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Medicamente revisado por Fedorchenko Olga Valeryevna, Farmácia Última atualização em 03.04.2022
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As cápsulas de macbutina são indicadas para a prevenção da doença disseminada do complexo Mycobacterium avium (MAC) em pacientes com infecção avançada pelo HIV.
Recomenda-se que as cápsulas de Macbutin sejam administradas na dose de 300 mg uma vez ao dia. Para aqueles pacientes com propensão a náusea, vômito ou outra perturbação gastrointestinal, a administração de Macbutin em doses de 150 mg duas vezes ao dia tomadas com alimentos pode ser útil.
Para pacientes com insuficiência renal grave (depuração da creatinina inferior a 30 mL / min), considere reduzir a dose de Macbutinina em 50%, se houver suspeita de toxicidade. Não é necessário ajuste posológico em pacientes com insuficiência renal leve a moderada. Também pode ser necessária uma redução da dose de Macbutin em pacientes que recebem tratamento concomitante com outros medicamentos (ver INTERAÇÕES DE DROGAS).
Compromisso hepático leve não requer uma modificação da dose. A farmacocinética da rifabutina em pacientes com insuficiência hepática moderada e grave não é conhecida.
As cápsulas de macbutina são contra-indicadas em pacientes que tiveram hipersensibilidade clinicamente significativa à rifabutina ou a quaisquer outras rifamicinas.
WARNINGS
Tuberculosis
Macbutin Capsules must not be administered for MAC prophylaxis to patients with active tuberculosis. Patients who develop complaints consistent with active tuberculosis while on prophylaxis with Macbutin should be evaluated immediately, so that those with active disease may be given an effective combination regimen of anti-tuberculosis medications. Administration of Macbutin as a single agent to patients with active tuberculosis is likely to lead to the development of tuberculosis that is resistant both to Macbutin and to rifampin.
There is no evidence that Macbutin is an effective prophylaxis against M. tuberculosis. Patients requiring prophylaxis against both M. tuberculosis and Mycobacterium avium complex may be given isoniazid and Macbutin concurrently.
Tuberculosis in HIV-positive patients is common and may present with atypical or extrapulmonary findings. Patients are likely to have a nonreactive purified protein derivative (PPD) despite active disease. In addition to chest X-ray and sputum culture, the following studies may be useful in the diagnosis of tuberculosis in the HIV-positive patient: blood culture, urine culture, or biopsy of a suspicious lymph node.
MAC Treatment With Clarithromycin
When Macbutin is used concomitantly with clarithromycin for MAC treatment, a decreased dose of Macbutin is recommended due to the increase in plasma concentrations of Macbutin (see DRUG INTERACTIONS, Table 2).
Hypersensitivity And Related Reactions
Hypersensitivity reactions may occur in patients receiving rifamycins. Signs and symptoms of these reactions may include hypotension, urticaria, angioedema, acute bronchospasm, conjunctivitis, thrombocytopenia, neutropenia or flu-like syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, fever, chills, aches, rash, itching, sweats, dizziness, shortness of breath, chest pain, cough, syncope, palpitations). There have been reports of anaphylaxis with the use of rifamycins.
Monitor patients receiving Macbutin therapy for signs and/or symptoms of hypersensitivity reactions. If these symptoms occur, administer supportive measures and discontinue Macbutin.
Uveitis
Due to the possible occurrence of uveitis, patients should also be carefully monitored when Macbutin is given in combination with clarithromycin (or other macrolides) and/or fluconazole and related compounds (see DRUG INTERACTIONS, Table 2). If uveitis is suspected, the patient should be referred to an ophthalmologist and, if considered necessary, treatment with Macbutin should be suspended (see also ADVERSE REACTIONS).
Clostridium Difficile Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Macbutin (rifabutin) Capsules, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Protease Inhibitor Drug Interaction
Protease inhibitors act as substrates or inhibitors of CYP3A4 mediated metabolism. Therefore, due to significant drug-drug interactions between protease inhibitors and rifabutin, their concomitant use should be based on the overall assessment of the patient and a patient-specific drug profile. The concomitant use of protease inhibitors may require at least a 50% reduction in rifabutin dose, and depending on the protease inhibitor, an adjustment of the antiviral drug dose. Increased monitoring for adverse events is recommended when using these drug combinations (see DRUG INTERACTIONS). For further recommendations, please refer to current, official product monographs of the protease inhibitor or contact the specific manufacturer.
PRECAUTIONS
General
Because treatment with Macbutin Capsules may be associated with neutropenia, and more rarely thrombocytopenia, physicians should consider obtaining hematologic studies periodically in patients receiving prophylaxis with Macbutin.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term carcinogenicity studies were conducted with rifabutin in mice and in rats. Rifabutin was not carcinogenic in mice at doses up to 180 mg/kg/day, or approximately 36 times the recommended human daily dose. Rifabutin was not carcinogenic in the rat at doses up to 60 mg/kg/day, about 12 times the recommended human dose.
Rifabutin was not mutagenic in the bacterial mutation assay (Ames Test) using both rifabutin-susceptible and resistant strains. Rifabutin was not mutagenic in Schizosaccharomyces pombe P1 and was not genotoxic in V-79 Chinese hamster cells, human lymphocytes in vitro, or mouse bone marrow cells in vivo.
Fertility was impaired in male rats given 160 mg/kg (32 times the recommended human daily dose).
Pregnancy
Rifabutin should be used in pregnant women only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant or breastfeeding women.
Reproduction studies have been carried out in rats and rabbits given rifabutin using dose levels up to 200 mg/kg (about 6 to 13 times the recommended human daily dose based on body surface area comparisons). No teratogenicity was observed in either species. In rats, given 200 mg/kg/day, (about 6 times the recommended human daily dose based on body surface area comparisons), there was a decrease in fetal viability. In rats, at 40 mg/kg/day (approximately equivalent to the recommended human daily dose based on body surface area comparisons), rifabutin caused an increase in fetal skeletal variants. In rabbits, at 80 mg/kg/day (about 5 times the recommended human daily dose based on body surface area comparisons), rifabutin caused maternotoxicity and increase in fetal skeletal anomalies. Because animal reproduction studies are not always predictive of human response, rifabutin should be used in pregnant women only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether rifabutin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness of rifabutin for prophylaxis of MAC in children have not been established. Limited safety data are available from treatment use in 22 HIV-positive children with MAC who received Macbutin in combination with at least two other antimycobacterials for periods from 1 to 183 weeks. Mean doses (mg/kg) for these children were: 18.5 (range 15.0 to 25.0) for infants 1 year of age, 8.6 (range 4.4 to 18.8) for children 2 to 10 years of age, and 4.0 (range 2.8 to 5.4) for adolescents 14 to 16 years of age. There is no evidence that doses greater than 5 mg/kg daily are useful. Adverse experiences were similar to those observed in the adult population, and included leukopenia, neutropenia, and rash. In addition, corneal deposits have been observed in some patients during routine ophthalmologic surveillance of HIV-positive pediatric patients receiving Macbutin as part of a multiple-drug regimen for MAC prophylaxis. These are tiny, almost transparent, asymptomatic peripheral and central corneal deposits which do not impair vision. Doses of Macbutin may be administered mixed with foods such as applesauce.
Geriatric Use
Clinical studies of Macbutin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see CLINICAL PHARMACOLOGY).
Reações adversas de ensaios clínicos
As cápsulas de macbutin foram geralmente bem toleradas nos ensaios clínicos controlados. A descontinuação da terapia devido a um evento adverso foi necessária em 16% dos pacientes que receberam Macbutin, em comparação com 8% dos pacientes que receberam placebo nesses estudos. As principais razões para a descontinuação da Macbutin foram erupção cutânea (4% dos pacientes tratados), intolerância gastrointestinal (3%) e neutropenia (2%).
A tabela a seguir enumera experiências adversas que ocorreram com uma frequência de 1% ou mais, entre os pacientes tratados com Macbutin nos estudos 023 e 027.
Tabela: 3 Experiências clínicas adversas relatadas em ≥ 1% dos pacientes tratados com macbutina
Evento adverso | Macbutin (n = 566)% | Placebo (n = 580)% |
Corpo como um todo | ||
Dor abdominal | 4 | 3 |
Astenia | 1 | 1 |
Dor no peito | 1 | 1 |
Febre | 2 | 1 |
Dor de cabeça | 3 | 5 |
Dor | 1 | 2 |
Sangue e sistema linfático | ||
Leucopenia | 10 | 7 |
Anemia | 1 | 2 |
Sistema Digestivo | ||
Anorexia | 2 | 2 |
Diarréia | 3 | 3 |
Dispepsia | 3 | 1 |
Erutação | 3 | 1 |
Flatulência | 2 | 1 |
Náusea | 6 | 5 |
Náusea e vômito | 3 | 2 |
Vômitos | 1 | 1 |
Sistema músculo-esquelético | ||
Mialgia | 2 | 1 |
Sistema nervoso | ||
Insônia | 1 | 1 |
Pele e anexos | ||
Erupção cutânea | 11 | 8 |
Sentidos especiais | ||
Proversão de sabor | 3 | 1 |
Sistema urogenital | ||
Urina descolorida | 30 | 6 |
Eventos adversos clínicos relatados em <1% dos pacientes que receberam macbutina
Considerando os dados dos ensaios principais 023 e 027, e de outros estudos clínicos, A macbutinina parece ser uma causa provável dos seguintes eventos adversos que ocorreram em menos de 1% dos pacientes tratados: síndrome do tipo gripe, hepatite, hemólise, artralgia, miosite, pressão torácica ou dor com dispnéia, descoloração da pele, trombocitopenia, pancitopenia e icterícia.
Os seguintes eventos adversos ocorreram em mais de um paciente que recebeu Macbutin, mas não foi estabelecido um papel etiológico: convulsão, parestesia, afasia, confusão e alterações inespecíficas da onda T no eletrocardiograma.
Quando Macbutin foi administrado em doses de 1050 mg / dia a 2400 mg / dia, foram relatadas artralgia e uveíte generalizadas. Essas experiências adversas diminuíram quando o Macbutin foi descontinuado.
Uveíte leve a grave e reversível foi relatada com menos frequência quando Macbutin é usado a 300 mg como monoterapia na profilaxia MAC versus Macbutin em combinação com claritromicina para tratamento com MAC (ver também AVISO).
A uveíte tem sido relatada com pouca frequência quando a macbutina é usada a 300 mg / dia como monterapia na profilaxia MAC de pessoas infectadas pelo HIV, mesmo com o uso concomitante de fluconazol e / ou antibacterianos macrólidos. No entanto, se doses mais altas de Macbutin são administradas em combinação com esses agentes, a incidência de uveíte é maior.
Os pacientes que desenvolveram uveíte apresentaram sintomas leves a graves que foram resolvidos após o tratamento com corticosteróides e / ou colírios midriáticos; em alguns casos graves, no entanto, a resolução dos sintomas ocorreu após várias semanas.
Quando a uveíte ocorre, recomenda-se a descontinuação temporária da Macbutin e a avaliação oftalmológica. Na maioria dos casos leves, o Macbutin pode ser reiniciado; no entanto, se os sinais ou sintomas se repetirem, o uso de Macbutin deve ser interrompido (Relatório Semanal sobre Morbidade e Mortalidade, 9 de setembro de 1994).
Depósitos de córnea foram relatados durante a vigilância oftalmológica de rotina de alguns pacientes pediátricos HIV positivos que receberam Macbutin como parte de um regime de múltiplos medicamentos para profilaxia MAC. Os depósitos são pequenos depósitos de córnea periférica e central assintomáticos e não prejudicam a visão.
A tabela a seguir enumera as alterações nos valores laboratoriais que foram consideradas anormalidades laboratoriais nos Estudos 023 e 027.
Tabela 4: Porcentagem de pacientes com anormalidades laboratoriais
Anormalidades laboratoriais | Macbutin (n = 566)% | PLACEBO (n = 580)% |
Química | ||
Fosfatase alcalina aumentada * | <1 | 3 |
SGOT aumentado † | 7 | 12 |
SGPT aumentado † | 9 | 11 |
Hematologia | ||
Anemia ‡ | 6 | 7 |
Eosinofilia | 1 | 1 |
Leucopenia § | 17 | 16 |
Neutropenia ¶ | 25 | 20 |
Trombocitopenia # | 5 | 4 |
Inclui toxicidades de grau 3 ou 4, conforme especificado : * Todos os valores> 4 50 U / L † Todos os valores> 150 U / L ‡ Todos os valores de hemoglobina <8,0 g / dL § Todos os valores do leucócitos <1.500 / mm³ ¶Todos os valores de ANC <750 / mm³ #Todos os valores de contagem de plaquetas <50.000 / mm³ |
A incidência de neutropenia em pacientes tratados com Macbutin foi significativamente maior do que em pacientes tratados com placebo (p = 0,03). Embora a trombocitopenia não tenha sido significativamente mais comum entre os pacientes tratados com Macbutin nesses ensaios, a Macbutin tem sido claramente ligada à trombocitopenia em casos raros. Um paciente do Estudo 023 desenvolveu púrpura trombocitopênica trombótica, que foi atribuída à Macbutin.
Reações adversas da experiência pós-comercialização
As reações adversas identificadas por meio da vigilância pós-comercialização por classe de órgãos do sistema (SOC) estão listadas abaixo :
Doenças do sangue e do sistema linfático: Distúrbios dos glóbulos brancos (incluindo agranulocitose, linfopenia, granulocitopenia, neutropenia, contagem de glóbulos brancos diminuída, contagem de neutrófilos diminuída), contagem de plaquetas diminuída.
Distúrbios do sistema imunológico: Hipersensibilidade, broncoespasmo, erupção cutânea e eosinofilia.
Distúrbios gastrointestinais: Clostridium difficile colite / Clostridium difficile diarréia associada.
Podem ocorrer pirexia, erupção cutânea e outras reações de hipersensibilidade, como eosinofilia e broncoespasmo, como foi observado em outros antibacterianos.
Um número limitado de descoloração da pele foi relatado.
Reações de hipersensibilidade à rifamicina
Foram relatadas hipersensibilidade às rifamicinas, incluindo sintomas semelhantes aos da gripe, broncoespasmo, hipotensão, urticária, angioedema, conjuntivite, trombocitopenia ou neutropenia.
Nenhuma informação está disponível sobre superdosagem acidental em humanos.
Tratamento
Embora não exista experiência no tratamento de sobredosagem com cápsulas de Macbutin, a experiência clínica com rifamicinas sugere que a lavagem gástrica evacue o conteúdo gástrico (algumas horas após a overdose) seguido pela instilação de uma pasta de carvão ativada no estômago, pode ajudar a absorver qualquer medicamento restante do trato gastrointestinal.
A rifabutina é 85% ligada às proteínas e distribuída extensivamente nos tecidos (Vss: 8 a 9 L / kg). Não é excretado principalmente pela via urinária (menos de 10% como medicamento inalterado); portanto, não se espera que a hemodiálise nem a diurese forçada melhorem a eliminação sistêmica da rifabutina inalterada do corpo em um paciente com overdose de Macbutin.
Some drugs that inhibit CYP3A may significantly increase the plasma concentration of rifabutin. Therefore, carefully monitor for rifabutin associated adverse events in those patients also receiving CYP3A inhibitors, which include fluconazole and clarithromycin. In some cases, the dosage of Macbutin may need to be reduced when it is coadministered with CYP3A inhibitors.
Table 2 summarizes the results and magnitude of the pertinent drug interactions assessed with rifabutin. The clinical relevance of these interactions and subsequent dose modifications should be judged in light of the population studied, severity of the disease, patient's drug profile, and the likely impact on the risk/benefit ratio.
Table 2 : Rifabutin Interaction Studies
Coadministered drug | Dosing regimen of coadministered drug | Dosing regimen of rifabutin | Study population (n) | Effect on rifabutin | Effect on coadministered drug | Recommendation |
ANTIVIRALS | ||||||
Amprenavir | 1200 mg BID x 10 days | 300 mg QD x 10 days | Healthy male subjects (6) | ↑ AUC by 193%, ↑ Cmax by 119% | ↔ | Reduce rifabutin dose by at least 50%. Monitor closely for adverse reactions. |
Delavirdine | 400 mg TID | 300 mg QD | HIV-infected patients (7) | ↑ AUC by 230%, ↑ Cmax by 128% | ↓ AUC by 80%, ↓ Cmax by 75%, ↓ Cmin by 17% | CONTRAINDICATED |
Didanosine | 167 or 250 mg BID x 12 days | 300 or 600 mg QD x 1 | HIV- infected patients (11) | ↔ | ↔ | |
Fosamprenavir/ ritonavir | 700 mg BID plus ritonavir 100 mg BID × 2 weeks | 150 mg every other day × 2 weeks | Healthy subjects (15) | ↔A UC* ↓ Cmax by 15% | ↑ AUC by 35%†, ↑ Cmax by 36%, ↑ Cmin by 36%, | Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with fosamprenavir/ritonavir combination. |
Indinavir | 800 mg TID x 10 days | 300 mg QD x 10 days | Healthy subjects (10) | ↑ AUC by 173%, ↑ Cmax by 134% | ↓ AUC by 34%, ↓ Cmax by 25%, ↓ Cmin by 39% | Reduce rifabutin dose by 50%, and increase indinavir dose from 800 mg to 1000 mg TID. |
Lopinavir/ ritonavir | 400/100 mg BID x 20 days | 150 mg QD x 10 days | Healthy subjects (14) | ↑ AUC by 203%‡ ↓ Cmax by 112% | ↔ | Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with lopinavir/ritonavir combination. Monitor closely for adverse reactions. Reduce rifabutin dosage further, as needed. |
Saquinavir/ ritonavir | 1000/100 mg BID x 14 or 22 days | 150 mg e ve ry 3 days x 21-22 days | Healthy subjects | ↑ AUC by 53%§ ↑ Cmax by 88% (n=11) | ↓ AUC by 13%, ↓ Cmax by 15%, (n=19) | Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with saquinavir/ritonavir combination. Monitor closely for adverse reactions. |
Ritonavir | 500 mg BID x 10 days | 150 mg QD x 16 days | Healthy subjects (5) | ↑ AUC by 300%, ↑ Cmax by 150% | ND | Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with lopinavir/ritonavir combination. Monitor closely for adverse reactions. Reduce rifabutin dosage further, as needed. |
Tipranavir/ ritonavir | 500/200 BID x 15 doses | 150 mg single dose | Healthy subjects (20) | ↑ AUC by 190%, ↑ Cmax by 70% | ↔ | Reduce rifabutin dose by at least 75% (to a maximum 150 mg every other day or three times per week) when given with tipranavir/ritonavir combination. Monitor closely for adverse reactions. Reduce rifabutin dosage further, as needed. |
Nenniavir | 1250 mg BIDx 7–8 days | 150 mg QD × 8 days | HIV- infected patients (11) | ↑ AUC by 83%,¶ ↑ Cmax by 19% | ↔ | Reduce rifabutin dose by 50% (to 150 mg QD) andincrease the nelfinavir dose to 1250 mg BID |
Zidovudine | 100 or 200 mg q4h | 300 or 450 mg QD | HIV- infected patients (16) | ↔ | ↓ AUC by 32%, ↓ Cmax by 48%, | Because zidovudine levels remained within the therapeutic range during coadministration of rifabutin, dosage adjustments are not necessary. |
ANTIFUNGALS | ||||||
Fluconazole | 200 mg QD x 2 weeks | g2 ExJS | HIV- infected patients (12) | ↑ AUC by 82%, ↑ Cmax by 88% | ↔ | Monitor for rifabutin associated adverse events. Reduce rifabutin dose or suspend Macbutin use if toxicity is suspected. |
Posaconazole | 200 mg QD x 10 days | 300 mg QD x 17 days | Healthy subjects (8) | ↑ AUC by 72%, ↑ Cmax< by 31% | ↓ AUC by 49%, ↓ Cmax by 43% | If co-administration of these two drugs cannot be avoided, patients should be monitored for adverse events associated with rifabutin administration, and lack o f po saco nazo le efficacy. |
Itraconazole | 200 mg QD | 300 mg QD | HIV-Infected patients (6) | ↑# | ↓ AUC by 70%, ↓ Cmax by 75%, | If co-administration of these two drugs cannot be avoided, patients should be monitored for adverse events associated with rifabutin administration, and lack of itraconazole efficacy. In a separate study, one case of uveitis was associated with increased serum rifabutin levels following coadministration of rifabutin (300 mg QD) with itraconazole (600900 mg QD). |
Voriconazole | 400 mg BID x 7 days (maintenance dose) | 300 mg QD x 7 days | Healthy male subjects (12) | ↑ AUC by 331%, ↑ Cmax by 195% | ↑ AUC by ~100%, ↑ Cmax by ~100%Þ | CONTRAINDICATED |
ANTI-PCP (Pneumocys tis carinii pneumonia) | ||||||
Dapsone | 50 mg QD | 300 mg QD | HIV- infected patients (16) | ND | ↓ AUC by 27 – 40% | |
Sulfamethoxazole- Trimethoprim | 800/160 mg | 300 mg QD | HIV- infected patients (12) | ↔ | ↓ AUC by 15– 20% | |
ANTI-MAC (Mycobacterium avium intracellulare complex) | ||||||
Azithromycin | 500 mg QD x 1 day, then 250 mg QD x 9 days | 300 mg QD | Healthy subjects (6) | ↔ | ↔ | |
Clarithromycin | 500 mg BID | 300 mg QD | HIV- infected patients (12) | ↑ AUC by 75% | ↓ AUC by 50% | Monitor for rifabutin associated adverse events. Reduce dose or suspend use of Macbutin if toxicity is suspected. Alternative treatment for clarithromycin should be considered when treating patients receiving rifabutin |
ANTI-TB (Tuberculosis) | ||||||
Ethambutol | 1200 mg | 300 mg QD x 7 days | Healthy subjects (10) | ND | ↔ | |
Isoniazid | 300 mg | 300 mg QD x 7 days | Healthy subjects (6) | ND | ↔ | |
OTHER | ||||||
Methadone | 20 - 100 mg QD | 300 mg QD x 13 days | HIV- infected patients (24) | ND | ↔ | |
Ethinylestradiol (EE)/N orethindrone (NE) | 35 mg EE / 1 mg NE x 21 days | 300 mg QD x 10 days | Healthy female subjects (22) | ND | EE: ↓ AUC by 35%, ↓ Cmax by 20% NE: ↓ AUC by 46% | Patients should be advised to use additional or alternative methods of contraception. |
Theophylline | 5 mg/kg | 300 mg x 14 days | Healthy subjects (11) | ND | ↔ | |
↑ indicates increase;↓ indicates decrease; ↔ indicates no significant change QD- once daily; BID- twice daily; TID - thrice daily ND - No Data AUC - Area under the Concentration vs. Time Curve; Cmax - Maximum serum concentration *compared to rifabutin 300 mg QD alone †compared to historical control (fosamprenavir/ritonavir 700/100 mg BID) ‡also taking zidovudine 500 mg QD §compared to rifabutin 150 mg QD alone ¶compared to rifabutin 300 mg QD alone #data from a case report Þcompared to voriconazole 200 mg BID alone |
However, we will provide data for each active ingredient