Prostin VR Pediatric Sterile Solution: See BOXED WARNING.

NOTE: Prostin VR Pediatric Sterile Solution must be diluted before it is administered. See DOSAGE AND ADMINISTRATION, Dilution Instructions.

The administration of Prostin VR Pediatric to neonates may result in gastric outlet obstruction secondary to antral hyperplasia. This effect appears to be related to duration of therapy and cumulative dose of the drug. Neonates receiving Prostin VR Pediatric ar recommended doses for more than 120 hours should be closely monitored for evidence of antral hyperplasia and gastric outlet obstruction.

Prostin VR Pediatric should be infused for the shortest time and at the lowest dose that will produce the desired effects. The risks of long-term infusion of Prostin VR Pediatric should be weighed against the possible benefits that critically ill infants may derive from its administration.

Caverject:

Prolonged erection defined as erection lasting > 4 to ≤ 6 hours in duration occurred in 4% of 1861 patients treated up to 18 months in studies of CAVERJECT Sterile Powder. The incidence of priapism (erections lasting > 6 hours in duration) was 0.4% with the same length of use. Pharmacologic intervention and/or aspiration of blood from the corpora cavernosum was performed in 2 of the 7 patients with priapism. To minimize the chances of prolonged erection or priapism, CAVERJECT Injection should be titrated slowly to the lowest effective dose (see DOSAGE AND ADMINISTRATION). The patient must be instructed to immediately report to his prescribing physician, or, if unavailable, to seek immediate medical assistance for any erection that persists longer than 4 hours. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

Prostin VR Pediatric Sterile Solution

General Precautions: Cortical proliferation of the long bones, first observed in dogs, has also been observed in infants during long-term infusions of alprostadil. The cortical proliferation in infants regressed after withdrawal of the drug.

In infants treated with Prostin VR Pediatric at the usual doses for 10 hours to 12 days and who died of causes unrelated to ductus structural weakness, tissue sections of the ductus and pulmonary arteries have shown intimal lacerations, a decrease in medial muscularity and disruption of the medial and internal elastic lamina. Localized and aneurysmal dilatations and vessel wall edema also were seen compared to a series of pathological specimens from infants not treated with Prostin VR Pediatric. The incidence of such structural alterations has not been defined.

Because alprostadil inhibits platelet aggregation, use Prostin VR Pediatric cautiously in neonates with bleeding tendencies.

Prostin VR Pediatric should not be used in neonates with respiratory distress syndrome. A differential diagnosis should be made between respiratory distress syndrome (hyaline membrane disease) and cyanotic heart disease (restricted pulmonary blood flow). If full diagnostic facilities are not immediately available, cyanosis (pO₂ less than 40 torr) and restricted pulmonary blood flow apparent on an X-ray are appropriate indicators of congenital heart defects.

Necessary Monitoring: In all neonates, arterial pressure should be monitored intermittently by umbilical artery catheter, auscultation, or with a Doppler transducer. Should arterial pressure fall significantly, decrease the rate of infusion immediately.

In infants with restricted pulmonary blood flow, measure efficacy of Prostin VR Pediatric by monitoring improvement in blood oxygenation. In infants with restricted systemic blood flow, measure efficacy by monitoring improvement of systemic blood pressure and blood pH.

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term carcinogenicity studies and fertility studies have not been done. The Ames and Alkaline Elution assays reveal no potential for mutagenesis.

1. The overall incidence of penile fibrosis, including Peyronie's disease, reported in clinical studies with CAVERJECT Sterile Powder was 3%. In one selfinjection clinical study where duration of use was up to 18 months, the incidence of fibrosis was 7.8%.
   Regular follow-up of patients, with careful examination of the penis, is strongly recommended to detect signs of penile fibrosis. Treatment with CAVERJECT should be discontinued in patients who develop penile angulation, cavernosal fibrosis, or Peyronie's disease.
2. Intracavernous injections of CAVERJECT can lead to increased peripheral blood levels of PGE1 and its metabolites, especially in those patients with significant corpora cavernosa venous leakage. Increased peripheral blood levels of PGE1 and its metabolites may lead to hypotension and/or dizziness.
3. Patients on anticoagulants, such as warfarin or heparin, may have increased propensity for bleeding after intracavernosal injection.
4. Underlying treatable medical causes of erectile dysfunction should be diagnosed and treated prior to initiation of therapy with CAVERJECT.
5. The safety and efficacy of combinations of CAVERJECT and other vasoactive agents have not been systematically studied. Therefore, the use of such combinations is not recommended.
6. The patient should be instructed not to re-use or to share needles or syringes. As with all prescription medicines, the patient should not allow anyone else to use his medicine.

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term carcinogenicity studies have not been conducted. Rat reproductive studies indicate that alprostadil at doses of up to 0.2 milligram/kilogram/day does not adversely affect or alter rat spermatogenesis, providing a 200-fold margin of safety compared with the usual human doses. The following battery of mutagenicity assays revealed no potential for mutagenesis: bacterial mutation (Ames), alkaline elution, rat micronucleus, sister chromatid exchange, CHO/HGPRT mammalian cell forward gene mutation, and unscheduled DNA synthesis (UDS).

A 1 year irritancy study was conducted in three groups of 5 male Cynomolgus monkeys injected intracavernosally twice weekly with either vehicle or 3 or 8.25 micrograms of alprostadil per injection. An additional two groups of 6 monkeys each were injected with vehicle or with 8.25 micrograms/injection twice weekly as described previously plus they received multiple doses during weeks 44, 48, and 52. Three monkeys from each group were retained for a 4-week recovery period. There was no evidence of drug-related penile irritancy or nonpenile tissue lesions, which could be directly related to alprostadil. The irritancy which was noted for control and treated monkeys was considered to be a result of the injection procedure itself, and any lesions noted were shown to be reversible. At the end of 4-week recovery period, the histological changes in the penis had regressed.

Pregnancy, Nursing Mothers, and Pediatric Use: Alprostadil is not indicated for use in newborns, children, or women.

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