CAVERJECT 20MCG STERILE POWDER AND DILUENT FOR INJECTION

Indications

• Maintenance of patent ductus arteriosus in neonates
• Treatment of edema resistant to loop diuretics in heart failure, renal disease, and hepatic disease

Dosage

Children: For neonates, initially 5 nanograms/kg/minute via continuous intravenous infusion, adjusted according to response. For children aged 1 month to 11 years, the oral dose is 100–200 micrograms/kg 1–2 times a day. For children aged 12–17 years, the oral dose is 5–10 mg once daily, increased if necessary.

Adults: Alprostadil should be administered based on clinical condition and response, with careful monitoring of vital signs. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Alprostadil acts by dilating blood vessels and inhibiting platelet aggregation through its action on prostaglandin receptors, which leads to increased blood flow and reduced vascular resistance.

Pharmacodynamics

Alprostadil has a vasodilatory effect, primarily affecting the pulmonary and systemic arterial circulation. It also promotes the relaxation of smooth muscle in the ductus arteriosus, facilitating right-to-left shunting of blood in certain congenital heart defects.

Pharmacokinetics

Alprostadil is rapidly metabolized in the body, primarily by the lungs and liver. The half-life is approximately 30 minutes to 1 hour, and it is excreted mainly in urine. Its pharmacokinetics may be altered in patients with renal or hepatic impairment.

Contra-indications

• Hyaline membrane disease

Adverse effects

• Chest pain
• Chills
• Cardiac arrest
• Disseminated intravascular coagulation
• Hypokalaemia
• Oedema
• Sepsis

Interactions

• Thiazide diuretics

Precautions

• History of haemorrhage
• Acute porphyrias

Pregnancy

No known risks; however, use should be evaluated based on benefits versus risks.

Breast-feeding

The amount present in milk is too small to be harmful. Large doses may suppress lactation.

Storage

Store at room temperature. Protect from light.

Formulations

• Solution for infusion: Prostin VR 500 micrograms/1 ml concentrate for solution for infusion ampoules

Mechanism of action

Alprostadil is a smooth muscle relaxant that promotes vasodilation and platelet aggregation inhibition. In neonatal patients with ductus arteriosus patency, alprostadil relaxes the ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This results in increased pulmonary or systemic blood flow in infants. Alprostadil appears to be most effective within 96 hours after birth since the DA rapidly loses its responsiveness to alprostadil. When administered by intracavernosal injection or as an intraurethral suppository, alprostadil acts locally to relax the trabecular smooth muscle of the corpora cavernosa and the cavernosal arteries. Swelling, elongation, and rigidity of the penis result when arterial blood rapidly flows into the corpus cavernosum to expand the lacunar spaces. The entrapped blood reduces the venous blood outflow as sinusoids compress against the tunica albuginea leading to penile rigidity. This is referred to as the corporal veno-occlusive mechanism.

Pharmacodynamics

Prostaglandin E1 is produced endogenously to relax vascular smooth muscle and cause vasodilation. As a synthetic form of prostaglandin E1, alprostadil has the same pharmacodynamic effects. Alprostadil inhibits platelet aggregation, has anti-inflammatory effects, interferes with immune responses, and stimulates factor X, a blood coagulation enzyme. In adult males, the use of alprostadil may lead to prolonged erection and priapism, penile fibrosis, hypotension, and injection site bleeding. In patients treated up to 24 months with alprostadil, the incidence of prolonged erections (>4 hours long) was 4% of all, and the incidence of priapism (erections greater than 6 hours in duration) was <1%. Patients with preexisting cardiovascular disease treated with alprostadil may also have higher cardiac risk. Neonates with congenital heart defects treated with alprostadil may experience apnea. Apnea is experienced by 10-12% of neonates and is more common in those weighing less than 2 kg at birth. The administration of alprostadil to neonates may also result in gastric outlet obstruction secondary to antral hyperplasia.