Xifyrm
Meloxicam · Injection · Intravenous
• Non-steroidal 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. [ see Warnings and Precautions ( 5.1 ) ].
• XIFYRM is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [ see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 ) ]. Gastrointestinal Risk
• 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…
Uses
1 INDICATIONS AND USAGE XIFYRM is indicated for use in adults for the management of moderate-to-severe pain, alone or in combination with non-NSAID analgesics. Limitation of Use Because of delayed onset of analgesia, XIFYRM alone is not recommended for use when rapid onset of analgesia is required. XIFYRM contains meloxicam, which is an NSAID, and is indicated for use in adults for the management of moderate-to-severe pain, alone or in combination with non-NSAID analgesics. Limitation of Use Because of delayed onset of analgesia, XIFYRM alone is not recommended for use when rapid onset of analgesia is required. ( 1 )
Dosage and administration
Use for the shortest duration consistent with individual patient treatment goals [ see Warnings and Precautions ( 5 ) ]. For intravenous administration only. The recommended dosage of XIFYRM is 30 mg once daily, administered by intravenous bolus injection over 15 seconds. When initiating XIFYRM, monitor patient analgesic response. Because the median time to meaningful pain relief was 2 and 3 hours after XIFYRM administration in two clinical studies, a non-NSAID analgesic with a rapid onset of effect may be needed, for example, upon anesthetic emergence or resolution of local or regional anesthetic blocks [ see Clinical Studies ( 14 ) ]. Some patients may not experience adequate analgesia for the entire 24-hour dosing interval and may require administration of a short-acting, non-NSAID, immediate-release analgesic [ see Clinical Studies ( 14 ) ]. To reduce the risk of renal toxicity, patients must be well hydrated prior to administration of XIFYRM. Visually inspect parenteral drug products for particulate matter and discoloration prior to administration. Should the contents appear discolored or contain particulate matter, discard the vial [ see Dosage Forms and Strengths ( 3 ) ].
• Use for the shortest duration consistent with individual patient treatment goals. ( 2 )
• Recommended dosage: 30 mg once daily, administered by intravenous bolus injection over 15 seconds. ( 2 )
• Monitor patient analgesic response and administer a short-acting, non-NSAID, immediate-release analgesic if response is inadequate. ( 2 )
• Patients must be well hydrated before XIFYRM administration. ( 2 )
Dosage forms and strengths
(meloxicam injection) is a sterile, clear, pale yellow to yellow color solution intended for intravenous use available as a clear, single-dose vial containing 30 mg/mL per vial. XIFYRM (meloxicam injection), single-dose vial containing 30 mg/mL per vial. ( 3 )
Contraindications
4 CONTRAINDICATIONS XIFYRM is contraindicated in the following patients:
• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see Warnings and Precautions ( 5.7 ) ].
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal anaphylactic-like reactions to NSAIDs have been reported in such patients [ see Warnings and Precautions ( 5.8 ) ].
• In the setting of coronary artery bypass graft (CABG) surgery [ see Warnings and Precautions ( 5.1 ) ].
• Moderate to severe renal insufficiency patients who are at risk for renal failure due to volume depletion [ see Warnings and Precautions ( 5.6 )].
• Known hypersensitivity to meloxicam or any components of the drug product. ( 4 )
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. ( 4 )
• In the setting of coronary artery bypass graft (CABG) surgery. ( 4 )
• Moderate to severe renal insufficiency patients who are at risk for renal failure due to volume depletion. ( 4 )
Warnings and precautions
• Hepatotoxicity : Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue XIFYRM immediately 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 XIFYRM injection, monitor blood pressure. ( 5.4 , 7 )
• Heart Failure and Edema : Avoid use of XIFYRM 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 XIFYRM in patients with advanced renal disease 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 : XIFYRM is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity). ( 5.8 )
• Serious Skin Reactions : Discontinue XIFYRM 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 )
• Hematologic Toxicity : Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia. ( 5.12 , 7 )
• Fetal Toxicity : Limit use of NSAIDs, including XIFYRM, between about 20 to 30 weeks in pregnancy due to the risk of renal oligohydramnios/fetal 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. ( 5.11 , 8.1 ) 5.1 Cardiovascular Thrombotic Events Clinical trials of several 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. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. 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 meloxicam, 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 for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs 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 XIFYRM in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If XIFYRM is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. 5.2 Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation NSAIDs, including meloxicam, 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 XIFYRM. 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 3-6 months, and in about 2-4% of patients treated for one year. However, even short- term NSAID therapy is not without risk. Risk Factors for GI Bleeding, Ulceration, and Perforation 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.
Side effects
The following adverse reactions are discussed in greater detail in the 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 ) ]
• Serious Skin Reactions [ see Warnings and Precautions ( 5.9 ) ]
• Hematologic Toxicity [ see Warnings and Precautions ( 5.12 ) ] The most common adverse reactions (≥ 2% and greater than placebo) in controlled clinical trials include constipation, GGT increased, and anemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449 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 rates in the clinical trials of another drug and may not reflect the rates observed in practice. During clinical development, 1426 patients were exposed to meloxicam injection in controlled and open- label Phase 2 and Phase 3 trials. Meloxicam injection was studied across a range of surgical procedures, including bunionectomy, abdominoplasty, soft tissue surgery, total knee replacement surgery, gynecologic surgery, complex foot surgery and total hip replacement surgery. In these trials, 381 patients received a single dose of meloxicam injection and 1045 patients received multiple doses of meloxicam injection daily for up to 7 days. The incidence rates of adverse reactions listed in Table 1 are derived from the three Phase 3 trials comparing meloxicam injection to placebo in patients who may have also received opioid rescue medication. Table 1: Proportion of Patients Experiencing Common Adverse Reactions in Placebo- Controlled Phase 3 Clinical Trials occurring in greater than or equal to 2% of Patients Treated with Meloxicam injection and at a greater frequency than Placebo Meloxicam injection Placebo Adverse Reaction N=748 N=393 Constipation 57 (7.6%) 24 (6.1%) Gamma-Glutamyl transferase Increased 21 (2.8%) 6 (1.5%) Anemia 18 (2.4%) 4 (1.0%) The following is a list of adverse drug reactions occurring in <2% of patients receiving meloxicam injection in clinical trials. Table 2: Additional Adverse Reactions for Meloxicam Injection Body as a Whole asthenia, back pain, edema, fatigue, hyperthermia, infusion site reactions (including pain, pruritus, phlebitis and thrombosis), muscle spasms, non-cardiac chest pain, pyrexia, vaginal discharge, weight decrease Central and Peripheral Nervous System disturbance in attention, migraine, presyncope, somnolence, syncope Gastrointestinal abdominal discomfort, abdominal distension, abdominal pain, diarrhea, dry mouth, epigastric discomfort, flatulence, frequent bowel movements, gastritis, gastroesophageal reflux, gastrointestinal pain, rectal hemorrhage Heart Rate and Rhythm tachycardia Hematologic increased bleeding time, neutropenia, thrombocytosis Infections and Infestations cellulitis, gastroenteritis, urinary tract infection, vulval abscess Liver and Biliary System liver function test abnormal Metabolic and Nutritional hypokalemia, hypomagnesemia Procedural Complications incision site hemorrhage, incision site rash, wound dehiscence, wound hematoma Psychiatric confusion, hallucination, insomnia Respiratory dyspnea, epistaxis, hypoxia, oropharyngeal pain Skin and Appendages contact dermatitis, ecchymosis, rash Urinary System pollakiuria, urinary retention 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of meloxicam. 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. Adverse reactions reported in worldwide post marketing experience or the literature include: acute urinary retention; agranulocytosis; alterations in mood (such as mood elevation); anaphylactoid reactions including shock; erythema multiforme; exfoliative dermatitis; interstitial nephritis; jaundice; liver failure; Stevens-Johnson syndrome; toxic epidermal necrolysis, and infertility female.
Drug interactions
See Table 3 for clinically significant drug interactions with meloxicam. Table 3: Clinically Significant Drug Interactions with Meloxicam Drugs That Interfere with Hemostasis Clinical Impact: Meloxicam and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of meloxicam 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 XIFYRM with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [se e Warnings and Precautions ( 5.12 ) ]. Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. 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 ) ]. Intervention: Concomitant use of XIFYRM and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [ see Warnings and Precautions ( 5.12 ) ]. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding [ see Warnings and Precautions ( 5.2 ) ]. XIFYRM 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 angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (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 XIFYRM and ACE-inhibitors, ARBs, or beta- blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of XIFYRM 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 post-marketing 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. However, studies with furosemide agents and meloxicam have not demonstrated a reduction in natriuretic effect. Furosemide single and multiple dose pharmacodynamics and pharmacokinetics are not affected by multiple doses of meloxicam. Intervention: During concomitant use of XIFYRM 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 ) ]. 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. [ see Clinical Pharmacology ( 12.3 ) ]. Intervention: During concomitant use of XIFYRM 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). Intervention: During concomitant use of XIFYRM and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact: Concomitant use of XIFYRM and cyclosporine may increase cyclosporine’s nephrotoxicity. Intervention: During concomitant use of XIFYRM and cyclosporine, monitor patients for signs of worsening renal function. NSAIDs and Salicylates Clinical Impact: Concomitant use of meloxicam with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [ see Warnings and Precautions ( 5.2 ) ]. Intervention: The concomitant use of meloxicam with other NSAIDs or salicylates is not recommended. Pemetrexed Clinical Impact: Concomitant use of XIFYRM and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). Intervention: During concomitant use of XIFYRM and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. Patients taking meloxicam should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration. In patients with creatinine clearance below 45 mL/min, the concomitant administration of meloxicam with pemetrexed is not recommended.
Use in specific populations
• Infertility: NSAIDs are associated with reversible infertility. Consider withdrawal of XIFYRM in women who have difficulties conceiving. ( 8.3 ) 8.1 Pregnancy Risk Summary Use of NSAIDs, including XIFYRM, 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 XIFYRM use between about 20 and 30 weeks of gestation, and avoid XIFYRM 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 XIFYRM, 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 potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.32- and 3.24-times the maximum recommended human dose (MRHD) of 30 mg of XIFYRM. Increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 39-times the MRHD. In pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.04-times the MRHD. No teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 1.3- and 13-times the MRHD (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 meloxicam, 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. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, 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% to 4% and 15% to 20%, respectively. 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 XIFYRM, 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 XIFYRM treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue XIFYRM and follow up according to clinical practice (see Data). Labor or delivery There are no studies on the effects of meloxicam during labor or delivery. In animal studies, NSAIDs, including meloxicam, 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 Meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (1.3-times the MRHD of 30 mg based on body surface area (BSA) comparison). Administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (39-times the MRHD based on BSA comparison). The no effect level was 20 mg/kg/day (13-times the MRHD based on BSA comparison).
Pregnancy
8.1 Pregnancy Risk Summary Use of NSAIDs, including XIFYRM, 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 XIFYRM use between about 20 and 30 weeks of gestation, and avoid XIFYRM 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 XIFYRM, 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 potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.32- and 3.24-times the maximum recommended human dose (MRHD) of 30 mg of XIFYRM. Increased incidence of septal heart defects were observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 39-times the MRHD. In pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.04-times the MRHD. No teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 1.3- and 13-times the MRHD (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 meloxicam, 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. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, 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% to 4% and 15% to 20%, respectively. 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 XIFYRM, 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 XIFYRM treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue XIFYRM and follow up according to clinical practice (see Data). Labor or delivery There are no studies on the effects of meloxicam during labor or delivery. In animal studies, NSAIDs, including meloxicam, 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 Meloxicam was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (1.3-times the MRHD of 30 mg based on body surface area (BSA) comparison). Administration of meloxicam to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day (39-times the MRHD based on BSA comparison). The no effect level was 20 mg/kg/day (13-times the MRHD based on BSA comparison).
Pediatric use
8.4 Pediatric Use The safety and efficacy of XIFYRM has not been established in pediatric patients.
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 monitor patients for adverse effects [ see Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.6 , 5.4 ) ]. Of the total number of patients in clinical studies of meloxicam injection, 197 patients were age 65 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.
Overdosage
Symptoms following acute NSAID overdoses 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 ) ]. Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may be employed but are not likely to be useful due to high protein binding. There is limited experience with meloxicam overdose. In four reported cases of meloxicam overdose, patients took 6 to 11 times the highest available oral dose of meloxicam tablets (15 mg); all recovered. Cholestyramine is known to accelerate the clearance of meloxicam. Accelerated removal of meloxicam by 4 g doses of cholestyramine given three times a day was demonstrated in a clinical trial. Administration of cholestyramine may be useful following an overdosage. In case of an overdosage, discontinue XIFYRM therapy and contact a regional poison control center at 1-800-222-1222.
Description
(meloxicam injection) is a nonsteroidal anti-inflammatory drug (NSAID). It is a sterile clear, pale-yellow to yellow color solution, containing the active pharmaceutical ingredient meloxicam for intravenous administration. Each mL of aqueous solution contains 30 mg of meloxicam, 150 mg of hydroxypropyl betadex, 20 mg of meglumine, 60 mg of povidone and water for injection. The pH of the meloxicam injection is 8.0 to 9.5. The meloxicam drug substance is polymorph I. It is pale yellow powder. It is soluble in dimethylformamide, slightly soluble in acetone, very slightly soluble in ethanol 96% and in methanol, and practically insoluble in water. Meloxicam is designated chemically as 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2- benzothiazine-3-carboxamide-1,1-dioxide. The molecular weight is 351.4. Its molecular formula is C 14 H 13 N 3 O 4 S 2 and the structural formula of meloxicam is: Figure-1 Structure
Mechanism of action
12.1 Mechanism of Action Meloxicam has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of meloxicam, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Meloxicam is a potent inhibitor of prostaglandin synthesis in vitro. Meloxicam concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because meloxicam is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.
How supplied
(meloxicam injection) is a clear, pale-yellow to yellow color solution intended for intravenous use supplied as a 1 mL fill (30 mg/mL) in a clear, single-dose vial with a blue tamper-evident top. NDC Number Package Size 24338-153-02 10 x 1 mL Single-Dose Vials 24338-153-01 1 mL Single-Dose Vial Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep vial in carton to protect from light. Discard unused portion.
Patient information
Inform patients of the following information before initiating therapy with XIFYRM. Cardiovascular Thrombotic Effects 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 healthcare 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 healthcare provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for 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, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, instruct patients to stop XIFYRM and seek immediate medical therapy [ see Warnings and Precautions ( 5.3 ) ]. 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 XIFYRM 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 ) ]. Female Fertility Advise females of reproductive potential who desire pregnancy that NSAIDs, including XIFYRM, 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 XIFYRM and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with XIFYRM 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 ( 5.11 ) and Use in Specific Populations ( 8.1 ) ]. Avoid Concomitant Use of NSAIDs Inform patients that the concomitant use of XIFYRM 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 XIFYRM until they talk to their healthcare provider [ see Drug Interactions ( 7 ) ]. This Prescribing Information has been approved by the US Food and Drug Administration. Distributed by: Azurity Pharmaceuticals, Inc. Woburn, MA 01801 06/2025 Rev00
Label text from the FDA structured product label by Azurity Pharmaceuticals, Inc. (revised Jun 18, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Meloxicam in 1 product
Xifyrm NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 24338-153 | Meloxicam 30 mg/mL Injection | Azurity Pharmaceuticals, Inc. | NDA |
Frequently asked questions
What is Xifyrm used for?
1 INDICATIONS AND USAGE XIFYRM is indicated for use in adults for the management of moderate-to-severe pain, alone or in combination with non-NSAID analgesics. Limitation of Use Because of delayed onset of analgesia, XIFYRM alone is not recommended for use when rapid onset of analgesia is required. XIFYRM contains meloxicam, which is an NSAID, and is indicated for use in adults for the management…
What are the side effects of Xifyrm?
The following adverse reactions are discussed in greater detail in the 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… See the full label for the complete list.
Who makes Xifyrm?
Xifyrm is listed by 1 labeler in the FDA NDC directory, including Azurity Pharmaceuticals, Inc..