Interacting drugs- summary

 Alprostadil +

 Anticoagulants incr Vasoactive agents

 + Antiocoagulants

  Patients on anticoagulants such as heparin or warfarin may have increased propensity for bleeding after intracavernosal injection 

+ Vasoactive agents

Safety and efficacy of combinations of alprostadil and other vasoactive agents have not been systematically studied. Therefore the use of such combinations is not recommended

Fever,seizures,cerebral bleeding, hyperextension of the neck, hyperirritability, hypothermia, jitteriness, lethargy.

Flushing, bradycardia, hypotension, tachycardia, cardiac arrest.

Apnea, bradypnea, bronchial wheezing, respiratory depression.

Diarrhoea, anuria, haematuria, cortical proliferation of long bones.

Local- Penile pain - after intracavernosal administration was reported by 37% of patients at least once in clinical studies of up to 18 months in duration.

Systemic- CNS- headache, dizzines

Respiratory- upper respiratory infection, flu syndrome, sinusitis, nasal congestion, cough

Miscellaneous- hypertension, localized pain, trauma, prostatic disorder, back pain

Hemodynamic changes- manifested as decreases in blood pressure and increases inpulse rate, principally at doses > 20mcg, were observed during clinical studies, and apperared to be dose dependent.

Other reactions- testicular pain/disorder, scrotal disorder/edema, hematuria, impaired urination, urinary frequency/ urgency,

pelvic pain, hypotension, vasodilation, peripheral vascular disorder, supraventricular extrasystoles, vasovagal reactions,

hypesthesia, non-generalized weakness,

diaphoresis, rash, non-application site pruritus, skin neoplasm,

nausea, dry mouth,

increased serum creatinine,

leg cramps, mydriasis.

Hypersensitivity to the drug. conditions that might predispose patients to priapism(eg. sickle anemia ortrailt, multiple myeloma, leukemia)

patients with anatomical deformation of the penis(eg. angulation, cavernosal fibrosis

, Peyronies disease) patients with penile inplants, use in women, children or newborns:

use in men for whom sexual activity is inadvisable or contraindicated

Special precautions:

Apnea occurs in 10%- 12% of neonates with congenital heart defects treated with Alprostadil. Apnea is noticed in neonates weighing less than 2kg at birth and usually appears during the first hour of drug infusion.

Monitor respiratory status throughout treatment. Cortical poliferation of long bones has been observed in infants during long term infusions of alprosadil.

Infuse for the shortest time and at the lowest dose. Use cautiously in neonates with bleeding tendency. Do not use alprostadil in respiratory syndrome.

Erectile dysfunction- Diagnose and treat underlying treatable medical causes of erctile dysfunction prior to initiation of therapy

Pulmonary disease- the pulmonary extraction of alprostadil following intravascular administration was reduced by 15% in patients with acute respiratory distress syndrome (ARDS) compared with a control group of patients with normal respiratory function who were undergoing cardiopulmonary bypass surgery.

Renal/hepatic function impairment- pulmonary first pass metabolism is the primary factor influencing the systemic clearance of alprostadil.

Pregnancy- Caverject is not indicated for use in women

Children- Caverject is not indicated for use in newborns or children.

Indications:

For palliative,not definitive therapy to temporarily maintain the patency of ductus arteriosus until surgery on neonates on congenital heart can be performed.

Dosage:

Continuous IV infusion into large vein or umbilical artery. Start with 0.05 to 0.1mcg/kg/min. A starting dose of 0.1mcg/kg/min is recommended. Storage: Refrigerate at 2 to 8C. Discard and prepare fresh infusion every 24 hours.

Overdosage

If intracaverous overdose of alprostadil occurs, the patient should be underr medical supervision until any systemic effects have resolved or until penil detumescene has occured. Symptomatic treatment of any systemic symptoms would be appropriate

Missed dose

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Alprostadil

1.Use only under medical advice.

2. Individual allergy - Tell your doctor if you ever had any unusual or allergic reaction to alprostadil.

3. Other medicines - Certain medicines are known to interact with alporostadil. Tell your doctor if you are taking any other prescription or non-prescription OTC( over the counter ) medicines

4. Other medical problems - Tell your doctor, if you have other medical problems,viz., bledding problems or liver disease or history of priapism. Sickle cell disease- Patients with these conditions have an increased risk of priapism (erection lasting lasting longer than 4 hours) while using alprostadil

5.Dose - The dose of alprostdil will be different for different patients. Follow your doctors advise.

6. Storage - Keep out of reach of children. Refigerate. Keep the medicine from freezing

Pharmacology:

Alprostadil has a wide variety of pharmacological actions, vasodilation and inhibition of platelet aggregation are among the most notable effects.

Alprostadil induces erection by relaxation of trabecular smooth muscle and by dilation of cavernosal arteries.This leads to expansion of lacunar spaces and entrapment of blood by compressing the venules against tunia albuginea, a process refered to as corporal veno-occulsive mechanism.

Pharmocokinetics:

For treatment of erctile dysfunction, alprostadil is administered by injection into corpora cavernosa. The absolute bioavailability ha s not been established. Alprostadil is rapidly converted to compounds which are further metabolised before excretion.

The metabolites are excreted primarily by the kidney, with almost 90% administered IV dose excreted in urine within 24 hours post dose. The remainder of the dose is execreted in the feces There is no evidence of tissue retention of alprostadil or its metabolites following IV use..

Pregnancy

Not indicated for use in women.

Lactation

Not indicated for use in new borns or children