Vibramycin (doxycycline hyclate for injection) Intravenous is a broad-spectrum antibiotic synthetically derived from oxytetracycline, and is available as Vibramycin Hyclate (doxycycline hydrochloride hemiethanolate hemihydrate). The chemical designation of this light-yellow crystalline powder is alpha-6-deoxy-5-oxytetracycline. Doxycycline has a high degree of lipoid solubility and a low affinity for calcium binding. It is highly stable in normal human serum.

Vibramycin has the following structural formula:

Last updated on RxList: 3/4/2008

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 be resistant to tetracyclines, culture and susceptibility testing are recommended.

Doxycycline is indicated for treatment of infections caused by the following gram-negative microorganisms 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-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: Streptococcus species:

Up to 44 percent of strains of Streptococcus pyogenes and 74 percent of Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used for streptococcal disease unless the organism has been demonstrated to be sensitive.

For upper respiratory infections due to group A beta-hemolytic streptococci, penicillin is the usual drug of choice, including prophylaxis of rheumatic fever.

Diplococcus pneumoniae,

Staphylococcus aureus, respiratory skin and soft tissue infections. Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infections.

Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of infections 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 not always eliminated, as judged by immunofluorescence.

Note: Rapid administration is to be avoided. Parenteral therapy is indicated only when oral therapy is not indicated. Oral therapy should be instituted as soon as possible. If intravenous therapy is given over prolonged periods of time, thrombophlebitis may result.

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF VIBRAMYCIN I.V. (100-200 MG/DAY) DIFFERS FROM THAT OF THE OTHER TETRACYCLINES (1-2 G/DAY). EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Studies to date have indicated that Vibramycin at the usual recommended doses does not lead 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 treatment administered in one or two infusions. Subsequent daily dosage is 100 to 200 mg depending upon the severity of infection, with 200 mg administered in one or two infusions.

In the treatment of primary and secondary syphilis, the recommended dosage is 300 mg daily for at least 10 days.

In the treatment of inhalational anthrax (post-exposure) the recommended dose is 100 mg of doxycycline, twice a day. Parenteral therapy is only indicated when oral therapy is not indicated and should not be continued over a prolonged period of time. Oral therapy should 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 children weighing 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 body weight given as one or two infusions, depending on the severity of the infection. For children over 100 pounds the usual adult dose should be used. (See WARNINGS Section for 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 be continued over a prolonged period of time. Oral therapy should be instituted as soon as possible. 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 is usually one to four hours. A recommended minimum infusion time for 100 mg of a 0.5 mg/mL solution is one hour. Therapy should be continued for at least 24-48 hours after symptoms and fever have subsided. The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

Intravenous solutions should not be injected intramuscularly or subcutaneously. Caution should be taken to avoid the inadvertent introduction of the intravenous solution into the adjacent soft tissue.

PREPARATION OF SOLUTION

To prepare a solution containing 10 mg/mL, the contents of the vial should be reconstituted with 10 mL (for the 100 mg/vial container) or 20 mL (for the 200 mg/vial container) of Sterile Water for Injection or any of the ten intravenous infusion solutions listed below. Each 100 mg of Vibramycin (i.e., withdraw entire solution from the 100 mg vial) 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 further diluted with 200 mL to 2000 mL of the following intravenous solutions:

1. Sodium Chloride Injection, USP

2. 5% Dextrose Injection, USP

3. Ringer's Injection, USP

4. Invert Sugar, 10% in Water

5. Lactated Ringer's Injection, USP

6. Dextrose 5% in Lactated Ringer's

7. 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 than 0.1 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% in Water, or Normosol-M^® in D5-W (Abbott), or Normosol-R^® in D5-W (Abbott), or Plasma-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 completely infused within 12 hours after reconstitution to ensure adequate stability. During infusion, the solution must be protected from direct sunlight. 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.

When diluted with Lactated Ringer's Injection, USP, or Dextrose 5% in Lactated Ringer's, infusion of the solution (ca. 1.0 mg/mL) or lower concentrations (not less than 0.1 mg/mL) must be completed within six hours after reconstitution to ensure adequate stability. During infusion, the solution must be protected from direct sunlight. Solutions must be used within this time period or discarded.

Solutions of Vibramycin (doxycycline hyclate for injection) at a concentration of 10 mg/mL in Sterile Water for Injection, when frozen immediately after reconstitution are stable for 8 weeks when stored at -20°C. If the product is warmed, care should be taken to avoid heating it after the thawing is complete. Once thawed the solution should not be refrozen.

Vibramycin (doxycycline hyclate for injection) Intravenous is available as a sterile powder in a vial containing doxycycline hyclate equivalent to 100 mg of doxycycline with 480 mg of ascorbic acid; packages of 5 (0049-0960-77), and in individually packaged vials containing doxycycline hyclate equivalent to 200 mg of doxycycline with 960 mg of ascorbic acid (0049-0980-81).

©2001 Pfizer Inc Roerig, Division of Pfizer Inc, NY, NY 10017, 69-1940-00-3, Revised November 2001

Last updated on RxList: 12/8/2004

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 the oral and parenteral administration of tetracyclines.

Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See WARNINGS.)

Renal toxicity: Rise in BUN has been reported and is apparently dose related. (See WARNINGS.)

Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, pericarditis and exacerbation of systemic lupus erythematosus.

Bulging fontanels in infants and benign intracranial hypertension in adults have been reported in individuals receiving full therapeutic dosages. These conditions disappeared rapidly when the drug was discontinued.

Blood: Hemolytic anemia, thrombocytopenia, neutropenia and eosinophilia have been reported.

When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function studies are known to occur.

No information available.

Last updated on RxList: 12/8/2004

THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY AND CHILDHOOD TO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (YELLOW-GRAY-BROWN). This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP, EXCEPT FOR ANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE), UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light, should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.

The antianabolic action of the tetracyclines may cause an increase in BUN. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.

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 in pregnant women unless, in the judgment of the physician, it is essential for the welfare of the patient.

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early 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 given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.

Tetracyclines are present in the milk of lactating women who are taking a drug in this class.

As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.

In venereal diseases when coexistent syphilis is suspected, a dark field examination should be done before treatment is started and the blood serology repeated monthly for at least 4 months.

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies should be performed.

All infections due to group A beta-hemolytic streptococci should be treated for at least 10 days.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline in conjunction with penicillin.

Last updated on RxList: 12/8/2004

No information available.

This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

Last updated on RxList: 12/8/2004

ACTIONS

Doxycycline is primarily bacteriostatic and thought to exert its antimicrobial effect by the inhibition of protein synthesis. Doxycycline is active against a wide range of gram-positive and gram-negative organisms.

The drugs in the tetracycline class have closely similar antimicrobial spectra and cross resistance among them is common. Microorganisms may be considered susceptible to doxycycline (likely to respond to doxycycline therapy) if the minimum inhibitory concentration (M.I.C.) is not more than 4.0 mcg/mL. Microorganisms may be considered intermediate (harboring partial resistance) if the M.I.C. is 4.0 to 12.5 mcg/mL and resistant (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 a doxycycline-susceptible bacterial strain. A tetracycline disc may be used to determine microbial susceptibility. If the Kirby-Bauer method of disc susceptibility testing is used, a 30 mcg tetracycline disc should give a zone of at least 19 mm when tested against a tetracycline-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 high concentrations 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 a concentration 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 with normal function (creatinine clearance about 75 mL/min.). This percentage excretion may fall as low as 1-5 percent/72 hours in individuals with severe renal insufficiency (creatinine clearance 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 impaired renal function.

Hemodialysis does not alter this serum half-life of doxycycline.

Last updated on RxList: 12/8/2004

No separate information available. Please however See the WARNINGS and PRECAUTIONS sections

Last updated on RxList: 12/8/2004

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DOXYCYCLINE - INJECTION

(dox-ee-SYE-kleen)

USES: Doxycycline is used to treat a wide variety of bacterial infections. This medication is known as a tetracycline antibiotic. It works by stopping the growth of bacteria.

This antibiotic treats only bacterial infections. It will not work for viral infections (e.g., common cold, flu). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to control the build-up of fluid around the lungs (pleural effusion) caused by tumors that have spread to the lungs. For this condition, doxycycline is placed in the space around the lungs through a chest tube.

HOW TO USE: This medication is given by injection into a vein by a health care professional, usually once or twice daily or as directed by your doctor. Doxycycline must be mixed with the proper IV fluids. Before using this product, check it visually for particles or discoloration. If either is present, do not use the liquid. This medication should be infused slowly over at least 1 hour (usual range is 1 to 4 hours). If you have questions about the use of this medication, consult your pharmacist.

The dosage is based on your medical condition and response to treatment. When treating children older than 8 years, the dosage is also based on weight.

Antibiotics work best when the amount of medicine in your body is kept at a constant level. Therefore, use this drug at evenly spaced intervals.

Continue to use this medication for the full time prescribed, even if symptoms disappear after a few days. Stopping the medication too early may result in a return of the infection.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Diarrhea, loss of appetite, nausea, vomiting, headache, or rectal discomfort may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: sunburn-like skin reaction (sun sensitivity), unusual change in the amount of urine, weakness, unusual tiredness, brown/gray tooth discoloration, redness/swelling/pain at the injection site.

Tell your doctor immediately if any of these rare but very serious side effects occur: hearing changes (e.g., ringing in the ears, decreased hearing), persistent/severe headache, vision changes (e.g., blurred vision), easy bruising/bleeding, new signs of infection (e.g., persistent sore throat, fever, chills), stomach/abdominal pain, persistent nausea/vomiting, yellowing eyes/skin, dark urine.

This medication may rarely cause a severe intestinal condition (pseudomembranous colitis) due to a type of resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have any of the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction, including: rash, skin sores/blisters, itching, swelling, severe dizziness, trouble breathing, new or worsening swelling/pain in the joints, chest pain, fast/irregular heartbeat.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking doxycycline, tell your doctor or pharmacist if you are allergic to it; or to other tetracycline medication (e.g., minocycline, tetracycline); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, lupus.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Before having surgery, tell your doctor or dentist that you are using doxycycline.

This medication should not be used in children younger than 8 years of age because it may cause permanent tooth discoloration and other problems. Tooth discoloration has also occurred in older children and young adults. Consult your doctor for more information.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details and to discuss reliable forms of birth control. If this medication is used to treat a life-threatening infection and treatment options are limited, discuss the risks and benefits with your doctor.

This medication passes into breast milk in very small amounts. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: certain retinoids (acitretin, isotretinoin, tretinoin).

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting doxycycline.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anti-seizure medications (e.g., carbamazepine, phenytoin), digoxin, live bacterial vaccines, penicillins, phenobarbital, warfarin.

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. Ask your doctor or pharmacist for details. Discuss whether you should use additional reliable birth control methods while taking this medication.

This product can affect the results of certain lab tests (e.g., some urine tests for sugar), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless told to do so by your doctor. A different medication may be necessary in that case.

With prolonged use, laboratory and/or medical tests (e.g., complete blood count, kidney and liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store the unmixed vials at or below room temperature at 77 degrees F (25 degrees C). Protect the vials and mixed solution from light. Consult your pharmacist about how long you can use the medication after it is mixed. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.