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| Product NDC Code | 71863-208 | ||||
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| Drug Name | Biorphen |
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| Type | Brand | ||||
| Pharm Class | Adrenergic alpha1-Agonists [MoA], alpha-1 Adrenergic Agonist [EPC] |
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| Route | INTRAVENOUS | ||||
| Dosage Form | INJECTION, SOLUTION | ||||
| RxCUI drug identifier | 1666372, 2262018, 2533434, 2533437 |
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| Application Number | NDA212909 | ||||
| Labeler Name | Eton Pharmaceuticals, Inc. | ||||
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Overdosage of Biorphen
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE Overdose of BIORPHEN (phenylephrine hydrochloride) can cause a rapid rise in blood pressure. Symptoms of overdose include headache, vomiting, hypertension, reflex bradycardia, a sensation of fullness in the head, tingling of the extremities, and cardiac arrhythmias including ventricular extrasystoles and ventricular tachycardia.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS Adverse reactions to BIORPHEN are primarily attributable to excessive pharmacologic activity. Adverse reactions reported in published clinical studies, observational trials, and case reports of BIORPHEN are listed below by body system. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Cardiac disorders: Reflex bradycardia, lowered cardiac output, ischemia, hypertension, arrhythmias Gastrointestinal disorders: Epigastric pain, vomiting, nausea Nervous system disorders: Headache, blurred vision, neck pain, tremors Vascular disorders: Hypertensive crisis Respiratory, Thoracic and Mediastinal Disorders: Dyspnea Skin and subcutaneous tissue disorders: Pruritis Most common adverse reactions during treatment: nausea, vomiting, and headache. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Eton Pharmaceuticals, Inc. at 1-855-224-0233 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Biorphen Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS Agonistic Effects (increase in BIORPHEN blood pressure effect) can occur with monoamine oxidase inhibitors (MAOI), oxytocin and oxytocic drugs, tricyclic antidepressants, angiotensin and aldosterone, atropine, steroids, norepinephrine transporter inhibitors, ergot alkaloids. ( 7.1 ) Antagonistic Effects (decrease in BIORPHEN blood pressure effect) can occur with α-adrenergic antagonists, phosphodiesterase Type 5 inhibitors, mixed α- and β-receptor antagonists, calcium channel blockers, benzodiazepines and ACE inhibitors, centrally acting sympatholytic agents. ( 7.2 ) 7.1 Interactions that Augment the Pressor Effect The increasing blood pressure effect of BIORPHEN is increased in patients receiving: Monoamine oxidase inhibitors (MAOI) Oxytocin and oxytocic drugs Tricyclic antidepressants Angiotensin, aldosterone Atropine Steroids, such as hydrocortisone Norepinephrine transporter inhibitors, such as atomoxetine Ergot alkaloids, such as methylergonovine maleate 7.2 Interactions that Antagonize the Pressor Effect The increasing blood pressure effect of BIORPHEN is decreased in patients receiving: α-adrenergic antagonists Phosphodiesterase Type 5 inhibitors Mixed α- and β-receptor antagonists Calcium channel blockers, such as nifedipine Benzodiazepines ACE inhibitors Centrally acting sympatholytic agents, such as reserpine, guanfacine
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Phenylephrine hydrochloride is an α-1 adrenergic receptor agonist. 12.2 Pharmacodynamics Interaction of phenylephrine with α-1 adrenergic receptors on vascular smooth muscle cells causes activation of the cells and results in vasoconstriction. Following phenylephrine hydrochloride intravenous administration, increases in systolic and diastolic blood pressures, mean arterial blood pressure, and total peripheral vascular resistance are observed. The onset of blood pressure increase following an intravenous bolus phenylephrine hydrochloride administration is rapid, typically within minutes. As blood pressure increases following intravenous administration, vagal activity also increases, resulting in reflex bradycardia. Phenylephrine has activity on most vascular beds, including renal, pulmonary, and splanchnic arteries. 12.3 Pharmacokinetics Following an intravenous infusion of phenylephrine hydrochloride, the observed effective half-life was approximately 5 minutes. The steady-state volume of distribution of approximately 340 L suggests a high distribution into organs and peripheral tissues. The average total serum clearance is approximately 2100 mL/min. The observed phenylephrine plasma terminal elimination half-life was 2.5 hours. Phenylephrine is metabolized primarily by monoamine oxidase and sulfotransferase. After intravenous administration of radiolabeled phenylephrine, approximately 80% of the total dose was eliminated within first 12 h; and approximately 86% of the total dose was recovered in the urine within 48 h. The excreted unchanged parent drug was 16% of the total dose in the urine at 48 h post intravenous administration. There are two major metabolites, with approximately 57 and 8% of the total dose excreted as m -hydroxymandelic acid and sulfate conjugates, respectively. The metabolites are considered not pharmacologically active.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action Phenylephrine hydrochloride is an α-1 adrenergic receptor agonist.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Interaction of phenylephrine with α-1 adrenergic receptors on vascular smooth muscle cells causes activation of the cells and results in vasoconstriction. Following phenylephrine hydrochloride intravenous administration, increases in systolic and diastolic blood pressures, mean arterial blood pressure, and total peripheral vascular resistance are observed. The onset of blood pressure increase following an intravenous bolus phenylephrine hydrochloride administration is rapid, typically within minutes. As blood pressure increases following intravenous administration, vagal activity also increases, resulting in reflex bradycardia. Phenylephrine has activity on most vascular beds, including renal, pulmonary, and splanchnic arteries.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Following an intravenous infusion of phenylephrine hydrochloride, the observed effective half-life was approximately 5 minutes. The steady-state volume of distribution of approximately 340 L suggests a high distribution into organs and peripheral tissues. The average total serum clearance is approximately 2100 mL/min. The observed phenylephrine plasma terminal elimination half-life was 2.5 hours. Phenylephrine is metabolized primarily by monoamine oxidase and sulfotransferase. After intravenous administration of radiolabeled phenylephrine, approximately 80% of the total dose was eliminated within first 12 h; and approximately 86% of the total dose was recovered in the urine within 48 h. The excreted unchanged parent drug was 16% of the total dose in the urine at 48 h post intravenous administration. There are two major metabolites, with approximately 57 and 8% of the total dose excreted as m -hydroxymandelic acid and sulfate conjugates, respectively. The metabolites are considered not pharmacologically active.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS None. None ( 4 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION Phenylephrine is an alpha-1 adrenergic receptor agonist. The chemical name of phenylephrine hydrochloride is (-)- m -hydroxy-α-[(methylamino) methyl] benzyl alcohol hydrochloride, its molecular formula is C 9 H 13 NO 2 · HCl (Molecular Weight: 203.67g/mol). Its structural formula is depicted below: Phenylephrine hydrochloride is soluble in water and ethanol, and insoluble in chloroform and ethyl ether. BIORPHEN Injection, 0.1 mg/mL: BIORPHEN (phenylephrine hydrochloride) injection, 0.1 mg/mL, is a sterile, nonpyrogenic, clear and colorless solution for intravenous use. It MUST NOT BE DILUTED before administration as an intravenous bolus. Each mL contains: phenylephrine hydrochloride 0.1 mg (equivalent to 0.08 mg of phenylephrine base), sodium chloride 9.0 mg in water for injection. The pH is adjusted with hydrochloric acid if necessary. The pH range is 3.0 to 5.0. BIORPHEN Injection, 10 mg/mL: BIORPHEN (phenylephrine hydrochloride) injection, 10 mg/mL, is a sterile, nonpyrogenic, clear and colorless solution for intravenous use. It MUST BE DILUTED before administration as an intravenous bolus or continuous intravenous infusion. Each mL contains: phenylephrine hydrochloride 10 mg (equivalent to 8.2 mg of phenylephrine base), sodium chloride 6.0 mg in water for injection. The pH is adjusted with hydrochloric acid if necessary. The pH range is 3.0 to 5.0. Chemical Structure
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION BIORPHEN 0.1 mg/mL injection MUST NOT BE DILUTED before administration as an intravenous bolus. It is supplied as a READY-TO-USE formulation. ( 2 ) BIORPHEN 10 mg/mL injection MUST BE DILUTED before administration as an intravenous bolus or continuous intravenous infusion to achieve the desired concentration. ( 2 ) Dosing for treatment of hypotension during anesthesia Bolus intravenous injection: Initial dose is 40 mcg to 100 mcg. Additional boluses up to 200 mcg may be administered every 1 to 2 minutes as needed. ( 2 ) Adjust the dose according to the pressor response (i.e., titrate to effect). ( 2 ) Biorphen 10 mg/mL Only: Continuous intravenous infusion: 10 mcg/min to 35 mcg/min, titrating to effect, not to exceed 200 mcg/min. ( 2 ) 2.1 General Dosage and Administration Instructions During BIORPHEN administration: Correct intravascular volume depletion. Correct acidosis. Acidosis may reduce the effectiveness of phenylephrine. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use if the solution is colored or cloudy, or if it contains particulate matter. Discard any unused portion. BIORPHEN 0.1 mg/mL and 10 mg/mL Injection have important differences in administration instructions: Administration Instructions for BIORPHEN 0.1 mg/mL Injection: BIORPHEN 0.1 mg/mL injection MUST NOT BE DILUTED before administration as an intravenous bolus. It is supplied as READY-TO-USE formulation. Administration Instructions for BIORPHEN 10 mg/mL Injection: BIORPHEN 10 mg/mL injection MUST BE DILUTED before administration as an intravenous bolus or continuous intravenous infusion to achieve the desired concentration: • Bolus : Dilute with normal saline or 5% dextrose in water. • Continuous infusion : Dilute with normal saline or 5% dextrose in water. The diluted solution should not be held for more than 4 hours at room temperature or for more than 24 hours under refrigerated conditions. 2.2 Dosing for Treatment of Hypotension during Anesthesia The following are the recommended dosages for the treatment of hypotension during anesthesia. BIORPHEN 0.1 mg/mL Injection: The recommended initial dose is 40 mcg to 100 mcg administered by intravenous bolus. Additional boluses up to 200 mcg may be administered every 1 to 2 minutes as needed. Adjust dosage according to the blood pressure goal. BIORPHEN 10 mg/mL Injection: • The recommended initial dose is 40 mcg to 100 mcg administered by intravenous bolus. Additional boluses up to 200 mcg may be administered every 1 to 2 minutes as needed. • If blood pressure is below the target goal, start a continuous intravenous infusion with an infusion rate of 10 mcg/minute to 35 mcg/minute; not to exceed 200 mcg/minute. • Adjust dosage according to the blood pressure goal. 2.3 Preparation of a 100 mcg/mL Solution for Bolus Intravenous Administration from BIORPHEN 10 mg/mL Injection For bolus intravenous administration, prepare a solution containing a final concentration of 100 mcg/mL of BIORPHEN 10 mg/mL Injection: • Withdraw 10 mg i.e. 1 mL of BIORPHEN 10 mg/mL Injection and dilute with 99 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. • Withdraw an appropriate dose from the 100 mcg/mL solution prior to bolus intravenous administration. 2.4 Preparation of Solution for Continuous Intravenous Administration from BIORPHEN 10 mg/mL Injection For continuous intravenous infusion, prepare a solution containing a final concentration of 20 mcg/mL of BIORPHEN 10 mg/mL Injection in 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. • Withdraw 10 mg i.e. 1 mL of BIORPHEN 10 mg/mL Injection and dilute with 500 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP.
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS BIORPHEN 0.1 mg/mL Injection: Ampule BIORPHEN injection, 0.1 mg/mL, for intravenous use, is a clear and colorless solution available in a type I one point cut, clear, colorless glass, 5 mL single-dose ampule containing 5 mL of solution for injection, corresponding to 0.5 mg of phenylephrine hydrochloride per ampule (equivalent to 0.41 mg of phenylephrine base). Vial BIORPHEN injection, 0.1 mg/mL, for intravenous use, is a clear and colorless solution available in a type I clear colorless glass single-dose vial containing 5 mL of solution for injection, corresponding to 0.5 mg of phenylephrine hydrochloride per vial (equivalent to 0.41 mg of phenylephrine base). BIORPHEN 10 mg/mL Injection: BIORPHEN injection, 10 mg/mL, for intravenous use, is a clear and colorless solution available in a type I one point cut clear colorless glass single-dose ampule containing 1 mL of solution for injection, corresponding to 10 mg of phenylephrine hydrochloride per ampule (equivalent to 8.2 mg of phenylephrine base). Biorphen 0.1 mg/mL Injection: Single-dose ampule containing 5 mL of solution for injection corresponding to 0.5 mg of phenylephrine hydrochloride per ampule. ( 3 ) Biorphen 0.1 mg/mL Injection: Single-dose vial containing 5 mL of solution for injection corresponding to 0.5 mg of phenylephrine hydrochloride per vial.( 3 ) Biorphen 10 mg/mL Injection: Single-dose ampule containing 1 mL of solution for injection corresponding to 10 mg of phenylephrine hydrochloride per ampule. ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE BIORPHEN is indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia. BIORPHEN 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 )
Spl product data elements
Usually a list of ingredients in a drug product.Biorphen Phenylephrine hydrochloride PHENYLEPHRINE HYDROCHLORIDE PHENYLEPHRINE SODIUM CHLORIDE HYDROCHLORIC ACID WATER NITROGEN Biorphen Phenylephrine hydrochloride PHENYLEPHRINE HYDROCHLORIDE PHENYLEPHRINE SODIUM CHLORIDE HYDROCHLORIC ACID WATER NITROGEN Biorphen Phenylephrine hydrochloride PHENYLEPHRINE HYDROCHLORIDE PHENYLEPHRINE SODIUM CHLORIDE HYDROCHLORIC ACID WATER NITROGEN
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Long-term animal studies that evaluated the carcinogenic potential of orally administered phenylephrine hydrochloride in F344/N rats and B6C3F 1 mice were completed by the National Toxicology Program using the dietary route of administration. There was no evidence of carcinogenicity in mice administered approximately 270 mg/kg/day (131 times the human daily dose (HDD) of 10 mg/60 kg/day based on body surface area) or rats administered approximately 50 mg/kg/day (48 times the HDD). Mutagenesis: Phenylephrine hydrochloride tested negative in the in vitro bacterial reverse mutation assay ( S. typhimurium strains TA98, TA100, TA1535 and TA1537), the in vitro chromosomal aberrations assay, the in vitro sister chromatid exchange assay, and the in vivo rat micronucleus assay. Positive results were reported in only one of two replicates of the in vitro mouse lymphoma assay. Impairment of Fertility: Phenylephrine did not impair mating, fertility, or reproductive outcome in normotensive male rats treated with 3 mg/kg/day phenylephrine via continuous intravenous infusion over 1 hour (2.9 times the HDD) for 28 days prior to mating and for a minimum of 63 days prior to sacrifice and female rats treated with the same dosing regimen for 14 days prior to mating and through Gestation Day 6. This dose was associated with increased mortality in both male and female rats and decreased body weight gain in treated males. There were decreased caudal sperm density and increased abnormal sperm reported in males treated with 3 mg/kg/day phenylephrine (2.9 times the HDD).
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Long-term animal studies that evaluated the carcinogenic potential of orally administered phenylephrine hydrochloride in F344/N rats and B6C3F 1 mice were completed by the National Toxicology Program using the dietary route of administration. There was no evidence of carcinogenicity in mice administered approximately 270 mg/kg/day (131 times the human daily dose (HDD) of 10 mg/60 kg/day based on body surface area) or rats administered approximately 50 mg/kg/day (48 times the HDD). Mutagenesis: Phenylephrine hydrochloride tested negative in the in vitro bacterial reverse mutation assay ( S. typhimurium strains TA98, TA100, TA1535 and TA1537), the in vitro chromosomal aberrations assay, the in vitro sister chromatid exchange assay, and the in vivo rat micronucleus assay. Positive results were reported in only one of two replicates of the in vitro mouse lymphoma assay. Impairment of Fertility: Phenylephrine did not impair mating, fertility, or reproductive outcome in normotensive male rats treated with 3 mg/kg/day phenylephrine via continuous intravenous infusion over 1 hour (2.9 times the HDD) for 28 days prior to mating and for a minimum of 63 days prior to sacrifice and female rats treated with the same dosing regimen for 14 days prior to mating and through Gestation Day 6. This dose was associated with increased mortality in both male and female rats and decreased body weight gain in treated males. There were decreased caudal sperm density and increased abnormal sperm reported in males treated with 3 mg/kg/day phenylephrine (2.9 times the HDD).
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.PRINCIPAL DISPLAY PANEL - BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 0.1 mg/ml Ampule Label - NDC 71863-202-05 PRINCIPAL DISPLAY PANEL - BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 0.1 mg/ml Carton Label (10 Single Dose Ampules) - NDC 71863-202-06 PRINCIPAL DISPLAY PANEL - BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 10 mg/ml Ampule Label - NDC 71863-203-01 PRINCIPAL DISPLAY PANEL - BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 10 mg/mL Carton Label (10 Single Dose Ampules) - NDC 71863-203-02 BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 10 mg/mL Carton Label (10 Single Dose Ampules) - NDC 71863-203-02 BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 10 mg/ml Ampule Label (10 Single Dose Ampules) - NDC 71863-203-01 BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 0.1 mg/ml Carton Label (10 Single Dose Ampules) - NDC 71863-202-06 BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 0.1 mg/ml Ampule Label - NDC 71863-202-05
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.RECENT MAJOR CHANGES Dosage and Administration. ( 2 ) 03/2021
Biorphen: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION If applicable, inform patient, family member, or caregiver that certain medical conditions and medications might influence how BIORPHEN injection works. Manufactured for: Eton Pharmaceuticals, Inc. Deer Park, IL 60010 USA Rev. 03/2022 LB5B1PR1
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14 CLINICAL STUDIES The evidence for the efficacy of BIORPHEN, is derived from studies of phenylephrine hydrochloride in the published literature. The literature support includes 16 studies evaluating the use of intravenous phenylephrine to treat hypotension during anesthesia. The 16 studies include 9 studies where phenylephrine was used in low-risk (ASA 1 and 2) pregnant women undergoing neuraxial anesthesia during Cesarean delivery, 6 studies in non-obstetric surgery under general anesthesia, and 1 study in non-obstetric surgery under combined general and neuraxial anesthesia. Phenylephrine has been shown to raise systolic and mean blood pressure when administered either as a bolus dose or by continuous infusion following the development of hypotension during anesthesia.
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use 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.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary Data from randomized controlled trials and meta-analyses with phenylephrine hydrochloride injection use in pregnant women during caesarean 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 is 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 2-4% and 15-20%, 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 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).
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Data from randomized controlled trials and meta-analyses with phenylephrine hydrochloride injection use in pregnant women during caesarean 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 is 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 2-4% and 15-20%, 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 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). 8.2 Lactation Risk Summary There are no data on the presence of Phenylephrine Hydrochloride Injection 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 injection and any potential adverse effects on the breastfed infant from phenylephrine hydrochloride injection or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use 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. 8.6 Hepatic Impairment 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. 8.7 Renal Impairment 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.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING BIORPHEN (phenylephrine hydrochloride) injection is supplied as follows: Unit of Sale Strength Each NDC No. 71863-208-05 5 mL single-dose vial 0.1 mg/mL NDC No. 71863-208-05 5 mL single-dose vial NDC No. 71863-202-06 Pack of 10 single-dose ampules 0.1 mg/mL NDC No. 71863-202-05 5 mL single-dose ampule NDC No. 71863-203-02 Pack of 10 single-dose ampules 10 mg/mL NDC No. 71863-203-01 1 mL single-dose ampule Store BIORPHEN (phenylephrine hydrochloride) injection at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Discard any unused portion.
| Unit of Sale | Strength | Each |
|---|---|---|
| 0.1 mg/mL | ||
| 0.1 mg/mL | ||
| 10 mg/mL |
Storage and handling
Information about safe storage and handling of the drug product.Store BIORPHEN (phenylephrine hydrochloride) injection at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Discard any unused portion.
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API