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Intravenous Dilution Guidelines

Carbamazepine- CARNEXIV™ injection

[ Usual Diluents ] [ Standard Dilution ] [ Storage and Stability ]
DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
PRESCRIBING HIGHLIGHTS:  Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.  

Drug UPDATES:   [Drug information  /  PDF]  
 

Usual Diluents top of page

NS,  D5W, LR

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

[Prescribed dose ]
[0 - 280mg]  [100 ml]  [30 minutes]


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
Total Daily Oral Carbamazepine Dose (mg/day) Corresponding Total Daily Dose of CARNEXIV
(mg/day)
Dose of CARNEXIV to be administered every 6 hours (mg)
400   280   70
600   420   105
800   560   140
1,000   700   175
1,200   840   210
1,400   980   245
1,600 1,120   280

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


WARNINGS  top of page

WARNING: SERIOUS DERMATOLOGIC REACTIONS AND APLASTIC ANEMIA AND AGRANULOCYTOSIS
  • Serious Dermatologic Reactions and HLA-B*1502 Allele
    Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have occurred in patients treated with carbamazepine. There is a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene that is found almost exclusively in patients with Asian ancestry. Avoid use of CARNEXIV in patients testing positive for the allele unless the benefit clearly outweighs the risk. Discontinue CARNEXIV if you suspect that the patient is having a serious dermatologic reaction [see Warnings and Precautions (5.1)].
  • Aplastic Anemia and Agranulocytosis
    Aplastic anemia and agranulocytosis can occur during treatment with CARNEXIV. Obtain a complete blood count (CBC) before beginning treatment with CARNEXIV, and monitor CBC periodically. Consider discontinuing CARNEXIV if significant bone marrow depression develops


DESCRIPTION  top of page

Description:
CARNEXIV (carbamazepine) injection is available as a clear, colorless, sterile solution for intravenous infusion.

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: top of page

Mechanism of Action:
The mechanism by which carbamazepine exerts its anticonvulsant activity is unknown. The principal metabolite of carbamazepine, carbamazepine-10,11-epoxide, has demonstrated anticonvulsant activity in in vivo animal models of seizures. However, its contribution to the therapeutic effect of carbamazepine is unknown.

INDICATIONS AND USAGE  top of page

INDICATIONS AND USAGE:
CARNEXIV is indicated as replacement therapy for oral carbamazepine formulations, when oral administration is temporarily not feasible, in adults with the following seizure types (1):

-Partial seizures with complex symptomatology

-Generalized tonic-clonic seizures

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

CONTRAINDICATIONS top of page

Contraindications:
Bone marrow depression (4, 5.2)
Hypersensitivity to carbamazepine (4, 5.4)
Hypersensitivity to tricyclic antidepressants (4, 7.1)
Concomitant use of boceprevir (4, 7.1).
Use of MAOIs within the past 14 days (4,7.3)
Concomitant use of nefazodone (4, 7.1)
Concomitant use with delavirdine or other non-nucleoside reverse transcriptase inhibitors (4, 7.1)

PRECAUTIONS top of page

WARNINGS AND 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 top of page

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  top of page

DOSAGE AND ADMINISTRATION:
2.1 Dosage Information
CARNEXIV is a replacement therapy for oral carbamazepine. Carbamazepine treatment should generally be initiated with an oral carbamazepine formulation.

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

Total Daily Oral Carbamazepine Dose (mg/day) Corresponding Total Daily Dose of CARNEXIV
(mg/day)
Dose of CARNEXIV to be administered every 6 hours (mg)
400   280   70
600   420   105
800   560   140
1,000   700   175
1,200   840   210
1,400   980   245
1,600 1,120   280

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

CARNEXIV Single Dose (mg/every 6 hours)

CARNEXIV

Single Dose Volume

(Vials Required)

 

Diluent Volume

 

Infusion Duration

Dose Frequency

70

7 mL (1)

 

 

 

100 mL

 

 

 

 

 

 

30 min

 

 

 

 

 

 

Every 6 hours

105

10.5 mL (1)

140

14 mL (1)

175

17.5 mL (1)

210

21 mL (2)

245

24.5 mL (2)

280

28 mL (2)

 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  top of page

DOSAGE FORMS AND STRENGTHS:
CARNEXIV (carbamazepine) 200 mg/20 mL (10 mg/mL) injection is a clear, colorless, sterile solution. It is supplied in single-dose 20 mL glass vials, available in cartons of one vial (NDC 67386-621-52). Not made with natural rubber latex.

Storage and Stability top of page

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).


Disclaimer
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.
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