Intravenous lipid emulsions (ILEs) are fat emulsions primarily indicated as a source of calories and essential fatty acids for parenteral nutrition and as a source of essential fatty acids when a deficiency occurs when oral or enteral nutrition is not possible, insufficient, or contraindicated. ILEs are also used off-label for lipid rescue therapy (LRT) in cases of potentially fatal local anesthetic toxicity and cases of lipophilic agent overdose or poisoning when there is hemodynamic instability unresponsive to resuscitation measures, such as fluid replacement, inotropes, and vasopressors. ILEs are primarily composed of medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) and/or fish oil triglycerides, egg phospholipids, and glycerol. They are classified into various generations based on their fatty acid derivative as well as their inflammatory response. First-generation ILEs are composed of 100% soybean oil (i.e., Intralipid, Nutrilipid) and are considered pro-inflammatory. Second-generation ILEs are comprised of a 50:50 ratio of MCTs to soybean oil. Third-generation ILEs are olive-oil containing products with an 80:20 ratio of olive oil to soybean oil. Second- and third-generation lipid emulsions are considered inflammatory neutral. Fourth-generation ILEs are fish-oil containing products in varying ratios and are considered anti-inflammatory. SMOFlipid is comprised of soybean oil, MCTs, olive oil, and fish oil in a 30:30:25:15 ratio, while Omegaven is 100% fish oil. About 60% of the content of first-generation ILEs is in the form of linoleic acid (omega-6; 50%) and alpha-linolenic acid (omega-3; 10%). Additionally, they contain LCTs. ILEs with high concentrations of omega-6 have been shown to be pro-inflammatory, and studies have suggested a link between LCTs and an increase in the risk of infection and parenteral nutrition-associated liver disease (PNALD). Thus, newer generations of ILEs were developed with a different composition of fatty acids in order to reduce these complications. Omegaven has a total omega-3 fatty acid content of 40% to 54%, compared to an approximately 2% to 4% omega-6 fatty acid content. Although clinical data have supported the use of newer generation ILEs for their reduction in inflammatory response, outcomes and adverse reaction data are limited. Most ILEs are indicated for adults and pediatric patients as young as neonates. Omegaven is indicated as a source of calories and essential fatty acids for pediatric patients with parenteral nutrition-associated cholestasis (PNAC).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Preparation of Total Nutrient Admixture (TNA)
-30% Intralipid should only be administered as part of a 3-in-1 total nutrient admixture (TNA); it is NOT indicated for direct IV infusion. Diluting 30% formulations to a 20% concentration does not produce a solution equivalent to the commercially available 20% emulsions, and such a dilution should not be given by direct intravenous administration.
-Pharmacy Bulk Packages are not for direct IV administration.
-Prepare TNA using strict aseptic techniques.
-Do not add intravenous lipid emulsion (ILE) to the parenteral nutrition (PN) container first; destabilization of the lipid may occur. The proper mixing sequence is dextrose, amino acids, and then lipid emulsion. Simultaneous transfer of dextrose, amino acids, and ILE to the PN container is also permitted.
-Use gentle agitation during admixing; shake bags gently after each addition.
-Do not add additives directly to ILE; additives to the TNA solution should be evaluated by a pharmacist for compatibility.
-Storage: Use the Pharmacy Bulk Package within 4 hours after opening. Admixtures should be used promptly with storage under refrigeration not to exceed 24 hours and must be completely infused within 24 hours after removal from refrigeration.
Preparation of Bags for Direct Infusion
-Inspect bag overwrap and primary bag; do not use if damaged. Inspect oxygen indicator and do not use if oxygen indicator is pink or dark pink (Nutrilipid) or black (SMOFlipid). Use only if container and seals are intact.
-Remove infusion bag and discard oxygen indicator, oxygen absorber, and overwrap.
-Discard bag if there is a separation of the lipid emulsion or any signs of discoloration and/or leakage.
-Remove outlet port and attach administration set.
-Additives may only be added to the medication port under strict aseptic techniques and only after evaluation by a pharmacist for compatibility.
-Storage: After removing from the overwrap, ILE should be used immediately. If not used immediately, the product should not be stored longer than 24 hours under refrigeration. After removal from storage, the emulsion should be used within 24 hours.
Intravenous Infusion Administration
-For intravenous infusion only through a peripheral or central line. When administered with dextrose and/or amino acids, solutions with an osmolarity of 900 mOsm/L or higher must be infused through a central line.
-Use a 1.2 micron in-line filter for administration of intravenous lipid emulsion. This recommendation applies when administering PN as TNA as well as when giving dextrose and amino acids (2-in-1) and the IV lipid emulsion as a separate infusion. When administering the dextrose-amino acid component of the PN and the ILE as separate infusions, attach the filter below the Y-site where the infusions meet. If an occluded filter needs to be removed, replace it with a new filter. Do not allow an unfiltered admixture to continue to infuse.
-Protect admixture from light during infusion. This includes containers and administration sets. The use of light-exposed parenteral nutrition products containing amino acids and/or lipids, particularly in admixtures with vitamins and/or trace elements, may lead to severe adverse effects, particularly in premature neonates. This is because exposure of these solutions to light causes the formation of peroxides and other degradation products.
-Administration tubing and filter should be changed every 24 hours for TNA, dextrose/amino acid solutions (2-in-1), or lipid emulsions. When lipids are infused separately, ILE should hang for no more than 12 hours to minimize microbial growth potential. When administered as part of a 3-in-1 TNA, IV fat emulsions can hang for 24 hours.
-To prevent air embolism, use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible bags in series, fully evacuate residual gas in the bag prior to administration, do not pressurize the flexible bag to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the bag runs dry.
-Do not use infusion sets and lines that contain di-2-ethyl hexyl phthalate (DEHP); administration sets that contain polyvinyl chloride (PVC) components have DEHP as a plasticizer.
-Soybean oil-based lipid emulsions (i.e., Intralipid, Nutrilipid, SMOFlipid):-Adult patients: Initial infusion rate is 0.2 mL/kg/hour for first 15 to 30 minutes; gradually increase to the required rate after 30 minutes. Max: 0.5 mL/kg/hour (0.1 g/kg/hour). Infuse over 12 to 24 hours, depending on clinical situation.
-Pediatric patients 11 to 17 years: Initial infusion rate is 0.2 to 0.4 mL/kg/hour for first 15 to 30 minutes; gradually increase to the required rate after 30 minutes. Max: 0.5 mL/kg/hour (0.1 g/kg/hour). Infuse over 12 to 24 hours, depending on clinical situation.
-Pediatric patients 1 to 10 years: Initial infusion rate is 0.2 to 0.4 mL/kg/hour for first 15 to 30 minutes; gradually increase to the required rate after 30 minutes. Max: 0.75 mL/kg/hour (0.15 g/kg/hour). Infuse over 12 to 24 hours, depending on clinical situation.
-Neonates and Infants:-Initial infusion rate is 0.1 to 0.2 mL/kg/hour for first 15 to 30 minutes; gradually increase to the required rate after 30 minutes. Max: 0.75 mL/kg/hour (0.15 g/kg/hour). Infuse over 24 hours to promote lipid tolerance.
-The use of a dextrose/amino acids PN solution with ILE infused separately is recommended in neonates and infants due to the increased risk of calcium-phosphate precipitation in total nutrient admixtures.
-Soybean oil/olive oil lipid emulsion (i.e., Clinolipid)
--Adult patients: Initial infusion rate is 0.5 mL/minute for first 15 to 30 minutes; gradually increase to the required rate after 30 minutes. Max: 0.5 mL/kg/hour (0.1 g/kg/hour). Infuse over 12 to 24 hours, depending on clinical situation.
-Fish oil triglycerides lipid emulsion (i.e., Omegaven)-Pediatric patients (all ages): Initial infusion rate is 0.2 mL/kg/hour for the first 15 to 30 minutes; gradually increase to the required rate after 30 minutes. Max: 1.5 mL/kg/hour (0.15 g/kg/hour). Infuse over 8 to 24 hours, depending on clinical situation.
Lipid Resuscitation Therapy (LRT) for Lipophilic Agent Overdose
-LRT can be administered through a peripheral intravenous catheter.
-Administer bolus over 1 to 3 minutes
-After the bolus, attach the lipid emulsion bag to an intravenous pump for continuous infusion.
-Continue infusion for at least 10 minutes after achievement of hemodynamic stability but no more than 60 minutes.
The deposition of a brown pigmentation in the reticuloendothelial system, known as "intravenous fat pigment", has been reported with intravenous lipid emulsions. The cause and significance of this phenomenon are unknown. Some data suggest that pediatric patients may be at higher risk due to the immaturity of enzyme systems and other differences in metabolic systems resulting in less efficient handling of lipids; additionally, infusion rates above 0.5 g/kg/hour have been associated with a higher frequency of pigment deposition in children.
Catheter-related bloodstream infection (1% to 2%), pneumonia (1% or less), sepsis (2%), and nosocomial infection (6%) have been reported with intravenous lipid emulsions. Monitor for signs and symptoms of early infections (fever and chills), including laboratory test results that may indicate infection, such as leukocytosis (1% or less) and hyperglycemia. Increased C-reactive protein (4% or less) has also been reported. Frequently assess the parenteral access device and insertion site for edema, erythema, and discharge.
Early adverse reactions associated with intravenous lipid emulsions include dyspnea (1% or less), cyanosis (less than 1%), allergic reactions (less than 1%), hypercoagulability (less than 1%), hyperglycemia (2% to 5%), nausea (9% to 11%), vomiting (5% to 9%), diarrhea (2% or less), flatulence (2% to 4%), abdominal pain (2% to 4%), dyspepsia (2%), dysgeusia (1% or less), drowsiness (less than 1%), headache (1% or less), dizziness (1% or less), hypertension (3% to 4%), chest pain (unspecified) (less than 1%), back pain (less than 1%), sinus tachycardia (2% or less), flushing (less than 1%), fever (4% or less), diaphoresis (less than 1%), thrombo-phlebitis (1% or less), rash (1% or less), pruritus (1% or less), decreased hematocrit (1% or less), metabolic acidosis (1% or less), fluid overload or fluid retention (1% or less), and thrombocytopenia in pediatric patients (2%). In clinical trials with Omegaven (fish oil lipid emulsion) in pediatric patients (n = 189), adverse reactions reported in more than 5% of patients included vomiting (46%), agitation (35%), bradycardia (35%), apnea (20%), viral infection (16%), erythema (12%), rash (8%), abscess (7%), neutropenia (7%), hypertonia (6%), and injection site reaction (erythema, 6%). Patients in the study had a complicated medical and surgical history (i.e., prematurity, necrotizing enterocolitis, ventilator dependence, coagulopathy, sepsis) prior to receiving Omegaven.
Fat overload syndrome, characterized by sudden deterioration in the patient's condition including fever, anemia, leukopenia, thrombocytopenia, coagulopathy, hyperlipidemia, hepatomegaly, hepatic failure, splenomegaly, and central nervous system manifestations (e.g., coma), has rarely been reported with intravenous lipid emulsions. A reduced or limited ability to metabolize lipids accompanied by prolonged plasma clearance may result in this syndrome, although the etiology of the fat overload syndrome is unclear. Although it has been most frequently observed when the recommended lipid dose was exceeded, cases have also been reported where the intravenous lipid emulsion was administered at recommended doses. The syndrome is usually reversible when the lipid infusion is stopped. Additionally, hepatomegaly, splenomegaly, anemia, thrombocytopenia, and leukopenia have been reported with long-term use of intravenous lipid emulsions.
Hepatobiliary adverse reactions reported with long-term use of intravenous lipid emulsions include hepatomegaly, jaundice due to cholestasis (1% or less), hepatic steatosis, steato-hepatitis, gallbladder sludge, liver function test abnormalities (i.e., elevated hepatic enzymes, 1% or less), and intestinal failure-associated liver disease (IFALD) or parenteral nutrition-associated liver disease (PNALD). Cholecystitis and cholelithiasis have also been observed. In clinical trials with SMOFlipid in pediatric patients (n = 170; 149 neonatal patients), hepatobiliary adverse reactions reported included increased GGT (6%), cholestasis (4%), hyperbilirubinemia (3%), increased conjugated bilirubin (2%), and increased alanine aminotransferase (1% or less). Premature neonates may be at particular risk for IFALD due to a decreased ability to clear intravenous lipid emulsions and increased free fatty acid plasma concentrations after administration. Parenteral nutrition-associated cholestasis (PNAC; defined as direct bilirubin more than 2 mg/dL with a second confirmed elevation more than 2 mg/dL at least 7 days later), which is a precursor to IFALD, occurred less frequently in patients treated with SMOFlipid compared with 100% soybean oil lipid emulsion in clinical trials (2.4% vs. 11.5%). Most PNAC events occurred in patients who were treated for longer than 28 days. Monitor liver function parameters closely in patients receiving parenteral nutrition, particularly premature infants. If liver function test abnormalities develop, consider discontinuation or dose reduction of intravenous lipid emulsion. In clinical trials with Omegaven (fish oil lipid emulsion) in pediatric patients (n = 189), 60% of patients (n = 113 patients) achieved direct bilirubin concentrations less than 2 mg/dL and AST or ALT concentrations less than 3 times the upper limit of normal; median AST and ALT concentrations for Omegaven-treated patients were 80 and 65 units/L, respectively, by study end.
Hypertriglyceridemia may occur in patients receiving intravenous lipid emulsions, particularly in conditions such as inherited lipid disorders, obesity, diabetes mellitus, and metabolic syndrome. Reported rates of hypertriglyceridemia range from 1% or less to 38%, and depend on the population studied and intravenous lipid emulsion dose used. Measure serum triglyceride concentrations at baseline, at the time of dosage increase, and routinely (i.e., weekly) during treatment to assess the patient's ability to eliminate and metabolize lipid emulsion. In adult patients with triglyceride concentrations more than 400 mg/dL, reduce the dose of intravenous lipid emulsion and monitor serum triglyceride concentrations to avoid adverse reactions associated with hypertriglyceridemia. Serum triglyceride concentrations more than 1,000 mg/dL have been associated with an increased risk of pancreatitis. In pediatric patients with hypertriglyceridemia, lower triglyceride concentrations (i.e., below 400 mg/dL) may be associated with adverse reactions. Monitor serum triglyceride concentrations to avoid potential complications with hypertriglyceridemia such as pancreatitis, lipid pneumonitis, and neurologic changes, including kernicterus. Maintain serum triglyceride concentrations at less than 150 mg/dL to 200 mg/dL in neonates.
Intravenous lipid emulsions contain no more than 25 mcg/L of aluminum. However, aluminum toxicity may occur with prolonged administration in high-risk patients, including those with renal impairment and premature neonates. Premature neonates are at particular risk for aluminum toxicity because of immature renal function, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, who receive parenteral aluminum at rates more than 4 to 5 mcg/kg/day, may develop aluminum toxicity (central nervous system and bone toxicity). Tissue loading may occur at lower administration rates.
In clinical trials with Omegaven (fish oil lipid emulsion) in pediatric patients (n = 189), adverse reactions associated with bleeding were reported in 74 (39%) patients. In postmarketing surveillance, life-threatening hemorrhage after a central venous catheter change was reported in a 9-month old infant with intestinal failure who received parenteral nutrition with Omegaven as the sole lipid source; he had no prior history of bleeding, coagulopathy, or portal hypertension.
30% intravenous lipid emulsion formulations are contraindicated to be given by direct intravenous administration. Diluting 30% formulations to a 10% or 20% concentration does not produce a solution equivalent to the commercially available 10% or 20% emulsions, and such a dilution should not be given by direct intravenous administration.
Intravenous lipid emulsions are contraindicated in patients with fish hypersensitivity, egg hypersensitivity, soybean hypersensitivity (soya lecithin hypersensitivity), or peanut hypersensitivity, or hypersensitivity to any active ingredients or excipients of the products. Signs or symptoms of a hypersensitivity reaction may include tachypnea, dyspnea, hypoxia, bronchospasm, tachycardia, hypotension, cyanosis, vomiting, nausea, headache, sweating, dizziness, altered mentation, flushing, rash, urticaria, erythema, pyrexia, or chills. Discontinue intravenous lipid emulsion infusion immediately if a hypersensitivity reaction occurs, and institute appropriate treatment and supportive measures.
Intravenous lipid emulsions are contraindicated in patients with severe hyperlipidemia or severe disorders of lipid metabolism if characterized by hypertriglyceridemia (serum triglyceride concentrations more than 1,000 mg/dL). Impaired lipid metabolism may occur in conditions such as inherited lipid disorders, obesity, diabetes mellitus, and metabolic syndrome. Measure serum triglyceride concentrations at baseline, at the time of dosage increase, and routinely during treatment to assess patient's ability to eliminate and metabolize lipid emulsion. In adult patients with triglyceride concentrations more than 400 mg/dL, reduce the dose of intravenous lipid emulsion and monitor serum triglyceride concentrations to avoid adverse effects associated with hypertriglyceridemia. Serum triglyceride concentrations more than 1,000 mg/dL have been associated with an increased risk of pancreatitis. Clinical practice guidelines recommend the safe use of intravenous fat emulsion in patients with acute pancreatitis as long as serum triglyceride concentrations are closely monitored and remain less than 400 mg/dL.
Serious adverse reactions, including acute respiratory distress, metabolic acidosis, and death, have been reported in neonates and infants after rapid infusion of intravenous lipid emulsions. Hypertriglyceridemia was commonly reported. Strictly adhere to the recommended total daily dosage and maximum hourly infusion rate (0.15 g/kg/hour). Premature neonates and low-birth-weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. Monitor carefully the infant's ability to eliminate the infused fat from the circulation with an assessment of serum triglyceride and/or plasma free fatty acid concentrations. If signs of poor clearance of lipids from the circulation occur, stop the infusion and initiate a medical evaluation. Serum triglyceride concentrations should be maintained at less than 150 to 200 mg/dL in neonates. Light protection is recommended during the administration of parenteral nutrition (PN) products containing amino acids and/or lipids, especially in neonates, infants, and children younger than 2 years of age to reduce the risk of serious adverse effects. This includes containers and administration sets. The use of light-exposed PN products containing amino acids and/or lipids, particularly in admixtures with vitamins and/or trace elements, may lead to severe adverse effects, particularly in premature neonates. This is because exposure of these solutions to light causes the formation of peroxides and other degradation products. Premature infants are considered at high risk of oxidative stress related to multiple risk factors, including oxygen therapy, phototherapy, weak immune system, and inflammatory response with reduced oxidant defense. A meta-analysis of 4 randomized clinical trials in 800 premature neonates comparing light-exposed (LE) vs. light-protected (LP) PN revealed a 50% reduction in mortality in the LP group compared with the LE group (OR, 0.53; 95% CI, 0.32 to 0.87; p = 0.01). Mortality was also twice as high in males compared with females (20% vs. 9% in the LE group; 11% vs. 4% in the LP group; p less than 0.01).
Use parenteral nutrition with caution in patients with hepatic disease. Hepatobiliary disorders, including cholestasis, hepatic steatosis, steato-hepatitis, gallbladder sludge, fibrosis, and cirrhosis (intestinal failure-associated liver disease [IFALD] or parenteral nutrition-associated liver disease [PNALD]), potentially leading to hepatic failure, may occur in patients without preexisting hepatic disease who receive parenteral nutrition. Cholecystitis and cholelithiasis have also been observed. Premature neonates may be at particular risk for IFALD due to a decreased ability to clear intravenous lipid emulsions and increased free fatty acid plasma concentrations after administration. Monitor liver function parameters closely in patients receiving parenteral nutrition, particularly premature infants. If liver function test abnormalities develop, consider discontinuation or dose reduction of intravenous lipid emulsion.
Intravenous lipid emulsions contain no more than 25 mcg/L of aluminum. However, aluminum toxicity may occur with prolonged administration in high-risk patients, including those with renal impairment and premature neonates. Premature neonates are at particular risk for aluminum toxicity because of immature renal function, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, who receive parenteral aluminum at rates more than 4 to 5 mcg/kg/day, may develop aluminum toxicity (central nervous system and bone toxicity). Tissue loading may occur at lower administration rates.
Refeeding syndrome may occur in patients with severe malnutrition or critically ill patients when parenteral nutrition is initiated. Refeeding syndrome is characterized by the intracellular shift of potassium, phosphorus, and magnesium as the patient becomes anabolic. In high-risk patients, feedings should be initiated gradually to minimize the potential for refeeding syndrome. Additionally, monitor electrolytes carefully in patients at risk for refeeding syndrome, and correct electrolyte imbalance prior to initiation of nutrition support.
Intravenous lipid emulsions may support microbial growth and are an independent risk factor for development of catheter-related bloodstream infections. Patients with malnutrition-associated immunosuppression, long-term use and poor maintenance of intravenous catheters, or concomitant conditions or drugs associated with immunosuppression are at higher risk for infection. To decrease the risk of infection, ensure adherence to aseptic techniques in catheter placement, catheter maintenance, and preparation and administration of intravenous lipid emulsions. Monitor for signs and symptoms of early infections (fever and chills), including laboratory tests that may indicate infection (leukocytosis and hyperglycemia). Frequently assess the parenteral access device and insertion site for edema, redness, and discharge.
Use intravenous lipid emulsions with caution in trauma patients with bone fractures of the pelvis and long bone as these patients are at high risk for fat embolism.
Use soybean oil-based intravenous lipid emulsions with caution in patients with pulmonary disease (i.e., chronic obstructive pulmonary disease (COPD) or chronic lung disease (CLD)) or acute respiratory distress syndrome (ARDS). Alterations in lung function and hemodynamics may occur after administration, due to the proinflammatory properties of soybean oil-based IV lipid emulsions. Clinical practice guidelines recommend withholding or limiting traditional soybean oil-based lipid emulsions in the first week following initiation of parenteral nutrition in critically ill adult patients.
There are no data available on the risks associated with intravenous lipid emulsion during pregnancy. Animal reproduction studies have not been performed with intravenous lipid emulsion, and it is not known if intravenous lipid emulsion can cause fetal harm when administered during pregnancy. Consider the risks and benefits of using intravenous lipid emulsion during pregnancy. Parenteral nutrition should be considered if the pregnant woman's nutritional requirements cannot be met with oral or enteral intake.
There are no data available regarding the presence of intravenous lipid emulsion in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for intravenous lipid emulsion, and any potential adverse effects on the breast-fed infant from intravenous lipid emulsion, or from the underlying maternal condition.
Omegaven (fish oil lipid emulsion) is contraindicated in patients with severe bleeding disorders or coagulopathy due to a potential effect on platelet aggregation. Caution is recommended when using soybean oil-based lipid emulsions in patients with blood coagulation disorders.
The lipids contained in the intravenous lipid emulsions may cause laboratory test interference with some laboratory tests such as hemoglobin, lactate dehydrogenase (LDH), bilirubin, and oxygen saturation, if blood is sampled before lipids have cleared from the bloodstream. Lipids are normally cleared 5 to 6 hours after the lipid infusion is stopped. The vitamin K content of intravenous lipid emulsions may counteract anticoagulant activity.
General dosage information:
-Although clinical data have supported the use of newer generation intravenous lipid emulsions for their reduction in inflammatory response, outcomes and adverse reaction data are limited. The FDA-approved product labeling states that the omega-6:omega-3 fatty acid ratio in SMOFlipid or Omegaven has not been shown to improve clinical outcomes compared to other intravenous lipid emulsions.
-Guidelines for nutrition support in critically ill patients recommend withholding or limiting soybean oil-based ILE during the first week after initiation of parenteral nutrition to a maximum of 100 g/week (usually given as 250 mL once or twice weekly) if there is concern for fatty acid deficiency.
For the treatment of essential fatty acid deficiency when oral or enteral nutrition is not possible:
Intravenous dosage (soybean oil-based lipid emulsions [i.e., Intralipid, Nutrilipid]):
Adults: 8% to 10% of the caloric intake should be supplied by intravenous lipid emulsion for correction of fatty acid deficiency.
Infants, Children, and Adolescents: 8% to 10% of the caloric intake should be supplied by intravenous lipid emulsion for correction of fatty acid deficiency.
Neonates: 8% to 10% of the caloric intake should be supplied by intravenous lipid emulsion for correction of fatty acid deficiency.
For nutritional supplementation to provide calories and essential fatty acids as part of parenteral nutrition therapy (essential fatty acid deficiency prophylaxis):
Intravenous dosage (soybean oil/MCT-based lipid emulsions [i.e., Intralipid, Nutrilipid, SMOFlipid]):
Adults: 1 to 2 g/kg/day IV; may advance to a maximum of 2.5 g/kg/day. Fat emulsion should not comprise more than 60% of the patient's total caloric intake. Dosing is highly variable and should be calculated according to individual requirements. For the prevention of fatty acid deficiency, provide at least 2% to 4% of the total caloric intake as linoleic acid and 0.25% to 0.5% as alpha-linolenic acid, which for most adults can be supplied as 250 mL of 20% IV lipid emulsion once or twice weekly.
Children and Adolescents 11 to 17 years: 1 g/kg/day IV; may advance to a maximum dose of 2.5 g/kg/day. Fat emulsion should not comprise more than 60% of the patient's total caloric intake. Dosing is highly variable and should be calculated according to individual requirements. For the prevention of fatty acid deficiency, provide at least 2% to 4% of the total caloric intake as linoleic acid and 0.25% to 0.5% as alpha-linolenic acid, or approximately 0.5 to 1 g/kg/day.
Infants and Children 1 to 10 years: 1 to 2 g/kg/day IV; may advance to a maximum dose of 3 g/kg/day. Fat emulsion should not comprise more than 60% of the patient's total caloric intake. Dosing is highly variable and should be calculated according to individual requirements. For the prevention of fatty acid deficiency, provide at least 2% to 4% of the total caloric intake as linoleic acid and 0.25% to 0.5% as alpha-linolenic acid, or approximately 0.5 to 1 g/kg/day.
Neonates: 0.5 to 1 g/kg/day IV; advance by 0.5 g/kg/day, up to a maximum dose of 3 g/kg/day. Fat emulsion should not comprise more than 60% of the patient's total caloric intake. Dosing is highly variable and should be calculated according to individual requirements. For the prevention of fatty acid deficiency, provide at least 2% to 4% of the total caloric intake as linoleic acid and 0.25% to 0.5% as alpha-linolenic acid, or approximately 0.5 to 1 g/kg/day.
Intravenous dosage (soybean oil/olive oil lipid emulsions [i.e., Clinolipid]):
Adults: 1 to 1.5 g/kg/day IV; may advance to a maximum of 2.5 g/kg/day. Fat emulsion should not comprise more than 60% of the patient's total caloric intake. Dosing is highly variable and should be calculated according to individual requirements. For the prevention of fatty acid deficiency, provide at least 2% to 4% of the total caloric intake as linoleic acid and 0.25% to 0.5% as alpha-linolenic acid, which for most adults can be supplied as 250 mL of 20% IV lipid emulsion once or twice weekly.
-for nutritional supplementation in patients with parenteral nutrition-associated cholestasis (PNAC):
Intravenous dosage (fish oil lipid emulsion [i.e., Omegaven]):
NOTE: Omegaven is not indicated for the prevention of PNAC. It has not been demonstrated that Omegaven prevents PNAC in patients on parenteral nutrition.
Infants, Children, and Adolescents: 1 g/kg/day IV; initial doses may be lower and should be calculated according to individual requirements. Initiate Omegaven dosing as soon as direct or conjugated bilirubin concentrations are 2 mg/dL or greater in patients expected to require parenteral nutrition (PN) for at least 2 weeks. Administer until direct or conjugated bilirubin concentrations are less than 2 mg/dL or until the patient no longer requires PN.
Neonates: 1 g/kg/day IV; initial doses may be lower and should be calculated according to individual requirements. Initiate Omegaven dosing as soon as direct or conjugated bilirubin concentrations are 2 mg/dL or greater in patients expected to require parenteral nutrition (PN) for at least 2 weeks. Administer until direct or conjugated bilirubin concentrations are less than 2 mg/dL or until the patient no longer requires PN.
For lipid resuscitation therapy (LRT)* to treat lipophilic agent overdose (e.g., local anesthetic toxicity*, calcium-channel blocker toxicity*, beta-blocker toxicity*):
Intravenous dosage (20% soybean oil-based lipid emulsions [i.e., Intralipid, Nutrilipid]):
Adults: 1.5 mL/kg (lean body weight) IV bolus administered over 1 to 3 minutes followed by 0.25 mL/kg/minute IV infusion for 30 to 60 minutes. If the patient remains unstable after the initial bolus, rebolus once or twice and double the infusion rate. If a significant response occurs quickly, adjust infusion to one-tenth of the initial rate (0.025 mL/kg/minute). If instability re-emerges, increase infusion back to 0.25 mL/kg/minute, or, in severe cases, repeat bolus. Suggested Max: 10 to 12 mL/kg. The safety of infusions beyond 1 hour has not been established.
Infants, Children, and Adolescents: 1 to 1.5 mL/kg IV bolus, repeated every 3 to 5 minutes as needed (Max cumulative bolus: 3 mL/kg) followed by 0.25 mL/kg/minute IV infusion for no more than 60 minutes. American College of Medical Toxicology guidance recommends adjusting the infusion to one-tenth of the initial rate (0.025 mL/kg/minute) if a significant response occurs quickly. If instability re-emerges, increase infusion back to 0.25 mL/kg/minute, or, in severe cases, repeat bolus. Suggested Max: 10 mL/kg.
Neonates: Very limited data; 1 mL/kg IV bolus was reported in a 2-day-old neonate with bupivacaine-induced cardiotoxicity.
Therapeutic Drug Monitoring:
Dosage Adjustment for Hypertriglyceridemia
Adults: When triglyceride concentrations rise above 400 mg/dL, limit doses of IV lipid emulsion (ILE) to the provision of essential fatty acids (e.g., 250 mL of 20% ILE, give once or twice weekly). Consider holding ILE when serum triglyceride concentrations are more than 500 mg/dL.
Pediatric patients: Temporary interruption of ILE is recommended when serum triglyceride concentrations exceed 250 mg/dL in neonates and infants and 400 mg/dL in older children. Maintain serum triglyceride concentrations at less than 150 to 200 mg/dL in neonates.
-Soybean oil-based lipid emulsion (i.e., Intralipid, Nutrilipid): A decrease in the infusion rate by 0.02 to 0.04 g/kg/hour is suggested when ILE is restarted.
-Fish oil lipid emulsion (i.e., Omegaven): If triglycerides remain elevated, consider a reduced dose of 0.5 to 0.7 g/kg/day, with an incremental increase to 1 g/kg/day.
Maximum Dosage Limits:
-Adults
2.5 g/kg/day IV for nutritional supplementation (soybean oil-based lipid emulsions); safety and efficacy of Omegaven has not been established; 12 mL/kg IV maximum cumulative dose recommended for lipid resuscitation therapy (off-label).
-Geriatric
2.5 g/kg/day IV for nutritional supplementation (soybean oil-based lipid emulsions); safety and efficacy of Omegaven has not been established; 12 mL/kg IV maximum cumulative dose recommended for lipid resuscitation therapy (off-label).
-Adolescents
2.5 g/kg/day IV (soybean oil-based lipid emulsions); 1 g/kg/day IV (Omegaven).
-Children
11 to 12 years: 2.5 g/kg/day IV (soybean oil-based lipid emulsions); 1 g/kg/day IV (Omegaven).
1 to 10 years: 3 g/kg/day IV (soybean oil-based lipid emulsions); 1 g/kg/day IV (Omegaven).
-Infants
3 g/kg/day IV (soybean oil-based lipid emulsions); 1 g/kg/day IV (Omegaven).
-Neonates
3 g/kg/day IV (soybean oil-based lipid emulsions); 1 g/kg/day IV (Omegaven).
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; the dose should be individualized based on clinical goals. Exercise caution when administering to patients with hepatic impairment as the liver is responsible for converting circulating free fatty acids to low density lipoproteins that enter the bloodstream. Additionally, hepatobiliary disorders are known to occur in patients receiving parenteral nutrition.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; the dose should be individualized based on clinical goals.
*non-FDA-approved indication
Abciximab: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Acebutolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Acetaminophen; Aspirin: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Alteplase: (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Amiloride: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Amlodipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Amlodipine; Atorvastatin: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Amlodipine; Benazepril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Amlodipine; Celecoxib: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Amlodipine; Olmesartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Amlodipine; Valsartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Anagrelide: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Angiotensin II receptor antagonists: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Angiotensin-converting enzyme inhibitors: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Anticoagulants: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Antithrombin III: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Apixaban: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Argatroban: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Aspirin, ASA: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Caffeine: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Dipyridamole: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased. (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Omeprazole: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Aspirin, ASA; Oxycodone: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Atenolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Atenolol; Chlorthalidone: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Azilsartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Azilsartan; Chlorthalidone: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Benazepril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Beta-adrenergic blockers: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Betaxolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Betrixaban: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Bisoprolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Bivalirudin: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Brimonidine; Timolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Bumetanide: (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased.
Calcium-channel blockers: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Candesartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Captopril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Carteolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Carvedilol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Central-acting adrenergic agents: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Chlorothiazide: (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Chlorthalidone: (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Cilostazol: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Clevidipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Clonidine: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Clopidogrel: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Dabigatran: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Dalteparin: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Diazoxide: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Diltiazem: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Dipyridamole: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Dorzolamide; Timolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Doxazosin: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Edoxaban: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Enalapril, Enalaprilat: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Enoxaparin: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Eplerenone: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Epoprostenol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Eprosartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Eptifibatide: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Esmolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Ethacrynic Acid: (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Felodipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Fenoldopam: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Fondaparinux: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Fosinopril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Furosemide: (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Guanfacine: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Heparin: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Hydralazine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Irbesartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Isradipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Labetalol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Levamlodipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Levobunolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Lisinopril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Loop diuretics: (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Losartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Mecamylamine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Methyldopa: (Moderate) Monitor blood pressure during concomitant fish oil and central-acting adrenergic agent use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Metolazone: (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Metoprolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Minoxidil: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Moexipril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Nadolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Nebivolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Nebivolol; Valsartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Nicardipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
NIFEdipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Nimodipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Nisoldipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Nitroprusside: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Olmesartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Pentosan: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Perindopril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Perindopril; Amlodipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Phenoxybenzamine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Pindolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Platelet Inhibitors: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Prasugrel: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Prazosin: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Propranolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Quinapril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Ramipril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Reteplase, r-PA: (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Rivaroxaban: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Sacubitril; Valsartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Spironolactone: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Telmisartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Telmisartan; Amlodipine: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Tenecteplase: (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Thiazide diuretics: (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Thrombolytic Agents: (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Ticagrelor: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Timolol: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Tirofiban: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Torsemide: (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Trandolapril: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Trandolapril; Verapamil: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Triamterene: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure during concomitant fish oil and potassium-sparing diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Valsartan: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) Monitor blood pressure during concomitant fish oil and thiazide diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Vasodilators: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Verapamil: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
Vorapaxar: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
Warfarin: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly. (Moderate) Monitor coagulation parameters closely during coadministration. Anticoagulant activity of warfarin may be counteracted by coadministration of intravenous lipid emulsions due to the natural vitamin K content of soybean and olive oils contained in the product.
Intravenous lipid emulsions (ILEs) are utilized as a source of energy causing an increase in heat production, decrease in respiratory quotient, and increase in oxygen consumption. The most common mechanism of action for energy production derived from fatty acid metabolism is beta oxidation. Fatty acids are important for membrane structure and function, precursors for bioactive molecules (such as prostaglandins), and as regulators for gene expression. ILEs will prevent the biochemical lesions of essential fatty acid deficiency (EFAD) and correct the clinical manifestations of EFAD syndrome. ILEs are oil-in-water emulsions consisting of 1 or more triglyceride-containing oils, a phospholipid emulsifier, and glycerin. Phospholipid emulsifying agents, such as egg phosphatide, produce a barrier to prevent coalescence of oil droplets dispersed in the internal phase of the emulsion. The purpose of the emulsifying agent is to keep the particle size less than 0.5 micrometer. The phospholipid emulsifier provides stability to ILEs by functioning as both a mechanical and electrical barrier. Intravenous lipid emulsions are available as 10% concentration (lipid content of 0.1 g/mL), providing 1.1 kcal/mL, 20% concentration (lipid content of 0.2 g/mL), providing 2 kcal/mL, and 30% concentration (lipid content of 0.3 g/mL), providing 3 kcal/mL.
Lipid Resuscitation Therapy (LRT)
There are 3 proposed mechanisms for the efficacy of LRT, which include lipid sink sponge: ILEs sequester lipophilic drugs within serum, separating drug molecules from aqueous phase thus removing effects on end-organ tissues; mass action: ILEs provide abundance of free fatty acids as substrate to drive myocyte's preferred energy pathway, mitochondrial beta-oxidation; and ion channel activation: ILEs activate voltage-gated calcium channels increasing intracellular calcium and cardiac contractility.
Lipid emulsions are administered intravenously. The infused fat particles are cleared from the bloodstream in a way thought to be similar to the clearing of naturally produced chylomicrons formed after enteral fat intake. After infusion, there is a transient increase in plasma triglycerides. The triglycerides are hydrolyzed to free fatty acids and glycerol by the enzyme lipoprotein lipase. The free fatty acids either enter the tissues (where they may be oxidized or resynthesized into triglycerides and stored) or circulate in the plasma, bound to albumin. In the liver, circulating free fatty acids are oxidized or converted to very low-density lipoproteins that re-enter the bloodstream. Lipids are normally cleared 5 to 6 hours after the lipid infusion is stopped. Three factors affect the plasma clearance of lipids: phospholipid content (both 20% and 30% intravenous lipid emulsions (ILEs) contain 1.2%), particle size, and infusion rate. Phosphatides are the hydrophobic components of membranes and provide electrically insulated layers. They are involved in the formation of membrane structures. Choline prevents deposition of fat in the liver. Glycerol is metabolized to carbon dioxide and glycogen or is used in the synthesis of body fats. The mean essential fatty acid content of SMOFlipid is 35 mg/mL (range: 28 to 50 mg/mL) of linoleic acid (omega-6) and 4.5 mg/mL (range: 3 to 7 mg/mL) of linolenic acid (omega-3). This represents a linoleic acid content of 14% to 25% and a linolenic content of 1.5% to 3.5%. This compares with 44% to 62% for linoleic acid and 4% to 11% for linolenic acid for soybean oil ILE products. The main fatty acid components of the fish oil in Omegaven are EPA (13% to 26%) and DHA (14% to 27%), which are omega-3 fatty acids. Omegaven also contains 1.5% and 1.1% of linoleic and alpha linolenic acid, respectively. The fish oil component has a total omega-3 fatty acid content of 40% to 54%. The osmolality of Omegaven is 342 mOsm/kg of water which represents an osmolarity of 273 mOsm/L. The osmolality of 20% ILEs is approximately 350 to 390 mOsm/kg of water, which represents an osmolarity of 260 to 280 mOsm/L. The osmolality of 30% ILEs is approximately 310 mOsm/kg of water, representing an osmolarity of 200 mOsm/L. The pH of ILEs ranges from 6 to 9.