Vibramycin injection prescribing information

VIBRAMYCIN
doxycycline hyclate for injection
INTRAVENOUS
FOR INTRAVENOUS USE ONLY
DESCRIPTION
Vibramycin (doxycycline hyclate for injection) Intravenous is a broad-spectrum antibioticsynthetically derived from oxytetracycline, and is available as Vibramycin Hyclate(doxycycline hydrochloride hemiethanolate hemihydrate). The chemical designation of thislight-yellow crystalline powder is alpha-6-deoxy-5-oxytetracycline. Doxycycline has a highdegree of lipoid solubility and a low affinity for calcium binding. It is highly stable innormal human serum.
Doxycycline is primarily bacteriostatic and thought to exert its antimicrobial effect by theinhibition of protein synthesis. Doxycycline is active against a wide range of gram-positiveand gram-negative organisms.
The drugs in the tetracycline class have closely similar antimicrobial spectra and crossresistance among them is common. Microorganisms may be considered susceptible todoxycycline (likely to respond to doxycycline therapy) if the minimum inhibitoryconcentration (M.I.C.) is not more than 4.0 mcg/mL. Microorganisms may be consideredintermediate (harboring partial resistance) if the M.I.C. is 4.0 to 12.5 mcg/mL andresistant (not likely to respond to therapy) if the M.I.C. is greater than 12.5 mcg/mL.
Susceptibility plate testing: If the Kirby-Bauer method of disc susceptibility testing is used,a 30 mcg doxycycline disc should give a zone of at least 16 mm when tested against adoxycycline-susceptible bacterial strain. A tetracycline disc may be used to determinemicrobial susceptibility. If the Kirby-Bauer method of disc susceptibility testing is used, a30 mcg tetracycline disc should give a zone of at least 19 mm when tested against atetracycline-susceptible bacterial strain.
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree.
They are concentrated by the liver in the bile, and excreted in the urine and feces at highconcentrations and in a biologically active form.
Following a single 100 mg dose administered in a concentration of 0.4 mg/mL in a one-hour infusion, normal adult volunteers average a peak of 2.5 mcg/mL, while 200 mg of aconcentration of 0.4 mg/mL administered over two hours averaged a peak of 3.6 mcg/mL.
Excretion of doxycycline by the kidney is about 40 percent/72 hours in individuals withnormal function (creatinine clearance about 75 mL/min.). This percentage excretion mayfall as low as 1-5 percent/72 hours in individuals with severe renal insufficiency (creatinineclearance below 10 mL/min.). Studies have shown no significant difference in serum half-life of doxycycline (range 18-22 hours) in individuals with normal and severely impairedrenal function.
Hemodialysis does not alter this serum half-life of doxycycline.
INDICATIONS
Doxycycline is indicated in infections caused by the following microorganisms: Rickettsiae (Rocky Mountain spotted fever, typhus fever, and the typhus group,Q fever, rickettsialpox and tick fevers).
Mycoplasma pneumoniae (PPLO, Eaton Agent).
Agents of psittacosis and ornithosis.
Agents of lymphogranuloma venereum and granuloma inguinale.
The spirochetal agent of relapsing fever (Borrelia recurrentis).
The following gram-negative microorganisms: Haemophilus ducreyi (chancroid),Pasteurella pestis and Pasteurella tularensis,Bartonella bacilliformis,Bacteroides species,Vibrio comma and Vibrio fetus,Brucella species (in conjunction with streptomycin).
Because many strains of the following groups of microorganisms have been shown to beresistant to tetracyclines, culture and susceptibility testing are recommended.
Doxycycline is indicated for treatment of infections caused by the following gram-negativemicroorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli,Enterobacter aerogenes (formerly Aerobacter aerogenes),Shigella species,Mima species and Herellea species,Haemophilus influenzae (respiratory infections),Klebsiella species (respiratory and urinary infections).
Doxycycline is indicated for treatment of infections caused by the following gram-positivemicroorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:Streptococcus species: Up to 44 percent of strains of Streptococcus pyogenes and 74 percent of Streptococcusfaecalis have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used for streptococcal disease unless the organism has been demonstrated tobe sensitive.
For upper respiratory infections due to group A beta-hemolytic streptococci, penicillin isthe usual drug of choice, including prophylaxis of rheumatic fever.
Diplococcus pneumoniae,Staphylococcus aureus, respiratory skin and soft tissue infections. Tetracyclines are notthe drugs of choice in the treatment of any type of staphylococcal infections.
Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure): toreduce the incidence or progression of disease following exposure to aerosolized Bacillusanthracis.
When penicillin is contraindicated, doxycycline is an alternative drug in the treatment ofinfections due to: Neisseria gonorrhoeae and N. meningitidis,Treponema pallidum and Treponema pertenue (syphilis and yaws),Listeria monocytogenes,Clostridium species,Fusobacterium fusiforme (Vincent’s infection),Actinomyces species.
In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides.
Doxycycline is indicated in the treatment of trachoma, although the infectious agent is notalways eliminated, as judged by immunofluorescence.
CONTRAINDICATIONS
This drug is contraindicated in persons who have shown hypersensitivity to any of thetetracyclines.
WARNINGS
THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTHDEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY AND CHILDHOODTO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OFTHE TEETH (YELLOW-GRAY-BROWN). This adverse reaction is more commonduring long-term use of the drugs but has been observed following repeated short-termcourses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS,THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP, EXCEPT FORANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE),UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARECONTRAINDICATED.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in someindividuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultravioletlight, should be advised that this reaction can occur with tetracycline drugs, and treatmentshould be discontinued at the first evidence of skin erythema.
The antianabolic action of the tetracyclines may cause an increase in BUN. Studies to dateindicate that this does not occur with the use of doxycycline in patients with impaired renalfunction.
Usage in Pregnancy
(See above WARNINGS about use during tooth development.)
Vibramycin Intravenous has not been studied in pregnant patients. It should not be used inpregnant women unless, in the judgment of the physician, it is essential for the welfare ofthe patient.
Results of animal studies indicate that tetracyclines cross the placenta, are found in fetaltissues and can have toxic effects on the developing fetus (often related to retardation ofskeletal development). Evidence of embryotoxicity has also been noted in animals treatedearly in pregnancy.
Usage in Children
The use of Vibramycin Intravenous in children under 8 years is not recommended because
safe conditions for its use have not been established.
(See above WARNINGS about use during tooth development.) As with other tetracyclines, doxycycline forms a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures givenoral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to bereversible when the drug was discontinued.
Tetracyclines are present in the milk of lactating women who are taking a drug in thisclass.
PRECAUTIONS
As with other antibiotic preparations, use of this drug may result in overgrowth ofnonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic shouldbe discontinued and appropriate therapy instituted.
In venereal diseases when coexistent syphilis is suspected, a dark field examination shouldbe done before treatment is started and the blood serology repeated monthly for at least 4months.
Because tetracyclines have been shown to depress plasma prothrombin activity, patientswho are on anticoagulant therapy may require downward adjustment of their anticoagulantdosage.
In long-term therapy, periodic laboratory evaluation of organ systems, includinghematopoietic, renal, and hepatic studies should be performed.
All infections due to group A beta-hemolytic streptococci should be treated for at least 10days.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it isadvisable to avoid giving tetracycline in conjunction with penicillin.
ADVERSE REACTIONS
Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis,and inflammatory lesions (with monilial overgrowth) in the anogenital region.
Hepatotoxicity has been reported rarely. These reactions have been caused by both theoral and parenteral administration of tetracyclines.
Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported butis uncommon. Photosensitivity is discussed above. (See WARNINGS.) Renal toxicity: Rise in BUN has been reported and is apparently dose related. (SeeWARNINGS.) Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoidpurpura, pericarditis and exacerbation of systemic lupus erythematosus.
Bulging fontanels in infants and benign intracranial hypertension in adults have beenreported in individuals receiving full therapeutic dosages. These conditions disappearedrapidly when the drug was discontinued.
Blood: Hemolytic anemia, thrombocytopenia, neutropenia and eosinophilia have beenreported.
When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid functionstudies are known to occur.
DOSAGE AND ADMINISTRATION
Note: Rapid administration is to be avoided. Parenteral therapy is indicated only when oraltherapy is not indicated. Oral therapy should be instituted as soon as possible. Ifintravenous therapy is given over prolonged periods of time, thrombophlebitis may result.
THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OFVIBRAMYCIN I.V. (100-200 MG/DAY) DIFFERS FROM THAT OF THE OTHERTETRACYCLINES (1-2 G/DAY). EXCEEDING THE RECOMMENDED DOSAGEMAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.
Studies to date have indicated that Vibramycin at the usual recommended doses does notlead to excessive accumulation of the antibiotic in patients with renal impairment.
Adults: The usual dosage of Vibramycin I.V. is 200 mg on the first day of treatmentadministered in one or two infusions. Subsequent daily dosage is 100 to 200 mgdepending upon the severity of infection, with 200 mg administered in one or twoinfusions.
In the treatment of primary and secondary syphilis, the recommended dosage is 300 mgdaily for at least 10 days.
In the treatment of inhalational anthrax (post-exposure) the recommended dose is 100 mgof doxycycline, twice a day. Parenteral therapy is only indicated when oral therapy is notindicated and should not be continued over a prolonged period of time. Oral therapyshould be instituted as soon as possible. Therapy must continue for a total of 60 days.
For children above eight years of age: The recommended dosage schedule for childrenweighing 100 pounds or less is 2 mg/lb of body weight on the first day of treatment,administered in one or two infusions. Subsequent daily dosage is 1 to 2 mg/lb of bodyweight given as one or two infusions, depending on the severity of the infection. Forchildren over 100 pounds the usual adult dose should be used. (See WARNINGS Sectionfor Usage in Children.) In the treatment of inhalational anthrax (post-exposure) the recommended dose is 1 mg/lb(2.2 mg/kg) of body weight, twice a day in children weighing less than 100 lb (45 kg).
Parenteral therapy is only indicated when oral therapy is not indicated and should not becontinued over a prolonged period of time. Oral therapy should be instituted as soon aspossible. Therapy must continue for a total of 60 days.
General: The duration of infusion may vary with the dose (100 to 200 mg per day), but isusually one to four hours. A recommended minimum infusion time for 100 mg of a0.5 mg/mL solution is one hour. Therapy should be continued for at least 24-48 hoursafter symptoms and fever have subsided. The therapeutic antibacterial serum activity willusually persist for 24 hours following recommended dosage.
Intravenous solutions should not be injected intramuscularly or subcutaneously. Cautionshould be taken to avoid the inadvertent introduction of the intravenous solution into theadjacent soft tissue.
PREPARATION OF SOLUTION
To prepare a solution containing 10 mg/mL, the contents of the vial should bereconstituted with 10 mL (for the 100 mg/vial container) or 20 mL (for the 200 mg/vialcontainer) of Sterile Water for Injection or any of the ten intravenous infusion solutionslisted below. Each 100 mg of Vibramycin (i.e., withdraw entire solution from the 100 mgvial) is further diluted with 100 mL to 1000 mL of the intravenous solutions listed below.
Each 200 mg of Vibramycin (i.e., withdraw entire solution from the 200 mg vial) is furtherdiluted with 200 mL to 2000 mL of the following intravenous solutions: 1. Sodium Chloride Injection, USP2. 5% Dextrose Injection, USP3. Ringer’s Injection, USP4. Invert Sugar, 10% in Water5. Lactated Ringer’s Injection, USP6. Dextrose 5% in Lactated Ringer’s7. Normosol-M in D5-W (Abbott)8. Normosol-R in D5-W (Abbott)9. Plasma-Lyte 56 in 5% Dextrose (Travenol) 10. Plasma-Lyte 148 in 5% Dextrose (Travenol) This will result in desired concentrations of 0.1 to 1.0 mg/mL. Concentrations lower than0.1 mg/mL or higher than 1.0 mg/mL are not recommended.
Stability
Vibramycin IV is stable for 48 hours in solution when diluted with Sodium Chloride
Injection, USP, or 5% Dextrose Injection, USP, to concentrations between 1.0 mg/mL
and 0.1 mg/mL and stored at 25°C. Vibramycin IV in these solutions is stable under
fluorescent light for 48 hours, but must be protected from direct sunlight during storage
and infusion. Reconstituted solutions (1.0 to 0.1 mg/mL) may be stored up to 72 hours
prior to start of infusion if refrigerated and protected from sunlight and artificial light.
Infusion must then be completed within 12 hours. Solutions must be used within these
time periods or discarded.
Vibramycin IV, when diluted with Ringer’s Injection, USP, or Invert Sugar, 10% inWater, or Normosol-M in D5-W (Abbott), or Normosol-R in D5-W (Abbott), orPlasma-Lyte 56 in 5% Dextrose (Travenol), or Plasma-Lyte 148 in 5% Dextrose(Travenol) to a concentration between 1.0 mg/mL and 0.1 mg/mL, must be completelyinfused within 12 hours after reconstitution to ensure adequate stability. During infusion,the solution must be protected from direct sunlight. Reconstituted solutions (1.0 to0.1 mg/mL) may be stored up to 72 hours prior to start of infusion if refrigerated andprotected from sunlight and artificial light. Infusion must then be completed within 12hours. Solutions must be used within these time periods or discarded.
When diluted with Lactated Ringer’s Injection, USP, or Dextrose 5% in LactatedRinger’s, infusion of the solution (ca. 1.0 mg/mL) or lower concentrations (not less than0.1 mg/mL) must be completed within six hours after reconstitution to ensure adequate stability. During infusion, the solution must be protected from direct sunlight. Solutionsmust be used within this time period or discarded.
Solutions of Vibramycin (doxycycline hyclate for injection) at a concentration of10 mg/mL in Sterile Water for Injection, when frozen immediately after reconstitution arestable for 8 weeks when stored at −20°C. If the product is warmed, care should be takento avoid heating it after the thawing is complete. Once thawed the solution should not berefrozen.
HOW SUPPLIED
Vibramycin (doxycycline hyclate for injection) Intravenous is available as a sterile powderin a vial containing doxycycline hyclate equivalent to 100 mg of doxycycline with 480 mgof ascorbic acid; packages of 5 (0049-0960-77), and in individually packaged vialscontaining doxycycline hyclate equivalent to 200 mg of doxycycline with 960 mg ofascorbic acid (0049-0980-81).
2001 Pfizer Inc
Roerig
Division of Pfizer Inc, NY, NY 10017

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