Indications
IV, PO: Treatment of tonic-clonic, mixed, and complex-
partial seizures. PO: Management of pain in trigeminal
neuralgia. Equetro only: Acute manic or
mixed episodes associated with bipolar I disorder. Unlabeled
Use: Other forms of neurogenic pain.
Action
Decreases synaptic transmission in the CNS by affecting
sodium channels in neurons. Therapeutic Effects:
Prevention of seizures. Relief of pain in trigeminal neuralgia.
Decreased mania.
Pharmacokinetics
Absorption: Oral absorption is slow but complete.
Suspension produces earlier, higher peak, and lower
trough levels. IV administration results in complete bioavailability.
Distribution: Widely distributed. Crosses the bloodbrain
barrier. Crosses the placenta rapidly and enters
breast milk in high concentrations.
Protein Binding: Carbamazepine—75–90%;
epoxide—50%.
Metabolism and Excretion: Extensively metabolized
in the liver by cytochrome P450 3A4 to active
epoxide metabolite; epoxide metabolite has anticonvulsant
and antineuralgic activity.
Half-life: Carbamazapine—single dose—25–65
hr, chronic dosing—Children—8–14 hr; Adults—
12–17 hr; epoxide—349 hr.
TIME/ACTION PROFILE (anticonvulsant
activity)
ROUTE ONSET PEAK DURATION
PO up to 1 mo† 4–5 hr‡ 6–12 hr
PO-ER up to 1 mo† 2–3–12 hr‡ 12 hr
IV unknown unknown unknown
†Onset of antineuralgic activity is 8–72 hr.
‡Listed for tablets; peak level occurs 1.5 hr after a chronic
dose of suspension.
Contraindications/Precautions
Contraindicated in: Hypersensitivity to carbamazepine
or tricyclic antidepressants; Bone marrow suppression;
Concomitant use or use within 14 days of
MAO inhibitors; Concurrent use of nefazodone or
NNRTIs that are CYP3A4 substrates; Moderate-to-severe
renal impairment (IV only); OB: Use only if potential benefits outweigh risks to the fetus; additional vitamin K
during last wk of pregnancy has been recommended;
Lactation: Discontinue drug or bottle feed.
Use Cautiously in: All patients (mayqrisk of suicidal
thoughts/behaviors); Cardiac or hepatic disease;
Renal failure (dosing adjustment required for CCr 10
mL/min); Mild renal impairment (IV only);qintraocular
pressure; Geri: Older men with prostatic hyperplasia
may be atqrisk for acute urinary retention or difficulty
initiating stream; Pedi: Safety and effectiveness of IV formulation
not established.
Exercise Extreme Caution in: Patients positive
for HLA-B*1502 or HLA-A*3101 alleles (unless benefits
clearly outweigh the risks) (qrisk of serious skin reactions).
Adverse Reactions/Side Effects
CNS: SUICIDAL THOUGHTS, ataxia, drowsiness, fatigue,
psychosis, sedation, vertigo. EENT: blurred vision,
corneal opacities, nystagmus. Resp: pneumonitis. CV:
HF, edema, heart block, hypertension, hypotension,
syncope. GI: HEPATOTOXICITY, PANCREATITIS,qliver enzymes,
weight gain. GU: hesitancy, renal impairment
(IV only), urinary retention. Derm: DRUG REACTION
WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS),
STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS,
nail shedding, photosensitivity, rash, urticaria. F
and E: syndrome of inappropriate antidiuretic hormone
(SIADH), hyponatremia. Hemat: AGRANULOCYTOSIS,
APLASTIC ANEMIA, THROMBOCYTOPENIA, eosinophilia,
leukopenia, lymphadenopathy. Misc: chills,
fever.
Interactions
Drug-Drug: May significantlyplevels of nefazodone
or NNRTIs that are CYP3A4 substrates; concurrent
use contraindicated. Concurrent or recent (within
2 wk) use of MAO inhibitors may result in hyperpyrexia,
hypertension, seizures, and death; use contraindicated.
Mayplevels/effectiveness of acetaminophen,
alprazolam, aprepitant, buprenorphine, bupropion,
calcium channel blockers, citalopram, clonazepam,
corticosteroids, cyclosporine, doxycycline,
estrogen-containing contraceptives,
everolimus, haloperidol, imatinib, itraconazole,
lamotrigine, levothyroxine, methadone. midazolam,
olanzapine, paliperidone, phenytoin, protease
inhibitors, risperidone, sertraline, sirolimus,
tacrolimus, tadalafil, theophylline, tiagabine, topiramate,
tramadol, trazodone, tricyclic antidepressants,
valproic acid, warfarin, ziprasidone,
and zonisamide. Mayparipiprazole levels; double
the aripiprazole dose. Mayptemsirolimus and lapatinib
levels; avoid concurrent use. Aprepitant, cimetidine,
ciprofloxacin, clarithromycin, danazol,
dantrolene, diltiazem, erythromycin, fluconazole,
fluoxetine, fluvoxamine, isoniazid, itraconazole,
ketoconazole, loratadine, olanzapine,
omeprazole, oxybutynin, protease inhibitors,
trazodone, voriconazole, and verapamil mayq
carbamazepine levels; mayqrisk of toxicity. Enzyme inducers
such as rifampin, phenobarbital, and phenytoin
mayplevels. Mayqrisk of hepatotoxicity from
isoniazid. Mayqrisk of CNS toxicity from lithium.
Maypeffects of nondepolarizing neuromuscular
blocking agents. Mayqrisk of toxicity from cyclophosphamide.
Drug-Food: Grapefruit juiceqserum levels and
oral bioavailability by 40% and therefore mayqeffects.
Route/Dosage
IV route should only be used when oral administration
is not possible. When converting from immediate-release
to extended-release formulation, administer same
total daily dose (in 2 divided doses).
Seizures
PO (Adults and Children 12 yr): 200 mg twice
daily (immediate-release [IR] tablets and extended-release
[ER] tablets/capsules) or 100 mg 4 times daily
(suspension);qby up to 200 mg/day in divided doses
(every 12 hr for ER tablets; every 6–8 hr for IR tablets
and suspension) every 7 days until therapeutic levels
are achieved (usual range600–1200 mg/day); not
to exceed 1000 mg/day in children 12–15 yrs old or
1200 mg/day in children 15–18 yrs old or 1600 mg/
day in adults.
PO (Children 6–12 yr): 100 mg twice daily (IR tablets
or ER tablets/capsules) or 50 mg 4 times daily
(suspension).qby up to 100 mg/day in divided doses
(every 12 hr for ER tablets; every 6–8 hr for IR tablets
and suspension) every 7 days until therapeutic levels
are achieved (usual range400–800 mg/day); not to
exceed 1000 mg/day.
PO (Children 6 yr): 10–20 mg/kg/day in 2–3 divided
doses (IR tablets) or in 4 divided doses (suspension);
may beqat weekly intervals until optimal response
and therapeutic levels are achieved; not to
exceed 35 mg/kg/day.
IV (Adults): Total daily dose70% of total daily oral
carbamazepine dose. Divide total daily dose into 4 separate
doses administered every 6 hr. Should not be
used for 7 days.
Trigeminal Neuralgia
PO (Adults): 100 mg twice daily (IR or ER tablets),
200 mg once daily (ER capsules), or 50 mg 4 times
daily (suspension);qby up to 200 mg/day in divided
doses (every 12 hr for IR tablets or ER tablets/capsules;
every 6 hr for suspension) as needed until pain is relieved
(usual range400–800 mg/day); not to exceed
1200 mg/day.
Acute Manic or Mixed Episodes Associated
with Bipolar I Disorder
PO (Adults): Equetro—200 mg twice daily;qby 200
mg/day until optimal response is achieved; not to exceed
1600 mg/day.
Availability (generic available)
Tablets: 200 mg. Cost: Generic—$7.18/100. Chewable
tablets: 100 mg, 200 mg. Cost: Generic—
$23.11/100. Extended-release capsules (Carbatrol,
Equetro): 100 mg, 200 mg, 300 mg. Cost: Generic—
All strengths $214.48/60. Extended-release
tablets (Tegretol XR): 100 mg, 200 mg, 400 mg.
Cost: Generic—200 mg $113.31/100, 400 mg
$224.76/100. Oral suspension (citrus/vanilla flavor):
100 mg/5 mL. Cost: Generic—$74.77/450 mL.
Solution for injection (requires dilution): 10 mg/
mL.
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