A Practitioner’s Guide to Prescribing Carbamazepine for Adults with Intellectual Disabilities

Abstract

We developed this carbamazepine guideline using drug prescribing ­information and reviewing the available literature on relevant neuropsychiatric disorders in populations without intellectual disabilities because of the dearth of available literature on the population with intellectual disabilities. This guideline includes indications, contraindications, assessments prior to and during treatment, dosing with particular focus on dosing modifications required by drug–drug interactions or personal characteristics, and adverse drug reactions. The procedures contained in this guideline may not fully account for all of the possible risks of treatment in this population because of the limited studies available; thus, there will be a need to periodically update this guideline as new information becomes available. Nevertheless, we believe that this guideline provides a useful resource for clinicians who treat epilepsy, mood disorders, and/or challenging behaviors in adult individuals with intellectual disabilities. A carbamazepine drug utilization review that ­summarizes this guideline is described.

Appendix Drug Utilization Review: Carbamazepine

DRUG UTILIZATION REVIEW CRITERIA				CRITERIA MET CARBAMAZEPINE FOR ADULTS WITH IDs
				YES	NO	NA
1) Indication: Check one of the following indications for use
	Epilepsy: Partial in onset with or without secondary generalization.
	Bipolar disorder I: It has particularly been approved for acute manic and mixed episodes. There is less data on its use as a prophylactic agent.
	Trigeminal neuralgia.
	Off-label indications, including schizoaffective disorder, aggressive behavior in schizophrenia or organic brain disorders, posttraumatic stress disorder, ethanol ­withdrawal, restless leg syndrome, and neuropathic pains, including diabetic neuropathy with a lancinating component. Specify_________________________ When carbamazepine is used for off-label indications, the chart specifically includes an explanatory note (Y___ N___).
To meet indication criteria, at least one indication is present and documented.					
2) Dose: Specify formulation_____________
	Does the chart document the consideration of vitamin D and/or calcium supplements? (Y__ N__).					
	Suspension is given three to four times/day (Y__ N__) unless otherwise recommended by a consultant with expertise in the area (Y__). It is scheduled at least 1–2 h apart from other liquid medicine (Y__ N__) and given with meals (Y__ N__).					
	Extended release capsules are given two times/day (Y__ N__) unless otherwise recommended by a consultant with expertise in the area (Y__). The capsules are not crushed or chewed (Y__ N__).					
	Extended release tablets are given two to three times/day (Y__ N__) unless otherwise recommended by a consultant with expertise in the area (Y__). The tablets are not crushed or chewed (Y__ N__).					
	Tablets are given two to four times/day (Y__ N__) unless otherwise recommended by a consultant with expertise in the area (Y__) and are given with meals (Y__ N__).					
	The first anticonvulsive dose was ≤ 400 mg/day (Y__ N__) unless otherwise recommended by a consultant with expertise in the area (Y__).					
	The maximum antiepileptic dose was ≤ 1,600 mg/day (Y__ N__) or justification is provided (Y__).					
	The first dose for bipolar disorder was ≤ 400 mg/day (Y__ N__) or justification is provided (Y__).					
	The maximum dose for bipolar disorder was ≤ 1,600 mg/day (Y__ N__) or justification is provided (Y__).
	Taking phenytoin__, phenobarbital__, or primidone__. The chart documents the interaction (Y___ N___). The dosage of carbamazepine may need to be increased when any of these antiepileptic drugs were added and the discontinuation of any of these inducers may need to be followed by a decrease of carbamazepine dosage.					
	Taking other inducers_____________________________. The chart documents the interaction (Y___ N___). The dosage of carbamazepine may need to be increased when an inducer is added, and the discontinuation of the inducer may need to be followed by a decrease of carbamazepine dosage.					
	Taking potent CYP3A inhibitors (ketoconazole___, itraconazole___, fluconazole___, clarithromycin___, erythromycin___, fluoxetine___, fluvoxamine___, diltiazem___, or propoxyphene___). Other______. The chart documents the interaction (Y___ N___). The dosage of carbamazepine may need to be decreased when any of these inhibitor drugs were added and the discontinuation of any of these inhibitors may need to be followed by an increase of carbamazepine dosage.					
	Taking valproate___. Valproate may contribute to increased epoxide levels, free carbamazepine levels, and neurotoxicity. The chart documents the interaction and indicates that particular attention was paid to carbamazepine toxicity (Y___ N___).					
	Taking felbamate___. Felbamate can have complex effects on carbamazepine metabolism. The chart documents the interaction and indicates that particular attention was paid to carbamazepine toxicity (Y___ N___).					
	Taking other antiepileptics (e.g., gabapentin___, ­lamotrigine___, levetiracetam___, or oxcarbazepine___) that may increase carbamazepine toxicity. The chart documents the interaction (Y___ N___).					
	Taking lithium___. The combination may contribute to increased neurotoxicity. The chart documents the interaction and indicates that particular attention was paid to neurotoxicity (Y___ N___).					
	Taking clonazepam___, diazepam___, ethosuximide___, felbamate___, lamotrigine___, oxcarbazepine___, tiagabine___, topiramate___, valproate___, or zonisamide___. The chart documents the interaction (Y___ N___). The dosage of these antiepileptics may need to be increased when carbamazepine is added, and the discontinuation of carbamazepine may need to be followed by a dose decrease of any of these antiepileptics.					
	Taking phenytoin___. Carbamazepine can have complex effects on phenytoin metabolism. The chart documents the interaction and indicates that particular attention was paid to phenytoin levels (Y___ N___). Measuring free phenytoin concentrations was considered (Y___ N___).					
	Taking psychiatric drugs possibly induced by carbamazepine (e.g., haloperidol___, quetiapine___, risperidone___, aripiprazole___, olanzapine___, bupropion___, clonazepam___ or alprazolam___). Other_________. The chart documents the interaction (Y___ N___). The dosage of these drugs may need to be increased when carbamazepine is added, and the discontinuation of carbamazepine may need to be followed by a dose decrease of any of these drugs.					
	Taking tricyclic antidepressant (TCAs)___. Carbamazepine can have complex effects on TCA metabolism. The chart documents the interaction and indicates that particular attention was paid to toxicity (Y___ N___).					
	Taking CYP3A substrates (e.g., some calcium channel blockers, statins and immunosuppressants). List drugs___________________________________ The chart documents the interaction (Y___ N___). The dosage of these drugs may need to be increased when carbamazepine is added, and the discontinuation of carbamazepine may need to be followed by a dose decrease of any of these drugs.					
	Taking oral contraceptive___. The chart documents that the oral contraceptive may not be effective (Y___ N___).					
	Taking warfarin___. The chart documents the interaction (Y___ N___). The warfarin dosage may need to be increased when carbamazepine is added, and the discontinuation of carbamazepine may need to be followed by a warfarin dose decrease.					
	Taking CYP1A2 substrates (e.g., theophylline). List drugs_______________. The chart documents the interaction (Y___ N___). The dosage of these drugs may need to be increased when carbamazepine is added, and the discontinuation of carbamazepine may need to be followed by a dose decrease of any of these drugs.					
	Taking acetaminophen in standard scheduled doses___. The chart documents that there is more risk for ­hepatotoxicity (Y___ N___).					
	Hepatic impairment_____. The chart documents the use of lower carbamazepine doses (Y___ N___).					
	Patient ≥ 65 years of age_____. The chart documents the use of lower initial doses (≤ 100 mg) (Y___ N___).					
	Pregnancy is associated with an increase in carbamazepine metabolism in the third trimester. Carbamazepine levels are measured (Y___ N___).					
To meet dose criteria, all are Yes or NA.					
3) Relative contraindications: Check left boxes of any present.
	Pregnancy (Category D) or breast feeding.
	Hypersensitivity to other antiepileptics, including phenytoin, oxcarbazepine, felbamate, lamotrigine, phenobarbital, or primidone.
	HLA-B*1502 allele.
	Hyponatremia secondary to polydipsia associated with mental illnesses or use of medication that may cause hyponatremia.
	Any hematological dyscrasia.
	Cardiac problems, particularly conduction problems.
	Hepatic or renal insufficiency.
	If a female patient has potential to be pregnant, a pregnancy test is completed.
Answer Yes if none is checked, or if any of the above are checked but rationale is documented in the chart to meet relative contraindication criteria. Answer No if rationale is NOT documented in the chart.					
4) Baseline monitoring studies:
	Weight, height (with body mass index), and waist circumference.
	EKG.
	CBC with differential.
	Basic metabolic panel___, lipid profile___, TSH___, and liver function tests___.
	Serum concentrations of the concomitantly administered antiepileptics that are usually followed with therapeutic drug monitoring.
	If a female patient has potential to be pregnant, a pregnancy test is completed.
Answer Yes (all completed) or No. If information is not available, check NA.						
5) Additional baseline monitoring in people with Asian ancestry:
	Genotyping for HLA-B*1502 allele.
Answer Yes or No. If information is not applicable, check NA.						
6) Monthly monitoring studies:
	Monthly monitoring includes serum sodium levels at least for the first 3 months. If low sodium levels are present but physicians consider them “subclinical,” the chart should show that the patient has “subclinical hyponatremia” and levels should be monitored at least monthly.
	Liver function tests___, and CBC with differential___, are monitored every month until the dosage is stable.
Answer Yes (all completed) or No. If information is not applicable, check NA.						
7) Semiannual monitoring:
	Serum sodium___, liver function test___, and CBC____.
	Lipid profile.
	Carbamazepine level.
Answer Yes (all completed) or No. If information is not applicable, check NA.						
8) Annual monitoring:
	Body mass index and waist circumference.
Answer Yes (all completed) or No. If information is not applicable, check NA.						
9) Annual monitoring needed only after abnormal results:
	Thyroid tests if the results have been abnormal before or after carbamazepine treatment.				
	EKG if the results have been abnormal before or after carbamazepine treatment.				
Answer Yes (all completed) or No. If information is not applicable, check NA.						
10) Discontinuation:
	Carbamazepine is or was withdrawn slowly to minimize the potential of increased seizure frequency (Y___ N___). Abrupt withdrawal was justified by a major medical reason (Y___ N___).					
11) Adverse drug reactions (ADRs) due to carbamazepine: Check left boxes to indicate which ADRs are present.
11.1) Common ADRs:
	CNS, including dizziness, headaches, somnolence, ataxia, slurred speech, and blurred vision.		Gastrointestinal: Nausea and vomiting.
11.2) Relatively uncommon ADRs:
	Movement disorders: Dyskinesias, dystonias, asterixis, and tics.		Arrythmias (sinus bradycardia and varying degrees of atrioventricular conduction).
	Hyponatremia.		Decreases in free T4 or free T3.
	Low calcium or osteoporosis.		Seizure exacerbation.
	Seizure exacerbation.		Benign dermatological ADRs, including rashes, urticaria, and pruritus.
	Elevations on liver function tests.		Other_____________.
11.3) Potentially lethal ADRs:
	Stevens–Johnson syndrome/epidermal necrolysis and multiorgan hypersensitivity reactions.		Idiosyncratic hepatitis.
	Agranulocytosis or aplastic anemia. Other mild leukopenia.		Suicidal ideation or behavior.
11.4) Metabolic syndrome:
	Weight gain.		Increases in total cholesterol.
Answer Yes (intervention or benefit/risk discussion after ADRs developed) or No (neither intervention nor benefit/risk discussion after ADRs developed) or NA (no abnormality developed).