The P-I-E-N-O Parkinsn's List Drug Database
carbamazepine / TegretolTM
PAIN ASSOCIATED WITH SHINGLES
& TRIGEMINAL NEURALGIA, /
exacerbate PD symptoms
Description: Carbamazepine is an oral anticonvulsant drug, structurally similar to tricyclic antidepressants. It is used in the treatment of partial complex and tonic-clonic seizures, and is preferred over phenobarbital for children because it has fewer adverse effects on behavior and alertness. Carbamazepine is also effective in treating pain of neurologic origin such as trigeminal neuralgia. Finally, carbamazepine has been shown to be effective in the treatment of certain psychiatric disorders including manic-depressive illness and explosive aggression, although these are not approved uses. Carbamazepine was approved by the FDA in 1968. A sustained-release dosage form is currently under investigation.
Mechanism of Action: Anticonvulsant properties of carbamazepine are not fully understood. Carbamazepine blocks use-dependent sodium channels, inhibiting sustained repetitive firing. Like phenytoin, carbamazepine reduces post-tetanic potentiation of synaptic transmission in the spinal cord. This effect may explain its ability to limit the spread of seizures. Individual patient response to carbamazepine is variable. Pain relief is believed to be associated with blockade of synaptic transmission in the trigeminal nucleus. Carbamazepine is a complex drug that also possesses anticholinergic, antidiuretic (syndrome of inappropriate antidiuretic hormone, SIADH), antiarrhythmic, muscle relaxant, antidepressant (possibly through blockade of norepinephrine release), sedative, and neuromuscular-blocking properties. Carbamazepine is a potent enzyme inducer and can induce its own metabolism.
Pharmacokinetics: Carbamazepine is administered orally. Absorption of carbamazepine from the GI tract is slow and variable. The suspension is more rapidly absorbed than tablets and should be administered at least every 8 hours. Bioavailability is roughly 85%. Plasma concentrations peak within 4-5 hours after administration of tablets and within 1.5 hours after administration of suspension. Steady-state concentrations may require several days of therapy. Serum concentrations of 4-12 ęg/ml are considered to be therapeutic in the treatment of seizure disorders. Carbamazepine is lipophilic and appears in CSF, brain, duodenal fluids, bile, and saliva. Carbamazepine has been shown to accumulate in the fetus after crossing the placenta, and it is distributed into breast milk. Concentrations in breast milk reach 60% of serum concentrations. The drug is 76% protein-bound in adults and 57% in children.
Carbamazepine is metabolized in the liver by oxidation to an active metabolite, carbamazepine 10,11-epoxide, which undergoes further metabolism. Carbamazepine is a potent enzyme inducer and can induce its own metabolism. Onset of enzyme induction is at about 3 days, with maximum effect at about 30 days. There is high interindividual variability in the extent to which induction occurs. The plasma half-life is 25-65 hours initially and 12-17 hours after repeated dosing. Induction of microsomal enzymes also affects the metabolism of other concomitantly used drugs via induction of the cytochrome P-450 2D6 enzyme system. Carbamazepine is excreted in the urine, 72% as unconjugated metabolites and only about 3% as unchanged drug, and the remainder is excreted in the feces.
CONTRAINDICATIONS/PRECAUTIONS: Carbamazepine is not recommended for use in petit mal (absence) seizures, atonic seizures, or myoclonic seizures because it can exacerbate them. If a worsening of seizures occurs when therapy is initiated, this possibility should be considered.
Although uncommon, carbamazepine can cause hematological toxicity consisting of leukopenia, thrombocytopenia, and/or aplastic anemia. For this reason, carbamazepine should not be used in patients with preexisting blood dyscrasias or known hematological disease because of the increased possibility of hematologic toxicity.
Carbamazepine should be used with caution in any patient with cardiac disease, such as congestive heart failure or coronary artery disease, because symptoms can be potentiated or exacerbated. It should not be used in patients with heart block. Myocardial infarction has been associated with other tricyclic compounds.
Carbamazepine should be used with caution in the elderly. This patient population is more susceptible to confusion or agitation, AV block, bradycardia, or syndrome of inappropriate antidiuretic hormone. Latent psychosis can become activated, especially in geriatric patients.
Carbamazepine is not recommended for use in women who are breast- feeding because about 60% of maternal blood concentrations appear in breast milk.
Carbamazepine should be used with caution in patients with alcoholism because they can experience increased CNS depression and have an increased risk for hepatotoxicity. In addition, concomitant use of carbamazepine and ethanol can decrease the ability to perform tasks requiring mental alertness.
Carbamazepine should be used with caution in patients with hepatic disease because the drug is metabolized in the liver. Carbamazepine hepatotoxicity also has been reported but is rare. It may be associated with rash and eosinophilia.
Carbamazepine should be used with caution in patients with renal disease, such as renal failure or renal impairment, because carbamazepine metabolites are eliminated renally. Dose reduction may be necessary.
Carbamazepine has mild anticholinergic effects and should be used with caution in glaucoma because of a possible increase in intraocular pressure.
Carbamazepine is classified as pregnancy category C and should be used with caution during pregnancy because it crosses the placenta and has been implicated in a number of fetal abnormalities. Maintenance of anticonvulsant therapy, however, may be essential for the mother, and sudden discontinuation of therapy also presents a risk to the mother and the fetus. Regular evaluation of blood concentrations should be made because higher levels are more likely to be harmful.
DRUG INTERACTIONS: Interactions between carbamazepine and other anticonvulsants are complex. Despite the fact that one anticonvulsant nearly always interacts with another, combinations of anticonvulsants are frequently used in patients who are refractory to one agent alone.
Carbamazepine induces hepatic microsomal enzymes, which, in turn, can accelerate its own metabolism or the metabolism of other drugs. Drugs that can be potentially affected include: other anticonvulsants such as phenytoin, phenobarbital, primidone, and valproic acid; barbiturates; clozapine; corticosteroids; cyclosporine; dacarbazine; doxycycline; estrogens and oral contraceptives; felodipine; haloperidol; levothyroxine; quinidine; tricyclic antidepressants; warfarin; and xanthines such as caffeine and theophylline. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with any of these agents.
Drugs that can inhibit the metabolism of carbamazepine and increase its plasma concentrations include: cimetidine, clarithromycin,I danazol, diltiazem, erythromycin, fluoxetine, influenza virus vaccine, isoniazid, INH, propoxyphene, terfenadine, troleandomycin, and verapamil. Fluvoxamine may also increase carbamazepine serum concentrations, however, data are limited and somewhat contradictory. Metronidazole may also inhibit the clearance of carbamazepine, however, this observation is based only on a single case report. Serum carbamazepine concentrations should be monitored closely if one of these agents is added. It may be necessary to reduce the dose of carbamazepine in this situation.
MAOIs should not be used concurrently with carbamazepine because of the possibility of hyperpyrexia, hypertensive crisis, convulsions, or death. At least 2 weeks should elapse between discontinuation of one and initiation of therapy with the other.
Increased CNS depressant effects can occur during combined use of carbamazepine and loxapine, maprotiline, molindone, phenothiazines, pimozide, or thioxanthenes. In addition, decreased anticonvulsant efficacy is a possibility when these agents are administered to patients with a seizure disorder.
Carbamazepine and lithium are sometimes used together therapeutically. In some patients, however, adverse CNS reactions occur, despite therapeutic serum concentrations of both agents. Patients receiving these two drugs together should be monitored closely for signs of neurotoxicity (e.g., ataxia, lethargy, hyperreflexia, tremor) despite abscence of toxic serum concentrations of either agent.
Concurrent administration of carbamazepine with colestipol results in a modest reduction in carbamazepine bioavailability. Although the reduction in carbamazepine bioavailability may not be clinically significant, staggering the times of administration of these agents should alleviate any drug interaction. In the same study, cholestyramine did not affect carbamazepine bioavailability.
ADVERSE REACTIONS: Hematologic toxicity is possible during therapy with carbamazepine. Patients should undergo routine monitoring of hematologic function, and any serious indication of bone marrow depression warrants discontinuation of the drug. Early symptoms of toxicity can include fever, pharyngitis, oral ulceration, or unusual bruising or bleeding. Leukopenia, thrombocytopenia, leukocytosis, eosinophilia, agranulocytosis, pancytopenia, or aplastic anemia have been reported with carbamazepine.
CNS effects of carbamazepine include dizziness, drowsiness, fatigue, ataxia, blurred vision, diplopia, and hallucinations. Sedation may be seen for the first few days of therapy or following a dosage increase. Tolerance usually develops. Confusion and agitation are more likely to occur in geriatric patients, and dose adjustments may be necessary. Those requiring mental alertness should be warned of the possible effects of carbamazepine therapy. To minimize adverse reactions, carbamazepine should be instigated at the lowest possible dosage. These reactions can occur more frequently with the oral suspension due to more rapid absorption.
To minimize adverse GI effects, the drug may be taken with food and at equally spaced intervals. Adverse GI effects include diarrhea, nausea/vomiting, constipation, xerostomia, abdominal pain, or anorexia. Rarely, hepatitis has occurred with carbamazepine.
Hyponatremia can occur, especially in elderly patients with cardiac disease. Water intoxication may be attributed to syndrome of inappropriate antidiuretic hormone (SIADH). Nausea/vomiting, abdominal pain, confusion, agitation, and seizures can result from carbamazepine-induced stimulation of antidiuretic hormone release.
Cardiovascular adverse effects that can develop during carbamazepine therapy include cardiac arrhythmias, AV block, syncope, congestive heart failure, hypertension, hypotension, and/or thrombophlebitis.
Dermatological effects of carbamazepine include photosensitivity, alopecia, urticaria, and erythema multiforme, but these can indicate a more serious adverse reaction such as Stevens-Johnson syndrome. Although structurally dissimilar, carbamazepine can cross-react with phenytoin in patients who develop hypersensitivity reactions to phenytoin. Both drugs are metabolized to a similar intermediate.
Other side effects including sexual dysfunction, such as impotence, and interstitial nephritis have been reported.
PATIENT INFORMATION:
What do carbamazepine tablets do?
Carbamazepine (TegretolTM ) can help with seizure (convulsion) control in certain types of epilepsy. Carbamazepine also treats nerve-related pain such as trigeminal neuralgia, or the pain associated with shingles. It is not for common trivial aches and pains. Generic carbamazepine tablets are available, but not the chewable tablets.
What should my doctor, dentist, or pharmacist know before I take carbamazepine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take carbamazepine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Chewable tablets may be chewed first or swallowed whole. Take your doses at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for children under 6 years old.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with carbamazepine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking carbamazepine?
Serious side effects with carbamazepine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with carbamazepine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take carbamazepine?
Visit your doctor for a regular check on your progress. If you are taking carbamazepine for epilepsy (seizures) do not stop taking it suddenly. This increases the risk of seizures. Wear a Medic Alert bracelet or necklace. Carry an identification card with information about your condition, medications, and doctor.
You may get drowsy, dizzy, or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how carbamazepine affects you. To reduce dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can increase drowsiness and dizziness. Avoid alcoholic drinks.
If you are going to have surgery, tell your doctor or dentist that you are taking carbamazepine.
Carbamazepine can make your skin more sensitive to the sun or ultraviolet light. Keep out of the sun, or wear protective clothing outdoors and use a sunscreen (at least SPF 15). Do not use sun lamps or sun tanning beds or booths.
Do not rely on contraceptive pills for birth control. Carbamazepine may affect the way they work. Use a non-hormonal method of birth control.
Where can I keep my medicine?
Keep out of reach of children in a container that small children cannot open.
Store at room temperature below 30C (86F). Keep container tightly closed. Protect from moisture. Throw away any unused medicine after the expiration date.
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