FDA

Phenylephrine Hydrochloride

Approved 21 Dec 2018IntravenousSolution

The FDA lists this product in 60 strengths and forms.

Indications

Phenylephrine Hydrochloride Injection is indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia. 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 )

Contraindications

None None ( 4 )

Warnings and precautions

Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension: Phenylephrine Hydrochloride Injection 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 Injection 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 Injection can cause severe bradycardia and decreased cardiac output. ( 5.4 )

5.1Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension Because

of its increasing blood pressure effects, Phenylephrine Hydrochloride Injection can precipitate angina in patients with severe arteriosclerosis or history of angina, exacerbate underlying heart failure, and increase pulmonary arterial pressure.

5.2Peripheral and Visceral Ischemia Phenylephrine Hydrochloride

Injection can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, particularly in patients with extensive peripheral vascular disease.

5.3Skin and Subcutaneous Necrosis Extravasation of Phenylephrine Hydrochloride

Injection can cause necrosis or sloughing of tissue. The infusion site should be checked for free flow. Care should be taken to avoid extravasation of Phenylephrine Hydrochloride Injection.

At a glance

Brand name: Phenylephrine Hydrochloride
Route: Intravenous
Dosage form: Solution
Applicant: PH Health
Status: Discontinued
FDA approval: 21 Dec 2018
Application: ANDA210025-001

Indications

Warnings and precautions

5.1Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension Because

5.2Peripheral and Visceral Ischemia Phenylephrine Hydrochloride

Injection can cause excessive peripheral and visceral vasoconstriction and ischemia to vital organs, particularly in patients with extensive peripheral vascular disease.

5.3Skin and Subcutaneous Necrosis Extravasation of Phenylephrine Hydrochloride

Injection can cause necrosis or sloughing of tissue. The infusion site should be checked for free flow. Care should be taken to avoid extravasation of Phenylephrine Hydrochloride Injection.

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Data

from randomized controlled trials and meta-analyses with phenylephrine hydrochloride injection 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 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 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 injection during pregnancy. In addition, there are no data on the risk of miscarriage following fetal exposure to phenylephrine 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).

Phenylephrine Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension Because

5.2Peripheral and Visceral Ischemia Phenylephrine Hydrochloride

5.3Skin and Subcutaneous Necrosis Extravasation of Phenylephrine Hydrochloride

At a glance

Two medicines in one question?

Phenylephrine Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1Exacerbation of Angina, Heart Failure, or Pulmonary Arterial Hypertension Because

5.2Peripheral and Visceral Ischemia Phenylephrine Hydrochloride

5.3Skin and Subcutaneous Necrosis Extravasation of Phenylephrine Hydrochloride

At a glance

Two medicines in one question?

5.4Bradycardia Phenylephrine Hydrochloride

5.5Allergic Reactions Phenylephrine Hydrochloride

5.6Renal Toxicity Phenylephrine Hydrochloride

5.7Risk of Augmented Pressor Affect in Patients with Autonomic Dysfunction

5.8Pressor Effect with Concomitant Oxytocic Drugs

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Data

Adverse reactions

Composition

Strengths and forms

Official product information