Carbamazepine- Carnexiv™

Carbamazepine- CARNEXIV™ injection

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

Storage and Handling
Vials:
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)

Stability:
Solution:
Before administration, the prepared solution for infusion may be stored for a maximum of 4 hours at 20°C to 25°C (68°F to 77°F) or a maximum of 24 hours if refrigerated at 2°C to 8°C (36°F to 46°F).

Determination of Total Daily Dose for CARNEXIV Infusion

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

WARNINGS 

DESCRIPTION 

The chemical name of carbamazepine, an anticonvulsant, is 5H-dibenz[b,f]azepine-5-carboxamide, and its molecular weight is 236.27.
Carbamazepine is a white to off-white powder, practically insoluble in water and soluble in alcohol and in acetone.

CARNEXIV injection is supplied in single-dose 20 mL vials containing 200 mg carbamazepine. 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.

CLINICAL PHARMACOLOGY:

INDICATIONS AND USAGE 

-Partial seizures with complex symptomatology

-Generalized tonic-clonic seizures

-Mixed seizure patterns which include the above, or other partial or generalized seizures

CONTRAINDICATIONS

PRECAUTIONS

1. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: Monitor for hypersensitivity; discontinue if another cause cannot be established (5.4)
2. Suicidal Behavior and Ideation: Monitor for depression, suicidal thoughts or behavior, and unusual changes in mood or behavior (5.5)
3. Embryofetal Toxicity: Advise women of childbearing potential of possible risks to the fetus (5.6, 8.1)
4. Abrupt Discontinuation and Seizure Risk: Do not discontinue CARNEXIV treatment abruptly (5.7)
5. Hyponatremia: Consider discontinuing CARNEXIV in patients with significant symptomatic hyponatremia (5.8)
6. Hepatic Toxicity; Hepatic Porphyria: Evaluate liver function before and periodically during treatment; avoid CARNEXIV use in patients with hepatic porphyria (5.10, 5.12)

ADVERSE REACTIONS

Most common adverse reactions with CARNEXIV (incidence greater than or equal to 2%) were dizziness, somnolence, blurred vision, diplopia, headache, infusion-related reaction, infusion site pain, and anemia (6.1)

The most common adverse reactions with oral carbamazepine were dizziness, drowsiness, unsteadiness, nausea, and vomiting (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Lundbeck at 1-800-455-1141 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

DOSAGE AND ADMINISTRATION 

The total daily dose of CARNEXIV is 70% of the total daily oral carbamazepine dose from which patients are being switched (see Table 1). The total daily dose of CARNEXIV should be equally divided in four 30-minute infusions, separated by 6 hours.

Patients should be switched back to oral carbamazepine administration at their previous total daily oral dose and frequency of administration as soon as clinically appropriate. The use of CARNEXIV for periods of more than 7 days has not been studied.

Table 1. Determination of Total Daily Dose for CARNEXIV Infusion

2.2 Administration Information
CARNEXIV is for intravenous use only and must be diluted in a compatible diluent prior to infusion.

Using Table 2 as a guide, 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 solution, or 5% dextrose) and mixing gently.

Before administration, the prepared solution for infusion may be stored for a maximum of 4 hours at 20°C to 25°C (68°F to 77°F) or a maximum of 24 hours if refrigerated at 2°C to 8°C (36°F to 46°F).

Parenteral drug products should be inspected visually for particulate matter, cloudiness, or discoloration prior to administration, whenever solution and container permit. If any of these are present, discard the solution.

Administer each infusion intravenously over 30 minutes.

CARNEXIV injection vials are for single-dose only. Discard any unused portion.
 
Table 2. CARNEXIV Dose to Volume and Infusion Table

 2.3 Renal Function Monitoring
Patients with renal impairment may be at greater risk for an adverse effect of CARNEXIV on renal function, and should have close monitoring of renal function during treatment with CARNEXIV. CARNEXIV should generally not be used in patients with moderate or severe renal impairment.

2.4 Serum Level Monitoring
Monitor serum carbamazepine concentrations in conditions in which alterations in carbamazepine metabolism can occur. This includes patients who have hepatic impairment and patients on drugs that either induce or inhibit carbamazepine metabolism.

2.5 Laboratory Testing Prior to Carbamazepine Initiation
Prior to initial treatment with carbamazepine, test patients with ancestry in genetically at-risk populations for the presence of the HLA-B*1502 allele. The high resolution genotype test is positive if one or two HLA-B*1502 alleles are present. Avoid use of CARNEXIV in patients testing positive for the allele, unless the benefit clearly outweighs the risk [see Boxed Warning and Warnings and Precautions].

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 develops [see Warnings and Precautions (5.2)].

Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with carbamazepine because liver damage may occur. Discontinue CARNEXIV in cases of aggravated liver dysfunction or active liver disease.

HOW SUPPLIED 

Storage and Stability

Stability:
Solution:
Before administration, the prepared solution for infusion may be stored for a maximum of 4 hours at 20°C to 25°C (68°F to 77°F) or a maximum of 24 hours if refrigerated at 2°C to 8°C (36°F to 46°F).