Antituberculosis drugs

While the optimum dose and duration of therapy have not been established, rimantadine also has been used for the treatment of influenza A virus infection in children. While chemoprophylaxis with the drug should not be considered a substitute for annual vaccination with influenza virus vaccine, antiviral agents are an important adjunct to influenza vaccine for the control and prevention of influenza.

The most frequent adverse effects of dapsone are dose-related hemolytic anemia and methemoglobinemia. Hemolysis occurs in most patients receiving 200 mg or more of dapsone daily; however, symptomatic anemia occurs only occasionally. The manufacturer states that the hemoglobin level is generally decreased by 1-2 g/dL, the reticulocyte count is increased 2-12%, erythrocyte life span is shortened, and methemoglobinemia occurs in most patients receiving dapsone. Heinz body formation also occurs frequently.

Dapsone is administered orally. For administration to children, commercially available tablets of dapsone have been crushed and dissolved in strawberry syrup; however, studies evaluating bioavailability of the drug following administration of this preparation have not been published to date.

Dapsone is used in rifampin-based multiple-drug regimens for the treatment of multibacillary and paucibacillary leprosy. Although dapsone was used alone in the past for the treatment of leprosy, the World Health Organization (WHO) and most clinicians currently recommend that rifampin-based multiple-drug regimens be used for the treatment of all forms of leprosy. Multiple-drug regimens may reduce infectiousness of the patient more rapidly as well as delay or prevent the emergence of resistant organisms. Rifampin-based regimens are necessary because of the increasing incidence of dapsone-resistant Mycobacterium leprae, and these regimens are designed to be effective against all strains of M. leprae, regardless of their susceptibility to dapsone.

Clofazimine is administered orally. Clofazimine should be taken with a meal to maximize absorption of the drug. The usual adult dosage of clofazimine for the treatment of leprosy is 50-100 mg once daily. Clofazimine also is given in a dosage regimen that includes 50 mg once daily plus an additional 300-mg dose given once monthly.

Clofazimine is used in rifampin-based multiple-drug regimens for the treatment of multibacillary and paucibacillary leprosy. The drug also has been used in the treatment and prevention of erythema nodosum leprosum (ENL) reactions (lepra type 2 reactions) in leprosy patients.

Rifapentine has an antibacterial spectrum of activity similar to that of rifampin; however, on a molar basis, rifapentine and its active 25-desacetyl metabolite generally are more active than rifampin against Mycobacterium tuberculosis and more active than rifampin but less active than rifabutin against M. avium complex (MAC). The clinical relevance of activity of rifapentine against other mycobacterial species has not been established.

Rifapentine is used in conjunction with other antituberculosis agents in the treatment of clinical tuberculosis. The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) currently recommend several possible multiple-drug regimens for the treatment of culture-positive pulmonary tuberculosis.

In addition, HIV protease inhibitors and some NNRTIs (e.g., delavirdine) reduce the metabolism of rifamycins, leading to increased plasma concentrations of rifamycins and an increased risk of toxicity. The potential for alterations in the plasma concentrations of antimycobacterial agent(s) and/or antiretroviral agent(s) must be considered when antimycobacterial agents are indicated for the management of latent or active tuberculosis or the prophylaxis or treatment of Mycobacterium avium complex (MAC) infections in HIV-infected patients who are receiving or are being considered for antiretroviral therapy. Although pharmacokinetic data and clinical experience are limited, some experts state that concomitant use of ritonavir (with or without saquinavir) and usual dosages of rifampin for the treatment of tuberculosis (600 mg daily or 2 or 3 times weekly) is a possibility. These experts state that rifampin can be used for the treatment of active tuberculosis in patients receiving an antiretroviral regimen that includes ritonavir and one or more nucleoside reverse transcriptase inhibitors.

The most frequent adverse effects of rifampin are GI disturbances, which include heartburn, epigastric distress, nausea, vomiting, anorexia, abdominal cramps, flatulence, and diarrhea. Rarely, adverse GI effects may be severe enough to require discontinuance of the drug.