Alprostadil (Caverject, Vitaros) for erectile dysfunction

Alprostadil is used to treat erectile dysfunction and pulmonary hypertension in adults.

It is also used to maintain the patency of ductus arteriosus in neonates with congenital heart diseases (pulmonary stenosis and atresia, tricuspid atresia, transposition of great arteries and Fallot's tetralogy) until surgery can be performed.

Alprostadil injection for ED (erectile dysfunction):

It is considered as the second-line treatment in patients with ED. Phosphodiesterase inhibitors (like tadalafil, Verdenafil, and Sildenafil) are considered the first-line of treatment. TRIMIX is a combination of papaverine, phentolamine, and alprostadil that is administered as an intracavernous injection for the treatment of ED. However, this is not marketed and available in pharmacies authorized to produce such mixtures. Alprostadil injection or injection of TRIMIX is considered as second-line treatment and as effective as oral phosphodiesterase inhibitors.

Alprostadil Cream for ED and Sexual arousal in females:

Alprostadil cream may be used for ED in men and sexual arousal disorder in women as well. Topical application may be specifically useful in patients who have contraindications to the use of oral sildenafil and diabetic patients with autonomic neuropathy. Alprostadil cream can improve the quality of sexual life in diabetic patients. Furthermore, it is considered safe in cardiac patients and does not have any interactions with food or alcohol [Ref]. It is considered to be safe & effective and can be administered in patients on alpha-blockers, nitrates, and antihypertensive agents [Ref]. One study evaluated the intra-meatal administration of alprostadil (Vitaros) in patients with ED. The intra-meatal administration of the drug was found to be more efficacious as assessed by the change in the International Index of Erectile Function (IIEF-5) score [Ref].

Alprostadil suppository for ED:

Alprostadil suppository for intraurethral administration is considered as the second-line treatment as it is associated with more side effects. Side effects of the suppositories include penile burning, stinging, pain, and hypotension. Alprostadil may be combined with oral phosphodiesterase inhibitors in patients who have a poor response to prior therapy with either of the drug [Ref].

Contraindications to Alprostadil:

Alprostadil allergy in patients
Respiratory distress syndrome
Permanent fetal circulation or hyaline membrane disease
Patients with certain conditions, such as leukemia, sicklecell anemia and multiple myeloma, are more likely to experience penile erection.
Patients with anatomically deformed penile shafts and patients with penile implanted peniles
Patients taking nitrates and patients who are not advised to have sexual activity.
Fibrosis may be caused by Peyronie Disease of the Penis
Patients with urethral strictures are advised to avoid intraurethral suppositories.
Females who are pregnant

Warnings and precautions

(US Boxed Warning):
Apnea is more common in newborns who are underweight (less than 2 kg).
Alprostadil is prescribed to patients with erectile dysfunction. Patients should inform their physician if they experience an erection lasting more than four hours.
Alprostadil should not be administered to neonates.
Alprostadil over 120 hours for more than one hour has been linked to antral hyperplasia, gastric outlet obstruction, and gastric hyperplasia.
Pregnant women with bleeding tendencies need to be cautious with the drug.

Alprostadil Dose in Adults

Alprostadil injection dosage for intracavernous administration (in the treatment of Erectile dysfunction):

(Note: Doses greater than 40 mcg (Edex®) or greater than 60 mcg (Caverject®) are not recommended)

The patient may be given the first two doses in the physician's office one hour apart. After administration, the patient should remain in the physician's office until erection subsides.
The second dose is given to those who do not respond to the first dose.
If an erection does not occur, the third dose should be given at intervals of 24 hours.
The dose should be titrated upwards, starting from 2.5 mcg.
A second dose of 7.5 mcg and then an incremental increase in the dose by 5-10 mcg may be followed if the response is not achieved.
Patients who have erectile dysfunction of neurogenic origin like those with spinal cord injury should be initiated with a lower dose i.e. 2.5 mcg.
Once the optimum dose has been determined, the patient may self administer the dose at a frequency of no more than 3 times/ week at least 24 hours between the doses.

Alprostadil injection dosage for Intraurethral administration:

125-250 mcg (use only two systems per day.

Alprostadil Dose in Childrens

Alprostadil (Caverject) injection dose in Children with PDA (Patent ductus arteriosus):

0.05-0.1 mcg/kg/minute as a continuous intravenous infusion. The dose should be reduced to the lowest possible effective dose once the therapeutic response is achieved.

Alprostadil Dose in renal disease:

The manufacturer does not provide any dose adjustment in renal disease

Alprostadil Dose in Liver disease:

The manufacturer does not provide any dose adjustment in Liver disease.

How to administer Alprostadil in patients with PDA (Patent ductus arteriosus):

Alprostadil should be given as a continuous intravenous infusion into a large vein or through an umbilical artery catheter in patients with patent ductus arteriosus. T
he maximum concentration of the infusion should not exceed 20 mcg/ml.

How to administer alprostadil in patients with erectile dysfunction:

Inject alprostadil into the dorsolateral aspect of the proximal one-third of the penis using a 1 / 2 inch, 27- to 30-gauge needle.
The injection should be given on alternate sides of the penis and intravenous injections should be avoided.

Pregnancy Risk Factor X

Alprostadil is toxic to the fetus and is not indicated in females.
It is embryotoxic in animal studies. It is not indicated for use in women. Breastfeeding mothers should not use it.

Alprostadil (Caverject) Side effects (Severe):

Rapid:
- Bradycardia
Early:
- cardiac arrest,
- ventricular fibrillation,
- penile edema,
- visual impairment,
Delayed:
- apnea,
- seizures,
- phimosis,
- myocardial infarction,
- heart failure,
- disseminated intravascular coagulation,
- anuria, and
- hyperkalemia.

Alprostadil Side effects (Moderate):

Rapid:
- Penile pain,
- Urethral pain,
- Hypotension,
- Sinus tachycardia,
- wheezing,
- Respiratory depression, and
- peripheral vasodilation
Early:
- Hematoma,
- erythema,
- Hypertension,
- bleeding,
- tachypnea,
- Supraventricular tachycardia,
- priapism,
- hypoglycemia, and
- urinary retention
Delayed:
- Penile fibrosis,
- peripheral edema,
- hypertriglyceridemia,
- edema,
- hyperemia,
- thrombocytopenia,
- anemia,
- hyperbilirubinemia,
- hematuria,
- hypercholesterolemia, and
- hyperglycemia.

Alprostadil Side effects (mild):

Rapid:
- Injection site reaction,
- flushing, and
- pruritis,
Early:
- Fever,
- testicular pain,
- dizziness,
- headache,
- rhinitis,
- diarrhea,
- lethargy,
- syncope,
- mydriasis,
- nausea,
- xerostomia,
- rash,
- diaphoresis,
- weakness,
- urinary urgency, and
- increased urinary frequency
Delayed:
- Ecchymosis,
- back pain,
- hypothermia,
- irritability,
- muscle cramps,
- gastroesophageal reflux, and
- hypoesthesia

Monitoring Parameters:

Monitor Blood pressure, heart rate, and temperature.
Monitor for apnea i.e. monitor the respiratory rate in neonates on intravenous infusion.
Monitor for the degree and duration of erection in men.

Alprostadil mechanism of Action:

Smooth muscle relaxation is caused by Alprostadil in the vessels, cavernosal and ductus arteriosus.

TheThe beginning of actionRapid and lasts one hour Around 75% of by is metabolized via oxidation in one passage via the lungs.

Half-life elimination is 5-10 minutes

Excretion is mostly via Urine (90% as metabolites) within 24 hours

Alprostadil in Pakistan and Price:

CAVERJECT (PFIZER LABORATORIES LTD)

Injection : 20 mcg/ml :

one injection pack : Rs. 9500

PROSTAVASIN (ATCO LABORATORIES LIMITED)