DRUG INTERACTIONS

 Antiplatelet Agents and Anticoagulants: Prolonged bleeding time has been reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. 

Periodically monitor bleeding time in patients receiving Omegaven and concomitant antiplatelet agents or anticoagulants

BRIEF SUMMARY

FISH OIL TRIGLYCERIDES- (July 2018)

Indn-   As   source of calories and fatty acids in pediatric patients  with parentral nutrion-associated endometriosis

Comp-   Injectable Emulsion: 5 g/50 mL and 10 g/100 mL (0.1 g/mL) in a single-dose bottle.

CI-   • Known hypersensitivity to fish or egg protein or to any of the active ingredients or excipients.  • Severe hemorrhagic disorders.  • Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides greater than 1,000 mg/dL.

 WARNINGS -                                                                                                                      • Risk of Death in Preterm Infants due to Pulmonary Lipid Accumulation:       Deaths in preterm infants after infusion of intravenous soybean oil-based lipid emulsions have been reported in literature, and autopsy findings included intravascular fat accumulation in the lungs.

Pat Inform-

Inform patients, their families, or caregivers of the following risks of Omegaven:      • Risk of death in preterm infants due to pulmonary lipid accumulation • Hypersensitivity reactions [see Warnings and Precautions                                  • Risk of infections [see Warnings and precautions.                                                   • Fat overload syndrome.      

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U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  25

ADVERSE REACTIONS-

 Most common adverse drug reactions (>15%) are: vomiting, agitation, bradycardia, apnea and viral infection.

CONTRAINDICATIONS-                                                                                                     • Known hypersensitivity to fish or egg protein or to any of the active ingredients or excipients.

 • Severe hemorrhagic disorders. 

 • Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides greater than 1,000 mg/dL.

 WARNINGS AND PRECAUTIONS-                                                                                    • Risk of Death in Preterm Infants due to Pulmonary Lipid Accumulation:       Deaths in preterm infants after infusion of intravenous soybean oil-based lipid emulsions have been reported in literature, and autopsy findings included intravascular fat accumulation in the lungs.

Risk with Omegaven is unknown. Monitor for signs and symptoms of pleural or pericardial effusion.    

 • Hypersensitivity Reactions:                                                                                 Monitor for signs or symptoms. Discontinue infusion if reaction occurs.                            

 • Risk of Infections, Fat Overload Syndrome, Refeeding Syndrome, and Hypertriglyceridemia: Monitor for signs and symptoms; monitor laboratory parameters.  

• Aluminum Toxicity: Increased risk in patients with renal impairment, including preterm infants.   

 • Monitoring and Laboratory Tests: Routine laboratory monitoring is recommended, including monitoring for essential fatty acid deficiency.

INDICATIONS AND USAGE

 Omegaven is indicated as a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis (PNAC).

  Limitations of Use:                                                                                                           • Omegaven is not indicated for the prevention of PNAC. It has not been demonstrated that Omegaven prevents PNAC in parenteral nutrition (PN)-dependent patients.  

• It has not been demonstrated that the clinical outcomes observed in patients treated with Omegaven are a result of the omega-6:omega-3 fatty acid ratio of the product.

DOSAGE AND ADMINISTRATION                                                                                     • For infusion into a central or peripheral vein.   

 • May be infused directly from the bottle or admixed in a parenteral nutrition (PN) container.      

• Prior to administration, correct severe fluid and electrolyte disorders and measure serum triglycerides to establish a baseline level.         

• Initiate dosing in PN-dependent pediatric patients as soon as direct or conjugated bilirubin levels are 2 mg/dL or greater.     

• Recommended dosage depends on age, energy expenditure, clinical status, body weight, tolerance, ability to metabolize, and consideration of additional energy sources given to the patient.   

• The recommended daily dose (and the maximum dose) in pediatric patients is 1 g/kg/day.           

• For information on infusion rate when initiating dosing and in patients with elevated triglyceride levels, see the full prescribing information.   

• The recommended duration for infusion is between 8 and 24 hours, depending on the clinical situation.       

 • Administer Omegaven until direct or conjugated bilirubin levels are less than 2 mg/dL or until the patient no longer requires PN.

HOW SUPPLIED/STORAGE AND HANDLING

Omegaven (fish oil triglycerides) injectable emulsion, 5 g/50 mL and 10 g/100 mL (0.1 g/mL) is a white, homogenous, sterile emulsion supplied as follows:

 50 mL single-dose glass bottle - Carton of 10 x 50 mL ,                                                    100 mL single-dose glass bottle- Carton of 10 x 100 mL                                                     The stopper used as the bottle closure is not made with natural rubber latex, PVC, or DEHP.

Storage and Handling

 Store below 25°C (77°F).                                                                                                   

 Avoid excessive heat.                                                                                                         

 Do not freeze.                                                                                                                     

If accidentally frozen, discard product.                                                                               

 Once the bottle is connected to the infusion set, use Omegaven immediately.

Complete infusion within 12 hours when using a Y-connector.   

 Infuse admixtures containing Omegaven immediately.

 If not used immediately, admixtures can be stored for up to 6 hours at room temperature or up to 24 hours under refrigeration.        

Complete the infusion within 24 hours after removal from storage.

 PATIENT COUNSELING INFORMATION

 Inform patients, their families, or caregivers of the following risks of Omegaven:    

 • Risk of death in preterm infants due to pulmonary lipid accumulation

 • Hypersensitivity reactions [see Warnings and Precautions

 • Risk of infections [see Warnings and precautions.   

 • Fat overload syndrome.      

  • Refeeding syndrome.                                                                                                     

   • Hypertriglyceridemia (see Warnings and precautions.)   

   • Aluminum toxicity.

Fresenius Kabi and Omegaven are registered trademarks of Fresenius Kabi.           Manufactured by: Graz, Austria www.fresenius-kabi.com

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                                     Omegaven provides a biologically utilizable source of calories and essential fatty acids. Fatty acids serve as an important substrate for energy production. The most common mechanism of action for energy production derived from fatty acid metabolism is beta oxidation.

Fatty acids are also important for membrane structure and function, as precursors for bioactive molecules (such as prostaglandins), and as regulators of gene expression.

2.Pharmacokinetics-                                                                                                           The plasma concentrations of EPA and DHA, the major fatty acids in Omegaven, as well as linoleic acid and alpha-linolenic acid (essential fatty acids) were measured along with the markers of essential fatty acid status in 58 pediatric patients with PNAC after an intravenous infusion of 1 mg/kg/day of Omegaven over 10 weeks.

Five patients received Omegaven as the exclusive lipid source, and all others received concurrent enteral or oral nutrition.  

USE IN SPECIFIC POPULATIONS-         

 Pregnancy Risk Summary -                                                                                              There are no available data on Omegaven use in pregnant women to establish a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with fish oil triglycerides.  

The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

 In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.                                             

2. Lactation Risk Summary-                                                                                               No data are available regarding the presence of fish oil triglycerides from Omegaven in human milk, the effects on the breastfed infant, or the effects on milk production. Lactating women receiving oral omega-3 fatty acids have been shown to have higher levels of omega-3 fatty acids in their milk.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Omegaven, and any potential adverse effects of Omegaven on the breastfed infant.

3. Pediatric Use-                                                                                                                 The effectiveness of Omegaven was established in two open-label clinical trials of 82 pediatric patients, 3 to 42 weeks of age, including preterm neonates with estimated gestational age of greater than 24 weeks at birth.

The most common adverse reactions in Omegaven-treated patients were vomiting, agitation, and bradycardia.

4.Geriatric Use-                                                                                                                   Clinical trials of Omegaven did not include patients 65 years of age and older. 

 OVERDOSAGE-                                                                                                                 In the event of an overdose, fat overload syndrome may occur,Stop the infusion of Omegaven until triglyceride levels have normalized and any symptoms have abated. The effects are usually reversible by stopping the lipid infusion. If medically appropriate, further intervention may be indicated. Lipids are not dialyzable from serum.