continuing education for pharmacists Volume XXXV, No. 1 New Drugs: Briviact, Cinqair, Nuplazid, Taltz

Mona T. Thompson, R.Ph., PharmD, BCPS

Dr. Mona T. Thompson has no relevant which is thought to contribute to disorders such as Down syndrome, financial relationships to disclose. the anticonvulsant effect. or other neurological diseases such Epilepsy and Partial-Onset as Alzheimer’s Disease. In two out Goal. The goal of this lesson is to Seizures. Epilepsy, defined as the of three cases of epilepsy, the cause provide information on brivarace- occurrence of at least two unpro- is unknown. tam (Briviact®), reslizumab (Cinq- voked seizures separated by at Seizures are classified into two air®), pimavanserin (Nuplazid™) least 24 hours, is one of the most main groups: generalized, which and ixekizumab (Taltz™). common debilitating neurologic affects both hemispheres of the disorders. Data from the Centers brain, and focal, which affects only Objectives. At the completion of for Disease Control and Preven- one hemisphere. Focal seizures are this activity, the participant will be tion (CDC) indicate that about 5.1 also called partial seizures. Focal able to: million people in the United States or partial seizures can be further 1. demonstrate an understand- have a history of epilepsy, with 2.5 classified as simple, complex, and ing of the pathogenesis and patho- million people having active epilep- secondary generalized seizures. physiology of the disease states for sy. A seizure results from an exces- In complex partial seizures, an which these new drugs are indi- sive discharge of cortical neurons impairment of consciousness occurs cated; and is characterized by changes in which is not exhibited with simple 2. select the indication(s), phar- electrical activity as measured by partial seizures. Secondary gen- macologic action(s), clinical appli- the electroencephalogram (EEG). eralized seizures occur when the cations, dosing regimens, mode of Various mechanisms contribute to seizure begins in one hemisphere of administration, and availability for the hyperexcitability that results the brain, but then spreads to both each drug; in seizure activity. These include sides of the brain. These are also 3. recall adverse effects and alterations of ion channels in referred to as secondary general- toxicities, warnings, precautions, neuronal membranes; biochemical ized tonic-clonic seizures (SGTC). contraindications, and significant modification of receptors; changes The indication for use of brivar- drug-drug or drug-food interactions in extracellular ion concentrations; acetam is limited to partial-onset reported for each agent; and and local imbalances between seizures. Therefore, discussion of 4. list important counseling the main neurotransmitters (e.g., other types of seizures will not be information to convey to patients glutamate and gaba-aminobutyric covered in this lesson. and/or their caregivers. acid [GABA]) and neuromodulators Secondary generalized tonic- (e.g., acetylcholine, norepinephrine, clonic seizures are associated with Brivaracetam (Briviact) and serotonin). increased morbidity and mortality, Brivaracetam (Briviact [briv-ee- Not all individuals who experi- including an increased risk of falls, akt]) is a new anticonvulsant ap- ence a seizure will be diagnosed head trauma, and fractures. A low- proved for add-on therapy for the with epilepsy. Other causes of sei- er quality of life has been observed treatment of partial-onset seizures zures include high fever, low blood in patients with SGTC, captured by in patients aged 16 years and older sugar, and alcohol or drug with- lower scores related to work/social with epilepsy. Brivaracetam is drawal. Several conditions that function, energy/fatigue, health a third-generation antiepileptic affect a person’s brain may cause discouragement, emotional well- drug (AED) characterized by high- epilepsy such as stroke, brain being, seizure worry, social isola- affinity binding to synaptic vesicle tumor, traumatic brain injury, tion, health perception, bodily protein 2A (SV2A) in the brain loss of oxygen to the brain, genetic pains, social support, overall health, and overall quality of life. were inadequately controlled with Intractable convulsive seizures are one to two AEDs. In each trial, pa- Table 1 regarded as one of the strongest tients had an eight-week baseline Patient counseling risk factors for sudden unexpected in which patients were required to information for Briviact* death in epilepsy (SUDEP). Most have at least eight partial-onset cases of SUDEP occur during or seizures, followed by a 12-week Inform patients, their caregivers, and/or families: immediately following a seizure, treatment period. Doses between •to read the Medication Guide for and are believed to be related to 50 mg and 200 mg per day were Briviact; apnea or arrhythmias that occur as used in the treatment arm of each •that antiepileptic drugs, including a result of the seizure. It is esti- study with no dose titration. The Briviact, may increase the risk of mated that there are 1.16 cases of percent reduction in partial-onset suicidal thoughts and behaviors; be SUDEP for every 1,000 people with seizure frequency in patients tak- alert for new or worsening signs of epilepsy. Risk factors for SUDEP ing brivaracetam over placebo was depression, changes in mood/behav- include uncontrolled seizures and significant. Additional studies are iors, or thoughts and behaviors about generalized seizures. needed to determine the efficacy self-harm; •that Briviact can cause somnolence, The goals of epilepsy treat- of brivaracetem in comparison to fatigue, dizziness, and gait distur- ment are to control or reduce the levetiracetam, its role in patients bance. These are more likely to occur frequency and severity of seizures, who are levetiracetam treatment early in treatment, but can occur at minimize side effects, and ensure naïve, and its long-term safety any time. Patients should not drive compliance while allowing the profile. or operate machinery until they are patient to live as normal a life as Contraindications, Warn- treatment-experienced and know the possible. Complete suppression of ings, and Precautions. Bri- effects the medication may have on seizures is balanced against toler- varacetam is contraindicated in them; ability of side effects and the pa- patients with a history of a hy- •that hypersensitivity reactions such as bronchospasm and angioedema tient’s quality of life. Patients with persensitivity to the agent, or any can occur and to seek immediate drug-resistant focal epilepsy are at of the inactive ingredients in the medical care should this occur; an increased risk for a number of AED. Bronchospasm and angio- •not to stop Briviact without con- physical and psychosocial complica- edema have been reported with sulting their healthcare provider. It tions. use. As with other AEDs, patients should be slowly withdrawn to reduce According to the National should be monitored for suicidal be- potential for increased seizure fre- Institute for Health and Care havior or ideation; somnolence and quency and status epilepticus; Excellence’s (NICE) 2012 clini- fatigue; and advised not to drive •to notify their healthcare provider cal guidelines, carbamazepine or or operate machinery until they if they become pregnant or intend to become pregnant. Encourage patients lamotrigine should be offered as are treatment-experienced and can to enroll in the North American Anti- first-line treatment in adults with gauge the adverse effects the drug epileptic Drug Pregnancy Registry if newly diagnosed focal seizures. may have on them to complete they become pregnant. If these agents are not tolerated these tasks. Briviact may cause or are unsuitable, levetiracetam, psychiatric adverse reactions, as *A complete list of information is avail- oxcarbazepine, or sodium valproate observed in 13 percent of adult pa- able in the product’s Medication Guide. may be used. If the first AED uti- tients in Phase 3 controlled trials. lized is ineffective, any of these five Brivaracetam should be gradu- also interact with other AEDs. AEDs may be trialed. Adjunctive or ally withdrawn when possible to When prescribed with carbam- add-on treatment may be consid- minimize risk of increased seizure azepime, increased exposure to ered after a second well-tolerated frequency. Briviact is listed as a carbamazepine metabolite may AED is found to be ineffective. Schedule V controlled substance occur affecting tolerability. In this Brivaracetam, the latest AED due to potential for abuse. instance, clinicians should consider to be approved by FDA, has a Adverse Reactions. The most reducing the dose of carbamaze- chemical structure similar to leve- common adverse reactions observed pine. Phenytoin levels should be tiracetam and may be a potentially in clinical trials were somnolence/ closely monitored as well. Brivar- useful treatment for patients with sedation, dizziness, fatigue, and acetem has no added benefit when drug-resistant focal seizures. nausea and vomiting. Fatigue- used with levetiracetam; therefore, Efficacy and Safety. The related adverse reactions appeared the combination should be avoided. effectiveness of brivaracetam as to increase dose-dependently. Administration, Dosing, adjunct therapy in partial-onset Drug Interactions. Increas- and Availability. Briviact is seizures, with or without general- ing the dose of brivaracetam by available as an oral tablet, oral ization, was established in three up to 100 percent (i.e., double the solution (can also be administered fixed-dose, randomized, double- dose) is recommended when used via nasogastric or gastrostomy blind, placebo-controlled, multi- concomitantly with rifampin, a tube), and an injectable solution for center studies. Enrolled patients potent inducer. Brivaracetam can intravenous use. The recommended starting dosage for brivaracetam tion and Prevention Program detail IL-5 antagonist, benralizumab, is is 50 mg twice daily. Based on the a stepwise approach to treating being studied in phase III trials. patient’s response and tolerability, adults and children with asthma. While reslizumab and mepolizum- the dose may be adjusted down to Treatment is individualized based ab are indicated for select patients 25 mg twice daily or up to 100 mg on the severity of the disease, with severe asthma, recommenda- twice daily. However, gradual dose which is classified as either in- tions for use of these agents have escalation is not required. In the termittent or persistent, ranging not yet been incorporated into presence of hepatic impairment, from mild, to moderate or severe. national asthma treatment recom- the recommended starting dose is Reporting of symptoms, nighttime mendations. 25 mg twice daily with a maximum awakening, use of short-acting beta Efficacy and Safety. While dose of 75 mg twice daily. The in- agonists, interference with normal the exact mechanism of action of travenous formulation may be used activity, lung function, and asthma reslizumab has not been estab- at the same dose and frequency exacerbations are utilized to place lished, reduction in blood eosino- when oral administration is not patients into severity levels cor- phil counts was observed in clinical feasible, and is infused over two to responding with treatment recom- trials following the first dose and 15 minutes. Briviact is available as mendations. While most patients was maintained throughout treat- 10 mg, 25 mg, 50 mg, 75 mg, and are able to gain control of asthma ment. However, eosinophils did 100 mg tablets, as well as a 10mg/ symptoms with bronchodilators return to baseline after the treat- mL oral solution and a 50 mg/ and low to moderate doses of in- ment period had ended. Systemic 5 mL single-dose vial for injection. haled corticosteroids, some remain exposure to reslizumab appeared Patient counseling information for uncontrolled. to be unaffected by the presence brivaracetam is summarized in Patients with severe asthma of treatment-emergent anti-resl- Table 1. represent only about 5 to 10 per- izumab antibodies. Literature in cent of asthma patients. Severe animal models suggests that IL-5 Reslizumab (Cinqair) asthma is difficult to treat and and eosinophils are part of an early Reslizumab (Cinqair [sink-ayr’]) is difficult to define due to patient inflammatory reaction at the site an interleukin-5 (IL-5) antagonist presentation, type of inflamma- of tumorigenesis and can promote monoclonal antibody (IgG4 kappa) tory process, comorbidities, and tumor rejection. This conflicts with indicated for add-on maintenance the affects of treatment adherence other animal reports indicating treatment of patients with severe in each patient. Beyond the initial that eosinophils can promote tumor asthma aged 18 years and older, asthma therapies such as bron- growth. Therefore, the malignancy and with an eosinophilic pheno- chodilators and inhaled corticoste- risk in humans from an antibody to type. IL-5 is the major cytokine roids, alternative treatments may IL-5 is unknown. responsible for the growth and be used to target other inflammato- Reslizumab was approved differentiation, recruitment, activa- ry pathways. These include leuko- following four randomized, double- tion, and survival of eosinophils. triene modifiers such as monteku- blind, placebo-controlled studies 16 Eosinophils are among the many last or zafirkulast, or omalizumab to 52 weeks in duration involving cell types (also mast cells, neu- which targets immunoglobulin-E 981 patients. All subjects contin- trophils, macrophages, and lym- (IgE) for severe allergic asthma. ued their current asthma regimen phocytes), along with mediators As previously stated, there are throughout the duration of the such as histamine, leukotrienes, many cells and mediators involved study. The primary endpoint for and cytokines, that are involved in in the inflammatory pathways studies I and II was the frequency inflammation and are a component that lead to asthma. Eosinophilic of asthma exacerbations for each in the pathogenesis of asthma. asthma is a phenotype of asthma patient during the 52-week treat- Therefore, antagonizing IL-5 re- characterized by the persistence of ment period. Patients receiving duces the production and survival eosinophils in the lung and spu- Cinqair experienced significant of eosinophils and offers another tum. The number of eosinophils reductions in the rate of all asthma mechanism for treating asthma. in the blood and bronchial fluid exacerbations compared to placebo. Eosinophilic Asthma. can correlate with asthma sever- The time to first asthma exacerba- Asthma is a chronic disease of the ity. IL-5 has been recognized as tion was also significantly longer airways of the lungs character- the most specific cytokine in the for the groups receiving Cinqair ized by airflow obstruction and eosinophilic lineage and has been and improvements in lung func- airway hyper-responsiveness and identified as a key common denom- tion were observed based on forced inflammation. CDC estimates that inator in inflammatory pathways expiratory volumes (FEV1). 17.1 million adults and 6.3 million in asthma. Contraindications, Warn- children have asthma in the U.S, Mepolizumab was the first IL-5 ings, and Precautions. In clinical which is approximately 8 percent antagonist for the treatment of trials, 6/1028 (0.6 percent) patients of the U.S. population. Guidelines severe asthma with an eosinophilic receiving the reslizumab treatment from the National Asthma Educa- phenotype to be approved. Another dose reported malignancies follow- Administration, Dosing, and a portion of the substantia nigra Table 2 Availability. The recommended located in the midbrain. PD slowly Patient counseling dosing regimen for Cinqair is 3 mg/ progresses and remains relatively information for Cinqair kg by intravenous infusion once asymptomatic until profound deple- every four weeks. Administration tion of substantia nigra pars com- Inform patients: directions call for the weight-based pacta neurons has occurred. Initial •that hypersensitivity reactions, dosage to be further diluted in symptoms may be sensory, but as including anaphylaxis, have occurred 50 mL of 0.9 percent sodium with the administration of Cinqair. the disease progresses the classic Educate patients on the signs and chloride and infused, immediately primary features present as rest- symptoms of hypersensitivity reac- after preparation, over 20 to 50 ing tremor, rigidity, bradykinesia, tions and anaphylaxis, such as skin minutes using an in-line 0.2 micron and postural instability. A positive or mucous involvement, airway com- filter. It should never be given as diagnosis of PD can be made with a promise, and reduced blood pressure; an intravenous push or bolus, and high level of confidence when clini- •that Cinqair does not treat acute must be administered in a health- cal presentation is coupled with a asthma symptoms or acute exacerba- care setting where patients can be positive response to dopaminergic tions. Patients should seek medical monitored throughout the infusion medication. attention if asthma remains uncon- and for a period following infusion. trolled or worsens after initiating PD has been increasingly Cinqair; Healthcare professionals must be recognized as having a multitude •about the risk of malignancies; and prepared to manage anaphylaxis. of non-motor symptoms, including •not to discontinue systemic or in- Reslizumab is available as a 100 psychosis, cognitive impairment haled corticosteroids except under the mg/10 mL solution in single-use and dementia, mood disturbances, direction of a physician. This may be vials. Patient counseling informa- fatigue, apathy, and sleep dis- associated with withdrawal symp- tion for Cinqair is summarized in orders. More than 50 percent of toms and/or unmask conditions previ- Table 2. patients with Parkinson’s disease ously masked by corticosteroid use. have psychosis at some time. Psy- Pimavanserin (Nuplazid) chosis affects up to 75 percent of Nuplazid (noo-plá-zid) is an atypi- patients with Parkinson’s disease ing exposure compared to 2/730 cal antipsychotic indicated for the dementia. The primary psychosis (0.3 percent) in the placebo group. treatment of hallucinations and symptoms expressed in Parkinson’s The observed malignancies were delusions associated with Par- disease are hallucinations and diverse in nature without a cluster- kinson’s disease psychosis. It is a delusions which can cause distress ing of any particular type. Upon selective serotonin 5-HT inverse for both patients and caregivers. initiation of therapy with Cinqair, 2A agonist and, unlike other atypical Psychotic episodes are a challenge patients should not discontinue antipsychotics, lacks dopaminer- for treatment and care, are associ- systemic or inhaled corticosteroids gic, adrenergic, histaminergic, or ated with increased morbidity and abruptly. If appropriate, corticoste- muscarinic affinity. At the time of mortality, and increase the likeli- roids may be gradually decreased writing, a phase II study to evalu- hood of nursing home placement. under the direction of a physician. ate the efficacy of pimavanserin as Best-practice treatment guide- Eosinophils may be involved in treatment for Alzheimer’s disease lines have traditionally recom- the immunological response to psychosis is currently recruiting mended consideration of comorbidi- some helminth infections, and it is patients. ties and reduction of dopaminergic unknown if Cinqair will interfere Parkinson’s Disease Psycho- therapy to treat psychosis. Typical with the immune response against sis. Parkinson’s disease (PD) is a antipsychotics can cause dopamine parasitic infections. Therefore, neurodegenerative disorder with antagonism and worsen Parkinson- patients with pre-existing helminth a clinical presentation including ism and are, therefore, rarely used. infections must be treated prior to motor deficits, and possibly fol- Previously, clozapine was the “gold initiation of Cinqair. lowed by mental deterioration. As standard” treatment for PD psy- Adverse Reactions. In clinical many as one million Americans chosis, with efficacy in treating studies, the most common adverse live with PD, with approximately psychosis without worsening motor reaction noted for Cinqair was oro- 60,000 new diagnoses each year. symptoms demonstrated in ran- pharyngeal pain. Anaphylaxis has Worldwide, it is estimated that domized clinical trials. Clozapine been observed in placebo-controlled seven to 10 million people have PD. selectively binds to D1 mesolim- studies in 0.3 percent of patients, While the incidence of Parkinson’s bic receptors, sparing the striatal and was reported as early as the disease increases with age, a small dopamine D2 receptors, which second dose. The events occurred percentage of people with PD are along with its greater serotoner- during infusion or within 20 min- diagnosed before age 50. gic 5-HT affinity, leads to its utes after completion. 2A/2C Parkinson’s disease is charac- favorable motor profile in PD. It is Drug Interactions. No formal terized by the death of dopaminer- the only antipsychotic medication drug interaction studies have been gic neurons in the pars compacta, that has consistently been found performed with Cinqair. to be efficacious in PD psychosis- improvement. Primary efficacy was dose is 34 mg taken orally as two randomized controlled trials. evaluated based on change from 17 mg tablets once daily. It may be However, its use is limited due to baseline to Week 6 in SAPS-PD taken with or without food. Each the risk of agranulocytosis which total score. With statistical signifi- tablet contains 20 mg of pimavan- can be very dangerous. Quetiapine cance, Nuplazid was superior to serin tartrate, which is equivalent is structurally similar to clozapine placebo in decreasing the frequency to 17 mg of pimavanserin free and is also frequently used for the and/or severity of hallucinations base. No dosage adjustments are treatment of PD psychosis, despite and delusions in patients with required in patients with mild or less consistently supportive data in PD as measured by central, inde- moderate renal impairment. Use clinical trials. Quetiapine also has pendent, and blinded raters using of Nuplazid is not recommended in a greater serotonergic affinity to the SAPS-PD scale. Additionally, patients with severe renal impair-

5-HT2 receptors than to D2 recep- Nuplazid was not found to have an ment or hepatic impairment. tors, which confers a more favor- effect on motor function. able motor profile in PD. Despite Contraindications, Warn- Ixekizumab (Taltz) insufficient evidence for its use in ings, and Precautions. All atypi- Ixekizumab is a humanized IgG4 PD psychosis, quetiapine is often cal antipsychotics carry a black box monoclonal antibody that selective- used as it has an acceptable safety warning from the Food and Drug ly binds with the interleukin-17A profile and doesn’t require frequent Administration (FDA) for use in (IL-17A) cytokine and acts as an blood testing. elderly patients, especially those antagonist. It is indicated for the

In PD, the binding of 5-HT2A with underlying dementia, due treatment of adults with moderate- receptors is increased in the neo- to increased risk of mortality and to-severe plaque psoriasis who are cortex, and visual hallucinations cerebrovascular events. Nuplazid candidates for systemic therapy or are associated with increased num- is not approved for the treatment phototherapy. IL-17A is a naturally bers of 5-HT2A receptors in visual of patients with dementia-related occurring cytokine that is involved processing areas. Post-mortem and psychosis unrelated to hallucina- in normal inflammatory and im- genetic studies suggest that in PD tions or delusions. Nuplazid in- mune responses. Ixekizumab inhib- dementia, dementia with Lewy creases the QT interval and should its the release of proinflammatory bodies and Alzheimer’s disease, be avoided in patients with existing cytokines and chemokines. delusions and hallucinations are QT prolongation, taking other med- Plaque Psoriasis. Psoriasis linked to alterations in the 5-HT ications that are known to increase is a chronic, immune-mediated, system. While other atypical the QT interval or in patients inflammatory disease characterized antipsychotics target the 5-HT2A with risk factors for prolonged QT by recurrent exacerbations and system with varying levels, pima- interval, such as hypokalemia and remissions of thickened, erythema- vanserin, with its high selectivity hypomagnesemia. tous, and scaling plaques. Plaque of 5-HT2A, was developed to provide Adverse Reactions. The most psoriasis, also called psoriasis vul- antipsychotic benefits without the common adverse reactions observed garis, is seen in 90 percent of pso- adverse effects of current atypical in six-week, placebo-controlled tri- riasis patients. Lesions are usually antipsychotics. als include peripheral edema and erythematous, red-violet in color, Efficacy and Safety. The confusional state. It is important to at least 0.5 cm in diameter, well de- efficacy of Nuplazid was demon- note the short study period of six marcated, and covered with silver strated in a six-week, randomized, weeks and, thus, the ability to as- flaking scales. They may appear as placebo-controlled, parallel group sess for incidence for other adverse single lesions in predisposed areas study. Study patients had a diag- events that are commonly associ- such as knees or elbows, or gen- nosis of PD with psychotic symp- ated with atypical antipsychotics. eralized over a large body surface toms warranting antipsychotic Drug Interactions. Strong area. Associated lesion pruritus treatment, but without dementia. CYP3A4 inhibitors may reduce may be severe, and lesions may Patients were required to have a the metabolism of Nuplazid. It is cause physical debilitation or social Mini-Mental State Examination recommended to reduce the dose isolation. Psoriatic arthritis (PsA) (MMSE) score >/= 21 and be able of Nuplazid by half when taking can be progressive and destructive to self report symptoms. The PD- with a strong CYP3A4 inhibitor involving both psoriatic lesions and adapted Scale for the Assessment such as itraconazole, ketoconazole, inflammatory arthritis-like symp- of Positive Symptoms (SAPS-PD) clarithromycin, and indinavir. toms leading to impaired function was used to evaluate the efficacy Increased doses of Nuplazid may be and physical deformities. Psoriasis of Nuplazid 34 mg. Each item is required when taken concomitantly is classified as mild, moderate, or scored on a scale of 0-5; therefore, with a strong CYP3A4 inducer severe, and is based on affected the total score can range from 0 such as rifampin, carbamazepine, body surface area and Psoriasis to 45 with higher scores reflect- phenytoin, and St. John’s wort. Area and Severity Index (PASI) ing greater severity of illness. A Administration, Dosing, and measurements. negative change in score indicates Availability. The recommended The pathophysiology of pso- steroids and moisturizers, and may etanercept 50 mg twice weekly on Table 3 lead to combination phototherapy sPGA and PASI scores during the Patient counseling and/or systemic therapy. Systemic 12-week treatment period. Patients information for Taltz* therapy with biologic response who were responders at week 12 in modifiers (BRMs) is considered in Trial 1 and Trial 2 were then ran- Inform patients and caregivers: moderate-to-severe psoriasis when domized to receive an additional •to read the Medication Guide for other systemic therapies are inad- 48 weeks of an 80 mg every four Taltz; •on proper subcutaneous injection equate or contraindicated. Prior to weeks maintenance dose of Taltz technique, including aseptic tech- the approval of Taltz (tol[t]s) which or placebo to evaluate the mainte- nique, and how to use the autoinjec- targets IL-17, available BRMs nance and durability of response. tor or prefilled syringe correctly; included adalimumab, a monoclonal Contraindications, Warn- •to store Taltz in the refrigerator; to TNF-alpha antibody; etanercept, a ings, and Precautions. Taltz is remove the syringe from the refrig- fusion protein that binds to TNF- contraindicated in patients with erator and allow it to reach room alpha; infliximab, a chimeric mono- a previous serious hypersensitiv- temperature prior to injection; to clonal antibody directed to TNF- ity reaction, such as anaphylaxis, inject the full amount (1 mL) pro- alpha; alefacept, a fusion protein to ixekizumab or to any of the viding 80 mg of Taltz; and to rotate injection sites (upper arms, thighs, or that binds to CD2 on T cells; and excipients. Serious hypersensitiv- any quadrant of abdomen); ustekinumab, an IL-12/23 monoclo- ity reactions have occurred with •that if a dose is missed, it should nal antibody. use, including angioedema and be administered as soon as possible The cytokine IL-17A promotes urticaria. Taltz may increase the followed by resumption of dosing at joint inflammation and damage by risk of infection. In clinical trials, regular scheduled time; triggering the activation of immune upper respiratory tract infections, •that Taltz may lower the ability of cells, inducing proinflammatory cy- oral candidiasis, conjunctivitis, their immune system to fight infec- tokines and chemokines. Increased and tinea infections occurred more tions, to communicate any history of numbers of IL-17A-producing cells frequently in the Taltz group than infections, and contact the healthcare provider if they develop any symp- are present in the peripheral blood, in the placebo group. All patients toms of infection; and synovial tissue and fluid, and skin should be evaluated prior to initiat- •to seek immediate medical attention plaques of patients with PsA. Ixeki- ing Taltz therapy and should not if they experience any symptoms of zumab, the first IL-17A antagonist, receive Taltz if he/she has an active serious hypersensitivity reactions. represents an emerging targeted TB infection or untreated latent approach to plaque psoriasis. TB infection. Crohn’s disease and *A complete list of information is avail- Efficacy and Safety. Three ulcerative colitis, including exacer- able in the product’s Medication Guide. multicenter, randomized, double- bations, also occurred at a greater

blind, placebo-controlled trials en- frequency in the Taltz group com- rolled over 3800 subjects 18 years of pared to placebo. It is also recom- riasis involves cutaneous inflam- age and older with plaque psoriasis mended that patients complete all matory T-cell-mediated activation who met criteria for disease sever- age-appropriate immunizations by surface proteins and antigen- ity and were candidates for photo- prior to treatment with Taltz. presenting cells. Activated T-cells therapy or systemic therapy. In all Adverse Reactions. Adverse migrate from lymph nodes and the three trials, subjects were random- reactions, that occurred at a rate of bloodstream into skin, and secrete ized to either placebo or Taltz at a at least 1 percent and at a higher cytokines such as interferon-gam- dose of 80 mg every two weeks for rate in the Taltz group than in the ma and interleukin-2 that result in 12 weeks, following a 160 mg initial placebo group during the 12-week pathologic changes. Local kerati- dose. In two of the three trials, an study period of pooled clinical tri- noctyes and neutrophils produce active comparator arm was included als, include injection site reactions, other cytokines such as tumor in which subjects were also random- upper respiratory tract infections, necrosis factor-alpha (TNF-alpha) ized to receive etanercept 50 mg nausea, and tinea infections. and interleukin-8. T-cell production twice weekly (U.S. approved dose) Adverse reactions that occurred and activation result in keratino- for 12 weeks. The coprimary ef- at rates less than 1 percent in the cyte proliferation. Research has ficacy endpoints were proportion of Taltz group and more frequently revealed a significant genetic com- patients achieving a static Physi- than in the placebo group dur- ponent to the disease. cian Global Assessment (sPGA) ing the 12-week induction period Goals of treatment include score of 0 or 1 (clear or minimal) included rhinitis, oral candidiasis, minimizing or eliminating skin and 75 percent or greater improve- urticaria, influenza, conjunctivitis, lesions, alleviating pruritus, reduc- ment in PASI score at week 12. An inflammatory bowel disease and ing flare-ups, treating co-morbid integrated analysis of the U.S. sites angioedema. conditions, and avoiding adverse in the two active comparator stud- Drug Interactions. The use of effects. Based on disease severity ies using etanercept resulted in live vaccinations should be avoided and treatment response, treat- Taltz demonstrating superiority to in patients being treated with ment algorithms begin with topical Taltz. The formation of CYP450 en- zymes can be altered by increased levels of certain cytokines during chronic inflammation. Therefore, as Taltz antagonizes IL-17A, it may result in normalized levels of CYP450 enzymes. It is recom- mended that upon initiation or discontinuation of Taltz in patients receiving concomitant drugs which are CYP450 substrates, to increase monitoring, especially in medica- tions with a narrow therapeutic index. Administration, Dosing, and Availability. Taltz is available as an 80 mg/mL single-dose autoin- jector or a pre-filled syringe, and is packaged with detailed instruc- tions on how to prepare and admin- ister either product. Patients may self-administer the injection after receiving training. Taltz is admin- istered by subcutaneous injection at the recommended dose of 160 mg (two 80 mg injections) at initia- tion (week 0), followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12; then 80 mg every four weeks. Patient coun- seling information for ixekizumab may be found in Table 3.

The author, the Ohio Pharmacists Founda- tion and the Ohio Pharmacists Association disclaim any liability to you or your patients resulting from reliance solely upon the infor- mation contained herein. Bibliography for additional reading and inquiry is available upon request.

This lesson is a knowledge-based CPE activity and is targeted to pharmacists in all practice settings. Disclosure. The OPF trustees and other indi- viduals responsible for planning OPF continuing pharmacy education activities have no relevant financial relationships to disclose.

Program 0129-0000-17-001-H01-P Release date: 1-15-17 Expiration date: 1-15-20 CPE Hours: 1.5 (0.15 CEU)

The Ohio Pharmacists Foundation Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Please print. Program 0129-0000-17-001-H01-P continuing education quiz 0.15 CEU Name______New Drugs: Briviact, Cinqair, Nuplazid, Address______Taltz City, State, Zip______

1. Brivaracetam is indicated for which of the following types of Email______seizures? a. Absence c. Partial-onset NABP e-Profile ID______Birthdate______(MMDD) b. Generalized d. All of the above Return quiz and payment (check or money order) to 2. Brivaracetam is structurally similar to which of the following Correspondence Course, OPA, antiepileptic drugs? 2674 Federated Blvd, Columbus, OH 43235-4990 a. Carbamazepine c. Levetiracetam b. Valproic acid

3. The maximum dose of brivaracetam is 75 mg twice daily in 8. Pimavanserin is indicated in patients with Parkinson’s dis- the patients with: ease with which of the following? a. hepatic impairment. a. Dementia c. Confusion b. renal impairment. b. Hallucinations d. Cognitive impairment c. concomitant rifampin use. 9. Parkinson’s disease is characterized by loss of neurons se- 4. Reslizumab is indicated for: creting which of the following? a. focal seizures. a. Dopamine c. Norepinephrine b. Parkinson’s disease psychosis. b. Serotonin c. severe asthma with allergic (IgE) phenotype. d. severe asthma with eosinophilic phenotype. 10. Pimavanserin’s unique mechanism of action is due to its selectivity for which of the following receptors? 5. Patients taking reslizumab should be counseled on which of a. Muscarinic c. Adrenergic the following safety concerns? b. Histaminic d. Serotonin 5-HT2A a. Risk of malignancy b. Fatigue and potential for inability to drive 11. The most common adverse reactions in placebo- c. Reduced ability to fight infection controlled clinical trials with pimavanserin included: a. fatigue and dizziness. 6. The most common adverse reaction observed in placebo-con- b. peripheral edema and confusional state. trolled clinical trials with reslizumab was: c. increased infections and malignancies. a. anaphylaxis. c. oropharyngeal pain. b. URI. d. parasitic infections. 12. Ixekizumab treats plaque psoriasis by antagonizing which of the following cytokines? 7. After the initial dose, reslizumab may be given by intrave- a. Interleukin-17A c. Interleukin-12/23 nous push. b. TNF-alpha d. Interleukin-5 a. True b. False 13. In clinical trials, ixekizumab increased risk of all of the following EXCEPT: a. tinea infections. c. ulcerative colitis. Completely fill in the lettered box corresponding to b. Crohn’s disease. d. malignancies. your answer. 1. [a] [b] [c] [d] 6. [a] [b] [c] [d] 11. [a] [b] [c] 14. Patients taking ixekizumab should be counseled on all of 2. [a] [b] [c] 7. [a] [b] 12. [a] [b] [c] [d] the following EXCEPT: 3. [a] [b] [c] 8. [a] [b] [c] [d] 13. [a] [b] [c] [d] a. rotate injection sites (upper arms, thighs, abdomen). 4. [a] [b] [c] [d] 9. [a] [b] [c] 14. [a] [b] [c] [d] b. store at room temperature. 5. [a] [b] [c] 10. [a] [b] [c] [d] 15. [a] [b] [c] c. administer the full amount 80 mg/mL. d. administer missed doses as soon as possible.  I am enclosing $10 (member); $15 (nonmember) for this month’s quiz made payable to: Ohio Pharmacists 15. The most common adverse reactions in placebo- Association. controlled clinical trials with ixekizumab included: a. fatigue and dizziness. 1. Rate this lesson: (Excellent) 5 4 3 2 1 (Poor) b. peripheral edema and confusional state. 2. Did it meet each of its objectives?  yes  no c. injection site reactions and upper respiratory tract infec- If no, list any unmet______tions. 3. Was the content balanced and without commercial bias?  yes  no If no, why?______4. Did the program meet your educational/practice needs?  yes  no To receive CPE credit, your quiz must be received no later than 5. How long did it take you to read this lesson and complete the January 15, 2020. A passing grade of 80% must be attained. CPE quiz? ______credit for successfully completed quizzes will be uploaded to the CPE 6. Comments/future topics welcome. Monitor. CPE statements of credit can be printed from the CPE Moni- tor website. Send inquiries to [email protected]. january 2017