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Alternative approaches pain treatment center winnipeg benemid 500mg order without a prescription, together with immunotherapies chronic pain syndrome treatment guidelines generic 500mg benemid amex, have been tried [36] joint pain treatment in homeopathy benemid 500mg cheap overnight delivery,[42],[43]. Anakinra, an interleukin-1 receptor antagonist [44], and the ketogenic food plan [45] have additionally shown some efficacy in uncontrolled case collection. It is often due to the complications related to extended unconsciousness and mechanical ventilation [36]. At least one-half of survivors are left with long-term cognitive and useful incapacity, and most will have epilepsy, requiring lifelong antiseizure treatment. These seizures sometimes happen a quantity of instances per day, alternate sides, may be triggered by motion or robust emotion, and are usually not associated with loss of awareness, although lack of awareness can on rare event occur. Perhaps most significantly, sufferers are often cognitively intact on the onset of this epileptic syndrome, offering window of alternative to treat prior to the development of limbic encephalitis [50], lessening the dangers of lasting cognitive deficits [51]. On the other hand, temporal lobe epilepsy with hippocampal sclerosis might develop after acute limbic encephalitis in a small however clinically relevant proportion of sufferers [52]. High frequency of seizures, usually occurring a quantity of occasions a day, ought to increase suspicion of an immune-mediated cause. In addition, seizures could comprise perisylvian semiologic options, similar to auras involving multiple sensory modalities, laryngeal motor or sensory manifestations, and/or language disturbance [56],[57]. Autonomic seizures are also incessantly associated with antineuronal antibodies [58] and will vary from ictal tachycardia, light-headedness, flushing, to postictal fever. Specifically, pilomotor seizures have been shown to be incessantly associated with antineuronal antibodies [59]. Compared to mesial temporal lobe epilepsy with hippocampal sclerosis with out clear autoimmune trigger, patients with autoimmune epilepsy have a higher chance of experiencing more frequent seizures, shorter seizure duration, and secondary generalized tonic�clonic seizures out of sleep, while postictal confusion is less doubtless [60]. Patients with autoimmune epilepsy are likely to expertise comorbid psychiatric disturbance. This disturbance might range from mood disturbance [55],[56] to agitation, aggressiveness, and psychosis [4]. A distinct neuropsychiatric profile has not yet been described in comparability with focal epilepsy of different etiology. A mixture of the above clinical characteristics ought to raise suspicion of an underlying autoimmune etiology when assessing any epilepsy of new-onset or undetermined etiology. A predictive mannequin of antibody positivity in epilepsy has been developed [4] and validated [63] for such use (Table 28. This rating makes use of a mix of clinical and ancillary testing options, with a rating of four or larger being predictive of a constructive antineuronal antibody. Indeed, a syndrome consistent with autoimmune epilepsy could exist without an as-ofyet associated antineuronal antibody and will warrant an immunotherapy trial, which might help help the diagnosis [62]. Approach to Diagnostic Testing Listen Antibody Testing Detection of antibodies is a key step in the definite analysis of autoimmune encephalitis causing epilepsy. Clinicians must pay consideration to potential limitations in testing methods and pitfalls in interpretation of take a look at results. On the opposite hand, most antibodies towards synaptic receptors, ion channels, and different neuronal surface proteins acknowledge target epitopes only if their threedimensional conformation is preserved. Their detection requires applicable cell-based assays, that are commercially out there, immunohistochemistry of mind tissue, or immunocytochemistry of dissociated neurons, which are often restricted to analysis laboratories. Nonspeci c Seropositivity 741 Positive testing ought to at all times be fastidiously considered in a medical context. Only titers one hundred to 1000 times greater than low titers or intrathecal manufacturing of antibodies are associated with neurologic symptoms, including encephalitis [22]. In the case of autoimmune encephalitis, 60% to 80% of patients might have a light to average (<100 cells/dL) pleocytosis [29], while in antibody-positive epilepsy, only 22% may have this discovering [63]. Similarly, oligoclonal banding and elevated IgG index may be seen in roughly 50% of autoimmune encephalitis [29] and 29% of autoimmune encephalitis sufferers with seizures [57]. In one examine, elevated protein, white blood cells, or oligoclonal banding was present in 31% of autoimmune epilepsy sufferers [54]. Imaging Characteristics the range of imaging traits mirrors the medical traits described within the part "Specific Epilepsy Syndromes and Autoimmune Epilepsy Characteristics. Voxel-based morphometry analysis has proven that the amygdala is extra enlarged compared to the hippocampus in limbic encephalitis. Paralleling the perisylvian semiology seen in autoimmune epilepsy, perisylvian cortical enlargement may be famous on follow-up imaging [72]. Bilateral hippocampal tail and fornix hyperintensities have been additionally current (arrowheads). Another uncommon and hanging imaging finding could also be that of hyperintensities involving the claustrum, the thin grey matter construction situated between the insula and the basal ganglia. Abnormalities are sometimes nonspecific and range from generalized slowing, which typically improves over the course of the disease [57], to focal slowing, typically involving the temporal areas. Interictal epileptiform discharges could additionally be seen in 53% to 63% of patients [54],[56],[57], regardless of the frequent seizures characterizing these patients. Frequent subclinical temporal seizures are often seen in sufferers with Lgi1 antibodies [80]. Extreme delta could function a surrogate marker of disease exercise in sufferers not responding to first-line immunotherapy [82]. While the overwhelming majority of faciobrachial dystonic seizures could not 744 have a transparent electrographic correlate, extra extreme or extended seizures will correlate with a preceding frontocentral slow [48] and infraslow [49] activity, contralateral to the facet of the tonic spasm. Malignancy Screening the recognition that autoimmune neurologic syndromes could also be triggered by an underlying occult malignancy dates again to the initial descriptions of paraneoplastic limbic encephalitis. When autoimmune encephalitis or epilepsy is paraneoplastic, the malignancy is usually not recognized at the time of neurologic presentation and subsequently must be appropriately screened for. On the opposite hand, comorbid malignancy will increase the chance of carrying an antineuronal antibody [63]. While certain tumor varieties are related to explicit antibodies (see Table 28. Finally, in the case of a paraneoplastic antibody (such as anti-Hu, anti-Yo, anti-Ma2), surveillance is important if preliminary malignancy screening is unfavorable. Testicular biopsy in sufferers younger than 50 with Ma2 antibodies and microcalcifications on ultrasound. In circumstances of particular autoimmune etiology, immunotherapy presents the only definitive remedy option, given the dearth of fine response to symptom-targeted treatment (antiseizure medicine, epilepsy surgery) [85]. Notably, no randomized clinical trials exist within the subject of autoimmune encephalitis and epilepsy. Therefore, this section stems from retrospective or observational research and skilled opinion. Regardless of the type of first-line immunotherapy chosen, the clinician ought to get hold of goal documentation of disease severity previous to therapy initiation to have the ability to verify therapy response. This step is essential to decide whether or not escalation to second-line immunotherapy is important (in the case of minimal or lack of response to first-line immunotherapy and goal evidence of autoimmunity) or whether or not the affected person would profit from maintenance and eventual taper of the therapy that supplied objective benefit. Some patients could additionally be at heightened risk of unwanted effects from one type of first-line immunotherapy, for instance, worsened glucose management in a diabetic patient in whom steroids are being thought-about. Second Line In sufferers with incomplete or no response to first-line immunotherapy and goal proof of autoimmunity. Treatment Algorithm the principle objectives of the immunotherapeutic strategy are to induce immunosuppression and keep that response. Short period of illness previous to initiation of immunotherapy predicts higher outcome (9. Risk Mitigation When contemplating the above therapies, a number of threat mitigation strategies can be applied. If longterm steroid use is being thought of (due to relapse throughout steroid taper or severe disease), steroid-sparing agents ought to be thought-about and preventive measures taken to minimize long-term issues of glucocorticoid use. In sufferers with pre-existing diabetes mellitus, poorly controlled hypertension, cataract or glaucoma, peptic ulcer disease, and osteoporosis, shut monitoring for worsening of the above conditions ought to be carried out in conjunction with main care. Osteoporosis prevention must be pursued through sufficient calcium and vitamin D intake. Immunotherapy trials may help solidify a prognosis of autoimmune epilepsy and are often more effective than typical epilepsy therapy but must be performed with wise threat mitigation methods.
Diseases
Factors associated to successful antiepileptic drug withdrawal after anterior temporal Al-Kaylani M pain treatment center baton rouge buy 500 mg benemid free shipping, Konard P pain treatment center riverbend calgary benemid 500 mg buy cheap on line, Lazeby B pain treatment satisfaction scale (ptss) benemid 500mg generic free shipping, et al. Psychologic and behavioral results of antiepileptic medicine in children: a American Academy of Neurology, Quality Standards Subcommittee. Practice parameter: a tenet for discontinuing epilepticus in Richmond, Virginia. Therefore, caregivers might need to bear in mind that breakthrough seizures might happen at some point, and so they may need to be educated on tips on how to respond appropriately to different seizure displays. Most seizures are self-limited and final <5 minutes, each in children [5] and adults [6]. When seizures last more than 5 minutes, a situation termed impending standing epilepticus, current guidelines counsel initial remedy with a benzodiazepine [7] to decrease the danger of evolution into established status epilepticus. Status epilepticus is a life-threatening emergency that requires immediate and aggressive treatment and is mentioned in additional element in Chapter 36. This concept can be referred to as "seizure clusters," "flurry of seizures," or "serial seizures" [8]. Some of these definitions embody 2 seizures in <48 hours [9], 2 seizures in 24 hours [10], or 3 seizures in 24 hours [8],[11], [12], [13]. In distinction, a statistical strategy is individualized and evidence-based but requires a sometimes infeasible estimation of the baseline seizure frequency in every patient. Population research tend to have the lowest prevalence, and studies in epilepsy monitoring units, the place medications are sometimes lowered or withheld, have the highest prevalence. In addition, respondents or their caregivers reported marked impairments in their high quality of life [27]. The mechanisms of seizure self-termination are solely partially understood [30], and their degree of operate or dysfunction in several individuals and in different conditions could partially explain why some seizures selfterminate, some evolve into status epilepticus, and once more others self-terminate solely to recur in clusters. These findings are consistent with the hypothesis that seizures inside a cluster are too quick to activate self-termination mechanisms [31]. A current survey on a hundred pediatric sufferers or their caregivers confirmed that roughly 90% of patients had received a rescue treatment prescription [35]. However, in only 41% the dose was in the really helpful range, it was decrease than recommended in 51% of cases and higher than beneficial in 8% [35]. Only 61% of families reported having acquired training on how to administer rescue medicine [35]. However, the results of these surveys suggest that ensuring that sufferers and caregivers are acquainted with no much less than some seizure action plan may be of larger sensible impact than deciding on essentially the most efficacious rescue medication. The median seizure count in the 12 hours following administration was lower with diazepam than with placebo (0 vs. The superior efficacy of rectal diazepam over placebo began early after the treatment and was maintained for the 12 hours of remark [34]. Adverse effects had been more frequent with rectal diazepam application than with placebo (46% vs. The proportion of patients who required additional treatment in an emergency room or within the hospital was lower than half within the rectal diazepam arm than in the placebo arm (3 of fifty six patients [5%] vs. In this study, youngsters obtained 2 doses of medication (at onset and at four hours), and adults obtained three doses of treatment (at onset, at four hours, and at 12 hours) [38]. The median seizure count per hour was lower with rectal diazepam than with placebo (approximately zero seizures per hour vs. The world remedy end result, a composite score composed of an assessment of frequency and severity of seizures and drug toxicity by the caregiver, demonstrated higher outcomes within the rectal diazepam arm than in the placebo arm [38]. Adverse effects were greater in the rectal diazepam arm than within the placebo arm (47% vs. None of the patients in the diazepam group required emergency medical care, whereas 13% of sufferers within the placebo arm did [38]. Subanalyses of those knowledge demonstrated that the superior efficacy of rectal diazepam over placebo occurred in both kids [39] and adults [40]. However, it must be emphasised that these studies compared rectal diazepam with placebo, and never with different rescue drugs. Most research on the treatment of epilepsy exacerbations concentrate on the therapy of extended seizures. A network meta-analysis of 16 research (15 together with solely pediatric patients) on the efficacy of preliminary nonintravenous rescue medicines for acute convulsive seizures confirmed that essentially the most efficacious nonintravenous rescue drugs were intramuscular midazolam and intranasal midazolam [41]. Intramuscular midazolam was probably the most efficacious with regard to endpoints of time to seizure termination after administration, time to seizure cessation after arrival on the hospital, and time to treatment initiation [41]. Intranasal midazolam was probably the most efficacious considering the endpoint of seizure cessation inside 10 minutes of administration [41]. Rectal diazepam was inferior to these medications attaining seizure cessation inside 10 minutes in only approximately 70% of sufferers (approximately 20 percentage factors decrease than intranasal midazolam), with sustained seizure cessation for greater than 1 hour in only roughly 55% of patients [41]. The most cost-effective medication was buccal midazolam followed by intranasal midazolam [42]. Rectal diazepam was not a cheap different in comparison with the other choices, and this conclusion remained extraordinarily strong to broad variations of the input parameters on cost and effectiveness [42]. Nonintravenous rescue medications for pediatric standing epilepticus: a cost-effectiveness evaluation. Of note, pooled efficacy estimates could not pretty examine the effectiveness of rescue medicines as completely different research administered them in numerous circumstances and totally different affected person populations. However, 1069 direct head-to-head comparisons in prospective randomized research also suggest that intranasal midazolam has similar or superior effectiveness compared to rectal diazepam [43], [44], [45], [46]. Apart from having a superior efficacy profile [47], intranasal midazolam seems to be higher tolerated by caregivers and college personnel than rectal diazepam. In a survey in Australia, among the 15 caregivers who had used rectal diazepam and intranasal midazolam, 13 (87%) found the intranasal route simpler to administer and 14 (93%) expressed a choice to use intranasal midazolam as a substitute of rectal diazepam [48]. In a survey within the United States, 68 of 91 families (75%) expressed a desire for a nonrectal rescue medication if it had the same efficacy as the rectal treatment, and this proportion elevated to 90% for families of children with regular development [35]. A survey distributed amongst families who had been prescribed oral clonazepam wafers showed that 38 of 56 (68%) households considered clonazepam efficacious, with efficacy outlined as stopping seizures within 10 minutes of administration greater than 50% of the times [49]. Among the 16 households who had used each oral clonazepam and rectal diazepam, 7 (44%) thought that oral clonazepam was equally efficacious than rectal diazepam, 4 (25%) thought-about that oral clonazepam was more efficacious than rectal diazepam, and 5 (31%) thought that rectal diazepam was extra efficacious than oral clonazepam [49]. Although the efficacy of intravenous clonazepam stopping seizures is high and much like that of intravenous lorazepam or intravenous midazolam [50],[51], no objective measures of the efficacy of oral clonazepam are available. What we thought of the best available evidence on the time of this writing is introduced as the default within the metaanalysis. We consider that an evidence-based meta-analysis primarily based on data enriches the dialogue, and we strongly advocate that our readers actively consider obtainable evidence on the time of studying and when new proof turns into obtainable. A concerning proportion of caregivers report unfamiliarity with seizure action plans, and clinicians should make certain that caregivers perceive and are in a position to implement probably the most appropriate rescue plan for the person affected person. The course of childhood-onset epilepsy over the first two decades: a prospective, longitudinal research. Occurrence of seizure clusters and status epilepticus during inpatient videoSillanpaa M, Schmidt D. The association between seizure clustering and convulsive standing epilepticus in Fogarasi A, Janszky J, Faveret E, et al. The syndrome of frontal lobe epilepsy: characteristics and surgical Bauer J, Burr W. Pharmaco-resistant seizures: self-triggering capability, scale-free properties and S�nchez Fern�ndez I, Abend N, Loddenkemper T. Treating repetitive seizures with a rectal diazepam formulation: a Ga�nza-Lein M, Benjamin R, Stredny C, et al. Efficacy of nonvenous drugs for acute convulsive seizures: a network metaS�nchez Fern�ndez I, Ga�nza-Lein M, Loddenkemper T. Nonintravenous rescue drugs for pediatric standing Bhattacharyya M, Kalra V, Gulati S. A comparability of midazolam nasal spray and diazepam rectal answer Fisgin T, Gurer Y, Tezic T, et al. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: Holsti M, Dudley N, Schunk J, et al. Practice variability and efficacy of clonazepam, lorazepam, and midazolam in Navarro V, Dagron C, Elie C, et al. Prehospital remedy with levetiracetam plus clonazepam or placebo plus analysis.
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Prophylaxis Phenytoin is often used following neurosurgical procedures and cerebrovascular accidents pain medication for pregnant dogs order benemid 500 mg on-line. A randomized pain treatment topics generic 500 mg benemid fast delivery, double-blind trial compared the efficacy pain treatment center orland park order 500 mg benemid, tolerability, and impact on high quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin versus valproate in one hundred sufferers following craniotomy [136]. No main between-treatment differences emerged in efficacy, tolerability, influence on quality of life, or cognitive functioning [136]. A doubleblind comparability of phenytoin or carbamazepine with no remedy after supratentorial craniotomy famous no important differences however the next incidence of unwanted effects in the treated group [137]. This finding was reaffirmed by a Cochrane Review examining 10 randomized managed trials administering antiseizure drugs submit craniotomy [138]. The efficacy of phenytoin within the prevention of posttraumatic seizures was studied in a randomized, doubleblind trial of 404 patients with severe head trauma [139]. Patients acquired a phenytoin-loading dose within 24 hours of damage; free phenytoin serum levels have been maintained in a spread from zero. From the time of drug loading to day 7, significantly fewer seizures occurred within the phenytoin group than within the placebo group (3. No benefit was seen within the phenytoin group after day 8, nonetheless, leading to the conclusion that phenytoin had an early suppressive effect, however not a real prophylactic impact, on seizures and that it lowered the incidence of seizures only through the first week after harm. In a secondary evaluation of this study [140], no significant difference in mortality was found between sufferers assigned to phenytoin and those assigned to placebo. Fosphenytoin Fosphenytoin itself has no recognized anticonvulsant activity; it derives its utility from its speedy and complete conversion to phenytoin [14],[16]. The two primary conditions by which fosphenytoin are used are throughout standing epilepticus, or as a brief substitute for oral phenytoin in a nonemergency hospital situation, similar to in a patient undergoing a 1333 neurosurgical process. Fosphenytoin could be diluted in quite a lot of automobiles, such as dextrose 5% and 10%, lactated Ringer answer, and mannitol 20% [143]. Fosphenytoin (rather than phenytoin) has turn out to be part of the standard-of-care therapy protocols for convulsive status epilepticus in adults and youngsters in plenty of U. It is preferred to phenytoin because of higher tolerability at the infusion web site, lack of cardiovascular problems, and total ease of administration [144]. For the prophylaxis of seizures in neurosurgical patients, a single nonemergency loading dose is given both intravenously or intramuscularly. Fosphenytoin (given both intravenously or intramuscularly) is beneficial as a quick lived substitute for oral phenytoin when the affected person is unable to take oral medications. A variety of research and editorials have reported pharmacoeconomic comparisons between fosphenytoin and intravenous phenytoin [108],[145], [146], [147]. The total value of affected person care with intravenous fosphenytoin was lower than with intravenous phenytoin in an emergency department setting [147]. Substitution of intravenous fosphenytoin for intravenous phenytoin was associated with reduced "adverse occasions at an affordable enhance in total hospital prices" in a second research [146]. An editorial instructed that pharmacoeconomic decisions should be based on consequence cost, not acquisition costs [145]. Overall, by means of costeffectiveness, studies in the past decade showed that regardless of higher acquisition value, use of intravenous fosphenytoin appeared to be a minimum of equivalent to , if not better than, intravenous phenytoin. This end result suggests that intravenous fosphenytoin may not be more cost-effective than is intravenous phenytoin. Adverse Effects Listen Phenytoin Concentration-Dependent E fects the most typical concentration-dependent phenytoin unwanted side effects are associated to the central nervous system and consist of nystagmus, ataxia, incoordination, diplopia (vestibulo-oculo-cerebellar syndrome), and drowsiness [149]. Some sufferers may experience outstanding unwanted effects at concentrations within the decrease finish of the therapeutic vary, while others could also be free of complaints despite elevated drug concentrations. Although small decreases may fully alleviate complaints, vital dose alterations might dramatically lower serum concentrations, resulting in a recurrence of seizures. Nausea, vomiting, and epigastric pain are often improved by dividing the dose or taking it with meals (or both). In basic, nonetheless, results appear modest when serum concentrations are saved within standard therapeutic ranges, and polypharmacy is prevented [155],[156]. Unfortunately, patients taking phenytoin may suffer from cognitive side effects even when these guidelines are adopted [157]. The in vivo and in vitro cross-reactivity between phenytoin, phenobarbital, and carbamazepine is as excessive as 70% to 80% [161]. The phenytoin rash rate in sufferers who also had a rash to carbamazepine (n = 59) was 57. A more severe dermatologic idiosyncratic reaction is the "hypersensitivity syndrome. Adverse E fects with Long-Term Therapy Long-term administration of phenytoin has been related to gingival hyperplasia [166],[167], hirsutism, pimples, and rash. In the latter report, youthful age and poorer oral hygiene seemed to predispose to the severest stage of gingival involvement [169]. Cerebellar atrophy has been reported after long-term [172],[173] and acute use [174] of excessive doses, although whether the true etiologic agent was phenytoin or the seizures is unclear [175],[176]; single photon emission computed tomography scans could also be a means for early detection [175]. Among different effects of long-term phenytoin therapy are alterations in laboratory values, including reduction in bone mineral density [177], low folate ranges [178], macrocytosis, and decreases in levels of carnitine [179], low-density lipoprotein ldl cholesterol, and apolipoprotein B [180]. Levels of prolactin [181] and apolipoprotein A and A1 [180] enhance, as does high-density lipoprotein cholesterol, although at doses of 100 mg/day, this lipid fraction was unchanged [182]. Phenytoin might decrease levels of free testosterone and enhance its conversion to estradiol [183]. The thyroxine (T4) and free T4 index, total T4 and triiodothyronine (T3), free T4, and free T3 all lower. Increases in serum ranges of thyroid-stimulating hormone [185],[186] may involve protein-binding displacement and induction of mobile metabolism [187]. Phenytoin remedy may suppress immunoglobulin (Ig) production, resulting in decreases in IgG [188],[189] and IgA [188],[190]. Panhypoglobulinemia was reported in a single affected person infected with the human immunodeficiency virus [191]. It is unclear whether these modifications are a direct result of phenytoin or epilepsy [188] or if they occur with any drug with arene oxide intermediates [188],[192]. Teratogenicity "Fetal hydantoin syndrome" was described in 1975 and consisted of progress retardation, microcephaly, psychological retardation, and quite a few "minor" congenital anomalies [193]. One research confirmed an elevated risk for cleft palate within the offspring with phenytoin use throughout pregnancy [195]. Intravenous Administration 1336 Administration of parenteral phenytoin solution is associated with local reactions, including ache and burning at the infusion website, phlebitis, and vessel cording [7],[10],[201]. A distinctive impact of unknown etiology, purple glove syndrome [202], [203], begins with discoloration and progresses to a petechial rash; extreme cases may require surgical intervention. Intravenously administered phenytoin also can lead to cardiovascular complications, corresponding to hypotension, atrial and ventricular conduction depression, and ventricular fibrillation [7]. The major threat components for these complications include preexisting disease, advanced age, and speedy infusion [7],[201]. In sufferers without cardiovascular disease, phenytoin could be administered at 40 to 50 mg/min [205]. Fosphenytoin Concentration-Dependent E fects Intravenous fosphenytoin infusion has a positive facet effect profile [10],[207]. The native reactions associated with administration of parenteral phenytoin resolution (infusion web site pain, phlebitis, and vessel cording) occur considerably less typically with fosphenytoin [10]. Pruritus or tingling appears quickly after an infusion starts, abates quickly when the infusion stops, and may be lowered or abolished by slowing the infusion. Dizziness, somnolence, and ataxia have been noticed with a frequency similar to that after phenytoin infusion [208]. Adverse results have been even less notable after intramuscular fosphenytoin injection [209],[210]. Mild local irritation occurred in solely 5% of 60 sufferers who acquired intramuscular loading doses, even though the quantity of injected resolution was often 15 to 20 mL (mean, 17. Idiosyncratic Reactions, Long-Term Adverse Reactions, Teratogenicity No idiosyncratic reactions are associated particularly with fosphenytoin. As fosphenytoin is used solely on a short-term basis, information about long-term adverse reactions are lacking. Venous irritation associated to intravenous administration of phenytoin versus DeLorenzo R, Sun D.