Interactions between Ranolazine and Seglentis
3 drug interactions and 65 additional warnings found for the following 2 drugs:
- ranolazine
- Seglentis (celecoxib/tramadol)
Drug interactions
Moderate drug interactions
Moderate:
traMADol celecoxib
Applies to: Seglentis (celecoxib / tramadol) and Seglentis (celecoxib / tramadol)
Monitor
Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.
Management
Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.
References (1)
- (2001) "Product Information. Celebrex (celecoxib)." Searle
Moderate:
traMADol ranolazine
Applies to: Seglentis (celecoxib / tramadol) and ranolazine
Monitor
Ranolazine can cause dose-related prolongation of the QT interval. Tramadol may also prolong the QT interval, and theoretically, coadministration of multiple agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death, although there is little experience in this setting. At Tmax following repeat dosing of 1000 mg twice daily, the mean effect of ranolazine on QTc is approximately 6 msec. However, in 5% of the population with the highest plasma concentrations, the prolongation of QTc is 15 msec or more. The apparent linear relationship is much steeper in cirrhotic subjects with mild or moderate hepatic impairment. In contrast, there have also been no reported cases of torsade de pointes in clinical studies of ranolazine comprising 3,669 patient-years of treatment. In Study CVT3036 (MERLIN-TIMI36), no proarrhythmic effects were observed on 7-day Holter recordings in 3,162 acute coronary syndrome (ACS) patients treated with ranolazine. In addition, there was a significantly lower incidence of arrhythmias (ventricular tachycardia, bradycardia, supraventricular tachycardia, and new atrial fibrillation) in patients treated with ranolazine (80%) versus placebo (87%), including ventricular tachycardia of 3 or more beats (52% versus 61%). The effect of tramadol on the QT interval was evaluated in a randomized, double-blind, 4-way crossover, placebo- and positive-controlled, multiple-dose ECG study of 62 healthy subjects. The maximum placebo-adjusted mean change from baseline in the Fridericia-corrected QT interval (QTcF) was 5.5 msec in the 400 mg/day treatment arm (100 mg every 6 hours on days 1 through 3 with a single 100 mg dose on day 4) and 6.5 msec in the 600 mg/day treatment arm (150 mg every 6 hours on days 1 through 3 with a single 150 mg dose on day 4), both occurring at the 8-hour time point. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
Monitor
Coadministration with ranolazine may decrease the opioid-like effects of tramadol, a substrate of the CYP450 2D6 isoenzyme. The mechanism is decreased conversion of tramadol to its active metabolite, M1, due to inhibition of CYP450 2D6 activity by ranolazine. Ranolazine has been shown in vitro to be an inhibitor of CYP450 2D6. In animal studies, M1 was up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in binding to mu-opioid receptors.
Management
Concomitant use of ranolazine and tramadol should generally be avoided. If coadministration is required, careful consideration of the effects on tramadol and M1 is required. Patients should be monitored for opioid withdrawal, seizures, and serotonin syndrome, and care should be exercised in patients suspected to be at an increased risk of torsade de pointes. Since the magnitude of QTc prolongation increases with increasing plasma concentrations of ranolazine, the maximum recommended dosage of 1000 mg twice daily should not be exceeded. Particular care should be exercised in patients suspected to be at an increased risk of torsade de pointes. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Ranolazine is contraindicated in patients with liver cirrhosis because of the profound effect on QT prolongation in this population.
References (2)
- (2006) "Product Information. Ranexa (ranolazine)." Calmoseptine Inc
- European Medicines Agency (2008) CHMP Assessment Report for Latixa. International nonproprietary name: ranolazine. Procedure No. EMEA/H/C/805. http://www.emea.europa.eu/humandocs/PDFs/EPAR/latixa/H-805-en6.pdf
Minor drug interactions
Minor:
celecoxib ranolazine
Applies to: Seglentis (celecoxib / tramadol) and ranolazine
Coadministration with inhibitors of CYP450 2D6 may modestly increase the plasma concentrations of ranolazine, which is partially metabolized by the isoenzyme. When ranolazine 1000 mg twice a day was given to healthy volunteers with the potent CYP450 2D6 inhibitor paroxetine at 20 mg once a day, mean steady-state ranolazine plasma concentrations increased by 1.2-fold. This is not considered clinically significant, and no dosage adjustment of ranolazine is required when used with CYP450 2D6 inhibitors.
References (1)
- (2006) "Product Information. Ranexa (ranolazine)." Calmoseptine Inc
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
traMADol Food/Lifestyle
Applies to: Seglentis (celecoxib / tramadol)
Generally avoid
Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur. In addition, alcohol may affect opioid release from sustained-release formulations.
Generally avoid
Grapefruit or grapefruit juice may increase the plasma concentrations of opioid analgesics by inhibiting CYP450 3A4-mediated metabolism of these agents, although the interaction has not been studied. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
Management
Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with opioid analgesics. Any history of alcohol or illicit drug use should be considered when prescribing an opioid analgesic, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with opioid analgesics should preferably avoid the consumption of grapefruit and grapefruit juice.
References (18)
- (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
- (2024) "Product Information. TraMADol Hydrochloride (traMADol)." Advagen Pharma Ltd
- (2024) "Product Information. Jamp Tramadol (tramadol)." Jamp Pharma Corporation
- (2025) "Product Information. Tramadol (tramadol)." Sigma Pharmaceuticals Plc
- (2024) "Product Information. Tramedo (tRAMadol)." Alphapharm Pty Ltd
- (2022) "Product Information. Alfentanil (alfentanil)." Hameln Pharma Ltd
- (2024) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
- (2024) "Product Information. Codeine Sulfate (codeine)." Lannett Company Inc
- (2024) "Product Information. Meperidine Hydrochloride (meperidine)." Genus Lifesciences Inc.
- (2023) "Product Information. Dsuvia (SUFentanil)." AcelRx Pharmaceuticals
- (2024) "Product Information. Dzuveo (sufentanil)." Aguettant Ltd
- (2025) "Product Information. Pethidine (pethidine)." Martindale Pharmaceuticals Ltd
- (2023) "Product Information. Meperidine Hydrochloride (meperidine)." Sandoz Canada Incorporated
- (2024) "Product Information. Pethidine (Juno) (pethidine)." Juno Pharmaceuticals Pty Ltd
- Cherrier MM, Shen DD, Shireman L, et al. (2021) "Elevated customary alcohol consumption attenuates opioid effects." Pharmacol Biochem Behav, 4, p. 1-27
- Fuhr LM, Marok FZ, Fuhr U, Selzer D, Lehr T (2023) "Physiologically based pharmacokinetic modeling of bergamottin and 6,7-dihydroxybergamottin to describe CYP3A4 mediated grapefruit-drug interactions." Clin Pharmacol Ther, 114, p. 470-82
- (2025) "Product Information. TraMADol Hydrochloride ER (traMADol)." Trigen Laboratories Inc
- (2025) "Product Information. Codeine Contin (codeine)." Purdue Pharma
Major:
ranolazine Food/Lifestyle
Applies to: ranolazine
Generally avoid
Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.
Management
Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.
References (1)
- (2006) "Product Information. Ranexa (ranolazine)." Calmoseptine Inc
Disease interactions
63 potential interactions Applies to: 48 conditions, including High Blood Pressure, Depression, Heart Failure, Asthma, and Gastritis/Duodenitis.
Alcoholism
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Alcoholism.
The CNS depressant effects of tramadol may be additive with those of alcohol and may lead to profound sedation, respiratory depression, coma, and death. Therapy with tramadol should be administered cautiously (and only when alternative treatment options are inadequate) in patients who might be prone to acute alcohol intake. Dosages and durations should be limited to the minimum required and patients should be monitored for signs and symptoms of respiratory depression and sedation. Prescribing naloxone for the emergency treatment of opioid overdose should be considered; naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, but it also increases the risk of seizures.
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Alcoholism.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Alcoholism.
Tramadol exposes patients and other users to the risks of addiction, abuse, and misuse. Each patient's risk should be assessed before prescribing tramadol, and all patients should be monitored regularly for development of such behaviors and conditions. Risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); the potential for such risks should not prevent proper pain management in any given patient. Patients at increased risk may be prescribed tramadol, but use in such patients requires intensive counseling about the risks and proper use of tramadol, as well as intensive monitoring for signs of addiction, abuse, and misuse; prescribing naloxone for the emergency treatment of opioid overdose should be considered.
Opioids are sought by drug abusers and patients with addiction disorders and are subject to criminal diversion. These risks should be considered when prescribing or dispensing tramadol. Strategies to reduce such risks include prescribing the smallest appropriate quantity and advising the patient about proper disposal of unused drug.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Alcoholism.
Tramadol should not be prescribed for patients who are suicidal or addiction-prone. The use of nonnarcotic analgesics should be considered for patients who are suicidal or depressed. Tramadol should be prescribed with caution for patients with history of misuse and/or are currently taking CNS-active drugs, antidepressant drugs, alcohol in excess, and patients who suffer from emotional disturbance or depression. Patients should be advised not to exceed the recommended dose and to limit their intake of alcohol.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Alcoholism.
Seizures have been reported in patients receiving tramadol within the recommended dosage range. The risk appears to increase with doses above the recommended range and with concomitant use of certain drugs (e.g., those that reduce the seizure threshold). Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (e.g., head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizures.
Altered Consciousness
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Altered Consciousness.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Anemia
Moderate:
Seglentis
The celecoxib in Seglentis has a moderate potential interaction with Anemia.
Anemia has been reported in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). This may be due to fluid retention, occult/gross blood loss, or an incompletely described effect on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients with any signs/symptoms of anemia or blood loss, especially during long-term therapy. NSAIDs may increase risk of bleeding events; comorbid conditions (e.g., coagulation disorders; concomitant use of warfarin/other anticoagulants, antiplatelet agents, serotonin/serotonin norepinephrine reuptake inhibitors) may increase this risk, and patients with these conditions should be monitored for signs of bleeding. Therapy with NSAIDs should be administered cautiously in patients with or predisposed to anemia. Clinical monitoring of hematopoietic function may be appropriate, particularly during chronic therapy.
Asphyxia
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Asphyxia.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Asthma
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Asthma.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated in patients with 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. A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps, severe potentially fatal bronchospasm, and/or intolerance to aspirin and other NSAIDs. Since cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, therapy with any NSAID should be avoided in patients with this form of aspirin sensitivity. NSAIDs should be used with caution in patients with preexisting asthma (without known aspirin sensitivity), and these patients should be monitored for changes in the signs and symptoms of asthma.
Biliary Obstruction
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Biliary Obstruction.
Tramadol may cause spasm of the sphincter of Oddi. Opioids may increase serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be monitored for worsening symptoms.
Bleeding Disorder
Moderate:
Seglentis
The celecoxib in Seglentis has a moderate potential interaction with Bleeding Disorder.
Anemia has been reported in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). This may be due to fluid retention, occult/gross blood loss, or an incompletely described effect on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients with any signs/symptoms of anemia or blood loss, especially during long-term therapy. NSAIDs may increase risk of bleeding events; comorbid conditions (e.g., coagulation disorders; concomitant use of warfarin/other anticoagulants, antiplatelet agents, serotonin/serotonin norepinephrine reuptake inhibitors) may increase this risk, and patients with these conditions should be monitored for signs of bleeding. Therapy with NSAIDs should be administered cautiously in patients with or predisposed to anemia. Clinical monitoring of hematopoietic function may be appropriate, particularly during chronic therapy.
Brain Tumor
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Brain Tumor.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Cachexia
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Cachexia.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Central Nervous System Disorders
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Central Nervous System Disorders.
Seizures have been reported in patients receiving tramadol within the recommended dosage range. The risk appears to increase with doses above the recommended range and with concomitant use of certain drugs (e.g., those that reduce the seizure threshold). Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (e.g., head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizures.
Cerebral Vascular Disorder
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Cerebral Vascular Disorder.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Cerebrovascular Insufficiency
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Cerebrovascular Insufficiency.
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. Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to 3 years duration have supported this increased risk. It is unclear from available data if the risk for cardiovascular thrombotic events is similar for all NSAIDs. Therapy with NSAIDs should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease. Patients should be treated with the lowest effective dosage for the shortest duration necessary. Appropriate antiplatelet therapy should be administered to patients requiring cardioprotection; however, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use, while the risk of serious gastrointestinal events is increased. Physicians and patients should remain alert for the development of adverse cardiovascular events throughout the entire duration of therapy, even without prior cardiovascular symptoms. Patients should be advised to promptly seek medical attention if they experience symptoms of cardiovascular thrombotic events (including chest pain, shortness of breath, weakness, or slurring of speech).
NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Two large clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.
The use of NSAIDs should be avoided in patients with a recent myocardial infarction unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. If an NSAID is used in patients with a recent myocardial infarction, they should be monitored for signs of cardiac ischemia.
Colonic Ulceration
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Colonic Ulceration.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
Cor Pulmonale
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Cor Pulmonale.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Dehydration
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Dehydration.
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in such patients, NSAIDs may cause a dose-dependent reduction in prostaglandin synthesis and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk for this reaction include those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction; those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; and older adult patients. Discontinuation of NSAID therapy generally leads to recovery to the pretreatment state. No information is available regarding NSAID use in patients with advanced renal disease; the renal effects of NSAIDs may hasten the progression of renal dysfunction in patients with preexisting renal disease. Volume status should be corrected in dehydrated or hypovolemic patients prior to initiating treatment. Renal function should be monitored in patients with renal or liver dysfunction, heart failure, dehydration, or hypovolemia during therapy. NSAIDs should be avoided in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if an NSAID is used in such patients, they should be monitored for signs of worsening renal function.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Dehydration.
Tramadol may cause severe hypotension (including orthostatic hypotension, syncope) in ambulatory patients. Risk is increased in patients whose ability to maintain blood pressure has already been compromised by reduced blood volume or coadministration of certain CNS depressant drugs; these patients should be monitored for signs of hypotension after starting or titrating tramadol. In patients with circulatory shock, tramadol may cause vasodilation that can further reduce cardiac output and blood pressure; tramadol should be avoided in patients with circulatory shock.
Depression
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Depression.
Tramadol exposes patients and other users to the risks of addiction, abuse, and misuse. Each patient's risk should be assessed before prescribing tramadol, and all patients should be monitored regularly for development of such behaviors and conditions. Risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); the potential for such risks should not prevent proper pain management in any given patient. Patients at increased risk may be prescribed tramadol, but use in such patients requires intensive counseling about the risks and proper use of tramadol, as well as intensive monitoring for signs of addiction, abuse, and misuse; prescribing naloxone for the emergency treatment of opioid overdose should be considered.
Opioids are sought by drug abusers and patients with addiction disorders and are subject to criminal diversion. These risks should be considered when prescribing or dispensing tramadol. Strategies to reduce such risks include prescribing the smallest appropriate quantity and advising the patient about proper disposal of unused drug.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Depression.
Tramadol should not be prescribed for patients who are suicidal or addiction-prone. The use of nonnarcotic analgesics should be considered for patients who are suicidal or depressed. Tramadol should be prescribed with caution for patients with history of misuse and/or are currently taking CNS-active drugs, antidepressant drugs, alcohol in excess, and patients who suffer from emotional disturbance or depression. Patients should be advised not to exceed the recommended dose and to limit their intake of alcohol.
Dermatitis, Drug-Induced
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Dermatitis, Drug-Induced.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious skin adverse reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis), which can be fatal. NSAIDs can also cause fixed drug eruption, and may present as generalized bullous fixed drug eruption, which can be life-threatening. These serious events may occur without warning. Patients should be advised to discontinue the NSAID and seek medical attention promptly at the first sign of skin rash or any other sign of hypersensitivity. NSAIDs are contraindicated in patients with previous serious skin reactions to these drugs.
Diabetes Mellitus
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Diabetes Mellitus.
Cases of tramadol-associated hypoglycemia have been reported, some resulting in hospitalization. In most cases, patients had predisposing risk factors (e.g., diabetes); caution is recommended in these patients. If hypoglycemia is suspected, blood glucose levels should be monitored and discontinuation of therapy should be considered as appropriate.
Drug Dependence
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Drug Dependence.
Tramadol exposes patients and other users to the risks of addiction, abuse, and misuse. Each patient's risk should be assessed before prescribing tramadol, and all patients should be monitored regularly for development of such behaviors and conditions. Risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); the potential for such risks should not prevent proper pain management in any given patient. Patients at increased risk may be prescribed tramadol, but use in such patients requires intensive counseling about the risks and proper use of tramadol, as well as intensive monitoring for signs of addiction, abuse, and misuse; prescribing naloxone for the emergency treatment of opioid overdose should be considered.
Opioids are sought by drug abusers and patients with addiction disorders and are subject to criminal diversion. These risks should be considered when prescribing or dispensing tramadol. Strategies to reduce such risks include prescribing the smallest appropriate quantity and advising the patient about proper disposal of unused drug.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Drug Dependence.
Seizures have been reported in patients receiving tramadol within the recommended dosage range. The risk appears to increase with doses above the recommended range and with concomitant use of certain drugs (e.g., those that reduce the seizure threshold). Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (e.g., head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizures.
Fluid Retention
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Fluid Retention.
Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), including some topical formulations. NSAIDs (including topicals) can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events. NSAIDs should be used with caution in patients with preexisting fluid retention, hypertension, or history of heart failure. NSAIDs should be avoided in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure; if an NSAID is used in such patients, they should be monitored for signs of worsening heart failure. Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Gallbladder Disease
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Gallbladder Disease.
Tramadol may cause spasm of the sphincter of Oddi. Opioids may increase serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be monitored for worsening symptoms.
Gastritis/Duodenitis
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Gastritis/Duodenitis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
Gastrointestinal Hemorrhage
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Gastrointestinal Hemorrhage.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
Gastrointestinal Obstruction
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Gastrointestinal Obstruction.
Opioid analgesics are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
Gastrointestinal Perforation
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Gastrointestinal Perforation.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
Head Injury
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Head Injury.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Head Injury.
Opioids may obscure the clinical course in a patient with a head injury. The use of tramadol should be avoided in patients with impaired consciousness or coma.
Heart Failure
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Heart Failure.
Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), including some topical formulations. NSAIDs (including topicals) can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events. NSAIDs should be used with caution in patients with preexisting fluid retention, hypertension, or history of heart failure. NSAIDs should be avoided in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure; if an NSAID is used in such patients, they should be monitored for signs of worsening heart failure. Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Heart Failure.
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in such patients, NSAIDs may cause a dose-dependent reduction in prostaglandin synthesis and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk for this reaction include those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction; those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; and older adult patients. Discontinuation of NSAID therapy generally leads to recovery to the pretreatment state. No information is available regarding NSAID use in patients with advanced renal disease; the renal effects of NSAIDs may hasten the progression of renal dysfunction in patients with preexisting renal disease. Volume status should be corrected in dehydrated or hypovolemic patients prior to initiating treatment. Renal function should be monitored in patients with renal or liver dysfunction, heart failure, dehydration, or hypovolemia during therapy. NSAIDs should be avoided in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if an NSAID is used in such patients, they should be monitored for signs of worsening renal function.
High Blood Pressure
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with High Blood Pressure.
Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), including some topical formulations. NSAIDs (including topicals) can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events. NSAIDs should be used with caution in patients with preexisting fluid retention, hypertension, or history of heart failure. NSAIDs should be avoided in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure; if an NSAID is used in such patients, they should be monitored for signs of worsening heart failure. Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
History, Peptic Ulcer
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with History, Peptic Ulcer.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
History - Cerebrovascular Disease
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with History - Cerebrovascular Disease.
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. Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to 3 years duration have supported this increased risk. It is unclear from available data if the risk for cardiovascular thrombotic events is similar for all NSAIDs. Therapy with NSAIDs should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease. Patients should be treated with the lowest effective dosage for the shortest duration necessary. Appropriate antiplatelet therapy should be administered to patients requiring cardioprotection; however, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use, while the risk of serious gastrointestinal events is increased. Physicians and patients should remain alert for the development of adverse cardiovascular events throughout the entire duration of therapy, even without prior cardiovascular symptoms. Patients should be advised to promptly seek medical attention if they experience symptoms of cardiovascular thrombotic events (including chest pain, shortness of breath, weakness, or slurring of speech).
NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Two large clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.
The use of NSAIDs should be avoided in patients with a recent myocardial infarction unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. If an NSAID is used in patients with a recent myocardial infarction, they should be monitored for signs of cardiac ischemia.
History - Myocardial Infarction
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with History - Myocardial Infarction.
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. Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to 3 years duration have supported this increased risk. It is unclear from available data if the risk for cardiovascular thrombotic events is similar for all NSAIDs. Therapy with NSAIDs should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease. Patients should be treated with the lowest effective dosage for the shortest duration necessary. Appropriate antiplatelet therapy should be administered to patients requiring cardioprotection; however, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use, while the risk of serious gastrointestinal events is increased. Physicians and patients should remain alert for the development of adverse cardiovascular events throughout the entire duration of therapy, even without prior cardiovascular symptoms. Patients should be advised to promptly seek medical attention if they experience symptoms of cardiovascular thrombotic events (including chest pain, shortness of breath, weakness, or slurring of speech).
NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Two large clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.
The use of NSAIDs should be avoided in patients with a recent myocardial infarction unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. If an NSAID is used in patients with a recent myocardial infarction, they should be monitored for signs of cardiac ischemia.
Hyperkalemia
Moderate:
Seglentis
The celecoxib in Seglentis has a moderate potential interaction with Hyperkalemia.
Increases in serum potassium concentration (including hyperkalemia) have been reported with use of nonsteroidal anti-inflammatory drugs (NSAIDs), even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. Caution is advised in patients with hyperkalemia.
Hyponatremia
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Hyponatremia.
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in such patients, NSAIDs may cause a dose-dependent reduction in prostaglandin synthesis and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk for this reaction include those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction; those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; and older adult patients. Discontinuation of NSAID therapy generally leads to recovery to the pretreatment state. No information is available regarding NSAID use in patients with advanced renal disease; the renal effects of NSAIDs may hasten the progression of renal dysfunction in patients with preexisting renal disease. Volume status should be corrected in dehydrated or hypovolemic patients prior to initiating treatment. Renal function should be monitored in patients with renal or liver dysfunction, heart failure, dehydration, or hypovolemia during therapy. NSAIDs should be avoided in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if an NSAID is used in such patients, they should be monitored for signs of worsening renal function.
Hypotension
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Hypotension.
Tramadol may cause severe hypotension (including orthostatic hypotension, syncope) in ambulatory patients. Risk is increased in patients whose ability to maintain blood pressure has already been compromised by reduced blood volume or coadministration of certain CNS depressant drugs; these patients should be monitored for signs of hypotension after starting or titrating tramadol. In patients with circulatory shock, tramadol may cause vasodilation that can further reduce cardiac output and blood pressure; tramadol should be avoided in patients with circulatory shock.
Ischemic Heart Disease
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Ischemic Heart Disease.
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. Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to 3 years duration have supported this increased risk. It is unclear from available data if the risk for cardiovascular thrombotic events is similar for all NSAIDs. Therapy with NSAIDs should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease. Patients should be treated with the lowest effective dosage for the shortest duration necessary. Appropriate antiplatelet therapy should be administered to patients requiring cardioprotection; however, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use, while the risk of serious gastrointestinal events is increased. Physicians and patients should remain alert for the development of adverse cardiovascular events throughout the entire duration of therapy, even without prior cardiovascular symptoms. Patients should be advised to promptly seek medical attention if they experience symptoms of cardiovascular thrombotic events (including chest pain, shortness of breath, weakness, or slurring of speech).
NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Two large clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.
The use of NSAIDs should be avoided in patients with a recent myocardial infarction unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. If an NSAID is used in patients with a recent myocardial infarction, they should be monitored for signs of cardiac ischemia.
Liver Disease
Major:
ranolazine
Ranolazine has a major potential interaction with Liver Disease.
Plasma concentrations of ranolazine increased by 30% in patients with mild (Child-Pugh Class A), and by 60% in patients with moderate (Child-Pugh B) hepatic impairment. The use of ranolazine is contraindicated in patients with clinically significant hepatic impairment.
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Liver Disease.
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in such patients, NSAIDs may cause a dose-dependent reduction in prostaglandin synthesis and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk for this reaction include those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction; those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; and older adult patients. Discontinuation of NSAID therapy generally leads to recovery to the pretreatment state. No information is available regarding NSAID use in patients with advanced renal disease; the renal effects of NSAIDs may hasten the progression of renal dysfunction in patients with preexisting renal disease. Volume status should be corrected in dehydrated or hypovolemic patients prior to initiating treatment. Renal function should be monitored in patients with renal or liver dysfunction, heart failure, dehydration, or hypovolemia during therapy. NSAIDs should be avoided in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if an NSAID is used in such patients, they should be monitored for signs of worsening renal function.
Moderate:
Seglentis
The celecoxib in Seglentis has a moderate potential interaction with Liver Disease.
Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) should be administered cautiously in patients with preexisting liver disease. Periodic monitoring of liver function is recommended during prolonged therapy. NSAIDs are also highly protein-bound and some are extensively metabolized by the liver. Metabolic activity and/or plasma protein binding may be altered in patients with hepatic impairment. A dosage reduction may be required in some cases.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Liver Disease.
Tramadol is converted by the liver to several metabolites, one of which (referred to as M1) is pharmacologically active and a more potent analgesic than tramadol itself. The metabolism of both tramadol and M1 has been shown to decrease in patients with advanced cirrhosis of the liver, resulting in increased exposure to tramadol as well as substantially prolonged elimination half-lives for both tramadol and M1. Therapy with tramadol should be administered cautiously in patients with liver dysfunction. In patients with severe liver dysfunction, dosage reduction is recommended with the immediate-release formulations, while the extended-release formulations should not be used.
Long QT Syndrome
Moderate:
ranolazine
Ranolazine has a moderate potential interaction with Long QT Syndrome.
Ranolazine prolongs the QT interval in a dose-related manner. Caution should be exercised if used in patients with long QT interval, or using other QT- prolonging drugs.
Noninfectious Colitis
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Noninfectious Colitis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
Pancreatitis
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Pancreatitis.
Tramadol may cause spasm of the sphincter of Oddi. Opioids may increase serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be monitored for worsening symptoms.
Peptic Ulcer
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Peptic Ulcer.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
Pseudotumor Cerebri
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Pseudotumor Cerebri.
Opioids may obscure the clinical course in a patient with a head injury. The use of tramadol should be avoided in patients with impaired consciousness or coma.
Psychiatric Disorders
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Psychiatric Disorders.
Tramadol exposes patients and other users to the risks of addiction, abuse, and misuse. Each patient's risk should be assessed before prescribing tramadol, and all patients should be monitored regularly for development of such behaviors and conditions. Risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); the potential for such risks should not prevent proper pain management in any given patient. Patients at increased risk may be prescribed tramadol, but use in such patients requires intensive counseling about the risks and proper use of tramadol, as well as intensive monitoring for signs of addiction, abuse, and misuse; prescribing naloxone for the emergency treatment of opioid overdose should be considered.
Opioids are sought by drug abusers and patients with addiction disorders and are subject to criminal diversion. These risks should be considered when prescribing or dispensing tramadol. Strategies to reduce such risks include prescribing the smallest appropriate quantity and advising the patient about proper disposal of unused drug.
Psychosis
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Psychosis.
Tramadol should not be prescribed for patients who are suicidal or addiction-prone. The use of nonnarcotic analgesics should be considered for patients who are suicidal or depressed. Tramadol should be prescribed with caution for patients with history of misuse and/or are currently taking CNS-active drugs, antidepressant drugs, alcohol in excess, and patients who suffer from emotional disturbance or depression. Patients should be advised not to exceed the recommended dose and to limit their intake of alcohol.
Pulmonary Impairment
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Pulmonary Impairment.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Renal Dysfunction
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Renal Dysfunction.
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in such patients, NSAIDs may cause a dose-dependent reduction in prostaglandin synthesis and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk for this reaction include those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction; those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; and older adult patients. Discontinuation of NSAID therapy generally leads to recovery to the pretreatment state. No information is available regarding NSAID use in patients with advanced renal disease; the renal effects of NSAIDs may hasten the progression of renal dysfunction in patients with preexisting renal disease. Volume status should be corrected in dehydrated or hypovolemic patients prior to initiating treatment. Renal function should be monitored in patients with renal or liver dysfunction, heart failure, dehydration, or hypovolemia during therapy. NSAIDs should be avoided in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if an NSAID is used in such patients, they should be monitored for signs of worsening renal function.
Moderate:
ranolazine
Ranolazine has a moderate potential interaction with Renal Dysfunction.
In patients with varying degrees of renal impairment, ranolazine plasma levels increased up to 50%, Caution is advised when used in patients with renal impairment. The pharmacokinetics of ranolazine has not been assessed in patients on dialysis.
Moderate:
Seglentis
The celecoxib in Seglentis has a moderate potential interaction with Renal Dysfunction.
Increases in serum potassium concentration (including hyperkalemia) have been reported with use of nonsteroidal anti-inflammatory drugs (NSAIDs), even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. Caution is advised in patients with hyperkalemia.
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Renal Dysfunction.
Tramadol and its metabolites, one of which (referred to as M1) is pharmacologically active and a more potent analgesic than tramadol itself, are primarily excreted in the urine. The rate and extent of excretion of both tramadol and M1 have been shown to decrease in patients with impaired renal function. Therapy with tramadol should be administered cautiously in such patients. In patients with CrCl less than 30 mL/min, dosage reduction is recommended with the immediate-release formulations, while the extended-release formulations should not be used.
Respiratory Arrest
Major:
Seglentis
The traMADol in Seglentis has a major potential interaction with Respiratory Arrest.
Tramadol is contraindicated in patients with significant respiratory depression. Serious, life-threatening, or fatal respiratory depression may occur with tramadol. Patients should be monitored closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and after a dosage increase.
The use of tramadol in patients with acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment is contraindicated. Tramadol-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression are at increased risk of decreased respiratory drive (including apnea), even at recommended dosages of tramadol. In patients who may be susceptible to the intracranial effects of carbon dioxide (CO2) retention (e.g., those with evidence of increased intracranial pressure or brain tumors), tramadol may reduce respiratory drive, and the resulting CO2 retention can further increase intracranial pressure; these patients should be monitored for signs of sedation and respiratory depression, especially when starting tramadol.
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics (or altered clearance) compared to younger, healthier patients. These patients should be monitored closely, especially when starting and titrating tramadol and when coadministering with other drugs that depress respiration; alternatively, the use of nonopioid analgesics should be considered.
Shock
Moderate:
Seglentis
The traMADol in Seglentis has a moderate potential interaction with Shock.
Tramadol may cause severe hypotension (including orthostatic hypotension, syncope) in ambulatory patients. Risk is increased in patients whose ability to maintain blood pressure has already been compromised by reduced blood volume or coadministration of certain CNS depressant drugs; these patients should be monitored for signs of hypotension after starting or titrating tramadol. In patients with circulatory shock, tramadol may cause vasodilation that can further reduce cardiac output and blood pressure; tramadol should be avoided in patients with circulatory shock.
Smoking
Major:
Seglentis
The celecoxib in Seglentis has a major potential interaction with Smoking.
Nonsteroidal anti-inflammatory drugs (NSAIDs) 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 develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating older adult or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.
More resources
ranolazine
A total of 578 drugs are known to interact with ranolazine.
- Ranolazine is in the drug class antianginal agents.
- Ranolazine is used to treat Angina.
Seglentis
A total of 1062 drugs are known to interact with Seglentis.
- Seglentis is in the drug class narcotic analgesic combinations.
- Seglentis is used to treat Pain.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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