Nonbacterial and Noninfectious Cystitis Medication

Updated: Mar 09, 2018
  • Author: Lynda A Frassetto, MD; Chief Editor: Edward David Kim, MD, FACS  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications. Depending on the cause, the agents used may include antimicrobials, antifungals, antivirals, anthelmintics, or antidotes.

A combination of isoniazid (INH), rifampin (RIF), ethambutol, and pyrazinamide is commonly used to treat mycobacterial cystitis, while oral fluconazole or bladder irrigations containing amphotericin B can be used against fungal cystitis.

The antiviral agents acyclovir and valacyclovir are administered for the treatment of cystitis caused by herpes simplex virus-1 (HSV-1) or HSV-2. Ganciclovir and the prodrug valganciclovir are employed against hemorrhagic cystitis caused by cytomegalovirus (CMV).

Praziquantel kills the parasites responsible for schistosomiasis, with the current recommended therapy being 2 oral doses, 40 mg/kg for 1 day; this regimen has an 83-100% cure rate.

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Antibiotics, Other

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Rifampin (Rifadin)

Rifampin inhibits ribonucleic acid (RNA) synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription. The dosage in adults is 600mg orally once daily for 6 months. Rifampin induces microsomal enzymes, which may decrease the effects of other drugs. Blood pressure may increase with coadministration of enalapril. Coadministration with isoniazid or pyrazinamide may result in a higher rate of hepatotoxicity than with either agent alone (discontinue 1 or both agents if alterations in liver function test results occur).

Obtain complete blood counts (CBCs) and baseline clinical chemistries prior to and throughout rifampin therapy. In liver disease, weigh the benefits of rifampin use against the risk of further liver damage. Interruption of therapy and high-dose, intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after the appearance of purpura, cerebral hemorrhage or death may occur. Rifampin is a pregnancy category C drug.

Isoniazid

Isoniazid is an isonicotinic acid hydrazide. This agent is used as part of a triple-drug regimen. The adult dosage is 300 mg orally once daily for 6 months. Previous isoniazid-associated hepatic injury or other severe adverse reactions are contraindications. Daily alcohol ingestion may predispose patients to isoniazid-related hepatitis.

Aluminum salts may decrease isoniazid serum levels (administer 1-2 hours before taking aluminum salts). Isoniazid may increase anticoagulants' effects with coadministration and may inhibit the metabolic clearance of benzodiazepines. Carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function).

Coadministration with cycloserine may increase central nervous system (CNS) side effects (eg, dizziness). Acute behavioral and coordination changes may occur with coadministration of disulfiram. Coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy.

Isoniazid may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin. Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during isoniazid therapy are recommended even when visual symptoms do not occur. Isoniazid is a pregnancy category C drug.

Pyrazinamide

Pyrazinamide is used only in combination with other effective antituberculous agents. Its mechanism of action is unknown. It is well absorbed from the gastrointestinal (GI) tract and hydrolyzed to its active metabolite in the liver. Note that 70% is excreted in urine within 24 hours.

Treat patients with drug-resistant disease with individualized regimens. The adult dose is 2g orally once daily for 2 months. Contraindications include severe hepatic damage and acute gout. Coadministration with rifampin may result in a higher rate of hepatotoxicity than with either agent alone (discontinue if alterations in liver function test results occur).

Pyrazinamide inhibits the renal excretion of urates and may result in hyperuricemia (usually asymptomatic). Perform baseline serum uric acid determinations, and discontinue the drug upon signs of hyperuricemia with acute gouty arthritis. Perform baseline liver function tests (closely monitor in liver disease) and discontinue the drug if signs of hepatocellular damage appear. Observe caution when there is a history of diabetes mellitus. Pyrazinamide is a pregnancy category C drug.

Ethambutol (Myambutol)

Ethambutol diffuses into actively growing mycobacterial cells, such as tubercle bacilli. It impairs cell metabolism by inhibiting synthesis of 1 or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated. Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with previously unadministered second-line drugs.

The adult dosage of ethambutol is 15mg/kg orally once daily for 2 months. Aluminum salts may delay and reduce absorption (give several hours before or after ethambutol dose). Reduce the dose in patients with impaired renal function. Optic neuritis may develop but is reversible if the drug is promptly discontinued. Ethambutol is a pregnancy category C drug.

Doxycycline (Adoxa, Doryx, Periostat, Vibramycin, Monodox)

Doxycycline is a broad-spectrum, synthetically derived, bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.

It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl transfer RNA (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. The adult dosage is 100mg orally twice daily. Severe hepatic dysfunction is a contraindication.

The bioavailability of doxycycline decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate. Tetracyclines can increase the hypoprothrombinemic effects of anticoagulants and can decrease the efficacy of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy. Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment.

Reduce the dose in patients with renal impairment. Consider drug serum level determinations in prolonged therapy. Tetracycline use during tooth development (the last half of pregnancy through age 8 years) can permanently discolor teeth. Fanconi-like syndrome may occur with outdated tetracyclines. Doxycycline is a pregnancy category D drug.

Azithromycin (Zithromax, Zmax)

Azithromycin is used to treat mild to moderate microbial infections. In adults, it is given in a single dose of 1g orally. Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. It concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that the concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Contraindications to azithromycin use include hepatic impairment. Do not administer with pimozide. Azithromycin may increase the toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids.

Nephrotoxicity and neurotoxicity may occur when this agent is coadministered with cyclosporine. Site reactions can occur when it is given by the IV route. Bacterial or fungal overgrowth may result from prolonged antibiotic use.

Azithromycin may increase hepatic enzymes and cholestatic jaundice. Use this agent with caution in patients with impaired hepatic function or prolonged QT intervals. Azithromycin is a pregnancy category B drug.

Ofloxacin

Ofloxacin penetrates the prostate well and is effective against Neisseria gonorrhoeae and Chlamydia trachomatis. It is a pyridine carboxylic acid derivative with a broad-spectrum bactericidal effect. The adult dosage is 300mg orally twice daily for 7 days.

Antacids, iron salts, and zinc salts may reduce serum levels. Patients should take antacids 2-4 hours before or after taking fluoroquinolones. Cimetidine may interfere with the metabolism of fluoroquinolones.

Ofloxacin may increase the toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels) and may increase the effects of anticoagulants (monitor the prothrombin time). In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic). Adjust the dose in patients with impaired renal function. Superinfections may occur with prolonged or repeated antibiotic therapy. Ofloxacin is a pregnancy category C drug.

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Antifungal, Systemic

Class Summary

The mechanism of action of antifungal agents may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Amphotericin B deoxycholate

Amphotericin B is produced from a strain of Streptomyces nodosus. The antifungal activity of amphotericin B results from its ability to insert itself into the fungal cytoplasmic membrane at sites containing ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium).

At low concentrations, the main effect of this agent is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105nm in the cytoplasmic membrane are produced, leading to large losses of ions and other molecules.

A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and the release of lethal free radicals. The main fungicidal activity of amphotericin B may reside in its ability to cause auto-oxidation of cell membranes. The adult dose is 0.5mg/kg intravenously once daily for 7-14 days; 50mcg/mL can be given as bladder irrigation continuously for 5 days.

Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension. Corticosteroids, digitalis, and thiazides may potentiate hypokalemia. The risk of renal toxicity is increased with cyclosporine. Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBCs, and hemoglobin concentrations. Resume therapy at the lowest dose level (eg, 0.25mg/kg) when therapy is interrupted for more than 7 days.

Hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (give amphotericin infusions at different times than leukocyte transfusions). Fever and chills are not uncommon after the first few doses of the drug. Rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock. Amphotericin B is a pregnancy category B drug.

Fluconazole (Diflucan)

Fluconazole is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation; this prevents the conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. The drug has little affinity for mammalian cytochromes, which is believed to explain its low toxicity.

Fluconazole is available in tablet form for oral administration, as a powder for oral suspension, and as a sterile solution for intravenous use. It has fewer adverse effects and better tissue distribution than older systemic imidazoles. The adult dosage is 200mg orally or intravenously once daily for 7-14 days. Probenecid, zidovudine, or cimetidine coadministration prolongs the half-life and increases CNS toxicity. Adjust the dose for renal insufficiency; closely monitor if rashes develop, and discontinue the drug if lesions progress.

Fluconazole may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) in patients with certain underlying medical conditions (eg, AIDS, malignancy) or in those taking multiple, concomitant medications. It is not recommended for breastfeeding mothers.

The convenience and efficacy of a single-dose regimen for treatment of vaginal yeast infections should be weighed against the difficulties resulting from the higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents. Fluconazole is a pregnancy category C drug.

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Antivirals, Others

Class Summary

Nucleoside analogues are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase.

Acyclovir (Zovirax)

Acyclovir is activated via phosphorylation by virus-specific thymidine kinase. Guanylate kinase converts the monophosphate form into diphosphate and triphosphate analogues that inhibit viral DNA replication. Acyclovir has affinity for viral thymidine kinase and, once phosphorylated, causes DNA-chain termination when acted on by DNA polymerase.

Acyclovir inhibits the activity of HSV-1 and HSV-2. Patients experience less pain and faster resolution of cutaneous lesions when this agent is started within 48 hours of rash onset. It may prevent recurrent outbreaks. Early initiation of therapy is imperative. The adult dosage is 400mg orally 5 times daily for 7 days.

Concomitant use of probenecid or zidovudine prolongs the half-life and increases the CNS toxicity of acyclovir. Use this agent with caution in patients with renal failure or those using nephrotoxic drugs. Acyclovir is a pregnancy category B drug.

Valacyclovir (Valtrex)

Valacyclovir is a prodrug that is rapidly converted to the active drug acyclovir. It is more expensive than acyclovir but has a more convenient dosing regimen. The adult dosage is 500mg orally twice daily for 5-10 days.

The risk of hyperkalemia is increased in patients taking angiotensin-converting enzyme (ACE) inhibitors, cyclosporine, and potassium-sparing diuretics. Use valacyclovir with caution in patients with renal failure (decrease the dose) and in patients who are also taking nephrotoxic drugs. Valacyclovir is associated with the onset of hemolytic uremic syndrome. Valacyclovir is a pregnancy category B drug.

Valganciclovir (Valcyte)

Valganciclovir is an L-valyl ester prodrug of ganciclovir used for CMV disease prophylaxis in various solid organ transplants. Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Viral activity is halted due to the inhibition of viral DNA synthesis.

This agent has the advantage of once- or twice-daily oral administration. It achieves serum levels comparable to those obtained with intravenous ganciclovir. The adult dosage is 450mg orally twice daily for 21 days. Contraindications include severe renal dysfunction or hemodialysis, pregnancy, breastfeeding, or an absolute neutrophil count of less than 500 cells/µL, a platelet count of less than 25,000/µL, or a hemoglobin level of less than 8g/dL.

Interactions with valganciclovir are similar to those reported with ganciclovir. Coadministration with cytotoxic drugs such as dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogues may result in additive toxicity of rapidly dividing cell populations, including bone marrow, spermatogonia, germinal layers of skin, and GI mucosa. Coadminister with these agents only if the benefits outweigh the risks.

Coadministration with imipenem-cilastatin may cause generalized seizures (use only if the benefits outweigh the risks). Serum creatinine levels may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B. In the presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 hours before or simultaneously with ganciclovir.

The bioavailability of ganciclovir may decrease in the presence of zidovudine, while the bioavailability of zidovudine is increased in the presence of ganciclovir.

Strict adherence to dosage guidelines of valganciclovir is essential to avoid overdose. Valganciclovir tablets may not be substituted for ganciclovir capsules on a one-to-one basis; adjust the dose according to the creatinine clearance (CrCl) in patients with impaired renal function.

Valganciclovir may cause granulocytopenia, anemia, and thrombocytopenia. It is not indicated for CMV disease prevention in liver transplantation (the incidence of CMV disease in liver transplant recipients is higher with valganciclovir than with ganciclovir). Valganciclovir is a pregnancy category C drug.

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Antiparasitic Agents

Class Summary

The biochemical pathways of schistosomes are sufficiently different from those of the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Praziquantel (Biltricide)

Praziquantel increases cell membrane permeability in susceptible worms, resulting in the loss of intracellular calcium, massive contractions, and paralysis of musculature. In addition, it produces vacuolization and disintegration of schistosome tegument. This is followed by attachment of phagocytes to the parasite and death.

Tablets should be swallowed whole with some liquid during meals. Keeping the tablets in the mouth may reveal their bitter taste, which can produce nausea or vomiting. The adult dosage is 40mg/kg orally twice daily for 1 day.

Ocular cysticercosis is a contraindication. Hydantoins may reduce serum praziquantel concentrations, possibly leading to treatment failures.

Destruction of parasites within the eyes can cause irreparable lesions (ocular cysticercosis should not be treated with praziquantel). Patients should use caution while driving or performing other tasks requiring alertness on the day of treatment and on the following day. Minimal increases in liver enzymes have been reported. When schistosomiasis or fluke infection is associated with cerebral cysticercosis, hospitalize the patient for duration of treatment. Praziquantel is a pregnancy category B drug.

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Antidotes, Other

Class Summary

These agents counteract the toxic effects of drugs.

Mesna (Mesnex)

In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. It inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. The adult dosage is 240mg intravenously at 0, 4, 8 hours after the ifosfamide or cyclophosphamide dose.

Mesna may increase warfarin effects. Mesna does not prevent hemorrhagic cystitis in all patients (monitoring for hematuria in the morning prior to ifosfamide or cyclophosphamide dose is required). It does not prevent or alleviate other toxicities associated with ifosfamide or cyclophosphamide. Common adverse effects include hypotension, headache, GI toxicity, and limb pain. Mesna is a pregnancy category B drug.

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