FDA

Akovaz

Approved 29 Apr 2016IntravenousSolution

The FDA lists this product in 2 strengths and forms.

Indications

AKOVAZ (ephedrine sulfate injection) is indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia. AKOVAZ injection is an alpha- and beta-adrenergic agonist and a norepinephrine-releasing agent that is indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia. ( 1 )

Contraindications

None None ( 4 )

Warnings and precautions

Pressor Effects with Concomitant Use with Oxytocic Drugs : Pressor effect of sympathomimetic pressor amines is potentiated ( 5.1 )
Tachyphylaxis and Tolerance : Repeated administration of ephedrine may cause tachyphylaxis ( 5.2 )

5.1Pressor Effect with Concomitant Oxytocic Drugs

Serious postpartum hypertension has been described in patients who received both a vasopressor (i.e., methoxamine, phenylephrine, ephedrine) and an oxytocic (i.e., methylergonovine, ergonovine) [ see Drug Interactions (7) ]. Some of these patients experienced a stroke. Carefully monitor the blood pressure of individuals who have received both ephedrine and an oxytocic.

5.2Tolerance and Tachyphylaxis

Data indicate that repeated administration of ephedrine can result in tachyphylaxis. Clinicians treating anesthesia-induced hypotension with AKOVAZ (ephedrine sulfate injection) should be aware of the possibility of tachyphylaxis and should be prepared with an alternative pressor to mitigate unacceptable responsiveness.

5.3Risk of Hypertension When Used Prophylactically

When used to prevent hypotension, ephedrine has been associated with an increased incidence of hypertension compared with when ephedrine is used to treat hypotension.

Interactions

Interactions that Augment the Pressor Effect Oxytocin and oxytocic drugs Clinical Impact: Serious postpartum hypertension has been described in patients who received both a vasopressor (i.e., methoxamine, phenylephrine, ephedrine) and an oxytocic (i.e., methylergonovine, ergonovine). Some of these patients experienced a stroke. Intervention: Carefully monitor the blood pressure of individuals who have received both ephedrine and an oxytocic.

At a glance

Brand name: Akovaz
Active substance: ephedrine sulfate
Route: Intravenous
Dosage form: Solution
Applicant: Exela Pharma
Status: Prescription
FDA approval: 29 Apr 2016
Application: NDA208289-001

Indications

Warnings and precautions

Pressor Effects with Concomitant Use with Oxytocic Drugs : Pressor effect of sympathomimetic pressor amines is potentiated ( 5.1 )
Tachyphylaxis and Tolerance : Repeated administration of ephedrine may cause tachyphylaxis ( 5.2 )

5.1Pressor Effect with Concomitant Oxytocic Drugs

5.2Tolerance and Tachyphylaxis

5.3Risk of Hypertension When Used Prophylactically

When used to prevent hypotension, ephedrine has been associated with an increased incidence of hypertension compared with when ephedrine is used to treat hypotension.

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Available data from randomized studies, case series, and reports of ephedrine sulfate use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are clinical considerations due to underlying conditions (see Clinical Considerations ) . In animal reproduction studies, decreased fetal survival and fetal body weights were observed in the presence of maternal toxicity after normotensive pregnant rats were administered 60 mg/kg intravenous ephedrine sulfate (12 times the maximum recommended human dose (MRHD) of 50 mg/day).

No malformations or embryofetal adverse effects were observed when pregnant rats or rabbits were treated with intravenous bolus doses of ephedrine sulfate during organogenesis at doses 1.9 and 7.7 times the MRHD, respectively [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 2-4% 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 decrease in uterine blood flow due to maternal hypotension may result in fetal bradycardia and acidosis.

Fetal/Neonatal Adverse Reactions Cases of potential metabolic acidosis in newborns at delivery with maternal ephedrine exposure have been reported in the literature. These reports describe umbilical artery pH of ≤7.2 at the time of delivery [see Clinical Pharmacology (12.3 )]. Monitoring of the newborn for signs and symptoms of metabolic acidosis may be required. Monitoring of infant’s acid-base status is warranted to ensure that an episode of acidosis is acute and reversible.

Data Animal Data Decreased fetal body weights were observed when pregnant rats were administered intravenous bolus doses of 60 mg/kg ephedrine sulfate (12 times the maximum recommended human dose (MRHD) of 50 mg based on body surface area) from Gestation Day 6-17. This dose was associated with evidence of maternal toxicity (decreased body weight of dams and abnormal head movements). No malformations or fetal deaths were noted at this dose.

No effects on fetal body weight were noted at 10 mg/kg (1.9 times the MRHD of 50 mg). No evidence of malformations or embryo-fetal toxicity were noted in pregnant rabbits administered intravenous bolus doses up to 20 mg/kg ephedrine sulfate (7.7 times the maximum recommended human dose (MRHD) of 50 mg based on body surface area) from Gestation Day 6-20. This dose was associated with expected pharmacological maternal effects (increased respiration rate, dilated pupils, piloerection).

Decreased fetal survival and body weights in the presence of maternal toxicity (increased mortality) were noted when pregnant dams were administered intravenous bolus doses of 60 mg/kg epinephrine sulfate (approximately 12 times the MRHD based on body surface area) from GD 6 through Lactation Day 20. No adverse effects were noted at 10 mg/kg (1.9 times the MRHD).

Akovaz

Indications

Contraindications

Warnings and precautions

5.1Pressor Effect with Concomitant Oxytocic Drugs

5.2Tolerance and Tachyphylaxis

5.3Risk of Hypertension When Used Prophylactically

Interactions

At a glance

Two medicines in one question?

Akovaz

Indications

Contraindications

Warnings and precautions

5.1Pressor Effect with Concomitant Oxytocic Drugs

5.2Tolerance and Tachyphylaxis

5.3Risk of Hypertension When Used Prophylactically

Interactions

At a glance

Two medicines in one question?

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Strengths and forms

Official product information