These guidelines for the management of PAH have been formulated by the American College of Chest Physicians (ACCP), based on evidence and the opinions of a multidisciplinary panel of experts.1

FLOLAN has an ACCP grade “A” recommendation for both NYHA Class III and Class IV patients with PAH1

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* Not in order of preference.

The recommended therapies presented in this algorithm have been evaluated mainly in those with IPAH, or PAH associated with connective tissue disease or anorexigen use. Extrapolation to other forms of PAH should be made with caution. Country-specific regulatory agency approval status and functional class indications for PAH medications vary. CCB=calcium channel blocker; INH=inhaled; IPAH=idiopathic pulmonary arterial hypertension; IV=intravenous; SC=subcutaneous.

American College of Chest Physicians’ Strength of Recommendations1
A = Strong recommendation
B  = Moderate recommendation
C = Weak recommendation
E/A = Strong recommendation based on expert opinion only
E/B = Moderate recommendation based on expert opinion only
E/C = Weak recommendation based on expert opinion only

New York Heart Association (NYHA) Functional Classification2
Class I = No symptoms with ordinary physical activity
Class II = Symptoms with ordinary activity. Slight limitation of activity
Class III = Symptoms with less than ordinary activity. Marked limitation of activity
Class IV = Symptoms with any activity or even at rest

Algorithm adapted from Badesch DB, et al. Chest. 2007;131(6):1917-1928.

ACCP Algorithm notes1

  1. Anticoagulation should be considered for patients with IPAH, and patients with an indwelling catheter for the administration of an IV prostanoid, in the absence of contraindications. Diuretics and oxygen should be added as necessary.
  2. A positive acute vasodilator response is defined as a fall in mean pulmonary arterial pressure (PAPm) ≥10 mm Hg, to a PAPm ≤40 mm Hg, with an unchanged or increased cardiac output when challenged with inhaled nitric oxide, IV epoprostenol, or IV adenosine.
  3. Consideration should be given to using a PAH-specific medication such as a phosphodiesterase 5 inhibitor, endothelin receptor antagonist, or prostanoid as first-line treatment instead of a CCB in patients with PAH that is not IPAH or PAH associated with anorexigen use, or in those in an advanced functional class, given the exceedingly low long-term response rate to CCB monotherapy in the former and poor prognosis in the latter.
  4. Sustained response to CCB therapy is defined as being in functional class I or II with normal or near-normal hemodynamics after several months of treatment.
  5. The risks and benefits of treatment in early PAH should be considered.
  6. First-line therapy for functional class III includes bosentan, sildenafil, epoprostenol, iloprost INH, and treprostinil.
  7. Most experts recommend IV epoprostenol as first-line treatment for unstable patients in functional class IV.
  8. Randomized clinical trials studying add-on combination treatment regimens are underway.

References: 1. Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. 2007;131(6):1917-1928. 2. Rubin LJ. Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(suppl 1):7S-10S.

INDICATION: FLOLAN is indicated for the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.


IMPORTANT SAFETY INFORMATION:
Chronic use of FLOLAN is contraindicated in patients with congestive heart failure due to severe left ventricular systolic dysfunction.

FLOLAN should not be used chronically in patients who develop pulmonary edema during dose initiation.

FLOLAN must be reconstituted only as directed using STERILE DILUENT for FLOLAN. FLOLAN must not be reconstituted or mixed with any other parenteral medications or solutions prior to or during administration.

Abrupt withdrawal or reductions in delivery of FLOLAN, as well as overdoses, may result in hemodynamic instability, including rebound pulmonary hypertension or fatal hypotension.

FLOLAN should be used only by clinicians experienced in the diagnosis and treatment of pulmonary hypertension.

FLOLAN is a potent inhibitor of platelet aggregation. Therefore, an increased risk for hemorrhagic complications should be considered, particularly for patients with other risk factors for bleeding.

During chronic use, FLOLAN is delivered continuously on an ambulatory basis through a permanent indwelling central venous catheter. Unless contraindicated, anticoagulant therapy should be administered to PPH and PH/SSD patients receiving FLOLAN to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale. In order to reduce the risk of infection, aseptic technique must be used in the reconstitution and administration of FLOLAN as well as in routine catheter care. Dosage of FLOLAN during chronic use should be adjusted at the first sign of recurrence or worsening of symptoms.

Chronic adverse events reported during clinical trials include headache, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms, and anxiety/nervousness.

Serious adverse events have been reported during post-approval use of FLOLAN.
These include sepsis, anemia, hypersplenism, thrombocytopenia, pancytopenia, splenomegaly, and hyperthyroidism.

Excessive doses of FLOLAN may acutely result in systemic hypotension, tachycardia, headache, flushing, nausea and vomiting, diarrhea; excessive doses administered chronically can lead to the development of a hyperdynamic state and high-output cardiac failure.*

*Badesch DB, Abman SH, Ahearn GS, et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004;126(1, suppl):35S-62S.

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