Egalet Announces a Large Regional Health Plan Placed ARYMO® ER and SPRIX® Nasal Spray in Preferred Formulary Positions
WAYNE, Pa., Feb. 28, 2018 /PRNewswire/ -- Egalet Corporation (Nasdaq: EGLT) ("Egalet"), a fully integrated specialty pharmaceutical company focused on developing, manufacturing and marketing innovative treatments for pain and other conditions, today announced that one of the largest Northeast regional health plans has placed ARYMO ER (morphine sulfate) extended-release (ER) tablets for oral use only -CII and SPRIX (ketorolac tromethamine) Nasal Spray in preferred formulary positions, effective immediately.
"Obtaining preferred coverage of both ARYMO ER and SPRIX Nasal Spray is important to ensure access to our products for healthcare providers and for the individuals covered by this large health plan," said Patrick Shea, chief commercial officer of Egalet. "With the ongoing opioid epidemic, we believe that improved access to non-narcotic and abuse-deterrent treatment options is critical to try and decrease prescription opioid abuse in our communities."
Please see safety information on SPRIX Nasal Spray and ARYMO ER, including boxed warning and medication guides, below. Abuse of ARYMO ER by injection, as well as by the oral and nasal routes, is still possible. For full prescribing information for SPRIX and ARYMO ER, please visit sprix.com and arymoer.com respectively.
IMPORTANT SAFETY INFORMATION ABOUT SPRIX NASAL SPRAY
WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS Cardiovascular Thrombotic Events Nonsteroidal anti-inflammatory drugs (NSAIDS) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. SPRIX(R) is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDS cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. ----------------------------------------------------------
Indications and Usage
Warnings and Precautions
Gastrointestinal Bleeding, Ulceration, and Perforation: contraindicated in patients with active peptic ulcers and/or GI bleeding and in patients with recent gastrointestinal bleeding or perforation. Can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms. Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors.
Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop.
Hypertension: NSAIDs, including SPRIX, can lead to new onset or worsening of preexisting hypertension. Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure.
Heart Failure and Edema: Avoid use of SPRIX in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure.
Renal Toxicity and Hyperkalemia: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of SPRIX in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function.
Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs.
Exacerbation of Asthma Related to Aspirin Sensitivity: Contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without known aspirin sensitivity).
Serious Skin Reactions: NSAIDs, including SPRIX, can cause serious skin reactions, which can be fatal. Discontinue SPRIX at first appearance of skin rash or other signs of hypersensitivity.
Premature Closure of Fetal Ductus Arteriosus: Avoid use in pregnant women starting at 30 weeks gestation.
Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia. Do not use SPRIX in patients for whom hemostasis is critical.
Limitations of Use: SPRIX should not be used concomitantly with IM/IV or oral ketorolac, aspirin, or other NSAIDs.
The most common adverse reactions (incidence ≥2%) in patients treated with SPRIX and occurring at a rate at least twice that with placebo include: nasal discomfort; rhinalgia; increased lacrimation; throat irritation; oliguria; rash; bradycardia; decreased urine output; increased ALT and/or AST; hypertension; rhinitis.
In controlled clinical trials in major surgery, primarily knee and hip replacements and abdominal hysterectomies, 1.5% of patients treated with SPRIX experienced serious adverse events of bleeding or hematoma at the operative site versus 0.4% of patients treated with placebo who experienced hematoma.
In patients taking ketorolac or other NSAIDs in clinical trials, the most frequently reported adverse reactions in approximately 1% to 10% of patients are:
Gastrointestinal (GI): abdominal pain, constipation/diarrhea, dyspepsia, flatulence, GI fullness, GI ulcers (gastric/duodenal), gross bleeding/perforation, heartburn, nausea (incidence >10%), stomatitis, vomiting.
Other: abnormal renal function, anemia, dizziness, drowsiness, edema, elevated liver enzymes, headache (incidence >10%), hypertension, increased bleeding time, injection site pain, pruritus, purpura, rash, tinnitus, sweating.
ACE inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers: may diminish the antihypertensive effect of these drugs; monitor blood pressure.
ACE Inhibitors and ARBs: In elderly, volume depleted, or those with renal impairment may result in deterioration of renal function; monitor for signs of worsening renal function.
Diuretics: reduces the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.
Digoxin: has been reported to increase the serum concentration and prolong the half-life of digoxin.
Use in Specific Populations
Infertility: NSAIDs are associated with reversible infertility. Consider withdrawal of SPRIX in women who have difficulties conceiving.
IMPORTANT SAFETY INFORMATION ABOUT ARYMO ER
WARNING: ADDICTION, ABUSE, and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; AND RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse ARYMO(TM) ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing ARYMO ER, and monitor all patients regularly for the development of these behaviors or conditions Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of ARYMO ER. Monitor for respiratory depression, especially during initiation of ARYMO ER or following a dose increase. Instruct patients to swallow ARYMO ER tablets whole; crushing, chewing, or dissolving ARYMO ER tablets can cause rapid release and absorption of a potentially fatal dose of morphine Accidental Ingestion Accidental ingestion of even one dose of ARYMO ER, especially by children, can result in a fatal overdose of morphine. Neonatal Opioid Withdrawal Syndrome Prolonged use of ARYMO ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life- threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of ARYMO ER and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. --------------------------------------------------------
Limitations of Use
Warnings and Precautions
Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of ARYMO ER, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases with ARYMO ER.
To reduce the risk of respiratory depression, proper dosing and titration of ARYMO ER are essential. Overestimating the ARYMO ER dose when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of ARYMO ER, especially by children, can result in respiratory depression and death due to an overdose of morphine.
Neonatal Opioid Withdrawal Syndrome: Prolonged use of ARYMO ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Profound sedation, respiratory depression, coma, and death may result from the concomitant use of ARYMO ER with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.
Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: The use of ARYMO ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease: ARYMO ER-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of ARYMO ER.
Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
Monitor such patients closely, particularly when initiating and titrating ARYMO ER and when ARYMO ER is given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients.
Interaction with Monoamine Oxidase Inhibitors: Monoamine oxidase inhibitors (MAOIs) may potentiate the effects of morphine, including respiratory depression, coma, and confusion. ARYMO ER should not be used in patients taking MAOIs or within 14 days of stopping such treatment.
Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
Severe Hypotension: ARYMO ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dose of ARYMO ER. In patients with circulatory shock, ARYMO ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use ARYMO ER in patients with circulatory shock.
Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), ARYMO ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with ARYMO ER.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of ARYMO ER in patients with impaired consciousness or coma.
Difficulty in Swallowing and Risk for Obstruction in Patients at Risk for a Small Gastrointestinal Lumen: Moistened ARYMO ER tablets may become sticky leading to difficulty in swallowing the tablets. Patients could experience choking, gagging, regurgitation and tablets stuck in the throat. Instruct patients not to pre-soak, lick, or otherwise wet ARYMO ER tablets prior to placing in the mouth, and to take one tablet at a time with enough water to ensure complete swallowing immediately after placing in the mouth.
Tablet stickiness and swelling may also predispose patients to intestinal obstruction and exacerbation of diverticulitis. Patients with underlying GI disorders such as esophageal cancer or colon cancer with a small gastrointestinal lumen are at greater risk of developing these complications. Consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying GI disorders resulting in a small gastrointestinal lumen.
Risks of Use in Patients with Gastrointestinal Conditions: ARYMO ER is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus. The morphine in ARYMO ER may cause spasm of the sphincter of Oddi. Opioids may cause increases in the serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
Increased Risk of Seizures in Patients with Seizure Disorders: The morphine in ARYMO ER may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during ARYMO ER therapy.
Withdrawal: Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including ARYMO ER. In these patients, mixed agonists/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.
When discontinuing ARYMO ER, gradually taper the dose. Do not abruptly discontinue ARYMO ER.
Risks of Driving and Operating Machinery: ARYMO ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of ARYMO ER and know how they will react to the medication.
Additional Drug Interactions
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: May reduce the analgesic effect of ARYMO ER and/or precipitate withdrawal symptoms; avoid concomitant use.
Muscle Relaxants: Morphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Cimetidine: The concomitant use of cimetidine can potentiate morphine effects and increase risk of hypotension, respiratory depression, profound sedation, coma, and death.
Diuretics: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Anticholinergic Drugs: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
P-Glycoprotein (P-gp) Inhibitors: The concomitant use of P-gp inhibitors can increase the exposure to morphine by about two-fold and can increase risk of hypotension, respiratory depression, profound sedation, coma, and death.
Use in Specific Populations
Geriatrics: The pharmacokinetics of ARYMO ER have not been studied in elderly patients. Elderly patients (aged 65 years or older) may have increased sensitivity to morphine.
Hepatic Impairment: Morphine pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. Start these patients with a lower than usual dosage of ARYMO ER and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension.
Renal Impairment: Morphine pharmacokinetics are altered in patients with renal failure. Start these patients with a lower than usual dosage of ARYMO ER and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension.
For full prescribing information on ARYMO ER, including the boxed warning and medication guide, please visit arymoer.com. For full prescribing information on SPRIX, including the boxed warning and medication guide, please visit sprix.com. For full prescribing information on OXAYDO, including the boxed warning and medication guide, please visit oxaydo.com.
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SOURCE Egalet Corporation
Company Codes: NASDAQ-NMS:EGLT