Alprostadil

Indications

Alprostadil is used for: Maintain Patency of Ductus Arteriosus, Erectile dysfunction

Adult Dose

Intracavernosal Erectile dysfunction Adult: Initially, 2.5 mcg, followed by 5 mcg if there is partial response or 7.5 mcg if there is no response. Subsequent increments of 5-10 mcg are given until suitable dose is reached. Usual dose range: 5-20 mcg. Max: 60 mcg. For neurogenic origin (e.g. spinal cord injury): Initially, 1.25 mcg, followed by 2.5 mcg then 5 mcg, and subsequent increments of 5 mcg until suitable dose at intervals of at least 1 day for responders; for non-responders, a higher dose may be given w/in 1 hr. Max frequency: once daily; 3 times wkly. Diagnosis of erectile dysfunction Adult: 5-20 mcg as a single dose. Urethral Erectile dysfunction Adult: Initially, 250 mcg, may be increased in stepwise manner to 1,000 mcg; or reduced to 125 mcg according to response. Max frequency: twice daily; 7 doses wkly. Diagnosis of erectile dysfunction Adult: 500 mcg as a single dose. Topical/Cutaneous Erectile dysfunction Adult: As cream: Initially, 300 mcg is applied to the tip of the penis, may be reduced to 200 mcg if patient cannot tolerate AR. Max frequency: once daily; 2-3 times wkly.

Child Dose

Intravenous Maintenance of patency of ductus arteriosus in neonates with congenital heart disease Child: Initially, 0.05-0.1 mcg/kg/min via continuous infusion, reduced to the lowest possible dosage that maintains the response. If response is inadequate, may be increased up to 0.4 mcg/kg/min.

Renal Dose

Administration

IV Preparation IV infusion: Dilute 1 mL (ie, 500 mcg) with sodium chloride for injection or dextrose Undiluted alprostadil solution may interact with plastic in volumetric infusion chambers resulting in a hazy solution (replace solution and volumetric infusion chamber if this occurs) Place appropriate amount of intravenous infusion solution (ie, sodium chloride, dextrose) in chamber first, then add undiluted alprostadil solution (avoid direct contact with walls of volumetric infusion chamber) Dilute to volumes appropriate for the pump delivery system available Prepare fresh infusion solutions q24hr; discard any solution >24 hr old IV Administration Administer via large vein or through umbilical catheter Administer IV injection via volumetric infusion pump

Contra Indications

History of recurrent priapism, sickle cell anaemia or trait, multiple myeloma, leukaemia, thrombocythaemia, polycythaemia, predisposition to venous thrombosis, anatomical penile deformation (e.g. angulation, cavernosal fibrosis, Peyronie's disease, stenosis of distal urethra, severe hypospadias and curvature, balanitis, acute/chronic urethritis), penile implants. Patient for whom sexual activity is inadvisable (e.g. unstable CV or cerebrovascular conditions). Concomitant use w/ other drugs for erectile dysfunction (e.g. phosphodiesterase type 5 (PDE5) inhibitors, papaverine). Neonates w/ resp distress syndrome. Childn (intracavernosal).

Precautions

Patient w/ bleeding tendencies, blood-borne and pulmonary diseases, transient ischaemic attacks, CHD, CHF, history of psychiatric disorder or addiction. Pregnancy (use condom barrier if female partner is or may be pregnant). Patient Counselling This drug may cause dizziness, syncope, and hypotension, if affected, do not drive or operate machinery. Monitoring Parameters Monitor for BP, resp and heart rates, temp, degree of penile pain, duration of erection, adequate detumescence after dosing, and signs of infection.

Pregnancy-Lactation

Pregnancy Category: X Lactation: Not indicated for use in women

Interactions

Reduced effect w/ sympathomimetics, decongestants, and appetite suppressants. May enhance the effects of antihypertensives, vasoactive drugs, anticoagulants and platelet aggregation inhibitors. Potentially Fatal: Enhanced AR, including prolonged erections, w/ PDE5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) and other drugs that induce erection (e.g. papaverine).

Adverse Effects

Side effects of Alprostadil : >10% Fever (14%) Apnea (12%) Flushing (>10%) 1-10% Bradycardia (7%) Hypotension (4%) Seizures (4%) Tachycardia (3%) Diarrhea (2%) Sepsis (2%) Cardiac arrest (1%) Edema (1%) Intravascular coagulation (1%) Hypokalemia (1%) <1% Cerebral bleeding Hyperextension of the neck Hyperirritability Hypothermia Jitteriness Lethargy Stiffness Congestive heart failure Hyperemia Second degree heart block Shock Spasm of the right ventricle infundibulum Supraventricular tachycardia Ventricular fibrillation Bradypnea Bronchial wheezing Hypercapnia Respiratory depression Respiratory distress Tachypnea Gastric regurgitation Hyperbilirubinemia Anemia Bleeding Thrombocytopenia Peritonitis Hypoglycemia Hyperkalemia

Mechanism of Action

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.