Vigabatrin, an oral anticonvulsant, was synthesized in 1974 as a structural analog of gamma-aminobutyric acid (GABA) and was designed to inhibit the metabolism of GABA. Decreased concentrations of GABA have been associated with certain forms of epilepsy. Vigabatrin has been investigated for the treatment of many seizure types but appears to be most effective in treating complex partial seizures and infantile spasms, particularly those associated with tuberous sclerosis complex (TSC). Vigabatrin was the first drug to be FDA-approved for the treatment of infantile spasms, and it was the first real pharmacologic advancement in the treatment of this refractory seizure type since the introduction of ACTH in the late 1950s. It has been used to treat patients with infantile spasms and refractory complex partial seizures in other countries for over 20 years and is available in over 50 countries worldwide. The approval for the use of vigabatrin in the United States was delayed due to the FDA's request for additional research on the visual field defects that are associated with vigabatrin use. Due to the risk of permanent vision loss, vigabatrin is only available through a restricted distribution program. Only prescribers and pharmacies registered with the program may prescribe and dispense vigabatrin.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 3
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Eye/face and respiratory protection may be needed during preparation and administration.
Route-Specific Administration
Oral Administration
-Vigabatrin may be administered with or without food.
Oral Liquid Formulations
Powder for Oral Solution
-Each packet contains vigabatrin 500 mg.
-Reconstitute dose immediately before administration.
-Empty the entire contents of the appropriate number of packets into an empty clean cup.
-For each packet, dissolve the powder with 10 mL cold or room temperature water (i.e., use 10 mL for 1 packet, 20 mL for 2 packets, or 30 mL for 3 packets). The final solution concentration will be 50 mg/mL. Do not use any other liquid to reconstitute.
-Using a clean spoon or stirring device, carefully stir the contents of the cup until all of the powder has dissolved leaving a clear solution.
-Measure the appropriate dose using a calibrated oral syringe, and administer immediately. For infants and small children, place the tip of the oral syringe between the cheek and gum and slowly administer the solution in small increments.
-Discard remaining solution. Each dose must be reconstituted immediately before administration.
Due to the risk of ocular toxicity, vigabatrin should be used at the lowest dose and shortest duration necessary to achieve clinical goals. Vigabatrin causes permanent visual impairment and vision loss in a high percentage of patients. Vigabatrin causes permanent bilateral concentric visual field constriction in 30% or more of adult patients; the incidence in pediatric patients is not well defined. The visual field defect can range in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation. Vigabatrin can also cause decreased visual acuity due to central retina damage. The onset of the vision disturbance can occur at any time during therapy, including after months or years, and may worsen quickly. The risk increases with increasing dose and duration; however, there is no known risk-free exposure. Vision may worsen after vigabatrin discontinuation. Due to the risk for irreversible vision damage, vigabatrin should be discontinued if a significant clinical response is not achieved within 3 months of initiation for complex partial seizures, within 2 to 4 weeks of initiation for infantile spasms, or if clinical failure is obvious at any time point. Vision loss is difficult to detect in pediatric patients and may not be detected until it is severe. Vision assessment at baseline (no later than 4 weeks after vigabatrin initiation), at least every 3 months during therapy, and approximately 3 to 6 months after vigabatrin discontinuation is recommended; assessment should include both acuity and visual fields whenever possible. In patients who cannot be tested, treatment may continue according to clinical judgment, with appropriate patient counseling. Vision assessment must be performed by an ophthalmic professional with expertise in visual field interpretation and the ability to perform a dilated indirect ophthalmoscopy of the retina. Other eye disorders, in addition to visual impairment, have been reported in association with vigabatrin use. In a dose-response study in pediatric patients with infantile spasms, strabismus occurred in 5% of patients in both the low dose group (18 to 36 mg/kg/day, n = 114) and the high dose group (100 to 148 mg/kg/day, n = 108). Conjunctivitis occurred in 5% of the low dose group and 2% of the high dose group. During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following eye disorders were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo treatment groups: blurred vision (13% to 16% vs. 5%), diplopia (7% to 16% vs. 3%), asthenopia (2% vs. 0%), and ocular pain (5% or less vs. 0%). In pediatric trials for complex partial seizures (patient age range: 3 to 16 years), diplopia (3%) and blurred vision (2%) were reported in the vigabatrin-treated patients. Optic neuritis has been reported during postmarketing use; however, the frequency is unknown and causality to the drug has not been established.
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following centrally-mediated effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: headache (26% to 33% vs. 31%), drowsiness/somnolence (22% to 26% vs. 13%), fatigue (23% to 40% vs. 16%), dizziness (24% to 26% vs. 17%), nystagmus (13% to 19% vs. 9%), tremor (15% to 16% vs. 8%), memory impairment (7% to 16% vs. 3%), abnormal coordination (7% to 16% vs. 2%), disturbance in attention (up to 9% vs. 1%), sensory disturbance (4% to 7% vs. 2%), hyporeflexia (4% to 5% vs. 1%), paresthesias (2% to 7% vs. 1%), lethargy (4% to 7% vs. 2%), hyperreflexia (2% to 4% vs. 3%), hypoesthesia (4% to 5% vs. 1%), sedation (up to 4% vs. 0%), status epilepticus (2% to 5% vs. 0%), postictal state (up to 2% vs. 1%), dysarthria (2% vs. 1%), and sensory loss (up to 5% vs. 0%). Fatigue (10% vs. 7%), drowsiness (6% vs. 5%), tremor (4% vs. 2%), nystagmus (4% vs. 3%), and status epilepticus (2% vs. 1%) were reported in the vigabatrin and placebo groups, respectively, during pediatric trials for complex partial seizures (patient age range: 3 to 16 years). Hyperkinesis has been reported in children. Pooled data from 3 pediatric trials (n = 165) reported drowsiness/somnolence and fatigue occurred in 6% and 10%, respectively, of vigabatrin-treated patients compared to 5% and 7%, respectively, in placebo-treated patients. In a dose-response study in pediatric patients with infantile spasms, status epilepticus occurred in 6% of patients in the low dose group (18 to 36 mg/kg/day, n = 114) and 4% of patients in the high dose group (100 to 148 mg/kg/day, n = 108). Other CNS effects reported in the low dose and high dose groups, respectively, included sedation (19% vs. 17%), drowsiness/somnolence (17% vs. 19%), lethargy (5% vs. 7%), seizures (4% vs. 7%), hypotonia (4% vs. 6%), and insomnia (10% vs. 12%). During postmarketing use, dystonic reaction, encephalopathy, hypertonia, hypotonia, muscle spasticity, dyskinesia, and myoclonia have been reported; however, the frequencies are unknown and causality to the drug has not been established. Approximately 1% of patients discontinued vigabatrin during adult clinical trials due to drowsiness or fatigue. Because vigabatrin can cause significant drowsiness, patients should be advised to avoid activities requiring mental alertness until they are aware of the effects of the drug on their cognition.
Pooled data from controlled trials showed that edema occurred in 1% of vigabatrin patients compared to 0% of placebo patients, and peripheral edema occurred in 2% of vigabatrin patients compared to 1% of placebo patients. The development of edema did not appear to be associated with cardiovascular adverse events, such as heart failure or hypertension, and it was not associated with laboratory findings suggestive of renal or hepatic dysfunction. Facial edema was reported during world-wide postmarketing experience; however, incidence and causality have not been established. Clinical trials were not designed to determine whether vigabatrin causes edema in pediatric patients.
Abnormal magnetic resonance imaging (MRI) signal changes, characterized by increased T2 signal and restricted diffusion in a symmetric pattern involving the thalamus, basal ganglia, brain stem, and cerebellum, have been observed in infants receiving vigabatrin for infantile spasms. In a retrospective epidemiologic study (n = 205), the prevalence of MRI changes was 22% in vigabatrin-treated infants vs. 4% in those treated with other therapies. In most cases, the abnormalities resolve after vigabatrin discontinuation. Some infants experience simultaneous motor abnormalities; however, a causal relationship has not been established. MRI changes have also been reported during postmarketing use of vigabatrin in patients 6 years and younger being treated for complex partial seizures. The specific pattern of signal changes observed in this younger age group was not observed in older pediatric and adult patients treated with vigabatrin. No difference in anatomic distribution or prevalence of MRI signal changes between vigabatrin- and placebo-treated patients was observed in a blinded review of MRI images obtained from patients 3 years and older with refractory complex partial seizures (n = 656). Intramyelinic edema (IME) has been reported during postmortem examination of infants receiving vigabatrin for infantile spasms. IME, characterized by fluid accumulation and separation of the outer layers of myelin, has also been observed in brain white matter tracts of several animal species. In addition, neurological toxicity, including seizures, hypomyelination, retinal dysplasia, and learning deficits, was observed in rats exposed to vigabatrin in utero and during the neonatal and juvenile periods, and brain histopathological changes were observed in dogs exposed to vigabatrin during the juvenile period. Vacuolar changes in grey matter, which are considered to be different than IME, have also been observed in neonatal and juvenile rats and juvenile dogs receiving vigabatrin. These effects occurred at plasma vigabatrin concentrations substantially lower than those achieved clinically in human children. It has not been determined whether this neurotoxicity in animals is related to the MRI changes observed in human infants.
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following psychiatric effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: irritability (7% to 23% vs. 7%), depression (6% to 14% vs. 3%), confusion (4% to 14% vs. 1%), anxiety (up to 4% vs. 3%), depressed mood (up to 5% vs. 1%), abnormal thinking (3% to 7% vs. 0%), abnormal behavior (3% to 5% vs. 1%), expressive language disorder (1% to 7% vs. 1%), nervousness (2% to 5% vs. 2%), and abnormal dreams (1% to 5% vs. 1%). Abnormal behavior (7% vs. 6%), aggression (6% vs. 2%), and disorientation (3% vs. 0%) were reported in vigabatrin- and placebo-treated patients, respectively, during a pediatric clinical trial for complex partial seizures (patient age range: 3 to 16 years). In a dose-response study in pediatric patients with infantile spasms, irritability occurred in 16% of patients in the low dose group (18 to 36 mg/kg/day, n = 114) and 23% of patients in the high dose group (100 to 148 mg/kg/day, n = 108). An analysis by the FDA of previously gathered drug data showed that patients receiving anticonvulsants had approximately twice the risk of suicidal ideation or behavior (0.43%) as patients receiving placebo (0.24%). The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions. Age was not a determining factor. The increased risk of suicidal ideation and behavior occurred between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. All patients beginning treatment with anticonvulsants or currently receiving such treatment should be closely monitored for emerging or worsening suicidal thoughts/behavior, unusual moods or behaviors, or depression. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. During postmarketing use, acute psychosis, apathy, delirium, hypomania, neonatal agitation, and psychotic disorder (unspecified) have been reported; however, the frequencies are unknown and causality to the drug has not been established. Very rarely, hallucinations have occurred.
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following adverse general effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: gait disturbance (6% to 12% vs. 7%), asthenia (5% to 7% vs. 1%), chest pain (unspecified) (1% to 5% vs. 1%), thirst/polydipsia (up to 2% vs. 0%), and malaise (up to 5% vs. 0%). General effects reported during post-market use include developmental delay, delayed puberty, malignant hyperthermia, and multi-organ failure; however, the frequencies are unknown and causality to the drug has not been established.
In controlled trials in adults, anemia or a potentially clinically important hematological effect involving hemoglobin, hematocrit, and/or red blood cell indices occurred in 5.7% (16/280) of patients receiving vigabatrin compared to 1.6% (3/188) of those receiving placebo. In pre-marketing controlled trials in the US, there were mean decreases in hemoglobin of approximately 3% and 0% in vigabatrin and placebo groups respectively. In addition, there was a decline in hematocrit of about 1% in vigabatrin-treated patients versus an increase of about 1% in placebo-treated patients. In epilepsy trials, 0.06% of patients receiving vigabatrin discontinued treated due to anemia and 2 vigabatrin-treated patients experienced a decline in hemoglobin to less than 8 g/dL and/or a hematocrit below 24%.
In North American placebo-controlled trials of vigabatrin for the treatment of epilepsy in adults, 1.4% (4/280) of patients developed signs and/or symptoms of peripheral neuropathy compared to 0% of patients who received placebo. In a pooled analysis of North American controlled and uncontrolled trials, 4.2% (19/457) developed signs and/or symptoms of peripheral neuropathy. These clinical studies were not designed to investigate peripheral neuropathy and did not include nerve conduction studies. There is insufficient data to determine whether there is a relationship between the development of peripheral neuropathy and vigabatrin dose or duration, and it is not known if the neuropathy is completely reversible after vigabatrin discontinuation. Clinical trials were not designed to determine whether vigabatrin causes peripheral neuropathy in pediatric patients.
During clinical trials of vigabatrin as an add-on therapy for refractory complex partial seizures in adults, weight gain was reported in 6% to 14% of patients in the vigabatrin groups versus 3% of patients in the placebo groups. Pooled data from randomized controlled trials indicate that 17% (77/443) of adult patients who received vigabatrin experienced a weight gain of 7% or more of baseline body weight compared to 8% (22/275) of patients who received placebo. The mean weight gain was 3.5 kg in the vigabatrin group compared to 1.6 kg in the placebo group. Appetite stimulation was reported in 1% to 5% of vigabatrin-treated patients versus 1% of placebo-treated patients. During pediatric clinical trials for refractory complex seizures (patient age range: 3 to 16 years), weight gain was reported in 15% of patients in the vigabatrin groups versus 2% of patients in the placebo groups. Pooled data from pediatric trials found that 47% (77/163) of vigabatrin-treated patients compared to 19% (19/102) of placebo-treated patients gained 7% or more of their baseline body weight. In all epilepsy trials, 0.6% (31/4,855) of patients discontinued vigabatrin due to weight gain. Weight gain was not related to the presence of edema. In a dose-response study in pediatric patients with infantile spasms, decreased appetite occurred in 9% of patients in the low dose group (18 to 36 mg/kg/day, n = 114) and 7% of patients in the high dose group (100 to 148 mg/kg/day, n = 108).
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following adverse gastrointestinal (GI) effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: diarrhea (10% to 16% vs. 7%), nausea (2% to 10% vs. 8%), vomiting (7% to 9% vs. 6%), constipation (5% to 8% vs. 3%), upper abdominal pain (5% vs. 1%), dyspepsia (4% to 5% vs. 3%), stomach discomfort (2% to 4% vs. 1%), abdominal pain (2% to 3% vs. 1%), dental pain (toothache 2% to 5% vs. 2%), and abdominal distention (up to 2% vs. 1%). Upper abdominal pain (4% vs. 3%) and constipation (2% vs. 1%) were reported in the vigabatrin- and placebo-treatment groups, respectively, during pediatric trials for complex partial seizures (patient age range: 3 to 16 years). In a dose-response study in pediatric patients with infantile spasms, vomiting occurred in 14% of patients in the low dose group (18 to 36 mg/kg/day, n = 114) and 20% of patients in the high dose group (100 to 148 mg/kg/day, n = 108). In this same trial, constipation was reported in 14% and 12% of the low and high dose groups, respectively, diarrhea was reported in 13% and 12%, and anorexia was reported in 9% and 7%. Very rarely, hepatitis has occurred. During postmarketing use, GI bleeding, esophagitis, and cholestasis have been reported; however, the frequencies are unknown and causality to the drug has not been established.
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, rash was reported in 4% to 5% of vigabatrin-treated patients vs. 4% of placebo-treated patients. In a dose-response study in pediatric patients with infantile spasms, rash occurred in 8% of the low dose group (18 to 36 mg/kg/day) and 11% of the high dose group (100 to 148 mg/kg/day). Acne vulgaris (3% vs. 0% placebo) has been reported during pediatric clinical trials for complex partial seizures (patient age range: 10 to 16 years). In postmarketing experience worldwide, maculopapular rash, pruritus, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis, and alopecia have been reported. Although it is not known whether postmarketing reports of multi-organ system failure are related to drug hypersensitivity, it is important to note that Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been associated with multiple antiepileptic agents (most commonly aromatic agents such as phenytoin and carbamazepine). Initial manifestations of DRESS typically include pyrexia, rash, and/or lymph node involvement. If a severe hypersensitivity reaction is suspected, discontinue vigabatrin immediately.
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following musculoskeletal effects or injuries were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: arthralgia (5% to 10% vs. 3%), back pain (4% to 7% vs. 2%), extremity pain (2% to 6% vs. 4%), myalgia (3% to 5% vs. 1%), muscle twitching (1% to 9% vs. 1%), muscle cramps/spasm (up to and including 3% vs. 1%), contusion (3% to 5% vs. 2%), joint sprain (1% to 2% vs. 1%), muscle strain (1% to 2% vs. 1%), and wound secretion (up to and including 2% vs. 0%).
In clinical trials of vigabatrin, infection was a relatively common adverse event reported. During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following infections or related effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: pharyngitis (nasopharyngitis 9% to 14% vs. 10%), upper respiratory tract infection (7% to 9% vs. 6%), influenza (5% to 7% vs. 4%), urinary tract infection (4% to 5% vs. 0%), bronchitis (up to and including 5% vs. 1%), and fever (4% to 7% vs. 3%). Infectious adverse effects occurred at similar rates during pediatric clinical trials for refractory complex seizures (patient age range: 3 to 16 years); upper respiratory tract infection (15% vs. 11%), influenza (7% vs. 3%), otitis media (6% vs. 4%), streptococcal pharyngitis (4% vs. 3%), and viral gastroenteritis (2% vs. 0%) were reported in vigabatrin- and placebo-treatment groups, respectively. In clinical trials of pediatric patients with infantile spasms, infections, particularly those that are common in all infants and children, occurred at a higher rate. In a dose-response study in pediatric patients with infantile spasms (n = 222), the following infectious or related adverse events were reported in the low dose group (18 to 36 mg/kg/day) versus the high dose group (100 to 148 mg/kg/day), respectively: upper respiratory tract infection (51% vs. 46%), otitis media (44% vs. 30%), viral infection (20% vs. 19%), pneumonia (13% vs. 11%), candidiasis (8% vs. 3%), ear infection (7% vs. 14%), viral gastroenteritis (6% vs. 5%), sinusitis (5% vs. 9%), urinary tract infection (5% vs. 6%), influenza (5% vs. 3%), croup infections (5% vs. 1%), and fever (29% vs. 19%).
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following adverse respiratory and thoracic effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: pharyngolaryngeal pain (7% to 14% vs. 5%), cough (2% to 14% vs. 7%), pulmonary congestion (up to and including 5% vs. 1%), and sinus headache (2% to 6% vs. 1%). In a dose response study in pediatric patients with infantile spasms, the following respiratory disorders were reported in the low dose group (18 to 36 mg/kg/day) versus the high dose group (100 to 148 mg/kg/day), respectively: nasal congestion (13% vs. 4%) and cough (3% vs. 8%). In post-marketing experience of vigabatrin worldwide, laryngeal edema, pulmonary embolism, respiratory depression (respiratory failure), and stridor have been reported; however, incidence and causal relationship is not established.
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following adverse otic effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: tinnitus (up to and including 2% vs. 1%) and vertigo (2% to 5% vs. 1%). Deafness (hearing loss) has been reported during post-market use; however, the frequency is unknown and causality to the drug has not been established.
During clinical trials of vigabatrin as add-on therapy for refractory complex partial seizures in adults, the following adverse reproductive effects were reported in at least 2% of patients in the vigabatrin treatment groups and more frequently than in patients in the placebo groups: dysmenorrhea (5% to 9% vs. 3%) and impotence (erectile dysfunction) (up to and including 5% vs. 0%). Dysmenorrhea (3%) was also reported in pubescent females during pediatric clinical trials for complex partial seizures (patient age range: 10 to 16 years).
Vigabatrin causes permanent bilateral concentric visual field constriction in 30% or more of adult patients; the incidence in pediatric patients is not well defined, but is estimated at 20%. The visual field defect and resultant visual impairment can range in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation. Vigabatrin can also cause decreased visual acuity due to central retina damage. The onset of the vision disturbance can occur at any time during therapy, even after months or years. The risk increases with increasing dose and duration; there is no known risk-free exposure. Vision may worsen after vigabatrin discontinuation. Vigabatrin should be used at the lowest dose and shortest duration necessary to achieve clinical goals. Vigabatrin should not be used in patients with other risk factors for irreversible vision loss unless the benefits outweigh the risks. Vigabatrin also should not be used in patients taking other drugs that may cause serious ophthalmic adverse effects. Due to the risk for irreversible vision damage, vigabatrin should be discontinued if a significant clinical response is not achieved within 3 months of initiation for complex partial seizures, within 2 to 4 weeks of initiation for infantile spasms, or if clinical failure is obvious at any time point. Vision loss is difficult to detect in pediatric patients and may not be detected until it is severe. Vision assessment at baseline (no later than 4 weeks after vigabatrin initiation), at least every 3 months during therapy, and approximately 3 to 6 months after vigabatrin discontinuation is recommended; assessment should include both acuity and visual fields whenever possible. In patients who cannot be tested, treatment may continue according to clinical judgment, with appropriate patient counseling. Vision assessment requires an experienced clinician, specifically an ophthalmic professional with expertise in visual field interpretation and the ability to perform a dilated indirect ophthalmoscopy of the retina.
In January 2008, the FDA alerted healthcare professionals of an increased risk of suicidal ideation and behavior in patients receiving anticonvulsants to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). This alert followed an initial request by the FDA in March 2005 for manufacturers of marketed anticonvulsants to provide data from existing controlled clinical trials for analysis. Prior to this request, preliminary evidence had suggested a possible link between anticonvulsant use and suicidality. The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (5 years of age and older). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation (0.43%) as patients receiving placebo (0.24%), corresponding to an estimated 2.1 per 1,000 (95% CI: 0.7 to 4.2) more patients in the drug treatment groups who developed suicidal behavior or ideation. The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. Data were analyzed from drugs with adequately designed clinical trials including carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. However, this risk is considered to be a class effect. All patients beginning treatment with vigabatrin should be closely monitored for emerging or worsening depression or suicidal thoughts/behavior. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Anticonvulsants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.
Abrupt discontinuation of vigabatrin should not be undertaken. If discontinuation becomes necessary, vigabatrin should be withdrawn gradually.
Vigabatrin may cause somnolence and fatigue. Patients should be advised to avoid driving or operating machinery, or performing other tasks that require mental alertness until they are aware of whether vigabatrin adversely affects their cognitive and/or motor performance. Patients should also be informed of the possibility for enhanced drowsiness or dizziness with concurrent use of alcohol.
Vigabatrin can cause laboratory test interference. Use caution in interpreting liver function tests in patients with hepatic disease. Vigabatrin decreases alanine transaminase (ALT) and aspartate transaminase (AST) plasma activity in up to 90% of patients; these enzymes may become undetectable in some patients. AST and ALT reductions may invalidate the use of these markers to detect hepatic decompensation and early hepatic disease. Also, vigabatrin may increase the amount of amino acids in the urine, which could result in a false positive test for certain rare genetic metabolic diseases (e.g., alpha aminoadipic aciduria).
Vigabatrin is primarily renally eliminated. A dosage adjustment is required for patients with any degree of renal impairment.
Clinical studies of vigabatrin did not include enough geriatric persons aged 65 years and older to determine whether they responded differently from younger adults. Vigabatrin is primarily eliminated via the kidney, and geriatric patients are more likely to have decreased renal function. Care should be taken in dose selection based on the degree of renal impairment, and it may be useful to monitor renal function. In one small study, 4 out of 5 geriatric patients with reduced renal function (CrCl less than 50 mL/minute) experienced moderate to severe sedation and confusion after receiving a single dose of vigabatrin 1.5 grams PO; the adverse effects lasted up to 5 days. Other reported clinical experience has not identified differences in responses between older and younger adults. According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications in geriatric adults with a history of falls or fractures and should be avoided in these patient populations, except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If vigabatrin must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk.
Pediatric patients, particularly those with pre-existing myelin abnormalities, should be monitored closely for neurotoxicity during vigabatrin therapy. Abnormal magnetic resonance imaging (MRI) signal changes have been observed in infants receiving vigabatrin for infantile spasms. MRI abnormalities tend to peak after 3 to 6 months of vigabatrin exposure and typically resolve, even with continued use of the drug. Simultaneous motor abnormalities have been reported in some infants; however, a causal relationship has not been established. MRI abnormalities affect infants and children 6 years and younger and are associated with high dose therapy. Some investigators believe MRI changes are associated with developmental changes in myelination or an unknown underlying metabolic disorder. The clinical significance of MRI changes is unknown and the potential for long-term clinical sequelae has not been adequately studied. Animal models have suggested neurotoxicity may be more prevalent in neonates, infants, and children compared to adults. Neurotoxicity has been observed in rats with vigabatrin exposure during late gestation and the neonatal and juvenile periods of development, and in dogs exposed to vigabatrin during the juvenile period. Neurohistopathological (brain vacuolation, hypomyelination, retinal dysplasia) and neurobehavioral (seizures, neuromotor impairment, learning deficits) abnormalities occurred in young rats at vigabatrin doses lower than those producing neurotoxicity in adult animals and were associated with drug plasma concentrations substantially lower than those achieved clinically in human infants and children. Although neurobehavioral effects were not assessed, similar neurohistopathological abnormalities were observed in juvenile dogs. White matter vacuolation and intramyelinic edema (IME) have been associated with vigabatrin in animal studies involving several species. Although these findings have never been observed in pediatric or adult human studies, there is a single case report of vigabatrin-induced white matter vacuolation, IME, and subsequent encephalopathy in an infant with pre-existing white matter abnormalities due to prematurity. A relationship between MRI abnormalities in infants and neurotoxicity has not been established.
Vigabatrin is not classified as a controlled substance; however, the manufacturer advises caution in patients with a history of substance abuse since the drug has CNS active properties and has not been formally evaluated for its abuse, tolerance, or physical dependence potential.
There are no adequate data on the developmental risk associated with the use of vigabatrin during human pregnancy. Limited data from case reports and cohort studies have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, animal data suggest vigabatrin use may result in fetal harm. Vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (hippocampal vacuolation, decreased myelination, retinal dysplasia) abnormalities, when administered to pregnant animals at clinically relevant doses during organogenesis and the latter part of pregnancy. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to vigabatrin; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.
Breast-feeding is not recommended because of the potential for serious adverse reactions in the nursing infant. If a breast-fed infant is exposed to vigabatrin, observe for potential adverse effects. Vigabatrin is excreted in human milk. The effects of vigabatrin on the breast-fed infant and on milk production are unknown.
For the treatment of infantile spasms:
Oral dosage:
Infants and Children 1 month to 2 years: 50 mg/kg/day PO given in 2 divided doses initially. Titrate in 25 to 50 mg/kg/day increments every 3 days as needed based on patient response. Max: 150 mg/kg/day. Discontinue therapy if significant clinical benefit is not achieved within 2 to 4 weeks of initiation, or earlier if clinical failure is evident. To withdraw, decrease daily dose by 25 to 50 mg/kg every 3 to 4 days. Rapid discontinuation may be considered for serious adverse reactions. A post hoc analysis of a Canadian Pediatric Epilepsy Network study suggests a total duration of 6 months is adequate for treatment of infantile spasms; however, use clinical judgment regarding appropriate length of therapy.
For the adjunctive treatment of refractory complex partial seizures:
Oral dosage:
Adults: 500 mg PO twice daily initially. Titrate in 500 mg/day increments at weekly intervals based on patient response. Recommended dose: 1,500 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by 1,000 mg/day at weekly intervals. Rapid discontinuation may be considered for serious adverse events.
Adolescents 17 years: 500 mg PO twice daily initially. Titrate in 500 mg/day increments at weekly intervals based on patient response. Recommended dose: 1,500 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by 1,000 mg/day at weekly intervals. Rapid discontinuation may be considered for serious adverse events.
Children and Adolescents 2 to 16 years weighing more than 60 kg: 500 mg PO twice daily initially. Titrate in 500 mg/day increments at weekly intervals based on patient response. Recommended dose: 1,500 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by 1,000 mg/day at weekly intervals. Rapid discontinuation may be considered for serious adverse events.
Children and Adolescents 2 to 16 years weighing 26 to 60 kg: 250 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 1,000 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.
Children and Adolescents 2 to 16 years weighing 21 to 25 kg: 250 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 750 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.
Children and Adolescents 2 to 16 years weighing 16 to 20 kg: 225 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 650 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.
Children and Adolescents 2 to 16 years weighing 10 to 15 kg: 175 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 525 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.
Infants* and Children younger than 2 years*: Limited data suggest that vigabatrin may be effective; however, dosage recommendations have not been clearly defined. An initial dose of 40 to 50 mg/kg/day PO given in 2 divided doses, gradually titrated to a maintenance dose of 40 to 150 mg/kg/day has been suggested. However, initial doses ranging from 10 to 85 mg/kg/day (reported mean: 50 to 70 mg/kg/day) have been used with a reported mean maintenance dose of 50 to 80 mg/kg/day. In 1 review, doses up to 200 mg/kg/day were used in children with incomplete control after 2 weeks of vigabatrin therapy. A mean dose of 83.4 mg/kg/day PO (range: 10 to 150 mg/kg/day) for a mean duration of 21.75 months (range: 1 to 144 months) has been described in a retrospective review of 73 patients (mean age: 8.5 years; range: 1 month to 21 years) with various seizure disorders.
Maximum Dosage Limits:
-Adults
3,000 mg/day PO.
-Geriatric
3,000 mg/day PO.
-Adolescents
17 years : 3,000 mg/day PO.
13 to 16 years weighing more than 60 kg : 3,000 mg/day PO.
13 to 16 years weighing 26 to 60 kg: 2,000 mg/day PO.
13 to 16 years weighing 21 to 25 kg: 1,500 mg/day PO.
-Children
2 to 12 years weighing more than 60 kg : 3,000 mg/day PO.
2 to 12 years weighing 26 to 60 kg: 2,000 mg/day PO.
2 to 12 years weighing 21 to 25 kg: 1,500 mg/day PO.
2 to 12 years weighing 16 to 20 kg: 1,300 mg/day PO.
2 to 12 years weighing 10 to 15 kg: 1,050 mg/day PO.
1 year : 150 mg/kg/day PO for infantile spasms. Safety and efficacy have not been established for other seizure types.
-Infants
150 mg/kg/day PO for infantile spasms. Safety and efficacy have not been established for other seizure types.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
NOTE: Although dosage adjustment is recommended for pediatric patients with renal impairment, specific guidelines are not available for infants and children younger than 2 years.
Based on estimated CrCl, the following dosage adjustments are recommended for patients 2 years and older:
CrCl more than 80 mL/minute: No dosage adjustment necessary.
CrCl 51 to 80 mL/minute: Reduce dose by 25%.
CrCl 31 to 50 mL/minute: Reduce dose by 50%.
CrCl 11 to 30 mL/minute: Reduce dose by 75%.
Intermittent hemodialysis
The effect of dialysis on vigabatrin elimination has not been determined. In case reports of patients with renal failure receiving therapeutic doses of vigabatrin, hemodialysis reduced vigabatrin plasma concentrations by 40% to 60%. Dosing recommendations are not available.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Chlorpheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with dichloralphenazone.
Acetaminophen; Diphenhydramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acetaminophen; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Acetaminophen; Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Acrivastine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Albuterol; Budesonide: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Alfentanil: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Alprazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Amobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Aspirin, ASA; Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Avanafil: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Azathioprine: (Major) Vigabatrin should not be used with other drugs like azathioprine that are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Azelastine; Fluticasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Barbiturates: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Beclomethasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Belladonna; Opium: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Benzhydrocodone; Acetaminophen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Benzodiazepines: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Betamethasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Brompheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Brompheniramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Brompheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Budesonide: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Budesonide; Formoterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Budesonide; Glycopyrrolate; Formoterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Bupivacaine; Meloxicam: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as meloxicam, may occur during concurrent use of vigabatrin.
Buprenorphine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with buprenorphine.
Buprenorphine; Naloxone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with buprenorphine.
Buspirone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with buspirone.
Butalbital; Acetaminophen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Butorphanol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with butorphanol.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and vigabatrin. CNS depressants can potentiate the effects of cannabidiol.
Carbinoxamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Celecoxib; Tramadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Chlophedianol; Dexbrompheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorcyclizine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlordiazepoxide: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Chlordiazepoxide; Clidinium: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Chloroquine: (Major) Vigabatrin should not be used with chloroquine due to potential retinal toxicity associated with both drugs, unless the benefits of treatment clearly outweigh the risks.
Chlorpheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Dextromethorphan: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Chlorpromazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Ciclesonide: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Clemastine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Clomipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Clonazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Clorazepate: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Codeine; Guaifenesin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Codeine; Phenylephrine; Promethazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Codeine; Promethazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Corticosteroids: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Cortisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Cyproheptadine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Deferoxamine: (Major) Vigabatrin should not be used with deferoxamine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Deflazacort: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Desipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as vigabatrin, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexamethasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Dexbrompheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Dexchlorpheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Diazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Diclofenac: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as diclofenac, may occur during concurrent use of vigabatrin.
Diclofenac; Misoprostol: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as diclofenac, may occur during concurrent use of vigabatrin.
Dimenhydrinate: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Diphenhydramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Diphenhydramine; Ibuprofen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Diphenhydramine; Naproxen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers. (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
Diphenhydramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Doxepin: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Doxylamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Doxylamine; Pyridoxine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Dronabinol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with dronabinol, THC.
Droperidol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with droperidol.
Estazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Eszopiclone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
Ethambutol: (Major) Vigabatrin should not be used with ethambutol, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Fentanyl: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Finasteride; Tadalafil: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Fludrocortisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Flunisolide: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Fluphenazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Flurazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Fluticasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Fluticasone; Salmeterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Fluticasone; Umeclidinium; Vilanterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Fluticasone; Vilanterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Formoterol; Mometasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Fosphenytoin: (Moderate) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. Decreased exposure of drugs that are extensively metabolized by CYP2C9, such as phenytoin, may occur during concurrent use of vigabatrin. During clinical trials, average reductions in total phenytoin plasma levels of 16% to 20% were reported during concurrent use of vigabatrin. If combination therapy is indicated, determinations for dosage adjustments of phenytoin should be made on an individual basis. Because fosphenytoin is hydrolyzed to phenytoin, a change in phenytoin plasma levels would also be expected to occur during concurrent administration of vigabatrin and fosphenytoin.
Guaifenesin; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Homatropine; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Hydrocodone; Ibuprofen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Hydrocodone; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Hydrocortisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Hydromorphone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Hydroxychloroquine: (Major) Vigabatrin should not be used with hydroxychloroquine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. Additionally, hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
Hydroxyzine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Ibuprofen; Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Imipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Interferon Alfa-2b: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Interferon Alfa-n3: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Interferon Beta-1a: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Interferon Beta-1b: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Interferon Gamma-1b: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Interferons: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Levorphanol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Lorazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Losartan: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as losartan, may occur during concurrent use of vigabatrin.
Losartan; Hydrochlorothiazide, HCTZ: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as losartan, may occur during concurrent use of vigabatrin.
Loxapine: (Major) Vigabatrin should not be used with loxapine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Maprotiline: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
Mecasermin, Recombinant, rh-IGF-1: (Major) Vigabatrin should not be used with mecasermin, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Meclizine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors. Some, but not all anticonvulsants, induce CYP3A4 and may increase the metabolism of mefloquine. Use of enzyme-inducing anticonvulsants can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria.
Meloxicam: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as meloxicam, may occur during concurrent use of vigabatrin.
Meperidine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Meprobamate: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
Methadone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Methohexital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Methylprednisolone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Midazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Mirtazapine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with mirtazapine.
Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
Mometasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Morphine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Morphine; Naltrexone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Nabilone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with nabilone.
Nalbuphine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with nalbuphine.
Naproxen: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
Naproxen; Esomeprazole: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
Naproxen; Pseudoephedrine: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
Nateglinide: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as nateglinide, may occur during concurrent use of vigabatrin.
Nortriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Oliceridine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Olopatadine; Mometasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Opiate Agonists: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Oxazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Oxymorphone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Peginterferon Alfa-2a: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Peginterferon Alfa-2b: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Peginterferon beta-1a: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Pentazocine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with pentazocine.
Pentazocine; Naloxone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with pentazocine.
Pentobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Pentostatin: (Major) Vigabatrin should not be used with pentostatin, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Perphenazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Perphenazine; Amitriptyline: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Phenobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Phenothiazines: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Phenytoin: (Moderate) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. Decreased exposure of drugs that are extensively metabolized by CYP2C9, such as phenytoin, may occur during concurrent use of vigabatrin. During clinical trials, average reductions in total phenytoin plasma levels of 16% to 20% were reported during concurrent use of vigabatrin. If combination therapy is indicated, determinations for dosage adjustments of phenytoin should be made on an individual basis.
Phosphodiesterase inhibitors: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Prednisolone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Prednisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Primidone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Prochlorperazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Promethazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Promethazine; Dextromethorphan: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Promethazine; Phenylephrine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Protriptyline: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Pseudoephedrine; Triprolidine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Quazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Ramelteon: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with ramelteon.
Remifentanil: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Remimazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Ropeginterferon alfa-2b: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
Secobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
Sedating H1-blockers: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Sildenafil: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and vigabatrin. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as sulfamethoxazole, may occur during concurrent use of vigabatrin.
Sumatriptan; Naproxen: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
Tadalafil: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Tapentadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Temazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Thioridazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Thiothixene: (Major) Vigabatrin should not be used with thiothixene, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Tramadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Tramadol; Acetaminophen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Triamcinolone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Triazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Trifluoperazine: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Trimipramine: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Triprolidine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Vardenafil: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Warfarin: (Moderate) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as warfarin, may occur during concurrent use of vigabatrin.
Zaleplon: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
Zolpidem: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
The exact mechanism by which vigabatrin exerts its anticonvulsant effects is unknown; however, it is believed to be the result of increased GABA concentrations in the central nervous system (CNS). Vigabatrin is a structural analog of GABA and is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), which is the enzyme that metabolizes GABA. GABA is the major inhibitory neurotransmitter in the CNS and acts on postsynaptic membranes to open chloride channels, thereby leading to membrane hyperpolarization and preventing propagation of neural impulses. By inhibiting GABA metabolism, vigabatrin allows more GABA to be available for receptor binding on post-synaptic cells. There does not appear to be a direct correlation between plasma vigabatrin concentrations and efficacy; the duration of action is thought to be dependent on the rate of GABA synthesis rather than vigabatrin elimination.
Another drug that is used for the treatment of partial seizures, tiagabine, also affects GABA CNS concentrations but by a different mechanism. Whereas vigabatrin inhibits the metabolism of GABA, tiagabine inhibits the reuptake of GABA. Unlike tiagabine and vigabatrin, the mechanisms of action of other drugs indicated for adjunctive treatment of partial seizures (e.g., lamotrigine, gabapentin, topiramate) are not primarily mediated through GABA transmission.
Vigabatrin is administered orally. Vigabatrin does not bind to plasma proteins and is widely distributed throughout the body. The mean steady state volume of distribution is 1.1 L/kg. Vigabatrin is not significantly metabolized. It is eliminated primarily through renal excretion. In healthy adult male volunteers who received radiolabeled vigabatrin, approximately 95% of the total radioactivity was recovered in the urine over 72 hours; approximately 80% was parent drug. Drug clearance is 7 L/hour in adult patients. The half-life in adults is approximately 10.5 hours. Of note, a direct correlation between plasma vigabatrin concentrations and efficacy has not been established; the duration of action is thought to be dependent on the rate of GABA synthesis rather than vigabatrin elimination.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9
Vigabatrin induces CYP2C9, but does not appear to induce other hepatic cytochrome P450 enzymes. Vigabatrin is not metabolized by hepatic enzymes.
-Route-Specific Pharmacokinetics
Oral Route
Bioequivalence has been established between the oral solution and oral tablets. In adults, vigabatrin displays linear pharmacokinetics after single doses of 0.5 g to 4 g and after repeated doses of 0.5 g and 2 g twice daily. After oral administration, vigabatrin is completely and rapidly absorbed with a time to maximum plasma concentration (Tmax) in adults of approximately 1 hour after single or multiple doses; minimal accumulation occurs after multiple doses. In healthy volunteers, administration with food resulted in a 33% reduction in maximum plasma concentration (Cmax), an increase in Tmax to 2 hours, and unchanged AUC compared to administration under fasting conditions.
-Special Populations
Renal Impairment
Because vigabatrin is primarily eliminated via the kidneys, renal impairment slows elimination and increases exposure. In adult patients with mild renal impairment (CrCl more than 50 to 80 mL/minute), the mean AUC increased by 30%, and the terminal half-life increased by 55% compared to subjects with normal renal function. In adult patients with moderate renal impairment (CrCl more than 30 to 50 mL/minute), the mean AUC and terminal half-life increased by 2-fold. In adult patients with severe renal impairment (CrCl more than 10 to 30 mL/minute), the mean AUC increased by 4.5-fold, and the terminal half-life increased by 3.5-fold.
In healthy patients 65 years and older, the renal clearance of vigabatrin was 36% less than that of healthy young patients.
Pediatrics
Children and Adolescents 3 to 16 years
Vigabatrin absorption is more rapid and complete in older children and adults compared to infants and young children. After oral administration, Tmax is approximately 1 hour. In patients 10 to 16 years, clearance is 5.8 L/hour, and the half-life is 9.5 hours. In patients 3 to 9 years, clearance is 5.1 L/hour, and half-life is 6.8 hours. The pharmacokinetic parameters of vigabatrin's S(+) and R(-) enantiomers were studied after administration of a single oral 50 mg/kg dose to pediatric patients with refractory seizures (n = 12; group I: 5 to 22 months; group II: 4 to 14 years). Pharmacokinetic parameters of the pharmacologically active enantiomer did not vary significantly with age; however, AUC and half-life of the inactive enantiomer increased linearly with age. A Cmax of 24 mg/L was obtained in 1.4 hours for the active enantiomer. When corrected for weight, AUC values of both enantiomers were greater in the older group [S(+) AUC = 117 +/- 26 mg x hour/L; R(-) AUC = 147 +/- 34 mg x hour/L] compared to the younger group [S(+) AUC = 91 +/- 28 mg x hour/L; R(-) AUC = 106 +/- 29 mg x hour/L]. Renal clearance (0.5 to 2 mL/kg/minute) was similar to that reported in adults (1.27 mL/kg/minute). In addition, half-life of the active enantiomer (5.5 hours), was similar to that in younger children (5.7 hours).
Infants and Children 1 to 23 months
Vigabatrin absorption is less rapid and complete in infants and young children compared to older populations. Tmax is approximately 2.5 hours. Clearance is 2.4 L/hour, and half-life is 5.7 hours. The pharmacokinetic parameters of vigabatrin's S(+) and R(-) enantiomers were studied after administration of a single oral 50 mg/kg dose to pediatric patients with refractory seizures (n = 12; group I: 5 to 22 months; group II: 4 to 14 years). Pharmacokinetic parameters of the pharmacologically active enantiomer did not vary significantly with age; however, AUC and half-life of the inactive enantiomer increased linearly with age. A Cmax of 14 mg/L was obtained in 2.85 hours for the active enantiomer. When corrected for weight, AUC values of both enantiomers were lower in the younger group [S(+) AUC = 91 +/- 28 mg x hour/L; R(-) AUC = 106 +/- 29 mg x hour/L] than those reported in older children [S(+) AUC = 117 +/- 26 mg x hour/L; R(-) AUC = 147 +/- 34 mg x hour/L] and adults. Renal clearance (0.5 to 2 mL/kg/minute) was similar to that reported in adults (1.27 mL/kg/minute). In addition, half-life of the active enantiomer (5.7 hours) was similar to that in older children (5.5 hours).
Neonates
Absorption of vigabatrin's pharmacologically active enantiomer is similar between neonates, infants, and children; a mean Cmax of 14 mg/L is attained in 2.1 hours in neonates. However, total drug exposure is higher (142.6 +/- 44 mg x hour/L), and elimination half-life is longer (7.5 +/- 2.1 hours) in neonates compared to values reported for infants and children, most likely due to the reduced renal function of neonates. Based on these parameters and a favorable pharmacokinetic profile (e.g., no protein binding, linear pharmacokinetics, no hepatic metabolism, and unchanged renal elimination), it has been suggested similar dosing regimens can be used in neonates, infants, and children.
Geriatric
In healthy patients 65 years and older, the renal clearance of vigabatrin was 36% less than that of healthy young patients.
Gender Differences
In clinical trials, no gender differences were noted for vigabatrin pharmacokinetic parameters.