Flagyl

Generic Name: Metronidazole
Class: Antiprotozoals, Miscellaneous
VA Class: AM900
CAS Number: 443-48-1

• 
  

  Carcinogenic in mice and rats.^{152 156 197 430 495}

  
  


• 
  

  Avoid unnecessary use; reserve for use in approved indications..^{152 156 197 430 495} (See Uses.)

  
  

Introduction

Antibacterial and antiprotozoal;.^{152 197 430 494 495} nitroimidazole derivative.⁴⁹⁴

Uses for Flagyl

Bone and Joint Infections

Adjunct for treatment of bone and joint infections caused by Bacteroides, including the B. fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus).^{152 197 495}

Endocarditis

Treatment of endocarditis caused by Bacteroides (including the B. fragilis group).^{152 197 495}

Gynecologic Infections

Treatment of gynecologic infections (including endometritis, endomyometritis, tubo-ovarian abscess, postsurgical vaginal cuff infection) caused by Bacteroides (including the B. fragilis group), Clostridium, Peptococcus niger, or Peptostreptococcus.^{152 197 495}

Treatment of acute pelvic inflammatory disease (PID); used in conjunction with other anti-infectives.^{199 341 496} Metronidazole is included in PID regimens to provide coverage against anaerobes.³⁴¹

When a parenteral regimen is indicated for PID, an initial regimen of IV cefoxitin and IV or oral doxycycline is recommended followed by oral doxycycline; if tubo-ovarian abscess is present, some experts recommend that the oral follow-up regimen include metronidazole (or clindamycin) in addition to doxycycline.³⁴¹

When an oral regimen is indicated for PID, an single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or cefotaxime is recommended in conjunction with oral doxycycline (with or without oral metronidazole).^{199 341 496} Alternatively, if a parenteral cephalosporin is not feasible and the community prevalence and individual risk for gonorrhea is low, a regimen of oral levofloxacin or oral ofloxacin (with or without oral metronidazole) may be considered.⁴⁹⁶

Intra-abdominal Infections

Treatment of intra-abdominal infections (including peritonitis, intra-abdominal abscess, liver abscess) caused by susceptible Bacteroides (including the B. fragilis group), Clostrium, Eubacterium, P. niger, or Peptostreptococcus.^{152 197 495}

Meningitis and Other CNS Infections

Treatment of CNS infections (including meningitis, brain abscess) caused by Bacteroides (including the B. fragilis group).^{152 197 495}

Respiratory Tract Infections

Treatment of respiratory tract infections (including pneumonia) caused by Bacteroides (including the B. fragilis group).^{152 197 495}

Septicemia

Treatment of septicemia caused by Bacteroides (including the B. fragilis group) or Clostridium.^{152 197 495}

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by Bacteroides (including the B. fragilis group), Clostridium, Fusobacterium, P. niger, or Peptostreptococcus.^{152 197 495}

Amebiasis

Treatment of acute intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica.^{100 152 153 197 364 368 370} Oral metronidazole or oral tinidazole followed by a luminal amebicide (iodoquinol, paromomycin) is the regimen of choice for mild to moderate or severe intestinal disease and for amebic hepatic abscess.^{100 153 364 368 370}

Bacterial Vaginosis

Treatment of bacterial vaginosis (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in pregnant or nonpregnant women.^{199 292 297 298 302 341 365 366 430}

CDC recommends treatment of bacterial vaginosis in all symptomatic women (including pregnant women).³⁴¹ In addition, asymptomatic pregnant women at high risk for complications of pregnancy should be screened (preferably at the first prenatal visit) and treatment initiated if needed.³⁴¹

Treatment recommendations for bacterial vaginosis in HIV-infected women are the same as those for women without HIV infection.³⁴¹

Regimens of choice in nonpregnant women are a 7-day regimen of oral metronidazole, a 5-day regimen of intravaginal metronidazole gel, or a 7-day regimen of intravaginal clindamycin cream;³⁴¹ alternative regimens are a 7-day regimen of oral clindamycin or 3-day regimen of intravaginal clindamycin suppositories.³⁴¹ The preferred regimens for pregnant women are a 7-day regimen of oral metronidazole or a 7-day regimen of oral clindamycin.³⁴¹

Regardless of regimen used, relapse or recurrence is common;^{287 295 297 298 300 302 307 341 365} an alternative regimen (e.g., topical therapy when oral therapy was used initially) may be used in such situations.^{297 341}

Routine treatment of asymptomatic male sexual contacts of women who have relapsing or recurrent bacterial vaginosis not recommended.³⁴¹

Balantidiasis

Alternative to tetracycline for treatment of balantidiasis† caused by Balantidium coli.^{100 153}

Blastocystis hominis Infections

Treatment of infections caused by Blastocystis hominis†.^{100 153 368 371 372} May be effective, but metronidazole resistance may be common.¹⁵³

Clinical importance of B. hominis as a cause of GI pathology is controversial;^{100 153 368 371 372} unclear when treatment is indicated.^{100 368 371} Some clinicians suggest treatment be reserved for certain individuals (e.g., immunocompromised patients) when symptoms persist and no other pathogen or process is found to explain their GI symptoms.^{100 368}

Clostridium difficile-associated Diarrhea and Colitis

Treatment of Clostridium difficile-associated diarrhea and colitis† (CDAD; also known as antibiotic-associated diarrhea and colitis, C. difficile diarrhea, C. difficile colitis, and pseudomembranous colitis).^{100 125 126 127 128 129 131 132 312 313 314 315 316 344 345 443 444 445 446 447}

Drugs of choice are metronidazole and vancomycin; ^{100 312 313 314 315 316} metronidazole generally preferred and vancomycin reserved for those with severe or potentially life-threatening colitis, patients in whom metronidazole-resistant C. difficile is suspected, patients in whom metronidazole is contraindicated or not tolerated, or those who do not respond to metronidazole.^{100 126 127 312 313 314 315 316 322 323 406 443 444 445 446 447 448}

Crohn’s Disease

Mangement of Crohn’s disease† as an adjunct to conventional therapies.^{101 102 103 104}

Has been used with^{467 468 471 475 476 477 485} or without ciprofloxacin;^{101 102 103 104 105 469 470 471 472 473 474 478 479 484 485 486} for induction of remission of mildly to moderately active Crohn’s disease†.^{101 102 103 104 105 467 468 469 471 472 473 474 475 476 477 478 479 484}

Has been used for refractory perianal Crohn’s disease†.^{102 104 105 470 471 474 478 479 485 486}

Dientamoeba fragilis Infections

Treatment of infections caused by Dientamoeba fragilis†.¹⁵³ Drugs of choice are iodoquinol, paromomycin, tetracycline, or metronidazole.¹⁵³

Dracunculiasis

Treatment of dracunculiasis† caused by Dracunculus medinensis (guinea worm disease).¹⁵³

Treatment of choice is slow extraction of worm combined with wound care.¹⁵³ Metronidazole is not curative, but decreases inflammation and facilitates worm removal.¹⁵³

Giardiasis

Treatment of giardiasis†.^{100 153 367 452} Drugs of choice are metronidazole, tinidazole, or nitazoxanide;^{100 153 367 452} alternatives are paromomycin, furazolidone (no longer commercially available in the US), or quinacrine (not commercially available in the US).^{100 153 367}

Treatment of asymptomatic carriers of giardiasis†.^{100 367} Treatment of such carriers not generally recommended, except possibly in patients with hypogammaglobulinemia or cystic fibrosis or in an attempt to prevent household transmission of the disease from toddlers to pregnant women.¹⁰⁰

Helicobacter pylori Infection and Duodenal Ulcer Disease

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

Used in a multiple-drug regimen that includes metronidazole, tetracycline, and bismuth subsalicylate and a histamine H₂-receptor antagonist.⁴⁵⁵ If initial 14-day regimen does not eradicate H. pylori, a retreatment regimen that does not include metronidazole should be used.⁴⁵⁵

Nongonococcal Urethritis

Treatment of recurrent and persistent urethritis† in patients with nongonococcal urethritis who have already been treated with a recommended regimen (i.e., azithromycin, doxycycline, erythromycin, ofloxacin or levofloxacin).³⁴¹

Oral metronidazole or oral tinidazole used in conjunction with oral azithromycin (if azithromycin was not used in the initial regimen) is the regimen recommended by CDC for recurrent and persistent urethritis in patients who were compliant with their initial regimen and have not been re-exposed.³⁴¹

Rosacea

Treatment of inflammatory lesions (papules and pustules) and erythema associated with rosacea† (acne rosacea).^{137 139 145 146 148 168 180 181} Topical metronidazole may be preferred to oral metronidazole.^{137 181}

Tetanus

Adjunct in treatment of tetanus caused by C. tetani.^{100 489}

Trichomoniasis

Treatment of symptomatic and asymptomatic trichomoniasis when Trichomonas vaginalis has been demonstrated by an appropriate diagnostic procedure (e.g., wet smear and/or culture, OSOM Trichomonas Rapid Test, Affirm VP III).^{100 152 153 197 199 297 298 302 337 338 339 341}

Drug of choice is metronidazole or tinidazole.^{100 153 199 297 302 337 338 339 341} Goal of treatment is to provide symptomatic relief, achieve microbiologic cure, and reduce transmission; to achieve this goal, both the index patient and sexual (particularly steady) partner(s) should be treated.^{153 199 297 302 339 341}

If treatment failure occurs with initial metronidazole treatment and reinfection is excluded, alternative regimens using metronidazole or tinidazole can be used.^{153 199 341} If retreatment is ineffective, consultation with an expert (available through CDC) is recommended.³⁴¹

Perioperative Prophylaxis

Perioperative prophylaxis to reduce the incidence of postoperative anaerobic bacterial infections in patients undergoing colorectal surgery.^{109 110 111 112 156 495} Preferred regimens are IV cefoxitin alone; IV cefazolin and IV metronidazole; oral erythromycin and oral neomycin; or oral metronidazole and oral neomycin.^{110 112 490}

Perioperative prophylaxis in patients undergoing appendectomy†;^{109 111 110 112 113} used in conjunction with cefazolin.¹¹⁰ Preferred regimens for appendectomy (nonperforated) are IV cefoxitin alone or IV cefazolin and IV metronidazole.¹¹⁰

Prophylaxis in Sexual Assault Victims

Empiric anti-infective prophylaxis in sexual assault victims†; used in conjunction with IM ceftriaxone and oral azithromycin or doxycycline.^{199 341}

Flagyl Dosage and Administration

Administration

Administer orally^{152 197 430} or by continuous or intermittent IV infusion.^{156 495} Do not administer by rapid IV injection because of the low pH of the reconstituted product.^{156 495}

In the treatment of serious anaerobic infections, parenteral route usually is used initially and oral metronidazole substituted when warranted by patient’s condition.^{152 197}

Oral Administration

Administer extended-release tablets at least 1 hour before or 2 hours after meals.⁴³⁰

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Commercially available metronidazole injection for IV infusion does not need to be diluted or neutralized prior to IV administration.^{156 495}

Metronidazole hydrochloride powder for injection must by reconstituted, diluted, and then neutralized prior to IV administration.¹⁵⁶

Reconstitution and Dilution

Reconstitute metronidazole hydrochloride powder for injection by adding 4.4 mL of sterile or bacteriostatic water for injection, 0.9% sodium chloride injection, or bacteriostatic sodium chloride injection to the vial containing 500 mg of metronidazole.¹⁵⁶ The reconstituted solution contains approximately 100 mg of metronidazole/mL and has a pH of 0.5–2.¹⁵⁶

The reconstituted metronidazole hydrochloride solution must be further diluted with 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer’s injection to a concentration of ≤8 mg/mL.¹⁵⁶

The reconstituted and diluted metronidazole hydrochloride solution must then be neutralized by adding approximately 5 mEq of sodium bicarbonate injection for each 500 mg of metronidazole.¹⁵⁶ The addition of sodium bicarbonate to the metronidazole hydrochloride solution may generate carbon dioxide gas and it may be necessary to relieve gas pressure in the container.¹⁵⁶

Rate of Administration

IV infusions usually are infused over 1 hour.^{156 495}

Dosage

Available as metronidazole^{152 156 197 430 495} and metronidazole hydrochloride;¹⁵⁶ dosage expressed in terms of metronidazole.¹⁵⁶

Pediatric Patients

General Dosage in Neonates†

Oral or IV

Neonates <1 week of age: AAP recommends 7.5 mg/kg every 24–48 hours in those weighing <1.2 g, 7.5 mg/kg every 24 hours in those weighing 1.2–2 kg, or 7.5 mg/kg every 12 hours in those weighing >2 kg.¹⁰⁰

Neonates 1–4 weeks of age: AAP recommends 7.5 mg/kg every 24–48 hours in those weighing <1.2 kg, 7.5 mg/kg every 12 hours in those weighing 1.2–2 kg, and 15 mg/kg every 12 hours in those weighing >2 kg.¹⁰⁰

General Dosage in Children ≥1 Month of Age†

Oral

15–35 mg/kg daily in 3 divided doses.¹⁰⁰ AAP states oral route inappropriate for severe infections.¹⁰⁰

Amebiasis

Entamoeba histolytica Infections

Oral

35–50 mg/kg daily in 3 divided doses given for 7–10 (usually 10) days;^{152 153 197 370} follow-up with a luminal amebicide (e.g., iodoquinol, paromomycin).¹⁵³

Bacterial Vaginosis†

Oral

Children weighing <45 kg: 15 mg/kg daily (up to 1 g) in 2 divided doses given for 7 days.¹⁰⁰

Adolescents: 500 mg twice daily for 7 days.¹⁰⁰

Balantidiasis†

Oral

35–50 mg/kg daily in 3 divided doses given for 5 days.¹⁵³

Blastocystis hominis Infections†

Oral

20–35 mg/kg daily in 3 divided doses given for 10 days may improve symptoms in some patients.¹⁰⁰

Crohn’s Disease†

Oral

10–20 mg/kg daily (up to 1 g daily) has been recommended for children with mild perianal Crohn’s disease† or those intolerant to sulfasalazine or mesalamine.⁴⁸⁷

Clostridium difficile-associated Diarrhea and Colitis†

Oral

30–50 mg/kg daily in 3 or 4 equally divided doses given for 7–10 days (not to exceed adult dosage).^{100 445 446}

Dientamoeba fragilis Infections†

Oral

20–40 mg/kg daily in 3 divided doses given for 10 days.¹⁵³

Dracunculiasis†

Oral

25 mg/kg daily (up to 750 mg) in 3 divided doses given for 10 days.¹⁵³ Is not curative, but may decrease inflammation and facilitate worm removal.¹⁵³

Giardiasis†

Oral

15 mg/kg daily in 3 divided doses given for 5–7 days.^{153 367 452}

Nongonococcal Urethritis†

Oral

Recurrent or persistent urethritis in adolescents: A single 2-g dose given in conjunction with a single 1-g dose of oral azithromycin (if azithromycin not used in the initial regimen).³⁴¹

Tetanus†

Oral

30 mg/kg daily (up to 4 g daily) in 4 doses given for 10–14 days.¹⁰⁰

IV

30 mg/kg daily (up to 4 g daily) in 4 doses given for 10–14 days.¹⁰⁰

Trichomoniasis†

Oral

Prepubertal children weighing <45 kg: 15 mg/kg daily in 3 divided doses (up to 2 g daily) given for 7 days.^{100 153}

Adolescents: A single 2-g dose or 500 mg twice daily for 7 days.¹⁰⁰

Prophylaxis in Sexual Assault Victims†

Oral

Preadolescent children weighing <45 kg: 15 mg/kg daily given in 3 divided doses for 7 days given in conjunction with IM ceftriaxone and either oral azithromycin or oral erythromycin.^{100 341}

Adolescents and preadolescent children weighing ≥45 kg: A single 2-g dose given in conjunction with IM ceftriaxone and either oral azithromycin or oral doxycycline.^{100 341}

Adults

Anaerobic Bacterial Infections

Serious Infections

Oral

7.5 mg/kg every 6 hours (up to 4 g daily).^{152 156 197}

IV, then Oral

An initial IV loading dose of 15 mg/kg followed by IV maintenance doses of 7.5 mg/kg every 6 hours.^{156 495} After clinical improvement occurs, switch to oral metronidazole (7.5 mg/kg every 6 hours).^{156 495}

Total duration of treatment usually is 7–10 days, but infections of bone and joints, lower respiratory tract, or endocardium may require longer treatment.^{156 495}

Gynecologic Infections

Pelvic Inflammatory Disease

Oral

500 mg twice daily given for 14 days; used in conjunction with a single IM dose of ceftriaxone (250 mg), cefoxitin (2 g with oral probenecid 1 g), or another parenteral cephalosporin (e.g., cefotaxime) and 14-day regimen of oral doxycycline (100 mg twice daily).^{341 496}

Alternatively, 500 mg twice daily given for 14 days; used in conjunction with a 14-day regimen of oral ofloxacin (400 mg twice daily) or levofloxacin (500 mg once daily).^{199 341 496} Regimens containing a fluoroquinolone should only be considered when a parenteral cephalosporin is not feasible and the community prevalence and individual risk of gonorrhea is low.⁴⁹⁶

Amebiasis

Entamoeba histolytic Infections

Oral

750 mg 3 times daily given for 5–10 (usually 10) days for intestinal amebiasis^{152 153 197 364 368 370} or 500–750 mg 3 times daily given for 5–10 (usually 10) days for amebic liver abscess.^{152 197 364 368 370} Alternatively, amebic liver abscess has been treated with 2.4 g once daily given for 1 or 2 days.³⁶⁴

Follow-up with a luminal amebicide (e.g., iodoquinol, paromomycin) after metronidazole.^{153 364 368 370}

IV

500 mg every 6 hours for 10 days.³⁶⁴

Bacterial Vaginosis

Nonpregnant Women

Oral

Conventional tablets: 500 mg twice daily given for 7 days.^{100 199 286 297 298 300 301 302 341 366} A single 2-g dose has been used (e.g., for patients who may be noncompliant with the multiple-dose regimen),^{120 122 199 292 297} but appears to be less effective than other regimens and is no longer recommended by CDC.³⁴¹

Extended-release tablets: 750 mg once daily given for 7 days.^{199 341 416 417 430}

Pregnant Women

Oral

Conventional tablets: 500 mg twice daily or 250 mg 3 times daily given for 7 days.^{341 416 417}

Contraindicated during first trimester of pregnancy.^{152 197 430} In addition, single-dose regimens not recommended in pregnant women because of the slightly higher serum concentrations attained, which may reach fetal circulation.¹⁵²

Balantidiasis†

Oral

750 mg 3 times daily given for 5 days.¹⁵³

Blastocystis hominis Infections†

Oral

750 mg 3 times daily given for 10 days may improve symptoms in some patients.^{100 153}

Crohn’s Disease†

Oral

400 mg twice daily^{101 103 105} or 1 g daily has been effective for treatment of active Crohn’s disease†.^{467 472 473 475 476 482} For treatment of refractory perineal disease, 20 mg/kg (1–1.5 g) given in 3–5 divided doses daily has been employed.^{102 103 104 105 478 486}

Clostridium difficile-associated Diarrhea and Colitis†

Oral

750 mg to 2 g daily in 3 or 4 divided doses given for 7–14 days.^{125 126 129 131 132 133 313 314}

Dose-ranging studies to determine comparative efficacy have not been performed; most commonly employed regimens are 250 mg 4 times daily or 500 mg 3 times daily given for 10 days.^{443 444 445 446}

IV

500–750 mg every 6–8 hours; use when oral therapy is not feasible.^{134 161 162 313 342 343 445}

Dientamoeba fragilis Infections†

Oral

500–750 mg 3 times daily given for 10 days.¹⁵³

Dracunculiasis†

Oral

250 mg 3 times daily given for 10 days.¹⁵³ Is not curative, but may decrease inflammation and facilitate worm removal.¹⁵³

Giardiasis†

Oral

250 mg 3 times daily given for 5–7 days.^{153 367 452}

Helicobacter pylori Infection and Duodenal Ulcer Disease

Oral

250 mg in conjunction with tetracycline (500 mg) and bismuth subsalicylate (525 mg) 4 times daily (at meals and at bedtime) for 14 days; these drugs should be given concomitantly with an H₂-receptor antagonist in recommended dosage.⁴⁵⁵

Nongonococcal Urethritis†

Oral

Recurrent or persistent urethritis: A single 2-g dose given in conjunction with a single 1-g dose of oral azithromycin (if azithromycin not used in the initial regimen).³⁴¹

Tetanus†

IV

500 mg every 6 hours given for 7–10 days.⁴⁸⁹

Trichomoniasis

Initial Treatment

Oral

2 g as a single dose^{152 153 199 341} or in 2 divided doses.¹⁵² Alternatively, 500 mg twice daily given for 7 days^{153 199 341} or 375 mg twice daily given for 7 days.^{199 197} Manufacturer also recommends 250 mg 3 times daily given for 7 days.¹⁵²

Retreatment

Oral

500 mg twice daily given for 7 days.^{297 341} If repeated failure occurs, CDC recommends 2 g once daily given for 5 days.^{297 341} Others recommend retreatment with 2–4 g daily for 7–14 days if metronidazole-resistant strains are involved.^{153 199}

Do not administer repeat courses of treatment unless presence of T. vaginalis is confirmed by wet smear and/or culture and an interval of 4–6 weeks has passed since the initial course.^{152 197}

If treatment of resistant infection is guided by in vitro susceptibility testing under aerobic conditions, some clinicians recommend that T. vaginalis strains exhibiting low-level resistance (minimum lethal concentration [MLC] <100 mcg/mL) be treated with 2 g daily for 3–5 days, those with moderate (intermediate) resistance (MLC 100–200 mcg/mL) be treated with 2–2.5 g daily for 7–10 days, and those with high-level resistance (MLC >200 mcg/mL) be treated with 3–3.5 g daily for 14–21 days.^{124 302 338 340} Because strains with high-level resistance are difficult to treat,^{124 297 302 338 340} CDC recommends that patients with culture-documented infection who do not respond to repeat regimens at dosages up to 2 g daily for 3–5 days and in whom the possibility of reinfection has been excluded should be managed in consultation with an expert (available through CDC).^{297 341}

Perioperative Prophylaxis

Colorectal Surgery

IV

0.5 g given at induction of anesthesia (within 0.5–1 hour prior to incision); used in conjunction with IV cefazolin (1–2 g).¹¹⁰

Manufacturer recommends 15 mg/kg by IV infusion over 30–60 minutes 1 hour prior to the procedure and, if necessary, 7.5 mg/kg by IV infusion over 30–60 minutes at 6 and 12 hours after the initial dose.^{156 495} The initial preoperative dose must be completely infused approximately 1 hour prior to surgery to ensure adequate serum and tissue concentrations of metronidazole at the time of incision.^{156 495} Prophylactic use of metronidazole should be limited to the day of surgery and should not be continued for more than 12 hours after surgery.^{156 495}

Oral

2 g with oral neomycin sulfate (2 g) given at 7 p.m. and 11 p.m. on day before surgery; used in conjunction with appropriate diet and catharsis.¹¹⁰

Prophylaxis in Sexual Assault Victims†

Oral

A single 2-g dose given in conjunction with IM ceftriaxone and either oral azithromycin or oral doxycycline.^{100 341}

Special Populations

Hepatic Impairment

Decrease dosage in patients with severe hepatic impairment and monitor plasma concentrations of the drug.^{152 156 160 197 430 495}

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic function.^{152 197 430}

Cautions for Flagyl

Contraindications

• 
  

  Hypersensitivity to metronidazole or other nitroimidazole derivatives.^{152 156 197 430 495} Cautious desensitization has been used in some situations when use of metronidazole was considered necessary.^{341 436} (See Hypersensitivity Reactions and Desensitization under Cautions.)

  
  


• 
  

  First trimester of pregnancy.^{152 197 430}

  
  


• 
  

  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.⁴⁵⁵

  
  

Warnings/Precautions

Warnings

Seizures and Peripheral Neuropathy

Seizures and peripheral neuropathy (characterized by numbness or paresthesia of an extremity) reported with metronidazole.^{152 156 197 430 495}

Persistent peripheral neuropathy reported in some patients receiving prolonged therapy.⁴³⁰ If abnormal neurologic signs develop, promptly discontinue drug..^{152 156 197 430}

Use with caution in those with CNS diseases.^{152 197 430}

Sensitivity Reactions

Hypersensitivity Reactions and Desensitization

Hypersensitivity reactions, including urticaria, pruritus, erythematous rash, flushing, nasal congestion, fever, and fleeting joint pains sometimes resembling serum sickness, have been reported with metronidazole.^{152 156 197 430 495}

Because there are no effective alternatives to metronidazole in the US for treatment of trichomoniasis, CDC states that desensitization can be attempted in patients with metronidazole hypersensitivity.³⁴¹ The possibility that desensitization may be hazardous should be considered⁴³⁵ and adequate procedures (e.g., established IV access, BP monitoring) and therapies (e.g., epinephrine, corticosteroids, antihistamines, oxygen) for management of an acute hypersensitivity reaction should be readily available.⁴³⁵ Pretreatment (e.g., with an antihistamine and/or corticosteroid) also should be considered.⁴³⁵

Desensitization has been performed by administering increasing doses of IV metronidazole incrementally until a therapeutic dose was achieved, at which time oral dosing was initiated.⁴³⁵ In this regimen, an initial 5-mcg dose of IV metronidazole was given and the dose increased at 15- to 20-minute intervals to 15, 50, 150, and 500 mcg and then to 1.5, 5, 15, 30, 60, and 125 mg.⁴³⁵ After the 125-mg IV dose, dosing was switched to oral metronidazole and doses of 250, 500, and 2 g were given at 1-hour intervals.⁴³⁵ For trichomoniasis, desensitization dosing can be stopped after the 2-g dose.⁴³⁵ Patient should be monitored for ≥4 hours after the last dose (24 hours if there was any evidence of a reaction).⁴³⁵

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of metronidazole and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^{152 197 430 495}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{152 197 430 495} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{152 197 430 495}

Surgical procedures should be performed in conjunction with metronidazole therapy when indicated.^{152 156 197 430 495}

In mixed aerobic and anaerobic infections, anti-infectives appropriate for treatment of aerobic bacteria should be used in conjunction with metronidazole.^{152 156 197 430 495}

History of Blood Dyscrasia

Kytril

Generic Name: Granisetron Hydrochloride
Class: 5-HT3 Receptor Antagonists
Chemical Name: endo-1-Methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H-indazole-3-carboxamide monohydrochloride
Molecular Formula: C₁₈H₂₄N₄O•ClH
CAS Number: 107007-99-8

Introduction

Antiemetic; selective inhibitor of type 3 serotonergic (5-HT₃) receptors.^{1 2 3}

Uses for Kytril

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin.^{1 33}

Postoperative Nausea and Vomiting

Prevention and treatment of postoperative nausea and vomiting.¹

Routine prophylaxis not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.¹

Recommended for patients who, in the clinician’s judgment, must avoid nausea and/or vomiting postoperatively, even when anticipated incidence is low.¹

Radiation-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with radiation, including total body irradiation and daily fractionated abdominal radiation.³³

Kytril Dosage and Administration

Administration

Administer orally, by IV infusion, or by direct IV injection.^{1 33}

Oral Administration

May use oral solution and tablets interchangeably.³³

For prevention of nausea and vomiting associated with chemotherapy, administer once or twice daily.³³ Administer only on days when emetogenic chemotherapy is administered.³³

For prevention of radiation-induced nausea and vomiting, administer within 1 hour of radiation.³³

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

For prevention of nausea and vomiting associated with chemotherapy, administer approximately 30 minutes before administration of emetogenic drug, only on days when emetogenic chemotherapy is administered.¹

For prevention of postoperative nausea and vomiting, administer before induction of or immediately before reversal of anesthesia.¹

Dilution

IV infusion: Dilute in 5% dextrose or 0.9% sodium chloride injection¹ to a total volume of 20–50 mL.^HID

Rate of Administration

Direct IV injection: Administer undiluted over 30 seconds.¹

IV infusion: Infuse over 5 minutes.¹

Dosage

Available as granisetron hydrochloride; dosage expressed in terms of granisetron.^{1 33}

Pediatric Patients

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

IV

Children 2–16 years of age: 10 mcg/kg by IV infusion or direct IV injection within 30 minutes before administration of chemotherapy.¹

Adults

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

Oral

2 mg once daily up to 1 hour before administration of chemotherapy.³³

Alternatively, 1 mg twice daily (first dose up to 1 hour before chemotherapy and second dose 12 hours after first dose).³³

IV

10 mcg/kg by IV infusion or direct IV injection within 30 minutes before administration of chemotherapy.¹

Postoperative Nausea and Vomiting

Prevention

IV

1 mg as a single dose by direct IV injection before induction of or immediately before reversal of anesthesia.¹

Treatment

IV

1 mg as a single dose by direct IV injection.¹

Radiation-induced Nausea and Vomiting

Prevention

Oral

2 mg once daily within 1 hour of radiation.³³

Special Populations

Hepatic Impairment

No dosage adjustment required.^{1 33}

Geriatric Patients

No dosage adjustment required.^{1 33}

Cautions for Kytril

Contraindications

• 
  

  Known hypersensitivity to granisetron or any ingredient in the formulation.^{1 33}

  
  

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including anaphylactic reaction, shortness of breath, hypotension, and urticaria, reported rarely.^{1 33}

Possible hypersensitivity reactions in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists.^{1 33}

General Precautions

GI Precautions

Does not stimulate gastric or intestinal peristalsis; do not use as a substitute for nasogastric suction.¹

May mask progressive ileus and/or gastric distention when used in patients undergoing abdominal surgery or in those with chemotherapy-induced nausea and vomiting.¹

Specific Populations

Pregnancy

Category B.^{1 33}

Lactation

Not known whether granisetron is distributed into milk.^{1 33} Caution advised if used in nursing women.^{1 33}

Pediatric Use

Safety and efficacy of IV granisetron for chemotherapy-induced nausea and vomiting not established in children <2 years of age; safety and efficacy of IV granisetron for prevention and treatment of postoperative nausea and vomiting not established in children of any age.¹

Safety and efficacy of oral granisetron not established in children of any age.³³

Geriatric Use

No substantial differences in safety and efficacy for chemotherapy-induced nausea and vomiting in geriatric patients relative to younger adults.^{1 33}

Insufficient experience with IV granisetron for postoperative nausea and vomiting in patients≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Common Adverse Effects

Headache^{1 33} , constipation^{1 33} , pain¹ , diarrhea^{1 33} , fever¹ , abdominal pain^{1 33} , increased hepatic enzymes^{1 33} , asthenia^{1 33} , dyspepsia³³ .

Interactions for Kytril

Apparently metabolized by CYP3A; does not induce or inhibit CYP isoenzymes.^{1 33}

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered granisetron clearance and half-life) with inhibitors or inducers of CYP isoenzymes.^{1 33}

Specific Drugs

Drug	Interaction
Antineoplastic agents	No apparent interaction with emetogenic cancer chemotherapies1 33
Ketoconazole	Inhibition of granisetron metabolism in vitro33

Kytril Pharmacokinetics

Absorption

Bioavailability

Dose of oral solution is bioequivalent to corresponding dose of oral tablets.³³

Food

Food has minimal effect on extent of absorption; may increase peak plasma concentration by 30%.³³

Distribution

Extent

Distributes freely between plasma and red blood cells.^{1 33} Not known whether granisetron distributed into milk.^{1 33}

Plasma Protein Binding

Approximately 65%.^{1 33}

Elimination

Metabolism

Metabolized via N-demethylation and aromatic ring oxidation followed by conjugation; metabolism appears to be mediated by CYP3A subfamily.^{1 33}

Elimination Route

Excreted in urine as unchanged drug (11–12%) and metabolites (48–49%) and in feces as metabolites (34–38%).^{1 33}

Half-life

IV administration: Terminal half-life is approximately 9 hours in adult cancer patients or adults undergoing surgery.¹

Oral administration: Terminal half-life is approximately 6.2 hours in healthy adults.¹

Special Populations

In pediatric cancer patients, pharmacokinetic profile is similar to that in adult cancer patients.¹

In geriatric patients, mean clearance may be decreased and half-life increased compared with younger adults.¹

In patients with hepatic impairment due to neoplastic liver involvement, total clearance following a single IV dose is reduced by approximately 50% compared with patients without hepatic impairment.¹

In patients with severe renal impairment, total clearance following a single 40-mcg/kg IV dose is not altered.¹

Stability

Storage

Oral

Tablets

Tight container at 15–30°C; protect from light.³³

Solution

Tight container at 25°C (may be exposed to 15–30°C).³³ Store in upright position; protect from light.³³

Parenteral

Injection

25°C (may be exposed to 15–30°C).¹ Do not freeze; protect from light.¹ Once multiple-dose vial is penetrated, use contents within 30 days.¹

Following dilution with sodium chloride 0.9% or dextrose 5% injection, stable for at least 24 hours at room temperature under normal lighting conditions.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible
Dextrose 5% in sodium chloride 0.45 or 0.9%HID
Dextrose 5% in waterHID
Sodium chloride 0.9%HID

Drug Compatibility

Admixture CompatibilityHID

Compatible
Dexamethasone sodium phosphate
Methylprednisolone sodium succinate

Y-Site CompatibilityHID

Compatible
Acyclovir sodium
Allopurinol sodium
Amifostine
Amikacin sulfate
Aminophylline
Amphotericin B cholesteryl sulfate complex
Ampicillin sodium
Ampicillin sodium–sulbactam sodium
Amsacrine
Aztreonam
Bleomycin sulfate
Bumetanide
Buprenorphine HCl
Butorphanol tartrate
Calcium gluconate
Carboplatin
Carmustine
Cefazolin sodium
Cefepime HCl
Cefotaxime sodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Chlorpromazine HCl
Cimetidine HCl
Ciprofloxacin
Cisplatin
Cladribine
Clindamycin phosphate
Co-trimoxazole
Cyclophosphamide
Cytarabine
Dacarbazine
Dactinomycin
Daunorubicin HCl
Dexamethasone sodium phosphate
Dexmedetomidine HCl
Diphenhydramine HCl
Dobutamine HCl
Docetaxel
Dopamine HCl
Doxorubicin HCl
Doxorubicin HCl liposome injection
Doxycycline hyclate
Droperidol
Enalaprilat
Etoposide
Etoposide phosphate
Famotidine
Fenoldopam mesylate
Filgrastim
Floxuridine
Fluconazole
Fludarabine phosphate
Fluorouracil
Furosemide
Gallium nitrate
Ganciclovir sodium
Gemcitabine HCl
Gentamicin sulfate
Haloperidol lactate
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydrocortisone sodium phosphate
Hydrocortisone sodium succinate
Hydromorphone HCl
Hydroxyzine HCl
Idarubicin HCl
Ifosfamide
Imipenem–cilastatin sodium
Leucovorin calcium
Levoleucovorin calcium
Linezolid
Lorazepam
Magnesium sulfate
Melphalan
Meperidine HCl
Mesna
Methotrexate sodium
Methylprednisolone sodium succinate
Metoclopramide HCl
Metronidazole
Mitomycin
Mitoxantrone HCl
Morphine sulfate
Nalbuphine HCl
Ofloxacin
Oxaliplatin
Paclitaxel
Pemetrexed disodium
Piperacillin sodium–tazobactam sodium
Potassium chloride
Prochlorperazine edisylate
Promethazine HCl
Propofol
Ranitidine HCl
Sargramostim
Sodium bicarbonate
Streptozocin
Teniposide
Thiotepa
Ticarcillin disodium–clavulanate potassium
Tobramycin sulfate
Topotecan HCl
Vancomycin HCl
Vinblastine sulfate
Vincristine sulfate
Vinorelbine tartrate
Zidovudine
Incompatible
Amphotericin B

ActionsActions

• 
  

  Antiemetic activity appears to be mediated both centrally (in medullary chemoreceptor trigger zone) and peripherally (in GI tract) via inhibition of 5-HT₃ receptors.^{4 5 6 8 11 12 13 29 30}

  
  

Advice to Patients

• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Granisetron Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	1 mg (of granisetron) per 5 mL	Kytril	Roche
	Tablets, film-coated	1 mg (of granisetron)	Kytril	Roche
Parenteral	Injection, for IV use	0.1 mg (of granisetron) per mL (0.1 mg)	Kytril (available in single-use preservative-free vials)	Roche
		1 mg (of granisetron) per mL (1 and 4 mg)	Kytril (available in single-use, preservative-free vials and in multiple-dose, benzyl alcohol-preserved vials)	Roche

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Granisetron HCl 1MG Tablets (TEVA PHARMACEUTICALS USA): 2/$45.99 or 6/$125.96

Kytril 1MG Tablets (GENENTECH): 2/$131.98 or 6/$385.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Roche. Kytril (granisetron hydrochloride) injection prescribing information. Nutley, NJ; 2002 Aug.

2. Jay GT, Wallace M, DeFusco P et al. Focus on granisetron: the second 5-HT₃ receptor antagonist approved for chemotherapy-induced emesis. Hosp Formul. 1994; 29:191-201.

3. Seynaeve C, De Mulder PHM, Verweij J. Pathophysiology of cytotoxic drug-induced emesis: far from crystal-clear. Pharm Weekbl [Sci]. 1991; 13:1-6. [IDIS 278161] [PubMed 1674600]

4. McKeage MJ. Comparative adverse effect profile of platinum drugs. Drug Saf. 1995; 13:228-44. [PubMed 8573296]

5. Cubeddu LX, Hoffmann IS. Participation of serotonin on early and delayed emesis induced by initial and subsequent cycles of cisplatinum-based chemotherapy: effects of antiemetics. J Clin Pharmacol. 1993; 33:691-7. [IDIS 319277] [PubMed 7691898]

6. Hesketh PJ, Gandara DR. Serotonin antagonists: a new class of antiemetic agents. J Natl Cancer Inst. 1991; 83:613-20. [PubMed 1850806]

7. du Bois A, Meerpohl HG, Vach W et al. Course, patterns, and risk-factors for chemotherapy-induced emesis in cisplatin pretreated patients: a study with ondansetron. Eur J Cancer. 1992; 28:450-7. [PubMed 1534250]

8. Gebbia V, Cannata G, Testa A et al. Ondansetron versus granisetron in the prevention of chemotherapy-induced nausea and vomiting. Results of a prospective randomized trial. Cancer. 1994; 74:1945-52. [IDIS 336138] [PubMed 8082100]

9. Perez EA. Review of the preclinical pharmacology and comparative efficacy of 5- hydroxytryptamine-3 receptor antagonists for chemotherapy-induced emesis. J Clin Oncol. 1995; 13:1036-43. [IDIS 344879] [PubMed 7707101]

10. Ruff P, Paska W, Goedhals L et al for the Ondansetron and Granisetron Emesis Study Group. Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced acute emesis: a multicentre double-blind, randomised, parallel-group study. Oncology. 1994; 51:113-8. [PubMed 8265095]

11. Gralla RJ. Adverse effects of treatment: antiemetic therapy. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia: J.B. Lippincott Company; 1993:2338-48.

12. De Mulder PHM, Seynaeve C, Vermorken JB et al. Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, crossover study. Ann Intern Med. 1990; 113:834-40. [IDIS 274419] [PubMed 2146911]

13. Kris MG, Pisters KM, Hinkley L. Delayed emesis following anticancer chemotherapy. Support Care Cancer. 1994; 2:297-300. [PubMed 8000726]

14. Italian Group for Antiemetic Research. Ondansetron + dexamethasone vs metoclopramide + dexamethasone + diphenhydramine in prevention of cisplatin-induced emesis. Lancet. 1992; 340:96-99. [IDIS 298926] [PubMed 1352024]

15. du Bois A, Vach W, Thomssen C et al. Comparison of emetogenic potential between cisplatin and carboplatin in combination with akylating agents. Acta Oncol. 1994; 33:531-5. [PubMed 7917367]

16. Smith DB, Newlands ES, Rustin GJS et al. Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy. Lancet. 1991; 338:487-90. [IDIS 284481] [PubMed 1714532]

17. Anon. Ondansetron vs dexamethasone for chemotherapy-induced emesis. Lancet. 1991; 338:478-9. [PubMed 1714531]

18. Navari R, Gandara D, Hesketh P et al. Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group. J Clin Oncol. 1995; 13:1242-8. [IDIS 347756] [PubMed 7738628]

19. Marty M. A comparison of granisetron as a single agent with conventional combination antiemetic therapies in the treatment of cytostatic-induced emesis. The Granisetron Study Group. Eur J Cancer. 1992; 28A(Suppl 1):S12-6.

20. Ohmatsu H, Eguchi K, Shinkai T et al. A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin. Jpn J Cancer Res. 1994; 85:1151-8. [PubMed 7829401]

21. Heron JF, Goedhals L, Jordaan JP et al. Oral granisetron alone and in combination with dexamethasone: a double-blind randomized comparison against high-dose metoclopramide plus dexamethasone in prevention of cisplatin- induced emesis. The Granisetron Study Group. Ann Oncol. 1994; 5:579-84. [PubMed 7993831]

22. The Granisetron Study Group. The antiemetic efficacy and safety of granisetron compared with metoclopramide plus dexamethasone in patients receiving fractionated chemotherapy over 5 days. J Cancer Res Clin Oncol. 1993; 119:555-9. [PubMed 8392077]

23. Cunningham D, Hill M, Dicato M et al. Optimal anti-emetic therapy for cisplatin induced emesis over repeat courses. Proc Ann Meet Am Soc Clin Oncol. 1994; 13:A1553.

24. Tyson LB, Gralla RJ, Clark RA et al. Combination antiemetic trials with metoclopramide. Proc Am Soc Clin Oncol. 1983; 2:91.

25. Ahn MJ, Lee JS, Lee KH et al. A randomized double-blind trial of ondansetron alone versus in combination with dexamethasone versus in combination with dexamethasone and lorazepam in the prevention of emesis due to cisplatin-based chemotherapy. Am J Clin Oncol. 1994; 17:150-6. [IDIS 329909] [PubMed 8141107]

26. Bruera ED, Roca E, Cedaro L et al. Improved control of chemotherapy- induced emesis by the addition of dexamethasone to metoclopramide in patients resistant to metoclopramide. Cancer Treat Rep. 1983; 67:381-3. [IDIS 171263] [PubMed 6342770]

27. Malik IA, Khan WA, Qazilbash M et al. Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol. 1995; 18:170-5. [IDIS 344756] [PubMed 7900711]

28. Clerico M, Bertetto O, Cardinali C et al. Antiemetic activity of lorazepam in the prophylactic treatment of vomiting induced by cisplatin: a double-blind placebo controlled study with cross-over design. Ann Oncol. 1992; 3(Suppl 5):188.

29. Plosker GL, Goa KL. Granisetron: a review of its pharmacological properties and therapeutic use as an antiemetic. Drugs. 1991;42:805-24.

30. Grunberg SM, Hesketh PJ. Control of chemotherapy-induced emesis. N Engl J Med. 1993; 329:1790-6. [IDIS 322575] [PubMed 8232489]

31. Mitchelson F. Pharmacological agents affecting emesis: a review (part I). Drugs. 1992; 43:295-315. [PubMed 1374316]

32. Aapro MS. 5- HT₃ receptor antagonists: an overview of their present status and future potential in cancer therapy-induced emesis. Drugs. 1991; 42:551-68. [PubMed 1723361]

33. Roche. Kytril (granisetron hydrochloride) tablets and oral solution prescribing information. Nutley, NJ; 2001 Jun.

34. Spitzer TR, Friedman CJ, Bushnell W et al. Oral granisetron (Kytril) and ondansetron (Zofran) in the prevention of hyperfractionated total body irradiation induced emesis: the results of a double-blind, randomized parallel group study. Blood. 1998; 92(Suppl 1):278a.

35. Lanciano R, Sherman DM, Michalski J et al. The efficacy and safety of Kytril tablets (2 mg) once daily in patients receiving at least 10 fractions of uppper abdominal radiation for malignancy. Int J Radiat Oncol Biol Phys. 1998; 42(Suppl 1)204. Abstract.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:816-25.

More Kytril resources

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

• Kytril Prescribing Information (FDA)


• Kytril Consumer Overview


• Kytril Advanced Consumer (Micromedex) - Includes Dosage Information


• Kytril MedFacts Consumer Leaflet (Wolters Kluwer)


• Granisetron Prescribing Information (FDA)


• Granisol Prescribing Information (FDA)


• Sancuso Prescribing Information (FDA)


• Sancuso Consumer Overview


• Sancuso Advanced Consumer (Micromedex) - Includes Dosage Information


• Sancuso MedFacts Consumer Leaflet (Wolters Kluwer)

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• Nausea/Vomiting, Chemotherapy Induced
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Ketoconazole Gel and Pyrithione Zinc Shampoo Gel

Pronunciation: KEE-toe-KON-a-zole/PIR-i-THYE-one zink
Generic Name: Ketoconazole Gel and Pyrithione Zinc Shampoo
Brand Name: Xolegel Duo

Ketoconazole Gel and Pyrithione Zinc Shampoo Gel is used for:

Treating and preventing itching, flaking, and scaling of the skin and scalp caused by seborrheic dermatitis and dandruff.

Ketoconazole Gel and Pyrithione Zinc Shampoo Gel is a convenience pack containing an antifungal gel and antiseborrheic shampoo. The antifungal works by killing the fungus causing the skin condition. The antiseborrheic works by slowing the production of skin cells, which helps to reduce flakiness.

Do NOT use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel if:

• you are allergic to any ingredient in Ketoconazole Gel and Pyrithione Zinc Shampoo Gel

Contact your doctor or health care provider right away if any of these apply to you.

Before using Ketoconazole Gel and Pyrithione Zinc Shampoo Gel:

Some medical conditions may interact with Ketoconazole Gel and Pyrithione Zinc Shampoo Gel. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a condition that covers a large area of the body


• if you have a weakened immune system, liver problems, or the blood disease porphyria

Some MEDICINES MAY INTERACT with Ketoconazole Gel and Pyrithione Zinc Shampoo Gel. Because little, if any, of Ketoconazole Gel and Pyrithione Zinc Shampoo Gel is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Ketoconazole Gel and Pyrithione Zinc Shampoo Gel may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel:

Use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• FOR THE GEL: Wash your hands before and right after using Ketoconazole Gel and Pyrithione Zinc Shampoo Gel. Spread a thick layer of Ketoconazole Gel and Pyrithione Zinc Shampoo Gel onto the affected skin with the tips of your fingers. Gently rub it in. Be sure to cover the entire affected area and the healthy skin around it. Do not touch your eyes or nose while you are applying Ketoconazole Gel and Pyrithione Zinc Shampoo Gel.


• Wait for at least 20 minutes after you apply the gel before you apply makeup or sunscreen.


• Do not wash the area where you applied the gel for at least 3 hours after you apply it.


• FOR THE SHAMPOO: Shake well before each use. Wet hair thoroughly. Apply the shampoo and work it into a lather. Rinse thoroughly. You may repeat if desired unless your doctor tells you otherwise.


• For best results, use the shampoo at least 2 times per week or as directed by your doctor. Do not use more often than once daily.


• IF YOU MISS A DOSE OF THE GEL, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once. IF YOU MISS A DOSE OF THE SHAMPOO, use the dose when you remember. Continue to use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel as directed by your doctor or the package labeling.

Ask your health care provider any questions you may have about how to use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel.

Important safety information:

• Ketoconazole Gel and Pyrithione Zinc Shampoo Gel is for external use only. Do not get it in your eyes, nose, or mouth. If you get it in any of these areas, rinse at once with cool tap water. Do not get Ketoconazole Gel and Pyrithione Zinc Shampoo Gel in your vagina.


• Check with your doctor before you use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel if your condition covers a large area of your body.


• If your symptoms do not improve with regular use or if they become worse, consult your doctor.


• Do not use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel for other skin conditions at a later time.


• The gel in this convenience pack is flammable. Do not store or use near an open flame. Do not smoke during or right after use of Ketoconazole Gel and Pyrithione Zinc Shampoo Gel.


• Ketoconazole Gel and Pyrithione Zinc Shampoo Gel should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Ketoconazole Gel and Pyrithione Zinc Shampoo Gel while you are pregnant. It is not known if Ketoconazole Gel and Pyrithione Zinc Shampoo Gel is found in breast milk after topical use. If you are or will be breast-feeding while you use Ketoconazole Gel and Pyrithione Zinc Shampoo Gel, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Ketoconazole Gel and Pyrithione Zinc Shampoo Gel:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Mild burning at the application site.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blisters, irritation, pain, redness, or severe burning at the application site.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Ketoconazole Gel and Pyrithione Zinc Shampoo Gel is harmful if swallowed.

Proper storage of Ketoconazole Gel and Pyrithione Zinc Shampoo Gel:

Store Ketoconazole Gel and Pyrithione Zinc Shampoo Gel at room temperature, at 77 degrees F (25 degrees C). Brief storage between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do NOT store near an open flame. Keep Ketoconazole Gel and Pyrithione Zinc Shampoo Gel out of the reach of children and away from pets.

General information:

• If you have any questions about Ketoconazole Gel and Pyrithione Zinc Shampoo Gel, please talk with your doctor, pharmacist, or other health care provider.


• Ketoconazole Gel and Pyrithione Zinc Shampoo Gel is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Ketoconazole Gel and Pyrithione Zinc Shampoo Gel. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

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• Ketoconazole Gel and Pyrithione Zinc Shampoo Use in Pregnancy & Breastfeeding
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• 0 Reviews for Ketoconazole and Pyrithione Zinc - Add your own review/rating

Compare Ketoconazole Gel and Pyrithione Zinc Shampoo with other medications

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Liver Aid

Generic Name: silybum marianum seed, chelidonium majus, goldenseal, potassium chloride, sodium phosphate, dibasic anhydrous and sodium sulfate granules

Dosage Form: FOR ANIMAL USE ONLY
Liver Aid

Reduces toxins, plus stimulates liver and pancreatic functioning

Indications: Homeopathic liver and pancreatic tonic.

Dosage: Administer 3 times daily.  Cats and dogs under 20 lbs: Sprinkle 1 pinch into the mouth.  Dogs 20-50 lbs: 2 pinches sprinkled into the mouth. Dogs over 50 lbs: 1/4 cap.

Caution: Consult your vet if symptoms persist or worsen. Keep this and all medicines from the reach of children.

Ingredients: Each dose contains equal parts of Carduus mar (3X) (HPUS), Chelidonium maj (3X) (HPUS), Hydrastis (3X) (HPUS), Kali mur (6C) (HPUS), Nat phos (6C) (HPUS), Nat sulphuricum (6C) (HPUS)

Sucrose (inactive ingredient).

Contains no gluten, artificial flavors, colors or preservatives.

All Native Remedies health products are especially formulated by experts in the field of natural health and are manufactured according to the highest pharmaceutical standards for maximum safety and effectiveness. For more information, visit us at www.petalive.com

Distributed by

Native Remedies, LLC

6531 Park of Commerce Blvd. 

Suite 160

Boca Raton, FL 33487

Phone: +1.877.289.1235

International: +1.561.999.8857

The letters HPUS indicate that the component(s) in this product is (are) officially monographed in the Homeopathic Pharmacopoeia of the United States.

Keep this and all medicines from the reach of children.

LIVERAID  carduus mar, chelidonium maj, hydrastis, kali mur, nat phos, nat sulphuricum   granule

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 68647-136 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SILYBUM MARIANUM SEED (SILYBUM MARIANUM SEED) SILYBUM MARIANUM SEED 3 [hp_X]  in 33.3 mg CHELIDONIUM MAJUS (CHELIDONIUM MAJUS) CHELIDONIUM MAJUS 3 [hp_X]  in 33.3 mg GOLDENSEAL (GOLDENSEAL) GOLDENSEAL 3 [hp_X]  in 33.3 mg POTASSIUM CHLORIDE (POTASSIUM CATION) POTASSIUM CHLORIDE 6 [hp_C]  in 33.3 mg SODIUM PHOSPHATE, DIBASIC ANHYDROUS (SODIUM CATION) SODIUM PHOSPHATE, DIBASIC ANHYDROUS 6 [hp_C]  in 33.3 mg SODIUM SULFATE (SODIUM CATION) SODIUM SULFATE 6 [hp_C]  in 33.3 mg

Inactive Ingredients Ingredient Name Strength SUCROSE 20000 mg  in 20000 mg

Product Characteristics Color white (white sucrose granules) Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 68647-136-10 20000 mg In 1 BOTTLE, GLASS None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved homeopathic		01/01/2010

Labeler - Feelgood Health (538418296)

Establishment
Name	Address	ID/FEI	Operations
W. Last		567284153	manufacture

Revised: 09/2010Feelgood Health

Zinnat Suspension

1. Name Of The Medicinal Product

Zinnat Suspension 125mg/5ml

2. Qualitative And Quantitative Composition

Cefuroxime 125mg/5ml (as 150 mg cefuroxime axetil)

3. Pharmaceutical Form

Granules for constitution with water to form a suspension for oral administration.

4. Clinical Particulars

4.1 Therapeutic Indications

Cefuroxime axetil is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most β-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms.

It is indicated for the treatment of infections caused by sensitive bacteria.

Indications include: Lower respiratory tract infections for example, acute bronchitis, acute exacerbations of chronic bronchitis and pneumonia.

Upper respiratory tract infections for example, ear, nose, throat infections, such as otitis media, sinusitis, tonsillitis and pharyngitis.

Genito-urinary tract infections for example, pyelonephritis, cystitis and urethritis.

Skin and soft tissue infections for example, furunculosis, pyoderma and impetigo.

Gonorrhoea acute uncomplicated gonococcal urethritis, and cervicitis.

Treatment of early Lyme disease and subsequent prevention of late Lyme disease in adults and children over 12 years old.

Cefuroxime is also available as the sodium salt (Zinacef) for parenteral administration. This permits the use of sequential therapy with the same antibiotic, when a change from parenteral to oral therapy is clinically indicated.

Where appropriate Zinnat is effective when used following initial parenteral Zinacef (cefuroxime sodium) in the treatment of pneumonia and acute exacerbations of chronic bronchitis.

4.2 Posology And Method Of Administration

Adults: Most infections will respond to 250mg b.d. In mild to moderate lower respiratory tract infections e.g. bronchitis 250mg b.d. should be given. For more severe lower respiratory tract infections, or if pneumonia is suspected then 500mg b.d. should be given. For urinary tract infections a dose of 125mg b.d. is usually adequate; in pyelonephritis the recommended dose is 250mg b.d. A single dose of one gram is recommended for the treatment of uncomplicated gonorrhoea.

Lyme disease in adults and children over the age of 12 years: the recommended dose is 500mg b.d. for 20 days.

Sequential therapy:

Pneumonia:

1.5g Zinacef bd (iv or im) for 48-72 hours, followed by 500mg bd Zinnat (cefuroxime axetil) oral therapy for 7 days.

Acute exacerbations of chronic bronchitis:

750mg Zinacef bd (iv or im) for 48-72 hours, followed by 500mg Zinnat (cefuroxime axetil) oral therapy for 5-7 days.

Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.

Children: The usual dose is 125mg b.d. (1 x 125mg tablet or 5ml of suspension or 1 x 125mg sachet), or 10mg/kg b.d. to a maximum of 250mg daily. For otitis media, in children less than 2 years of age the usual dosage is 125mg b.d. (1 x 125mg tablet or 5ml of suspension or 1 x 125mg sachet), or 10mg/kg b.d. to a maximum of 250mg daily and in children over 2 years of age, 250mg b.d. (1 x 250mg tablet or 10ml of suspension or 2 x 125mg sachets), or 15mg/kg b.d. to a maximum of 500mg daily. There is no experience in children under 3 months of age.

Zinnat Tablets should not be crushed, therefore in younger children the suspension is more appropriate.

Elderly and Patients with Renal Impairment: No special precautions are necessary in patients with renal impairment or on renal dialysis or in the elderly at dosages up to the normal maximum of 1g per day.

The usual course of therapy is seven days.

Zinnat should be taken after food for optimum absorption.

4.3 Contraindications

Hypersensitivity to cephalosporin antibiotics.

4.4 Special Warnings And Precautions For Use

Special care is indicated in patients who have experienced an allergic reaction to penicillins or other beta-lactams.

As with other antibiotics, use of cefuroxime axetil may result in the overgrowth of Candida. Prolonged use may also result in the overgrowth of non-susceptible organisms (e.g. Enterococci and Clostridium difficile), which may require interruption of treatment.

Pseudomembranous colitis has been reported with the use of broad-spectrum antibiotics, therefore, it is important to consider its diagnosis in patients who develop serious diarrhoea during or after antibiotic use.

The Jarisch-Herxheimer reaction has been seen following Zinnat treatment of Lyme disease. It results from the bactericidal activity of Zinnat on the causative organism of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limited consequence of antibiotic treatment of Lyme disease.

With a sequential therapy regime the timing of change to oral therapy is determined by severity of the infection, clinical status of the patient and susceptibility of the pathogens involved. The change to oral therapy should only be made once there is a clear clinical improvement. If there has been no clinical improvement after 72 hours of parenteral treatment, then the patient's treatment should be reviewed. Please refer to the relevant prescribing information for cefuroxime sodium before initiating sequential therapy.

The sucrose content of Zinnat Suspension and granules (see section 6.1 List of Excipients) should be taken into account when treating diabetic patients, and appropriate advice provided.

Zinnat suspension contains aspartame, which is a source of phenylalanine and so should be used with caution in patients with phenylketonuria.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In common with other antibiotics, Zinnat may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime axetil. This antibiotic does not interfere in the alkaline picrate assay for creatinine.

4.6 Pregnancy And Lactation

There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime axetil but, as with all drugs, it should be administered with caution during early months of pregnancy. Cefuroxime is excreted in human milk, and consequently caution should be exercised when cefuroxime axetil is administered to a nursing mother.

4.7 Effects On Ability To Drive And Use Machines

As this medicine may cause dizziness, patients should be warned to be cautious when driving or operating machinery.

4.8 Undesirable Effects

Adverse drug reactions to cefuroxime axetil are generally mild and transient in nature.

The following convention has been used for the classification of undesirable effects:- very common (

Infections and infestations

Common: Candida overgrowth

Blood and lymphatic system disorders

Common: Eosinophilia

Uncommon: Positive Coombs' test, thrombocytopenia, leukopenia (sometimes profound)

Very rare: Haemolytic anaemia

Cephalosporins as a class tend to be absorbed onto the surface of red cells membranes and react with antibodies directed against the drug to produce a positive Coombs' test (which can interfere with cross-matching of blood) and very rarely haemolytic anaemia.

Immune system disorders

Hypersensitivity reactions including

Uncommon: Skin rashes

Rare: Urticaria, pruritus

Very rare: Drug fever, serum sickness, anaphylaxis

Nervous system disorders

Common: Headache, dizziness

Gastrointestinal disorders

Common: Gastrointestinal disturbances including diarrhoea, nausea, abdominal pain

Uncommon: Vomiting

Rare: Pseudomembranous colitis

Hepatobiliary disorders

Common: Transient increasesof hepatic enzyme levels, [ALT (SGPT), AST (SGOT), LDH]

Very rare: Jaundice (predominantly cholestatic), hepatitis

Skin and subcutaneous tissue disorders

Very rare: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthematic necrolysis)

Renal and Urinary tract disorders

Very Rare: interstitial nephritis

4.9 Overdose

Overdosage of cephalosporins can cause cerebral irritancy leading to convulsions.

Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Cefuroxime axetil is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most beta-lactamases and is active against a wide range of gram-positive and gram-negative organisms.

Microbiology:

Cefuroxime axetil owes its in vivo bactericidal activity to the parent compound, cefuroxime. Cefuroxime is a well-characterized and effective antibacterial agent which has broad-spectrum bactericidal activity against a wide range of common pathogens, including beta-lactamase-producing strains. Cefuroxime has good stability to bacterial beta-lactamase and consequently, is active against many ampicillin-resistant and amoxicillin-resistant strains. The bactericidal action of cefuroxime results from inhibition of cell-wall synthesis by binding to essential target proteins.

Cefuroxime is usually active against the following organisms in vitro:

Aerobes, Gram-negative: Haemophilus influenzae (including ampicillin-resistant strains); Haemophilus parainfluenzae; Moraxella catarrhalis; Escherichia coli; Klebsiella species; Proteus mirabilis; Proteus inconstans; Providencia species; Proteus rettgeri and Neisseria gonorrhoea (including penicillinase and non-penicillinase-producing strains).

Some strains of Morganella morganii, Enterobacter species and Citrobacter species have been shown by in vitro tests to be resistant to cefuroxime and other beta-lactam antibiotics.

Aerobes, Gram-positive: Staphylococcus aureus (including penicillinase-producing strains but excluding methicillin-resistant strains); Staphylococcus epidermidis, (including penicillinase producing strains but excluding methicillin-resistant strains); Streptococcus pyogenes (and betahaemolytic streptococci), Streptococcus pneumoniae; Streptococcus Group B (Streptococcus agalactiae) and Propionibacterium species.

Certain strains of enterococci, eg. Streptococcus faecalis, are resistant.

Anaerobes, Gram-positive and Gram-negative cocci (including Peptococcus and Peptostreptococcus species); Gram-positive bacilli (including Clostridium species) and Gram-negative bacilli (including Bacteroides and Fusobacterium species). Most strains of Bacteroides fragilis are resistant.

Other organisms, Borrelia burgdorferi.

Pseudomonas species, Campylobacter species, Acinetobacter calcoaceticus, Listeria monocytogenes, Legionella species and most strains of Serratia and Proteus vulgaris and Clostridium difficile are resistant to many cephalosporins including cefuroxime.

5.2 Pharmacokinetic Properties

After oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolysed in the intestinal mucosa and blood to release cefuroxime into the circulation. Optimum absorption occurs when it is administered after a meal. Peak serum cefuroxime levels occur approximately two to three hours after oral dosing. The serum half life is about 1.2 hours. Approximately 50% of serum cefuroxime is protein bound. Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion.

Concurrent administration of probenecid increases the area under the mean serum concentration time curve by 50%. Serum levels of cefuroxime are reduced by dialysis.

5.3 Preclinical Safety Data

No additional data of relevance.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Aspartame

Xanthan gum

Acesulfame potassium

Povidone K30

Stearic Acid

Sucrose

Tutti Frutti Flavour

Purified Water

Sucrose Quantities:

125 mg/5ml Suspension 3.062 g/5ml

125 mg Sachet 3.062 g

6.2 Incompatibilities

None.

6.3 Shelf Life

The shelf life of unconstituted Zinnat Suspension from date of manufacture is 24 months stored below 30°C. The reconstituted suspension, when refrigerated between 2 and 8°C can be kept for up to 10 days.

6.4 Special Precautions For Storage

Zinnat Suspension granules should be stored below 30^°C.

Multidose Bottles: The reconstituted suspension must be refrigerated as soon as possible at between 2 and 8°C.

Sachets : Reconstituted suspension should be taken immediately.

6.5 Nature And Contents Of Container

Zinnat Suspension 125mg/5ml, granules for oral suspension are supplied in multidose bottles* *of 50, 70, 100, 140 and 200ml (Delete as appropriate) and in 125 and 250mg sachets (heat-sealed laminate of paper/polyethylene/foil/ethylene-methacrylic acid ionomer).

125mg sachets are packed as either 1 duplex sachet in a carton or 7 duplex sachets in a carton (i.e. 2 or 14 doses).

250mg sachets are packed as 7 duplex sachets in a carton (i.e. 14 doses).

*Ph Eur Type III amber glass multiple unit bottles with a closure containing a heat-sealed induction membrane and a re-seal liner.

6.6 Special Precautions For Disposal And Other Handling

The bottle should always be shaken vigorously before administration.

The reconstituted suspension in multidose bottles when refrigerated between 2 and 8°C can be kept for up to 10 days.

If desired, Zinnat Suspension from multidose bottles can be further diluted in cold fruit juices, or milk drinks and should be taken immediately.

The reconstituted suspension or granules should not be mixed with hot liquids.

Directions for reconstituting suspension in multidose bottles: -

1. Shake the bottle to loosen the granules. Remove the cap and the heat-seal membrane. If the latter is damaged or not present, the product should be returned to the pharmacist.

2. Add the total amount of water to the bottle as stated on its label. Replace the cap.

3. Invert the bottle and rock vigorously (for at least 15 seconds) as shown below.

4. Turn the bottle into an upright position and shake vigorously.

5. Refrigerate as soon as possible at between 2 and 8°C.

Directions for reconstituting suspension from sachets: -

1. Empty granules from sachet into a glass.

2. Add a small volume of water.

3. Stir well and drink immediately.

Administrative Data

7. Marketing Authorisation Holder

Glaxo Wellcome UK Limited

t/a Glaxo Laboratories

Stockley Park West

Uxbridge

Middlesex UB11 1BT

8. Marketing Authorisation Number(S)

PL10949/0094

9. Date Of First Authorisation/Renewal Of The Authorisation

1 July 1993

10. Date Of Revision Of The Text

3 July 2008

11. Legal Status

POM

Micronefrin Nebulizer Solution

Pronunciation: ep-i-NEF-rin
Generic Name: Epinephrine
Brand Name: Generic only. No brands available.

Micronefrin Nebulizer Solution is used for:

Treating shortness of breath, chest tightness, and wheezing associated with asthma, emphysema, and other breathing problems. It may also be used for other conditions as determined by your doctor.

Micronefrin Nebulizer Solution is an alpha- and beta-receptor stimulant. It works by widening the airway, which makes it easier to breathe.

Do NOT use Micronefrin Nebulizer Solution if:

• you are allergic to any ingredient in Micronefrin Nebulizer Solution

Contact your doctor or health care provider right away if any of these apply to you.

Before using Micronefrin Nebulizer Solution:

Some medical conditions may interact with Micronefrin Nebulizer Solution. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have taken furazolidone or a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the past 14 days


• if you have an overactive thyroid, urinary problems, an enlarged prostate, diabetes, high blood pressure, ischemic heart disease, an irregular heartbeat, or other heart problems

Some MEDICINES MAY INTERACT with Micronefrin Nebulizer Solution. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Beta-blockers (eg, propranolol), droxidopa, or phenothiazines (eg, chlorpromazine) because the risk of high or low blood pressure and fast or slow heartbeat may be increased


• Bromocriptine, furazolidone, MAOIs (eg, phenelzine), or tricyclic antidepressants (eg, amitriptyline) because the risk of side effects, such as headache, high temperature, and high blood pressure, may be increased


• Catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), digoxin, or medicines for irregular heartbeat (eg, quinidine) because they may increase the risk of Micronefrin Nebulizer Solution's side effects


• Guanethidine because its effectiveness may be decreased by Micronefrin Nebulizer Solution

This may not be a complete list of all interactions that may occur. Ask your health care provider if Micronefrin Nebulizer Solution may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Micronefrin Nebulizer Solution:

Use Micronefrin Nebulizer Solution as directed by your doctor. Check the label on the medicine for exact dosing instructions. Check the label on the medicine for exact dosing instructions.

• If the medicine turns pink to brown in color or is cloudy, do not use it.


• Micronefrin Nebulizer Solution is only for use by oral inhalation through a breathing machine (nebulizer). Carefully follow the procedures taught to you by your health care provider.


• If you miss a dose of Micronefrin Nebulizer Solution, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Micronefrin Nebulizer Solution.

Important safety information:

• Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.


• If your symptoms do not get better or if they get worse, check with your doctor.


• Micronefrin Nebulizer Solution may cause dry mouth or an unpleasant taste in your mouth. Rinsing your mouth with water after each dose may help relieve these effects.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Micronefrin Nebulizer Solution while you are pregnant. Micronefrin Nebulizer Solution is found in breast milk. If you are or will be breast-feeding while you use Micronefrin Nebulizer Solution, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Micronefrin Nebulizer Solution:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Difficulty sleeping; fast heartbeat; headache; loss of appetite; nausea; nervousness; tremors.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); wheezing.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include headache; irregular heartbeat; nausea; tremor; vomiting; weakness.

Proper storage of Micronefrin Nebulizer Solution:

Store Micronefrin Nebulizer Solution at room temperature, between 36 and 68 degrees F (2 and 20 degrees C). Store away from heat, moisture, and light. Keep Micronefrin Nebulizer Solution out of the reach of children and away from pets.

General information:

• If you have any questions about Micronefrin Nebulizer Solution, please talk with your doctor, pharmacist, or other health care provider.


• Micronefrin Nebulizer Solution is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Micronefrin Nebulizer Solution. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Micronefrin resources

• Micronefrin Use in Pregnancy & Breastfeeding
• Micronefrin Drug Interactions
• Micronefrin Support Group
• 11 Reviews for Micronefrin - Add your own review/rating

Compare Micronefrin with other medications

• Adams-Stokes Syndrome
• Allergic Reactions
• Asthma, acute
• Asystole
• AV Heart Block
• COPD, Acute
• Electromechanical Dissociation
• Shock

interferon beta-1a

Generic Name: interferon beta-1a (in ter FEAR on BAY ta)

Brand Names: Avonex, Avonex Prefilled Syringe, Rebif

What is interferon beta-1a?

Interferon beta-1a is made from human proteins. Interferons help the body fight viral infections.

Interferon beta-1a is used to treat relapsing multiple sclerosis (MS). This medication will not cure MS, it will only decrease the frequency of relapse symptoms.

Interferon beta-1a may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about interferon beta-1a?

This medication may be harmful to an unborn baby, or may cause a miscarriage. Do not use interferon beta-1a if you are pregnant. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Before using interferon beta-1a, tell your doctor if you are allergic to any drugs, or if you have liver disease, a thyroid disorder, epilepsy or other seizure disorder, heart disease, chest pain (angina), congestive heart failure, a heart rhythm disorder, or a history of depression or suicidal behavior.

Some patients using interferon medications have become very depressed or had thoughts of suicide. Stop using interferon beta-1a if you have symptoms of depression (sadness, crying, loss of interest in things you once liked) or if you have any thoughts of hurting yourself. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your liver or thyroid function may also need to be tested. Visit your doctor regularly.

What should I discuss with my healthcare provider before using interferon beta-1a?

Do not use this medication if you are allergic to interferons or human albumin. Some patients using interferon medications have become very depressed or had thoughts of suicide. Stop using interferon beta-1a if you have symptoms of depression (sadness, crying, loss of interest in things you once liked) or if you have any thoughts of hurting yourself.

If you have any of these other conditions, you may need a dose adjustment or special tests:

• 
  

  liver disease;

  
  


• 
  

  epilepsy or other seizure disorder;

  
  


• 
  

  heart disease, chest pain (angina), congestive heart failure, or a heart rhythm disorder;

  
  


• 
  

  a thyroid disorder; or

  
  


• 
  

  a history of depression or suicidal behavior.

  
  

FDA pregnancy category C. This medication may be harmful to an unborn baby, or may cause a miscarriage. Do not use interferon beta-1a if you are pregnant. Tell your doctor if you become pregnant during treatment. It is not known whether interferon beta-1a passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Avonex powder contains albumin, but the Avonex prefilled syringe does not. Albumin comes from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

How should I use interferon beta-1a?

Avonex is injected into a muscle. It is usually given once weekly at bedtime, on the same day each week (such as every Monday). Follow your doctor's instructions.

Rebif is injected under the skin. It is usually given 3 times per week (such as Monday, Wednesday, and Friday) at the same time on each dosing day. Follow your doctor's instructions.

You may be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Use a different place on your body each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row.

The powder form of Avonex must be mixed with a liquid (diluent) in the medicine vial. Gently swirl but do not shake the vial after mixing the medicine. The mixture should be clear or light yellow. Do not use the mixture if it has changed colors or has any particles in it. Mix a new dose or call your doctor for a new prescription.

Do not draw your dose into a syringe until you are ready to give yourself an injection.

Each prefilled syringe or single use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left after injecting your dose.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Interferon beta-1 can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Your liver or thyroid function may also need to be tested. Visit your doctor regularly.

Store interferon beta-1a in a refrigerator. Do not freeze. You may take the Avonex prefilled syringe out of the refrigerator and allow it to reach room temperature before giving the injection. Do not heat the medicine before using. Interferon beta-1a may be kept at room temperature for short periods if protected from light. Avonex powder or Rebif prefilled syringes can be stored at room temperature for up to 30 days. Avonex prefilled syringes can be stored at room temperature for only 7 days. After mixing Avonex powder with a diluent, store in the refrigerator and use it within 6 hours.

Throw away any interferon beta-1a that has become frozen or has been exposed to light or high heat.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of this medication. Your injections should be at least 48 hours apart. Do not use interferon beta-1a injections 2 days in a row.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while using interferon beta-1a?

Avoid drinking alcohol. It may increase your risk of liver damage.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Interferon beta-1a side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  depressed mood, anxiety, trouble sleeping, restlessness, or thoughts of suicide or hurting yourself;

  
  


• 
  

  easy bruising or bleeding, weakness;

  
  


• 
  

  seizure (convulsions);

  
  


• 
  

  numbness or tingling in your hands or feet;

  
  


• 
  

  pain or burning when you urinate;

  
  


• 
  

  pain, swelling, or skin changes where the injection was given;

  
  


• 
  

  fever, chills, body aches, flu symptoms; or

  
  


• 
  

  nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

• 
  

  headache, dizziness;

  
  


• 
  

  stomach pain; or

  
  


• 
  

  runny or stuffy nose.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Interferon beta-1a Dosing Information

Usual Adult Dose for Multiple Sclerosis:

Rebif: Start at 8.8 mcg subcutaneously three times per week for 2 weeks, then give 22 mcg subcutaneously three times per week for 2 weeks, on week 5 start the recommended daily dose of 44 mcg subcutaneously three times per week.

Avonex: 30 mcg IM once weekly.

Usual Adult Dose for Neuritis:

Study (n=192)
Avonex: 30 mcg IM once per week.

Usual Pediatric Dose for Multiple Sclerosis:

Study (n=14)

>11 years old:
Avonex: 30 mcg IM every week
Rebif: 22 mcg subcutaneously three times per week

>10.5 years old:
Avonex: 15 mcg IM every week

Study (n=51)

>8.1 years old:
Rebif: 22 mcg subcutaneously three times per week, up to 44 mcg subcut three times per week, for a mean duration of 1.8 years (range 1 month to 4.4 years).

What other drugs will affect interferon beta-1a?

Interferon beta-1a can harm your liver. This effect is increased when you also use other medicines harmful to the liver. Many other drugs (including some over-the-counter medicines) can be harmful to the liver, such as:

• 
  

  acetaminophen (Tylenol);

  
  


• 
  

  cancer medications;

  
  


• 
  

  tuberculosis medications;

  
  


• 
  

  birth control pills or hormone replacement therapy;

  
  


• 
  

  methotrexate (Rheumatrex, Trexall);

  
  


• 
  

  arthritis medications such as auranofin (Ridaura);

  
  


• 
  

  an antibiotic;

  
  


• 
  

  HIV/AIDS medications;

  
  


• 
  

  cholesterol medications such atorvastatin (Lipitor), simvastatin (Zocor), and others;

  
  


• 
  

  an ACE inhibitor such as benazepril (Lotensin), captopril (Capoten), lisinopril (Prinivil, Zestril), and others;

  
  


• 
  

  an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), indomethacin (Indocin), and others; or

  
  


• 
  

  seizure medications such as carbamazepine (Carbatrol, Tegretol), phenytoin (Dilantin), or valproic acid (Depakene).

  
  

This list is not complete and other drugs may interact with interferon beta-1a. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More interferon beta-1a resources

• Interferon beta-1a Side Effects (in more detail)
• Interferon beta-1a Use in Pregnancy & Breastfeeding
• Interferon beta-1a Drug Interactions
• Interferon beta-1a Support Group
• 27 Reviews for Interferon beta-1a - Add your own review/rating

• interferon beta-1a Intramuscular, Subcutaneous, Injection Advanced Consumer (Micromedex) - Includes Dosage Information


• Interferon Beta-1a Professional Patient Advice (Wolters Kluwer)


• Interferon Beta-1a MedFacts Consumer Leaflet (Wolters Kluwer)


• Avonex Prescribing Information (FDA)


• Avonex Consumer Overview


• Avonex Prefilled Syringes MedFacts Consumer Leaflet (Wolters Kluwer)


• Rebif Prescribing Information (FDA)


• Rebif Consumer Overview

Compare interferon beta-1a with other medications

• Multiple Sclerosis
• Neuritis

Where can I get more information?

• Your doctor or pharmacist can provide more information about interferon beta-1a.

See also: interferon beta-1a side effects (in more detail)