Vibramycin
( Doxycycline Hydrochloride)
DESCRIPTION :
VIBRAMYCIN brand of doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline and is available as VIBRAMYCIN Monohydrate (doxycycline monohydrate) and VIBRAMYCIN Hyclate (doxycycline hydrochlonde 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. Doxycycline will not degrade into an epianhydro form.
VIBRAMYCIN is available in Egypt as: Capsules containing 100 mg of doxycycline hyclate with the following inert
ingredients: Lactose, maize starch, alginic acid, magnesium stearate and sodium lauryl sulfate.
ACTIONS :
VIBRAMYCIN is primarily bacteriostatic and is thought to exert its antimicrobial effect by the mhibition of protein synthesis. VIBRAMYCIN is active against a wide range of gram-positive and gram-negative microorganisms.
Tetracyctines 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 torm. VIBRAMYCIN is virtually completely absorbed after oral administration. Studies reported 10 date indicate that the absorption of VIBRAMYCIN. unlike certain other
tetracyclines, IS not notably influenced by the ingestion of food or milk. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcglml of VIBRAMYCIN at 2 hours decreasing 10 1.45 mcg/ml al24 hours. Excretion of doxycycline by the kidney is about 40% , 72 hours in individuals with normal renal function (creatinine clearance about 75 ml/min.). This percentage excretion may fall to a range as sow as 1-5% 172 hours in individuals
with severe renal insufficiency (creatinine clearance below 10 mllmin.). Studies have shown no significant difference in serum half-hfe of VIBRAMYCIN (range 18 to 22 hours) in individuals with normal and severely impaired renal function. Hemodtalvsts does not alter the serum half-life of VIBRAMYCIN
INDICATIONS :
– VIBRAMYCIN is indicated in infections caused by the following microorganisms: Rickettsiae: Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rtckettslalpox, and tick fevers.
– Mycoplasma pneumoniae (PPLO, Eaton Agent), Chlamydia psittaci (formerly agents of psittacosis and ornithosis), Chlamydia trachomatis (formerly agents of lymphogranuloma venereum), VIBRAMYCIN is indicated for the treatment of uncomplicated urethral. endocervical, or rectal infections in adults caused by Chlamydia trachomatls.
– calymmatobacterium (Donovania) granulomatis (formerly agents of granuloma inguinale), Borrelia recurrentls and B. duttonii: the sprrocnetat agent of louse and tick-borne relapsing fevers. Ureaplasma urealyticum (T -Mycoplasma), as an agent of nongonococcal urethritis and in males associated with infertility.
Plasmodium falclparum (chloroquine-resistant falciparum malaria).
– The following gram-negative microorganisms Haemophilus ducreyi (chancroid), Yersinia pestis (formerly Pasteurella pestis), Franclsella tutarensls (formerly Pasteurella tularensis), Bartonella bacilliformis, Bacteroides species, Fusobacterium species, Campylobacter fetus (formerly Vibrio fetus), Brucella species (in conjunction with streptomycin)
– Because many strains of the following groups of microorganisms have been shown to be resistant to tetracychnes. culture and susceptibility testing are recommended.
– VIBRAMYCIN is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic tastinq indicates appropriate susceptibility to the drug: Neisseria gonorrhoeae, Vibrio cholerae (formerly Vibrio comma), Escherichia coli, Enterobacter aerogenes, Shigella species, Acinetobacter species (formerly Mlma species and Herellea species), Haemophllus influenzae (respiratory infections), Klebsiella species (respiratory
and urinary infections). Branhamella catarrhalls.
– VIBRAMYCIN is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:
Streptococcus species: A certain percentage of strains of Streptococcus
pyogenes and Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore. tetracyciines should not be used for streptococcal disease unless the organism has been demonstrated to be sensitive.
– For upper respiratory infections due 10 group A beta-hemolytic streptococci, penicillin is Ihe usual drug of choice, including prophylaxis of rheumatic fever. Streptococcus pneumoniae (formerly Diplococcus pneumoniae) , Staphylococcus aureus, respiratory, skm and soft-tissue infections. Tetracyclines are not the drug of choice in the treatment of any type of staphylococcal infection.
– When penicillin is contraindicated, VIBRAMYCIN is an alternative drug in the treatment of infections due to:
Treponema pallidum and Treponema pertenue (syphilis and yaws), Listeria monocytogenes. Clostridium species. Bacillus anthracis, Leptotrichia buccalis (former!y Fusobacterium fuslforme) Vincent’s Infection, Actinomyces species.
– In acute intestinal amebtasis VIBRAMYCIN may be a useful adjunct to amebicides.
– In severe acne doxycycline may be useful adjunctive therapy.
– VIBRAMYCIN is indicated in the treatment of trachoma, although the Intectrous agent is not always eliminated, as judqed by immunofluorescence.
– VIBRAMYCIN is indicated for the treatment of Stage I Lyme disease Inclusion conjunctivitis may be treated with oral Vibramycin alone. or with a cornbmanon at topical agents
– VIBRAMYCIN is indicated for the prophylaxIs and treatment of Leptospuosis
– VIBRAMYCIN is indicated for the treatment and setectrve prophylaxis of cholera
– VIBRAMYCIN is indicated for prophylaxis in the following conditions :scrub typhus (Rickettsia tsutsugamushi), traveters crarmea (enterotoxigenic Escherichia coli), Malana (In areas with chloroquine resistant Plasmodium falciparum).
CONTRAINDICATIONS :
This drug IS contraindicated In persons who have shown hypersensitivity to any of the tetracyclines
WARNING :
– The use of drugs 01 the tetracycline class durmg 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) Ttus adverse reaction LS more common dunnq long term use of the drugs but has been observed following repeated short term courses Enamel hypoplasia has also been reported
VIBRAMYCIN. therefore. should nOI be used m these groups 0f patients unless other drugs are not available. are not likely 10 be effective or are contraindicated
– Photosensitivity manifested by an exaggerated sunburn react-on has been observed in some individuals taking tetracyclines (Paltents likely to be exposed to direct sunlight or ultraviolet light should be aovised that ttus reaction can occur with tetracycline drugs. and treatment should be discontinued at the first evrdence of skin erythema)
– The antranabohc acuon of the tetracycllnes may cause an iocrease m BUN Studies to date moicate that thts does not occur With the use of doxycycline in patients with Impaired renal function
Use In Pregnancy :
(See “warnings” section about use during tooth development) VIBRAMYCIN has not been studied in pregnant patients It should not be used in pregnant women unless, In the Judgment 01 the ohvsrcran. It is essential for the welfare of the patient
Results of ammat studies indicate that tetracyctines cross the placenta. are found in fetal tissues and can have toxic effects on Ihe devetoomq fetus (often related to retardation of skeletal development) EVidence of embryotoxtcny has also been noted in animals treated early In pregnancy
Use in Children :
(See “Warnings” section about use dUring loath development) As With other tetracychnes, VIBRAMYCIN forms a stable calcium complex In any bone-forming tissue. A decrease in the ftbula growth rate has been observed,” 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 ottactaunq women who are taking a drug of this class and should therefore be avoided in nursing mothers
PRECAUTIONS :
– The use of antibiotics may occasionally result in overgrowth at non susceptible organisms. Constant observation of the patient is essential. If a resistant organism appearsi the antibiotic should be discontinued and appropriate therapy instituted.
– When treating venereal disease when coexistent syphilis is suspected, proper diagnostic procedures, including dark-field examinations, should be utilized. In all such cases monthly serological tests should be made for at least four months.
– in long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic renal. and hepatic studies should be performed.
– Infections due to group A beta-hernotyttc streptococci should be treated for at least 10 days
Drug Interactions :
– Because the tetracycHnes have been shown to depress plasma prothrombin activity. patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage
– Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving doxycycline in conjunction with penicillin.
– Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium; iron-containing preparations; and bismuth salts.
– Alcohol, barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline
– The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.
– There have been anecdotal reports that concurrent use of tetracyclines may render oral contraceptives less effective.
ADVERSE REACTIONS :
– Due 10 virtually complete absorption 01 VIBRAMYCIN, gastrointestinal side effects are infrequent. The following adverse reactions have been observed in patients receiving tetracyctines.
– Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphaqia, enterocolitis: and inflammatory lesions (with monilial overgrowth) in the anogenital region. Abnormal hepatic function has been reported rarely. These reactions have been caused by both the oral and parenteral administration of tetracyclines.
Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule form of drugs in the tetracycline class. Most of these patients took medications immediately before going to bed. – Skin: maculopapular and erythematous rasnes.Exfonatlve dermatitis has been reported but is uncommon. Photosensitivity is discussed in the “Warnings” section
– Renal Toxicity: Rise in BUN has been reported with tetracyciines and is apparently dose related. (See “Warnings”).
– Hypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, 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 with tetracyclines.
– When given over prolonged periods, tetracycHnes have been reported to produce brown-black rnicroscopic discoloration of thyroid glands. No abnormalities of thyroid function studies are known to occur.
DOSAGE AND ADMINISTRATION :
Dosage
– It must be remembered that the usual dosage and frequency of administration of VtBRAMYCIN differs from that of most other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of side effects. Therapy should be continued at least 24 to 48 hours after symptoms and fever have subsided. When used in streptococcal infections, therapy should be continued for 10 days to prevent the development of rheumatic fever or glomerulonephritis.
– The usual dose of VIBRAMYCIN in adults is 200 mg on the first day of treatment (administered as a single dose or as 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day (administered as a single dose). In the management of more severe infections (particularly chronic infections of the unnary tract). 200 mg daily should be given throughout the treatment period.
– For children above 8 years of age: the recommended dosage schedule for children weighing 50 kg or less is 4 mg/kg of body weight (given as a single daily dose or divided into two doses on the first day of treatment). followed by 2 mg/kg of body weight {given as a single daily dose or divided into two doses), on subsequent days. For more severe infections up to 4 mg/kg of body weight may be used. For children over 50 kg the usual adult dose should be used.
(See”Warnings” section about use in children.)
– Acne Vulgaris : One capsule 1 00 mg orally every other day in the morning with breakfast, for up to 12 weeks.
– Uncomplicated gonococcal infections (except anorectal infections in men): 100 mg by mouth twice daily tor 7 days. As an alternative single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose should be administered with food, including milk or carbonated beverage, as required.
– Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatl.: 100 mg, by mouth, twice daily lor 7 days. Acute epididymo-orchitis caused by C. trachomatls or N. gonorrhoeae 100 mg by mouth twice a day for at least 10 days. tn Ureaplasma urealytlcum (T-Mycoplasma) infections in the male genital tract associated with unexplained infertility, both the infected male and his wife should be treated with 100′ mg twice daily for four weeks.
– Nongonococcal urethritis caused by Ureaplasma urealytlcum 100 mg, by mouth, twice daily for 7 days. Primary and secondary syphiliS:’ 300 mg a day in divided doses for at least 10 days.
– Acute pelvic inflammatory disease (PlO):
Ambulatory — Cefoxitin 2 9 IM or amoxicillin 3 9 by mouth or ampicillin 3.5 g by mouth or aqueous procaine penicillin G 4.8 million units IM at 2 sites or ceftriaxone 250 mg IM. Each of these regimens except ceftriaxone is accompanied by probenecid 1 Q by mouth, followed bv ooxvcvcnne 100 mo by
– For treatment at chjoroqutoe-res.stent falciparum malaria: 200 mg dally for at least 7 days. Due to the potential seventy of the infection, a rapid-acting schizonticide such as quinine should always be given to comuncncn with VIBRAMYCIN ; qemtne dosage recommendations vary 10 different areas
– For prophylaxis of malaria” 100 mg daily in adults; for children over 8 years of age the dose is 2 mglkg given once dally up to the adult dose. Prophylaxis can begin 1-2 days before travel to malarious areas. It should be continued daily during travel in the malarious areas and for 4 weeks aher the traveler leaves the malarious area.
– Tick and louse-borne relapsing levers and louse-borne typhus have been successfully treated with a single oral dose of 100 or 200 mg according to severity.
– For the treatment and selective propnylaxrs of cholera in adults’ 300 mg In a single dose.
– For the prevention of scrub typhus: 200 mg as a single oral dose.
– For the prevention of travelers’ diarrhea in adults: 200 mg on the first day of travel (administered as a single dose or as 100 mg every 12 hours) followed by 100 mg dally throughout the stay in the area. Data on the use of the drug prophylactically are not available beyond 21 days.
– For the prevention of Leptospirosis: 200 mg orally on a weekly basis throughout the stay in the area and 200 mg at the completion of the trip.Data on the use of the drug prophylactically are not available beyond 21 days.
– For the treatment of leptospirosis: lOO mg orally twice daily tor 7 days. Studies to date have indicated that administration of VIBAAMYCIN at the usual recommended doses does not lead to excessive accumulation of the antibiotic in patients with renal impairment.
Administration
– Administration of adequate amounts of fhnd along with capsule form of drugs in the tetracycline dass is recommended to reduce the risk of esophageal initauon and ulceration.
– If gastric irritation occurs, it is recommended that VIBRAMYCIN be given with food Of milk. Studies indICate that the ebsorpnon of VIBRAMYCIN IS not markedty influenced by simultaneous ingestion of food or milk.
OVERDOSAGE :
In case overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum halt·hfe and thus would not be of benefit in treating cases of overdosage.
HOW SUPPLIED :
Capsules (as the hyclate), blister pack of 10 capsules, 100 mg each
Manufactured by :
Pflzer Egypt S.A.E. Cairo A.R.E.
under authority of Pflzer INC., USA.
