Get your patient on Erythrocin Lactobionate - Erythromycin Lactobionate injection, Powder, Lyophilized, For Solution (Erythromycin Lactobionate)

Erythrocin Lactobionate-IV (erythromycin lactobionate for injection, USP) is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the diseases listed below when oral administration is not possible or when the severity of the infection requires immediate high serum levels of erythromycin. Intravenous therapy should be replaced by oral administration at the appropriate time.

Upper respiratory tract infections of mild to moderate degree caused by Streptococcus pyogenes (Group A beta-hemolytic streptococci); Streptococcus pneumoniae (Diplococcus pneumoniae) ; Haemophilus influenzae (when used concomitantly with adequate doses of sulfonamides, since many strains of H. influenzae are not susceptible to the erythromycin concentrations ordinarily achieved). (See appropriate sulfonamide labeling for prescribing information)

Lower respiratory tract infections of mild to moderate severity caused by Streptococcus pyogenes (Group A beta-hemolytic streptococci); Streptococcus pneumoniae (Diplococcus pneumoniae) .

Respiratory tract infections due to Mycoplasma pneumoniae .

Skin and skin structure infections of mild to moderate severity caused by Streptococcus pyogenes and Staphylococcus aureus (resistant staphylococci may emerge during treatment).

Diphtheria: As an adjunct to antitoxin infections due to Corynebacterium diphtheriae to prevent establishment of carriers and to eradicate the organism in carriers.

Erythrasma: In the treatment of infections due to Corynebacterium minutissimum .

Acute pelvic inflammatory disease caused by Neisseria gonorrhoeae : Erythrocin Lactobionate-IV (erythromycin lactobionate for injection, USP) followed by erythromycin stearate or erythromycin base orally, as an alternative drug in treatment of acute pelvic inflammatory disease caused by N. gonorrhoeae in female patients with a history of sensitivity to penicillin.

Before treatment of gonorrhea, patients who are suspected of also having syphilis should have a microscopic examination for T. pallidum (by immunofluorescence or darkfield) before receiving erythromycin and monthly serologic tests for a minimum of 4 months thereafter.

Legionnaires' Disease caused by Legionella pneumophila . Although no controlled clinical efficacy studies have been conducted, in vitro and limited preliminary clinical data suggest that erythromycin may be effective in treating Legionnaires' Disease.

Prevention of Initial Attacks of Rheumatic Fever
Penicillin is considered by the American Heart Association to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of Group A beta-hemolytic streptococcal infections of the upper respiratory tract e.g., tonsillitis, or pharyngitis). ¹ Erythromycin is indicated for the treatment of penicillin-allergic patients. The therapeutic dose should be administered for ten days.

Prevention of Recurrent Attacks of Rheumatic Fever
Penicillin or sulfonamides are considered by the American Heart Association to be the drugs of choice in the prevention of recurrent attacks of rheumatic fever. In patients who are allergic to penicillin and sulfonamides, oral erythromycin is recommended by the American Heart Association in the long-term prophylaxis of streptococcal pharyngitis (for the prevention of recurrent attacks of rheumatic fever). ¹

Prevention of Bacterial Endocarditis
Although no controlled clinical efficacy trials have been conducted, oral erythromycin has been recommended by the American Heart Association for prevention of bacterial endocarditis in penicillin-allergic patients with prosthetic cardiac valves, most congenital cardiac malformations, surgically constructed systemic pulmonary shunts, rheumatic or other acquired valvular dysfunction, idiopathic hypertrophic subaortic stenosis (IHSS), previous history of bacterial endocarditis and mitral valve prolapse with insufficiency when they undergo dental procedures and surgical procedures of the upper respiratory tract. ²

To reduce the development of drug-resistant bacteria and maintain the effectiveness of erythromycin and other antibacterial drugs, erythromycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

For the treatment of severe infections in adults and pediatric patients, the recommended intravenous dose of erythromycin lactobionate is 15 to 20 mg/kg/day. Higher doses, up to 4 g/day, may be given for severe infections.

Administration of doses of ≥4 g/day may increase the risk for the development of erythromycin-induced hearing loss in elderly patients, particularly those with reduced renal or hepatic function. Erythrocin Lactobionate-IV (erythromycin lactobionate for injection, USP) in the ADD-Vantage system must be administered by intermittent intravenous infusion only. Due to the irritative properties of erythromycin, IV push is an unacceptable route of administration.

Intravenous erythromycin should be replaced by oral erythromycin as soon as possible.

The drug should be administered as a single dose from the ADD-Vantage flexible diluent container. Discard any unused portion.

For intermittent infusion: administer one-fourth the total daily dose of erythromycin lactobionate by intravenous infusion in 20 to 60 minutes at intervals not greater than every six hours. The final diluted solution of erythromycin lactobionate is prepared to give a concentration of 1 to 5 mg/mL. No less than 100 mL of IV diluent should be used. Infusion should be sufficiently slow to minimize pain along the vein.

For treatment of acute pelvic inflammatory disease caused by N. Gonorrhoeae , in female patients hypersensitive to penicillins, administer 500 mg erythromycin lactobionate every six hours for three days, followed by oral administration of 250 mg erythromycin stearate or base every six hours for seven days.

For treatment of Legionnaires' Disease: Although optimal doses have not been established, doses utilized in reported clinical data were 1 to 4 grams daily in divided doses.

Administration of doses of ≥4 g/day may increase the risk for the development of erythromycin-induced hearing loss in elderly patients, particularly those with reduced renal or hepatic function.

In the treatment of Group A beta-hemolytic streptococcal infections of the upper respiratory tract (e.g., tonsillitis or pharyngitis), the therapeutic dosage of erythromycin should be administered for ten days. The American Heart Association suggests a dosage of 250 mg of erythromycin orally, twice a day in long-term prophylaxis of streptococcal upper respiratory tract infections for the prevention of recurring attacks of rheumatic fever in patients allergic to penicillin and sulfonamides. ¹

In prophylaxis against bacterial endocarditis (See INDICATIONS AND USAGE ) the oral regimen for penicillin allergic patients is erythromycin 1 gram, 1 hour before the procedure followed by 500 mg six hours later. ²

Preparation of Solution:
The Erythrocin Lactobionate-IV ADD-Vantage vial may be used with either 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP in the ADD-Vantage flexible diluent container. The 500 mg ADD-Vantage vials must be used as single doses with the 100 mL ADD-Vantage flexible diluent containers. The resulting solution will contain erythromycin activity equal to approximately 5 mg/mL.

Do not administer unless solution is clear and container is undamaged. Discard any unused portion.

INSTRUCTIONS FOR USE

To Use Vial in ADD-Vantage Flexible Diluent Container

To Open:
Peel overwrap at corner and remove solution container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container:
(Use Aseptic Technique)

1. Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
   1. To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (See FIGURE 1.), then pull straight up to remove the cap. (See FIGURE 2.) NOTE: Do not access vial with syringe.

Figure 1                                                                    Figure 2

• • To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (See FIGURE 3.)
• Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (See FIGURE 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go.
  NOTE: Once vial is seated, do not attempt to remove. (See FIGURE 4.)

Figure 3                                                                         Figure 4

1. 3 Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.
2. Label appropriately.

To Reconstitute the Drug:

• Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.
• With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (See FIGURE 5.)
• Pull the inner cap from the drug vial. (See FIGURE 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.
• Mix container contents thoroughly and use within the specified time.

Figure 5                                                                     Figure 6

Preparation for Administration:
(Use Aseptic Technique)

1. Confirm the activation and admixture of vial contents.
2. Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.
3. Close flow control clamp of administration set.
4. Remove cover from outlet port at bottom of container.
5. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated.

NOTE: See full directions on administration set carton.

1. Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.
2. Squeeze and release drip chamber to establish proper fluid level in chamber.
3. Open flow control clamp and clear air from set. Close clamp.
4. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.
5. Regulate rate of administration with flow control clamp.

WARNING: Do not use flexible containers in series connections.

Stability:

In 0.9% Sodium Chloride Injection, USP
The final diluted solution of erythromycin lactobionate should be completely administered within 8 hours in order to assure proper potency.

In 5% Dextrose Injection, USP
The final diluted solution of erythromycin lactobionate should be completely administered within 2 hours in order to assure proper potency.

No drug or chemical agent should be added to an Erythrocin Lactobionate-IV fluid admixture unless its effect on the chemical and physical stability of the solution has first been determined.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
WARNING: Do not use flexible container in series connections.

Erythromycin is contraindicated in patients with known hypersensitivity to this antibiotic. Erythromycin is contraindicated in patients taking terfenadine or astemizole, cisapride, pimozide, ergotamine, or dihydroergotamine (See WARNINGS and PRECAUTIONS – Drug Interactions ).

Do not use erythromycin concomitantly with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors (statins) that are extensively metabolized by cytochrome P450 isoform 3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis (See WARNINGS and PRECAUTIONS – Drug Interactions ).

Erythromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes. (See WARNINGS ).

Side effects following the use of intravenous erythromycin are rare. Occasional venous irritation has been encountered, but if the infusion is given slowly, in dilute solution, preferably by continuous intravenous infusion or intermittent infusion in no less than 20 to 60 minutes, pain and vessel trauma are minimized.

Allergic reactions ranging from urticaria to anaphylaxis have occurred. Skin reactions ranging from mild eruptions to erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely.

There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin.

Elderly patients, particularly those with reduced renal or hepatic function, may also be at increased risk for developing this effect when Erythrocin ^TM doses of 4 grams/day or higher are given (See DOSAGE AND ADMINISTRATION ).

Erythrocin ^TM Lactobionate-IV (erythromycin lactobionate for injection, USP) is a lyophilized powder for intravenous infusion only. It is available as a sterile, white to off-white lyophilized powder in single dose ADD-Vantage ^TM vials. Each vial contains the equivalent of 500 mg of erythromycin activity. It is prepared as a solution and lyophilized in its final container. The lactobionic acid content is 244 mg per vial. Lactobionic acid and/or erythromycin is used to adjust the pH during the manufacture of the product. The Erythrocin Lactobionate-IV ADD-Vantage ^TM vial is designed for use only with the ADD-Vantage flexible diluent container. After appropriate dilution, the Erythrocin Lactobionate-IV ADD-Vantage Delivery System contains erythromycin lactobionate equivalent to 500 mg of erythromycin activity in 100 mL. The pH of the reconstituted solution is 6.5 - 7.5.

The solutions contain no bacteriostat, antimicrobial agent (except erythromycin) or buffer and are intended for use as a single-dose injection only with the ADD-Vantage flexible diluent container.

Erythromycin is produced by a strain of Streptomyces erythraeus and belongs to the macrolide group of antibiotics. It is basic and readily forms salts with acids. Erythromycin lactobionate has the following structure:

Erythromycin diffuses readily into most body fluids. In the absence of meningeal inflammation, low concentrations are normally achieved in the spinal fluid but the passage of the drug across the blood-brain barrier increases in meningitis. Erythromycin crosses the placental barrier and is excreted in breast milk. Erythromycin is not removed by peritoneal dialysis or hemodialysis.

In the presence of normal hepatic function, erythromycin is concentrated in the liver and is excreted in the bile; the effect of hepatic dysfunction on biliary excretion of erythromycin is not known. From 12 to 15 percent of intravenously administered erythromycin is excreted in active form in the urine.

Intravenous infusion of 500 mg of erythromycin lactobionate at a constant rate over 1 hour in fasting adults produced a mean serum erythromycin level of approximately 7 mcg/mL at 20 minutes, 10 mcg/mL at 1 hour, 2.6 mcg/mL at 2.5 hours, and 1 mcg/mL at 6 hours.

Microbiology

Mechanism of Action
Erythromycin acts by inhibition of protein synthesis by binding 50 S ribosomal subunits of susceptible organisms. It does not affect nucleic acid synthesis.

Resistance
Resistance to erythromycin in S. aureus may emerge during therapy. Many isolates of Haemophilus influenzae are resistant to erythromycin but are susceptible to erythromycin and sulfonamides when used concomitantly.

Interactions with other Antimicrobials

Antagonism has been demonstrated in vitro between erythromycin and clindamycin, lincomycin and chloramphenicol.

Antimicrobial Activity

Erythromycin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections (See INDICATIONS AND USAGE ):

Aerobic bacteria

Gram-positive bacteria

• Corynebacterium diphtheriae
• Corynebacterium minutissimum
• Staphylococcus aureus
• Streptococcus pneumoniae
• Streptococcus pyogenes

Gram-negative bacteria

• Legionella pneumophila
• Neisseria gonorrhoeae

Other Microorganisms

• Mycoplasma pneumoniae

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for erythromycin against isolates of similar genus or organism group. However, the efficacy of erythromycin in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

Aerobic bacteria

Gram-negative bacteria

• Moraxella catarrhalis

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see:

Erythrocin Lactobionate-IV (erythromycin lactobionate for injection, USP) is supplied as a sterile, white to off-white lyophilized powder as follows:

Store at 20 to 25ºC (68 to 77ºF). [See USP Controlled Room Temperature].