Continuing Education

Drugs Approved in 2018

Authors: Madison Browning, Pharm.D. Auburn University, Harrison School of Pharmacy

Inna Majdalani, Pharm.D. Auburn University, Harrison School of Pharmacy

Corderra Seay, Pharm.D. Auburn University, Harrison School of Pharmacy

Corresponding Author: Bernie R. Olin, Pharm.D. Associate Clinical Professor and Director Drug Information and Learning Resource Center Harrison School of Pharmacy, Auburn University

Universal Activity #: 0178-0000-19-103-H01-P | 1.5 contact hours (.15 CEUs)

Initial Release Date: December 10, 2019 | Expires: October 1, 2021

Alabama Pharmacy Association | 334.271.4222 | www.aparx.org | [email protected]

Objectives accompanied with nausea, vomiting, light and ● Outline the mechanism of action of new sound sensitivity, and lasting 4 to 72 hours or medications more. It may be accompanied by focal ● Discuss administration and storage neurological symptoms. Frequent migraines information of new medications result in a reduced quality of life, reduced ● Identify the appropriate indications and productivity, medication overuse, and patient populations for the new medications absenteeism. Due to the disabling nature of the ● Describe counseling points for new pain, patients with chronic migraine and high medications frequency of episodic migraine usually receive preventive therapy. However, up to 50% of Introduction: chronic migraine patients discontinue their A variety of new pharmacological agents and conventional preventive therapy due to biological products are being approved by the ineffectiveness or safety concerns, and those FDA each year, with the average of around 30 who continue may settle for suboptimal drugs per calendar year. For instance, 45 drugs response. Preventative therapy may be were approved in 2015, 22 in 2016, and 46 in considered in patients with more than three 2017. Up until the end of August, 33 drugs have headache days per month, headache related been already approved in 2018. Sometimes disability, inability to take Serotonin 5-HT1 they offer entirely new ways to address disease Receptor Agonists (Triptans) or other states, and sometimes they represent vasoconstrictors, and those with infrequent but upgraded, safer or more efficient variances of very severe attacks.3 known medications.1 Following the course of the disease, about This short overview will introduce pharmacists 2.5% of patients with episodic migraine may to several drugs approved in 2018, and progress to chronic migraine per year. summarize their indications, method of Prevention is recommended in all chronic administration, and patient-oriented specifics. It migraine patients and most of frequent episodic also provides concise background information migraine patients. Epidemiologic studies on how these medications fit within current demonstrate that up to 38% of migraine recommendations for specific disease states. sufferers would benefit from preventive The focus is on medications that are more therapy.3 Until now, a few drugs are approved likely to be encountered in general practice, and for prevention of episodic migraine applicable to a variety of patients; the (propranolol, timolol, divalproex sodium or therapeutics encompasses infectious disease, sodium valproate, topiramate) and only one is neurology, and internal medicine. approved for prevention of chronic migraine (onabotulinumtoxin A, or Botox®). However, a Aimovig® (erenumab-aooe): large number of medications are used off-label, Aimovig® (erenumab-aooe) is a new with varying degrees of efficacy. By blocking the monoclonal antibody (MAB) calcitonin gene- action of calcitonin gene-related peptide related peptide receptor antagonist, (CGRP), Aimovig® provides an additional manufactured by Amgen. It received FDA mechanism of pain relief.3 approval in May 2018 for the prevention of Physiologically, neuropeptides, including episodic and chronic migraine in patients over CGRP, are released upon stimulation of the 18 years of age.2 trigeminovascular system. CGRP is a potent Migraine is a frequently encountered and vasodilator, and also exhibits features of a disabling CNS disorder, that involves activation neurotransmitter, with confirmed sites of action of the trigeminovascular system, and manifests on nerve fibers and blood vessels. It is as disabling, usually unilateral headache of established that CGRP plays role in migraine pulsatile character. It is sometimes pathogenesis.4,5

Aimovig® belongs to a class of human muscle cramps (up to 2%). The incidence of monoclonal antibodies; it binds CGRP receptors, adverse drug reactions (ADRs) increased with effectively blocking the signaling associated dose. The risk of neutralizing antibody with nociception and vasodilation. Due to its development is 2.6-6.2%, with unknown clinical relatively large molecular size, Aimovig® cannot consequences, however, due to the fully effectively cross the blood-brain barrier, and humanized nature of this MAB, immunologic exhibits most of its action peripherally, at the potential is minimized, and clinical studies did endings of the trigeminal nerve, or on receptors not demonstrate differences in effectiveness in in the trigeminal ganglion and dura mater. patients with and without neutralizing antibody MABs offer a number of advantages over development.6,8,9,10 conventional pharmacological agents, namely, Aimovig® safety and efficacy was accessed in 3 longer duration of action, specificity and randomized placebo-controlled trials, that efficacy, metabolism by proteolysis, and low enrolled a total of 2,105 patients with episodic probability of drug interactions.4,5,6 and chronic migraine.8,9,10 The longest Due to the protein nature, it is administered documented observation period was six as a 70 mg SQ injection once monthly months. Patients were allowed to continue (abdomen, thigh, or upper arm); some patients using conventional medications for treating may require 140 mg as two successive same- acute migraine, however preventive treatments time injections. It is supplied as a single-dose were discouraged. Reduction in mean monthly prefilled SureClick® autoinjector and a single- migraine days was achieved in all trials, and the dose prefilled syringe. Before administration, results in treatment vs placebo groups are as the solution should be inspected for uniformity follows: up to 3.7 days vs 1.8 days in episodic and discoloration: it is manufactured as clear- migraine population (mean migraine duration 8 to-opalescent, colorless-to-light-yellow solution. days per month), and up to 6.6 days vs 4.2 days Aimovig® should be protected from light and in chronic migraine population (mean migraine stored in the refrigerator but allowed to reach duration 18 days per month). Up to 50% of room temperature prior to injection. Patients participants in episodic and 40% in chronic should be discouraged from shaking the syringe migraine populations reported ≥50% reduction or using any heat source to warm Aimovig® in monthly migraine days.8,9,10 before administration, since it can damage the Price may be a factor in decision-making protein structure and result in dose before initiating treatment. In August 2018 the deterioration.6,7 cost was $345 for Aimovig® 70 mg/ml single No contraindications have been listed by the dose.7 Nonetheless, some estimations predict manufacturer; packaging contains latex, that cost-benefit in combined direct and indirect may be of a concern in an allergic individual. loss-of-productivity costs, and quality of life Due to its mechanism of action that results in a improvement in favor of Aimovig®, with the degree of vasodilation impairment, long-term average treatment period of 2 years.11 safety data is not available in populations at high risk of cardiovascular events, where Epidiolex® (cannabidiol): appropriate vasodilation (coronary, cerebral) Epidiolex® is a cannabinoid derived from the may be compromised. Available safety studies plant Cannabis sativa L.12 Cannabidiol appears did not reveal an increase in cardiovascular risk, as a white to yellow substance after extraction, however, patients overtly suffering from and is insoluble in water.12 On June 25, 2018, ischemic conditions were not included in Epidiolex® was approved by the FDA for use in populations studied at the time of drug two seizure disorders, Lennox-Gastaut approval.6,7 syndrome and Dravet syndrome, in patients Most notable side effects are injection site older than 2 years.13,14 Epidiolex® is the first FDA reaction (6%), constipation (up to 3%) and approved drug containing a component derived

from marijuana.15 Lennox-Gastaut syndrome is should be closely monitored or modified to a rare seizure disorder that appears in reduce risk of toxicity.13 Epidiolex® is primarily individuals between the age of 3 and 5.13,15 metabolized by hepatic enzymes, CYP 3A4 and Most people with the condition will present CYP 2C19, and may interact with inducers and with uncontrollable, frequent tonic seizures. inhibitors of these enzymes as well.13,14 Dravet syndrome is also a rare seizure disorder; Common ADRs (>10%) associated with oral however, this condition is genetic and presents cannabidiol use include: fatigue, diarrhea, skin during the first year of life as frequent febrile rash, weight loss, infections, and sleep disorder. seizures.13,15 Both disorders delay the Some patients may also experience rare development of motor skills and limit adverse reactions such as suicidal ideations, individuals from engaging in typical everyday elevated liver enzymes, and respiratory tasks.13,15 Researchers continue to speculate on dysfunction. Do not use the agent if the patient the exact anticonvulsant mechanism of has a history of hypersensitivity to oral Epidiolex®, but it is known that the agent does cannabidiol or any component of the affect cannabinoid receptors to produce formulation. Monitor AST, ALT, and bilirubin efficacy in seizure disorders.12,13,14 before initiating therapy and throughout Epidiolex® currently is not available for treatment.13 distribution to the consuming public.13 Several studies have validated Epidiolex® Manufacturers are awaiting drug scheduling efficacy in patients with Lennox-Gastaut from the Drug Enforcement Administration syndrome and Dravet syndrome. For Lennox- (DEA) since cannabidiol is a component of Gastaut syndrome, one trial with 121 marijuana, a Schedule I drug.12,15 The participants compared the efficacy of Epidiolex® recommended initial treatment dose for seizure 20 mg/kg/day versus placebo and resulted in a disorders is 2.5 mg/kg twice daily. If the dose is 41% reduction in total seizure frequency tolerated and additional control is required, compared to 14% reduction in placebo. Another may titrate to a maintenance dose of 5 mg/kg trial conducted with 225 participants compared twice daily after one week of initial therapy. 10 mg/kg/day and 20 mg/kg/day Epidiolex Prescribers can also slowly titrate maintenance versus placebo and revealed a 36% reduction in doses to 10 mg/kg twice daily, if needed.12,13,14 the 10 mg/kg/day arm, 38% reduction in the 20 Cannabidiol requires no dosage adjustments for mg/kg/day arm, and 18% reduction in the patients with renal impairment.13,14 However, in placebo arm in total seizure frequency. For the patients with moderate (Child-Pugh class B) or Dravet syndrome, a single randomized, double severe (Child-Pugh class C) hepatic impairment, blind, placebo-controlled trial has been dose adjustment is necessary. Discontinue conducted comparing Epidiolex® 20 mg/kg/day cannabidiol if the patient experiences with placebo in 120 participants. In that trial, hepatotoxicity during therapy.13 Epidiolex® significantly decreased the frequency Oral cannabidiol should be given at the same of convulsive seizures (39% vs 13% reduction; time each day without regard to meals.13 p= 0.01).12 Epidiolex® is an oral solution and should be stored at temperatures between 20°C and 25°C Biktarvy® (bictegravir, emtricitabine, tenofovir (68°F and 77°F). The medication should not be alafenamide): refrigerated or frozen. Also, use contents within Biktarvy® (FDA approved February 7, 2018) is 12 weeks of initially opening the bottle. Be sure a new combination medication for the to use a 1 ml or 5 ml oral syringe when management of HIV-1 infection. Biktarvy® is administering the dose. Epidiolex® may alter made up of the following three medications: the serum concentration of citalopram, bictegravir 50 mg, emtricitabine 200 mg, and cilostazol, clobazam, and clopidogrel.13,14 tenofovir alafenamide 25 mg. Biktarvy® is FDA Furthermore, coadministration of these agents indicated for the treatment of HIV-1 infections

in patients who have no history of antiretroviral the enzyme integrase. NRTIs inhibit the actions therapy (ART) or to replace a current regimen in of HIV RNA-dependent DNA polymerase, patients who have a viral load of <50 copies/mL interrupting the replication of the virus.16,17 of HIV-RNA for at least three months, with no In a double-blind, multicenter, phase 3, history of treatment failure. Biktarvy® is priced randomized controlled non-inferiority trial, at $117.83 per unit, or $3,534.90 for a 30-day including 631 patients, Biktarvy® supply. (bictegravir/emtricitabine/tenofovir The advantage of Biktarvy® is that it is only alafenamide) was compared to Triumeq® dosed once per day as one tablet, taken by (dolutegravir/abacavir/lamivudine) used for mouth. There is no need to refrigerate this initial treatment. Adults who were confirmed to medication, and it may be taken irrespective of have HIV-1 infection, had no history of meals. The most common side effects include antiretroviral therapy, had no documented headache, diarrhea, and nausea. Rare but resistance to the medications, and had plasma serious side effects include lactic acidosis, levels of HIV-1 RNA of 500 copies/mL or greater hepatitis B infection exacerbation, were eligible to enter this study. Patients were hepatomegaly, immune reconstitution randomly assigned to receive one fixed dose, syndrome, acute renal failure, Fanconi daily, of either the Biktarvy® combination syndrome, and renal impairment. (n=314) or the Triumeq® combination (n=315). Patients with severe renal impairment (CrCl The duration of the study was 48 weeks. The <30 mL/min) or severe hepatic impairment study’s primary outcome was the proportion of (Child-Pugh class C) should not take Biktarvy®. patients who had <50 copies/mL of HIV-1 RNA Biktarvy® should not be taken if patients are at week 48 of treatment. The results of the also taking dofetilide or rifampin because of study concluded that Biktarvy® was noninferior drug interactions. Coadministration of dofetilide to Triumeq® regarding the primary outcome, with Biktarvy® will increase the concentration where 92.4% of patients on Biktarvy® met the of dofetilide, increasing the likelihood of a primary outcome and 93% of patients on patient experiencing severe cardiovascular Triumeq® met the primary outcome.18 ADRs, such as Torsades de pointes. In a phase 1b, multicenter, randomized, Coadministration of Biktarvy® with rifampin will double-blind, adaptive, sequential cohort reduce the efficacy of Biktarvy® as rifampin placebo-controlled study, the effect of heavily induces CYP3A4, which is responsible for bictegravir as 10-day monotherapy was the metabolism of Biktarvy®. evaluated in 20 participants. Adults with HIV-1 Monitor patients who are taking Biktarvy® and CD4 counts of >200 cells/μL, HIV-1 RNA closely. Laboratory monitoring should be done between 10,000 and 400,000 copies/mL, and at baseline, evaluating CD4 count, HIV/RNA either treatment naïve or INSTI-naïve were levels, serum creatinine, urinalysis, liver eligible to participate in the study. Patients enzymes, fasting blood glucose and hemoglobin were randomized into a few treatment arms to A1c, pregnancy, and the presence of hepatitis B receive either bictegravir (a different dose per and C viruses. Every three to six months, liver group) or placebo every 24 hours for 10 days. enzymes and fasting blood glucose or HgA1c Seven days after the end of dosing, HIV-1 RNA should be re-evaluated. Urinalysis should be levels were measured to see the effect of conducted annually. bictegravir as monotherapy. A dose-dependent Biktarvy® is made up of an integrase inhibitor response was observed, demonstrating a rapid (bictegravir) and two nucleotide reverse decrease in viral load from baseline, compared transcriptase inhibitors, or NRTIs, (emtricitabine to placebo.19 and tenofovir alafenamide). Integrase inhibitors The Department of Health and Human prevent the HIV RNA from becoming integrated Services Panel on Antiretroviral Guidelines into the human DNA by blocking the function of released a statement this year, adding fixed

dose Biktarvy® as a first-line therapy option for improvement in CD4 levels, a decrease in treatment naïve patients on the basis of the HIV/RNA levels, and any sign of infusion-related previously presented clinical trial results. The reactions.21,22 panel determined that Biktarvy® is suitable for A phase 3, single group, open-label study was most treatment naïve patients with HIV-1 designed to evaluate the role of ibalizumab in infection.20 patients with multidrug-resistant HIV-1 In summary, Biktarvy® is a new, single-tablet, infection. The study included 40 adults with combination medication that has been FDA and multidrug-resistant HIV-1 infection who had a Antiretroviral Guideline approved as a first-line viral load of >1,000 copies/mL. Each patient agent for the treatment of HIV-1 infection in received 2,000 mg of ibalizumab as a loading most patients who are HIV treatment naïve. dose, followed by a maintenance dose of 800 mg of ibalizumab every 14 days for a duration Trogarzo® (ibalizumab-uiyk): of 25 weeks, in combination with the patients’ Trogarzo® (FDA approved March 6, 2018) is a individually optimized background regimens. new injectable monoclonal antibody for the Each patient’s background regimen had to treatment of HIV-1 infection. Trogarzo® include at least one fully active agent. The (ibalizumab-uiyk) acts by binding CD4 T-cells to results demonstrated 43% of patients had a interfere with the post-attachment steps of reduction in HIV-1 RNA viral load to <50 infection, preventing the HIV-1 virus from copies/mL and 50% of patients had a reduction entering the cell. Trogarzo® is used in in HIV-1 RNA viral load to <200 copies/mL.23 combination with other antiretroviral treatment Similarly, in a phase 1b, multicenter, open- in patients who are heavily treatment label, multidose study, safety and antiretroviral experienced and who have multi-drug resistant activity of ibalizumab was evaluated in 19 HIV-1 infections or those who are failing their patients. Patients were eligible to participate if current regimen. they were HIV-1 infected adults with HIV-1 RNA Trogarzo® must be administered via viral loads of >5,000 copies/mL and with a CD4 intravenous infusion of 2,000 mg as a single count of 100-500 cells/mm3. The patients were dose, diluted in normal saline, and infused over randomized into three treatment arms, each of longer than 30 minutes. Maintenance doses are which received different dosing regimens of 800 mg every 14 days, diluted in normal saline, ibalizumab. All three treatment groups and infused over longer than 15 minutes. demonstrated anti-HIV activity by clinically Intravenous lines must be flushed with 30 mL of meaningful reductions in HIV-1 RNA viral load normal saline after each administration. and increases in CD4 counts. While these values Currently, there are no contraindications to were clinically meaningful, none were Trogarzo®, no renal dose adjustments, and no statistically significant. Enough information was hepatic dose adjustments. gathered, however, to move forward to other Trogarzo® is available in a 2 mL vial, phases of clinical trials.24 containing 200 mg/1.33mL, at a cost of According to the Guidelines for the Use of $1,024.06. The cost of an initial treatment dose Antiretroviral Agents in Adults and Adolescents (2,000 mg) is approximately $10,240. The cost Living with HIV, ibalizumab remains classified as of 30 days of treatment as two maintenance an investigational new drug. The guidelines doses is approximately $8,192. recommend its use only in patients who have Common side effects associated with multidrug resistance without fully active ART Trogarzo® include dizziness, skin rash, diarrhea, options, have ongoing detectable viral loads, nausea, and an increase in serum creatinine. and do not have sufficient treatment options to Rare but serious ADRs include immune construct a fully suppressive regimen.25 reconstitution syndrome. Patients taking In summary, Trogarzo® is an injectable Trogarzo® should be monitored for an medication that suppresses HIV-1 infection. It is

a last-line agent, recommended for use in Lokelma® is administered by mixing the patients who have HIV-1 infection that is contents of the package in 3 or more resistant to most combinations of therapies. tablespoons of water and taking it immediately; patients are advised to make sure all of the Lokelma® (sodium zirconium cyclosilicate, dose has been taken and they may use more ZS9): water to finish the contents of the package. It is Lokelma® (sodium zirconium cyclosilicate) is a recommended to use Lokelma® two hours selective potassium-removal agent, before or after any medication, since it is able manufactured by Astra Zeneca. It was approved to temporarily alter the pH of the GI tract and by the FDA in May 2018.26 Lokelma® is a non- affect absorption. In trials, Lokelma® was taken absorbable zirconium silicate potassium binder, with or right before meal.28,29 that preferentially captures potassium (K) ions There are no stated contraindications to the in the gastrointestinal tract, in exchange for use of Lokelma®, but its use in patients with hydrogen and sodium. Presence of other ions constipation, obstruction, and other disorders does not affect its functioning. Bound of motility should be avoided, since it has not potassium cannot be absorbed, and gets been studied in those populations. Lokelma® eliminated in feces, thus reducing potassium poses a risk of edema, due to its sodium levels in the lumen, and reducing the associated content of 400 mg of sodium per 5 g packet. In potassium levels in the blood.27 clinical trials, the frequency of edema ranged Lokelma® is approved for treatment of from 4.5 to 16%. Caution should be exercised in hyperkalemia in adults. Hyperkalemia (K levels patients with sodium or fluid restriction (heart above 5 mEq/L) is a serious complication of failure or renal failure patients); it is advised to heart or kidney failure, that can lead to heart monitor for edema and adjust dietary salt arrhythmia, muscle weakness and paralysis, and intake. Also, hypokalemia developed in 4% of death. Commonly, it develops as a result of patients.27,28,30 reduced renal excretion, metabolic acidosis, use The FDA approval process was based on the of salt substitutes, and concomitant therapy results of one double-blind, placebo-controlled with agents affecting the renin-angiotensin- trial and one open-label trial, enrolling a total of aldosterone system (RAAS) or K-sparing 1,011 patients.1,28,30 Both trials included diuretics.27 ambulatory patients with mild-to-moderate Lokelma® is manufactured as 5 g and 10 g hyperkalemia - severely ill patients were packets for suspension for oral administration, excluded; however, Lokelma® exhibited dose- with the recommended starting dose of 10 g dependent effects with maximal reduction in three times a day, for up to 48 hours. the group of patients with higher K levels (50% Thereafter, 10 g once daily is recommended; achieved reduction to 5.5 mEq/L in 4 hours). the dose may be adjusted once a week based Within 48 hours, 92% of patients achieved on the results of potassium levels in blood; normalization. A small inconsequential rise in average maintenance doses vary from 5 g every plasma bicarbonate was observed in the other day to 15 g daily. The maximum daily treatment group.26-28 dose is 30 g. If potassium levels fall below the Overall, Lokelma® offers a good alternative to desired range, doses should be decreased or other existing potassium-binding agents discontinued. As any oral binder, it does not (sodium polystyrene sulfonate (SPS), produce immediate results, and therefore it is superabsorbent polymer (CLP), and patiromer) not indicated for emergency treatment. In due to high efficacy, relative safety, and clinical trials, it was demonstrated that applicability to patients undergoing treatment Lokelma® starts working after 1 hour, and with renin-angiotensin system inhibitors, which median time to potassium level normalization allows them to continue life-saving therapy was determined around 2.2 hours.27,28,29 while normalizing their serum potassium level.31

As of August 2018, suspension packages were cascade.32,34 Factor Xa inhibitors, rivaroxaban priced at $26.20 per each 5 g or 10 g dose.29 and apixaban, are extremely effective oral anticoagulants and serve a vital role in the Andexxa® (andexanet alfa): treatment and prevention of several Andexxa® is a recombinant variant of human cardiovascular conditions.35,36 However, these factor Xa.32-34 It gained approval from the FDA agents significantly increase an individual’s risk on May 3, 2018 for reversal of anticoagulation for major bleeding and, until Andexxa®, had no from Factor Xa inhibitors, apixaban or antidote to consistently reverse their rivaroxaban in individuals with life threatening effects.35,36 or uncontrolled hemorrhage.32 The agent is Andexxa® is only available as a 100 mg proven effective post apixaban or rivaroxaban intravenous reconstituted solution.32 The administration and is only indicated for those reconstituting and dosing of Andexxa® should Factor Xa inhibitors.32-34 Andexxa® exerts only be completed by a healthcare professional multiple mechanisms to reverse bleeding due to the complexity of the dosing caused by rivaroxaban or apixaban.32,33 It regimen.32,34 Factors to consider when dosing selectively binds and sequesters either the antidote include the specific Factor Xa agent.33,34 Andexxa® also binds and inhibits inhibitor, dose of the Factor Xa inhibitor, and tissue factor pathway inhibitor (TFPI).34 time since last administration of the Factor Xa Inhibition of TFPI leads to increased circulation inhibitor.34 of thrombin and upregulation of the clotting

Andexxa® Dosing Regimen32,33,34 Factor Xa inhibitor Factor Xa inhibitor Last Timing of Last Factor Xa inhibitor Dose administration

< 8 h or unknown > 8 h

Rivaroxaban < 10 mg Low Dose Low Dose

> 10 mg or unknown High Dose

Apixaban < 5 mg Low Dose

> 5mg or unknown High Dose

Low Dose: Administer initial IV bolus 400 mg minutes. Infusion doses should be administered dose at a rate of 30 mg/min followed by a 4 within two minutes of bolus completion.32,33,34 mg/min IV infusion for no more than 120 Andexxa® vials should be stored intact at 2°C minutes. Infusion doses should be administered to 8°C (36°F to 46°F).32,33 It is not appropriate to within two minutes of bolus completion.32,33,34 freeze the vials. Reconstituted vials are stable at High Dose: Administer initial IV bolus 800 mg room temperature for at least eight hours or at dose at a rate of 30 mg/min followed by 8 least 24 hours at 2°C to 8°C (36°F to 46°F). mg/min IV infusion for no more than 120 Reconstituted IV bags are also stable for at least

8 hours; however, only store reconstituted IV Conclusion bags at 2°C to 8°C (36°F to 46°F) for 16 hours or In conclusion, the year 2018 has introduced less. Any unused volume should be discarded. several novel agents that may improve the The price for each 100 mg vial is $3,30032, and quality of life for many patients, suffering from an average treatment regimen could cost over chronic disorders that may be poorly controlled $30,000. with conventional therapies. HIV patients would No drugs interact with Andexxa®.32,33 Also, no benefit from the addition of medications that contraindications exist for the agent.28,29 address different stages of disease progression However, several serious warnings, such as and halt virus resistance development. cardiac arrest, sudden death, thromboembolic Biktarvy® offers a convenient combination risk, and ischemic risks, are associated with the tablet for treatment-naïve patients, and thus agent and should be monitored for at least 30 has a potential to promote adherence while days post administration.32,33,34 The most displaying comparable efficacy. Trogarzo® frequently occurring adverse reaction provides an option for patients who have associated with Andexxa® is infusion site undergone multiple therapies and/or failed to reaction (18%). Individuals may also experience achieve suppression of a highly resistant virus. (1% to 10%) deep vein thrombosis, ischemic Seizure disorders are particularly challenging to stroke, acute myocardial infarction, pulmonary treat while preserving a balance between drug embolism, cardiogenic shock, exacerbation of efficacy and acceptability of side effects, congestive heart failure, urinary tract infection, especially in the pediatric population. pneumonia, and acute respiratory failure.32 No Epidiolex®, a cannabinoid derivative, offers an dose adjustment is required for individuals with opportunity to dramatically decrease frequency renal or hepatic impairment.32,33 of seizures in two rare diseases, especially in In the ANNEXA-4 trial, investigators evaluated patients that are poorly controlled on current the efficacy of andexanet alfa in participants medications, and help promote normal experiencing a life-threatening, acute major neuropsychiatric development. Aimovig® offers bleeding event.34,37 The trial was designed as a an alternative mechanism of preventing multicenter, prospective, open-label, single- episodic and chronic migraine attacks in group, ongoing study. Inclusion criteria for migraine sufferers that may not prefer or participants in the study were: age at least 18 tolerate established agents, with the years, administration of apixaban, rivaroxaban, convenience of once monthly administration. edoxaban, or enoxaparin in the past 18 hours, Lokelma® provides a safe and effective option and acute major bleeding. Trial participants of lowering serum potassium levels for patients were to receive an andexanet alfa bolus over 15 with heart, kidney, and other medical to 30 minutes, followed by a two-hour infusion conditions, that result in dangerously high rises of the drug. The two coprimary outcomes were in serum potassium. Additionally, patients may the percent change in the anti-factor Xa activity continue their current therapy with RAAS and the rate of excellent or good hemostatic inhibitors or K-sparing diuretics, to better efficacy 12 hours after the Andexxa® infusion. control the underlying condition. Finally, a long- Results from 67 patients with an average age of awaited recombinant factor-Xa-inhibitor 77 years was included in the trial. Most of the antidote, Andexxa®, may be life-saving to participants either received rivaroxaban or patients with severe bleeding post consumption apixaban before experiencing major of factor Xa inhibitors, such as apixaban or gastrointestinal or intracranial bleeding. Twelve rivaroxaban. The other new molecular agents hours post administration of Andexxa®, clinical that were approved through August 22, 2018, hemostasis was determined excellent or good are included in the table below. in 79% of patients.37,38

New Drugs Approved in 2018 (through August 23, 2018)1

Drug Name Date Approved Indication

Lutathera® (lutetium Lu 177 1/26/2018 Treatment of gastroenteropancreatic neuroendocrine dotatate) tumors

Biktarvy® (bictegravir, 2/7/2018 Treatment of HIV in treatment-naïve patients embitcitabine, tenofovir alafenamide)

Symdeko® 2/13/2018 Treatment of cystic fibrosis in patients older than 12 (tezacaftor;ivacaftor) years

Erleada® (apalutamide) 2/14/2018 Treatment of certain prostate cancer type with study endpoint

Trogarzo® (ibalizumab-uiyk) 3/6/3018 Treatment of multidrug resistant HIV

Ilumya® (tildrakizumab) 3/20/2018 Treatment of moderate to severe plaque psoriasis certain adults

Tavalisse® (fostamatinib) 4/17/2018 Treatment of thrombocytopenia in adults with persistent or chronic immune thrombocytopenia

Crysvita® (burosumab-twza) 4/17/2018 Treatment of a rare form of rickets

Akynzeo® (fosnetupitant and 4/19/2018 Prevention of acute and delayed nausea and vomiting palonosetron) associated with initial and repeat courses of highly emetogenic cancer chemotherapy

Lucermyra® (lofexidine 5/16/2018 Non-opioid treatment for management of opioid hydrochloride) withdrawal symptoms in adults

Aimoviq® (erenumab-aooe) 5/17/2018 Migraine prevention

Lokelma® (sodium zirconium 5/18/2018 Treatment of hyperkalemia cyclosilicate)

Doptelet® (avatrombopag) 5/21/2018 Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cancer chemotherapy

Palynziq® (pegbaiase-pqpz) 5/24/2018 Treatment of phenylketonuria (PKU)

Olumiant® (baricitinib) 5/31/2018 Treatment of moderately to severely active rheumatoid arthritis

Moxidectin® (moxidectin) 6/13/2018 Treatment of onchocerciasis due to Onchocerca volvulus in patients 12 years and older

Epidiolex® (cannabidiol) 6/25/2018 Treatment of two rare seizure disorders in patients older than 2 years

Zemdri® (plazomicin) 6/25/2018 Treatment of complicated urinary tract infections in adults

Mektovi® (binimetinib) 6/27/2018 Treatment of unresectable or metastatic melanoma

Braftovi® (encorafenib) 6/27/2018 Treatment of unresectable or metastatic melanoma

TPOXX® (tecovirimat) 7/13/2018 Treatment of smallpox

Tibsovo® (ivosidenib) 7/20/2018 Treatment of patients with relapsed or refractory acute myeloid leukemia

Krintafel® (tafenoquine) 7/20/2018 Prevention of relapse of Plasmodium vivax malaria

Orilissa® (elagolix sodium) 7/23/2018 Management of moderate or severe pain from endometriosis

Omegaven® (fish oil 7/27/2018 As a source of calories and fatty acids in pediatric triglycerides) patients with parenteral nutrition-associated cholestasis

Mulpleta® (lusutrombopag) 7/31/2018 Treatment of thrombocytopenia in adults with chronic liver disease who are scheduled for a procedure

Poteligeo® 8/8/2018 Treatment of two rare forms of non-Hodgkin (mogamulizumab-kpkc) lymphoma

Onpattro® (patisiran) 8/10/2018 Treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults

Annovera® (segesterone 8/10/2018 Vaginal contraceptive device for entire year acetate and ethinyl estradiol vaginal system)

Galafold® (migalastat) 8/10/2018 Treatment of Fabry disease

Diacomit® (stiripentol) 8/20/2018 Treatment of Dravet syndrome in patients older than 2 years taking clobazam

Exervate® (cenegermin-bkbj) 8/22/2018 Treatment of neurotrophic keratitis

Takhzyro® (lanadelumab) 8/23/2018 Treatment of types I and II hereditary angioedema

References: 1. Drug Innovation - Novel Drug Approvals for 2018 [Internet]. U S Food and Drug Administration Home Page. Center for Biologics Evaluation and Research; 2018 [cited 2018 Aug21]. Available from: https://www.fda.gov/drugs/developmentapprovalprocess/druginnovation/ucm592464.htm

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