|
Drug
class
|
Drug
|
Type of PH It
Shows Promise For/WHO Class
|
Who Should Not
Use It
|
Evidence
|
Form
|
Side Effects
|
Sometimes Used
Along With
|
Where Available
|
Manufacturer/Comments
|
|
Arginine
|
|
Sickle cell/pH, but
trials still underway |
|
Case reports; A food
supplement not regulated by FDA; Clinical trials underway |
oral
|
|
|
|
Our bodies need arginine
to make NO. |
|
Calcium
Channel
Blockers
|
amlodipine besylate
(Norvasc) |
PPH*, if patient responds
really well to an acute vasodilator challenge, and is not
in right-heart failure |
Most other pH patients |
|
pill
|
Edema, headache, dizziness,
fatigue, hypotension |
True responders might
not need any other pH drug, but occ. used with most other
pH drugs |
Essentially worldwide. |
|
| nifedipine (Procardia
XL - Adalat [Canada]) |
PPH*, if patient responds
really well to an acute vasodilator challenge, and is not
in right-heart failure |
Most other pH patients |
Clinical trial, but
not perfect design |
pill
|
Headache, fatigue,
dizziness, constipation, nausea, hypotension, edema |
True responders might
not need any other pH drug, but occ. used with most other
pH drugs |
Essentially worldwide. |
|
| diltiazem |
PPH*, if patient responds
really well to an acute vasodilator challenge, and is not
in right-heart failure |
Most other pH patients |
Clinical trial, but
not perfect design |
pill
|
Hypotension, bradycardia,
dizziness, flushing |
True responders might
not need any other pH drug. |
Essentially worldwide |
|
|
Endothelin Antagonists
|
ambrisentan |
PAH patients in Class
II-IV |
|
Clinical trial underway |
pill
|
Teratogenic, headache,
edema, flushing |
|
|
Myogen |
| bosentan
(Tracleer) |
PAH patients in Class
III-IV (US) and Class III (EU) |
|
Clinical trials |
pill
|
Inc. liver enzymes,
teratogen, headache, edema, flushing, hypotension, dyspnea,
nausea/vomiting, abdominal pain, influenza, dizziness |
Epoprostenol (study
underway), beraprost, aerosol iloprost. Combination therapy
still experimental. |
US, EU, Aust., Can.,
Brazil, Iceland, Israel, Nor., Switz. |
|
| sitaxsentan (Thelin) |
PAH patients in Class
II-IV |
|
Clinical trial underway |
pill
|
Edema, headache, dizziness,
nasal congestion, increased prothrombin time/INR |
|
|
Encysive Pharmaceuticals |
| IBC3711 |
PAH? |
|
Still in trial |
pill
|
|
|
|
|
|
Nitric
Oxide
(NO)
|
|
Newborns with persistent
pH and older pH patients with other lung disease, too, such
as some patients with scleroderma, sarciodosis, sickle cell
disease, portopulmonary hypertension. |
|
Clinical trials (for
full-term PPHN infants)
For older patients, used in acute vasodilator trials and chronically
in a few cases |
inhaled gas
|
Sometimes severe rebound
after discontinuation, fainting when temporarily stop use |
Always used along with
oxygen |
Only in hospitals or
as participant in study |
NO is not an FDA-regulated
drug, but a commercial product. |
|
Phospho-
diesterase
Inhibitors
|
sildenafil (Revatio) |
PPHN, PAH, chronic
thromboembolic pH |
Patients taking nitroglycerine,
other nitrates |
Case reports; Still
in trial - Phase III clinical trial results expected in mid-2004 |
pill
|
When used for erectile
dysfunction: headaches, flushing, upset stomach, visual disturbances,
nasal congestion |
Bosentan, prostanoids
(trial in 2004 of sildenafil + epoprostenol) |
Essentially worldwide |
Pfizer
Orphan drug status in EU for PAH and chronic thromboembolic
pH |
| vardenafil (Levitra) |
Probably similar to
sildenafil |
Patients taking nitroglycerine,
other nitrates |
|
pill
|
When used for erectile
dysfunction: headache, flushing, indigestion, nasal congestion,
mild color vision disturbance |
|
Essentially worldwide |
Bayer |
| tadalafil (Cialis) |
Probably similar to
sildenafil |
Patients taking nitroglycerine,
other nitrates |
Planned trial is possible |
pill
|
When used for erectile
dysfunction: headache, indigestion, back pain, muscle ache,
nasal congestion, flushing, skin rash, and possible color
vision disturbance |
|
Essentially worldwide |
Lilly ICOS |
|
Prostanoids
|
beraprost sodium (Domar
-[Europe], Beradrak, Procyclin) |
Classes II-III |
Class IV patients |
Uncontrolled, retrospective
trial in Japan with gen. favorable results; No active trials
in US |
pill
|
Jaw pain, headache,
flushing, nausea, diarrhea, vomiting, heel pain |
|
Japan, Europe, Kuwait |
Toray Industries (United
Therapeutics license in US); Trials stopped early in US as
patients did better at 3 and 6 months but benefits later disappeared;
Under evaluation by Eur. Agency for the Evaluation of Medical
Product |
| epoprostenol
(Flolan) |
FDA approved for PPH*,
PAH associated with scleroderma spectrum of diseases. Medicare
will also cover it for pH associated with thromboembolic disease,
HIV, cirrhosis, diet pills, and congenital left-to-right shunt
in heart; Classes III-IV |
Pulmonary venous hypertension,
pH due to congestive heart failure or severe left ventricular
systolic function |
Clinical trials |
IV & pump
|
Jaw pain, headache,
flushing, nausea, diarrhea, vomiting, pain in calves and feet,
risk of infection |
Bosentan, sildenafil |
US, EU, Ger., UK, Japan
(hard to get) |
GlaxoSmithKline; No
controlled studies yet on whether it's useful for pH secondary
to HIV infection, portopulmonary hypertension, or congenital
heart disease/pH; Must be mixed shortly before use and kept
cold; Half life measured in minutes; Available in US only
through Accredo Therapeutics or Theracom |
| iloprost
(Ventavis [Europe]) |
PPH* Class III patients
benefit most, and approved only for them in EU; Also perhaps
for pH assoc. with scleroderma, diet pills, and distal or
chronic thromboembolic disease |
|
EU clinical trial and
approval |
inhaled aerosol
|
Cough, flushing, headache,
jaw pain |
Bosentan, sildenafil |
EU, US (ltd), New Zealand
(even though no controlled trials avail.) |
Schering (US license:
CoTherix); An oral form of iloprost for pH/scleroderma is
in trial; Inhaled iloprost being studied for several other
forms of pH
Can also be used intravenously (UK) |
| treprostinil
(Remodulin) |
FDA approved for PPH*,
connective tissue/pH, maybe portopulmonary hypertension/II-IV |
|
Clinical trials |
Under-the-skin catheter
|
Site pain, jaw pain,
headache, nausea, diarrhea, flushing, heel pain |
Sildenafil, CCBs, bosentan |
US, Can., Israel |
United Tx; Poss. of
inhaled or catheter versions in future; Premixed, refrigeration
not needed; 2-3 hour half life. When used subcutaneously,
less potent than Flolan; Avail. in US only through Accredo
TX, Caremark, and Priority Healthcare |
|
* PPH is a loose term used historically
to include idiopathic PAH, familial PAH, and PAH caused
by anorectic diet pills and the HIV virus
|
