What are the main uses of alprostadil. How does alprostadil work for erectile dysfunction. What are the most common side effects of alprostadil. Are there any serious drug interactions with alprostadil. What precautions should be taken when using alprostadil.

Understanding Alprostadil and Its Primary Uses

Alprostadil is a medication that belongs to the class of drugs known as prostaglandin analogs. It has two primary medical uses:

• Treatment of erectile dysfunction (ED) in adult males
• Maintaining patency of the ductus arteriosus in newborns with certain congenital heart defects

For erectile dysfunction, alprostadil is considered a second-line treatment option after oral medications like sildenafil (Viagra). It can be used alone or in combination with other ED medications.

In newborns, alprostadil helps keep the ductus arteriosus open temporarily before corrective heart surgery can be performed. This allows blood to bypass the lungs in infants with ductus-dependent circulation.

How Common is Erectile Dysfunction?

Erectile dysfunction affects over 150 million men worldwide. The prevalence increases with age, with up to 40% of men experiencing ED by age 40 and nearly 70% by age 70. Given its widespread impact, effective treatments like alprostadil play an important role in men’s sexual and overall health.

Mechanism of Action: How Alprostadil Works

Alprostadil exerts its effects through several mechanisms:

• Relaxation of smooth muscle in blood vessels, leading to vasodilation
• Increased blood flow to the penis
• Inhibition of platelet aggregation
• Stimulation of intestinal and bronchial secretions

For erectile dysfunction, the key action is vasodilation of the penile blood vessels. This increased blood flow to the penis helps achieve and maintain an erection sufficient for sexual activity.

In newborns, alprostadil keeps the ductus arteriosus open by relaxing the smooth muscle in its walls. This allows blood to continue flowing through this fetal blood vessel until corrective surgery can be performed.

How Quickly Does Alprostadil Take Effect?

When used for ED, alprostadil typically produces an erection within 5-20 minutes after administration. The duration of effect is usually 30-60 minutes but can last up to 2-3 hours in some cases. For neonatal use, the effects on the ductus arteriosus are seen within minutes of intravenous administration.

Administration Methods and Dosing for Alprostadil

Alprostadil can be administered through several routes, depending on the indication:

For Erectile Dysfunction:

• Intracavernosal injection: Directly into the penis
• Intraurethral suppository: Inserted into the urethra
• Topical cream: Applied to the tip of the penis

For Neonatal Use:

• Intravenous infusion: Continuous administration through an IV

Dosing varies based on the route of administration and individual patient response. For ED, typical starting doses are:

• Intracavernosal: 1.25-2.5 micrograms
• Intraurethral: 125-1000 micrograms
• Topical: 200-300 micrograms

Doses may be adjusted based on efficacy and tolerability. For neonatal use, the typical starting dose is 0.05-0.1 micrograms/kg/minute, adjusted as needed.

Common Side Effects and Adverse Reactions

While alprostadil is generally well-tolerated, it can cause some side effects. The most common adverse reactions include:

For Erectile Dysfunction Use:

• Penile pain or burning sensation
• Prolonged erection (priapism)
• Minor bleeding or spotting at the site of administration
• Dizziness
• Headache

For Neonatal Use:

• Apnea
• Flushing
• Fever
• Seizures
• Hypotension

Most side effects are mild and transient. However, priapism (an erection lasting more than 4 hours) is a serious condition requiring immediate medical attention to prevent permanent damage to the penis.

Can Alprostadil Cause Allergic Reactions?

While rare, allergic reactions to alprostadil can occur. Symptoms may include rash, itching, swelling, severe dizziness, or difficulty breathing. Patients should seek immediate medical attention if they experience signs of a severe allergic reaction.

Contraindications and Precautions for Alprostadil Use

Alprostadil should not be used in certain situations due to increased risks. Contraindications include:

• Known hypersensitivity to alprostadil or related prostaglandins
• Conditions that predispose to priapism (e.g., sickle cell anemia, multiple myeloma)
• Penile implants or anatomical deformities of the penis
• Active penile infections or inflammation

Caution is advised in patients with:

• Bleeding disorders
• History of priapism
• Cardiovascular diseases
• Pulmonary diseases

Patients should inform their healthcare provider of all medical conditions and medications before starting alprostadil therapy.

Is Alprostadil Safe for Use in Pregnancy?

Alprostadil is classified as Pregnancy Category C, meaning risk cannot be ruled out. It should only be used during pregnancy when the potential benefits outweigh the risks. For its primary indications (ED and neonatal use), pregnancy is generally not a concern.

Drug Interactions with Alprostadil

Alprostadil can interact with several medications, potentially altering their effects or increasing the risk of side effects. Some important drug interactions include:

Moderate Interactions:

• Anticoagulants (e.g., warfarin, heparin): May increase bleeding risk
• Antihypertensive medications: May enhance hypotensive effects
• Other ED medications (e.g., sildenafil, tadalafil): May increase risk of priapism
• Sympathomimetics: May antagonize the effects of alprostadil

Minor Interactions:

• NSAIDs (e.g., ibuprofen, naproxen): May increase bleeding risk
• Alcohol: May enhance hypotensive effects

Patients should always inform their healthcare provider about all medications, supplements, and herbal products they are taking to avoid potential interactions.

Can Alprostadil Be Used with Viagra or Cialis?

While combining alprostadil with oral ED medications like Viagra (sildenafil) or Cialis (tadalafil) can enhance efficacy, it also increases the risk of prolonged erections and other side effects. Such combinations should only be used under close medical supervision and with caution.

Monitoring and Follow-up for Alprostadil Therapy

Proper monitoring is essential for safe and effective use of alprostadil. Key aspects of monitoring include:

• Regular assessment of efficacy and side effects
• Adjustment of dosing as needed
• Monitoring for signs of priapism
• Evaluation of cardiovascular health, especially in older patients
• For neonatal use, continuous monitoring of vital signs and ductus arteriosus patency

Patients using alprostadil for ED should have regular follow-up appointments to assess treatment response and address any concerns. For neonatal use, constant medical supervision is required during administration.

How Often Should Patients Be Evaluated When Using Alprostadil?

For ED treatment, initial follow-up is typically recommended after 1-3 months of use, with subsequent visits every 6-12 months if therapy is stable. More frequent monitoring may be needed if dose adjustments are required or side effects occur. Neonates receiving alprostadil require continuous monitoring in a hospital setting.

Off-label Uses and Emerging Research on Alprostadil

While primarily used for ED and maintaining ductus arteriosus patency, alprostadil has been studied for several off-label uses:

• Treatment of Raynaud’s phenomenon
• Improving peripheral vascular disease symptoms
• Enhancing wound healing in diabetic foot ulcers
• Potential applications in female sexual arousal disorder

Research is ongoing to explore these and other potential therapeutic applications of alprostadil. However, more studies are needed to establish efficacy and safety for these off-label uses.

Is Alprostadil Effective for Raynaud’s Phenomenon?

Some studies have shown promising results for alprostadil in treating severe Raynaud’s phenomenon, particularly in cases resistant to other treatments. It may help improve blood flow and reduce pain and ulceration. However, this remains an off-label use, and more research is needed to fully establish its role in Raynaud’s management.

In conclusion, alprostadil is a versatile medication with important applications in erectile dysfunction and neonatal cardiology. While generally safe and effective when used as directed, it requires careful monitoring and consideration of potential side effects and drug interactions. As research continues, we may see expanded uses for this prostaglandin analog in the future. Patients considering alprostadil therapy should discuss the benefits and risks with their healthcare provider to determine if it’s an appropriate treatment option for their specific situation.

Alprostadil Interactions Checker – Drugs.com

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There are 38 drugs known to interact with
alprostadil, along with
3 disease interactions.

Of the total drug interactions,
36 are moderate, and 2 are minor.

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• View all 38 medications that may interact with alprostadil
• View alprostadil disease interactions (3)

Most frequently checked interactions

View interaction reports for alprostadil and the medicines listed below.

• Major
• Moderate
• Minor
• Unknown

• Activated Charcoal (charcoal)
• Alcohol (contained in alcoholic beverages) (ethanol)
• AndroGel (testosterone)
• Aspirin Low Strength (aspirin)
• Benadryl (diphenhydramine)
• Celebrex (celecoxib)
• Cialis (tadalafil)
• Claritin (loratadine)
• CoQ10 (ubiquinone)
• Crestor (rosuvastatin)
• Cymbalta (duloxetine)
• Eliquis (apixaban)
• Fish Oil (omega-3 polyunsaturated fatty acids)
• Flomax (tamsulosin)
• Flonase (fluticasone nasal)
• Humalog (insulin lispro)
• Lasix (furosemide)
• Levitra (vardenafil)
• Lyrica (pregabalin)
• Metoprolol Succinate ER (metoprolol)
• Metoprolol Tartrate (metoprolol)
• Nexium (esomeprazole)
• Paracetamol (acetaminophen)
• Paxlovid (nirmatrelvir / ritonavir)
• Tylenol (acetaminophen)
• Viagra (sildenafil)
• Vitamin B12 (cyanocobalamin)
• Vitamin C (ascorbic acid)
• Vitamin D3 (cholecalciferol)
• Xarelto (rivaroxaban)

Alprostadil disease interactions

There are 3 disease interactions with alprostadil which include:

• respiratory function
• bleeding
• hypotension

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.

Major	Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate	Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor	Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown	No interaction information available.

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Continuing Education Activity

Alprostadil is a medication used in the management and treatment of erectile dysfunction in males and for temporary patency of ductus arteriosus in newborns with congenital heart diseases before surgical intervention. It is in the prostaglandin analog class of medications. This activity reviews the indications, action, and contraindications for alprostadil as a valuable agent in the therapy of erectile dysfunction in males and presurgical management for newborns with congenital heart diseases with ductus arteriosus dependent circulation. This activity will also highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, monitoring, relevant interactions) pertinent for members of the interprofessional team in the management of those conditions.

Objectives:

• Review the indications for alprostadil.

• Describe the adverse effects and contraindications of alprostadil.

• Identify the appropriate monitoring and toxicity of alprostadil.

• Summarize interprofessional team strategies for enhancing care coordination and communication to advance the management of conditions that can be treated with alprostadil and improve patient outcomes.

Access free multiple choice questions on this topic.

Indications

Over 150 million people worldwide are affected by erectile dysfunction. Alprostadil is an approved second-line treatment for erectile dysfunction (oral phosphodiesterase-5 inhibitors like sildenafil are first-line therapy). [1] Another option is using alprostadil in combination with other medications, the combination of papaverine, phentolamine, and alprostadil, known as “trimix,” is particularly effective when used for intracavernous injection as a treatment for erectile dysfunction (ED). However, it is only available from compounding pharmacies authorized to produce such extemporaneous dosage forms as it is otherwise not produced commercially.[2]

Alprostadil can also be a therapeutic option for the temporary ductus arteriosus patency maintenance in heart conditions where duct patency is mandated for survival until the defect is corrected surgically. The defects are both cyanotic (e.g., TGA – transposition of great vessels, TOF – tetralogy of Fallot, tricuspid atresia, pulmonary stenosis, etc.) and acyanotic (e.g., coarctation of the aorta, interruption of the aortic arch).[3][4] Alprostadil IV is FDA-approved for the temporary maintenance of patency of ductus arteriosus in neonates with ductal-dependent congenital heart disease until surgery. Alprostadil causes vasodilation by a direct effect on vascular and ductus arteriosus smooth muscle. In infants exhibiting restricted systemic blood flow, alprostadil can increase systemic blood pressure, and decrease the pulmonary artery pressure to aortic pressure ratio. Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. Lipo-PGE1 can effectively improve the neural function of patients with DPN.[5]

Topical alprostadil has also shown promising results for the treatment of FSAD (female sexual arousal disorder) when used in a clinic on females with female sexual arousal disorder, but additional studies are necessary to define further a proper role of topical alprostadil in the treatment of FSAD.[6] Alprostadil is widely used to manage ischemic changes in patients with Raynaud phenomena.[7] Prostaglandin E1 analogs have shown to be efficacious as a modality for conservative treatment for patients with lumbar spinal canal stenosis.[8] Contrast-induced nephropathy (CIN) is one of the top five leading causes of hospital-acquired acute renal injury, using alprostadil has been shown to reduce the precontrast serum creatinine (SCr), blood urea nitrogen (BUN) levels, and a decrease in the incidence of contrast-induced nephropathy (CIN). [9]

Mechanism of Action

Alprostadil is a synthetic analog of prostaglandin E1 (PGE1) and shows a multifariousness of pharmacologic actions. Alprostadil binds as an agonist to prostaglandin receptors, e.g., EP2 which in turns activates adenylate cyclase leading to accumulation of 3’5′-cAMP (cyclic adenosine monophosphate) which is responsible for the pharmacologic effects of the medication including smooth muscle relaxation, causing vasodilation (increasing peripheral blood flow; helps in erectile dysfunction) and bronchodilation, and inhibits platelet aggregation.[10]

Administration

1. Intracavernous alprostadil is useful for its vasodilating properties, which act by relaxing the smooth muscle of the corpus cavernosum, hence increasing the diameter of the cavernous arteries leading to an erection. After intracavernous administration of alprostadil, it is either metabolized locally or via the lungs after being absorbed systematically. Short-term trials have shown that using alprostadil by an intracavernous route is equal to if not superior in inducing erection as compared to other drugs used via intracavernous routes such as papaverine or the combination therapy of papaverine and phentolamine, linsidomine, and topical nitroglycerine (glyceryl trinitrate). If used in therapeutic dosages, most patients tolerate intracavernous alprostadil well. Some potentially severe side effects of intracavernous alprostadil are priapism (4%) and fibrosis (8%).[11]

2. Topical alprostadil therapy is associated with a high rate of discontinuation, as are intracavernosal or transurethral therapies, which are inconvenient and invasive.[12]  Several studies, including four double-blind, placebo-controlled, phase II trials, show that alprostadil topical cream is efficacious and well-tolerated in ED patients with mild-to-severe symptoms, in those undergoing treatment for cardiovascular diseases and diabetes mellitus and in otherwise healthy ED patients. Thus, alprostadil topical cream is a potential first-choice alternative for ED patients who do not respond or who cannot tolerate or do not accept PDE-5 inhibitor therapy.

3. Intraurethral suppository/medicated urethral system for erection (muse) – alprostadil can be used as an intraurethral suppository or medicated urethral system for erection, but have shown to be less efficient in inducing cavernous smooth muscle relaxation and also have more side effects such as penile pain/burning, hypotension, and urethral bleeding. This is why self-injection therapy with alprostadil is still considered the first-line therapy/gold standard for the management of erectile dysfunction. The intraurethral suppository is usually only for patients who have refractory erectile dysfunction.[13]

4. Alprostadil cream is an option with vacuum devices with an elastic ring placed at the base of the penis to achieve sufficient rigidity to maintain an erection for satisfactory penetration.[14]

5. Intravenous prostacyclin (PGI2) analogs have shown to be more effective than aspirin for dealing with the rest pain and healing the ischaemic ulcers in Buerger disease.[15]

Adverse Effects

When used as an intraurethral suppository (medicated urethral system for erection)[16]:

• Urethral strictures 

• Hypotension

• Syncope

• Penile/urethral pain

• Priapism/prolonged erection

• Penile fibrosis

• Headache

• Dizziness

Side effects of alprostadil on intracavernosal use:

• Hypotension/hypertension

• Dizziness

• Headache

• Prolonged erection/priapism is less common

• Rash on the penis

• Swelling of the penis

• Penile infections

• Injuries to the penis including hematoma formation at the site of the injection

Side effects of prostaglandin E1 analog (alprostadil) on intravenous use:

• Flushing

• Hypotension/hypertension

• Tachycardia/bradycardia

• Dizziness

• Headache

• Electrolyte imbalances such as hypokalemia

• Nausea/vomiting

• Gastrointestinal upset

• Infection at the injection site or even sepsis

• Pain at the injection site

• Cough

• Flu-like symptoms

• GERD

• Bronchoconstriction

Contraindications

1. Known hypersensitivity to alprostadil or components of the dosage form.

2. Sickle cell disease or trait, multiple myeloma, leukemia, polycythemia vera, thrombocythemia as these conditions are known to precipitate priapism, and alprostadil can also predispose to prolonged erection or priapism.

3. Peyronie disease of the penis, as alprostadil, is known to cause penile fibrosis and may worsen the condition.

4. Alprostadil intraurethral suppository; “medicated urethral system for erection” should be avoided in patients with urethral strictures as using it can cause further injuries to the penis.

5. Clinicians should avoid using alprostadil as an intraurethral suppository in patients with urethritis.

Monitoring

When starting alprostadil for a patient complaining of erectile dysfunction, certain things are to be kept in mind to prevent and for the early identification of adverse effects for better overall outcomes. Alprostadil is known to cause hemodynamic instability causing hypotension/hypertension, and flushing.  It is advisable to monitor blood pressure, heart rate, and temperature before and after the use of the drug. Alprostadil is also known to cause penile pathologies such as stricture formation, fibrosis, and hematoma formation at the site of injection. Regular examination by a physician and timely attention by one on the onset of discomfort can bring about better possible outcomes. For a better understanding of drug-to-effect response, monitoring the duration of erection can be essential for tailoring management for the patient.

Toxicity

The use of alprostadil for the treatment of erectile dysfunction in men has correlations with prolonged erection, and sometimes priapism. The incidence of priapism as an adverse effect of alprostadil is more common with the intraurethral suppository, and priapism is a genitourinary emergency that requires detailed evaluation. The evaluation is primarily based on physical exam and possibly with the help of penile ultrasonography and penile blood gas analysis. Some of the management techniques include aspiration of cavernosal blood, cold saline irrigation, and penile injections with sympathomimetic agents.[17] Penile prosthesis implantation for priapism is also commonly used.[18]

Enhancing Healthcare Team Outcomes

Managing erectile dysfunction with alprostadil as an intracavernosal injection or as an intraurethral suppository requires an interprofessional team of healthcare providers, including a nurse, pharmacist, and several physicians in different specialties. Apart from classical causes of erectile dysfunction such as diabetes mellitus, hypertension, other common lifestyle factors such as obesity, limited or absence of physical exercise, lower urinary tract system infections are also linked to the development of erectile dysfunction requiring attention. Without proper management and patient education, the morbidity associated with the treatment itself can be dreadful. Patient education for the use of alprostadil as an intracavernosal injection form or as an intraurethral suppository is a must and is an essential aspect of the management. The patient should be monitored timely for the adverse effects of the drug, such as prolonged erection/priapism, penile fibrosis, urethritis, and penile fibrosis or stricture formation, and circulatory disturbances causing hypotension. Consult with a radiologist, urologist, to assess any penile pathology before starting alprostadil. Consult with a psychiatrist to evaluate for possible psychiatric issues that might cause erectile dysfunction. Consult a sex therapist for holistic management of erectile dysfunction. Consult a cardiologist as studies have shown an association of cardiovascular diseases with erectile dysfunction (ED), whereas ED can be a strong indicator of CAD (coronary artery disease), and the recommendation is for cardiovascular assessment of a noncardiac patient in a patient coming with the chief complaint of erectile dysfunction.[19] Also, using alprostadil can cause circulatory issues causing hypotension.

Pharmacists should be ready to counsel patients on the proper use of the intracavernous and suppository formulations since they require the patient to have solid administration technique skills. If the pharmacist has any concerns about the patient’s ability to self-administer the drug, or there are drug interactions on the medication review, they should contact the prescribing physician promptly. Nurses can also give counsel, and determine adherence and regimen effectiveness on follow-up visits, and check for any adverse medication effects, reporting any concerns to the physician. Only with this type of interprofessional team approach can alprostadil therapy be most effective. [Level V]

Patients discussing reproductive health, particularly men, can be challenging, and it is essential to be empathetic and maintain a professional attitude while establishing a rapport. Creating a positive and respectful approach for patient and provider, allows there to be an open discussion for subject matters such as erectile dysfunction.

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• Comment on this article.

References

1.

Hanchanale V, Eardley I. Alprostadil for the treatment of impotence. Expert Opin Pharmacother. 2014 Feb;15(3):421-8. [PubMed: 24369066]

2.

Vieillard V, Eychenne N, Astier A, Yiou R, Deffaux C, Paul M. Physicochemical stability study of a new Trimix formulation for treatment of erectile dysfunction. Ann Pharm Fr. 2013 Sep;71(5):358-63. [PubMed: 24075706]

3.

Coceani F, Olley PM, Bishai I, Bodach E, Heaton J, Nashat M, White E. Prostaglandins and the control of muscle tone in the ductus arteriosus. Adv Exp Med Biol. 1977;78:135-42. [PubMed: 899912]

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Aykanat A, Yavuz T, Özalkaya E, Topçuoğlu S, Ovalı F, Karatekin G. Long-Term Prostaglandin E1 Infusion for Newborns with Critical Congenital Heart Disease. Pediatr Cardiol. 2016 Jan;37(1):131-4. [PubMed: 26260095]

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Wu JD, Tao S, Jin X, Jiang LL, Shen Y, Luo Y, Zhang P, Lee KO, Ye L, Ma JH. PGE1 improves diabetic peripheral neuropathy in patients with type 2 diabetes. Prostaglandins Other Lipid Mediat. 2016 Nov;126:24-28. [PubMed: 27421690]

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Kielbasa LA, Daniel KL. Topical alprostadil treatment of female sexual arousal disorder. Ann Pharmacother. 2006 Jul-Aug;40(7-8):1369-76. [PubMed: 16757679]

7.

Marasini B, Massarotti M, Bottasso B, Coppola R, Del Papa N, Maglione W, Comina DP, Maioli C. Comparison between iloprost and alprostadil in the treatment of Raynaud’s phenomenon. Scand J Rheumatol. 2004;33(4):253-6. [PubMed: 15370722]

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Yoshihara H. Prostaglandin E1 Treatment for Lumbar Spinal Canal Stenosis: Review of the Literature. Pain Pract. 2016 Feb;16(2):245-56. [PubMed: 25612248]

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Zhang JZ, Kang XJ, Gao Y, Zheng YY, Wu TT, Li L, Liu F, Yang YN, Li XM, Ma YT, Xie X. Efficacy of alprostadil for preventing of contrast-induced nephropathy: A meta-analysis. Sci Rep. 2017 Apr 21;7(1):1045. [PMC free article: PMC5430773] [PubMed: 28432310]

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Neves-Zaph SR. Phosphodiesterase Diversity and Signal Processing Within cAMP Signaling Networks. Adv Neurobiol. 2017;17:3-14. [PubMed: 28956327]

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Lea AP, Bryson HM, Balfour JA. Intracavernous alprostadil. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction. Drugs Aging. 1996 Jan;8(1):56-74. [PubMed: 8785470]

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Becher E. Topical alprostadil cream for the treatment of erectile dysfunction. Expert Opin Pharmacother. 2004 Mar;5(3):623-32. [PubMed: 15013930]

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Porst H. Transurethral alprostadil with MUSE (medicated urethral system for erection) vs intracavernous alprostadil–a comparative study in 103 patients with erectile dysfunction. Int J Impot Res. 1997 Dec;9(4):187-92. [PubMed: 9442415]

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Mantovani F. Alprostadil plus Vacuum (VITARUM) in severe erectile dysfunction (ED). Arch Ital Urol Androl. 2017 Jun 30;89(2):146-147. [PubMed: 28679188]

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Cacione DG, Macedo CR, Baptista-Silva JC. Pharmacological treatment for Buerger’s disease. Cochrane Database Syst Rev. 2016 Mar 11;3(3):CD011033. [PMC free article: PMC7104255] [PubMed: 26967103]

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Porst H. [Transurethral alprostadil administration with MUSE (“Medicated Urethral System for Erection”). Current overview and personal experiences]. Urologe A. 1998 Jul;37(4):410-6. [PubMed: 9738294]

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Podolej GS, Babcock C. Emergency Department Management Of Priapism. Emerg Med Pract. 2017 Jan;19(1):1-16. [PubMed: 28027457]

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Yücel ÖB, Pazır Y, Kadıoğlu A. Penile Prosthesis Implantation in Priapism. Sex Med Rev. 2018 Apr;6(2):310-318. [PubMed: 28916463]

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Shamloul R, Ghanem H. Erectile dysfunction. Lancet. 2013 Jan 12;381(9861):153-65. [PubMed: 23040455]

Disclosure: Ashish Jain declares no relevant financial relationships with ineligible companies.

Disclosure: Omar Iqbal declares no relevant financial relationships with ineligible companies.

instructions for use, analogues, articles » Directory of drugs

List of trade names

Analogue of natural PgE1, has vasodilating (at the level of arterioles, precapillary sphincters, muscular arteries), antiaggregant and angioprotective action. Improves microcirculation and peripheral circulation, promotes the opening of collateral vessels. Reduces peripheral vascular resistance, blood pressure, reflexively increases heart rate, which leads to an increase in the IOC. Improves the rheological properties of blood, helping to increase the elasticity of red blood cells and reducing adhesion / aggregation of platelets. It has a fibrinolytic effect. It has an effect on metabolism, increases the utilization of glucose and oxygen, inhibits the release of free radicals and lysosomal enzymes from granulocytes and macrophages, stimulates protein synthesis, has a beneficial effect on lipid metabolism (suppressing cholesterol synthesis and lowering LDL concentration), inhibits the proliferation of smooth muscle cells. Stimulates the smooth muscles of the intestines, bladder and uterus; suppresses the secretion of gastric juice.

Pharmacokinetics

Alprostadil is an endogenous natural product with a short half-life (about 10 s). When administered intravenously, it is metabolized in the lungs (with a single passage up to 60-90%). As a result of enzymatic oxidation, 3 biologically active metabolites are formed: 15-keto-PgE1, 15-keto-13,14-dihydro-PgE1 and 13,14-dihydro-PgE1 (PgE0). Keto metabolites have a lower biological effect compared to alprostadil, the PgE0 metabolite has a comparable effect to PgE1. PgE0 acts longer, its T1 / 2 is about 1 min (alpha phase) and 30 min (beta phase). In all likelihood, the pharmacodynamic effect is mainly due to this biologically active stable metabolite. The main metabolites are excreted by the kidneys – up to 88% and with feces – 12%.

Obliterating diseases of arteries III-IV stage. (according to Fontaine’s classification), accompanied by pain at rest or trophic changes.
Obliterating endarteritis with severe “intermittent” claudication (with impossible surgical revascularization of the lower limb),
obliterating atherosclerosis,
diabetic angiopathy,
thromboangiitis obliterans (Buerger’s disease),
Raynaud’s syndrome with trophic disorders,
vasculitis ,
scleroderma,
spasms of the calf muscles,
damaging effects of physical factors, especially extreme vibration.
The need to temporarily maintain the functioning of the ductus arteriosus until the time of corrective surgery for congenital ductus-dependent heart defects in newborns (including mitral atresia, pulmonary atresia, tricuspid valve, tetralogy of Fallot).

Hypersensitivity, pregnancy, lactation. In newborns: respiratory depression, respiratory distress syndrome, a state of spontaneous persistently open arterial duct.
With care. Acute and subacute myocardial infarction, previous myocardial infarction within the last 6 months, severe or unstable angina pectoris, decompensated CHF, arterial hypotension, cardiovascular insufficiency (special attention should be paid to controlling the volume load of the carrier solution), pulmonary edema, severe arrhythmias heart, broncho-obstructive syndrome (severe with signs of respiratory failure), infiltrative changes in the lungs, liver failure (including history), increased risk of bleeding (gastric or duodenal ulcer, severe damage to cerebral vessels, proliferative retinopathy with a tendency to bleeding, extensive trauma, etc. ), hemodialysis (treatment with the drug should be carried out in the post-dialysis period), type 1 diabetes mellitus, especially with extensive vascular lesions (in elderly patients). Concomitant therapy with vasodilating or anticoagulant drugs. In newborns: bradypnea, arterial hypotension, tachycardia or hyperthermia.

In chronic obliterating diseases of the arteries, 10-20 mcg is administered intravenously (using an infusion device) for 1-2 hours 1 time per day. If the drug is administered through an established catheter, an intravenous infusion is carried out for 12 hours at a dose of 0.1-0.6 ng / kg / min (5-10 μg).
In / in – 40 mcg for 2 hours 2 times a day (after dissolving the contents of the ampoule in 50 ml of 0.9% NaCl solution) or 50-200 mcg 1 time per day (in more severe conditions – 50-100 mcg 2 times a day). As a solvent, use 200-500 ml 0.9% NaCl solution, 5-10% dextrose solution, the duration of the infusion should be at least 2 hours. The solution should be prepared immediately before administration. The duration of treatment is on average 14 days, with a positive effect, treatment with the drug can be continued for another 7-14 days. The course of treatment should not exceed 4 weeks. In the absence of a positive effect within 2 weeks from the start of treatment, further use of the drug should be discontinued.
In case of impaired renal function (serum creatinine concentration more than 1.5 mg / l), intravenous administration begins with 20 mcg. If necessary, after 2-3 days, a single dose is increased to 40-60 mcg. For patients with renal insufficiency and heart failure, the maximum volume of fluid administered is 50-100 ml / day. The course of treatment – 4 weeks. In congenital ductus-dependent malformations of newborns, it is administered continuously by infusion through an umbilical arterial catheter (led directly to the orifice of the arterial duct) or one of the large veins at an initial rate of 0.05-0.1 (up to 0.4) mcg / kg / min. After achieving a therapeutic effect, the infusion rate is reduced to the minimum maintenance – 0. 01-0.02 μg / kg / min. If severe side effects occur, the administered dose should be reduced.

From the digestive system: discomfort in the epigastric region, possible diarrhea, nausea, vomiting, increased activity of “liver” transaminases; rarely – hyperbilirubinemia.
From the CCC: lowering blood pressure, tachycardia, cardialgia; rarely – the development or aggravation of heart failure, cardiac arrhythmias, AV blockade, acute pulmonary edema.
From the nervous system: possible headache, dizziness, excessive fatigue, feeling unwell. Allergic reactions: possible skin rash, itching. On the part of the musculoskeletal system: with prolonged continuous administration (from 4 weeks or more) – reversible hyperostosis of tubular bones. Laboratory indicators: leukocytosis, leukopenia, rarely – an increase in the titer of C-reactive protein.
Local reactions: phlebitis (proximal to the site of intravenous injection, up to 40% of patients).
Other: increased sweating, hyperthermia, swelling of the limb, into the vein of which the infusion is carried out.
In newborns: hyperthermia, decreased blood pressure, hyperemia of the skin, diarrhea, bradycardia, tachycardia, skin rashes, convulsions, respiratory depression (up to apnea), rarely – disseminated intravascular coagulopathy. With a long course of treatment (within a few weeks): hyperostosis in the bones of the lower extremities. Extremely rare (up to 1% of cases): shock, acute HF, hyperbilirubinemia, bleeding, drowsiness, bradypnea, decreased respiratory function, tachypnea, anuria, impaired renal function, hypoglycemia, ventricular fibrillation, stage II AV block, supraventricular arrhythmia, tension neck muscles, irritability, hypothermia, hypercapnia, hyperemia of the skin, hematuria, peritoneal symptoms, tachyphylaxis, hyperkalemia, thrombocytopenia, anemia.
Overdose. Symptoms: decrease in blood pressure, hyperemia of the skin, weakness; in newborns, in addition: apnea, bradycardia.
Treatment: slowing down or stopping the infusion, if signs of depression of the respiratory center appear in newborns, mechanical ventilation is indicated.

Pharmaceutically incompatible with other solutions. Enhances the effect of antihypertensive drugs (including vasodilators), as well as anticoagulants and antiplatelet agents.

The prepared solution is recommended to be used immediately after preparation, it is possible to temporarily store the resulting solution for no more than 24 hours at a temperature of 2 to 8 degrees. C. Alprostadil can only be used by doctors with experience in angiology, familiar with modern methods of continuous monitoring of CVS and having the appropriate equipment for this. During the period of treatment, it is necessary to control blood pressure, heart rate, biochemical parameters of the blood, the blood coagulation system (in case of violations of the blood coagulation system or with simultaneous therapy with drugs that affect the coagulation system). Patients with ischemic heart disease, renal insufficiency (serum creatinine more than 1.5 mg / dl) should be monitored in a hospital during treatment with alprostadil and within 1 day after stopping treatment. To avoid the appearance of symptoms of overhydration in such patients, the volume of fluid administered should, if possible, not exceed 50-100 ml per day. It is necessary to dynamically monitor the patient’s condition (control of blood pressure and heart rate), if necessary – control of body weight, fluid balance, measurement of central venous pressure or echocardiography.
In newborns, the drug should be used under constant control of blood pressure, if there are conditions for mechanical ventilation. In patients with chronic obliterating diseases of the arteries of the lower extremities, infusion therapy is a necessary part of complex treatment. The clinical effect is long-term and may appear with a certain delay after the end of the course of treatment.
Phlebitis (proximal to the injection site) is usually not a reason to stop therapy, signs of inflammation disappear after a few hours after stopping the infusion or changing the injection site, specific treatment is not required in such cases. Catheterization of the central vein can reduce the incidence of this side effect of the drug.
Compliance with the dosage form of alprostadil used for specific indications for its use should be strictly observed.

official instructions for use, analogues, price, availability in pharmacies

Currently, the drug is not listed in the State Register of Medicines or the specified registration number has been excluded from the register.

Registration certificate P N012232/01

Trade name of the drug: Alprostan

International non-proprietary name of the drug. Alprostadil

Dosage form:

Concentrate for solution for infusion 0.1 mg/0.2 ml

Composition

Active substance: 1 ampoule contains 0.1 mg of alprostadil.
Excipients: absolute ethanol up to 0.2 ml.

Description

Clear, colorless solution.

Pharmacotherapeutic group

Vasodilator – preparation PGE ₁ .

ATX code: [C01EA01].

Pharmacological properties

The active substance of the drug Alprostan – alprostadil (synthetic analogue of natural prostaglandin E ₁ ) is a vasodilator, angioprotective agent. It acts in a complex manner, improving microcirculation and peripheral circulation, causing vasodilation at the level of arterioles, precapillary sphincters, and muscular arteries. With intracavernous administration, it relaxes the smooth muscles of the cavernous bodies, which helps to increase blood flow and improve microcirculation in them. With intra-arterial administration, it contributes to the temporary preservation of a functioning arterial duct in newborns.
Improves the rheological properties of blood, helping to increase the elasticity of erythrocytes; has an effect on hemocoagulation, reducing adhesion and aggregation of platelets. It has a fibrinolytic effect. It has an anti-atherogenic effect, slowing down the activation of neutrophils, excessive proliferation of vascular wall cells.
Reduces total peripheral vascular resistance, blood pressure, reflexively increases heart rate, which leads to an increase in cardiac output. Stimulates the smooth muscles of the intestines, bladder and uterus; suppresses the secretion of gastric juice.

Pharmacokinetics

The half-life is about 10 seconds. Metabolized in the lungs with a single passage up to 60-90%, as a result of enzymatic oxidation, three biologically active metabolites are formed: 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1 and 13,14-dihydro-PGE1 (PGE0) . Keto metabolites have a lower biological effect compared to alprostadil, the metabolite 13,14-dihydro-PGE1 (PGE0) has a comparable effect to PGE1. Important is the fact that PGE0 acts longer, its half-life is about 1 minute (alpha phase) and 30 minutes (beta phase). In all likelihood, the pharmacodynamic effect is mainly due to this biologically active stable metabolite. The main metabolites are excreted in the urine – up to 88%, and feces – up to 12%.

Indications for use

Chronic obliterating diseases of the arteries of the extremities III-IV stage (according to Fontaine’s classification), accompanied by pain at rest or trophic changes (obliterating endarteritis with severe “intermittent claudication”, when surgery is not indicated; atherosclerosis of the arteries of the extremities; diabetic angiopathy; Buerger’s disease, Raynaud’s syndrome with trophic disorders; vasculitis in systemic scleroderma; peripheral circulatory disorders as a result of exposure to overlimiting vibration).
The need for temporary preservation of a functioning ductus arteriosus before reconstructive cardiac surgery for congenital ductus-dependent heart defects in newborns.

Contraindications

Hypersensitivity to alprostadil; pregnancy and lactation; acute and subacute myocardial infarction, severe or unstable form of angina pectoris; heart failure in the stage of decompensation, cardiac arrhythmias; severe broncho-obstructive syndrome with signs of respiratory failure, edema or infiltrative changes in the lungs; severe liver dysfunction; conditions characterized by a risk of bleeding (gastric or duodenal ulcer, severe damage to cerebral vessels, proliferative retinopathy with a tendency to bleeding, extensive trauma, etc. ). Simultaneous appointment of vasodilators and anticoagulants.
Age under 18 (excluding neonatal period) and over 75 years of age.
In neonatology: hypersensitivity to alprostadil, respiratory depression, respiratory distress syndrome, state of spontaneous persistently open ductus arteriosus.
Caution should be exercised in patients with arterial hypotension, cardiovascular insufficiency (particular attention should be paid to controlling the load “volume” due to the solvent), the increase in infusion volume should be limited in patients with severe heart failure due to the risk of pulmonary edema and possible stop hearts; in elderly patients with insulin-dependent diabetes mellitus, especially with extensive vascular lesions; when prescribing the drug to newborns in case of bradypnea, arterial hypotension, tachycardia or hyperthermia.

Dosage and administration

Use strictly as directed by your doctor to avoid complications.
In the treatment of adult patients with chronic obliterating diseases of the arteries of the extremities, Alprostan is prescribed intravenously at a dose of 50 to 200 mcg 1 time per day or, in more severe conditions, from 50 to 100 mcg 2 times a day. As a solvent, 200-500 ml of saline, 5% or 10% glucose solution are used, the duration of the infusion should be at least 2 hours. The solution should be prepared immediately before administration. The duration of the course of treatment is on average 14 days, with a positive effect, treatment with the drug can be continued for another 7-14 days. The course of treatment should not exceed 4 weeks. In the absence of a positive effect within 2 weeks from the start of therapy, further use of the drug should be discontinued.
In newborns, with congenital ductus-dependent defects, Alprostan is administered by continuous infusion into large veins or into the umbilical artery. The initial infusion rate is 0.01 to 0.05 µg/kg/min. When a therapeutic effect is achieved, the dose is reduced to the minimum maintenance dose (usually 0.01-0.02 μg / kg / min). If necessary, as an exception, the dose can be increased to 0.1 mcg / kg / min. If severe side effects occur, the administered dose should be reduced.
Recommended dilution of Alprostan, concentrate for infusion.

When diluting 1 ampoule (0.2 ml) of Alprostan, a concentrate for infusion in 9.8 ml of a carrier solution (physiological saline, 5% or 10% glucose solution), a concentration of 100 μg of alprostadil in 10 ml of solution is obtained. The resulting solution can be diluted in a larger volume of solvent. The solution is recommended to be used immediately after preparation, temporary storage of the resulting solution is possible for no more than 24 hours at a temperature of 2 – 8 ° C.

Side effect

In the treatment of limb ischemia, intravenous administration of alprostadil may be complicated by the appearance of signs of phlebitis proximal to the injection site, signs of inflammation disappear a few hours after stopping the infusion or changing the injection site, specific treatment in such cases is not required. Catheterization of the central vein can reduce the incidence of this side effect of the drug.
The number of adverse reactions may increase depending on the concentration, volume and rate of infusion. When using the drug, headache, dizziness, increased fatigue, feeling unwell, increased sweating are possible; disorders of the digestive system in the form of a feeling of discomfort in the epigastric region, nausea, vomiting, diarrhea; swelling of the limb, into the vein of which the drug solution is infused; arterial hypotension, tachycardia, angina attack, hyperthermia, allergic reactions; transient increase in the activity of hepatic transaminases in the blood serum, hyperbilirubinemia, hematuria.
A long course of treatment (from 4 or more weeks) may be complicated by reversible hyperostosis of tubular bones. There may be changes in the blood in the form of leukocytosis, leukopenia, as an exception, an increase in the titer of C-reactive protein is possible.
In newborns: hyperthermia, arterial hypotension, hyperemia of the skin, diarrhea, bradycardia, tachycardia, skin rash, convulsions, decreased respiratory function (up to apnea), DIC may develop. With a long course of treatment (within several weeks), hyperostosis of the bones of the lower extremities may appear. Possible: shock, acute heart failure, hyperbilirubinemia, bleeding, drowsiness, decreased respiratory function (bradypnea, tachypnea), decreased renal function, anuria, hypoglycemia, cardiac arrhythmias, AV blockade, neck muscle hypertonicity, irritability, hypothermia, hypercapnia , hyperemia of the skin, hematuria, peritoneal symptoms, tachyphylaxis, increased levels of potassium in the blood, thrombocytopenia, anemia.
If side effects occur, the dose of the drug should be reduced.

Overdose

In case of overdose, the following symptoms may appear: lowering of blood pressure, flushing of the skin, general weakness. If signs of overdose appear, the infusion of the drug should be slowed down or stopped. There is usually no need for specific treatment. If signs of depression of the respiratory center appear in newborns, artificial lung ventilation should be resorted to.

Interaction with other drugs

With the simultaneous appointment of alprostadil, the effect of antihypertensive and vasodilators is enhanced. With the simultaneous appointment of alprostadil with anticoagulant and antiplatelet agents, the risk of bleeding increases.

Special instructions

Alprostadil should only be used by physicians experienced in angiology, familiar with modern methods of continuous monitoring of the state of the cardiovascular system and having the appropriate equipment for this.
During the period of treatment, it is necessary to control the hemodynamic parameters of the acid-base balance, the biochemical parameters of the blood, the blood coagulation system (in case of violations of the blood coagulation system or during simultaneous therapy with drugs that affect the coagulation system).
Patients with ischemic heart disease, renal insufficiency (serum creatinine more than 1.5 mg / l) should be monitored in a hospital during treatment with alprostadil and within 1 day after stopping treatment. In order to avoid the appearance of symptoms of overhydration in such patients, the volume of fluid administered should, if possible, not exceed 50-100 ml per day. It is necessary to dynamically monitor the patient’s condition (control of blood pressure and heart rate), if necessary, control of body weight, fluid balance, measurement of central venous pressure or echocardiography.
In newborns, the drug should be used under constant monitoring of blood pressure, if there are conditions for mechanical ventilation.
In patients on hemodialysis, treatment with the drug should be carried out in the post-dialysis period.
In patients with chronic obliterating diseases of the arteries of the lower extremities, the use of the drug is part of a complex treatment, the clinical effect is long-term and may occur with a certain delay after the end of the course of treatment.

Release form

0.2 ml in colorless glass ampoules. 5 ampoules are placed in a molded PVC container.