Tetracycline Hydrochloride

Class: Tetracyclines
VA Class: AM250
CAS Number: 60-54-8
Brands: Helidac Therapy, Sumycin

Introduction

Antibacterial; antibiotic derived from Streptomyces aureofaciens^{b c d} or produced semisynthetically from oxytetracycline.^b

Uses for Tetracycline Hydrochloride

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.^{c d 104}

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella.^{c d 104} Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.^{c d a}

Acne

Adjunctive treatment of moderate to severe inflammatory acne.^{a c d} Not indicated for treatment of noninflammatory acne.^a

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii;^{104 114 c d} oral tetracyclines (usually doxycycline or tetracycline) used as follow-up after initial parenteral penicillin G.¹¹⁴

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis.^{c d} Tetracyclines not included in current recommendations for treatment of amebiasis caused by Entamoeba.^{112 114}

Anthrax

Alternative to doxycycline for postexposure prophylaxis to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax).¹²² Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline;^{114 122 123 127} doxycycline is the preferred tetracycline because of ease of administration and proven efficacy in monkey studies.¹²²

Alternative to doxycycline for treatment of inhalational anthrax when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).^{c d 122 123} A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is preferred for treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{122 123 i}

Balantidiasis

Treatment of balantidiasis† caused by Balantidium coli; drug of choice.^{112 114}

Bartonella Infections

Treatment of bartonellosis caused by Bartonella bacilliformis.^{c d}

Brucellosis

Treatment of brucellosis;^{104 114 c d} tetracyclines (usually doxycycline or tetracycline) considered drugs of choice.^{104 114} Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),¹¹⁴ especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).¹¹⁴

Burkholderia Infections

Treatment of glanders† caused by Burkholderia mallei.^{104 m} Experience is limited regarding treatment of human cases; optimum regimens not identified.^{123 m} Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy.¹⁰⁴ Other clinicians suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.¹²³ Doxycycline is the preferred tetracycline for treatment of melioidosis caused by susceptible B. pseudomallei.^{123 m}

Campylobacter Infections

Treatment of infections caused by Campylobacter.^{c d} Tetracyclines (usually doxycycline) are alternatives,¹¹⁴ not drugs of choice for C. jejuni.^{104 114}

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi.^{c d} Not included in CDC recommendations for treatment of chancroid;¹⁰¹ CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin, or erythromycin.^{101 102}

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis.^{c d 102} Doxycycline is the preferred tetracycline for treatment of these infections, including presumptive treatment of chlamydial infections in patients with gonorrhea.¹⁰¹

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis.^{c d 104} Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.^{c d}

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis.^{c d 102 104} Doxycycline is the preferred tetracycline for these infections.^{101 114}

Treatment of psittacosis (ornithosis) caused by C. psittaci.^{100 104 114 c d} Doxycycline and tetracycline are drugs of choice.^{100 114} For initial treatment of severely ill patients, use IV doxycycline.¹⁰⁰

Clostridium Infections

Alternative for treatment of infections caused by Clostridium.^{c d} Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.¹⁰⁴

Dientamoeba fragilis Infections

Treatment of Dientamoeba fragilis infections.¹¹² Drugs of choice are iodoquinol, paromomycin, tetracycline, or metronidazole.¹¹²

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella.^{c d} Only use for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective^a and when in vitro susceptibility tests indicate the organism is susceptible.^{a c d}

Fusobacterium Infections

Alternative to penicillin G for the treatment of infections caused by Fusobacterium fusiforme (Vincent's infection).^{c d}

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae.^{c d} Tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.^{101 a}

Empiric treatment of epididymitis most likely caused by N. gonorrhoeae or C. trachomatis; used in conjunction with IM ceftriaxone.¹⁰²

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.^{c d} Doxycycline is the tetracycline recommended as drug of choice by CDC.¹⁰¹

Helicobacter pylori Infection and Duodenal Ulcer Disease

Treatment of Helicobacter pylori infection and duodenal ulcer (active or a history of duodenal ulcer);^{104 e} eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.^{104 e}

Used in a multiple-drug regimen that includes tetracycline, metronidazole, and bismuth subsalicylate and a histamine H₂-receptor antagonist.^e If initial 14-day regimen does not eradicate H. pylori, a retreatment regimen that does not include metronidazole should be used.^e

Leptospirosis

Tetracyclines are alternatives to penicillin G for treatment of leptosporosis†.¹⁰⁴ Doxycycline is the preferred tetracycline for treatment or prevention of these infections.^l

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes.^{c d} Not usually considered a drug of choice or alternative for these infections.^{104 114}

Malaria

Treatment of uncomplicated malaria† caused by chloroquine-resistant Plasmodium falciparum or chloroquine-resistant P. vivax and when the plasmodial species has not been identified.^{112 129}

CDC and others state treatments of choice for uncomplicated chloroquine-resistant P. falciparum malaria are a regimen of oral quinine in conjunction with oral doxycycline, tetracycline, or clindamycin or a regimen of atovaquone and proguanil.^{112 129} A regimen of quinine and doxycycline (or tetracycline) generally preferred over quinine and clindamycin,¹²⁹ except for young children or pregnant women who should not receive tetracyclines.¹²⁹ Quinine in conjunction with tetracycline (or doxycycline) also a regimen of choice for chloroquine-resistant P. vivax malaria.^{112 129}

Treatment of severe malaria caused by P. falciparum†;^{112 129} used in conjunction with IV quinidine gluconate initially and then oral quinine when an oral regimen is tolerated.^{112 129}

Active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. vivax malaria or provide a radical cure; primaquine usually also is indicated to eradicate hypnozoites and prevent relapse in patients treated for P. vivax malaria.^{112 129}

Assistance with diagnosis or treatment of malaria available from the CDC Malaria Epidemiology Branch by contacting the CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.¹²⁹

Nocardiosis

Tetracyclines are alternatives to co-trimoxazole for treatment of nocardiosis† caused by Nocardia.^{104 114}

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.^{c d 104} Doxycycline usually is the tetracycline of choice for NGU.^{101 102}

Consider that some cases of recurrent urethritis following tetracycline treatment may be caused by tetracycline-resistant U. urealyticum.¹⁰¹

Pasteurella multocida Infections

Treatment of infections caused by Pasteurella multocida†.^{104 114} Tetracyclines (usually doxycycline) are alternatives to penicillin G.^{104 114}

Plague

Treatment of plague caused by Yersinia pestis,^{c d 104 114 124} including naturally occurring or endemic bubonic, septicemic, or pneumonic plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.¹²⁴ Regimen of choice is streptomycin or gentamicin;^{104 114 123 124} alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol.^{123 124} For plague meningitis, some experts recommend that chloramphenicol be included in the treatment regimen.¹²³

Postexposure prophylaxis following a high-risk exposure to Y. pestis† (e.g., household, hospital, or other close contact with an individual who has pneumonic plague; laboratory exposure to viable Y. pestis; confirmed exposure in the context of biologic warfare or bioterrorism).^{123 124} Doxycycline may be drug of choice;^{114 123 124} alternatives are tetracycline, ciprofloxacin, or chloramphenicol.¹²³ Prophylaxis not required for asymptomatic contacts of individuals with bubonic plague, but observe such contacts for 1 week and initiate treatment if symptoms occur.¹²³

Rat-bite Fever

Treatment of rat-bite fever† caused by Streptobacillus moniliformis or Spirillum minus.^{104 114} Tetracyclines (usually doxycycline) are alternatives to penicillin G.^{104 114}

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis.^{104 c d} Tetracyclines are drugs of choice.¹⁰⁴

Rickettsial Infections

Treatment of rickettsial infections including Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.^{114 123 c d} Doxycycline is the drug of choice for most rickettsial infections.^{114 a j}

Syphilis

Alternative to penicillin G for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins.^{101 114 c d} Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.¹⁰¹

Tularemia

Treatment of tularemia caused by Francisella tularensis, including naturally occurring or endemic tularemia and tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.^{104 114 123 c d f} Drugs of choice are streptomycin or gentamicin; alternatives are tetracyclines (usually doxycycline), ciprofloxacin, or chloramphenicol.^{104 114 f} Risk of relapse and primary treatment failure may be higher with the alternatives.^f

Postexposure prophylaxis of tularemia† following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury) or in individuals exposed to the organism in the context of biologic warfare or bioterrorism.^{123 f} Drugs of choice are doxycycline, tetracycline, or ciprofloxacin.^{123 f} Postexposure prophylaxis usually not recommended after exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission does not occur.^f

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae.^{104 114 c d h} Doxycycline and tetracycline are drugs of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.^{104 114 c d h}

Treatment of severe V. parahaemolyticus† infection when anti-infective therapy is indicated in addition to supportive care.^h

Treatment of infections caused by V. vulnificus†.¹⁰⁴ Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.^{104 g h} Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.^g

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.^{104 c d}

Yersinia Infections

Treatment of plague or postexposure prophylaxis of plague†.^{c d 104 114 123 124} (See Plague in Uses.)

Treatment of GI infections caused by Yersinia enterocolitica† or Y. pseudotuberculosis†.¹¹⁴ These GI infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections or when septicemia or other invasive disease occurs.¹¹⁴ Some clinicians suggest the role of oral anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.¹¹⁴

Tetracycline Hydrochloride Dosage and Administration

Administration

Oral Administration

Administer orally.^{c d}

Administer capsules and tablets with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration.^{c d}

Dosage

Available as tetracycline^d and tetracycline hydrochloride;^c dosage expressed in terms of tetracycline hydrochloride.^{c d}

Pediatric Patients

General Pediatric Dosage

Oral

Children >8 years of age: 25–50 mg/kg daily in 4 divided doses.^c

Balantidiasis†

Oral

Children ≥8 years of age: 40 mg/kg daily (up to 2 g) in 4 divided doses given for 10 days.^{112 114}

Brucellosis

Oral

Children ≥8 years of age: 30–40 mg/kg daily (up to 2 g) in 4 divided doses.¹¹⁴ Duration of treatment usually is 4–6 weeks; more prolonged treatment may be necessary for severe infections or when there are complications.¹¹⁴

If infection is severe or if endocarditis, meningitis, or osteomyelitis are present, administer IM streptomycin or gentamicin during the first 7–14 days of tetracycline therapy.^{114 c d} Rifampin can be administered concomitantly (with or without an aminoglycoside) to decrease the risk of relapse.¹¹⁴

Dientamoeba fragilis Infection†

Oral

Children ≥8 years of age: 40 mg/kg daily (up to 2 g) in 4 divided doses given for 10 days.¹¹²

Malaria†

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).^{112 129}

Treatment of Uncomplicated P. vivax Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).¹²⁹

In addition, a 14-day regimen of oral primaquine (0.6 mg/kg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.¹²⁹

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹²⁹ If an IV tetracycline is necessary initially, use IV doxycycline until oral therapy can be tolerated.¹²⁹

Plague

Treatment of Pneumonic Plague

Oral

Children >8 years of age: 25–50 mg/kg daily in 4 divided doses^b given for ≥10–14 days.^{123 124}

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential.^{123 124} A parenteral regimen (e.g., IM streptomycin, IM or IV gentamicin, IV doxycycline) is preferred for initial treatment; an oral regimen may be substituted when the patient's condition improves or if a parenteral regimen is unavailable.^{123 124}

Postexposure Prophylaxis following High-risk Exposure†

Oral

Children >8 years of age: 25–50 mg/kg daily in 2 or 4 equally divided doses.^b

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days^{123 124} or the duration of exposure risk plus 7 days.¹²³

Syphilis

Primary or Secondary Syphilis

Oral

Children >8 years of age: 500 mg 4 times daily given for 14 days.^{101 102 114}

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

Children >8 years of age: 500 mg 4 times daily given for 14 days for early latent syphilis (duration <1 year) or 500 mg 4 times daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.^{101 102 114}

Vibrio Infections

Cholera

Oral

Children >8 years of age: 50 mg/kg daily in 4 divided doses given for 3 days.¹¹⁴

Adults

General Adult Dosage

Oral

1–2 g daily in 2–4 divided doses.^{c d}

500 mg twice daily or 250 mg 4 times daily may be adequate for mild to moderate infections; severe infections may required 500 mg 4 times daily.^{c d}

Respiratory Tract Infections

Mycoplasma pneumoniae Infections

Oral

1–2 g daily in 2–4 equally divided doses.^b Duration of treatment usually is 1–4 weeks.^b

Acne

Oral

1 g daily given in divided doses; when improvement occurs in 1–2 weeks, decrease slowly to a maintenance dosage of 125–500 mg daily.^{b c d} Continue maintenance dosage until clinical improvement allows discontinuation of the drug.^b

Actinomycosis

Oral

1–2 g daily for 6–12 months as follow-up to penicillin G.^b

Anthrax

Postexposure Prophylaxis following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

500 mg every 6 hours given for ≥60 days.¹²²

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,^{123 k} but prolonged postexposure prophylaxis usually required.^{122 123} A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure.^k CDC recommends that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) be continued for 60 days.^{122 123} The US Working Group on Civilian Biodefense and the US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.¹²³

Treatment of Inhalational Anthrax

Oral

500 mg every 6 hours.¹²²

Initial parenteral regimen preferred; use oral regimen for initial treatment only when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).^{122 i} Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{102 123 i}

Balantidiasis†

Oral

500 mg 4 times daily given for 10 days.¹¹²

Brucellosis

Oral

500 mg 4 times daily given for 3 weeks.^{c d}

If infection is severe or if endocarditis, meningitis, or osteomyelitis are present, administer IM streptomycin or gentamicin during the first 7–14 days of tetracycline therapy.^{114 c d} Rifampin can be administered concomitantly to decrease the risk of relapse (with or without an aminoglycoside).¹¹⁴

Burkholderia Infections†

Melioidosis†

Oral

2–3 g daily given for 1–3 months.^b In severe cases, some clinicians recommend concomitant chloramphenicol during the first month.^b In patients with extrapulmonary suppurative lesions, continue tetracycline therapy for 6–12 months.^b

Campylobacter Infections

Campylobacter fetus Infections

Oral

1–2 g daily given for 10 days.^b

Chancroid

Oral

1–2 g daily given for 2–4 weeks.^b

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

500 mg 4 times daily given for ≥7 days.^{102 c d}

Psittacosis (Ornithosis)

Oral

500 mg 4 times daily given for ≥10–14 days after defervescence.¹⁰⁰

Dientamoeba fragilis Infection†

Oral

500 mg 4 times daily for 10 days.¹¹²

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral

500 mg 4 times daily given for 7 days.^{c d} No longer recommended for gonorrhea by CDC or other experts.^{101 102}

Empiric Treatment of Epididymitis†

Oral

500 mg 4 times daily given for 10 days; as follow-up to a single dose of IM ceftriaxone.¹⁰²

Granuloma Inguinale (Donovanosis)

Oral

1–2 g daily given for 2–4 weeks.^b

Helicobacter pylori Infection and Duodenal Ulcer Disease

Oral

500 mg in conjunction with metronidazole (250 mg) and bismuth subsalicylate (525 mg) 4 times daily (at meals and at bedtime) for 14 days; these drugs should be given concomitantly with usual dosage of an H₂-receptor antagonist.¹¹⁰

Leptospirosis†

Oral

1–2 g daily given for 5–7 days.^b

Malaria†

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

250 mg 4 times daily given for 7 days; used in conjunction with quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).^{112 129}

Treatment of Uncomplicated P. vivax Malaria†

Oral

250 mg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).¹²⁹

In addition, a 14-day regimen of oral primaquine (30 mg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.¹²⁹

Treatment of Severe P. falciparum Malaria†

Oral

250 mg 4 times daily for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹²⁹ If an IV tetracycline is necessary initially, use IV doxycycline until oral therapy can be tolerated.¹²⁹

Plague

Treatment

Oral

2–4 g daily in 4 divided doses^b given for ≥10–14 days.^{b 123}

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential.^{123 124} A parenteral regimen (e.g., IM streptomycin, IM or IV gentamicin, IV doxycycline) is preferred for initial treatment; an oral regimen may be substituted when the patient's condition improves or if a parenteral regimen is unavailable.^{123 124}

Postexposure Prophylaxis following High-risk Exposure†

Oral

1–2 g daily in 2 or 4 divided doses.¹²³

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days^{123 124} or the duration of exposure risk plus 7 days.¹²³

Relapsing Fever

Oral

1–2 g daily until afebrile for 7 days.^b A single 500-mg dose may be effective in some patients.^b

Rickettsial Infections

Oral

1–2 g daily in 2–4 divided doses.^b Duration of treatment usually is ≥3–7 days or until patients has been afebrile for approximately 2–3 days.^b

Q Fever

Oral

500 mg every 6 hours given for ≥14 days for treatment of acute Q fever.¹²³

For prophylaxis against Q fever†, 500 mg every 6 hours given for ≥5–7 days may prevent clinical disease if initiated 8–12 days after exposure; such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1–7 days) after exposure.¹²³

Syphilis

Primary or Secondary Syphilis

Oral

500 mg 4 times daily given for 14 days recommended by CDC and others.^{101 102} Manufacturer recommends a total dosage of 30–40 g in equally divided doses given over 10–15 days.^{c d}

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

500 mg 4 times daily given for 14 days for early latent syphilis (duration <1 year) or 500 mg 4 times daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.^{101 102}

Tularemia

Treatment

Oral

500 mg 4 times daily¹²³ given for ≥14–21 days.^{123 f} Relapse may occur as long as 6 months after treatment with tetracycline; however, retreatment with the same dosage usually is curative.^b

Postexposure Prophylaxis following High-risk Exposure†

Oral

500 mg 4 times daily.¹²³

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.^{123 f}

Vibrio Infections

Cholera

Oral

1–2 g daily given for 2–3 days.^b 500 mg 4 times daily for 3 days also has been recommended.¹⁰³

Yaws

Oral

1–2 g daily given for 10–14 days.^b

Prescribing Limits

Pediatric Patients

Malaria

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: Maximum 1g daily.¹²⁹

Special Populations

Renal Impairment

Adjust dosage by decreasing doses or increasing dosing interval.^{c d}

Cautions for Tetracycline Hydrochloride

Contraindications

• 
  

  Known hypersensitivity to any tetracycline.^{c d}

  
  


• 
  

  Helidac Therapy (kit containing tetracycline, metronidazole, bismuth subsalicylate) contraindicated in pregnant or nursing women, pediatric patients, patients with hepatic or renal impairment, patients with known allergy to aspirin or salicylates, and those with known hypersensitivity to any component of the kit.^e

  
  

Warnings/Precautions

Warnings

Dental and Bone Effects

Use during tooth development (e.g., pregnancy, children <8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia.^{c d} Effects are most common following long-term use, but may occur following repeated short-term use.^{c d}

Tetracyclines form a stable calcium complex in any bone-forming tissue.^{c d} Reversible decrease in fibula growth rate has occurred in young animals receiving oral tetracycline.^{c d}

Use not recommended in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated or unless the benefits in certain indications (e.g., anthrax) outweigh the risks.^{114 c d} (See Pediatric Use under Cautions.)

Fetal/Neonatal Morbidity

Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity.^{c d} If used during pregnancy or if patient becomes pregnant while receiving tetracycline, patient should be apprised of the potential hazard to the fetus.^{c d} (See Pregnancy under Cautions.)

Renal Effects

Tetracyclines have antianabolic effects and may increase BUN.^{c d}

In patients with impaired renal function, high serum tetracycline concentrations may result in azotemia, hyperphosphatemia, and acidosis.^{c d} Excessive drug accumulation and possible liver toxicity may occur if usual dosage is used patients with renal impairment.^{c d} (See Renal Impairment under Dosage and Administration.)

Do not use tetracycline preparations past their expiration dates.^{c d} Outdated tetracycline preparations are highly nephrotoxic and have, on occasion, produced a Fanconi-like syndrome.^{c d}

Laboratory Monitoring

Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy.^{c d}

Helidac Therapy

When the kit containing tetracycline, metronidazole, and bismuth subsalicylate (Helidac Therapy) is used for the treatment of H. pylori infection and duodenal ulcer disease, the cautions, precautions, and contraindications associated with metronidazole and bismuth subsalicylate must be considered in addition to those associated with tetracycline.^e

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines.^{c d}

Photosensitivity reactions may develop within a few minutes to several hours after sun exposure and usually persist 1–2 days after discontinuance of the drug.^a Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions may also occur.^a

Discontinue drug at first evidence of skin erythema.^{c d}

Hypersensitivity Reactions

Oral suspension contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^d

Cross-sensitization occurs among the various tetracyclines.^{c d}

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.^{c d} Discontinue drug and institute appropriate therapy if superinfection occurs.^{c d}

Nervous System Effects

Possibility of bulging fontanels in infants and benign intracranial hypertension (pseudotumor cerebri) in adults.^{c d} Effects usually resolve when drug discontinued, but possibility for permanent sequelae exists.^{c d}

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of tetracycline and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^{c d}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{c d} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{c d}

Because many strains of Acinetobacter, Bacteroides, Enterobacter, E. coli, Klebsiella, Shigella, S. pyogenes (group A β-hemolytic streptococci), S. pneumoniae, enterococci, and α-hemolytic streptococci are resistant to tetracycline, in vitro susceptibility tests should be performed if the drug is used for treatment of infections caused by these bacteria.^{c d}

Incision and drainage or other surgical procedures should be performed in conjunction with tetracycline therapy when indicated.^{c d}

Specific Populations

Pregnancy

Category D.^{c d} (See Fetal/Neonatal Morbidity under Cautions.)

Should not be used in pregnant women unless, in the judgement of the clinician, it is essential for the welfare of the patient and benefits outweigh the risks.^{c d}

CDC and others state tetracyclines can be used when necessary for treatment of inhalational anthrax in pregnant women.^{122 i} Since adverse effects on developing teeth and bones are dose-related, CDC suggests the drug might be used for a short period (7–14 days) before 6 months of gestation;ⁱ some clinicians recommend periodic liver function testing if used in pregnant women.

Bowel Preparation Medications

Drugs associated with Bowel Preparation

The following drugs and medications are in some way related to, or used in the treatment of Bowel Preparation. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Bowel Preparation

Medical Encyclopedia:

• Colonoscopy

Drug List:

Alophen

Bisa-Lax-Suppositories

Bisa-Plex

Bisac-Evac

Bisco-Lax

Bisolax

Black-Draught

Carters-Little-Pills

Clearlax

Clenz-Lyte

Colax

Colyte-Solution

Correctol

Dosaflex

Doxidan-Tablet

Dr-Caldwell-Laxative

Dulcogen

Dulcolax

Dulcolax-Laxative

E-E-S-Granules-Suspension

E-E-S-200

E-E-S-400

E-E-S-400-Filmtab

Ery-Tab

Eryc-Delayed-Release-Particles-Capsules

Eryped-Drops

Erythrocin

Erythromycin-Lactobionate-I-V

Erythrocin-Stearate-Filmtab

Evac-U-Gen

Ex-Lax-Chewable-Tablets

Ex-Lax-Chocolated

Ex-Lax-Gentle-Nature

Ex-Lax-Maximum-Relief-Formula

Ex-Lax-Regular-Strength-Pills

Ex-Lax-Ultra

Feen-A-Mint

Fleet-Bisacodyl-Enema

Fleet-Enema

Fleet-Phospho-Soda-Solution

Fletchers-Castoria

Gavilax

Gen-Lax

Gentlax

Gentlax-Tablet

Gentle-Laxative

Glycolax-Powder-Packets-For-Oral-Solution

Golytely-Solution-Jug

Halflytely

Ilosone

Innerclean

Laxative-Gentle-Suppositories

Magic-Bullet

Miralax-Powder-Packets-For-Oral-Solution

Modane

Moviprep

Mycifradin

Neo-Fradin-Solution

Neo-Tab

Nulytely-Solution

Osmoprep

Pce

Fleet-Enema-For-Children

Peg-3350-With-Electolytes

Perdiem-Overnight

Purelax

Senexon-Liquid

Senna-Lax

Senna-Gen

Senokot

Senokot-Child

Senokot-Extra

Senolax

Senosol

Senosol-X

Suprep

Suprep-Bowel-Prep-Kit-Solution

Trilyte-Solution

Veracolate

Visicol

X-Prep

Aldurazyme 100 U / ml concentrate for solution for infusion

Aldurazyme 100 U/ml concentrate for solution for infusion

Laronidase

Read all of this leaflet carefully before you start using this medicine.

• Keep this leaflet. You may need to read it again.


• If you have any further questions, ask your doctor or your pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Aldurazyme is and what it is used for


• 2. Before you use Aldurazyme


• 3. How to use Aldurazyme


• 4. Possible side effects


• 5 How to store Aldurazyme


• 6. Further information

What Aldurazyme Is And What It Is Used For

Aldurazyme is used to treat patients with MPS I disease (Mucopolysaccharidosis I). It is given to treat the non-neurological manifestations of the disease.

People with MPS I disease have either a low level or no level of an enzyme called α-L-iduronidase, which breaks down specific substances (glycosaminoglycans) in the body. As a result, these substances do not get broken down and processed by the body as they should. They accumulate in many tissues in the body, which causes the symptoms of MPS I.

Aldurazyme is an artificial enzyme called laronidase. This can replace the natural enzyme which is lacking in MPS I disease.

Before You Use Aldurazyme

Do not use Aldurazyme

If you are allergic (hypersensitive) to any of the ingredients of Aldurazyme or if you have experienced a severe allergic reaction to laronidase.

Take special care with Aldurazyme

If you are treated with Aldurazyme, you may develop infusion-associated reactions. An infusion-associated reaction is any side effect occurring during the infusion or until the end of the infusion day (see 4 “Possible Side Effects”). Some of these reactions may be severe. When you experience such a reaction, you should immediately contact your doctor.

If these reactions occur, the Aldurazyme infusion should be stopped immediately and appropriate treatment will be started by your doctor.

These reactions may be particularly severe if you have a pre-existing MPS I-related upper airway obstruction.

You may be given additional medication such as antihistamines and paracetamol to help prevent allergic-type reactions.

Using other medicines

Please inform your doctor if you use medicines containing chloroquine or procaine, due to a possible risk of decreasing the action of Aldurazyme.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

There is not enough experience of the use of Aldurazyme in pregnant women. Aldurazyme should not be used during pregnancy unless clearly necessary. Ask your doctor or pharmacist for advice before taking any medicine.

It is not known whether Aldurazyme appears in breast milk. It is recommended to stop breast-feeding during treatment with Aldurazyme. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

The effects on the ability to drive and to use machines have not been studied.

Important information about some of the ingredients of Aldurazyme

This medicinal product contains 1.29 mmol sodium per vial. To be taken into consideration by patients on a controlled sodium diet.

How To Use Aldurazyme

Instruction for use - dilution and administration

The concentrate for solution for infusion has to be diluted before administration and is for intravenous use (see information for health care professionals).

Administration of Aldurazyme should be carried out in an appropriate clinical setting where resuscitation equipment to manage medical emergencies would be readily available.

Dosage

The recommended dosage regimen of Aldurazyme is 100 U/kg body weight given once every week as an intravenous infusion. The initial infusion rate of 2 U/kg/h may be gradually increased every fifteen minutes, if tolerated, to a maximum of 43 U/kg/h. The total volume of the administration should be delivered in approximately 3-4 hours.

If you forget to use Aldurazyme

If you have missed an Aldurazyme infusion, please contact your doctor.

If you use more Aldurazyme than you should

No case of overdose of Aldurazyme has been reported.

Possible Side Effects

Like all medicines, Aldurazyme can cause side effects, although not everybody gets them.

Side effects were mainly seen while patients were being given the medicine or shortly after (infusion-associated reactions). If you experience any reaction like this, please tell your doctor immediately. The number of these reactions decreased the longer that patients were on Aldurazyme. The majority of these reactions were mild or moderate in intensity. However, a few patients who had a prior history of severe MPS I related upper airway and pulmonary involvement, experienced severe reactions including bronchospasm, respiratory arrest, and swelling of the face.

The following side effects have been reported:

Very common (occurring in more than 1 in 10 patients)

• headache


• nausea


• abdominal pain


• rash


• joint disease, joint pain, back pain, pain in arms or legs


• flushing


• fever


• chills


• increased heart rate


• increased blood pressure


• less oxygen in the blood


• reaction at the infusion site

Common (occurring in more than 1 in 100 patients and less than 1 in 10 patients)

• increased body temperature


• tingling


• dizziness


• cough


• difficulty in breathing which may be extreme


• vomiting


• diarrhoea


• swelling of the face or neck


• hives


• itching


• hair loss


• cold sweat, heavy sweating


• muscle pain


• low blood pressure


• paleness


• cold hands or feet


• feeling hot, feeling cold


• fatigue


• influenza like illness


• allergic reaction


• restlessness

Unknown frequency

• Bluish color of the skin (due to lower levels of oxygen in the blood)


• Fast breathing


• redness of the skin


• Leakage of the drug into the surrounding tissue at the site of injection, which may cause swelling or redness

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Aldurazyme

Keep out of the reach and sight of children.

Do not use Aldurazyme after the expiry date which is stated on the label after the letters EXP.

Unopened vials:

Store in a refrigerator (2°C – 8°C).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information

What Aldurazyme contains

• The active substance is laronidase. One ml of the solution in the vial contains 100 U of laronidase. Each vial of 5 ml contains 500 U of laronidase.


• The other ingredients are:
  
  Sodium chloride, Sodium phosphate monobasic monohydrate, Sodium phosphate dibasic heptahydrate, Polysorbate 80, Water for injections

What Aldurazyme looks like and contents of the pack

Aldurazyme is supplied as a concentrate for solution for infusion. It is a solution that is clear to slightly opalescent, and colourless to pale yellow.

Pack size: 1, 10 and 25 vials per carton. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Genzyme Europe B.V.

Gooimeer 10

NL-1411 DD

Naarden

The Netherlands

Manufacturer

Genzyme Ltd.

37 Hollands Road

Haverhill

Suffolk

CB9 8PU

United Kingdom

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

United Kingdom/Ireland

Genzyme Therapeutics Ltd.

(United Kingdom)

Tel:+44 1865 405200

This leaflet was last approved in 04/2010

This medicine has been authorised under “exceptional circumstances”.

This means that because of the rarity of this disease it has been impossible to get complete information on this medicine.

The European Medicines Agency (EMEA) will review any new information on the medicine every year and this leaflet will be updated as necessary.

Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http://www.emea.europa.eu/. There are also links to other websites about rare diseases and treatments.

Carisoprodol and Aspirin

Carisoprodol and Aspirin TABLETS, USP 200 mg/325 mg

Carisoprodol and Aspirin Description

Carisoprodol and Aspirin Tablets, USP is a fixed-dose combination product containing the following two products:

• 200 mg of carisoprodol, a centrally-acting muscle relaxant


• 325 mg of aspirin, an analgesic with antipyretic and anti-inflammatory properties.

It is available as a round, two-layered lavender and white tablet for oral administration.

Carisoprodol: Chemically, carisoprodol is N-isopropyl-2-methyl-2-propyl-1,3-propanediol dicarbamate and its molecular formula is C12H24N2O4, with a molecular weight of 260.34. The structural formula of carisoprodol is:

Aspirin: Chemically, aspirin (acetylsalicyclic acid) is 2-(acetyloxy)-, benzoic acid and its molecular formula is C9H8O4, with a molecular weight of 180.16. The structural formula of aspirin is:

Each tablet, for oral administration, contains carisoprodol 200 mg and aspirin 325 mg. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, corn starch, croscarmellose sodium, FD&C Blue No.1, D&C Red No. 30 Aluminum Lake, magnesium stearate, microcrystalline cellulose, povidone, and stearic acid.

Carisoprodol and Aspirin - Clinical Pharmacology

Mechanism of Action

Carisoprodol

The mechanism of action of carisoprodol in relieving discomfort associated with acute painful musculoskeletal conditions has not been clearly identified. In animal studies, muscle relaxation induced by carisoprodol is associated with altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain.

Aspirin

The mechanism of action of aspirin in relieving pain is by inhibition of the body's production of prostaglandins, which are thought to cause pain sensations by stimulating muscle contractions and dilating blood vessels.

Pharmacodynamics

 

Carisoprodol

Carisoprodol is a centrally-acting muscle relaxant that does not directly relax skeletal muscles. A metabolite of carisoprodol, meprobamate, has anxiolytic and sedative properties. The degree to which these properties of meprobamate contribute to the safety and efficacy of carisoprodol is unknown.

 

Aspirin

Aspirin is a non-narcotic analgesic with anti-inflammatory and anti-pyretic activity. Inhibition of prostaglandin biosynthesis appears to account for most of its anti-inflammatory and for at least part of its analgesic and antipyretic properties. In the CNS, aspirin works on the hypothalamus heat-regulating center to reduce fever. Aspirin can cause serious gastrointestinal injury including bleeding, obstruction, and perforations from ulcers possibly by inhibition of the production of prostaglandins, compromising the defenses of the gastric mucosa and the activity of substances involved in tissue repair and ulcer healing (see WARNINGS). Aspirin inhibits platelet aggregation by irreversibly inhibiting prostaglandin cyclo-oxygenase. This effect lasts for the life of the platelet and prevents the formation of the platelet aggregating factor thromboxane A2.

Pharmacokinetics

Carisoprodol

The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a study of 24 healthy subjects (12 male and 12 female) who received single doses of 350 mg of carisoprodol (see Table 1). The Cmax of meprobamate was 2.5 ± 0.5 mcg/mL (mean ± SD) after administration of a single 350 mg dose of carisoprodol, which is approximately 30% of the Cmax of meprobamate (approximately 8 mcg/mL) after administration of a single 400 mg dose of meprobamate.

Table 1. Pharmacokinetic Parameters of Carisoprodol and Meprobamate (Mean ± SD, n=24)

	carisoprodol	meprobamate
Cmax (mcg/mL)	1.8 ± 1	2.5 ± 0.5
AUCinf (mcg·hour/mL)	7 ± 5	46 ± 9
Tmax (hour)	1.7 ± 0.8	4.5 ± 1.9
T1/2 (hour)	2 ± 0.5	9.6 ± 1.5

Absorption: Absolute bioavailability of carisoprodol has not been determined. After administration of a single dose of 350 mg of carisoprodol, the mean time to peak plasma concentrations (Tmax) of carisoprodol was approximately 1.5 to 2 hours. Co-administration of a high-fat meal with 350 mg of carisoprodol had no effect on the pharmacokinetics of carisoprodol.

 

Metabolism: The major pathway of carisoprodol metabolism is via the liver by cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see Patients with Reduced CYP2C19 Activity below).

 

Elimination: Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours after administration of a single dose of 350 mg of carisoprodol. The half-life of meprobamate is approximately 10 hours after administration of a single dose of 350 mg of carisoprodol.

 

Gender: Exposure of carisoprodol is higher in female than in male subjects (approximately 30 to 50% on a weight adjusted basis). Overall exposure of meprobamate is comparable between female and male subjects.

 

Patients with Reduced CYP2C19 Activity: Carisoprodol should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3 to 5% and in Asians is approximately 15 to 20%.

 

Aspirin

Absorption: The rate of aspirin absorption from the gastrointestinal (GI) tract is dependent upon the presence or absence of food, gastric pH (the presence or absence of GI antacids), and other physiologic factors. Following absorption, aspirin is hydrolyzed to salicylic acid in the gut wall and during first-pass metabolism with peak plasma levels of salicylic acid occurring within 1 to 2 hours of dosing.

 

Distribution: Salicylic acid is widely distributed to all tissues and fluids in the body including the central nervous system (CNS), breast milk, and fetal tissues. The highest concentrations are found in the plasma, liver, kidneys, heart, and lungs. The protein binding of salicylate is concentration dependent, i.e., nonlinear. At plasma concentrations of salicylic acid < 100 mcg/mL and > 400 mcg/mL, approximately 90 and 76 percent of plasma salicylate is bound to albumin, respectively.

 

Metabolism: Aspirin, which has a half-life of about 15 minutes, is hydrolyzed in the plasma to salicylic acid such that plasma levels of aspirin may not be detectable 1 to 2 hours after dosing. Salicylic acid, which has a plasma half life of approximately 6 hours, is conjugated in the liver to form salicyluric acid, salicyl phenolic glucuronide, salicyl acyl glucuronide, gentisic acid, and gentisuric acid. At higher serum concentrations of salicylic acid, the total clearance of salicylic acid decreases due to the limited ability of the liver to form both salicyluric acid and phenolic glucuronide. Following toxic doses of aspirin (e.g., > 10 grams), the plasma half-life of salicylic acid may be increased to over 20 hours.

 

Elimination: The elimination of salicylic acid is constant in relation to the plasma salicylic acid concentration. Following therapeutic doses of aspirin, approximately 75, 10, 10, and 5 percent is found excreted in the urine as salicyluric acid, salicylic acid, a phenolic glucuronide of salicylic acid, and an acyl glucuronide of salicylic acid, respectively. As the urinary pH rises above 6.5, the renal clearance of free salicylate increases from less than 5 percent to greater than 80 percent. Alkalinization of the urine is a key concept in the management of salicylate overdose (see OVERDOSAGE, Treatment of Overdosage). Clearance of salicylic acid is also reduced in patients with renal impairment.

Indications and Usage for Carisoprodol and Aspirin

Carisoprodol and Aspirin Tablets are indicated for the relief of discomfort associated with acute, painful musculoskeletal conditions in adults. Carisoprodol and Aspirin Tablets should only be used for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use has not been established and because acute, painful musculoskeletal conditions are generally of short duration (see DOSAGE AND ADMINISTRATION).

Contraindications

Carisoprodol and Aspirin Tablets are contraindicated in patients with a history of:

• a serious GI complication (i.e., bleeding, perforations, obstruction) due to aspirin use


• aspirin induced asthma (a symptom complex which occurs in patients who have asthma, rhinosinusitis, and nasal polyps who develop a severe, potentially fatal bronchospasm shortly after taking aspirin or other NSAIDs)


• hypersensitivity reaction to a carbamate such as meprobamate


• acute intermittent porphyria

Warnings

Carisoprodol

Sedation

Carisoprodol has sedative properties and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle or operating machinery. There have been post-marketing reports of motor vehicle accidents associated with the use of carisoprodol.

Since the sedative effects of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive, appropriate caution should be exercised with patients who take more than one of these CNS depressants simultaneously.

Drug Dependence, Withdrawal, and Abuse

In the postmarketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. Most cases of dependence, withdrawal, and abuse occurred in patients who have had a history of addiction or who used carisoprodol in combination with other drugs with abuse potential. However, there have been post-marketing adverse event reports of carisoprodol-associated abuse when used without other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. To reduce the chance of carisoprodol dependence, withdrawal, or abuse, carisoprodol should be used with caution in addiction prone patients and in patients taking other CNS depressants including alcohol, and carisoprodol should be not be used more than two to three weeks for the relief of acute musculoskeletal discomfort.

Carisoprodol, and one of its metabolites, meprobamate (a controlled substance), may cause dependence (see CLINICAL PHARMACOLOGY).

Aspirin

Serious Gastrointestinal Adverse Reactions

Aspirin can cause serious gastrointestinal (GI) adverse reactions including bleeding, perforation, and obstruction of the stomach, small intestine, or large intestine, which can be fatal. Aspirin-associated serious GI adverse reactions can occur anywhere along the GI tract, at any time, with or without warning symptoms. Patients at higher risk of aspirin-associated serious upper GI adverse reactions include patients with a history of aspirin-associated GI bleeding from ulcers (complicated ulcers), a history of aspirin-associated ulcers (uncomplicated ulcers), geriatric patients, patients with poor baseline health status, patients taking higher doses of aspirin, and patients taking concomitant anticoagulants, NSAIDs, and/or large amounts of alcohol. To minimize the risk for an aspirin-associated GI serious adverse reaction, the lowest effective aspirin dose should be used for the shortest possible duration.

Anaphylaxis and Anaphylactoid Reactions

Aspirin may cause an increased risk of serious anaphylaxis and anaphylactoid reactions, which can occur in patients without known prior exposure to aspirin (see CONTRAINDICATIONS). Patients with a serious anaphalaxis or anaphylactoid reaction should receive emergency care.

Precautions

Patients with impaired renal or hepatic function

The safety and pharmacokinetics of Carisoprodol and Aspirin Tablets in patients with renal or hepatic impairment have not been evaluated.

Carisoprodol

Since carisoprodol is excreted by the kidney and is metabolized in the liver, caution should be exercised if carisoprodol is administered to patients with impaired renal or hepatic function. Carisoprodol is dialyzable by hemodialysis and peritoneal dialysis.

Seizures

There have been postmarketing reports of seizures in patients who received carisoprodol. Most of these cases have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol) (see OVERDOSAGE).

Aspirin

Gastrointestinal Adverse Reactions

In addition to serious gastrointestinal adverse reactions, the use of aspirin is also associated with gastritis, gastrointestinal erosions, abdominal pain, heartburn, vomiting, and nausea (see WARNINGS, Serious Gastrointestinal Adverse Reactions).

Information for patients

Patients should be advised to contact their health care provider if they experience any adverse reactions to Carisoprodol and Aspirin Tablets .

Carisoprodol

1. Patients should be advised that carisoprodol may cause drowsiness and/or dizziness, and has been associated with motor vehicle accidents. Patients should be advised to avoid taking carisoprodol before engaging in potentially hazardous activities such as driving a motor vehicle or operating machinery (see WARNINGS, Sedation).


2. Patients should be advised to avoid alcoholic beverages while taking carisoprodol and to check with their doctor before taking other CNS depressants such as benzodiazepines, opioids, tricyclic antidepressants, sedating antihistamines, or other sedatives (see WARNINGS, Sedation).


3. Patients should be advised that treatment with carisoprodol should be limited to acute use (up to two or three weeks) for the relief of acute, musculoskeletal discomfort. In the post-marketing experience with carisoprodol, cases of dependence, withdrawal, and abuse have been reported with prolonged use. If the musculoskeletal symptoms still persist, patients should contact their healthcare provider for further evaluation.

Aspirin

1. Patients should be warned that aspirin can cause epigastric discomfort, gastric and duodenal ulcers, and serious GI adverse reactions, such as bleeding, perforation, and/or obstruction of the stomach or intestines, which may result in hospitalization and death. Although serious GI bleeding can occur without warning symptoms (e.g., hematemesis, melena, hematochezia), patients should be alert for these symptoms and should seek urgent medical care if any of these indicative symptoms occur (see WARNINGS, Serious Gastrointestinal Adverse Reactions). In addition, patients should be alert for symptoms of ulcers (e.g., night time epigastric discomfort, vomiting, weight loss) and should seek medical attention if these symptoms occur. Patients who consume three or more alcoholic drinks every day should be counseled about the GI bleeding risks involved with the use of aspirin with alcohol.


2. Patients should be informed of the symptoms of an anaphylactoid reaction or anaphylaxis (e.g., hives, difficulty breathing, swelling of the face or throat). If these symptoms occur, patients should be instructed to seek immediate emergency help.

Drug Interactions

Carisoprodol

The sedative effects of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may be additive. Therefore, caution should be exercised with patients who take more than one of these CNS depressants simultaneously. Concomitant use of carisoprodol and meprobamate, a metabolite of carisoprodol, is not recommended (see WARNINGS, Sedation).

Carisoprodol is metabolized in the liver by CYP2C19 to form meprobamate (see CLINICAL PHARMACOLOGY). Coadministration of CYP2C19 inhibitors, such as omeprazole or fluvoxamine, with carisoprodol could result in increased exposure of carisoprodol and decreased exposure of meprobamate. Co-administration of CYP2C19 inducers, such as rifampin or St. John's Wort, with carisoprodol could result in decreased exposure of carisoprodol and increased exposure of meprobamate. Low dose aspirin also showed an induction effect on CYP2C19. The full pharmacological impact of these potential alterations of exposures in terms of either efficacy or safety of carisoprodol is unknown.

Aspirin

Clinically important interactions may occur when certain drugs or alcohol are administered concomitantly with aspirin.

Alcohol: Concomitant use of aspirin with ≥ 3 alcoholic drinks may increase the risk of GI bleeding (see WARNINGS, Serious Gastrointestinal Adverse Reactions).

Anticoagulants: Concomitant use of aspirin with anticoagulants (e.g., heparin, warfarin, clopidogrel) increases the risk of GI bleeding (see WARNINGS, Serious Gastrointestinal Adverse Reactions). Additionally, aspirin can displace warfarin from protein binding sites, leading to prolongation of the international normalized ratio (INR).

Antihypertensives: The concomitant administration of aspirin with angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and diuretics may diminish the hypotensive effects of these anti-hypertensive products due to aspirin's inhibition of renal prostaglandins, which may lead to decreased renal blood flow and increased sodium and fluid retention. Concomitant use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide due to competition at the renal tubule for secretion.

Corticosteroids: Concomitant administration of aspirin and corticosteriods may decrease salicylate plasma levels.

Methotrexate: Aspirin may enhance the toxicity of methotrexate due to displacement of methotrexate from its plasma protein binding sites and/or reduction of the renal clearance of methotrexate.

Nonsteroidal anti-inflammatory drugs (NSAIDs): The concurrent use of aspirin with selective and nonselective NSAIDs increases the risk of serious GI adverse reactions (see WARNINGS, Serious Gastrointestinal Adverse Reactions).

Oral Hypoglycemics Agents: Aspirin may increase the serum glucose-lowering action of insulin and sulfonylureas leading to hypoglycemia.

Products that effect urinary pH: Ammonium chloride and other drugs that acidify the urine can elevate plasma salicylate concentrations. In contrast, antacids, by alkalinizing the urine, may decrease plasma salicylate concentrations.

Uricosuric Agents: Salicylates antagonize the uricosuric action of probenecid and sulfinpyrazone.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies of carcinogenesis have been done with Carisoprodol and Aspirin Tablets.

Carisoprodol

Long term studies in animals have not been performed to evaluate the carcinogenic potential of carisoprodol.

Carisoprodol was not formally evaluated for genotoxicity. In published studies, carisoprodol was mutagenic in the in vitro mouse lymphoma cell assay in the absence of metabolizing enzymes, but was not mutagenic in the presence of metabolizing enzymes. Carisoprodol was clastogenic in the in vitro chromosomal aberration assay using Chinese hamster ovary cells with or without the presence of metabolizing enzymes. Other types of genotoxic tests resulted in negative findings. Carisoprodol was not mutagenic in the Ames reverse mutation assay using S. typhimurium strains with or without metabolizing enzymes, and was not clastogenic in an in vivo mouse micronucleus assay of circulating blood cells.

Carisoprodol was not formally evaluated for effects on fertility. Published reproductive studies of carisoprodol in mice found no alteration in fertility although an alteration in reproductive cycles characterized by a greater time spent in estrus was observed at a carisoprodol dose of 1200 mg/kg/day. In a 13-week toxicology study that did not determine fertility, mouse testes weight and sperm motility were reduced at a dose of 1200 mg/kg/day. In both studies, the no effect level was 750 mg/kg/day, corresponding to approximately 2.6 times the human equivalent dosage of 350 mg four times a day, based on a body surface area comparison.

The significance of these findings for human fertility is not known.

Aspirin

Administration of aspirin for 68 weeks in the feed of rats was not carcinogenic. In the Ames Salmonella assay, aspirin was not mutagenic; however, aspirin did induce chromosome aberrations in cultured human fibroblasts. Aspirin has been shown to inhibit ovulation in rats (see Pregnancy.)

Pregnancy

Pregnancy Category D 

It is not known whether Carisoprodol and Aspirin Tablets can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Adequate animal reproduction studies have not been conducted with Carisoprodol and Aspirin Tablets. Carisoprodol and Aspirin Tablets should be given to a pregnant woman only if clearly needed.

Carisoprodol

There are no data on the use of carisoprodol during human pregnancy. Animal studies indicate that carisoprodol crosses the placenta and results in adverse effects on fetal growth and postnatal survival. The primary metabolite of carisoprodol, meprobamate, is an approved anxiolytic. Retrospective, post-marketing studies do not show a consistent association between maternal use of meprobamate and an increased risk for particular congenital malformations.

Teratogenic effects

Animal studies have not adequately evaluated the teratogenic effects of carisoprodol. There was no increase in the incidence of congenital malformations noted in reproductive studies in rats, rabbits, and mice treated with meprobamate. Retrospective, post-marketing studies of meprobamate during human pregnancy were equivocal for demonstrating an increased risk of congenital malformations following first trimester exposure. Across studies that indicated an increased risk, the types of malformations were inconsistent.

Nonteratogenic effects

In animal studies, carisoprodol reduced fetal weights, postnatal weight gain, and postnatal survival at maternal doses equivalent to 1 to 1.5 times the human dose (based on a body surface area comparison). Rats exposed to meprobamate in-utero showed behavioral alterations that persisted into adulthood. For children exposed to meprobamate in-utero, one study found no adverse effects on mental or motor development or IQ scores. Carisoprodol should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Aspirin

Teratogenic effects

Prior to 30 weeks gestation, aspirin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Starting at 30 weeks gestation, aspirin should be avoided by pregnant women as premature closure of the fetal ductus arteriosus which may result in fetal pulmonary hypertension and fetal death. Salicylate products have also been associated with alterations in maternal and neonatal hemostasis mechanisms, decreased birth weight, increased incidence of intracranial hemorrhage in premature infants, stillbirths, and neonatal death. Studies in rodents have shown salicylates to be teratogenic when given in early gestation, and embryocidal when given in later gestation in doses considerably greater than usual therapeutic doses in humans.

Labor and Delivery

Carisoprodol: There is no information about the effects of carisoprodol on the mother and the fetus during labor and delivery.

Aspirin: Ingestion of aspirin within one week of delivery or during labor may prolong delivery or lead to excessive blood loss in the mother, fetus, or neonate. Prolonged labor due to prostaglandin inhibition has been reported with aspirin use.

Nursing Mothers

Carisoprodol

Very limited data in humans show that carisoprodol is present in breast milk and may reach concentrations two to four times the maternal plasma concentrations. In one case report, a breast-fed infant received about 4 to 6% of the maternal daily dose through breast milk and experienced no adverse effects. However, milk production was inadequate and the baby was supplemented with formula. In lactation studies in mice, female pup survival and pup weight at weaning were decreased. This information suggests that maternal use of carisoprodol may lead to reduced or less effective infant feeding (due to sedation) and/or decreased milk production. Caution should be exercised when carisoprodol is administered to a nursing woman.

Aspirin

Nursing mothers should avoid the use of aspirin because salicylate is excreted in breast milk which may lead to bleeding in the infant.

Pediatric use

The efficacy, safety, and pharmacokinetics of Carisoprodol and Aspirin Tablets in pediatric patients less than 16 years of age have not been established.

Geriatric Use

The efficacy, safety, and pharmacokinetics of Carisoprodol and Aspirin Tablets in patients over 65 years old have not been established.

Adverse Reactions

The following adverse reactions which have occurred with the administration of the individual products alone may also occur with the use of Carisoprodol and Aspirin Tablets . The following events have been reported during post-approval individual use of Carisoprodol and Aspirin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Carisoprodol 

The following events have been reported during post-approval use of carisoprodol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

 

Cardiovascular: Tachycardia, postural hypotension, and facial flushing (see OVERDOSAGE).

 

Central Nervous System: Drowsiness, dizziness, vertigo, ataxia, tremor, agitation, irritability, headache, depressive reactions, syncope, insomnia, and seizures (see OVERDOSAGE).

 

Gastrointestinal: Nausea, vomiting, and epigastric discomfort.

 

Hematologic: Leukopenia, pancytopenia

Aspirin

 The most common adverse reactions associated with the use of aspirin have been gastrointestinal, including abdominal pain, anorexia, nausea, vomiting, gastritis, and occult bleeding (see WARNINGS, Serious Gastrointestinal AdverseReactions and PRECAUTIONS, Gastrointestinal AdverseReactions). Other adverse reactions associated with the use of aspirin include elevated liver enzymes, rash, pruritus, purpura, intracranial hemorrhage, interstitial nephritis, acute renal failure, and tinnitus. Tinnitus may be a symptom of high serum salicylate levels (see OVERDOSAGE).

Drug Abuse and Dependence

Carisoprodol is not a controlled substance (see WARNINGS).

Discontinuation of carisoprodol in animals or in humans after chronic administration can produce withdrawal signs, and there are published case reports of human carisoprodol dependence.

In vitro studies demonstrate that carisoprodol elicits barbiturate-like effects. Animal behavioral studies indicate that carisoprodol produces rewarding effects. Monkeys self administer carisoprodol. Drug discrimination studies using rats indicate that carisoprodol has positive reinforcing and discriminating effects similar to barbital, meprobamate, and chlordiazepoxide.

Overdosage

Signs and Symptoms: Any of the following signs and symptoms which have been reported with overdose of the individual products may occur with overdose of Carisoprodol and Aspirin Tablets and may be modified to a varying degree by the effects of the other products present in Carisoprodol and Aspirin Tablets.

Carisoprodol: Overdosage of carisoprodol commonly produces CNS depression. Death, coma, respiratory depression, hypotension, seizures, delirium, hallucinations, dystonic reactions, nystagmus, blurred vision, mydriasis, euphoria, muscular incoordination, rigidity, and/or headache have been reported with carisoprodol overdosage. Many of the carisoprodol overdoses have occurred in the setting of multiple drug overdoses (including drugs of abuse, illegal drugs, and alcohol). The effects of an overdose of carisoprodol and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) can be additive even when one of the drugs has been taken in the recommended dosage. Fatal accidental and non-accidental overdoses of carisoprodol have been reported alone or in combination with CNS depressants.

Aspirin: Salicylate toxicity may result from an overdose of an acute ingestion or chronic intoxication. Mild to moderate salicylate poisoning is usually associated with plasma salicylic concentrations about 200 mcg/mL and is characterized by tinnitus, hearing difficulty, headache, dim vision, dizziness, tachypnea, increased thirst, nausea, vomiting, sweating, and diarrhea. In the early stages of overdose, CNS stimulation and respiratory alkalosis can occur; however, in the later stages CNS depression and metabolic acidosis can occur.

Symptoms and signs of severe salicylate poisoning, associated with plasma salicylic concentrations greater than 400 mcg/mL, include hyperthermia, dehydration, delirium, GI hemorrhage, pulmonary edema, and CNS depression (e.g., coma). Death is usually due to respiratory failure or cardiovascular collapse.

Overdose of aspirin in pediatric patients: Salicylate poisoning should be considered in pediatric patients with symptoms of vomiting, hyperpnea, and hyperthermia. Salicylate poisoning should be considered in infants with metabolic acidosis and all pediatric patients with severe salicylate poisoning.

Treatment of Overdosage: Provide symptomatic and supportive treatment, as indicated. For more information on the management of an overdose of Carisoprodol and Aspirin Tablets, USP, contact a Poison Control Center.

Carisoprodol: Basic life support measures should be instituted as dictated by the clinical presentation of the carisoprodol overdose. Induced emesis is not recommended due to the risk of CNS and respiratory depression, which may increase the risk of aspiration pneumonia. Gastric lavage should be considered soon after ingestion (within one hour). Circulatory support should be administered with volume infusion and vasopressor agents if needed. Seizures should be treated with intravenous benzodiazepines and the reoccurrence of seizures may be treated with phenobarbital. In cases of severe CNS depression, airway protective reflexes may be compromised and tracheal intubation should be considered for airway protection and respiratory support. The following types of treatment have been used successfully with an overdose of meprobamate, a metabolite of carisoprodol: activated charcoal (oral or via nasogastric tube), forced diuresis, peritoneal dialysis, and hemodialysis (carisoprodol is also dialyzable). Careful monitoring of urinary output is necessary and overhydration should be avoided. Observe for possible relapse due to incomplete gastric emptying and delayed absorption.

Aspirin:  Since there are no specific antidotes for salicylate poisoning, the aim of treatment is to enhance elimination of salicylate;-reduce further salicylate absorption; correct fluid, electrolyte, or acid/base imbalances; and provide cardio-respiratory support. The acid-base status should be followed closely with serial serum pH determinations (using arterial blood gas). If acidosis is present, intravenous sodium bicarbonate should be given, along with adequate hydration, until salicylate levels decrease to within the therapeutic range. To enhance elimination, forced diuresis and alkalinization of the urine may be beneficial. Gastric emptying and/or lavage are recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of activated charcoal is beneficial, if less than 3 hours have passed since ingestion. Charcoal absorption should not be employed prior to emesis and lavage. In patients with renal insufficiency or in cases of life-threatening aspirin intoxication, hemodialysis or peritoneal dialysis is usually required.

Additional treatment of aspirin overdose in pediatric patients: Pediatric patients should be sponged with tepid water. Infusion of glucose may be required to control hypoglycemia. Exchange transfusion may be indicated in infants and young children.

Carisoprodol and Aspirin Dosage and Administration

The recommended dose of Carisoprodol and Aspirin Tablets is 1 or 2 tablets, four times daily in adults. One Carisoprodol and Aspirin Tablet contains 200 mg of carisoprodol and 325 mg of aspirin. The maximum daily dose (i.e., two tablets taken four times daily) will provide 1600 mg of carisoprodol and 2600 mg of aspirin per day. The recommended maximum duration of Carisoprodol and Aspirin Tablet use is up to two or three weeks.

How is Carisoprodol and Aspirin Supplied

Carisoprodol and Aspirin Tablets, USP are supplied as:

Carisoprodol 200 mg and Aspirin 325 mg, round, two layered lavender and white tablets; imprinted E724 and are available in bottles of 100, 500 and 1000.

NDC 0185-0724-01, bottles of 100 tablets

NDC 0185-0724-05, bottles of 500 tablets

NDC 0185-0724-10, bottles of 1000 tablets

Storage: Store at 20° to 25° C (68° to 77° F)[See USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Manufactured for

Sandoz Inc. Princeton, NJ 08540

Manufactured by

Epic Pharma, LLC

Laurelton, NY 11413

Rev. August 2010

MF0724REV08/10

0S7169

PRINCIPAL DISPLAY PANEL

NDC 0185-0724-05

Carisoprodol and Aspirin Tablets, USP

200 mg/325 mg

Rx only

500 Tablets

SANDOZ

Carisoprodol and Aspirin  Carisoprodol and Aspirin  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0185-0724 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CARISOPRODOL (CARISOPRODOL) CARISOPRODOL 200 mg ASPIRIN (ASPIRIN) ASPIRIN 325 mg

Inactive Ingredients Ingredient Name Strength SILICON DIOXIDE   STARCH, CORN   CROSCARMELLOSE SODIUM   FD&C BLUE NO. 1   D&C RED NO. 30   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   POVIDONE   STEARIC ACID

Product Characteristics Color PURPLE (lavender) , WHITE Score no score Shape ROUND Size 12mm Flavor Imprint Code E724 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0185-0724-01 100 TABLET In 1 BOTTLE None 2 0185-0724-05 500 TABLET In 1 BOTTLE None 3 0185-0724-10 1000 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA040116	04/25/1996

Labeler - Eon Labs, Inc. (012656273)

Revised: 06/2011Eon Labs, Inc.

More Carisoprodol and Aspirin resources

• Carisoprodol and Aspirin Side Effects (in more detail)
• Carisoprodol and Aspirin Use in Pregnancy & Breastfeeding
• Drug Images
• Carisoprodol and Aspirin Drug Interactions
• Carisoprodol and Aspirin Support Group
• 4 Reviews for Carisoprodol and Aspirin - Add your own review/rating

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