ELYXYB - celecoxib
celecoxib · Liquid · Oral
Uses
1 INDICATIONS AND USAGE ELYXYB is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use ELYXYB is not indicated for the preventive treatment of migraine. ELYXYB is a nonsteroidal anti-inflammatory drug indicated for the acute treatment of migraine with or without aura in adults ( 1 ) Limitations of Use ELYXYB is not indicated for the preventive treatment of migraine. ( 1 )
Dosage and administration
The recommended dose of ELYXYB is 120 mg taken orally, with or without food ( 2.1 ) The maximum dosage in a 24-hour period is 120 mg ( 2.1 ) Use ELYXYB for the fewest number of days per month, as needed ( 2.1 ) Hepatic Impairment: The recommended and maximum dose is 60 mg (2.4 mL) in patients with moderate hepatic impairment (Child-Pugh Class B) ( 2.2 , 8.6 , 12.3 ) Poor Metabolizers of CYP2C9 Substrates: The recommended and maximum dose is 60 mg (2.4 mL) in patients who are known or suspected to be CYP2C9 poor metabolizers ( 2.3 , 8.8 , 12.5 ) 2.1 Recommended Dosage The recommended dose of ELYXYB is 120 mg taken orally, with or without food [see Clinical Pharmacology ( 12.3 ) ] . The maximum dosage in a 24-hour period is 120 mg. The safety and effectiveness of a second dose in a 24-hour period have not been established. Use ELYXYB for the fewest number of days per month, as needed. 2.2 Dosage Modification in Patients with Hepatic Impairment The recommended and maximum dose in patients with moderate hepatic impairment (Child- Pugh Class B) is 60 mg (2.4 mL) [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device. Use of ELYXYB in patients with severe hepatic impairment is not recommended. 2.3 Dosage Modification in CYP2C9 Poor Metabolizers The recommended and maximum dose in patients who are known or suspected to be CYP2C9 poor metabolizers is 60 mg (2.4 mL) [see Use in Specific Populations ( 8.8 ) and Clinical Pharmacology ( 12.5 )]. A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device.
Dosage forms and strengths
Dosage form: Clear colorless oral solution Strength: 120 mg/4.8 mL (25 mg/mL) Oral solution, 120 mg/4.8 mL (25 mg/mL) ( 3 )
Contraindications
4 CONTRAINDICATIONS ELYXYB is contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to celecoxib, any components of the drug product [see Warnings and Precautions ( 5.7 , 5.9 )]. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions ( 5.7 , 5.8 )]. In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions ( 5.1 )]. In patients who have demonstrated allergic-type reactions to sulfonamides [see Warnings and Precautions ( 5.7 )]. Known hypersensitivity to celecoxib, any components of the drug product, or sulfonamides ( 4 ) History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs ( 4 ) In the setting of CABG surgery ( 4 )
Warnings and precautions
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 ( 5.3 ) Hypertension : Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure ( 5.4 , 7 ) Heart Failure and Edema : Avoid use of ELYXYB in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure ( 5.5 ) Renal Toxicity : Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of ELYXYB in patients with severe renal impairment unless benefits are expected to outweigh risk of worsening renal function ( 5.6 ) Anaphylactic Reactions : Seek emergency help if an anaphylactic reaction occurs ( 5.7 ) Exacerbation of Asthma Related to Aspirin Sensitivity : ELYXYB is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity) ( 5.8 ) Serious Skin Reactions : Discontinue ELYXYB at first appearance of skin rash or other signs of hypersensitivity ( 5.9 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) : Discontinue and evaluate clinically ( 5.10 ) Medication Overuse Headache : Detoxification may be necessary ( 5.11 ) Fetal Toxicity : Limit use of NSAIDs, including ELYXYB, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus ( 5.12 , 8.1 ) Hematologic Toxicity : Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia ( 5.13 , 7 ) 5.1 Cardiovascular Thrombotic Events Clinical trials of several cyclooxygenase (COX-2) selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. In a trial with celecoxib capsules, there was about a threefold increased risk of the composite endpoint of cardiovascular death, MI, or stroke for the celecoxib 400 mg twice daily and celecoxib 200 mg twice daily treatment arms compared to placebo. The increases in both celecoxib dose groups versus placebo-treated patients were mainly due to an increased incidence of myocardial infarction. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use ELYXYB for the fewest number of days per month as needed, based on individual treatment goals. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as ELYXYB, increases the risk of serious gastrointestinal (GI) events [see Warnings and Precautions ( 5.2 )]. Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID administered in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs, including ELYXYB, are contraindicated in the setting of CABG [see Contraindications ( 4 )]. Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of ELYXYB in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If ELYXYB is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. 5.2 Gastrointestinal Bleeding, Ulceration and Perforation NSAIDs, including ELYXYB, 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, in patients treated with celecoxib. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions ( 5.1 )] GI Bleeding, Ulceration, and Perforation [see Warnings and Precautions ( 5.2 )] Hepatotoxicity [see Warnings and Precautions ( 5.3 )] Hypertension [see Warnings and Precautions ( 5.4 )] Heart Failure and Edema [see Warnings and Precautions ( 5.5 )] Renal Toxicity and Hyperkalemia [see Warnings and Precautions ( 5.6 )] Anaphylactic Reactions [see Warnings and Precautions ( 5.7 )] Exacerbation of Asthma Related to Aspirin Sensitivity [see Warnings and Precautions ( 5.8 )] Serious Skin Reactions [see Warnings and Precautions ( 5.9 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions ( 5.10 )] Medication Overuse Headache [see Warnings and Precautions ( 5.11 )] Fetal Toxicity [see Warnings and Precautions ( 5.12 )] Hematologic Toxicity [see Warnings and Precautions ( 5.13 )] Most common adverse reaction (at least 3% and greater than placebo) is dysgeusia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact SCILEX Pharmaceuticals Inc. at 1-866-SCILEX3 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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 practice. The safety of ELYXYB was evaluated in 815 patients who received at least one dose of ELYXYB in two, randomized, double-blind, placebo-controlled trials (Study 1 and 2) in adult patients with migraine [see Clinical Studies ( 14 )]. The most common (at least 2% of patients who received ELYXYB and greater than placebo) adverse reaction in Study 1 and Study 2 was dysgeusia, which occurred in 3% of patients who received ELYXYB compared to 1% of patients who received placebo. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of celecoxib. 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. Cardiovascular: Vasculitis, deep venous thrombosis General: Anaphylactic reaction, angioedema Liver and biliary: Liver necrosis, hepatitis, jaundice, hepatic failure Hemic and lymphatic: Agranulocytosis, aplastic anemia, pancytopenia, leucopenia Metabolic: Hypoglycemia, hyponatremia Nervous: Aseptic meningitis, ageusia, anosmia, fatal intracranial hemorrhage Renal: Interstitial nephritis Skin and Appendages : Erythema multiforme, exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and fixed drug eruption (FDE) [ see Warnings and Precautions ( 5.9 ) ].
Drug interactions
See Table 1 for clinically significant drug interactions with celecoxib. Table 1: Clinically Significant Drug Interactions with Celecoxib Drugs That Interfere with Hemostasis Clinical Impact Celecoxib and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of celecoxib and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention Monitor patients with concomitant use of ELYXYB with anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding [see Warnings and Precautions ( 5.13 )]. Aspirin Clinical Impact In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions ( 5.2 )]. In two studies in healthy volunteers and in patients with established heart disease respectively, celecoxib (200 mg to 400 mg daily) has demonstrated a lack of interference with the cardioprotective antiplatelet effect of aspirin (100 mg to 325mg). Intervention Concomitant use of ELYXYB and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions ( 5.13 )]. ELYXYB is not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact NSAIDs may diminish the antihypertensive effect of ACE inhibiters, ARBs, or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention During concomitant use of ELYXYB and ACE inhibitors, ARBs, or beta- blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of ELYXYB and ACE inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [see Warnings and Precautions ( 5.6 )]. When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter. Diuretics Clinical Impact Clinical studies, as well as postmarketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. Intervention During concomitant use of ELYXYB with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions ( 5.6 )]. Digoxin Clinical Impact The concomitant use of celecoxib with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Intervention During concomitant use of ELYXYB and digoxin, monitor serum digoxin levels. Lithium Clinical Impact NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. Intervention During concomitant use of ELYXYB and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinical Impact Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Celecoxib has no effect on methotrexate pharmacokinetics. Intervention During concomitant use of ELYXYB and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact Concomitant use of celecoxib and cyclosporine may increase cyclosporine's nephrotoxicity. Intervention During concomitant use of ELYXYB and cyclosporine, monitor patients for signs of worsening renal function. NSAIDs and Salicylates Clinical Impact Concomitant use of celecoxib with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity [see Warnings and Precautions ( 5.2 )]. Intervention The concomitant use of ELYXYB with other NSAIDs or salicylates is not recommended. Pemetrexed Clinical Impact Concomitant use of celecoxib and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). Intervention During concomitant use of ELYXYB and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal, and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration. CYP2C9 Inhibitors or inducers Clinical Impact Celecoxib metabolism is predominantly mediated via cytochrome P450 (CYP) 2C9 in the liver.
Use in specific populations
Infertility : NSAIDs are associated with reversible infertility. Consider withdrawal of ELYXYB in women who have difficulties conceiving ( 8.3 ) 8.1 Pregnancy Risk Summary Use of NSAIDs, including ELYXYB, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of ELYXYB use between about 20 and 30 weeks of gestation, and avoid ELYXYB use at about 30 weeks of gestation and later in pregnancy ( see Clinical Considerations , Data ). Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including ELYXYB, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, administration of celecoxib during pregnancy resulted in adverse effects on development, including increases in embryonic death and fetal malformations, at doses or maternal plasma drug exposures greater than those used clinically ( see Data ). Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as celecoxib, resulted in increased pre- and post- implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including ELYXYB, can cause premature closure of the fetal ductus arteriosus (see Data ). Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If ELYXYB treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue ELYXYB and follow up according to clinical practice ( see Data ). Labor or Delivery There are no studies on the effects of celecoxib during labor or delivery. In animal studies, NSAIDs, including celecoxib, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. Data Human Data Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain. Animal data Administration of celecoxib to rats during early embryonic development resulted in increased pre- and postimplantation loss at oral doses ≥50 mg/kg/day, which was associated with plasma exposure (AUC) approximately 20 times that in humans at the maximum recommended dose (MRHD) of 120 mg/day. Administration of celecoxib to pregnant rats throughout the period of organogenesis resulted in increased incidences of a specific fetal malformation (diaphragmatic hernia) at oral doses ≥30 mg/kg/day, associated with plasma exposure (AUC) approximately 20 times that in humans at the MRHD. Administration of celecoxib to pregnant rabbits throughout organogenesis produced increased incidences of fetal visceral (ventricular septal defects) and skeletal malformations at oral doses ≥150 mg/kg/day, associated with maternal plasma AUC approximately 7 times that in humans at the MRHD.
Pregnancy
8.1 Pregnancy Risk Summary Use of NSAIDs, including ELYXYB, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of ELYXYB use between about 20 and 30 weeks of gestation, and avoid ELYXYB use at about 30 weeks of gestation and later in pregnancy ( see Clinical Considerations , Data ). Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including ELYXYB, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, administration of celecoxib during pregnancy resulted in adverse effects on development, including increases in embryonic death and fetal malformations, at doses or maternal plasma drug exposures greater than those used clinically ( see Data ). Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as celecoxib, resulted in increased pre- and post- implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including ELYXYB, can cause premature closure of the fetal ductus arteriosus (see Data ). Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If ELYXYB treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue ELYXYB and follow up according to clinical practice ( see Data ). Labor or Delivery There are no studies on the effects of celecoxib during labor or delivery. In animal studies, NSAIDs, including celecoxib, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. Data Human Data Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain. Animal data Administration of celecoxib to rats during early embryonic development resulted in increased pre- and postimplantation loss at oral doses ≥50 mg/kg/day, which was associated with plasma exposure (AUC) approximately 20 times that in humans at the maximum recommended dose (MRHD) of 120 mg/day. Administration of celecoxib to pregnant rats throughout the period of organogenesis resulted in increased incidences of a specific fetal malformation (diaphragmatic hernia) at oral doses ≥30 mg/kg/day, associated with plasma exposure (AUC) approximately 20 times that in humans at the MRHD. Administration of celecoxib to pregnant rabbits throughout organogenesis produced increased incidences of fetal visceral (ventricular septal defects) and skeletal malformations at oral doses ≥150 mg/kg/day, associated with maternal plasma AUC approximately 7 times that in humans at the MRHD.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Disseminated intravascular coagulation has occurred in pediatric patients [see Warnings and Precautions ( 5.16 )].
Geriatric use
8.5 Geriatric Use Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, treat for the fewest number of days per month, as needed, and monitor patients for adverse effects [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.6 , 5.15 )]. In the controlled clinical trials for migraine, approximately 70 patients were ≥ 65 years of age. Of the total number of patients who received celecoxib (for indications other than migraine) in pre-approval clinical trials, more than 3,300 were 65-74 years of age, while approximately 1,300 additional patients were 75 years and over. No substantial differences in effectiveness were observed between these subjects and younger subjects. In clinical studies comparing renal function as measured by the GFR, BUN and creatinine, and platelet function as measured by bleeding time and platelet aggregation, the results were not different between elderly and young volunteers. However, as with other NSAIDs, including those that selectively inhibit COX-2, there have been more spontaneous postmarketing reports of fatal GI events and acute renal failure in the elderly than in younger patients [see Warnings and Precautions ( 5.4 , 5.6 )].
Overdosage
Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions ( 5.1 , 5.2 , 5.4 , 5.6 )]. No overdoses of celecoxib were reported during clinical trials. No information is available regarding the removal of celecoxib by hemodialysis, but based on its high degree of plasma protein binding (>97%), dialysis is unlikely to be useful in overdose. Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdosage (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. For additional information about overdosage treatment contact a poison control center.
Description
11 DESCRIPTION ELYXYB is an oral solution of celecoxib, a nonsteroidal anti-inflammatory drug. Each unit dose of ELYXYB contains 120 mg of celecoxib. Celecoxib is a white or almost white, crystalline or amorphous powder with a pKa of 11. Celecoxib is hydrophobic (log P is 3.0) and practically insoluble in water. Celecoxib is chemically designated as p -[5- p -tolyl-3-(trifluoromethyl) pyrazol-1-yl] benzenesulfonamide. The empirical formula for celecoxib is C 17 H 14 F 3 N 3 O 2 S, and the molecular weight is 381.37. It has the following chemical structure: The inactive ingredients in ELYXYB include: acesulfame potassium, banana flavor, bubble gum flavor, ethyl alcohol, glycerin, glyceryl monocaprylate, L-menthol, lauroyl polyoxyl-32 glycerides, medium chain triglycerides, monoammonium glycyrrhizinate, peppermint flavor, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, propyl gallate, purified water, and sucralose. Chemical Structure
Mechanism of action
12.1 Mechanism of Action Celecoxib is a nonsteroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action by which celecoxib exerts therapeutic effects in migraine patients is not fully understood but may involve inhibition of prostaglandin synthesis, primarily via inhibition of COX-2.
How supplied
16.1 How Supplied ELYXYB (celecoxib) oral solution, 120 mg/4.8 mL (25 mg/mL) is a clear colorless oral solution supplied in a disposable glass bottle with a child resistant cap. Each carton (NDC 69557-333-01) contains six (6) glass bottles, a Full Prescribing Information, Medication Guide, and Instructions for Use. 16.2 Storage and Handling Store at room temperature 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]. Do not refrigerate or freeze. Unused portion should be discarded immediately after use. 16.1 How Supplied ELYXYB (celecoxib) oral solution, 120 mg/4.8 mL (25 mg/mL) is a clear colorless oral solution supplied in a disposable glass bottle with a child resistant cap. Each carton (NDC 69557-333-01) contains six (6) glass bottles, a Full Prescribing Information, Medication Guide, and Instructions for Use.
Storage
16.2 Storage and Handling Store at room temperature 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]. Do not refrigerate or freeze. Unused portion should be discarded immediately after use.
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use ). Administration Information For patients who are prescribed the recommended dosage of 120 mg, instruct them to drink the entire amount of ELYXYB directly from the bottle. For patients who are prescribed the reduced dosage (i.e., patients with moderate hepatic impairment or CYP2C9 poor metabolizers), instruct them to use an oral dosing syringe to correctly measure the prescribed amount of medication. Inform these patients that oral dosing syringes may be obtained from their pharmacy and that a household teaspoon is not an accurate measuring device. Instruct these patients to discard the unused portion of ELYXYB. Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [see Warnings and Precautions ( 5.1 )]. Gastrointestinal Bleeding, Ulceration, and Perforation Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding [see Warnings and Precautions ( 5.2 )]. Hepatotoxicity Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, instruct patients to stop ELYXYB and seek immediate medical therapy [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.6 )]. Heart Failure and Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see Warnings and Precautions ( 5.5 )]. Anaphylactic Reactions Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [see Contraindications ( 4 ) and Warnings and Precautions ( 5.7 )]. Serious Skin Reactions, including DRESS Advise patients to stop taking ELYXYB immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [see Warnings and Precautions ( 5.9 , 5.10 )]. Medication Overuse Headache Inform patients that use of acute migraine drugs for 10 or more days per month, including ELYXYB, may lead to an exacerbation of headache and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary). Instruct patients to contact their healthcare provider if the frequency of their migraines increases; withdrawal of ELYXYB may be necessary [see Warnings and Precautions ( 5.11 )]. Female Fertility Advise females of reproductive potential who desire pregnancy that NSAIDs, including ELYXYB, may be associated with a reversible delay in ovulation [see Use in Specific Populations ( 8.3 )]. Fetal Toxicity Inform pregnant women to avoid use of ELYXYB and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with ELYXYB is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours [see Warnings and Precautions ( 5.12 ) and Use in Specific Populations ( 8.1 )] . Avoid Concomitant Use of NSAIDs Inform patients that the concomitant use of ELYXYB with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7 )]. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia. Use of NSAIDs and Low-Dose Aspirin Inform patients not to use low-dose aspirin concomitantly with ELYXYB until they talk to their healthcare provider [see Drug Interactions ( 7 )]. ELYXYB is a trademark of SCILEX Pharmaceuticals Inc. Manufactured by: Contract Pharmaceuticals Limited, Mississauga, Ontario, Canada Manufactured for: SCILEX Pharmaceuticals Inc., Palo Alto, CA 94303 Active Ingredient Made in India ©2023 SCILEX Pharmaceuticals Inc. All rights reserved. ELY-00194 11/2024
Label text from the FDA structured product label by SCILEX PHARMACEUTICALS INC. (revised Nov 26, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Celecoxib in 1 product
ELYXYB - celecoxib NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 69557-333 | Celecoxib 120 mg/4.8mL Liquid | SCILEX PHARMACEUTICALS INC. | NDA |
Frequently asked questions
What is ELYXYB - celecoxib used for?
1 INDICATIONS AND USAGE ELYXYB is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use ELYXYB is not indicated for the preventive treatment of migraine. ELYXYB is a nonsteroidal anti-inflammatory drug indicated for the acute treatment of migraine with or without aura in adults ( 1 ) Limitations of Use ELYXYB is not indicated for the preventive treatment…
What are the side effects of ELYXYB - celecoxib?
The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions ( 5.1 )] GI Bleeding, Ulceration, and Perforation [see Warnings and Precautions ( 5.2 )] Hepatotoxicity [see Warnings and Precautions ( 5.3 )] Hypertension [see Warnings and Precautions ( 5.4 )] Heart Failure and Edema [see Warnings and… See the full label for the complete list.
Who makes ELYXYB - celecoxib?
ELYXYB - celecoxib is listed by 1 labeler in the FDA NDC directory, including SCILEX PHARMACEUTICALS INC..