnea index: 1   V/Q scan: low probability of thromboembolic disease   HRCT chest: normal without ILD or PD
Echocardiogram findings   Rest echo —  Significant dilation; PAP estimate of 40 mm Hg   Exercise echo —  RV strain with a mildly decreased RVEF   ECG: normal sinus rhythm without RAE, RVH, or ischemic changes with exercise   BP —  Rest: 120/70 mm Hg —  Exercise: 160/80 mm Hg   PAP —  Rest: 37 mm Hg —  Exercise: 44 mm Hg

*INDICATION
Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital systemic-to-pulmonary shunts (18%).

Considerations for use
Patients with WHO class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these benefits are sufficient to offset the risk of liver injury in WHO class II patients, which may preclude future use as their disease progresses.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Tracleer is contraindicated with cyclosporine A, glyburide, in females who are or may become pregnant, or in patients who are hypersensitive to bosentan or any component of Tracleer.

WARNINGS AND PRECAUTIONS
In clinical trials, Tracleer caused ALT/AST elevations (>3 × ULN) in 11% of patients accompanied by elevated bilirubin in a few cases. The combination of hepatocellular injury (increases in aminotransferases of >3 × ULN) and increases in total bilirubin (≥3 × ULN) is a marker for potential serious liver injury. Liver aminotransferase levels must be measured prior to initiation of treatment and then monthly. Avoid using Tracleer in patients with moderate or severe liver impairment or elevated ALT/AST >3 × ULN. If clinically significant fluid retention develops, with or without associated weight gain, the cause, such as Tracleer or underlying heart failure, must be determined. Patients may require treatment or Tracleer therapy may need to be discontinued. Preclinical data and an open-label safety study (N=25) showed a decline in sperm count of ≥50% in 25% of Tracleer-treated patients after 3 or 6 months. After 6 months, sperm count remained in normal range, with no changes in sperm morphology or motility, or hormone levels. Endothelin receptor antagonists such as Tracleer may adversely affect spermatogenesis. Treatment with Tracleer can cause a dose-related decrease in hemoglobin (Hgb) and hematocrit. Hgb should be checked after 1 and 3 months, and then every 3 months. Upon marked decrease in Hgb, determine the cause and need for specific treatment. If signs of pulmonary edema occur, the possibility of associated pulmonary veno-occlusive disease should be considered. Tracleer should be discontinued.

ADVERSE EVENTS
In Tracleer pivotal trials, the most common adverse events occurring more often in Tracleer-treated patients than in patients taking placebo (≥2%) were respiratory tract infection, edema, hypotension, sinusitis, arthralgia, liver function test abnormal, palpitations, and anemia.

Please see full Prescribing Information, including BOXED WARNING about liver injury and pregnancy.

Next page >