Alprostadil

Alprostadil is a vasodilator belonging to the Prostaglandin E1 class which is used to treat certain types of erectile dysfunction (impotence; inability to get or keep an erection) in men.

Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating alprostadil may be metabolized in one pass through the lungs, primarily by beta- and omega-oxidation.

The half-life of about 5-10 min.

The common side effects are Headache, flushing, hypotension, diarrhea; pain, hematoma, and ecchymoses at inj site; pain during erection, fibrotic nodules, Peyronie’s disease, priapism, etc.

Alprostadil is available in the form of a dosage form such as Injections.

Alprostadil is available in Switzerland, Europe, India, Japan, the U.S

Alprostadil causes vasodilation by means of a direct effect on vascular and ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This is because, as a form of prostaglandinE1 (PGE1) it has multiple effects on blood flow. This results in increased pulmonary or systemic blood flow in infants. In cyanotic congenital heart disease, alprostadil's actions result in an increased oxygen supply to the tissues. In infants with an interrupted aortic arch or very severe aortic coarctation, alprostadil maintains distal aortic perfusion by permitting blood flow through the DA from the pulmonary artery to the aorta.

Alprostadil (prostaglandin E1) is produced endogenously to relax vascular smooth muscle and cause vasodilation. In adult males, the vasodilatory effects of alprostadil on the cavernosal arteries and the trabecular smooth muscle of the corpora cavernosa result in rapid arteriolar inflow and expansion of the lacunar spaces within the corpora

The Duration of Action of Alprostadil was within <1 hr.

The onset of Action of Alprostadil was within 5-20 min.

The Tmax was about 30-60 min and Cmax was about 16.8 ± 18.9 pg/mL, respectively

Alprostadil is available in the form of injection and suppository

For Injections: Inject this medicine very slowly into the penis as shown by the doctor 10 to 30 minutes before intercourse. Allow 5 to 10 seconds to completely inject the dose. Do not inject more than one dose within 24 hours. Also, do not use this medicine for more than 2 days in a row or more than 3 times a week.

Alprostadil is a vasodilator belonging to the Prostaglandin E1 class which is used to treat certain types of erectile dysfunction (impotence; inability to get or keep an erection) in men.

Alprostadil, a naturally occurring prostaglandin E₁, is a vasodilating agent and a platelet aggregation inhibitor. It induces erection by relaxation of the trabecular smooth muscles and dilation of cavernosal arteries, allowing blood flow to the lacunar spaces of the penis. It also relaxes the smooth muscles of the ductus arteriosus.

Alprostadil is a vasodilator belonging to the Prostaglandin E1 class which is used to treat certain types of erectile dysfunction (impotence; inability to get or keep an erection) in men.

Erectile Dysfunction

• Vascular, Psychogenic, or Mixed Etiology

Initial 2.5 mcg intracavernosal injection

Titrate by 2.5 mcg, then by 5-10 mcg intervals until the erection of <1 hr maintained; not to exceed 40 mcg (Edex) or 60 mcg (Caverject)

If no absolute response to the 2.5 mcg dose, may increase the second dose to 7.5 mcg followed by increments of 5-10 mcg

Once the appropriate dose is defined, the patient may self-administer injections at a frequency <3 times/week with at least 24hr between doses

• Neurogenic ED

Initial 1.25 mcg intracavernosal injection

Titrate by 1.25 mcg-2.5 mcg, then by 2.5-5 mcg until the erection of <1 hr maintained

The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Alprostadil is available in various dosage strengths of 500mcg/ml, 125mcg, 250mcg, 500mcg, 1000mcg, 10mcg, 20mcg, 40mcg

Alprostadil is available in the form of injectables and suppositories.

Alprostadil should be used to treat certain types of erectile dysfunction (impotence; inability to get or keep an erection) in men.

Erectile dysfunction: Eating the recommended amount of fruit, vegetables, and whole grain products are all foods that can help reduce the risk of erectile dysfunction.

The dietary restriction should be individualized as per the patient's requirements.

Alprostadil may be contraindicated in the following

• Known hypersensitivity to alprostadil or components of the dosage form.
• Sickle cell disease or trait, multiple myeloma, leukemia, polycythemia vera, and thrombocythemia as these conditions are known to precipitate priapism, and alprostadil can also predispose to prolonged erection or priapism.
• Peyronie disease of the penis, as alprostadil, is known to cause penile fibrosis and may worsen the condition.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• Prolonged Erection And Priapism

Prolonged erection defined as an erection lasting between 4 to 6 hours in duration occurred in 4% of 1,861 patients treated up to 18 months in studies of ALPROSTADIL. The incidence of priapism (erections lasting more than 6 hours in duration) was 0.4%. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

To minimize the chances of prolonged erection or priapism, Alprostadil should be titrated slowly to the lowest effective dose. In addition, do not use Alprostadil in patients who have conditions that predispose them to priapism, such as sickle cell anemia or sickle cell trait, multiple myeloma, or leukemia.

• Penile Fibrosis

The overall incidence of penile fibrosis, reported in clinical studies with Alprostadil was 3%. In one self-injection clinical study where the duration of use was up to 18 months, the incidence of penile fibrosis was 7.8%.

Physical examination of the penis should be performed periodically, to detect signs of penile fibrosis. Treatment with Alprostadil should be discontinued in patients who develop penile angulation or cavernosal fibrosis.

• Hypotension

Intracavernous injections of Alprostadil can increase peripheral blood levels of alprostadil which can result in hypotension. Avoid the use of Alprostadil in patients with known cavernosal venous leakage.

• Injection Site Bleeding When Used With Anticoagulants

Patients on anticoagulants, such as warfarin or heparin, may have an increased propensity for injection site bleeding after intracavernosal injection with Alprostadil. Compress the site of injection with an alcohol swab or sterile gauze for 5 minutes.

• Cardiovascular Risk Related To Underlying Medical Conditions

There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including Alprostadil, generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. In addition, the evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.

• Risks Of Use In Combination With Other Vasoactive Medications Injected Intracavernosally

The safety and efficacy of combinations of Alprostadil and other vasoactive agents injected intracavernosal have not been established in clinical studies. The risks of prolonged erection, priapism, and hypotension may be increased.

• Needle Breakage

Separate needles should be used for reconstitution and administration. ALPROSTADIL uses a superfine needle for administration. As with all superfine needles, the possibility of needle breakage exists. Needle breakage, with a portion of the needle remaining in the penis, has been reported and, in some cases, required hospitalization and surgical removal. Careful instruction in proper patient handling and injection techniques may minimize the potential for needle breakage

Alcohol consumption with Alprostadil may increase the risk of low blood pressure and cause adverse effects, such as Dizziness, fainting, light-headedness, or headache.

Alprostadil use in breastfeeding patients is not recommended.

US FDA pregnancy category: C (suppositories)

Food Warning

Avoid smoking tobacco while taking Alprostadil. Alprostadil doses higher than 2.5 mg three times a day may be considered to match the exposure seen in nonsmoking patients. In patients who smoke tobacco, plasma concentrations of Alprostadil are reduced by 50% to 60% compared to nonsmokers.

Decreased serum concentration with St. John’s wort.

The adverse reactions related to the molecule Alprostadil can be categorized as

• Common Adverse effects:

Headache, flushing, hypotension, diarrhea; pain, hematoma, and ecchymoses at inj site.

• Less Common adverse effects:

Pain during erection, fibrotic nodules, Peyronie’s disease, priapism.

• Rare adverse effects:

Penile fibrosis. Apnoea, fever, bradycardia, tachycardia, convulsion, edema, cardiac arrest, hypokalaemia, disseminated intravascular coagulation, and the cortical proliferation of long bones (children).

The clinically relevant drug interactions of Alprostadil are briefly summarized here.

• Decreased serum concentration with antacids, PPI, and CYP3A4 inducers (e.g., phenytoin, rifampicin).
• Increased plasma concentration with CYP1A1 (e.g. erlotinib), CYP3A4 inhibitors (e.g., clarithromycin), potent P-GP/BCRP inhibitors (e.g. ciclosporin, azole antifungals, protease inhibitors).
• Potentially Fatal: Enhanced hypotensive effect with amyl nitrate, nitroglycerin, and PDE-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Symptoms:

Pronounced hypotension.

Management:

Supportive treatment.

Pharmacodynamics:

● Alprostadil (prostaglandin E1) is produced endogenously to relax vascular smooth muscle and cause vasodilation. In adult males, the vasodilatory effects of alprostadil on the cavernosal arteries and the trabecular smooth muscle of the corpora cavernosa result in rapid arteriolar inflow and expansion of the lacunar spaces within the corpora. As the expanded corporal sinusoids are compressed against the tunica albuginea, venous outflow through the subtunical vessels is impeded and penile rigidity develops. This is referred to as the corporal veno-occlusive mechanism. In infants, the vasodilatory effects of alprostadil increase pulmonary or systemic blood flow.

Pharmacokinetics:

• Absorption:

Time to peak plasma concentration: 30-60 min (intracavernosal); approx 16 min (urethral).

• Distribution:

Plasma protein binding: 81%, mainly to albumin; 55% to α-globulin IV-4 fraction.

• Metabolism:

Metabolized (approx 70-80%) in a single pass through the lungs via β- and omega-oxidation into 13,14-dihydro-PGE1, 15-keto-PGE1, and 15-keto-13,14-dihydro-PGE1 (IV).

• Excretion:

Via urine (90% as metabolites) and feces. Elimination half-life: 0.5-10 min.

1. https://www.webmd.com/drugs/2/drug-7744/alprostadil-vasodilator-urethral/details
2. https://go.drugbank.com/drugs/DB00770
3. https://www.webmd.com › guide › alprostadil Injection and Suppository for Erectile Dysfunction - WebMD