These Highlights Do Not Include All The Information Needed To Use Biorphen®

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.

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.

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.

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.

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 C₉H₁₃NO₂· 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, 500 mcg/5 mL (100 mcg/mL):

BIORPHEN (phenylephrine hydrochloride) injection, 500 mcg/5 mL (100 mcg/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 100 mcg (equivalent to 80 mcg 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.

BIORPHEN can cause severe bradycardia and decreased cardiac output.

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.

BIORPHEN can increase the need for renal replacement therapy in patients with septic shock. Monitor renal function.

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.

None.

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

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)

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.

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.

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.

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.

BIORPHEN is indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia.

Phenylephrine hydrochloride is an α-1 adrenergic receptor agonist.

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

• BIORPHEN 500 mcg/5 mL (100 mcg/mL)/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)

BIORPHEN 500 mcg/5 mL (100 mcg/mL) Injection:

Ampule

BIORPHEN injection, 500 mcg/5 mL (100 mcg/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 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, 500 mcg/5 mL (100 mcg/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).

If applicable, inform patient, family member, or caregiver that certain medical conditions and medications might influence how BIORPHEN injection works.

Distributed by:

Dr. Reddy’s Laboratories Inc.,

Princeton, NJ 08540



Made in Switzerland

Issued: 04/2024

Extravasation of BIORPHEN can cause necrosis or sloughing of tissue. Avoid extravasation by checking infusion site for free flow.

BIORPHEN (phenylephrine hydrochloride) injection is supplied as follows:

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

PRINCIPAL DISPLAY PANEL - BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 500 mcg/5 mL (100 mcg/mL) Ampule Label/Carton Label

500 mcg/5 mL (100 mcg/mL) Carton Label (10 single Dose Ampules per Carton)

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

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 500 mcg/5 mL (100 mcg/mL) and 10 mg/mL Injection have important differences in administration instructions:

Administration Instructions for BIORPHEN 500 mcg/5 mL (100 mcg/mL) Injection:

BIORPHEN 500 mcg/5 mL (100 mcg/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.

Oxytocic drugs potentiate the increasing blood pressure effect of sympathomimetic pressor amines including BIORPHEN [see Drug Interactions (7.1)], with the potential for hemorrhagic stroke.

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

The following are the recommended dosages for the treatment of hypotension during anesthesia.

BIORPHEN 500 mcg/5 mL (100 mcg/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.

The increasing blood pressure response to adrenergic drugs, including BIORPHEN, can be increased in patients with autonomic dysfunction, as may occur with spinal cord injuries.

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

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.

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.

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.

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.

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.

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.

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 C₉H₁₃NO₂· 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, 500 mcg/5 mL (100 mcg/mL):

BIORPHEN (phenylephrine hydrochloride) injection, 500 mcg/5 mL (100 mcg/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 100 mcg (equivalent to 80 mcg 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.

BIORPHEN can cause severe bradycardia and decreased cardiac output.

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.

BIORPHEN can increase the need for renal replacement therapy in patients with septic shock. Monitor renal function.

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.

None.

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

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)

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.

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.

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.

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.

BIORPHEN is indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia.

Phenylephrine hydrochloride is an α-1 adrenergic receptor agonist.

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

• BIORPHEN 500 mcg/5 mL (100 mcg/mL)/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)

BIORPHEN 500 mcg/5 mL (100 mcg/mL) Injection:

Ampule

BIORPHEN injection, 500 mcg/5 mL (100 mcg/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 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, 500 mcg/5 mL (100 mcg/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).

If applicable, inform patient, family member, or caregiver that certain medical conditions and medications might influence how BIORPHEN injection works.

Distributed by:

Dr. Reddy’s Laboratories Inc.,

Princeton, NJ 08540



Made in Switzerland

Issued: 04/2024

Extravasation of BIORPHEN can cause necrosis or sloughing of tissue. Avoid extravasation by checking infusion site for free flow.

BIORPHEN (phenylephrine hydrochloride) injection is supplied as follows:

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

PRINCIPAL DISPLAY PANEL - BIORPHEN (Phenylephrine Hydrochloride) Injection, USP 500 mcg/5 mL (100 mcg/mL) Ampule Label/Carton Label

500 mcg/5 mL (100 mcg/mL) Carton Label (10 single Dose Ampules per Carton)

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

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 500 mcg/5 mL (100 mcg/mL) and 10 mg/mL Injection have important differences in administration instructions:

Administration Instructions for BIORPHEN 500 mcg/5 mL (100 mcg/mL) Injection:

BIORPHEN 500 mcg/5 mL (100 mcg/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.

Oxytocic drugs potentiate the increasing blood pressure effect of sympathomimetic pressor amines including BIORPHEN [see Drug Interactions (7.1)], with the potential for hemorrhagic stroke.

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

The following are the recommended dosages for the treatment of hypotension during anesthesia.

BIORPHEN 500 mcg/5 mL (100 mcg/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.

The increasing blood pressure response to adrenergic drugs, including BIORPHEN, can be increased in patients with autonomic dysfunction, as may occur with spinal cord injuries.

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

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.

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.