PHENYLEPHRINE HYDROCHLORIDE injection

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PHENYLEPHRINE HYDROCHLORIDE (UNII: 04JA59TNSJ) (PHENYLEPHRINE - UNII:1WS297W6MV)

Available from:

Cardinal Health 107, LLC

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Phenylephrine hydrochloride injection, 10 mg/mL is indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia. None Risk Summary Data from randomized controlled trials and meta-analyses with phenylephrine hydrochloride use in pregnant women during Cesarean section have not established a drug-associated risk of major birth defects and miscarriage. These studies have not identified an adverse effect on maternal outcomes or infant Apgar scores [see Data] . There are no data on the use of phenylephrine during the first or second trimester. In animal reproduction and development studies in normotensive animals, evidence of fetal malformations was noted when phenylephrine was administered during organogenesis via a 1-hour infusion at 1.2 times the human daily dose (HDD) of 10 mg/60 kg/day. Decreased pup weights were noted in offspring of pregnant rats treated with 2.9 times the HDD [See Data]. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk Untreated hypotension associated with spinal anesthesia for Cesarean section is associated with an increase in maternal nausea and vomiting. A sustained decrease in uterine blood flow due to maternal hypotension may result in fetal bradycardia and acidosis. Data Human Data Published randomized controlled trials over several decades, which compared the use of phenylephrine hydrochloride injection to other similar agents in pregnant women during Cesarean section, have not identified adverse maternal or infant outcomes. At recommended doses, phenylephrine does not appear to affect fetal heart rate or fetal heart rate variability to a significant degree. There are no studies on the safety of phenylephrine hydrochloride injection exposure during the period of organogenesis, and therefore, it is not possible to draw any conclusions on the risk of birth defects following exposure to phenylephrine hydrochloride injection during pregnancy. In addition, there are no data on the risk of miscarriage following fetal exposure to phenylephrine hydrochloride injection. Animal Data No clear malformations or fetal toxicity were reported when normotensive pregnant rabbits were treated with phenylephrine via continuous intravenous infusion over 1 hour (0.5 mg/kg/day; approximately equivalent to a HDD based on body surface area) from Gestation Day 7 to 19. At this dose, which demonstrated no maternal toxicity, there was evidence of developmental delay (altered ossification of sternebra). In a non-GLP dose range-finding study in normotensive pregnant rabbits, fetal lethality and cranial, paw, and limb malformations were noted following treatment with 1.2 mg/kg/day of phenylephrine via continuous intravenous infusion over 1 hour (2.3-times the HDD). This dose was clearly maternally toxic (increased mortality and significant body weight loss). An increase in the incidence of limb malformation (hyperextension of the forepaw) coincident with high fetal mortality was noted in a single litter at 0.6 mg/kg/day (1.2-times the HDD) in the absence of maternal toxicity. No malformations or embryo-fetal toxicity were reported when normotensive pregnant rats were treated with up to 3 mg/kg/day phenylephrine via continuous intravenous infusion over 1 hour (2.9-times the HDD) from Gestation Day 6 to 17. This dose was associated with some maternal toxicity (decreased food consumption and body weights). Decreased pup weights were reported in a pre-and postnatal development toxicity study in which normotensive pregnant rats were administered phenylephrine via continuous intravenous infusion over 1 hour (0.3, 1.0, or 3.0 mg/kg/day; 0.29, 1, or 2.9 times the HDD) from Gestation Day 6 through Lactation Day 21). No adverse effects on growth and development (learning and memory, sexual development, and fertility) were noted in the offspring of pregnant rats at any dose tested. Maternal toxicities (mortality late in gestation and during lactation period, decreased food consumption and body weight) occurred at 1 and 3 mg/kg/day of phenylephrine (equivalent to and 2.9 times the HDD, respectively). Risk Summary There are no data on the presence of phenylephrine hydrochloride or its metabolite in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for phenylephrine hydrochloride and any potential adverse effects on the breastfed infant from phenylephrine hydrochloride or from the underlying maternal condition. Safety and effectiveness in pediatric patients have not been established.   Clinical studies of phenylephrine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In patients with liver cirrhosis [Child Pugh Class B and Class C], dose-response data indicate decreased responsiveness to phenylephrine. Start dosing in the recommended dose range, but more phenylephrine may be needed in this population. In patients with end stage renal disease (ESRD), dose-response data indicate increased responsiveness to phenylephrine. Consider starting at the lower end of the recommended dose range, and adjusting dose based on the target blood pressure goal.

Product summary:

Phenylephrine Hydrochloride Injection, USP is a sterile, clear, colorless solution and supplied in 1 mL single-dose glass vials. Each mL contains phenylephrine hydrochloride USP, 10 mg . 10 mg/mL (1 mL) Overbagged with 5 x 1 mL Single- dose Vial in a bag, NDC 55154-8226-5 Store phenylephrine hydrochloride injection USP, 10 mg/mL at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Store in carton until time of use. Vial stoppers are not manufactured with natural rubber latex. The diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions. Discard any unused portion.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

PHENYLEPHRINE HYDROCHLORIDE- PHENYLEPHRINE HYDROCHLORIDE INJECTION
CARDINAL HEALTH 107, LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PHENYLEPHRINE
HYDROCHLORIDE INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
PHENYLEPHRINE HYDROCHLORIDE INJECTION.
PHENYLEPHRINE HYDROCHLORIDE INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1954
INDICATIONS AND USAGE
Phenylephrine hydrochloride injection is an alpha-1 adrenergic
receptor agonist indicated for the treatment
of clinically important hypotension resulting primarily from
vasodilation in the setting of anesthesia. (1)
DOSAGE AND ADMINISTRATION
Phenylephrine hydrochloride injection, 10 mg/mL, is injected
intravenously either as a bolus or in a dilute
solution as a continuous infusion.
Dilute before administration. (2)
Dosing for treatment of hypotension during anesthesia
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•
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DOSAGE FORMS AND STRENGTHS
Injection (3)
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CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
Exacerbation of Angina, Heart Failure, or Pulmonary Arterial
Hypertension: Phenylephrine hydrochloride
can precipitate angina in patients with severe arteriosclerosis or
history of angina, exacerbate underlying
heart failure, and increase pulmonary arterial pressure. (5.1)
Peripheral and Visceral Ischemia: Phenylephrine hydrochloride can
cause excessive peripheral and visceral
vasoconstriction and ischemia to vital organs. (5.2)
Skin and Subcutaneous Necrosis: Extravasation during intravenous
administration may cause necrosis or
sloughing of tissue. (5.3)
Bradycardia: Phenylephrine hydrochloride can cause severe bradycardia
and decreased cardiac output.
(5.4)
ADVERSE REACTIONS
Most common adverse reactions during treatment: nausea, vomiting, and
headache. (6)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT AMNEAL PHARMACEUTICALS
AT 1-877-835-
5472 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
DRUG INTERACTIONS
Agonistic effects (increase in phenylephrine hydrochloride blood
pressure effect) can