Carbamazepine

Carbamazepine

[200mg tablets 15 cents]

ADMINISTRATION ROUTES:

  • PO, NG

ALTERNATIVE NAMES:

  • Tegretol

ICU INDICATIONS:

  1. epilepsy
  2. trigeminal neuralgia and other neuropathic pain
    [usually this medication is used in ICU in patients who were taking it for a pre-existing indication prior to ICU admission; it may be occasionally commence in patients with new seizures or neurogenic pain but is not first line]

PRESENTATION AND ADMINISTRATION:

  • PO / NG:
    Tegretol 200mg and 400mg tablets (white); tegretol CR tablets 200mg (beige/orange) and 400mg (brown/orange); tegretol syrup 100mg/5ml (white)
    Tegretol liquid is available for NG administration – it should be diluted in equal parts with water to prevent possible adsorption.

DOSAGE:

  • PO:
    Epilepsy
    Initial:
    Either 200 mg BD for tablets and extended-release tablets or 100mg QID for suspension. Increase at weekly intervals by adding up to 200 mg/day using a BD regimen of extended-release or TDS or QID regimen of the other formulations until the optimal response is obtained. Dosage generally should not exceed 1200 mg daily. Doses up to 1600 mg daily have been used in adults in rare instances.
    Maintenance:
    Adjust dosage to the minimum effective level, usually 800-1200 mg daily.

    Trigeminal neuralgia and other neuropathic pain
    Initial:
    On the first day, either 100 mg BD for tablets or extended-release tablets or 50mg QID for suspension for a total daily dose of 200 mg. This daily dose may be increased by up to 200mg/day using increments of 100 mg every 12 hours for tablets or extended- release tablets or 50 mg QID for suspension, only as needed to achieve freedom from pain. Do not exceed 1200 mg/daily.
    Maintenance:
    Control of pain can be maintained in most patients with 400-800 mg daily. However, some patients may be maintained on as little as 200 mg daily, while others may require as much as 1200 mg daily. At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or even to discontinue the drug.

    Carbamazepine suspension produces higher peak levels than the same dose given as the tablet, therefore it is recommended that patients given the suspension be dosed in lower doses more given more frequently. For conversion of patients from oral carbamazepine tablets to carbamazepine suspension, administer the same number of mg/day in smaller, more frequent doses (eg change dosing from twice daily to three times daily). When converting patients from carbamazepine conventional tablets to carbamazepine extended-release tablets, the same total daily mg dose of carbamazepine extended-release should be administered.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

  • 2mg/kg 8 hourly may increase over 2-4 weeks to 5-10mg/kg 8 hourly

CLINICAL PHARMACOLOGY:

  • Carbamazepine is an anticonvulsant

CONTRAINDICATIONS:

  1. history of previous bone marrow depression
  2. hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds such as amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc.

WARNINGS

  • The most serious complications of carbamazepine are those of bone marrow depression including aplastic anaemia, agranulocytosis, & pancytopenia. Patients with a history of adverse hematologic reaction to any drug may be particularly at risk. Severe dermatologic reactions including toxic epidermal necrolysis and Stevens-Johnson syndrome, have been reported with carbamazepine. Because of the relationship of the drug to other tricyclic compounds, the possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in mind.

PRECAUTIONS

  • General:
    Carbamazepine suspension produces higher peak levels than the same dose given as the tablet, therefore it is recommended that patients given the suspension be dosed in lower doses more given more frequently
    Hyponatremia has been reported in association with carbamazepine use, either alone or in combination with other drugs. Cessation of carbamazepine may lead to seizures.
  • Laboratory Tests:
    Carbamazepine levels (collect in red or yellow tube): Measure levels if:
    (i) there is concern about possible non-compliance
    (ii) there is concern about possible toxicity Induces its own metabolism so that following the initiation of therapy, it takes 2 – 4 weeks to obtain a steady state. Measure levels pre-dose (i.e. trough)
    Therapeutic range is 34-51μmol/L
    Potentially toxic levels and associated clinical features:
    >51μmol/L: nystagmus
    >85 μmol/L: CNS and anticholinergic effects
    >170 μmol/L:  Coma, seizures and cardiac conduction abnormalities
  • Drug/Laboratory Test Interactions :
    Interference with some pregnancy tests has been reported.

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • Carbamazepine may be used alone or with other anticonvulsants. When added to existing anticonvulsant therapy, the drug should be added gradually while the other anticonvulsants are maintained or gradually decreased, except phenytoin, which may have to be increased.
  • Clinically meaningful drug interactions have occurred with concomitant medications and include, but are not limited to, the following:
    CYP 3A4 inhibitors inhibit carbamazepine metabolism and can thus increase plasma carbamazepine levels.
  • Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include:
    Diltiazem, erythromycin, clarithromycin, fluoxetine, loratadine, terfenadine, isoniazid, verapamil, & valproate.
  • CYP 3A4 inducers can increase the rate of carbamazepine metabolism. Drugs that have been shown, or that would be expected, to decrease plasma carbamazepine levels include:
    Cisplatin, doxorubicin, rifampin, phenobarbital, phenytoin, & theophylline.

ADVERSE REACTIONS

  • The most frequently observed adverse reactions, particularly during the initial phases of therapy, are dizziness, drowsiness, unsteadiness, nausea, and vomiting. To minimise the possibility of such reactions, therapy should be initiated at the low dosage recommended.
  • Body as a whole:
    Multi-organ hypersensitivity reactions occurring days to weeks or months after initiating treatment have been reported in rare cases. Signs or symptoms may include, but are not limited to fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leukopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests.
  • Hemopoietic System:
    Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, acute intermittent porphyria.
  • Skin:
    Pruritic and erythematous rashes, urticaria, toxic epidermal necrolysis, Stevens- Johnson syndrome, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythematosus, alopecia, and diaphoresis.
  • Cardiovascular System:
    Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, thrombophlebitis, thromboembolism, and adenopathy or lymphadenopathy.
  • Gastrointestinal System:
    Abnormalities in liver function tests, cholestatic and hepatocellular jaundice, hepatitis; very rare cases of hepatic failure, pancreatitis, nausea, vomiting, gastric distress and abdominal pain, diarrhea, constipation, anorexia, and dryness of the mouth and pharynx, including glossitis and stomatitis.
  • Musculoskeletal System:
    Aching joints and muscles, and leg cramps.
  • Respiratory System:
    Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis or pneumonia.
  • Genitourinary System:
    Renal failure
  • Nervous System:
    Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus, and hyperacusis.

Critical Care Drug Manual

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