Generic drug: carbamazepine
Brand name: Carnexiv
What is Carnexiv (carbamazepine), and how does it work?
Carnexiv (carbamazepine) injection is an anticonvulsant 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.
What are the side effects of Carnexiv?
Common side effects of Carnexiv include:
- dizziness,
- drowsiness,
- blurred vision,
- double vision,
- headache,
- infusion-related reaction,
- infusion site pain, and
- anemia.
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.
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.
What is the dosage for Carnexiv?
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
What drugs interact with Carnexiv?
Effects Of Carnexiv On Other Drugs
- Carbamazepine is a potent inducer of hepatic CYP1A2, 2B6, 2C9/19 and 3A4 and may reduce plasma concentrations of concomitant medications mainly metabolized by CYP1A2, 2B6, 2C9/19, and 3A4 through induction of their metabolism (see Tables 5 and 6).
Table 5: Effects of Carbamazepine on Other Drugs
Concomitant Drug Name
Effect of Carbamazepine on Other Drugs
Clinical Recommendation
Boceprevir
Decrease in boceprevir levels
Coadministration of carbamazepine with boceprevir is contraindicated
Acetaminophen, albendazole, alprazolam, aprepitant, buprenorphone, bupropion, citalopram, clonazepam, clozapine, corticosteroids (e.g., prednisolone, dexamethasone), cyclosporine, dicumarol, dihydropyridine calcium channel blockers (e.g., felodipine), doxycycline, eslicarbazepine, ethosuximide, everolimus, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, mianserin, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, sertraline, sirolimus, tadalafil, theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide
Decrease in concomitant drug levels
Monitor the concentration and consider a dosage adjustment of the concomitant drug(s)
Cyclophosphamide
Increase in cyclophosphamide levels (potential for increased toxicity)
Monitor for signs of increased cyclophosphamide toxicity
Aripiprazole
Decrease in aripiprazole levels
When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled; additional dose increases should be based on clinical evaluation; when carbamazepine is withdrawn from the combination therapy, the aripiprazole dose should be reduced
Tacrolimus
Decrease in tacrolimus levels
Monitor tacrolimus blood concentrations and make appropriate dosage adjustments
Temsirolimus
Decrease in temsirolimus levels
The use of concomitant strong CYP3A4 inducers such as carbamazepine should be avoided with temsirolimus; if carbamazepine must be coadministered with temsirolimus, consider adjusting the dosage of temsirolimus
Lapatinib
Decrease in lapatinib levels
The use of carbamazepine with lapatinib should generally be avoided; dosage adjustment should be considered if lapatinib is coadministered with carbamazepine; if carbamazepine is started in a patient already taking lapatinib, the dose of lapatinib should be gradually titrated up; if carbamazepine is discontinued, the lapatinib dose should be reduced
Nefazodone
Decrease in nefazodone levels
Coadministration of carbamazepine with nefazodone is contraindicated
Valproate
Decrease in valproate levels
Monitor valproate concentrations when carbamazepine is introduced or withdrawn in patients using valproic acid
Table 6: Effects of Carbamazepine on Other Drugs (Continued)
Concomitant Drug Name
Effect of Carbamazepine on Other Drugs
Clinical Recommendation
Lithium
May increase the risk of neurotoxic side effects
Use with intensive monitoring
Isoniazid
May increase isoniazid-induced hepatotoxicity
Diuretics (e.g., hydrochlorothiazide, furosemide)
May lead to symptomatic hyponatremia
Hormonal contraceptives (e.g., oral and levonorgestrel subdermal implant contraceptives)
May render the contraceptives less effective because the plasma concentrations of the hormones may be decreased; breakthrough bleeding and unintended pregnancies have been reported
Consider alternative or back-up methods of contraception
Neuromuscular blocking agents (e.g., pancuronium, vecuronium, rocuronium, and cisatracurium)
Resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents
Closely monitor patients for more rapid recovery from neuromuscular blockade than expected; infusion rate may need to be higher
Direct acting oral anticoagulants (e.g., rivaroxaban, apixaban, dabigatran, and edoxaban)
Decreased plasma concentrations of these anticoagulants that may be insufficient to achieve the intended therapeutic effect
Coadministration with carbamazepine should generally be avoided
Delavirdine or other non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Decrease in delavirdine or NNRTI levels
Contraindicated with carbamazepine
Effects Of Other Drugs On Carnexiv
- CYP3A4 inhibitors inhibit Carnexiv metabolism and can thus increase plasma carbamazepine levels.
- CYP3A4 inducers can increase the rate of Carnexiv metabolism and thus decrease carbamazepine levels (see Table 7).
Table 7: Effects of Other Drugs on Carbamazepine
Concomitant Drug Name
Effect of Concomitant Drug on Carbamazepine
Clinical Recommendation
Aprepitant, cimetidine, ciprofloxacin, danazol, diltiazem, delavirdine, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, trazodone, olanzapine, loratadine, terfenadine, omeprazole, oxybutynin, dantrolene, isoniazid, niacinamide, nicotinamide, ibuprofen, propoxyphene, azoles (e.g., ketaconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil, ticlopidine, grapefruit juice, protease inhibitors
Increase in carbamazepine level (by CYP3A4 inhibition)
Closely monitor carbamazepine levels; dosage adjustment may be required
Cisplatin, doxorubicin HCl, felbamate, fosphenytoin, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline
Decrease in carbamazepine level (by CYP3A4 induction)
Loxapine, quetiapine and valproic acid
Decrease in carbamazepine level and increase in metabolite (carbamazepine-10,11-epoxide) levels (both by inhibition of human microsomal epoxide hydrolase)
Closely monitor carbamazepine levels; dosage adjustment may be required
Pharmacodynamic Drug Interactions
Monoamine Oxidase Inhibitors
- Concomitant treatment with Carnexiv is contraindicated during use of an MAOI or within 14 days after discontinuing an MAOI. Concomitant use can cause serotonin syndrome.
Is Carnexiv safe to use while pregnant or breastfeeding?
- Pregnancy registry and epidemiological data indicate that carbamazepine can cause fetal harm when administered to a pregnant woman.
- Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information regarding the effects of in utero exposure to
Carnexiv. To enroll, patients can call the toll-free number 1-888-233-2334. Information about the North American Antiepileptic Drug Pregnancy Registry can be found at http://www.aedpregnancyregistry.org - Carbamazepine and its epoxide metabolite are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants exposed to
Carnexiv, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.