2.1 Important Administration Instructions

KYNMOBI is for sublingual administration only.

Dose initiation should be supervised by a healthcare provider [see Dosage and Administration (2.3)].

KYNMOBI must be administered whole. Do not cut, chew, or swallow KYNMOBI. KYNMOBI will disintegrate in about 3 minutes.

2.2 Dosing Information

The dose range for KYNMOBI is 10 mg to 30 mg per dose, administered sublingually, as needed, for the acute, intermittent treatment of “off” episodes.

Doses should be separated by at least 2 hours. If a single dose of KYNMOBI is ineffective for a particular “off” episode, a second dose should not be given for that “off” episode. The efficacy or safety of administering a second dose for a single “off” episode has not been studied.

Do not administer more than 5 doses per day.

The maximum single dose of KYNMOBI is 30 mg.

2.3 Dose Titration

The initial dose is 10 mg. Dose initiation should occur when the patient is in an “off” state and in a setting where a healthcare provider can monitor blood pressure and pulse. In clinical studies of KYNMOBI, the “off” state was achieved by instructing patients to not take their regular morning dose of carbidopa/levodopa or any other adjunctive Parkinson's disease medications, and to take their last dose of carbidopa/levodopa and any other adjunctive Parkinson's disease medications no later than midnight the night before [see Clinical Studies (14)].

If the patient tolerates the 10 mg dose, and responds adequately, the starting dose should be 10 mg, used on an as-needed basis, up to 5 times per day, to treat “off” episodes. If the dose is tolerated but the response is insufficient, the patient's usual Parkinson's disease medications should be resumed and up-titration with KYNMOBI continued generally within 3 days. Increase dosage by increments of 5 mg and assess response. Continue to titrate in a similar manner, under the supervision of a healthcare provider, until an effective and tolerable dose is achieved [see Dosage and Administration (2.2) and Clinical Studies (14)].

5.1 Nausea and Vomiting

Patients taking KYNMOBI may experience nausea and vomiting when administered at recommended doses. Treatment with the antiemetic trimethobenzamide may be considered to pretreat or treat nausea and/or vomiting [see Dosage and Administration (2.1)].

In two clinical studies, KYNMOBI was titrated in an identical, open-label manner. In Study 1 [see Clinical Studies (14)] pretreatment with trimethobenzamide was a requirement during titration, while in a second, open-label study [NCT02542696] pretreatment was not a requirement in a subpopulation (n=176/449). In Study 1, treatment with the antiemetic trimethobenzamide, 300 mg by mouth three times daily, was required beginning 3 days before starting KYNMOBI. During the titration phase of Study 1, nausea was reported as an adverse reaction by 21% of patients treated with KYNMOBI, while vomiting was reported as an adverse reaction by 4% of patients treated with KYNMOBI. In the second open-label safety study, nausea and vomiting was reported as an adverse reaction by 13% and 1% of patients, respectively, who did not utilize an antiemetic as pretreatment during dose titration with KYNMOBI.

During the maintenance phase of Study 1, nausea was reported as an adverse reaction by 28% of patients treated with KYNMOBI, compared with 4% of patients who received placebo. During the maintenance phase of Study 1, vomiting was reported as an adverse reaction by 7% of patients treated with KYNMOBI, compared with 0% of patients who received placebo. Nausea or vomiting was the reason for withdrawal from the study in 2% of patients treated with KYNMOBI during the maintenance phase.

Concomitantly administered antiemetic drugs other than trimethobenzamide have not been studied. 5HT3 antagonist antiemetics are contraindicated [see Contraindications (4)]. Antiemetics with anti-dopaminergic actions (e.g., haloperidol, chlorpromazine, promethazine, prochlorperazine, metoclopramide) have the potential to worsen symptoms in patients with Parkinson's disease and should be avoided [see Drug Interactions (7.4)].

5.2 Falling Asleep During Activities of Daily Living and Somnolence

Patients treated with dopaminergic medications, including apomorphine, have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event.

During the titration phase of Study 1, somnolence was reported as an adverse reaction in 11% of patients treated with KYNMOBI. During the maintenance phase of Study 1, somnolence was reported as an adverse reaction in 13% of patients treated with KYNMOBI, compared with 2% of patients who received placebo.

Prescribers should reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.

Before initiating treatment with KYNMOBI, advise patients of the risk of drowsiness and ask them about factors that could increase the risk with KYNMOBI, such as concomitant sedating medications and the presence of sleep disorders. If a patient develops significant daytime sleepiness or falls asleep during activities that require active participation (e.g., conversations, eating, etc.), KYNMOBI should ordinarily be discontinued. If a decision is made to continue KYNMOBI, patients should be advised not to drive and to avoid other potentially dangerous activities. There is insufficient information to determine whether dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

5.3 Hypersensitivity

Oral soft tissue swelling (lips, tongue, gingiva, and mouth) was reported as an adverse reaction in 15% of patients treated with KYNMOBI during the maintenance phase of Study 1, compared with 0% of patients who received placebo; 11% of patients discontinued KYNMOBI because of this event.

Swelling of the face, oral allergy syndrome, hypersensitivity, or urticaria were reported as adverse reactions in 6% of patients treated with KYNMOBI during the maintenance phase of Study 1, compared with 0% of patients who received placebo; 4% of patients discontinued KYNMOBI because of this event.

It is not known whether these events are related to apomorphine, sodium metabisulfite, or another KYNMOBI excipient.

KYNMOBI rechallenge is not generally recommended after discontinuation as oral adverse reactions may recur and may be more severe than the initial reaction.

5.4 Syncope/Hypotension/Orthostatic Hypotension

KYNMOBI may cause syncope, hypotension, or orthostatic hypotension. During the titration phase of Study 1, syncope, pre-syncope, hypotension, or orthostatic hypotension were reported as adverse reactions in 4% of patients. During the maintenance phase of Study 1, syncope, pre-syncope, hypotension, or orthostatic hypotension were reported as adverse reactions in 2% of patients treated with KYNMOBI, compared with 0% of patients who received placebo.

During the maintenance phase of Study 1, systolic orthostatic hypotension (reduction of 20 mmHg or more in standing minus supine/sitting systolic blood pressure) or diastolic hypotension (10 mmHg or more for standing minus supine/sitting diastolic blood pressure) occurred in 43% of patients treated with KYNMOBI, and in 36% of patients who received placebo.

Patients treated with KYNMOBI should receive an assessment for hypotension/orthostatic hypotension, especially if they have a history of hypotension or cardiovascular disease, or if they are currently using antihypertensive medication. Inform patients of the risk of orthostatic hypotension.

The hypotensive effects of KYNMOBI may be increased by the concomitant use of alcohol, antihypertensive medications, and vasodilators (especially nitrates). Patients should avoid alcohol when using KYNMOBI [see Drug Interactions (7.3), Clinical Pharmacology (12.3)]. Patients taking KYNMOBI should lie down before and after taking sublingual nitroglycerin [see Drug Interactions (7.2), Clinical Pharmacology (12.3)].

Monitor patients taking concomitant antihypertensive medications for hypotension and orthostatic hypotension [see Drug Interactions (7.2, 7.3)].

5.5 Oral Mucosal Irritation

During the titration phase of Study 1, oral mucosal ulceration or stomatitis were reported as adverse reactions in 2% of patients treated with KYNMOBI. During the maintenance phase of Study 1, oral mucosal ulceration or stomatitis were reported as adverse reactions in 7% of patients treated with KYNMOBI, compared with 0% of patients who received placebo [see Adverse Reactions (6.1)].

During the titration of Study 1, oral soft tissue pain or paresthesia were reported as adverse reactions in 2% of patients treated with KYNMOBI. During the maintenance phase of Study 1, oral soft tissue pain or paresthesia were reported as adverse reactions in 13% of patients treated with KYNMOBI, compared with 2% of patients who received placebo.

In general, oral mucosal irritation reactions were mild to moderate in severity, and usually resolved with treatment discontinuation.

KYNMOBI rechallenge is not generally recommended after discontinuation as oral adverse reactions may recur and be more severe than the initial reaction.

Hypersensitivity adverse reactions may also occur during treatment with KYNMOBI [see Warnings and Precautions (5.3)].

5.6 Falls

Patients with Parkinson's disease are at risk of falling because of underlying postural instability, possible autonomic instability, and syncope caused by the blood pressure-lowering effects of the drugs used to treat Parkinson's disease [see Clinical Pharmacology (12.2)]. KYNMOBI might increase the risk of falling by simultaneously lowering blood pressure and altering mobility [see Warnings and Precautions (5.4)].

During the titration period of Study 1, falls were reported as an adverse reaction in 4% of patients treated with KYNMOBI. During the maintenance period of Study 1, falls were reported as an adverse reaction in 6% of patients treated with KYNMOBI, compared with 2% of patients who received placebo.

5.7 Hallucinations/Psychotic-Like Behavior

During the maintenance phase of Study 1, hallucinations, delusions, disorientation, or confusion were reported as adverse reactions in 6% of patients treated with KYNMOBI, compared with 2% of patients who received placebo. No patient developed hallucinations or psychotic-like behavior during the titration phase.

A total of 4% of patients treated with KYNMOBI discontinued treatment because of disorientation, confusional state, or delusions, compared with 2% of patients who received placebo.

Postmarketing reports with subcutaneous apomorphine indicate that patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior after starting or increasing the dose of apomorphine. Other drugs prescribed to improve the symptoms of Parkinson's disease can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of one or more of a variety of manifestations, including paranoid ideation, delusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium.

Patients with a major psychotic disorder should ordinarily not be treated with apomorphine because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of KYNMOBI [see Drug Interactions (7.4)].

5.8 Hemolytic Anemia

Hemolytic anemia requiring hospitalization has been reported with apomorphine treatment in the postmarketing setting. Many of the reported cases included a positive direct antiglobulin test (Coombs test), suggesting a potential immune-mediated hemolysis. Severe anemia, angina, and dyspnea have occurred with hemolytic anemia. Some patients were treated with high dose glucocorticoids or blood transfusions. Hemolytic anemia can appear at any time after apomorphine treatment. If a patient develops anemia while taking KYNMOBI, consider a workup for hemolytic anemia. If hemolytic anemia occurs, consider discontinuing KYNMOBI treatment.

5.9 Impulse Control/Compulsive Behaviors

Case reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, and other intense urges and the inability to control these urges while taking one or more medications, including KYNMOBI, that increase central dopaminergic tone. In some cases, although not all, these urges were reported to have stopped when the dose was reduced, or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, binge eating or other urges while being treated with KYNMOBI. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking KYNMOBI.

5.10 Withdrawal-Emergent Hyperpyrexia and Confusion

A symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, elevated serum creatine kinase, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy.

5.11 QTc Prolongation and Potential for Proarrhythmic Effects

At exposures achieved with therapeutic doses of subcutaneous apomorphine, a dose-related prolongation of QTc has been observed [see Clinical Pharmacology (12.2)]. Although the extent of the exposure and the Cmax of apomorphine are lower following the maximum recommended dose of KYNMOBI (30 mg) than following the maximum recommended dose of subcutaneous apomorphine (6 mg), QTc prolongation with KYNMOBI cannot be excluded.

Drugs that prolong the QTc interval have been associated with torsades de pointes and sudden death. The relationship of QTc prolongation to torsades de pointes is clearest for larger increases (20 msec and greater), but it is possible that smaller QTc prolongations may also increase risk, or increase it in susceptible individuals, such as those with hypokalemia, hypomagnesemia, bradycardia, concomitant use of other drugs that prolong the QTc interval, or genetic predisposition (e.g., congenital prolongation of the QT interval). Although torsades de pointes has not been observed in association with the use of KYNMOBI at recommended doses in clinical studies, experience is too limited to rule out an increased risk. Palpitations and syncope may signal the occurrence of an episode of torsades de pointes.

The risks and benefits of KYNMOBI treatment should be considered prior to initiating treatment with KYNMOBI in patients with risk factors for prolonged QTc.

5.12 Fibrotic Complications

Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, and cardiac valvulopathy have been reported in some patients treated with ergot-derived dopaminergic agents. While these complications may resolve when the drug is discontinued, complete resolution does not always occur. Although these adverse reactions are believed to be related to the ergoline structure of these dopamine agonists, whether other, non-ergot-derived dopamine agonists, such as KYNMOBI, can cause these reactions is unknown.

5.13 Priapism

Apomorphine may cause prolonged painful erections in some patients. Severe priapism may require surgical intervention.

5.14 Retinal Pathology in Albino Rats

In a 2-year carcinogenicity study of apomorphine in albino rat, retinal atrophy was detected at all subcutaneous doses tested (up to 0.8 mg/kg/day or 2 mg/kg/day in males or females, respectively). Retinal atrophy/degeneration has been observed in albino rats treated with other dopamine agonists for prolonged periods (generally during 2-year carcinogenicity studies). Retinal findings were not observed in a 39-week subcutaneous toxicity study of apomorphine in monkey at doses up to 1.5 mg/kg/day. The clinical significance of the finding in rat has not been established but cannot be disregarded because disruption of a mechanism that is universally present in vertebrates (e.g., disk shedding) may be involved.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

KYNMOBI safety data presented below is derived from a randomized, double blind, placebo-controlled study in patients with Parkinson's disease (Study 1) [see Clinical Studies (14)]. Study 1 included a titration phase, in which 141 patients received at least one dose of KYNMOBI, followed by a placebo-controlled 12-week maintenance phase. The mean age of patients in Study 1 was 63 years (range 43 to 86 years); 63% of patients were male, and 93% were Caucasian.

The most common adverse reactions (incidence at least 10% in patients treated with KYNMOBI and with an incidence greater than placebo) were nausea, oral/pharyngeal soft tissue swelling, oral/pharyngeal soft tissue pain and paraesthesia, dizziness, and somnolence.

Adverse reactions led to discontinuation of KYNMOBI in 9% of patients in the titration phase, and 28% of patients in the maintenance phase, compared with 7% of patients on placebo (in the maintenance phase). The most common adverse reactions leading to discontinuation during the maintenance phase were oral/pharyngeal soft tissue swelling, oral mucosal erythema, and nausea/vomiting.

Table 1 presents the adverse reactions that occurred in at least 5% of patients treated with KYNMOBI during the maintenance phase of Study 1, and with an incidence greater than in patients who received placebo.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of apomorphine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hematologic and Lymphatic Systems: Hemolytic anemia [see Warnings and Precautions (5.8)].

7.1 5HT3 Antagonists

Based on reports of profound hypotension and loss of consciousness when subcutaneous apomorphine was administered with ondansetron, the concomitant use of KYNMOBI with 5HT3 antagonists, including antiemetics (e.g., ondansetron, granisetron, palonosetron) and alosetron, is contraindicated [see Warnings and Precautions (5.4)].

7.2 Antihypertensive Medications and Vasodilators

In a study of healthy subjects, concomitant administration of 0.4 mg sublingual nitroglycerin with subcutaneous apomorphine caused greater decreases in blood pressure than with subcutaneous apomorphine alone [see Clinical Pharmacology (12.3)].

Patients taking KYNMOBI should lie down before and after taking sublingual nitroglycerin [see Warnings and Precautions (5.4)].

7.3 Alcohol

In a study of healthy subjects, concomitant administration of high-dose (0.6 g/kg) or low-dose (0.3 g/kg) ethanol with subcutaneous apomorphine caused greater decreases in blood pressure than with subcutaneous apomorphine alone [see Clinical Pharmacology (12.3)].

Patients should avoid drinking alcohol after using KYNMOBI [see Warnings and Precautions (5.4)].

7.4 Dopamine Antagonists

Since KYNMOBI is a dopamine agonist, it is possible that concomitant use of dopamine antagonists, such as the neuroleptics (e.g., phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of KYNMOBI. Antiemetics with anti-dopaminergic actions should be avoided [see Warnings and Precautions (5.1)]. Patients with major psychotic disorders receiving neuroleptics should be treated with dopamine agonists only if the potential benefits outweigh the risks [see Warnings and Precautions (5.7)].

7.5 Drugs Prolonging the QT/QTc Interval

Caution should be exercised when prescribing KYNMOBI concomitantly with drugs that prolong the QT/QTc interval [see Warnings and Precautions (5.11) and Clinical Pharmacology (12.2)].

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of KYNMOBI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In Study 1, 78 patients below 65 years of age and 63 patients 65 years of age or older received at least one dose of KYNMOBI. Clinical experience with subcutaneous use of apomorphine has shown that the following adverse reactions were reported more frequently in patients 65 years of age or older compared to patients less than 65 years of age: confusion; hallucinations; serious adverse reactions (life-threatening events or events resulting in hospitalization and/or increased disability); falls (experiencing bone and joint injuries); cardiovascular events; respiratory disorders; gastrointestinal events; and discontinuation of treatment as a result of one or more adverse reactions.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Renal Impairment

Avoid use of KYNMOBI in patients with severe and end-stage renal disease (ESRD) (CLcr <30 mL/min). No dosage adjustment is required for patients with mild or moderate renal impairment. However, because of a potential for increased exposure, titrate KYNMOBI under medical supervision [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

Avoid use of KYNMOBI in patients with severe hepatic impairment (Child-Pugh Class C). No dosage adjustment is required for patients with mild or moderate hepatic impairment (Child-Pugh Class A and B). However, because of a potential for increased exposure, titrate KYNMOBI under medical supervision [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

9.1 Controlled Substance

KYNMOBI contains apomorphine, which is not a controlled substance.

9.2 Abuse

In premarketing clinical experience, KYNMOBI did not reveal any tendency for a withdrawal syndrome or any drug-seeking behavior. However, there are rare postmarketing reports of abuse of medications containing apomorphine. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. In general, these reports for apomorphine consist of patients taking increasing doses of medication in order to achieve a euphoric state.

12.1 Mechanism of Action

KYNMOBI is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action of KYNMOBI as a treatment for “off” episodes associated with Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

16.1 How Supplied

KYNMOBI sublingual film is a blue to green rectangular film with a white printed number identifying the strength (e.g., “10” is 10 mg). Each sublingual film is individually packaged in a sealed foil pouch. Films are supplied in the following strengths and package configurations (Table 3):

16.2 Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature].

Keep KYNMOBI in the foil pouch until ready to use.

Administration of KYNMOBI

Advise patients that KYNMOBI is for sublingual use only [see Dosage and Administration (2.1)].

KYNMOBI must be administered whole. Advise patients not to cut, chew, or swallow KYNMOBI.

Nausea and Vomiting

Advise patients that KYNMOBI may cause nausea and vomiting when it is administered at recommended doses. Treatment with the antiemetic trimethobenzamide may be considered to pretreat or treat nausea and/or vomiting [see Dosage and Administration (2.1)]. Inform patients that they should discuss with their healthcare provider when the antiemetic can be discontinued [see Warnings and Precautions (5.1)].

Falling Asleep During Activities of Daily Living and Somnolence

Alert patients to the potential sedating effects of KYNMOBI, including somnolence and falling asleep while engaged in activities of daily living. Instruct patients not to drive a car or engage in other potentially dangerous activities until they have gained sufficient experience with KYNMOBI to gauge whether or not it affects their mental and/or motor performance adversely. Advise patients that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., watching television, passenger in a car, etc.) occur, they should not drive or participate in potentially dangerous activities until they have discussed this with their healthcare provider. Because of possible additive effects of alcohol use, advise patients to limit their alcohol intake [see Warnings and Precautions (5.2)].

Hypersensitivity/Allergic Reactions

Advise patients that hypersensitivity/allergic reaction (e.g., swelling of the lips, tongue and mouth, flushing, and, infrequently, urticaria and throat tightness) may occur because of apomorphine, sodium metabisulfite, or any KYNMOBI excipients. Inform patients with a sulfite sensitivity that KYNMOBI contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes [see Warnings and Precautions (5.3)]. Advise patients who experience any hypersensitivity/allergic reaction to KYNMOBI that they should avoid taking KYNMOBI again [see Contraindications (4)].

Hypotension/Orthostatic Hypotension

Advise patients that they may develop postural (orthostatic) hypotension with or without symptoms, such as dizziness, nausea, syncope, and sweating. Instruct patients to rise slowly after sitting or lying down after taking KYNMOBI. Instruct patients to avoid alcohol intake because it may potentiate the hypotensive effect of KYNMOBI. Instruct patients to lie down before and after taking sublingual nitroglycerin because it may potentiate the hypotensive effect of KYNMOBI [see Warnings and Precautions (5.4)].

Oral Mucosal Irritation

Inform patients that KYNMOBI may result in oral mucosal adverse reactions such as irritation, erythema, lip swelling, mouth ulceration, dry mouth, stomatitis, glossodynia, oropharyngeal pain, swollen tongue, ageusia, oral pain, lip ulceration, oral disorder and hypoaesthesia oral [see Warnings and Precautions (5.5) and Adverse Reactions (6.1)].

Falls

Alert patients that they may have increased risk for falling when using KYNMOBI [see Warnings and Precautions (5.6)].

Hallucinations and/or Psychotic-Like Behavior

Inform patients that KYNMOBI may cause hallucinations or other manifestations of psychotic-like behavior. Advise patients to inform their healthcare provider if they have a major psychotic disorder or are taking any treatments for psychosis [see Warnings and Precautions (5.7)].

Hemolytic Anemia

Inform patients and caregivers that hemolytic anemia may occur and to contact their healthcare provider if they develop any signs or symptoms [see Warnings and Precautions (5.8)].

Impulse Control/Compulsive Behaviors

Patients and their caregivers should be alerted to the possibility that they may experience intense urges to spend money uncontrollably, intense urges to gamble, increased sexual urges, binge eating and/or other intense urges and the inability to control these urges while taking KYNMOBI [see Warnings and Precautions (5.9)].

Withdrawal-Emergent Hyperpyrexia and Confusion

Advise patients to contact their healthcare provider if they wish to discontinue KYNMOBI or decrease the dose of KYNMOBI [see Warnings and Precautions (5.10)].

QTc Prolongation and Potential for Proarrhythmic Effects

Alert patients that KYNMOBI may cause QTc prolongation and might produce proarrhythmic effects that could cause torsades de pointes and sudden death. Palpitations and syncope may signal the occurrence of an episode of torsades de pointes [see Warnings and Precautions (5.11)].

Priapism

Advise patients that KYNMOBI may cause prolonged painful erections and that if this occurs that they should seek medical attention immediately [see Warnings and Precautions (5.13)].

Manufactured for:
Sunovion Pharmaceuticals Inc.
Marlborough, Massachusetts 01752 USA

KYNMOBI and are registered trademarks of Sunovion Pharmaceuticals Inc.
SUNOVION and are registered trademarks of Sumitomo Pharma Co., Ltd.
Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Sumitomo Pharma Co., Ltd.
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For more information, go to www.KYNMOBI.com or call Sunovion Customer Service at 1-888-394-7377.

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