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Posted: February 17, 2010

National Medical Policy



Subject: Alprostadil Intravenous for Raynauds
Syndrome

Policy Number: NMP112

Effective Date*: March 2004

Updated: February 2006, February 2008, February 2010

This National Medical Policy is subject to the terms in the
IMPORTANT NOTICE
at the end of this document

Current Policy Statement (Update February 2010 - A Medline search failed to
reveal any studies that would cause Health Net, Inc. to change its current position)

Health Net, Inc. considers alprostadil intravenous (IV) medically necessary for use in
ischemic conditions such as Raynaud's disease, with or without scleroderma, or
peripheral vascular disease to dilate small vessels during acute exacerbations of
finger, toe or limb vasospasm, sepsis and/or necrosis when other treatment
modalities have failed.

Note:
Under the FDA Orphan Drug designation, Alprostadil was approved in 1993 for
treatment of severe peripheral arterial occlusive disease (critical limb ischemia) in
patients where other procedures, grafts or angioplasty, are not indicated.

IV Alprostadil is medically necessary in any of the following:

1. A limb(s), finger(s), or toe(s) is severely ischemic, gangrenous or loss of a limb
or digit is possible,
or
2. As treatment of severe peripheral arterial occlusive disease (critical limb
ischemia) in patients where other procedures, such as grafts or angioplasty, are
not indicated,
or
3. Patients with non healing digital ulcers related to Raynaud's disease or severe
peripheral arterial occlusive disease, where amputation would otherwise be
unavoidable.

Codes Related To This Policy
ICD-9 Codes
440.23 Atherosclerosis of the extremities with ulceration
440.24 Atherosclerosis of the extremities with gangrene
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443 Other peripheral vascular disease
443.0 Raynauds syndrome
443.1 Thromboangiitis obliterans (Buergers disease)
443.9 Peripheral vascular disease, unspecified
707 Chronic ulcer of skin, non-healing ulcer
707.1 Ulcer of lower limbs, except decubitus
707.10 Ulcer of lower limb, unspecified
707.15 Ulcer of other part of foot; toes
785.4 Gangrene

CPT Codes
37202 Transcatheter therapy, infusion other than for thrombolysis, any type
(e.g. spasmolytic, vasoconstrictive)
90783 Therapeutic, prophylactic or diagnostic injection, intra-arterial (deleted
12/31/05)
90784 Therapeutic, prophylactic or diagnostic injection, intravenous (deleted
12/31/05)
96373 Therapeutic, prophylactic or diagnostic injection (specify substance or
drug); intra-arterial
96374 Therapeutic, prophylactic or diagnostic injection (specify substance or
drug); intravenous push, single or initial substance/drug

2006 CPT Codes
90773 Therapeutic, prophylactic or diagnostic injection (specify substance or
drug); intra-arterial (deleted 12/31/2008)
90774 Therapeutic, prophylactic or diagnostic injection (specify substance or
drug); intravenous push, single or initial substance/drug) (deleted
12/31/2008)

HCPCS Codes
J0270 Injection alprostadil, 1.25 mcg (code may be used for Medicare when
drug administered under direct supervision of a physician, not for use
when drug is self-administered

Scientific Rationale - Update February 2006
A Medline search of the published peer review literature revealed no new information
to support any revisions to this current policy. Most patients with intermittent
claudication are treated initially with medical therapy, risk factor modification,
exercise, pharmacology or with percutaneous intervention or surgery. Alprostadil
intravenous (IV) is considered medically necessary if these measures fail to reverse
the ischemia, or if the clinical presentation is severe as noted in the above criteria.
Alprostadil intravenous (IV) is not recommended for the routine treatment of
intermittent claudication.

Scientific Rationale - Initial
In Raynaud's phenomenon, exposure to the cold, or strong emotions, trigger blood
vessel spasms that result in interruption of blood flow to the fingers and toes.
Occasionally, an episode affects just one or two fingers or toes, and episodes don't
necessarily always affect the same digits. Although Raynaud's most commonly
affects the fingers and toes, the condition can also affect other areas of the body
including the nose, cheeks, ears and tongue. An attack may last less than a minute
to several hours. Over time, attacks may grow more severe. If the condition
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progresses, blood flow to the affected area(s) could become permanently decreased
causing the fingers to become thin and tapered, with smooth, shiny skin and slow
growing nails. If an artery becomes blocked completely, gangrene or ulcerations of
the skin can occur.

Raynauds phenomenon consists of three phases of color change: pallor, cyanosis,
and erythema, which represent phases of vasoconstriction, decreased blood flow,
and reperfusion, respectively. At first during an attack of Raynaud's, affected areas
of the skin turn pale or white. Color changes extend proximally from the tips of
digits to various levels, with a well-demarcated border. During this period of
vasospasm, endothelial injury is believed to result in intimal hyperplasia and fibrosis,
causing concentric narrowing of digital arteries by as much as 75-80% and occlusion
by intravascular thrombi. Affected areas often turn blue, feel cold and numb, and
sensory perception is dulled. The affected skin may look slightly swollen. As
circulation improves, the affected areas may turn red, throb, tingle or swell. Signs
and symptoms of Raynaud's depend on the frequency, duration and severity of the
blood vessel spasms that underlie the disorder.

Raynaud's occurs in two main types:
Primary Raynaud's. This is Raynaud's without an underlying disease or
associated medical problem that could provoke vasospasm. Also called
Raynaud's disease, it's the most common form of the disorder. Primary
Raynaud's typically affects both hands and both feet.

Secondary Raynaud's. This is Raynaud's caused by an underlying problem,
such as scleroderma, atherosclerosis, rheumatoid arthritis, Buergers
disease or systemic lupus erythematosus. Also called Raynaud's
phenomenon, secondary Raynaud's usually affects either both hands or
both feet. Although secondary Raynaud's is less common than the primary
form, it's often a more complex and serious disorder.

Raynaud's phenomenon has been documented in association with repetitive trauma
(i.e. carpal tunnel syndrome), chemical exposure (specifically, exposure to vinyl
chloride) and certain medications that promote vasocontriction (e.g. beta blockers, -
ergot alkaloids, oral contraceptives/estrogen replacement therapy, and certain
chemotherapy agents). Other risk factors include smoking, history of frostbite, and
history of injury to the hands and/or feet.

Medical management of Raynaud's phenomenon is aimed at preventing vasospasm,
reducing the number and severity of attacks and preventing tissue damage. The
most basic therapy is protection against vasoconstrictive stimuli such as cold, fright
or frustration. Other management options include teaching hand and body warming
techniques and smoking cessation. Improvement of resting digital skin temperature
has been noted after biofeedback training, however long-term maintenance of this
response is variable.

Medications are also a mainstay of Raynauds treatment and include calcium channel
blockers, alpha blockers, vasodilators, and topical nitropaste. In patients with
persistent symptoms, pentoxifylline (Trental) is used to improve circulation by
making red blood cells more flexible as they pass through narrowed blood vessels. In
severe cases, Alprostadil is used for nonhealing ulcers or severe ischemia.
Alprostadil Intravenous for Raynauds Syndrome Feb 10 3
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When medical management is insufficient, other treatment options to be considered
are cervical or digital sympathectomy, chemical injections into the affected area(s)
and/or amputation. Unfortunately, amputation is sometimes unavoidable in the
event of nonhealing digital ulcers.

Alprostadil (Prostaglandin E1, PGE1) is a hormone like substance known as a potent
arterial vasodilator and platelet-aggregation inhibitor. Prostaglandin infusions are
used in ischemic conditions such as Raynaud's disease and peripheral vascular
disease to dilate small vessels during acute exacerbations of finger sepsis and
necrosis.

The beneficial effects of prostaglandins on the peripheral microcirculation have been
documented in the published literature in numerous studies. Improved cold
tolerance was noted, and attacks of Raynaud's phenomenon were noted to be less
frequent, less severe, and shorter in duration following PGE1 infusions.
Hemodynamic assessments included measurements of skin temperature and finger
systolic pressure response to localized digital cooling. Non-healing wound
improvements have been measured by documentation of decreased ulcer size and
improved granulation following prostaglandin infusions. Many ischemic ulcers healed
between 2-6 weeks following treatment and the beneficial effects persisted for
between 1-18 months. Administration of a three day course of IV Alprostadil has
been documented to statistically improve outcome measures and effects have been
noted to last for at least three to four weeks. Unlike sympathectomy, it is a minor
procedure without prolonged side effects and is repeatable.

A study published by Bartolone et al in 1999 examined the effects of PGE1
(Alprostadil) in patients with scleroderma and severe Raynaud's disease. Twelve
females were included in the study. Six women received a 3-hour infusion of
alprostadil at the standard dosage of 60 micrograms in 250 cc of physiological
infusion for six consecutive days. The remaining six receiving placebo (250 cc of
physiological infusion administered in the same manner). After infusion, blood flow,
digitally measured by telethermography was increased only in patients treated with
alprostadil. The number, frequency and severity of attacks recorded were reduced
only in patients treated with alprostadil. The authors concluded, alprostadil is
effective in the management of Raynaud's phenomenon.

In a retrospective case study by Langevitz et al, twenty Prostaglandin E1 (PGE1)
infusions were administered to 12 patients with severe Raynaud's phenomenon,
associated with refractory ischemic skin ulcers. There was symptomatic
improvement following 17 of the 20 infusions, while 35 of the 65 ischemic ulcers
healed between 2-6 weeks following treatment. The beneficial effects persisted for
between 1-18 months.

Gardinali et al evaluated the efficacy and safety of prostaglandin (PG) E1alpha-
cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc).
Thirty-six women were given three 60 microg intravenous PGE1alpha-cyclodextrin
infusions on 5 consecutive days at 6 week intervals. RP symptoms and healing of
digital lesions were evaluated. Twenty age matched healthy women were the
controls. RP symptoms were improved 87% of the patients. The benefit of each 5
day cycle lasted 4 or more weeks in 75%. PGE1alpha-cyclodextrin reduced the daily
frequency of RP symptoms by 20% (p < 0.05), 41% (p < 0.005), and 53% (p <
0.0005) from baseline after the 1st, 2nd, and 3rd infusions, respectively. The
Alprostadil Intravenous for Raynauds Syndrome Feb 10 4
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severity of the attacks was reduced to a limited degree. In 12 of the 14 patients with
digital lesions, these healed completely. Ten patients had mild side effects during
treatment (headache, increased intestinal motility, flushing). The authors
concluded, PGE1alpha-cyclodextrin reduces RP symptoms and plasma levels of the
markers of endothelial injury in SSc, suggesting that an improvement of endothelial
dysfunction contributes to its prolonged therapeutic effect.

In 1981, Martin et al. tested twelve patients with systemic sclerosis (SS) and severe
Raynaud's phenomenon; each received infusions of prostaglandin E1 (PGE1) with
either saline or 5% dextrose, for 72 hours in a single-blind cross-over study.
Following the PGE1 infusion cold tolerance improved and attacks of Raynaud's
phenomenon were less frequent, less severe, and shorter in duration. This subjective
improvement was maintained for several weeks in most patients, and 2 noted
healing of ischaemic ulcers. There was no significant change in objective
measurements of hand function after either infusion. However, pain measured on a
10 cm visual analogue scale improved 2.19 cm with PGE1 and only 0.91 cm with
normal saline (P less than 0.05). Temperature of the fingers and hands recorded by
thermography did not change significantly with saline infusions, but did rise during
PGE1 infusions (mean rise 2.0 degrees C at 48 hours, p less than 0.001), and was
maintained when measured again 2 weeks later (mean rise 1.56 degrees C, p less
0.001).

Contraindications for use of IV Alprostadil include documented hypersensitivity, and
coadministration with anticoagulants may increase bleeding risk because of shared
effects on platelet aggregation. Precautions are warranted upon initiation of
alprostadil because infusions require experienced personnel and physiologic
monitoring. Side effects such as bradycardia, hypotension, and/or postural
hypotension, fever, headache, and flushing can occur.

Review History
March 16, 2004 Medical Advisory Council, initial approval
February 2006 Update no revisions
February 2008 Update no revisions. Updated HCPCS code.
February 2010 Update no revisions. Code updates

Patient Education Websites
English
1. National Institiute of Arthritis and Musculoskeletal and Skin Disease. Questions
and Answers about Raynaud's Phenomenon. Available at:
http://www.niams.nih.gov/hi/topics/raynaud/ar125fs.htm

Spanish
1. Arthritis Foundation. Fenmeno de Raynaud. Acesso en:
http://www.arthritis.org/Espanol/enfermedades/tipos_de_artritis/raynaud.asp

This policy is based on the following evidence-based guidelines:
1. National Guideline Clearinghouse. Guideline for management of wounds in
patients with lower-extremity arterial disease. Available at:
http://www.guideline.gov/summary/summary.aspx?doc_id=12613&nbr=006521
&string=lower-extremity+AND+arterial+AND+disease
2. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 guidelines for the
management of patients with peripheral arterial disease (lower extremity, renal,
Alprostadil Intravenous for Raynauds Syndrome Feb 10 5
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mesenteric, and abdominal aortic): a collaborative report [trunc]. Bethesda
(MD): American College of Cardiology Foundation; 2005. Available at:
http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=8503&nbr=0
04740&string=lower-extremity+AND+arterial+AND+disease

References Update February 2010
1. Clinical trials.gov. Alprostadil in Peripheral Arterial Occlusive Disease (PAOD)
Stage IV (ESPECIAL) Available at:
http://clinicaltrials.gov/ct2/show/NCT00596752
2. Di Stefano R, Barsotti MC, Melillo E, et al. The prostacyclin analogue iloprost
increases circulating endothelial progenitor cells in patients with critical limb
ischemia. Thromb Haemost. 2008 Nov;100(5):871-7.
3. Ikushima I, Hirai T, Ishii A, Yamashita Y. Combined stent placement and high
dose PGE1 drip infusion for chronic occlusion of the superficial femoral artery as a
modality to salvage chronic critical limb ischemia. Eur J Radiol. 2008
Apr;66(1):95-9.
4. Milio G, Novo G, Genova C, et al. Pharmacological treatment of patients with
chronic critical limb ischemia: L-propionyl-carnitine enhances the short-term
effects of PGE-1. Cardiovasc Drugs Ther. 2009 Aug;23(4):301-6.
5. Minar E. Critical limb ischaemia. Hamostaseologie. 2009 Jan;29(1):102-9.
6. U.S. Food and Drug Administration. List of Orphan Products Designations and
Approvals. Available at:
http://www.fda.gov/ohrms/dockets/dailys/00/mar00/030100/lst0094.pdf

References Update February 2008
1. Henness SA, Wigley FM. Current drug therapy for scleroderma and secondary
Raynaud's phenomenon: evidence-based review. Current Opinion in
Rheumatology. 19(6):611-618, November 2007.

References - Update February 2006
1. Marasini B, Massarotti M, Bottasso B, et al. Comparison between iloprost and
alprostadil in the treatment of Raynaud's phenomenon. Scand J Rheumatol.
2004;33(4):253-6.
2. Pokrovskii AV, Dan VN, Chupin AV, Kalinin AA. Alprostan for management of
critical lower limb ischemia. Angiol Sosud Khir. 2005;11(1):7-10.
3. Heidrich H, Schmidt T, Fahrig C. Are there predictors for the outcome of a PGE1
treatment in peripheral arterial disease with critical limb ischaemia? Vasa. 2005
May;34(2):101-7.
4. Mlekusch W, Schillinger M, Sabeti S, et al. Effects of intravenous prostaglandin E1
on arterial compliance: a randomized controlled trial. Vasa. 2004
Aug;33(3):131-6.
5. Schellong S, Altmann E, von Bilderling P, et al. Microcirculation and tolerability
following i.v. infusion of PGE1 and iloprost: a randomized cross-over study in
patients with critical limb ischemia. Prostaglandins Leukot Essent Fatty Acids.
2004 Jun;70(6):503-9.
6. Marchesi S, Pasqualini L, Lombardini R, et al. Prostaglandin E1 improves
endothelial function in critical limb ischemia. J Cardiovasc Pharmacol. 2003
Feb;41(2):249-53.
7. Bandiera G, Forletta M, Di Paola FM, Cirielli C. PGE(1) short term therapy in
critical lower limb ischemia. Int Angiol. 2003 Mar;22(1):58-63.
8. Grader-Beck T, Wigley FM. Raynaud's phenomenon in mixed connective tissue
disease. Rheum Dis Clin North Am. 2005, Aug ; 31(3): 465-81, vi
Alprostadil Intravenous for Raynauds Syndrome Feb 10 6
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9. Hiatt WR. Treatment of disability in peripheral arterial disease: new drugs.
Curr Drug Targets Cardiovasc Haematol Disord. 2004 Sep;4(3):227-31
10. Zeni S, Ingegnoli F. Raynaud's phenomenon. Reumatismo. 2004 Apr-
Jun;56(2):77-
11. Reiter, M, Bucek, R, Stumpflen, A, Minar, E. Prostanoids for intermittent
claudication. Cochrane Database Syst Rev 2004; 1:CD000986.
12. Amendt K. PGE1 and other prostaglandins in the treatment of intermittent
claudication: a meta-analysis. Angiology. 2005 Jul-Aug;56(4):409-15.
13. Hashiguchi M, Ohno K, Saito R. Studies on the effectiveness and safety of
cilostazol, beraprost sodium, prostaglandin E1 for the treatment of intermittent
claudication.Yakugaku Zasshi. 2004 Jun;124(6):321-32.

References - Initial
1. [No authors listed] Treatment of limb threatening ischaemia with intravenous
iloprost: a randomised double-blind placebo controlled study. U.K. Severe Limb
Ischaemia Study Group. Eur J Vasc Surg. 1991 Oct;5(5):511-6.
2. [No authors listed] Prostanoids for chronic critical leg ischemia. A randomized,
controlled, open-label trial with prostaglandin E1. The ICAI Study Group.
Ischemia Cronica degli Arti Inferiori. Ann Intern Med. 1999 Mar 2;130(5):412-21.
3. Balzer K, Rogatti W, Ruttgerodt K. Efficacy and tolerability of intra-arterial and
intravenous prostaglandin E1 infusions in occlusive arterial disease stage III/IV.
Vasa Suppl. 1989;28:31-8.
4. Bandiera G, Forletta M, Di Paola FM, Cirielli C. PGE(1) short term therapy in
critical lower limb ischemia. Int Angiol. 2003 Mar;22(1):58-63.
5. Bartolone S, Trifiletti A, De Nuzzo G, et al. Efficacy evaluation of prostaglandin
E1 against placebo in patients with progressive systemic sclerosis and significant
Raynaud's phenomenon. Minerva Cardioangiol. 1999 May;47(5):137-43.
6. Beitner H, Hammar H, Olsson AG, Thyresson N. Prostaglandin E1 treatment of leg
ulcers caused by venous or arterial incompetence. Acta Derm Venereol.
1980;60(5):425-30.
7. Belcaro G, Nicolaides AN, Cipollone G, et al. Nomograms used to define the
short-term treatment with PGE(1) in patients with intermittent claudication and
critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic
Critical Limb) Study Group. The European Study. Angiology. 2000 Aug;51(8 Pt
2):S3-13; discussion S14.
8. Belch JJ, Capell HA, Cooke ED, et al: Oral iloprost as a treatment for Raynaud's
syndrome: a double blind multicentre placebo controlled study. Ann Rheum Dis
1995 Mar; 54(3): 197-200
9. Belch JJ, Newman P, Drury JK, et al: Intermittent epoprostenol (prostacyclin)
infusion in patients with Raynaud's syndrome. A double-blind controlled trial.
Lancet 1983 Feb 12; 1(8320): 313-5.
10. Belch JJF & Ho M: Pharmacotherapy of Raynaud's phenomenon. Drugs 1996;
52:682-695.
11. Bellucci S, Kedra W, Ajzenberg N, et al.New treatments for Raynaud's syndrome.
Nouv Rev Fr Hematol. 1988;30(1-2):103-7.
12. Bettoni L, Geri A, Airo P, et al. Systemic sclerosis therapy with iloprost: a
prospective observational study of 30 patients treated for a median of 3 years.
Clin Rheumatol. 2002 Jun;21(3):244-50.
13. Borkowski M, Kruk M, Krolicki L, et al. Results of the treatment of peripheral
arterial diseases with PGE1. Pol Tyg Lek. 1990 Jun 18-25;45(25-26):505-8.
14. Castagno PL, Di Molfetta L, Merlo M, et al. Prospects of prostanoid therapy.
Preliminary results. Minerva Cardioangiol. 2000 Jan-Feb;48(1-2):9-18.
Alprostadil Intravenous for Raynauds Syndrome Feb 10 7
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15. Ceru S, Pancera P, Sansone S, et al. Effects of five-day versus one-day infusion
of iloprost on the peripheral microcirculation in patients with systemic sclerosis.
Clin Exp Rheumatol. 1997 Jul-Aug;15(4):381-5.
16. Cesarone MR, Belcaro G, Nicolaides AN, et al. Treatment of severe intermittent
claudication: ORACLE-PGE1 short term study. A randomised 40-week study.
Evaluation of efficacy and costs. Minerva Cardioangiol. 2002 Dec;50(6):683-90.
17. Clifford PC, Martin MF, Dieppe PA, et al. Prostaglandin E1 infusion for small
vessel arterial ischemia. J Cardiovasc Surg (Torino). 1983 Sep-Oct;24(5):503-8.
18. Clifford PC, Martin MFR, Sheddon EJ et al: Treatment of vasospastic disease with
prostaglandin E1. Br Med J 1980; 281:1031-1034.
19. Cohen LE, Faske I, Fenske NA, Greist MA. Prostaglandin infusion therapy for
intermittent digital ischemia in a patient with mixed connective tissue disease.
Case report and review of the literature. J Am Acad Dermatol. 1989 May;20(5 Pt
2):893-7.
20. Creutzig A, Creutzig H, Alexander K. Effects of intra-arterial prostaglandin E1 in
patients with peripheral arterial occlusive disease. Eur J Clin Invest. 1986
Dec;16(6):480-5.
21. Davidovic L, Vranes M, Cernak I, et al.Intra-arterial administration of
prostaglandin E1 in occlusive arterial diseases. Srp Arh Celok Lek. 1992 Jan-
Feb;120(1-2):9-14.
22. Destors JM, Gauthier E, Lelong S, Boissel JP: Failure of a pure anti-platelet drug
to decrease the number of attacks more than placebo in patients with Raynaud's
phenomenon. Angiology 1986 Aug; 37(8): 565-9
23. Diehm C, Balzer K, Bisler H, et al. Efficacy of a new prostaglandin E1 regimen in
outpatients with severe intermittent claudication: results of a multicenter
placebo-controlled double-blind trial. J Vasc Surg. 1997 Mar;25(3):537-44.
24. Dziadzio M, Denton CP, Smith R, et al: Losartan therapy for Raynaud's
phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week,
randomized, parallel-group, controlled trial. Arthritis Rheum 1999 Dec; 42(12):
2646-55
25. Eklund AE, Eriksson G, Olsson AG. A controlled study showing significant short
term effect of prostaglandin E1 in healing of ischemic ulcers of the lower limb in
man. Prostaglandins Leukot Med. 1982 Mar;8(3):265-71.
26. Gardinali M, Pozzi MR, Bernareggi M, et al. Treatment of Raynaud's phenomenon
with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell
injury in systemic sclerosis. J Rheumatol. 2001 Apr;28(4):786-94.
27. Gianetti J, De Caterina M, De Cristofaro T, et al. Intravenous prostaglandin E1
reduces soluble vascular cell adhesion molecule-1 in peripheral arterial
obstructive disease. Am Heart J. 2001 Oct;142(4):733-9.
28. Goldberg J & Dlesk A: Successful treatment of Raynaud's phenomenon with
pentoxifylline (letter). Arthritis Rheum 1986; 29:1055-1056.
29. Gruss JD, Bartels D, Haidar A, et al. Continuous intra-arterial perfusion of
prostaglandin E1 in inoperable stage-IV arteriopathies. J Mal Vasc.
1983;8(2):133-7.
30. Gruss JD, Bartels D, Ohta T, et al. Conservative treatment of inoperable arterial
occlusions of the lower extremities with intra-arterial prostaglandin E1. Br J Surg.
1982 Jun;69 Suppl:S11-3.
31. Hantel A, Rowinsky EK & Donehower RC: Nifedipine and oncologic Raynaud
phenomenon. Ann Inter Med 1988; 108:767.
32. Hauptman HW, Ruddy S, Roberts WN. Reversal of the vasospastic component of
lupus vasculopathy by infusion of prostaglandin E1. J Rheumatol. 1991
Nov;18(11):1747-52.
Alprostadil Intravenous for Raynauds Syndrome Feb 10 8
8
Posted: February 17, 2010
33. Heun-Letsch CA, Morl H. Severe Raynaud disease of all four extremities. Vasa.
1993;22(1):75-9.
34. Hirai M, Nakayama R. Haemodynamic effects of intra-arterial and intravenous
administration of prostaglandin E1 in patients with peripheral arterial disease. Br
J Surg. 1986 Jan;73(1):20-3.
35. Hirai M, Nanki M, Nakayama R. Hemodynamic effects of intravenous PGE1 on
patients with arterial occlusive disease of the leg. Angiology. 1985 Jul;36(7):407-
13.
36. Hoshi K, Mizushima Y, Kiyokawa S, Yanagawa A. Prostaglandin E1 incorporated in
lipid microspheres in the treatment of peripheral vascular diseases and diabetic
neuropathy. Drugs Exp Clin Res. 1986;12(8):681-5.
37. Hugh NJ, Csuka M, Watson H, et al. Infusion of iloprost, a prostacyclin analogue,
for treatment of Raynaud's phenomenon in systemic sclerosis. Ann Rheum Dis.
1988 Jan;47(1):43-7.
38. Jogestrand T, Olsson AG. The effect of intravenous prostaglandin E1 on ischemic
pain and on leg blood-flow in subjects with peripheral artery disease: a double-
blind controlled study. Clin Physiol. 1985 Dec;5(6):495-502.
39. Katoh K, Kawai T, Narita M, et al. Use of prostaglandin E1 (lipo-PGE1) to treat
Raynaud's phenomenon associated with connective tissue disease: thermographic
and subjective assessment. J Pharm Pharmacol. 1992 May;44(5):442-4.
40. Kaya IS, Senses DA & Dilmen U: Nifedipine in the treatment of Raynaud's disease
in childhood (letter). Lancet 1989; 1:1136.
41. Killion DD, Ambrus JL. Treatment of complications of peripheral obstructive
arterial disease with prostaglandin E1. Angiology. 1987 Jul;38(7):507-13.
42. Kowal-Gierczak B, Kurzawska-Mielecka M, Czarnacki M. Prostaglandin E1 in the
treatment of chronic ischemia of the extremities. Pol Arch Med Wewn. 1990
Nov;84(5):321-7.
43. Krawzak HW, Jakel F, Strosche H, Buchholz J. Intra-arterial infusion therapy of
progressive diabetic foot gangrene with prostaglandin E1 and cefotaxime. Vasa.
1989;18(4):312-5.
44. Kyle V, Parr G, Salisbury R, et al. Prostaglandin E1 vasospastic disease and
thermography. Ann Rheum Dis. 1985 Feb;44(2):73-8.
45. Langevitz P, Buskila D, Lee P, Urowitz MB: Treatment of refractory ischemic skin
ulcers in patients with Raynaud's phenomenon with PGE1 infusions. J Rheumatol
1989 Nov; 16(11):1433-5
46. Laurora G, Belcaro G, Cesarone MR, et al. Global analysis of data from studies
with PDE1 alpha-cyslodextrin. Minerva Cardioangiol. 1998 Oct;46(10 Suppl
1):65-8.
47. Linhart J. Prostaglandin therapy of peripheral occlusive arterial disease. Sb Lek.
1998;99(4):355-62.
48. Makita S, Nakamura M, Ohhira A, Itoh S, Hiramori K. Effects of prostaglandin E1
infusion on limb hemodynamics and vasodilatory response in patients with
arteriosclerosis obliterans. Cardiovasc Drugs Ther. 1997 Jul;11(3):441-8.
49. Martin MF, Dowd PM, Ring EF, et al. Prostaglandin E1 infusions for vascular
insufficiency in progressive systemic sclerosis. Ann Rheum Dis. 1981
Aug;40(4):350-4.
50. Martin MF, Tooke JE. Effects of prostaglandin E1 on microvascular
haemodynamics in progressive systemic sclerosis. Br Med J (Clin Res Ed). 1982
Dec 11;285(6356):1688-90.
51. McHugh NJ, Csuka M, Watson H, et al. Infusion of iloprost, a prostacyclin
analogue, for treatment of Raynaud's phenomenon in systemic sclerosis. Ann
Rheum Dis. 1988 Jan;47(1):43-7.
Alprostadil Intravenous for Raynauds Syndrome Feb 10 9
9
Posted: February 17, 2010
52. Milio G, Cospite V, Cospite M. Effects of PGE-1 in patients suffering from
peripheral arterial occlusive disease. Minerv Cardioangiol. 2003 Jun;51(3):311-6.
53. Mohrland JS, Porter JM, Smith EA, et al. A multiclinic, placebo-controlled, double-
blind study of prostaglandin E1 in Raynaud's syndrome. Ann Rheum Dis. 1985
Nov;44(11):754-60.
54. Murakami M, Takahashi K, Sekikawa T, et al. Effects of intravenous
lipoprostaglandin E1 on neurogenic intermittent claudication. J Spinal Disord.
1997 Dec;10(6):499-504.
55. Nakano T, Tominaga R, Shiraishi K, Yasui H. Prostaglandin E1 from the tip of an
intraaortic balloon catheter for lower limb ischemia. Ann Thorac Surg. 1998
Apr;65(4):1158-60.
56. Occhionorelli S, Mascoli F, Vasquez G, et al. Use of PGE1 in severe ischemia of
the lower extremities. Clinical study. Minerva Cardioangiol. 1995 Jun;43(6):247-
56.
57. Pardy BJ, Hoare MC, Eastcott HH, et al. Prostaglandin E1 in severe Raynaud's
phenomenon. Surgery. 1982 Dec;92(6):953-65.
58. Pardy BJ, Lewis JD, Eastcott HH. Preliminary experience with prostaglandins E1
and I2 in peripheral vascular disease. Surgery. 1980 Dec;88(6):826-32.
59. Pilger E, Bertuch H, Stark G, Honigl K. Prostaglandin E1 in decreased arterial
perfusion. Wien Klin Wochenschr. 1988 Jul 15;100(14):490-5.
60. Pilger E, Juan H. Preliminary results of prostaglandin E1 therapy in peripheral
obliterating arteriopathy. Wien Klin Wochenschr. 1983 Apr 15;95(8):263-6.
61. Pope J, Fenlon D, Thompson A, et al. Iloprost and cisaprost for Raynaud's
phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev.
2000;(2):CD000953.
62. Rademaker M, Cooke ED, Almond NE, et al. Comparison of intravenous infusions
of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients
with systemic sclerosis: a double blind randomised study. BMJ. 1989 Mar
4;298(6673):561-4.
63. Ranke C, Creutzig A, Alexander K. Hemodynamic effects of intermittent intra-
arterial infusion treatment with prostaglandin E1 in peripheral arterial occlusive
disease. Med Klin (Munich). 1991 Jul 15;86(7):349-52, 382.
64. Rhodes RS, Heard SE. Detrimental effect of high-dose prostaglandin E1 in the
treatment of ischemic ulcers. Surgery. 1983 Jun;93(6):839-42.
65. Rudofsky G. Intra-arterial infusion treatment with prostaglandin E1 in patients
with intermittent claudication. Wien Klin Wochenschr.1988 Jul 15;100(14):484-8.
66. Rudofsky G. Intravenous prostaglandin E1 in the treatment of venous ulcers--a
double-blind, placebo-controlled trial. Vasa Suppl. 1989;28:39-43.
67. Scheffler P, de la Hamette D, Leipnitz G. Therapeutic efficacy of intravenously
applied prostaglandin E1. Vasa Suppl. 1989;28:19-25.
68. Schuler JJ, Flanigan DP, Holcroft JW, et al. Efficacy of prostaglandin E1 in the
treatment of lower extremity ischemic ulcers secondary to peripheral vascular
occlusive disease. Results of a prospective randomized, double-blind, multicenter
clinical trial. J Vasc Surg. 1984 Jan;1(1):160-70.
69. Seemann J, Scholz J, Sielwicz M. Remission of secondary Raynaud phenomenon
using intra-arterial prostaglandin E1 infusion. A case report. Int Orthop.
1994;18(6):372-4.
70. Sethi GK, Bridgman AH, King L, Scott SM. Intravenous infusion of prostaglandin
E1 (PGE1) in management of limb ischemia. Am Surg. 1986 Sep;52(9):474-8.
71. Soreide O, Segadal L, Trippestad A, Engedal H. Salvage of the severely ischemic
limb by intra-arterial prostacyclin (PGI2) infusion. A case report. Scand J Thorac
Cardiovasc Surg. 1982;16(1):71-3.
Alprostadil Intravenous for Raynauds Syndrome Feb 10 10
10
Posted: February 17, 2010
72. Thum J, Caspary L, Creutzig A, Alexander K. Intra-arterial and intravenous
administration of prostaglandin E1 cause different changes to skin
microcirculation in patients with peripheral arterial occlusive disease. Vasa. 1998
May;27(2):100-5.
73. Tohjima T, Shiokawa Y. Effect of prostaglandin E1 in collagen disease patients
with inflammatory skin ulcer. Int J Tissue React. 1983;5(1):1-10.
74. Torley HI, Madhok R, Capell HA, et al. A double blind, randomised, multicentre
comparison of two doses of intravenous iloprost in the treatment of Raynaud's
phenomenon secondary to connective tissue diseases. Ann Rheum Dis. 1991
Nov;50(11):800-4.
75. Toyota T, Hirata Y, Ikeda Y, et al. Lipo-PGE1, a new lipid-encapsulated
preparation of prostaglandin E1: placebo-and prostaglandin E1-controlled
multicenter trials in patients with diabetic neuropathy and leg ulcers.
Prostaglandins. 1993 Nov;46(5):453-68.
76. Trifiletti A, Scamardi R, Pizzoleo MA, et al. Clinical and haemostatic effects of
intravenous prostaglandin E1 therapy in patients with peripheral arterial occlusive
disease. Panminerva Med. 1999 Mar;41(1):15-7.
77. Trubestein G, Ludwig M, Diehm C, et al. Prostaglandin E1 in stage III and IV
arterial occlusive diseases. results of a multicenter study. Dtsch Med Wochenschr.
1987 Jun 12;112(24):955-9.
78. Trubestein G, von Bary S, Breddin K, et al. Intravenous prostaglandin E1 versus
pentoxifylline therapy in chronic arterial occlusive disease--a controlled
randomised multicenter study. Vasa Suppl. 1989;28:44-9.
79. Weiss T, Griesshaber J, Rogatti W, et al. Effect of intra-arterial and intravenous
PGE1 infusions on transcutaneous oxygen pressure in patients with critical
ischemia of the extremities. Vasa Suppl. 1991;33:341-2.
80. Wigley FM, Flavahan NA: Raynaud's phenomenon. Rheum Dis Clin North Am
1996 Nov; 22(4): 765-81
81. Wigley FM, Seibold JR, Wise RA, et al. Intravenous iloprost treatment of
Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis. J
Rheumatol. 1992 Sep;19(9):1407-14.
82. Wigley FM, Wise RA, Seibold JR, et al. Intravenous iloprost infusion in patients
with Raynaud phenomenon secondary to systemic sclerosis. A multicenter,
placebo-controlled, double-blind study. Ann Intern Med. 1994 Feb 1;120(3):199-
206.
83. Wollersheim H & Thien T: Dose-response study of prazosin in Raynaud's
phenomenon: clinical effectiveness versus side effects. J Clin Pharmacol 1988;
28:1089-1093.
84. Wollersheim H, Thien T, Fennis J et al: Double-blind placebo-controlled study of
prasozin in Raynaud's phenomenon. Clin Pharmacol Ther 1986; 40:219-225.
85. Wooster DL, Shamess CJ, Madras PN, Keystone EC. Intra-arterial alprostadil for
nonatherosclerotic vasculopathy. JAMA. 1981 May 8;245(18):1846-9.

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