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Saturday, March 3, 2012

Voriconazole

Class: Azoles
VA Class: AM700
Chemical Name: (αR,βS) - α - (2,4, - difluorophenyl) - 5 - fluoro - β - methyl - α - (1H - 1,2,4 - triazol - 1 - yl - methyl) - 4 - pyrimidineethanol
Molecular Formula: C₁₆H₁₄F₃N₅O
CAS Number: 137234-62-9
Brands: Vfend

Introduction

Antifungal; azole (triazole); synthetic derivative of fluconazole.¹ ² ³ ⁴ ⁵ ⁶ ⁷

Uses for Voriconazole

Aspergillosis

Treatment of invasive aspergillosis.¹ A drug of choice.⁴²³ ⁴³⁶ ⁴⁴⁰ ⁴⁴¹

Has been effective for primary and salvage therapy of invasive aspergillosis, including treatment of invasive aspergillosis in patients intolerant of, or whose disease was refractory to, other antifungals.¹

IDSA considers voriconazole the drug of choice for primary treatment of invasive aspergillosis in most patients and amphotericin B the preferred alternative.⁴²³ For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends amphotericin B, caspofungin, micafungin, posaconazole, or itraconazole.⁴²³ For empiric or preemptive therapy of presumed aspergillosis, IDSA recommends amphotericin B, caspofungin, itraconazole, or voriconazole.⁴²³

For treatment of invasive aspergillosis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend voriconazole as the drug of choice;⁴⁴⁰ IV amphotericin B, IV caspofungin, and oral posaconazole are recommended as alternatives.⁴⁴⁰ Voriconazole also is considered the drug of choice for treatment of invasive aspergillosis in HIV-infected children†;⁴⁴¹ IV amphotericin B and IV caspofungin are alternatives.⁴⁴¹

Candidemia and Disseminated Candida Infections

Treatment of candidemia in nonneutropenic patients.¹ Has been effective in Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, or C. krusei infections.¹

Treatment of disseminated Candida infections involving the skin, abdomen, kidney, bladder wall, or wounds.¹

For the treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in such patients, IDSA recommends fluconazole or an IV echinocandin (caspofungin, micafungin, anidulafungin) for initial therapy;⁴²⁵ IV amphotericin B or voriconazole are the preferred alternatives.⁴²⁵ These experts state that voriconazole offers little advantage over fluconazole and generally has been reserved for step-down oral therapy for treatment of C. krusei candidiasis or for treatment of fluconazole-resistant, voriconazole-susceptible C. glabrata infections.⁴²⁵ Although an echinocandin is preferred for initial treatment of C. glabrata infections, if the patient initially received fluconazole or voriconazole, continuation of the azole antifungal until treatment completion is reasonable if the patient is clinically improved and follow-up cultures are negative.⁴²⁵

For the treatment of candidemia in neutropenic† patients, IDSA recommends an IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B for initial therapy;⁴²⁵ fluconazole is the preferred alternative in those who are less critically ill or have not recently received an azole;⁴²⁵ voriconazole can be used as an alternative when broader antifungal coverage is required.⁴²⁵ An echinocandin, amphotericin B, or voriconazole is recommended for C. krusei infections.⁴²⁵ An echinocandin is preferred for C. glabrata infections;⁴²⁵ fluconazole or amphotericin B is preferred for C. parapsilosis infections;⁴²⁵ an echinocandin, amphotericin B, or voriconazole is recommended for C. krusei infections.⁴²⁵ Although an echinocandin is preferred for initial treatment of C. glabrata infections, if the patient initially received fluconazole or voriconazole, continuation of the azole antifungal until treatment completion is reasonable if the patient is clinically improved and follow-up culture results are negative.⁴²⁵ For initial empiric treatment of suspected invasive candidiasis in neutropenic† patients, amphotericin B, caspofungin, or IV voriconazole is recommended;⁴²⁵ alternatives are fluconazole or itraconazole.⁴²⁵

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis† refractory to other antifungals.⁴²⁵

IDSA recommends topical treatment with clotrimazole lozenges or nystatin oral suspension for mild oropharyngeal candidiasis;⁴²⁵ oral fluconazole is recommended for moderate to severe disease.⁴²⁵ For refractory oropharyngeal candidiasis, including fluconazole-refractory infections, itraconazole oral solution, oral posaconazole, or oral voriconazole is recommended.⁴²⁵ An IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B also are recommended as alternatives for refractory infections.⁴²⁵

For the treatment of oropharyngeal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes;⁴⁴⁰ other drugs of choice are clotrimazole lozenges or nystatin oral suspension.⁴⁴⁰ Alternatives for initial episodes are itraconazole oral solution or oral posaconazole.⁴⁴⁰ For fluconazole-refractory infections in HIV-infected adults or adolescents, itraconazole oral solution or oral posaconazole is preferred;⁴⁴⁰ alternatives include IV amphotericin B, an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.⁴⁴⁰

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence is not usually recommended in patients adequately treated for oropharyngeal candidiasis, patients with frequent or severe recurrences (including HIV-infected adults, adolescents, and children) may benefit from secondary prophylaxis with oral fluconazole or itraconazole oral solution; however, the potential for azole resistance should be considered.⁴²⁵ ⁴⁴⁰ ⁴⁴¹ Patients with fluconazole-refractory oropharyngeal candidiasis who responded to treatment with an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.⁴⁴⁰

Esophageal Candidiasis

Treatment of esophageal candidiasis.¹ ¹² ⁴²⁵ ⁴³⁶ Has been effective in immunocompromised patients with esophageal candidiasis caused by C. albicans, C. glabrata, or C. krusei.¹ ¹²

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).⁴²⁵ ⁴⁴⁰

IDSA recommends oral fluconazole as the preferred drug of choice for the treatment of esophageal candidiasis;⁴²⁵ if oral therapy is not tolerated, IV fluconazole, IV amphotericin B, or an IV echinocandin (caspofungin, micafungin, anidulafungin) is recommended.⁴²⁵ For fluconazole-refractory infections, preferred alternatives are itraconazole oral solution, oral posaconazole, or oral or IV voriconazole;⁴²⁵ other alternatives are an IV echinocandin or IV amphotericin B.⁴²⁵

For the treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral or IV fluconazole as the preferred drug of choice and itraconazole oral solution as a preferred alternative.⁴⁴⁰ Other alternatives include an IV echinocandin (caspofungin, micafungin, anidulafungin), oral or IV voriconazole, oral posaconazole, or IV amphotericin B.⁴⁴⁰ For refractory esophageal candidiasis in HIV-infected adults or adolescents, including fluconazole-refractory infections, itraconazole oral solution or oral posaconazole is preferred;⁴⁴⁰ alternatives including IV amphotericin B, an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.⁴⁴⁰

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence is not usually recommended in patients adequately treated for esophageal candidiasis, patients with frequent or severe recurrences (including HIV-infected adults, adolescents, and children) may benefit from secondary prophylaxis with oral fluconazole or oral posaconazole; however, the potential for azole resistance should be considered.⁴²⁵ ⁴⁴⁰ ⁴⁴¹ Patients with fluconazole-refractory esophageal candidiasis who responded to treatment with an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.⁴⁴⁰

Fusarium and Scedosporium Infections

Treatment of serious Fusarium (including F. solani) or Scedosporium apiospermum (asexual form of Pseudallescheria boydii) infections in patients intolerant of, or whose disease is refractory to, other antifungals.¹

For treatment of fusariosis, select antifungal based on in vitro susceptibility testing.⁵⁷ IV amphotericin B may be preferred for infections caused by F. solani or F. verticillioides;⁵⁷ either voriconazole or amphotericin B are recommended for other Fusarium.⁵⁷

For treatment of scedosporiosis, some clinicians consider voriconazole the drug of choice and posaconazole the preferred alternative.⁴³⁶

Empiric Therapy in Febrile Neutropenic Patients

Has been used for empiric therapy of presumed fungal infections in febrile neutropenic patients†.⁵ ⁴³⁶

Voriconazole Dosage and Administration

Administration

Administer orally or by slow IV infusion.¹

IV route used for initial treatment of systemic fungal infections; oral route may replace IV when clinically indicated.¹

Correct electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia) prior to initiation of voriconazole.¹ (See IV Infusion under Dosage and Administration and see Cardiovascular Effects under Cautions.)

Oral Administration

Administer orally at least 1 hour before or 1 hour after a meal.¹

Prior to withdrawal of each dose, shake reconstituted oral suspension for approximately 10 seconds.¹ Administer using the oral dispenser supplied by the manufacturer.¹

If a dose is missed, take the missed dose as soon as possible; however, if it has been >6 hours since the missed dose, take the next scheduled dose at the appropriate time.¹ Do not take a double dose.¹

Reconstitution

Reconstitute powder for oral suspension by adding 46 mL of water to the bottle containing 45 g to provide a suspension containing 40 mg/mL.¹ Shake closed bottle vigorously for about 1 minute.¹

Do not mix oral suspension with other drugs or additional flavoring agents; do not dilute reconstituted suspension further with water or other vehicles.¹

IV Infusion

Do not administer voriconazole IV solutions concomitantly with short-term infusions of concentrated electrolytes, even if the 2 infusions are running in separate IV lines or cannulas.¹ Voriconazole IV solutions may be administered at the same time as other IV solutions containing nonconcentrated electrolytes; however, the drug must be infused through a separate line.¹

Do not administer voriconazole IV solutions concomitantly with any blood product, even if the 2 infusions are running in separate IV lines or cannulas.¹

Voriconazole IV solutions may be administered at the same time as total parenteral nutrition (TPN); however, the drug must be infused through a separate line.¹ If infused through a multiple-lumen catheter, TPN must be administered using a different port from the one used for voriconazole.¹

Reconstitution and Dilution

Reconstitute single-use 200-mg vial with exactly 19 mL of sterile water for injection to provide a solution containing 10 mg/mL.¹ The vial should be shaken until all powder is dissolved.¹

Reconstituted solution must be further diluted in a compatible IV infusion solution prior to administration.¹

Calculate the volume of reconstituted solution required to administer the appropriate weight-based dose; withdraw and discard a volume of diluent from the final infusion container that equals or exceeds that volume.¹ Withdraw appropriate dose from the required number of vials and add to the infusion container.¹ Final concentration should be ≥0.5 mg/mL but ≤5 mg/mL.¹ Discard any unused portion of reconstituted solution.¹

Rate of Administration

Administer by IV infusion over 1–2 hours at a maximum rate of 3 mg/kg per hour.¹ Do not administer by rapid IV infusion.¹

Dosage

Pediatric Patients

Treatment of Aspergillosis

Oral

Children 2 through 11 years of age†: 200 mg twice daily (without loading dose) has been recommended.⁴³⁶

Children ≥12 years of age weighing <40 kg: Loading dose of 200 mg every 12 hours for 2 doses, then maintenance dosage of 100 mg every 12 hours has been recommended; if response is inadequate, may be increased to 150 mg every 12 hours.⁶⁰

Children ≥12 years of age weighing ≥40 kg: Loading dose of 400 mg every 12 hours for 2 doses, then maintenance dosage of 200 mg every 12 hours has been recommended; if response is inadequate, may be increased to 300 mg every 12 hours.⁶⁰

Duration of treatment is based on severity of underlying disease, recovery from immunosuppression, and response to the drug.¹ IDSA recommends treatment of invasive pulmonary aspergillosis be continued for at least 6–12 weeks and continued throughout the period of immunosuppression.⁴²³

HIV-infected children†: 8 mg/kg (maximum 400 mg) twice daily on day 1, followed by maintenance dosage of 7 mg/kg (maximum 200 mg) twice daily has been recommended.⁴⁴¹ Continue treatment for ≥12 weeks; individualize treatment duration according to clinical response.⁴⁴¹

IV

Children 2 through 11 years of age†: 7 mg/kg twice daily (without loading dose) has been recommended.⁴³⁶

Children ≥12 years of age: Loading dose regimen of 6 mg/kg every 12 hours for 2 doses, followed by IV maintenance regimen of 4 mg/kg every 12 hours has been recommended.⁶⁰ Decrease IV maintenance dosage to 3 mg/kg every 12 hours if higher dosage not tolerated.⁶⁰

IDSA recommends that pediatric patients receive 5–7 mg/kg every 12 hours.⁴²³

Switch to oral maintenance when clinically indicated.⁹ Total duration of treatment is based on severity of underlying disease, recovery from immunosuppression, and response to the drug.¹

HIV-infected children†: Loading dose regimen of 6–8 mg/kg twice daily on day 1, followed by IV maintenance dosage of 7 mg/kg (maximum 200 mg) twice daily has been recommended.⁴⁴¹ Continue treatment for ≥12 weeks; individualize treatment duration according to clinical response.⁴⁴¹

HIV-infected adolescents: Loading dose regimen of 6 mg/kg twice daily on day 1, followed by IV maintenance dosage of 4 mg/kg twice daily.⁴⁴⁰ After clinical improvement, switch to an oral regimen of 200 mg twice daily.⁴⁴⁰ Optimal duration of therapy not established; continue antifungal therapy at least until CD4⁺ T-cell count increases to 200/mm³ as a result of potent antiretroviral therapy and there is evidence of clinical response.⁴⁴⁰

Candida Infections

Treatment of Candidemia and Disseminated Candida Infections

Oral

Children 2 through 11 years of age†: 200 mg twice daily (without loading dose) has been recommended.⁴³⁶

Manufacturer recommends that treatment be continued for at least 14 days after symptoms resolve or the last positive culture, whichever is longer.¹ IDSA and others recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolutions of signs and symptoms of candidemia.⁴²⁵ ⁴³⁶

Children 2 through 11 years of age†: 7 mg/kg twice daily (without loading dose) has been recommended.⁴³⁶

Children ≥12 years of age: Loading dose regimen of 6 mg/kg every 12 hours for 2 doses, followed by IV maintenance regimen of 4 mg/kg every 12 hours has been recommended⁶⁰ Decrease IV maintenance dosage to 3 mg/kg every 12 hours if higher dosage not tolerated.⁶⁰

Manufacturer recommends that treatment be continued for at least 14 days after symptoms resolve or the last positive culture, whichever is longer.¹ IDSA and others recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia.⁴²⁵ ⁴³⁶

Treatment of Oropharyngeal Candidiasis†

Oral

Children 2 through 11 years of age†: 200 mg twice daily (without loading dose) has been recommended.⁴³⁶

HIV-infected adolescents: 200 mg twice daily.⁴⁴⁰

IDSA and others recommend a treatment duration of 7–14 days.⁴²⁵ ⁴⁴⁰

Children 2 through 11 years of age†: 7 mg/kg twice daily (without loading dose) has been recommended.⁴³⁶

HIV-infected adolescents: 200 mg twice daily.⁴⁴⁰

IDSA and others recommend that a treatment duration of 7–14 days.⁴²⁵ ⁴⁴⁰

Treatment of Esophageal Candidiasis

Oral

Children 2 through 11 years of age†: 200 mg twice daily (without loading dose) has been recommended.⁴³⁶

Children ≥12 years of age weighing <40 kg: 100 mg every 12 hours has been recommended.⁶⁰

Children ≥12 years of age weighing ≥40 kg: 200 mg every 12 hours has been recommended.⁶⁰

HIV-infected adolescents: 200 mg twice daily.⁴⁴⁰

Manufacturer recommends that treatment be continued for at least 14 days and for at least 7 days after symptoms resolve.¹ IDSA and others recommend that a treatment duration of 14–21 days.⁴²⁵ ⁴³⁶ ⁴⁴⁰

Children 2 through 11 years of age†: 7 mg/kg twice daily (without loading dose) has been recommended.⁵¹ ⁴³⁶

HIV-infected adolescents: 200 mg twice daily.⁴⁴⁰

Manufacturer recommends that treatment be continued for at least 14 days and for at least 7 days after symptoms resolve.¹ IDSA and others recommend a treatment duration of 14–21 days.⁴²⁵ ⁴³⁶ ⁴⁴⁰

Treatment of Fusarium and Scedosporium Infections

Oral

Children 2 through 11 years of age†: 200 mg twice daily (without loading dose) has been recommended.⁴³⁶

Duration of treatment is based on severity of underlying disease, recovery from immunosuppression, and response to the drug.¹

IV

Children 2 through 11 years of age†: 7 mg/kg twice daily (without loading dose) has been recommended.⁵¹ ⁴³⁶

Duration of treatment is based on severity of underlying disease, recovery from immunosuppression, and response to the drug.¹

Adults

Treatment of Aspergillosis

Oral

Adults weighing <40 kg: After initial IV regimen, maintenance dosage of 100 mg every 12 hours; if response is inadequate, increase to 150 mg every 12 hours.¹ ¹⁰ If not tolerated, decrease dosage by increments of 50 mg to a minimum of 100 mg every 12 hours.¹ ¹⁰

Adults weighing ≥40 kg: After initial IV regimen, maintenance dosage of 200 mg every 12 hours; if response is inadequate, increase to 300 mg every 12 hours.¹ ¹⁰ If not tolerated, decrease dosage by increments of 50 mg to a minimum of 200 mg every 12 hours.¹ ¹⁰

IV

Loading dose regimen of 6 mg/kg every 12 hours for 2 doses, followed by IV maintenance regimen of 4 mg/kg every 12 hours.¹ ⁴³⁶ Decrease IV maintenance dosage to 3 mg/kg every 12 hours if higher dosage not tolerated.¹ Switch to oral maintenance when clinically indicated.¹ ⁴³⁶

HIV-infected adults: Loading dose regimen of 6 mg/kg twice daily on day 1, followed by IV maintenance regimen of 4 mg/kg twice daily.⁴⁴⁰ After clinical improvement, switch to an oral regimen of 200 mg twice daily.⁴⁴⁰ Optimal duration of therapy not established; continue antifungal therapy at least until CD4⁺ T-cell count increases to 200/mm³ as a result of potent antiretroviral therapy and there is evidence of clinical response.⁴⁴⁰

Candida Infections

Treatment of Candidemia and Disseminated Infections

Oral

Adults weighing <40 kg: After initial IV regimen, maintenance dosage of 100 mg every 12 hours; if response is inadequate, increase to 150 mg every 12 hours.¹ If not tolerated, decrease dosage by increments of 50 mg to a minimum of 100 mg every 12 hours.¹

Adults weighing ≥40 kg: After initial IV regimen, maintenance dosage of 200 mg every 12 hours; if response is inadequate, increase to 300 mg every 12 hours.¹ If not tolerated, decrease dosage by increments of 50 mg to a minimum of 200 mg every 12 hours.¹

Manufacturer recommends that treatment be continued for at least 14 days after symptoms resolve or the last positive culture, whichever is longer.¹ IDSA and others recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia.⁴²⁵ ⁴³⁶

Loading dose regimen of 6 mg/kg every 12 hours for 2 doses, followed by IV maintenance regimen of 3–4 mg/kg every 12 hours.¹ Decrease IV maintenance dosage to 3 mg/kg every 12 hours if higher dosage not tolerated.¹

In clinical studies, patients with candidemia received 3 mg/kg every 12 hours and those with deep tissue infections received 4 mg/kg every 12 hours as salvage therapy.¹

Switch to oral maintenance when clinically indicated.¹

Manufacturer recommends that treatment be continued for at least 14 days after symptoms resolve or the last positive culture, whichever is longer.¹ IDSA and others recommend antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia.⁴²⁵ ⁴³⁶

Treatment of Oropharyngeal Candidiasis†

Oral

200 mg twice daily.⁴²⁵ ⁴³⁶

HIV-infected adults: 200 mg twice daily.⁴⁴⁰

IDSA and others recommend that a treatment duration of 7–14 days.⁴²⁵ ⁴⁴⁰

HIV-infected adults: 200 mg twice daily.⁴⁴⁰

IDSA and others recommend a treatment duration of 7–14 days.⁴²⁵ ⁴⁴⁰

Treatment of Esophageal Candidiasis

Oral

Adults weighing <40 kg: 100 mg every 12 hours.¹

Adults weighing ≥40 kg: 200 mg every 12 hours.¹

HIV-infected adults: 200 mg twice daily.⁴⁴⁰

Treatment of Fusarium and Scedosporium Infections

Oral

Duration of treatment is based on severity of underlying disease, recovery from immunosuppression, and response to the drug.¹

IV

Loading dose regimen of 6 mg/kg every 12 hours for 2 doses, followed by IV maintenance regimen of 4 mg/kg every 12 hours.¹ Decrease IV maintenance dosage to 3 mg/kg every 12 hours if higher dosage not tolerated.¹

Switch to oral maintenance when clinically indicated.¹

Duration of treatment is based on severity of underlying disease, recovery from immunosuppression, and response to the drug.¹

Special Populations

Hepatic Impairment

Mild to moderate hepatic cirrhosis (Child-Pugh class A or B): Use usual loading dose regimen, but decrease maintenance dosages by 50%.¹ ¹⁰

Severe hepatic impairment: Use only if benefits outweigh risks.¹ Not studied in patients with severe cirrhosis (Child-Pugh class C) or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.¹ (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustment of oral voriconazole not needed.¹

Moderate to severe renal impairment (Cl_cr <50 mL/minute): Use IV voriconazole in only if possible benefits outweigh risks.¹ (See Renal Impairment under Cautions.) Monitor serum creatinine closely; if increases occur, consider switching to oral voriconazole.¹

Geriatric Patients

Dosage adjustments not necessary based on age.¹

Concomitant Therapy with Efavirenz or Phenytoin

If used with efavirenz or phenytoin, voriconazole dosage adjustment recommended.¹ ³⁴ ⁴³¹ ⁴⁴⁰ (See Specific Drugs under Interactions.)

Cautions for Voriconazole

Contraindications

Known hypersensitivity to voriconazole or any ingredient in the formulation.¹

Concomitant use with astemizole or terfenadine (drugs no longer commercially available in US), carbamazepine, cisapride (currently commercially available in the US only under a limited-access protocol), ergot alkaloids (e.g., ergotamine, dihydroergotamine), pimozide, quinidine, rifabutin, rifampin, sirolimus, St. John’s wort (Hypericum perforatum), or long-acting barbiturates (e.g., phenobarbital, mephobarbital).¹ ⁴⁰ ⁴³¹ (See Specific Drugs under Interactions.)

Concomitant use with full-dose ritonavir (≥400 mg twice daily) is contraindicated; avoid concomitant use with low-dose ritonavir (100 mg every 12 hours) unless benefits outweigh risks.¹ ⁴⁰ ⁴³¹ (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Ocular Effects

Visual disturbances (e.g., abnormal vision, blurred vision, color vision change, photophobia) reported; may be related to high dosage and high plasma voriconazole concentrations.¹

Postmarketing reports of prolonged visual disturbances, inlcuding optic neuritis and papilledema.¹

Effect on visual function unknown if duration of therapy is >28 days.¹ Monitor visual function (visual acuity, visual field, and color perception) if duration is >28 days.¹

Hepatic Effects

Hepatitis, cholestasis, and fulminant hepatic failure reported rarely.¹ Hepatic effects (including hepatitis and jaundice) have occurred in patients with no identifiable risk factors.¹ Hepatic effects usually are reversible when voriconazole discontinued, but fatalities have occurred.¹

Perform liver function tests prior to and during voriconazole therapy.¹

If abnormal liver function tests occur during therapy, monitor for development of more severe hepatic injury using appropriate laboratory evaluations (particularly liver function tests and bilirubin).¹ Consider discontinuing voriconazole if clinical signs and symptoms consistent with liver disease develop that may be attributable to the drug.¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals.¹ (See Pregnancy under Cautions.)

Pregnancy should be avoided.¹ Women of childbearing potential should use effective contraception during voriconazole treatment.¹ (See Specific Drugs under Interactions.)

If used during pregnancy or if patient becomes pregnant while receiving voriconazole, advise patient of the potential hazard to the fetus.¹

Fructose or Galactose Intolerance

Voriconazole tablets contain lactose and should not be used in those with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.¹

Voriconazole oral suspension contains sucrose and should not be used in those with fructose intolerance, sucrase-isomaltase deficiency, or glucose-galactose malabsorption.¹

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions (e.g., flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, rash) reported rarely immediately after initiation of voriconazole IV infusion.¹ Consider stopping the infusion if these reactions occur.¹

Serious cutaneous reactions (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis) and photosensitivity reactions reported rarely.¹ (See Dermatologic Effects under Cautions.)

Data regarding cross-sensitivity with other azole antifungals not available.¹ Use with caution in patients hypersensitive to other azoles.¹

General Precautions

Cardiovascular Effects

Prolonged QT interval reported with voriconazole and other azoles.¹ Arrhythmias (e.g., torsades de pointes), cardiac arrest, and sudden death reported rarely.¹

Most reported cases involved seriously ill patients with multiple confounding risk factors that may have contributed (e.g., history of cardiotoxic chemotherapy, cardiomyopathy, hypokalemia, concomitant drugs).¹

Use with caution in patients with potentially proarrhythmic conditions.¹

Rigorous attempts should be made to correct potassium, magnesium, and calcium before starting voriconazole.¹

Laboratory Monitoring

Evaluate liver function (e.g., liver function tests, bilirubin) prior to and during voriconazole therapy.¹

Evaluate serum electrolytes (i.e., potassium, magnesium, calcium) and correct any abnormalities prior to initiating therapy.¹

Monitor renal function (e.g., Serum creatinine) during voriconazole therapy.¹

Monitor adults and children with risk factors for acute pancreatitis (e.g., recent chemotherapy, hematopoietic stem cell transplantation [HSCT]) for the development of pancreatitis.¹

Dermatologic Effects

Serious cutaneous reactions (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis) reported rarely.¹ If an exfoliative cutaneous reaction occurs, discontinue voriconazole.¹

Squamous cell carcinoma of the skin and melanoma have been reported during long-term voriconazole therapy in patients with photosensitivity reactions.¹

Avoid intense or prolonged exposure to direct sunlight during voriconazole therapy.¹

If skin lesion consistent with squamous cell carcinoma or melanoma develops, discontinue voriconazole.¹

Renal Effects

Acute renal failure reported in severely ill patients with other factors predisposing to impaired renal function (e.g., underlying conditions, concomitant nephrotoxic drugs).¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

In animal studies, teratogenic effects (cleft palate, hydronephrosis/hydroureter) and embrytoxic effects reported.¹

Lactation

Not known whether distributed into milk.¹ Should not be used unless potential benefits clearly outweigh risks.¹

Pediatric Use

Safety and efficacy not established in children <12 years of age.¹

Has been recommended for treatment of fungal infections in children;⁵¹ ⁴²³ ⁴³⁶ ⁴⁴¹ dosage recommendations have been made for children 2 through 11 years of age†.⁴³⁶ (See Pediatric Patients under Dosage and Administration.) Some clinicians consider voriconazole the drug of choice for treatment of invasive aspergillosis in HIV-infected children†, but state that data are insufficient to recommend use of the drug for treatment of candidemia or esophageal candidiasis in these children.⁴⁴¹

Has been used in children 9 months to 15 years of age† in clinical studies.⁹

Adverse effects in pediatric patients similar to those reported in adults.⁹

Cases of pancreatitis in pediatric patients documented in postmarketing reports;¹ monitor for the development of pancreatitis in children with risk factors for acute pancreatitis (e.g., recent chemotherapy, HSCT).¹

Geriatric Use

Plasma voriconazole concentrations increased in geriatric patients, but overall safety profile is similar to that in younger adults.¹

Hepatic Impairment

Monitor carefully for adverse effects, including adverse hepatic effects.¹ (See Hepatic Effects under Cautions.)

Not evaluated in patients with severe hepatic cirrhosis (Child-Pugh class C) or with HBV or HCV infection.¹

Not recommended in patients with severe hepatic impairment unless potential benefits outweigh risks.¹

Renal Impairment

IV voriconazole contains sulfobutyl ether β-cyclodextrin sodium (SBECD) which may accumulate in patients with moderate-to-severe renal impairment (Cl_cr <50 mL/minute).¹

IV voriconazole should not be used in patients with Cl_cr <50 mL/minute, unless potential benefits outweigh risks.¹ If IV voriconazole is used in these patients, monitor serum creatinine concentrations closely; if increases occur, consider switching to oral voriconazole.¹

Common Adverse Effects

Visual disturbances (abnormal vision, blurred vision, color vision change, photophobia), GI effects (nausea, vomiting, diarrhea, abdominal pain), fever, rash, headache, sepsis, peripheral edema, respiratory disorder.¹

Interactions for Voriconazole

Metabolized by CYP2C9, 2C19, and 3A4.¹

Inhibits CYP2C9, 2C19, and 3A4; the major metabolite (voriconazole N-oxide) also inhibits these enzymes.¹ Voriconazole appears to be a less potent inhibitor of CYP3A4 than some other azoles (e.g., itraconazole, ketoconazole).¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions with drugs that are inhibitors, inducers, or substrates of CYP2C9, 2C19, or 3A4 with possible alteration in metabolism of voriconazole and/or other drug.¹

Specific Drugs

Drug	Interaction	Comments
Alfentanil	Increased mean AUC and elimination half-life of alfentanil when administered with voriconazole and naloxone¹ Increased incidence of delayed and persistent alfentanil-induced nausea and vomiting when administered with voriconazole¹	If voriconazole used concomitantly with alfentanil or other opiate agonist metabolized by CYP3A4 (e.g., sufentanil), reduced dosage of the opiate agonist may be necessary¹ ³⁴ Extended close monitoring for opiate-related adverse events (e.g., respiratory depression) may be necessary¹ ³⁴
Anticoagulants, oral (warfarin)	Potentiates warfarin’s effect on PT¹ ¹⁶ ³⁴	Monitor PT or other appropriate tests closely if used with warfarin; reduce anticoagulant dosage if necessary¹ ¹⁶ ³⁴
Antidiabetic agents, sulfonylureas (glipizide, glyburide, tolbutamide)	Possible increased concentrations of glipizide, glyburide, tolbutamide and risk of hypoglycemia¹	Monitor blood glucose and observe patient for signs and symptoms of hypoglycemia; adjust dosage of antidiabetic agent as necessary¹
Antihistamines (astemizole, terfenadine)	Possible pharmacokinetic interaction and potential for serious or life-threatening reactions (e.g., cardiac arrhythmias) with astemizole or terfenadine (drugs no longer commercially available in the US)¹	Concomitant use contraindicated¹
Antimycobacterials, rifamycins (rifabutin, rifampin)	Rifabutin: Decreased voriconazole concentrations and AUC and increased

Friday, March 2, 2012

Apri

Generic Name: ethinyl estradiol and desogestrel (EH thih nill ess tra DYE ole and des oh JESS trel)

Brand Names: Apri, Cesia, Cyclessa, Desogen, Kariva, Mircette, Ortho-Cept, Reclipsen, Solia, Velivet

What is Apri (ethinyl estradiol and desogestrel)?

Ethinyl estradiol and desogestrel contains a combination of female hormones that prevent ovulation (the release of an egg from an ovary). This medication also causes changes in your cervical mucus and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus.

Ethinyl estradiol and desogestrel are used as contraception to prevent pregnancy.

Ethinyl estradiol and desogestrel may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Apri (ethinyl estradiol and desogestrel)?

Do not use birth control pills if you are pregnant or if you have recently had a baby. Do not use this medication if you have any of the following conditions: a history of stroke or blood clot, circulation problems (especially if caused by diabetes), a hormone-related cancer such as breast or uterine cancer, abnormal vaginal bleeding, liver disease or liver cancer, severe high blood pressure, migraine headaches, a heart valve disorder, or a history of jaundice caused by birth control pills.

You may need to use back-up birth control, such as condoms or a spermicide, when you first start using this medication. Follow your doctor's instructions.

Taking hormones can increase your risk of blood clots, stroke, or heart attack, especially if you smoke and are older than 35.

Some drugs can make birth control pills less effective, which may result in pregnancy. Tell your doctor about all the prescription and over-the-counter medications you use, including vitamins, minerals and herbal products. Do not start using a new medication without telling your doctor.

What should I discuss with my healthcare provider before taking Apri (ethinyl estradiol and desogestrel)?

This medication can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking birth control pills (6 weeks if you are breast-feeding). Do not use this medication if you have:

a history of a stroke or blood clot;

circulation problems (especially if caused by diabetes);

a hormone-related cancer such as breast or uterine cancer;

abnormal vaginal bleeding;

liver disease or liver cancer;

severe high blood pressure;

severe migraine headaches;

a heart valve disorder; or

a history of jaundice caused by birth control pills.

Before using this medication, tell your doctor if you have any of the following conditions. You may need a dosage adjustment or special tests to safely take birth control pills.

high blood pressure, heart disease, congestive heart failure, angina (chest pain), or a history of heart attack;

high cholesterol or if you are overweight;

a history of depression;

gallbladder disease;

diabetes;

seizures or epilepsy;

a history of irregular menstrual cycles; or

a history of fibrocystic breast disease, lumps, nodules, or an abnormal mammogram.

The hormones in birth control pills can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby.

How should I take Apri (ethinyl estradiol and desogestrel)?

Take this medication exactly as it was prescribed for you. Do not take larger amounts, or take it for longer than recommended by your doctor. You will take your first pill on the first day of your period or on the first Sunday after your period begins (follow your doctor's instructions).

You may need to use back-up birth control, such as condoms or a spermicide, when you first start using this medication. Follow your doctor's instructions.

The 28-day birth control pack contains seven "reminder" pills to keep you on your regular cycle. Your period will usually begin while you are using these reminder pills.

You may have breakthrough bleeding, especially during the first 3 months. Tell your doctor if this bleeding continues or is very heavy.

Take one pill every day, no more than 24 hours apart. When the pills run out, start a new pack the following day. You may get pregnant if you do not use this medication regularly. Get your prescription refilled before you run out of pills completely.

If you need to have any type of medical tests or surgery, or if you will be on bed rest, you may need to stop using this medication for a short time. Any doctor or surgeon who treats you should know that you are using birth control pills.

Your doctor will need to see you on a regular basis while you are using this medication. Do not miss any appointments.

Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Missing a pill increases your risk of becoming pregnant. Follow the directions on the patient information sheet provided with your medicine. If you do not have an information sheet, call your doctor for instructions if you miss a dose.

If you miss one "active" pill, take two pills on the day that you remember. Then take one pill per day for the rest of the pack.

If you miss two "active" pills in a row in week one or two, take two pills per day for two days in a row. Then take one pill per day for the rest of the pack. Use back-up birth control for at least 7 days following the missed pills.

If you miss two "active" pills in a row in week 3, or if you miss three pills in a row during any of the first 3 weeks, throw out the rest of the pack and start a new one the same day if you are a Day 1 starter. If you are a Sunday starter, keep taking a pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new one that day.

If you miss three "active" tablets in a row during any of the first 3 weeks, throw out the rest of the pack and start a new pack on the same day if you are a Day 1 starter. If you are a Sunday starter, keep taking a pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new one that day.

If you miss two or more pills, you may not have a period during the month. If you miss a period for two months in a row, call your doctor because you might be pregnant.

If you miss any reminder pills, throw them away and keep taking one pill per day until the pack is empty. You do not need back-up birth control if you miss a reminder pill.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include nausea, vomiting, and vaginal bleeding.

What should I avoid while taking Apri (ethinyl estradiol and desogestrel)?

Do not smoke while using this medication, especially if you are older than 35. Smoking can increase your risk of blood clots, stroke, or heart attack caused by birth control pills.

This medication will not protect you from sexually transmitted diseases--including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

Apri (ethinyl estradiol and desogestrel) 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. Stop using this medication and call your doctor at once if you have any of these serious side effects:

sudden numbness or weakness, especially on one side of the body;

sudden headache, confusion, problems with vision, speech, or balance;

chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

a change in the pattern or severity of migraine headaches;

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

swelling in your hands, ankles, or feet;

a breast lump; or

symptoms of depression (sleep problems, weakness, mood changes).

Less serious side effects may include:

mild nausea, vomiting, bloating, stomach cramps;

breast pain, tenderness, or swelling;

freckles or darkening of facial skin;

increased hair growth, loss of scalp hair;

changes in weight or appetite;

problems with contact lenses;

vaginal itching or discharge;

changes in your menstrual periods, decreased sex drive; or

headache, nervousness, dizziness, tired feeling.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Apri (ethinyl estradiol and desogestrel)?

Some drugs can make birth control pills less effective, which may result in pregnancy. Before using this medication, tell your doctor if you are using any of the following drugs:

acetaminophen (Tylenol) or ascorbic acid (vitamin C);

an antibiotic;

phenylbutazone (Azolid, Butazolidin);

St. John's wort;

seizure medicines such as phenytoin (Dilantin), carbamazepine (Tegretol), topiramate (Topamax), and others;

a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Luminal, Solfoton); or

HIV medicines such as amprenavir (Agenerase), atazanavir (Reyataz), indinavir (Crixivan), saquinavir (Invirase), fosamprenavir (Lexiva), ritonavir (Norvir), and others.

This list is not complete and there may be other drugs that can affect birth control pills. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Apri resources

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

Apri Prescribing Information (FDA)

Caziant Prescribing Information (FDA)

Cesia Prescribing Information (FDA)

Cyclessa Prescribing Information (FDA)

Cyclessa Advanced Consumer (Micromedex) - Includes Dosage Information

Desogen Consumer Overview

Desogen MedFacts Consumer Leaflet (Wolters Kluwer)

Desogen Prescribing Information (FDA)

Emoquette Prescribing Information (FDA)

Kariva Prescribing Information (FDA)

Mircette Prescribing Information (FDA)

Mircette Consumer Overview

Ortho-Cept Prescribing Information (FDA)

Reclipsen Prescribing Information (FDA)

Solia Prescribing Information (FDA)

Velivet Prescribing Information (FDA)

Compare Apri with other medications

Abnormal Uterine Bleeding
Birth Control
Endometriosis
Gonadotropin Inhibition
Polycystic Ovary Syndrome

Where can I get more information?

Your pharmacist can provide more information about ethinyl estradiol and desogestrel.

See also: Apri side effects (in more detail)

Thursday, March 1, 2012

Foscarnet Sodium

Class: Antivirals, Miscellaneous
VA Class: AM800
Chemical Name: Dihydroxyphosphinecarboxylic acid oxide trisodium salt
Molecular Formula: CNa₃O₅P
CAS Number: 63585-09-1
Brands: Foscavir

The major toxicity is renal impairment.¹ It is imperative that adequate hydration be maintained, serum creatinine be monitored frequently, and dosage adjusted for changes in renal function.¹ (See Hydration under Dosage and Administration.)

Seizures related to alterations in plasma minerals and electrolytes may occur.¹ Carefully monitor for such changes and their potential sequelae.¹ Mineral and electrolyte supplementation may be required.¹

The only FDA-approved indications are treatment of cytomegalovirus (CMV) retinitis in HIV-infected patients or treatment of mucocutaneous acyclovir-resistant HSV infections in immunocompromised patients.¹

Introduction

Antiviral; organic analog of inorganic pyrophosphate.¹ ² ³ ⁴

Uses for Foscarnet Sodium

Cytomegalovirus (CMV) Infection

Treatment of CMV retinitis in HIV-infected patients.¹ ² ³ ⁴ ³³ Foscarnet is not curative; stabilization or improvement of ocular manifestations may occur, but progression of retinitis is possible during or following treatment.¹ ² ³ ⁴

Drugs of choice for initial induction and maintenance therapy of CMV retinitis are IV ganciclovir, IV foscarnet, IV cidofovir, oral valganciclovir, or intravitreal fomivirsen.³³ ⁶² A regimen of both ganciclovir and foscarnet is used for treatment of CMV retinitis in patients who have relapsed following monotherapy with either drug.¹ ⁶³ ⁶⁴

Long-term suppressive or maintenance therapy (secondary prophylaxis) of recurrent CMV disease† in HIV-infected adults, adolescents, or children†.³⁸ USPHS/IDSA recommends IV ganciclovir or IV foscarnet as drugs of choice for such prophylaxis.³⁸

Prophylaxis or preemptive treatment of CMV disease in adult and pediatric allogeneic or autologous hematopoietic stem cell transplant (HSCT) recipients†.³⁹ CDC, IDSA, and ASBMT recommend IV foscarnet as an alternative to IV ganciclovir in HSCT recipients, especially when ganciclovir cannot be tolerated or when ganciclovir-resistant CMV may be involved.³⁹

Safety and efficacy not established for treatment of extraocular CMV infections or for CMV infections in immunocompetent individuals.¹

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Treatment of acyclovir-resistant mucocutaneous HSV (HSV-1 and HSV-2) infections (e.g., orofacial, genital, digital) in immunocompromised patients (e.g., those with AIDS).¹ ³³ ⁴⁰ ⁴¹ ⁴² ⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁸ ⁴⁹ ⁵⁰ ⁵¹ ⁵⁶ ⁵⁷ ⁷³

Safety and efficacy not established for treatment of other HSV infections, such as retinitis, encephalitis, and congenital neonatal HSV disease, or for HSV infections in immunocompetent individuals.¹

Chronic suppressive or maintenance therapy (secondary prophylaxis) against recurrence of HSV infections† in HIV-infected individuals who have frequent or severe recurrences.⁵⁹

Drugs of choice for secondary prophylaxis are oral acyclovir or oral famciclovir in adults and adolescents and oral acyclovir in infants and children; IV foscarnet and IV cidofovir are alternatives for such prophylaxis if acyclovir-resistant HSV is suspected.⁵⁹

Varicella-Zoster Infections

Management of acyclovir-resistant varicella-zoster infections† in patients with AIDS.⁵⁰ ⁵² ⁵³ ⁷⁰

Foscarnet Sodium Dosage and Administration

General

Hydration

To minimize risk of nephrotoxicity, patients should be adequately hydrated before and during administration of foscarnet.¹ ² ⁶ ⁷ ⁹ ²¹ ²² ²³ ²⁴

The manufacturer recommends that diuresis be established before the first dose of foscarnet by administering 750–1000 mL of 0.9% sodium chloride or 5% dextrose solution.¹

With subsequent foscarnet doses, 750–1000 mL of fluid should be administered concurrently with each foscarnet dose of 90–120 mg/kg, and 500 mL of fluid should be administered concurrently with each foscarnet dose of 40–60 mg/kg.¹

The volume of fluid may be decreased if clinically appropriate.¹

Adequate hydration also may be possible orally in some patients.³⁷

Administration

Administer by slow IV infusion via a controlled infusion device (e.g., pump).¹ Do not administer by rapid IV infusion or direct IV injection since potentially toxic plasma foscarnet concentrations may result.¹

If manifestations of hypocalcemia or adverse nervous system effects (e.g., perioral tingling) develop during administration of the drug, the infusion should be stopped, at least temporarily.¹ (See Mineral and Electrolyte Imbalance under Cautions.)

IV Infusion

Can infuse foscarnet solutions via either a peripheral or central vein, but take care in selecting a vein that will provide adequate blood flow for rapid dilution and distribution of the drug.¹

Do not admix foscarnet IV solutions or administer through the same catheter as other drugs.¹

Dilution

For infusion via a peripheral vein, foscarnet injection containing 24 mg/mL must be diluted with a compatible infusion solution (i.e., 0.9% sodium chloride injection, 5% dextrose injection) to a final concentration of 12 mg/mL to minimize the risk of local irritation.¹ ⁴

Foscarnet injection containing 24 mg/mL does not need to be diluted if it is infused via a central vein.¹ ⁴

Rate of Administration

IV infusions usually are given over 1–2 hours depending on dosage.¹

Dosage

Available as the hydrated trisodium salt (i.e., foscarnet sodium); dosage is expressed in terms of foscarnet sodium.¹

Dosage must be carefully individualized according to body weight and renal function.¹ Do not exceed recommended doses, frequency of administration, and rates of IV infusion.¹

Pediatric Patients

Cytomegalovirus (CMV) Infections

Prevention of Recurrence (Secondary Prophylaxis) of CMV Disease in HIV-infected Children and Adolescents†

90–120 mg/kg once daily.⁵⁹ Initiate secondary prophylaxis after initial induction treatment.⁵⁹

HIV-infected children with a history of CMV disease should receive life-long suppressive therapy to prevent recurrence.⁵⁹ The safety of discontinuing secondary CMV prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.⁵⁹

Consideration can be given to discontinuing secondary prophylaxis in HIV-infected adolescents according to recommendations in adults.⁵⁹

Adults

Cytomegalovirus (CMV) Infections

Treatment of CMV Retinitis

Initial induction therapy: 60 mg/kg (infused over ≥1 hour) every 8 hours for 14–21 days¹ ² ⁴ ³³ or 90 mg/kg (infused over 1.5–2 hours) every 12 hours for 14–21 days.¹ ³³

Maintenance treatment: 90–120 mg/kg (infused over 2 hours) once daily.¹ ² ³ ⁴ ³³ Most patients should receive an initial IV maintenance dosage of 90 mg/kg daily since the higher dosage may be associated with increased toxicity;¹ ² ³ ⁴ dosage may be increased up to 120 mg/kg daily in patients in whom early reinduction is required because of further progression of CMV retinitis.¹

Some patients exhibiting excellent tolerance to the drug may benefit from early initiation of a maintenance dosage of 120 mg/kg daily.¹

Prevention of Recurrence (Secondary Prophylaxis) of CMV Disease in HIV-infected Adults

90–120 mg/kg once daily recommended by USPHS/IDSA.⁵⁹ Initiate secondary prophylaxis after initial induction treatment.⁵⁹

Consideration can be given to discontinuing secondary prophylaxis in adults with sustained (e.g., for ≥6 months) increase in CD4⁺ T-cell counts to >100–150/mm³ in response to potent antiretroviral therapy.⁵⁹ This decision should be made in consultation with an ophthalmologist and factors such as the magnitude and duration of CD4⁺ T-cell increase, anatomic location of the retinal lesion, vision in the contralateral eye, and feasibility of regular ophthalmic monitoring should be considered.⁵⁹

Relapse of CMV retinitis could occur following discontinuance of secondary prophylaxis, especially in those whose CD4⁺ T-cell count decreases to <50/mm³; relapse has been reported rarely in those with CD4⁺ T-cell counts >100/mm³.⁵⁹

Reinitiate secondary CMV prophylaxis if CD4⁺ T-cell count decreases to <100–150/mm³.⁵⁹

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Treatment of Acyclovir-resistant Mucocutaneous HSV Infections

40 mg/kg (infused IV over ≥1 hour) every 8 or 12 hours for 2–3 weeks or until clinical resolution is attained.¹ ³³ ⁴⁰ ⁴⁶ ⁷³

Varicella-Zoster Infections†

Management of Acyclovir-resistant Varicella-Zoster Infections†

40 mg/kg every 8 hours for 10–21 days³³ ⁵² ⁵³ or until complete healing occurs.⁵⁵ Higher dosage (e.g., 60 mg/kg every 8 hours, 100 mg/kg every 12 hours) also has been used.⁵⁵ ⁷⁰

Special Populations

Renal Impairment

Dosage must be modified according to the degree of renal impairment¹ ⁴ ⁶⁶ and is based on the patient’s measured or estimated Cl_cr.¹ ⁴

Consider that dosage adjustment may be required in patients with initially normal renal function since most patients experience a decrease in renal function during foscarnet therapy.¹ ² ⁴

Monitor renal function (i.e., measured and estimated Cl_cr) prior to initiating therapy, 2 or 3 times weekly during induction therapy, and at least once every 1 or 2 weeks during maintenance therapy.¹ ² ⁴ Cl_cr should be calculated even if serum creatinine is within the normal range, and dosage adjusted accordingly.¹

If Cl_cr declines to <0.4 mL/minute per kg during therapy, foscarnet should be discontinued and the patient should be hydrated and monitored daily until resolution of renal impairment is ensured.¹

Induction Dosage for CMV Retinitis or HSV Infections in Adults with Renal Impairment1
Cl_cr (mL/min per kg)	Induction Dosage for CMV (in mg/kg) Equivalent to 60 mg/kg Every 8 Hours	Induction Dosage for CMV (in mg/kg) Equivalent to 90 mg/kg Every 12 Hours	Induction Dosage for HSV (in mg/kg) Equivalent to 40 mg/kg Every 12 Hours	Induction Dosage for HSV (in mg/kg) Equivalent to 40 mg/kg Every 8 Hours
>1.4	60 every 8 hours	90 every 12 hours	40 every 12 hours	40 every 8 hours
>1–1.4	45 every 8 hours	70 every 12 hours	30 every 12 hours	30 every 8 hours
>0.8–1	50 every 12 hours	50 every 12 hours	20 every 12 hours	35 every 12 hours
>0.6–0.8	40 every 12 hours	80 every 24 hours	35 every 24 hours	25 every 12 hours
>0.5–0.6	60 every 24 hours	60 every 24 hours	25 every 24 hours	40 every 24 hours
≥0.4–0.5	50 every 24 hours	50 every 24 hours	20 every 24 hours	35 every 24 hours
<0.4	Not recommended	Not recommended	Not recommended	Not recommended

Maintenance Dosage for CMV Retinitis in Adults with Renal Impairment1
Cl_cr (mL/min per kg)	Maintenance Dosage (mg/kg) Equivalent to 90 mg/kg Once Daily	Maintenance Dosage (in mg/kg) Equivalent to 120 mg/kg Once Daily
>1.4	90 every 24 hours	120 every 24 hours
>1–1.4	70 every 24 hours	90 every 24 hours
>0.8–1	50 every 24 hours	65 every 24 hours
>0.6–0.8	80 every 48 hours	105 every 48 hours
>0.5–0.6	60 every 48 hours	80 every 48 hours
≥0.4–0.5	50 every 48 hours	65 every 48 hours
<0.4	Not recommended	Not recommended

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Foscarnet Sodium

Contraindications

Hypersensitivity to foscarnet.¹

Warnings/Precautions

Warnings

Nephrotoxicity

Renal impairment and/or failure, manifested mainly as an increase in serum creatinine concentration and/or a decrease in Cl_cr, is the major toxicity of foscarnet, occurring to some degree in most patients.¹ ² ⁴ ⁶ ²¹ ²² ²³ ²⁴ ²⁵ ²⁶

Based on measurement of serum creatinine, renal impairment is most likely to become clinically evident during the second week of induction therapy at a dosage of 180 mg/kg daily; however, renal impairment may occur at any time during therapy.¹ ²¹ ²² ²⁵

Foscarnet-induced increases in serum creatinine concentrations usually (but not always) are reversible following dosage adjustment or discontinuance of the drug;¹ ² ²¹ ²² maximum deterioration in renal function may not be apparent until several weeks after discontinuance.¹ ²⁵ Fatalities have been reported.¹

Hemodialysis may be useful in management of foscarnet-induced nephrotoxicity when elevated plasma concentrations are present and the degree of renal failure is severe.¹ ² ²⁵

Adequate hydration (e.g., inducing diuresis) is imperative before and during foscarnet therapy since it decreases the risk of foscarnet-induced renal impairment.¹ ² ⁶ ⁷ ⁹ ²¹ ²² ²³ ²⁴ (See Hydration under Dosage and Administration.)

Mineral and Electrolyte Imbalance

Alterations in serum electrolytes reported, including hypocalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, and hypokalemia.¹ ² ⁴ ⁶ ⁷ ⁹ ¹⁰

Dose-related decreases in ionized serum calcium may occur, which may not be reflected in total serum calcium.¹

Decreased serum concentrations of ionized calcium may result in symptoms such as perioral tingling, numbness in the extremities, or paresthesias.¹ Clinicians should be prepared to treat these or more severe manifestations such as tetany, seizures, or cardiac disturbances.¹

Foscarnet-induced changes in serum concentrations of calcium or other electrolytes most likely result from the drug’s ability to chelate and form stable coordination compounds with divalent metal ions such as calcium and magnesium.¹ ² ⁶

The decrease in ionized calcium may be affected by the foscarnet IV infusion rate.¹ An infusion pump must be used to prevent rapid IV infusion; slowing the infusion rate may decrease or prevent symptoms.¹

Particular caution and careful management of serum electrolytes is advised in patients who have altered baseline calcium or other electrolyte levels prior to initiation of foscarnet, especially those with neurologic or cardiac abnormalities and those receiving other drugs known to influence minerals and electrolytes (especially calcium).¹ ⁷

Seizures

Seizures related to mineral and electrolyte abnormalities (see Mineral and Electrolyte Imbalance under Cautions) have occurred; some seizures resulted in death.¹

Factors that may increase risk of seizures include renal impairment at baseline, low total serum calcium concentrations, and underlying CNS conditions.¹

General Precautions

Local Reactions

To avoid local irritation, care must be taken to infuse only into veins with adequate blood flow to permit rapid dilution and distribution of the drug.¹

Genitourinary Effects

Local irritation and ulcerations of penile epithelium (resembling fixed drug eruption grossly but not histologically) reported in male patients¹ ² ⁴ ⁶ ¹¹ ¹² ¹³ ¹⁴ ¹⁵ ¹⁶ and vulvovaginal ulcerations reported in at least 1 female.¹ ¹⁷

These effects possibly are related to high concentrations of unchanged drug in urine.¹ ¹⁴ ¹⁵ Use of adequate hydration with close attention to personal hygiene may minimize risk of these adverse effects.¹ ¹⁵

Hematologic Effects

Although foscarnet usually is not myelosuppressive,² ⁴ ⁶ ⁸ ¹⁸ ¹⁹ ²⁰ ³⁸ anemia and granulocytopenia may occur.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹ ⁵

Animal studies indicate foscarnet is deposited in teeth and bone in animals (particularly during early growth and development) and adversely affects tooth enamel development.¹ Also deposited to an unknown extent in bone in humans.¹

Use in children should be undertaken only after careful evaluation and only when potential benefits outweigh possible risks.¹

Geriatric Use

Adverse effects reported in adults ≥65 years of age are similar to those reported in younger adults.¹

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.¹ Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.¹

Renal Impairment

Because renal impairment is the principal toxicity of foscarnet and occurs to some degree in most patients, foscarnet must be used with particular caution in those with a history of renal impairment.¹ ² ²¹ ²² ²³ ²⁴ ²⁵ ²⁶

In patients with renal impairment, reduced plasma clearance of foscarnet will result in increased plasma concentrations; in addition, the drug potentially may further impair renal function in these patients.¹

Renal function must be assessed prior to and frequently during therapy; adjust dosage for decreased baseline renal function and for changes in renal function that may occur during treatment.¹ ² ²¹ ²² ²³ ²⁴ ²⁵ ²⁶ ³⁸ (See Renal Impairment under Dosage and Administration.)

In patients with renal impairment, dosage is adjusted based on Cl_cr (measured or calculated).¹ In addition, a 24-hour Cl_cr should be determined at baseline and periodically thereafter to ensure appropriate dosing (assuming verification of an adequate urine collection using the creatinine index).¹

If Cl_cr declines to <0.4 mL/minute per kg during foscarnet therapy, the drug should be discontinued and the patient should be hydrated and monitored daily until resolution of renal impairment is ensured.¹

Data are limited regarding safety and efficacy in patients with baseline measured Cl_cr <50 mL/minute or baseline serum creatinine concentrations >2.8 mg/dL¹ or in patients undergoing hemodialysis or peritoneal dialysis. Use in such patients is not recommended.³⁸

Common Adverse Effects

Nephrotoxicity; alterations in serum electrolytes; CNS effects (headache, seizures); GI effects (nausea, diarrhea, vomiting); fever.¹ ² ⁴ ⁶ ⁷ ⁸ ⁹ ²¹ ²² ²³ ²⁴ ²⁵ ²⁶

Interactions for Foscarnet Sodium

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	Possible increased nephrotoxicity¹	Avoid concomitant use unless potential benefits outweigh risks¹
Amphotericin B	Possible increased nephrotoxicity¹	Avoid concomitant use unless potential benefits outweigh risks¹
Drugs affecting calcium	Possible additive effects on serum calcium concentrations; foscarnet decreases calcium¹	Use concomitantly with particular caution¹
Ganciclovir	No apparent effect on ganciclovir or foscarnet pharmacokinetics with concomitant or alternating therapy with the drugs.¹ In vitro evidence of synergistic antiviral activity.¹
Pentamidine	Possible hypocalcemia when used with IV pentamidine;¹ not reported to date with aerosolized pentamidine¹	Avoid concomitant use unless potential benefits outweigh risks¹
Ritonavir	Possible abnormal renal function when used with ritonavir (with or without saquinavir)¹

Foscarnet Sodium Pharmacokinetics

Distribution

Extent

Distrubuted into bone; extent of accumulation unknown.¹

Distributed into CSF.¹

Plasma Protein Binding

14–17%.¹

Elimination

Half-life

Adults with normal renal function: 1.93 hours.¹

Special Populations

Clearance is decreased and half-life prolonged in patients with renal impairment.¹ Half-life is 3.35 hours in those with Cl_cr 50–80 mL/minute, 13 hours in those with Cl_cr 25–49 mL/minute, and 25.3 hours in those with Cl_cr 10–24 mL/minute.¹

Stability

Storage

Parenteral

Injection, for IV Infusion

15–30°C.¹ Protect from excessive heat (>40°C); protect from freezing.¹ Solution should be used within 24 hours after first entry into a sealed bottle.¹

Compatibility

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

Parenteral

Solution Compatibility^HID

Compatible
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID
Compatible
Potassium chloride

Y-Site CompatibilityHID
Compatible
Aldesleukin
Amikacin sulfate
Aminophylline
Ampicillin sodium
Aztreonam
Cefazolin sodium
Cefoperazone sodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Chloramphenicol sodium succinate
Cimetidine HCl
Clindamycin phosphate
Dexamethasone sodium phosphate
Dopamine HCl
Erythromycin lactobionate
Fluconazole
Flucytosine
Furosemide
Gentamicin sulfate
Heparin sodium
Hydrocortisone sodium succinate
Hydromorphone HCl
Hydroxyzine HCl
Imipenem–cilastatin sodium
Metoclopramide HCl
Metronidazole
Morphine sulfate
Nafcillin sodium
Oxacillin sodium
Penicillin G potassium
Ranitidine HCl
Ticarcillin disodium–clavulanate potassium
Tobramycin sulfate
Incompatible
Acyclovir sodium
Amphotericin B
Diazepam
Digoxin
Diphenhydramine HCl
Dobutamine HCl
Droperidol
Ganciclovir sodium
Haloperidol lactate
Leucovorin calcium
Midazolam HCl
Pentamidine isethionate
Prochlorperazine edisylate
Promethazine HCl
Trimetrexate glucuronate
Variable
Co-trimoxazole
Lorazepam
Vancomycin HCl

Actions and SpectrumActions

Organic analog of inorganic pyrophosphate with antiviral activity.¹

Mechanism of antiviral activity appears to involve selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.¹

Active against herpesviruses, including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2).¹

Some ganciclovir-resistant CMV and some acyclovir-resistant HSV may be susceptible to foscarnet.¹

CMV and HSV resistant to foscarnet can be selected in vitro and may occur in vivo in patients who receive the drug.¹

Advice to Patients

Advise patients that foscarnet is not a cure for CMV retinitis; they may continue to experience progression of retinitis during or following treatment.¹ Regular ophthalmologic examinations are necessary.¹

Advise patients that foscarnet is not a cure for HSV infection.¹ Complete healing is possible, but relapse occurs in most patients.¹ Repeated treatment with foscarnet may lead to resistance associated with poorer response; in vitro susceptibility testing may be necessary.¹

The major toxicities of foscarnet are renal impairment, electrolyte disturbances, and seizures; dosage adjustments or discontinuance may be required.¹

Importance of maintaining adequate hydration (diuresis should be maintained during dosing) to minimize risk of renal impairment.¹

Importance of informing clinician if symptoms of electrolyte imbalance (perioral tingling, numbness in the extremities, paresthesias) occur during or after IV infusion.¹ If these occur, the infusion should be stopped, electrolyte concentrations determined, and the clinician consulted before treatment is resumed.¹

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

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

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Foscarnet Sodium
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV infusion only	24 mg/mL*	Foscarnet Sodium Injection	Hospira
			Foscavir	AstraZeneca

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.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Astra. Foscavir (foscarnet sodium) injection prescribing information (dated 1998 Feb). In: Physician’s desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:564-7.

2. Chrisp P, Clissold SP. Foscarnet: a review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis. Drugs. 1991; 41:104-29. [PubMed 1706982]

3. Polis MA. Foscarnet and ganciclovir in the treatment of cytomegalovirus retinitis. J Acquir Immune Defic Syndr. 1992; 5(Suppl 1):S3-10. [PubMed 1318365]

4. Minor JR, Baltz JK. Foscarnet sodium. DICP. 1991; 25:41-7. [IDIS 277451] [PubMed 1848959]

5. Hwang SB (Astra Pharmaceutical, Westborough, MA): Personal communication; 1992 May 5.

6. Anon. Foscarnet. Med Lett Drugs Ther. 1992; 34:3-4. [PubMed 1309469]

7. Palestine AG, Polis MA, De Smet MD et al. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med. 1991; 115:665-73. [IDIS 286914] [PubMed 1656826]

8. Studies of Ocular Complications of AIDS Research Group, in Collaboration with the AIDS Clinical Trials Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. N Engl J Med. 1992; 326:213-20. [IDIS 290413] [PubMed 1345799]

9. Jacobson MA, Causey D, Polsky B et al. A dose-ranging study of daily maintenance intravenous foscarnet therapy for cytomegalovirus retinitis in AIDS. J Infect Dis. 1993; 168:444-8. [IDIS 318758] [PubMed 8393058]

10. Gearhart MO, Sorg TB. Foscarnet-induced severe hypomagnesemia and other electrolyte disorders. Ann Pharmacother. 1993; 27:285-9. [IDIS 312692] [PubMed 8384030]

11. Van Der Pijl JW, Frissen PHJ, Reiss P et al. Foscarnet and penile ulceration. Lancet. 1990; 335:286. [IDIS 263067] [PubMed 1967736]

12. Gilquin J, Weiss L, Kazatchkine MD. Genital and oral erosions induced by foscarnet. Lancet. 1990; 335:287. [IDIS 263068] [PubMed 1967737]

13. Feguex S, Salmon D, Picard C et al. Penile ulcerations with foscarnet. Lancet. 1990; 335:547.

14. Moyle G, Nelson M, Barton SE et al. Penile ulcerations with foscarnet. Lancet. 1990; 335:547-8.

15. Lernestedt JO, Chanas AC. Penile ulcerations with foscarnet. Lancet. 1990; 335:548. [IDIS 264319] [PubMed 1968563]

16. Connolly G, Gazzard B, Hawkins D. Fixed drug eruption due to foscarnet. Genitourin Med. 1990; 66:97-8. [PubMed 2160425]

17. Lacey HB, Ness A, Mandal BK. Vulval ulceration associated with foscarnet. Genitourin Med. 1992; 68:182. [PubMed 1535062]

18. Hirsch MS. The treatment of cytomegalovirus in AIDS—more than meets the eye. N Engl J Med. 1992; 326:264-6. [IDIS 290416] [PubMed 1309391]

19. Bachman DM. Treatment of CMV retinitis. N Engl J Med. 1992; 326:1702. [IDIS 298111] [PubMed 1317012]

20. Dieterich DT, Poles MA, Lew EA et al. Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients. J Infect Dis. 1993; 167:1184-8. [IDIS 313719] [PubMed 8387563]

21. Deray G, Martinez F, Katlama C et al. Foscarnet nephrotoxicity: mechanism, incidence and prevention. Am J Nephrol. 1989; 9:316-21. [PubMed 2554731]

22. Cacoub P, Deray G, Baumelou A et al. Acute renal failure induced by foscarnet: 4 cases. Clin Nephrol. 1988; 29:315-8. [PubMed 2840226]

23. Deray G, Katlama C, Jacobs C. Treatment of CMV retinitis. N Engl J Med. 1992; 326:1702. [IDIS 298110] [PubMed 1317011]

24. Deray G, Katlama C, Dohin E. Prevention of foscarnet nephrotoxicity. Ann Intern Med. 1990; 113:332. [IDIS 270492] [PubMed 2165372]

25. Deray G, Cacoub P, Le Hoang P et al. Foscarnet-induced acute renal failure and effectiveness of haemodialysis. Lancet. 1987; 2:216. [IDIS 233081] [PubMed 2885666]

26. Beaufils H, Deray G, Katlama C et al. Foscarnet and crystals in glomerular capillary lumens. Lancet. 1990; 336:755. [IDIS 271556] [PubMed 1975929]

27. Farese RV Jr, Schambelan M, Hollander H et al. Nephrogenic diabetes insipidus associated with foscarnet treatment of cytomegalovirus retinitis. Ann Intern Med. 1990; 112:955-6. [IDIS 267341] [PubMed 2160217]

28. Sjövall J, Bergdahl S, Movin G et al. Pharmacokinetics of foscarnet and distribution to cerebrospinal fluid after intravenous infusion in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother. 1989; 33:1023-31. [IDIS 256767] [PubMed 2528939]

29. Cotte L, Langlois M, Trepo C. Herpes simplex virus infection during foscarnet therapy. J Infect Dis. 1992; 166:447-8. [IDIS 299310] [PubMed 1321865]

30. Bendel AE, Gross TG, Woods WG et al. Failure of foscarnet in disseminated herpes zoster. Lancet. 1993; 341:1342. [IDIS 314782] [PubMed 8098465]

31. Kupfer C, Jabs D, Stein M et al. Clinical alert and HHS News: findings of the Foscarnet-Ganciclovir Cytomegalovirus Trial. Bethesda, MD: National Institutes of Health, National Eye Institute; 1991 Oct 17 and Rockville, MD: US Public Health Service; 1991 Oct 21.

32. Roche Laboratories. Cytovene-IV (ganciclovir sodium for injection) and cytovene (ganciclovir capsules) prescribing information. Nutley, NJ; 2000 Sep

33. Anon. Drugs for non-HIV viral infections. Med Lett Drugs Ther. 2002; 44:9-16. [PubMed 11828264]

35. Heinemann MH. Long-term intravitreal ganciclovir therapy for cytomegalovirus retinopathy. Arch Ophthalmol. 1989; 107:1767-72. [IDIS 261799] [PubMed 2556990]

36. Leport C, Puget S, Pepin JM et al. Cytomegalovirus resistant to foscarnet: clinicovirologic correlation in a patient with human immunodeficiency virus. J Infect Dis. 1993; 168:1329-30. [IDIS 321506] [PubMed 8228376]

37. Reviewers’ comments (personal observations).

38. Astra, Westborough, MA: personal communication.

39. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR Morb Mortal Wkly Rep. 2000; 49(No. RR-10):1-125. [IDIS 439515] [PubMed 10993565]

40. Safrin S, Crumpacker C, Chatis P et al. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. N Engl J Med. 1991;325:551-5.

41. Safrin S, Assaykeen T, Follansbee S et al. Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data. J Infect Dis. 1990; 161:1078-84. [IDIS 303052] [PubMed 2161035]

42. Erlich KS, Jacobson MA, Koehler JE et al. Foscarnet therapy for severe acyclovir-resistant herpes simplex virus type-2 infections in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1989; 110:

Uro-Mag

Generic Name: magnesium oxide (mag NEE see um OCK side)

Brand Names: Mag-200, Mag-Ox 400, MagGel, Uro-Mag

What is Uro-Mag (magnesium oxide)?

Magnesium is a naturally occurring mineral. Magnesium is important for many systems in the body especially the muscles and nerves.

Magnesium oxide is used as a supplement to maintain adequate magnesium in the body.

Magnesium oxide may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Uro-Mag (magnesium oxide)?

Before taking magnesium oxide, tell your doctor if you have any other medical conditions, allergies, or if you take other medicines or other herbal/health supplements. Magnesium oxide may not be recommended in some situations.

Who should not take Uro-Mag (magnesium oxide)?

Do not take magnesium oxide without first talking to your doctor if you have kidney disease.

It is not known whether magnesium oxide will harm an unborn baby. Do not take magnesium oxide without first talking to your doctor if you are pregnant or planning a pregnancy. It is not known whether magnesium oxide will harm an nursing baby. Do not take magnesium oxide without first talking to your doctor if you are breast-feeding a baby.

How should I take Uro-Mag (magnesium oxide)?

Take magnesium oxide exactly as directed by your doctor or as directed on the package. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take the tablets and capsules with a full glass of water.

To ensure that you get the correct dose, measure the liquid form of magnesium with a dose-measuring spoon or cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

Do not take more magnesium oxide than is directed. Store magnesium oxide at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the dose you missed and take only the next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of an magnesium oxide overdose include nausea, vomiting, flushing, low blood pressure, a slow heartbeat, drowsiness, coma, and death.

What should I avoid while taking Uro-Mag (magnesium oxide)?

There are no restrictions on food, beverages, or activity while taking magnesium oxide unless otherwise directed by your doctor.

Uro-Mag (magnesium oxide) side effects

Stop taking magnesium oxide and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Other, less serious side effects may be more likely to occur. Continue to take magnesium oxide and talk to your doctor if you experience diarrhea or an upset stomach.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Uro-Mag (magnesium oxide)?

Before taking magnesium oxide, talk to your doctor if you are taking

a tetracycline antibiotic such as tetracycline (Sumycin, Achromycin V, and others), demeclocycline (Declomycin), doxycycline (Vibramycin, Monodox, Doxy, and others), minocycline (Minocin, Dynacin, and others), or oxytetracycline (Terramycin, and others);

a fluoroquinolone antibiotic such as ciprofloxacin (Cipro), ofloxacin (Floxin), enoxacin (Penetrex), norfloxacin (Noroxin), sparfloxacin (Zagam), levofloxacin (Levaquin), lomefloxacin (Maxaquin), grepafloxacin (Raxar), and others;

penicillamine (Cuprimine);

digoxin (Lanoxin, Lanoxicaps); or

nitrofurantoin (Macrodantin, Furadantin, others).

You not be able to take magnesium oxide, or you may require a dosage adjustment or special monitoring during your treatment if you are taking any of the medicines listed above.

Drugs other than those listed here can also interact with magnesium oxide. Talk to your doctor and pharmacist before taking any over-the-counter or prescription medicines.

More Uro-Mag resources

Uro-Mag Side Effects (in more detail)
Uro-Mag Use in Pregnancy & Breastfeeding
Uro-Mag Drug Interactions
Uro-Mag Support Group
0 Reviews for Uro-Mag - Add your own review/rating

Uro-Mag MedFacts Consumer Leaflet (Wolters Kluwer)

Magnesium Oxide Professional Patient Advice (Wolters Kluwer)

Compare Uro-Mag with other medications

Constipation
Duodenal Ulcer
GERD
Hypomagnesemia
Indigestion
Pathological Hypersecretory Disorder
Stomach Ulcer
Urinary Tract Stones

Where can I get more information?

Your pharmacist has additional information about magnesium oxide written for health professionals that you may read.

See also: Uro-Mag side effects (in more detail)