Carnexiv

Serious side effects have been reported with Carnexiv. See "Carnexiv Precautions."

Common side effects of Carnexiv include:

• headache
• injection site reactions
• pain at the injection site
• tiredness
• dizziness
• blurred vision

This is not a complete list of Carnexiv side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Serious side effects have been reported with Carnexiv including the following:

• Life-threatening dermatologic reactions such as Stevens-Johnsons syndrome or toxic epidermal necrolysis. If you are of Asian descent, your doctor may order a genetic blood test to see if you are at a higher risk for these reactions. Seek emergency care immediately if you have some or all of the following symptoms of dermatologic reactions:
  • skin rash
  • hives
  • sores in your mouth
  • blistering or peeling of the skin
• Serious blood problems. Carnexiv may decrease the number of blood cells produced by your body enough to cause serious or life threatening health problems. Tell your healthcare provider right away if you have some or all of the following symptoms:
  • sore throat, fever, chills, or other signs of infection
  • easy bruising
  • bleeding gums or nose bleeds
  • feeling very tired
• Suicidal thoughts or actions. Tell your healthcare provider right away if you have some or all of the following symptoms, especially if they are new, worse, or worry you such as:
  • thoughts about suicide or dying
  • attempts to commit suicide
  • new or worse depression
  • new or worse anxiety
  • feeling agitated or restless
  • panic attacks
  • trouble sleeping
  • new or worse irritability
  • acting aggressive
  • being angry, or violent
  • acting on dangerous impulses
  • an extreme increase in activity and talking
  • other unusual changes in behavior or mood
• Life-threatening hypersensitivity that involves multiple organs in your body. Seek emergency care immediately if you have some or all of the following symptoms:
  • fever
  • rash
• Serious harm to your baby if you are pregnant. Carnexiv may cause serious congenital defects including spina bifida and cardiovascular malformation. Tell your doctor if you are pregnant.
• Serious risk of developing seizures and injuries. Talk to your doctor before discontinuing Carnexiv. Do not discontinue Carnexiv abruptly due to seizure risk and withdrawal signs and symptoms.
• Low level of sodium in your blood. Carnexiv may cause your body to retain more fluid than needed and decrease the concentration of serum sodium in your body. Tell your healthcare providers right away if you have some or all of the following symptoms such as
  • headache
  • confusion
  • muscle weakness
  • muscle cramps
  • restlessness 
  • feeling tired
  • vomiting 
• Liver problems. Tell your healthcare provider right away if you have some or all of the following symptoms:
  • yellowing if our skin or the whites of your eyes
  • dark urine
  • pain on the right side of your stomach area
  • easy bruising
  • loss of appetite
  • nausea or vomiting

Carnexiv can cause drowsiness, dizziness, and blurred vision. Do not drive or operate heavy machinery until you know how Carnexiv affects you.

Do not drink alcohol while taking Carnexiv. 

Do not take Carnexiv if you: 

• are allergic to Carnexiv or to any of its ingredients
• have bone marrow depression
• are allergic to any tricyclic antidepressants such as amitriptyline, imipramine and nortriptyline.
• are taking boceprevir
• have taken monoamine oxidase inhibitor within the last 14 days
• are taking nefazodone
• are taking delavirdine or other non-nucleoside reverse transcriptase inhibitor

Grapefruit and grapefruit juice may interact with Carnexiv and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Carbamazepine injection is used as a replacement therapy for oral carbamazepine to treat adults with certain types of seizures (epilepsy). Carbamazepine works in the brain and nervous system to control seizures. This medicine is an anticonvulsant.

This medicine is to be given only by or under the direct supervision of your doctor.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of carbamazepine injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of carbamazepine injection have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of carbamazepine injection in the elderly. However, elderly patients are more likely to have hyponatremia, which may require caution.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Artemether
• Atazanavir
• Boceprevir
• Clorgyline
• Cobicistat
• Daclatasvir
• Darunavir
• Dasabuvir
• Delamanid
• Delavirdine
• Efavirenz
• Elbasvir
• Elvitegravir
• Furazolidone
• Grazoprevir
• Iproniazid
• Isavuconazonium
• Isocarboxazid
• Linezolid
• Lumefantrine
• Lurasidone
• Maraviroc
• Methylene Blue
• Moclobemide
• Nefazodone
• Nialamide
• Ombitasvir
• Pargyline
• Paritaprevir
• Phenelzine
• Praziquantel
• Procarbazine
• Ranolazine
• Rasagiline
• Rilpivirine
• Ritonavir
• Selegiline
• Telaprevir
• Toloxatone
• Tranylcypromine
• Voriconazole

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abiraterone
• Adenosine
• Afatinib
• Alfentanil
• Almotriptan
• Alprazolam
• Amphetamine
• Amprenavir
• Apixaban
• Apremilast
• Aprepitant
• Aripiprazole
• Axitinib
• Bedaquiline
• Benzphetamine
• Blinatumomab
• Bosutinib
• Brexpiprazole
• Brigatinib
• Buprenorphine
• Bupropion
• Butorphanol
• Cabozantinib
• Calcifediol
• Cariprazine
• Ceritinib
• Chlorpromazine
• Clarithromycin
• Clonazepam
• Clozapine
• Cobimetinib
• Codeine
• Conivaptan
• Crizotinib
• Cyclophosphamide
• Cyclosporine
• Dabigatran Etexilate
• Dasatinib
• Deflazacort
• Desmopressin
• Desogestrel
• Desvenlafaxine
• Dextroamphetamine
• Dienogest
• Dihydrocodeine
• Diltiazem
• Dolasetron
• Dolutegravir
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Dronedarone
• Drospirenone
• Eliglustat
• Enzalutamide
• Erlotinib
• Erythromycin
• Eslicarbazepine Acetate
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Etravirine
• Everolimus
• Exemestane
• Ezogabine
• Felodipine
• Fentanyl
• Fluconazole
• Fluoxetine
• Fosamprenavir
• Fosaprepitant
• Fosphenytoin
• Gefitinib
• Gestodene
• Golimumab
• Granisetron
• Guselkumab
• Hydromorphone
• Hydroxytryptophan
• Ibrutinib
• Idelalisib
• Ifosfamide
• Imatinib
• Indinavir
• Irinotecan
• Irinotecan Liposome
• Isoniazid
• Itraconazole
• Ivabradine
• Ivacaftor
• Ixabepilone
• Ixazomib
• Ketoconazole
• Lamotrigine
• Lapatinib
• Ledipasvir
• Levomilnacipran
• Levonorgestrel
• Levorphanol
• Linagliptin
• Lisdexamfetamine
• Lomitapide
• Lopinavir
• Lorcaserin
• Loxapine
• Macitentan
• Manidipine
• Medroxyprogesterone
• Meperidine
• Mestranol
• Methadone
• Methamphetamine
• Midostaurin
• Mifepristone
• Mirtazapine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naloxegol
• Nelfinavir
• Netupitant
• Nifedipine
• Nilotinib
• Nimodipine
• Nintedanib
• Norethindrone
• Norgestimate
• Norgestrel
• Olanzapine
• Olaparib
• Orlistat
• Osimertinib
• Oxycodone
• Oxymorphone
• Palbociclib
• Palonosetron
• Panobinostat
• Pazopanib
• Pentazocine
• Perampanel
• Phenytoin
• Piperaquine
• Pixantrone
• Ponatinib
• Propoxyphene
• Quetiapine
• Quinine
• Regorafenib
• Remifentanil
• Ribociclib
• Rivaroxaban
• Rolapitant
• Romidepsin
• Saquinavir
• Secukinumab
• Simvastatin
• Sofosbuvir
• Sonidegib
• Sufentanil
• Sunitinib
• Tacrolimus
• Tapentadol
• Tasimelteon
• Telithromycin
• Temsirolimus
• Tenofovir Alafenamide
• Terfenadine
• Thioridazine
• Thiotepa
• Ticagrelor
• Tipranavir
• Tofacitinib
• Tolvaptan
• Trabectedin
• Tramadol
• Trazodone
• Ulipristal
• Valbenazine
• Vandetanib
• Velpatasvir
• Vemurafenib
• Venetoclax
• Verapamil
• Vigabatrin
• Vilazodone
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Vorapaxar
• Vortioxetine
• Ziprasidone

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetaminophen
• Acetylcysteine
• Aminophylline
• Amitriptyline
• Amoxapine
• Anisindione
• Caspofungin
• Dalfopristin
• Danazol
• Desipramine
• Dicumarol
• Doxepin
• Etretinate
• Felbamate
• Flunarizine
• Furosemide
• Ginkgo
• Haloperidol
• Hydrochlorothiazide
• Imipramine
• Influenza Virus Vaccine
• Levetiracetam
• Lithium
• Methylphenidate
• Methylprednisolone
• Metronidazole
• Mianserin
• Midazolam
• Miokamycin
• Nafimidone
• Niacinamide
• Nortriptyline
• Omeprazole
• Ospemifene
• Oxcarbazepine
• Paliperidone
• Phenobarbital
• Phenprocoumon
• Pipecuronium
• Primidone
• Protriptyline
• Psyllium
• Quinupristin
• Remacemide
• Rifampin
• Rifapentine
• Risperidone
• Rocuronium
• Rufinamide
• Sabeluzole
• Sertraline
• St John's Wort
• Theophylline
• Tiagabine
• Ticlopidine
• Topiramate
• Troleandomycin
• Valnoctamide
• Valproic Acid
• Vecuronium
• Viloxazine
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Black Tea

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Behavior or mood problems or
• Depression, history of or
• Glaucoma, or history of or
• Hyponatremia (low sodium in the blood) or
• Liver disease, or history of or
• Porphyria (an inherited disease)—Use with caution. May make these conditions worse.

• Asian ancestry (eg, Filipino, Chinese, Japanese, Korean, Taiwanese)—May increase the risk for serious skin reactions. Your doctor may order a special test before prescribing this medicine.

• Bone marrow depression or
• Kidney disease, moderate to severe—Should not be used in patients with this condition.

10.1   Signs, Symptoms and Laboratory Findings of Acute Oral Carbamazepine Overdosage

Acute Toxicity 
Lowest known lethal oral dose: adults, 3.2 g (a 24-year-old woman died of a cardiac arrest and a 24-year-old man died of pneumonia and hypoxic encephalopathy); children, 4 g (a 14-year-old girl died of a cardiac arrest), 1.6 g (a 3-year-old girl died of aspiration pneumonia).

The first signs and symptoms appear 1 to 3 hours after oral carbamazepine administration. Neurologic disturbances are the most prominent. Cardiovascular disorders are generally milder, and severe cardiac complications occur only when very high doses (greater than 60 g) have been ingested.

In a study of carbamazepine intoxications, peak serum levels of carbamazepine below 19.9 mcg/mL were associated with few incidences of severe toxicity (e.g., 1 out of 26 patients were in a coma). Peak serum levels of carbamazepine 19.9 to 39.9 mcg/mL were associated with increased incidences of severe toxicity (e.g., 9 out of 33 patients were in a coma), while peak levels above 40 mcg/mL were always (3 out of 3 patients) associated with a severe toxicity-like coma. Likewise, the incidences of seizures and requirement for mechanical ventilation were correlated with plasma concentrations.

Signs and Symptoms

Respiration

Irregular breathing, respiratory depression.

Cardiovascular System

Tachycardia, hypotension or hypertension, shock, conduction disorders.

Neurological Disturbances

Impairment of consciousness ranging in severity to deep coma. Convulsions, especially in small children. Motor restlessness, muscular twitching, tremor, athetoid movements, opisthotonos, ataxia, drowsiness, dizziness, mydriasis, nystagmus, adiadochokinesia, ballism, psychomotor disturbances, dysmetria. Initial hyperreflexia, followed by hyporeflexia.

Gastrointestinal Tract

Nausea, vomiting.

Kidneys and Bladder

Anuria or oliguria, urinary retention.

Laboratory Findings

Isolated instances of overdosage have included leukocytosis, reduced leukocyte count, glycosuria, and acetonuria. Electrocardiogram may show dysrhythmias.

Combined Poisoning

When alcohol, tricyclic antidepressants, barbiturates, or hydantoins are taken at the same time, the signs and symptoms of acute poisoning with carbamazepine may be aggravated or modified.

10.2   Management of Overdosage

Contact a certified Poison Control Center for up-to-date information on the management of overdose with carbamazepine. There is no specific antidote for overdose with Carnexiv. Consider the possibility of multiple drug overdose. Monitor cardiac rhythm and vital signs. Ensure an adequate airway, oxygenation, and ventilation.

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.  It has the following structural formula:

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.

12.1     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.

12.3     Pharmacokinetics

Carbamazepine
Plasma levels of carbamazepine are variable and may range from 0.5 to 25 mcg/mL, with no apparent relationship to the daily intake of the drug. Usual adult therapeutic levels are between 4 and 12 mcg/mL. In patients on concomitant medications, the concentration of carbamazepine and concomitant drugs may be increased or decreased, and drug effects may be altered [see Drug Interactions (7)].

Bioavailability
The conversion factor for switching patients from oral dose to intravenous dose is 70%. Following adjustment of the intravenous dose by the 70% conversion factor, daily plasma exposures of carbamazepine following 15-minute or 30-minute infusions every 6 hours were comparable to those observed following oral dosing. The pharmacokinetics of carbamazepine-10,11-epoxide were similar following both intravenous and oral dosing.

Distribution

Carbamazepine is 76% bound to plasma proteins and carbamazepine-10,11-epoxide is 50% bound to plasma proteins.

Metabolism

Carbamazepine is primarily metabolized in the liver. CYP3A4 was identified as the major isoform responsible for the formation of carbamazepine-10,11-epoxide. Human microsomal epoxide hydrolase has been identified as the enzyme responsible for the formation of the 10, 11-transdiol derivative from carbamazepine-10, 11-epoxide. Since carbamazepine induces its own metabolism, the half-life is also variable. Autoinduction is completed after 3 to 5 weeks of a fixed dosing regimen. Initial half-life values range from 25 to 65 hours, decreasing to  12 to 17 hours on repeated doses. The apparent oral clearance was 25±5 mL/min following a single dose and 80±30 mL/min following multiple dosing.

Elimination

After administration of 14C-carbamazepine, 72% of the administered radioactivity was found in the urine and 28% was found in the feces. This urinary radioactivity was composed largely of hydroxylated and conjugated metabolites with only 3% as unchanged carbamazepine.

Specific Populations

Age: Geriatric population

The pharmacokinetics of carbamazepine in geriatric patients have not been evaluated.

Age: Pediatric population

The pharmacokinetics of Carnexiv in pediatric and adolescent patients have not been evaluated.

Sex

No difference in the mean area under the concentration-time curve (AUC) and peak plasma concentrations (Cmax) of carbamazepine and carbamazepine-10,11-epoxide was found between males and females.

Race

The effect of race on the pharmacokinetics of carbamazepine has not been established.

Renal Impairment

Carbamazepine clearance was comparable between patients with normal renal function and patients with mild renal impairment (creatinine clearance 60 to 89 mL/min) for both oral carbamazepine and intravenous Carnexiv. The effects of moderate and severe renal impairment (creatinine clearance 30 to 59 mL/min and 15 to 29 mL/min, respectively) on carbamazepine pharmacokinetics are not known [see Dosage and Administration (2.3), Warnings and Precautions (5.3)].

The accumulation of sulfobutylether beta-cyclodextrin sodium salt, a potentially nephrotoxic ingredient of Carnexiv was comparable between patients with normal renal function and mild renal impairment after 7 days of Carnexiv treatment. Sulfobutylether beta-cyclodextrin sodium salt is known to accumulate in patients with moderate to severe renal impairment.  

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of carbamazepine is not known. Patients with hepatic impairment may experience elevated concentrations when switching from oral to intravenous carbamazepine administration (in comparison to patients with normal hepatic function) due to reduction of the first-pass effect [see Use in Specific Populations (8.7)].

NDC 67386-621-52
Single Use Vial
Carnexiv™
(carbamazepine)
Injection
200 mg/20mL
10 mg/mL
For Intravenous use only.
MUST BE DILUTED PRIOR TO INFUSION.

Applies to carbamazepine: compounding powder, intravenous solution, oral capsule extended release, oral suspension, oral tablet, oral tablet chewable, oral tablet extended release

Gastrointestinal

Very common (10% or more): Nausea (29%), vomiting (18%), constipation (10%)
Very rare (less than 0.01%): Colitis, glossitis, stomatitis, pancreatitis
Frequency not reported: Dryness of the mouth, with suppositories occasional rectal irritation may occur, diarrhea, oral ulceration
Postmarketing reports: Gastric distress, abdominal pain, anorexia[Ref]

A single case of chemical pancreatitis has been reported in association with carbamazepine intoxication.[Ref]

Endocrine

Carbamazepine increases the rate of T4 and T3 metabolism and may lead to hypothyroidism in patients with hypothyroidism who are being treated with T4. Carbamazepine may also cause a 20% to 40% decrease in serum total and free T4 concentrations and a smaller decrease in serum total and free T3 concentrations in patients who have no thyroid disease.

Chronic administration of carbamazepine (the active ingredient contained in Carnexiv) may increase total cholesterol and HDL cholesterol levels. Carbamazepine may also transiently increase serum triglyceride and LDL cholesterol levels. One study has suggested that demeclocycline may be useful in prophylaxis of carbamazepine-induced hyponatremia.[Ref]

Very rare (less than 0.01%): Increase in prolactin (with or without symptoms such as gynecomastia or galactorrhea), impaired male fertility and/or abnormal spermatogenesis, abnormal thyroid function tests (e.g., decreased L-thyroxine [FT4, T4, T3] and increased TSH)
Frequency not reported: Hyponatremia, pancreatitis, lower serum testosterone, lower free androgen indexes, increased cerebrospinal fluid thyrotropin-releasing hormone levels[Ref]

Hematologic

Very common (10% or more): Leucopenia
Common (1% to 10%): Eosinophilia, thrombocytopenia, neutropenia
Rare (0.01% to 0.1%): Leukocytosis, lymphadenopathy, folic acid deficiency
Very rare (less than 0.01%): Agranulocytosis, aplastic anemia, pure red cell aplasia, megaloblastic anemia, acute intermittent porphyria, reticulocytosis, hemolytic anemia
Frequency not reported: Aplastic anemia, pancytopenia, bone marrow depression, leukopenia, thrombophlebitis, thromboembolism, adenopathy[Ref]

Thrombocytopenia is the most common hematologic effect of carbamazepine and may be either mild and transient or severe. Significant decreases in white blood cell counts may occur although the values may still be within the normal range. Often counts will return to baseline during continued therapy, and therefore, discontinuation of carbamazepine may not be necessary. Dose reductions may also result in normalization of white blood cell counts. Aplastic anemia has been reported (although many of the reported cases had confounding exposures to other medications). The manufacturer reports an incidence of 2 per 1,000,000 patients for aplastic anemia and 6 per 1,000,000 patients for agranulocytosis. Cases of reticulocytosis have been reported rarely in association with carbamazepine therapy as well. In addition, cases of hemolytic anemia and erythroid arrest have been reported.

Both humoral and nonimmune mechanisms have been implicated in the etiology of carbamazepine-induced bone marrow suppression.[Ref]

Cardiovascular

Rare (0.01% to 0.1%): Disturbances of cardiac conduction
Very rare (less than 0.01%): Bradycardia, arrhythmias, AV-block with syncope, collapse, congestive heart failure, hypertension or hypotension, aggravation of coronary artery disease, thrombophlebitis, thromboembolism[Ref]

Most of the cases of cardiovascular effects reported have occurred in patients receiving carbamazepine for trigeminal neuralgia. The reported effects included congestive heart failure, edema, hypotension, syncope and arrhythmias. In general, the doses were titrated quickly because of severe pain. Many of the doses were higher than those used to treat epilepsy. Many of the reported cardiovascular effects resolved after discontinuation of carbamazepine.

Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose a patient to sudden unexpected death in epilepsy (SUDEP).[Ref]

Nervous system

Very common (10% or more): Dizziness (44%), somnolence (32%), ataxia (15%) Common (1% to 10%): Headache, tremor, vertigo
Uncommon (0.1% to 1%): Abnormal involuntary movements (tremor, asterixis, dystonia, tics)
Rare (less than 0.1%): Choreoathetotic disorders, orofacial dyskinesia, oculomotor disturbances, speech disorders (e.g., dysarthria or slurred speech), peripheral neuritis, paresthesia, paretic symptoms, neuroleptic malignant syndrome
Frequency not reported: Drowsiness, fatigue, fever and chills[Ref]

Rigidity and oculogyric crises have been reported. Euphoria has also been reported and has led to abuse of carbamazepine in some patients. Impairment of psychomotor function has been noted in association with use of the liquid suspension of carbamazepine. Additionally, impaired cognition, exacerbations of focal seizures and asterixis have been reported in association with carbamazepine treatment. One case of a lingual-facial-buccal extrapyramidal reaction has also been described.

One study has suggested that gradual withdrawal of carbamazepine over ten days results in significantly fewer generalized tonic-clonic seizures compared to rapid withdrawal over four days.

One study has suggested that the epoxide metabolite of carbamazepine may be responsible for the occasional occurrence of seizure exacerbations in patients receiving carbamazepine.[Ref]

Hypersensitivity

Rare (0.01% to 0.1%): A delayed multi-organ hypersensitivity disorder (of serum sickness type) with fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leucopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests, occurring in various combinations, other organs may also be affected (e.g., lungs, kidneys, pancreas, myocardium, colon)
Very rare (less than 0.01%): Aseptic meningitis (with myoclonus and peripheral eosinophilia), anaphylactic reaction, angioedema
Frequency not reported: Multiorgan hypersensitivity reactions occurring days, weeks, or months after initiating treatment[Ref]

Rash and pruritus often resolve after discontinuation of carbamazepine therapy. Both cases of lupus-like syndrome resolved after discontinuation of carbamazepine. Stevens-Johnson syndrome, erythema multiforme, and a mononucleosis-like syndrome have also been reported.[Ref]

Hepatic

Very common (10% or more): Elevated gamma-GT (due to hepatic enzyme induction) usually not clinically relevant
Common (1% to 10%): Elevated alkaline phosphatase
Uncommon (0.1% to 1%): Elevated transaminases
Rare (0.01% to 0.1%): Cholestatic and hepatocellular jaundice, hepatitis of cholestatic, parenchymal (hepatocellular), or mixed type
Very rare (less than 0.01%): Granulomatous hepatitis, hepatic failure
Frequency not reported: Liver function test abnormalities, variegate porphyria, porphyria cutanea tarda[Ref]

Alterations in liver function tests may progress to hepatotoxicity including cholangitis, granuloma formation, fever and hepatocellular necrosis. Discontinuation of carbamazepine often results in improvement in laboratory abnormalities and liver injury.[Ref]

Renal

Very rare (less than 0.01%): Interstitial nephritis, renal failure, renal dysfunction (including albuminuria, hematuria, oliguria, and elevated BUN/azotemia)[Ref]

Respiratory

Very rare (less than 0.01%): Pulmonary hypersensitivity (characterized by fever, dyspnea, pneumonitis or pneumonia), pulmonary embolism[Ref]

Dermatologic

Very common (10% or more): Allergic skin reactions, urticaria
Common (1% to 10%): Pruritus, rash, paresthesia
Uncommon (0.1% to 1%): Exfoliative dermatitis, erythroderma
Rare (0.01% to 0.1%): Systemic lupus erythematosus-like syndrome
Very rare (less than 0.01%): Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), photosensitivity, erythema multiforme, erythema nodosum, alterations in skin pigmentation, purpura, acne, sweating, alopecia, hirsutism, unusual bruising, pruritic and erythematous rashes, diaphoresis, onychomycosis, dermatitis
Frequency not reported: Psoriasiform eruption[Ref]

Dangerous, sometimes fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy are significantly more common in patients with the human leukocyte antigen (HLA) allele, HLA-B 1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. Patients with ancestry from areas in which HLA-B 1502 is present should be screened for the HLA-B 1502 allele before starting treatment with carbamazepine. If these individuals test positive, carbamazepine should not be started unless the expected benefit clearly outweighs the increased risk of serious skin reactions. Patients who have been taking carbamazepine for more than a few months without developing skin reactions are at low risk of these events ever developing from carbamazepine. This is true for patients of any ethnicity or genotype, including patients who test positive for HLA-B 1502.[Ref]

Ocular

Common (1% to 10%): Diplopia, accommodation disorders (blurred vision)
Very rare (less than 0.01%): Lens opacities, conjunctivitis
Postmarketing reports: Diplopia, oculomotor disturbances, nystagmus, photosensitivity, visual hallucinations, scattered punctate cortical lens opacities, overall impairment of the chromatic and achromatic systems, increased intraocular pressure[Ref]

Oncologic

Frequency not reported: Disorders mimicking lymphoma[Ref]

Immunologic

Frequency not reported: Antibody deficiency
Postmarketing reports: Aseptic meningitis (with myoclonus and peripheral eosinophilia)[Ref]

Psychiatric

Common (1% to 10%): Abnormal thinking
Rare (0.01% to 0.1%): Hallucinations (visual or acoustic), depression, loss of appetite, restlessness, aggressive behavior, agitation, confusion, talkativeness
Very rare (less than 0.01%): Activation of psychosis, rebound mania following discontinuation of therapy[Ref]

Genitourinary

Very rare (less than 0.01%): Sexual disturbances/impotence, abnormal spermatogenesis (with decreased sperm count and/or motility)
Frequency not reported: Urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, albuminuria, glycosuria, elevated BUN, microscopic deposits in the urine[Ref]

Metabolic

Common (1% to 10%): Hyponatremia, fluid retention, edema, weight gain, reduced plasma osmolarity due to an antidiuretic hormone (ADH)-like effect (leading in rare cases to water intoxication accompanied by lethargy)
Very rare (less than 0.01%): Disturbances of bone metabolism (decrease in plasma calcium and 25-OH-cholecalciferol) leading to osteomalacia, elevated cholesterol (including HDL cholesterol), elevated triglycerides[Ref]

Musculoskeletal

Rare (0.01% to 0.1%): Muscle weakness
Very rare (less than 0.01%): Arthralgia
Postmarketing reports: Leg cramps[Ref]

Other

Very rare (less than 0.01%): Taste disturbances, tinnitus, hyperacusis, hypoacusis, changes in pitch perception[Ref]

Some side effects of Carnexiv may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.