NOW APPROVED!

From oral to intravenous (IV) and back to oral*

CONTINUITY OF CARBAMAZEPINE THERAPY

CARNEXIV™ (carbamazepine) injection is indicated as replacement therapy for oral carbamazepine formulations, when oral administration is temporarily not feasible, in adults with the following seizure types:

  • Partial seizures with complex symptomatology
  • Generalized tonic-clonic seizures
  • Mixed seizure patterns which include the above, or other partial or generalized seizures

Limitations of Usage

CARNEXIV is not indicated for the treatment of absence seizures (including atypical absence). Carbamazepine has been associated with increased frequency of generalized convulsions in these patients.

 

CARNEXIV total daily dose is 70% of the total daily dose of oral carbamazepine; divide the total daily dose of CARNEXIV equally in four 30-minute infusions separated by 6 hours (q6h).1

  • CARNEXIV provides continuity of carbamazepine therapy.1,2 CARNEXIV is the only IV carbamazepine option available for adult epilepsy patients on a stable dose of oral carbamazepine who are temporarily NPO (“nothing by mouth”) due to illness, injury, surgery, or hospitalization1,2
  • Bioavailability similar to oral carbamazepine when dosed at 70% of patient's total daily oral dose1,2
  • CARNEXIV is contraindicated in patients with bone marrow depression or a known hypersensitivity to carbamazepine or tricyclic antidepressants1
  • Patients with renal impairment should have close monitoring of renal function during treatment with CARNEXIV; CARNEXIV should generally not be used in patients with moderate or severe renal impairment1
  • Carbamazepine is a potent inducer of hepatic CYP1A2, 2B6, 2C9/19, and 3A4 and may reduce plasma concentrations of concomitant medications mainly metabolized by these enzymes through induction of their metabolism
CARNEXIV IS DOSED AT
70% OF TOTAL DAILY
ORAL DOSE OF
CARBAMAZEPINE1
DAILY INFUSION
SCHEDULE:
4 EQUALLY
DIVIDED DOSES-
30-MIN INFUSIONS1

Important Dosing Information

  • CARNEXIV is supplied in a 200 mg/20 mL single-dose vial (10 mg/mL carbamazepine and 250 mg/mL of betadex sulfobutyl ether sodium)1 
  • CARNEXIV is for IV use only and must be diluted in a compatible diluent (0.9% sodium chloride, lactated Ringer's solution, or 5% dextrose) prior to infusion1
  • CARNEXIV is administered as replacement therapy at 70% of the established total daily dose of oral carbamazepine1
  • Switch patients back to oral carbamazepine at previously established total daily oral dose and frequency as soon as clinically appropriate1,2
    • Use of CARNEXIV for more than 7 days has not been studied and is not recommended1

 

Preparation, Handling, and Administration

  1. Inspect vial for particulate matter, cloudiness, or discoloration. If any of these are present, discard the vial1
  2. Determine the 70% adjusted total daily replacement IV dose from the patient’s established total daily oral dose. Divide the total daily dose of CARNEXIV equally in 4 infusions separated by 6 hours1
  3. Prepare the solution for each infusion by transferring the single-dose volume of CARNEXIV to 100 mL of diluent solution (0.9% sodium chloride, lactated Ringer’s, or 5% dextrose) and mixing gently1
    • The prepared solution for infusion may be stored for 4 hours at room temperature or may be stored for a maximum of 24 hours if refrigerated at 2°C to 8°C (36°F to 46°F) before administration1
    • Inspect the prepared solution for particulate matter, cloudiness, or discoloration. If any of these are present, discard the solution1
  4. Administer each infusion over 30 minutes every 6 hours1

CARNEXIV vials are designed for single-dose only. Discard any unused portion.1

 

Important Patient Monitoring Information

  • Complete pretreatment blood counts, including platelets and possibly reticulocytes and serum iron, should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of CARNEXIV should be considered if any evidence of significant bone marrow depression develops1
  • Monitor renal function and electrolytes during treatment with CARNEXIV. Closely monitor patients with renal impairment during treatment due to greater risk for an adverse effect on renal function. CARNEXIV should generally not be used in patients with moderate or severe renal impairment1
  • Monitor serum carbamazepine concentrations in patients with hepatic impairment. Hepatic effects, ranging from slight elevations in liver enzymes to rare cases of hepatic failure, have been reported, and may progress despite drug discontinuation. Rare instances of vanishing bile duct syndrome have also been reported
  • Evaluate liver function before and during treatment, particularly in patients with a history of liver disease
  • Discontinue CARNEXIV based on clinical judgment in the case of active liver disease, or with newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage. Avoid using CARNEXIV in patients with a history of hepatic porphyria

 

Storage and Handling

CARNEXIV is available as a clear, colorless, sterile solution for intravenous (IV) infusion.1 CARNEXIV is supplied in single-dose, 20-mL glass vials containing 200 mg carbamazepine, available in cartons of 1 vial.*1 CARNEXIV should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).✝︎1

Each mL contains 10 mg of carbamazepine, 250 mg of betadex sulfobutyl ether sodium, and 0.78 mg of sodium phosphate monobasic dihydrate in water for injection. The product may contain sodium hydroxide and/or hydrochloric acid for pH adjustment to pH 6.2. Not made with natural rubber latex.1
✝︎See USP Controlled Room Temperature.1

For more information, refer to Important Safety Information and the full Prescribing Information, including Boxed Warning for risk of serious dermatologic reactions and aplastic anemia and agranulocytosis.

 

Most common adverse reactions* reported in ≥2% of patients on CARNEXIV†1
Incidence greater than or equal to 2%.
✝︎Other significant adverse reactions observed in <2% of patients included hyponatremia, atrial tachycardia, and electrocardiogram T-wave inversion.1
3.6% of 4088 infusions of CARNEXIV were delivered over 2 to 5 minutes during the study. This was faster than the recommended 30-minute infusion rate. The most common adverse reaction was dizziness (11%).1
§Infusion rate two times more rapid than recommended.1
 
 
  • Most common adverse reactions with CARNEXIV (incidence ≥2%) were dizziness, somnolence, blurred vision, diplopia, headache, infusion-related reaction, infusion site pain, and anemia1
    • With oral carbamazepine, the most common adverse reactions, particularly during the initial phases of therapy, were dizziness, drowsiness, unsteadiness, nausea, and vomiting1
  • The safety and effectiveness of CARNEXIV have not been established in pediatric patients1


Important Safety Information

  • Antiepileptic drugs (AEDs), including CARNEXIV, increase the risk of suicidal thoughts or behavior. Monitor patients for the emergence or worsening of depression, any unusual changes in mood or behavior, or suicidal thoughts, behavior, or thoughts of self-harm; and instruct families and caregivers to report behaviors of concern immediately.1
  • CARNEXIV can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant while taking CARNEXIV, inform the patient of the potential risk to the fetus.
  • Discontinue CARNEXIV or discontinue nursing, taking into consideration the importance of the drug to the mother.
  • Do not discontinue CARNEXIV abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs/symptoms.
IMPORTANT SAFETY INFORMATION

Expand

WARNING: SERIOUS DERMATOLOGIC REACTIONS
and APLASTIC ANEMIA AND AGRANULOCYTOSIS

See full prescribing information for complete boxed warning.

Serious Dermatologic Reactions

  • Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have occurred with carbamazepine. Discontinue CARNEXIV if these reactions occur
  • Patients of Asian ancestry have a 10-fold greater risk of TEN/SJS, compared to other populations. Avoid use of CARNEXIV in genetically at-risk patients, including those positive for the HLA-B*1502 allele

Aplastic Anemia and Agranulocytosis

  • Aplastic anemia and agranulocytosis can occur with CARNEXIV
  • Obtain complete CBC prior to initiation of CARNEXIV. Consider discontinuing CARNEXIV if significant bone marrow depression develops
IMPORTANT SAFETY INFORMATION

Collapse

WARNING: SERIOUS DERMATOLOGIC REACTIONS
and APLASTIC ANEMIA AND AGRANULOCYTOSIS

See full prescribing information for complete boxed warning.

Serious Dermatologic Reactions

  • Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have occurred with carbamazepine. Discontinue CARNEXIV if these reactions occur
  • Patients of Asian ancestry have a 10-fold greater risk of TEN/SJS, compared to other populations. Avoid use of CARNEXIV in genetically at-risk patients, including those positive for the HLA-B*1502 allele

Aplastic Anemia and Agranulocytosis

  • Aplastic anemia and agranulocytosis can occur with CARNEXIV
  • Obtain complete CBC prior to initiation of CARNEXIV. Consider discontinuing CARNEXIV if significant bone marrow depression develops

Contraindications: Bone Marrow Depression, Hypersensitivity, and Concomitant Drugs

  • Patients with bone marrow depression or a known hypersensitivity to carbamazepine or tricyclic antidepressants. If patient or immediate family member has history of hypersensitivity, consider benefits and risks and closely monitor for symptoms
  • Concomitant use with boceprevir, nefazodone, and delavirdine or other non-nucleoside reverse transcriptase inhibitors
  • Use of monoamine oxidase inhibitors (MAOIs) within the past 14 days before beginning carbamazepine treatment

Toxic Epidermal Necrolysis (TEN), Stevens-Johnson syndrome (SJS), HLA-B*1502 Allele, and Aplastic Anemia and Agranulocytosis (see Boxed Warning)

Renal Impairment
CARNEXIV should generally not be used in patients with moderate or severe renal impairment. Closely monitor patients with renal impairment.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
DRESS, also known as multiorgan hypersensitivity, has occurred with carbamazepine. These events can be fatal or life-threatening. Advise patients to report signs and symptoms such as fever, rash, lymphadenopathy, and/or facial swelling immediately, and discontinue CARNEXIV if an alternative etiology cannot be established.

Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including CARNEXIV, increase the risk of suicidal thoughts or behavior. Monitor patients for the emergence or worsening of depression, any unusual changes in mood or behavior, or suicidal thoughts, behavior, or thoughts of self-harm; and instruct families and caregivers to report behaviors of concern immediately.

Pregnancy Registry and Nursing Mothers

  • CARNEXIV can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant while taking CARNEXIV, inform the patient of the potential risk to the fetus and carefully consider both the potential risks and benefits of treatment. Encourage patients to call the toll-free number 1-888-233-2334 to enroll in the Pregnancy Registry or visit http://www.aedpregnancyregistry.org/.
  • Discontinue CARNEXIV or discontinue nursing, taking into consideration the importance of the drug to the mother. 

Abrupt Discontinuation and Seizure Risk
Do not discontinue CARNEXIV abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs/symptoms.

Hyponatremia
Hyponatremia can result from treatment with CARNEXIV, and in many cases appears to be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The risk of SIADH appears to be dose-related. Elderly patients and patients treated with diuretics are at a greater risk. Consider discontinuing CARNEXIV in patients with symptomatic hyponatremia.

Neurologic Function
Carbamazepine has the potential to impair judgment, cognition, motor function, and motor coordination, and it may also cause dizziness, ataxia, and drowsiness. Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that carbamazepine does not affect them adversely.

Hepatic Toxicity
Hepatic effects, ranging from slight elevations in liver enzymes to rare cases of hepatic failure, have been reported, and may progress despite drug discontinuation. Rare instances of vanishing bile duct syndrome have also been reported. Evaluate liver function before and during treatment, particularly in patients with a history of liver disease. Discontinue CARNEXIV based on clinical judgment in the case of active liver disease, or with newly occurring or worsening clinical or laboratory evidence of liver dysfunction or hepatic damage.

Increased Intraocular Pressure
Carbamazepine has mild anticholinergic activity. Consider assessing intraocular pressure before initiating and periodically during therapy in patients with a history of increased intraocular pressure.

Hepatic Porphyria
Avoid using CARNEXIV in patients with a history of hepatic porphyria, as acute attacks have been reported in such patients and CARNEXIV increases porphyrin precursors in rodents.

Drug Interactions
Carbamazepine may reduce plasma concentrations of concomitant medications metabolized by CYP1A2, 2B6, 2C9/19 and 3A4; closely monitor carbamazepine levels and make appropriate dose adjustments. CYP3A4 inhibitors can increase plasma carbamazepine levels. CYP3A4 inducers can decrease carbamazepine levels.

Adverse Reactions
The most common adverse reactions with CARNEXIV (incidence ≥2%) were dizziness, somnolence, blurred vision, diplopia, headache, infusion-related reaction, infusion site pain, and anemia. The most common adverse reactions with oral carbamazepine were dizziness, drowsiness, unsteadiness, nausea, and vomiting.

Important Dosing Information
Use of CARNEXIV for more than 7 days has not been studied and is not recommended. At the end of intravenous (IV) replacement therapy, switch patients back to oral carbamazepine at their previous total daily oral dose and frequency as soon as clinically appropriate. 

 

Please see the full Prescribing Information, including Boxed Warning for serious dermatologic reactions and aplastic anemia and agranulocytosis, for complete details.

 

References: 1. CARNEXIV [package insert]. Deerfield, IL: Lundbeck. 2. Tolbert D, Cloyd J, Biton V, et al. Bioequivalence of oral and intravenous carbamazepine formulations in adult patients with epilepsy. Epilepsia. 2015:56(6):915-923.