Contraindicated in patients with a known hypersensitivity to ritonavir or any of product ingredients.
Unplanned antiretroviral therapy interruption may be necessary in specific situations, such as serious drug toxicity, intercurrent illness or surgery precluding oral intake, severe hyperemesis gravidarum unresponsive to antiemetics, or drug non-availability. If short-term treatment interruption (i.e., < 1—2 days) is necessary, in general it is recommended that all antiretroviral agents be discontinued simultaneously, especially if the interruption is because of serious toxicity. However, if a short-term treatment interruption is anticipated in the case of elective surgery, the pharmacokinetic properties and food requirements of specific drugs should be considered. When the antiretroviral regimen contains drugs with differing half-lives, stopping all drugs simultaneously may result in functional monotherapy of the drug with the longest half-life. For example, after discontinuation, the duration of detectable drug concentrations of efavirenz and nevirapine range from < 1 week to > 3 weeks. Simultaneously stopping all drugs in a regimen containing these agents may result in functional monotherapy with the NNRTI and may increase the risk of NNRTI-resistant mutations. Planned long-term treatment interruptions are not recommended due to the potential for HIV disease progression (i.e., declining CD4 counts, viral rebound, acute viral syndrome), development of minor HIV-associated manifestations or serious non-AIDS complications, development of drug resistance, increased risk of HIV transmission, and increased risk for opportunistic infections. If therapy must be discontinued, counsel patient on the potential risks and closely monitor for any clinical or laboratory abnormalities.[46638] [42452]
Due to its potent inhibition of the CYP3A4 enzyme system, ritonavir coadministration with other drugs should be done with extreme caution. Specifically, the administration of certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, and ergot alkaloids to patients receiving ritonavir can result in serious and potentially life-threatening adverse reactions due to inhibited metabolism and, hence, increased concentrations of the coadministered drug. See the Interactions section for more specific information.[28315]
Ritonavir should be used with caution in patients with pre-existing hepatic disease, liver enzyme abnormalities, jaundice, or hepatitis due to an increased risk for transaminase elevations during ritonavir therapy. Frequent monitoring of hepatic enzymes should be considered in these patients, especially during the first 3 months of therapy. Ritonavir should be used with caution in patients with moderate to severe hepatic impairment patients; dosage adjustment is not needed in patients with mild hepatic impairment. All patients presenting with HIV infection should be screened for hepatitis B virus (HBV) coinfection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts). HIV treatment guidelines recommend these patients receive an ARV regimen that contains tenofovir with either lamivudine or emtricitabine as a dual NRTI backbone. If tenofovir cannot be used, another agent with anti-HBV activity should be used in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection; avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, adefovir, entecavir, or telbivudine as the only active agent) as this may result in HIV and HBV resistant strains. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still requires treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate .[28315] [47165] [46638] [38918]
Patients with advanced acquired immunodeficiency syndrome (AIDS) may be at increased risk for developing hypertriglyceridemia and pancreatitis. Patients who exhibit signs or symptoms of pancreatitis should discontinue treatment with ritonavir. Fat redistribution and hyperlipidemia have become increasingly recognized side effects with the use of protease inhibitors. Triglyceride and cholesterol testing should be performed prior to beginning ritonavir and at regular intervals during treatment. According to CDC guidelines, patients with hypertriglyceridemia or hypercholesterolemia should be evaluated for risks for cardiovascular events and pancreatitis. If a patient develops hyperlipidemia during treatment with a protease inhibitor, possible interventions include dietary modification, use of lipid lowering agents, or discontinuation of the protease inhibitor. Clinicians should be aware of the potential drug interaction between certain cholesterol-lowering agents and ritonavir.
Patients with diabetes mellitus or hyperglycemia may experience an exacerbation of their condition during ritonavir treatment. Some patients may require either initiation or dose adjustments of insulin or oral hyperglycemic agents. Patients should be monitored closely for new onset diabetes mellitus, diabetic ketoacidosis, or hyperglycemia.
Protease inhibitors such as ritonavir should be used cautiously in patients with hemophilia A or B due to reports of spontaneous bleeding episodes requiring treatment with additional factor VIII. In many cases, treatment with protease inhibitors was continued or restarted. A casual relationship has not been established.
Testing for HIV antimicrobial resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform antimicrobial resistance testing prior to initiating or changing any HIV treatment regimen.[42452] [46638] Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. In the US and Europe, recent studies suggest that 6—16% of transmitted virus will be resistant to at least one antiretroviral drug, with 3—5% exhibiting reduced susceptibility to more than one class of drugs; therefore, resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. Varying degrees of cross-resistance among protease inhibitors have been observed. Continued administration of ritonavir following loss of viral suppression may increase the likelihood of antimicrobial resistance to other protease inhibitors. In studies of indinavir with ritonavir, saquinavir, and amprenavir, the extent and spectrum of cross-resistance varied with the specific HIV mutational patterns observed; the degree of cross-resistance typically increased with the accumulation of resistance-associated amino acid substitutions. Within a panel of 29 viral isolates from indinavir-treated patients that exhibited measurable phenotypic resistance to indinavir, all were resistant to ritonavir and of the indinavir resistant HIV isolates, 63% showed resistance to saquinavir and 81% to amprenavir.[46638]
The safety and effectiveness of ritonavir in neonates (i.e., those < 1 month of age) have not been established. Administering ritonavir oral solution to neonates before a postmenstrual age of 44 weeks (first day of the mother's last menstrual period to birth plus the time since birth) may result in significant alcohol and propylene glycol-related toxicities; use is not recommended. Premature neonates are especially at risk as they have a diminished ability to metabolize propylene glycol and ethanol may additionally competitively inhibit propylene glycol metabolism. If the benefits of using the oral solution in a neonate immediately after birth outweighs the potential risk, the manufacturer recommends monitoring for increases in serum osmolarity, serum creatinine, and for adverse events such as hyperosmolarity, lactic acidosis, renal toxicity, CNS depression (stupor, coma, apnea), seizures, hypotonia, cardiac arrhythmias (ECG changes), and hemolysis. In adolescents, children, and infants, the adverse events reported during clinical trials and post-marketing surveillance were similar to adults. When dosing and administering the oral solution to any pediatric patient, use caution to avoid an overdosage. The solution contains 43.2% (v/v) alcohol and 26.57% (w/v) propylene glycol; an accidental overdosage by a young child could result in significant propylene glycol or alcohol-related toxicities including death. For infants between the ages 1—6 months, health care providers are advised to calculate the total amounts of alcohol and propylene glycol from all medications that are being administered to patient.[28315] [47165]
Antiretroviral therapy should be provided to all women during pregnancy, rega
Contraindicated ในผู้ป่วยที่ มีความไวต่อยารู้จักริโตนาเวียร์หรือใด ๆ ของส่วนผสมผลิตภัณฑ์หยุดชะงักด้วยที่ไม่ได้วางแผนการรักษาอาจจำเป็นในสถานการณ์ที่เฉพาะเจาะจง เช่นความเป็นพิษของยาเสพติดร้ายแรง intercurrent เจ็บป่วย หรือผ่าตัด precluding ปาก บริโภค gravidarum hyperemesis รุนแรงที่ไม่ตอบสนองการ antiemetics ไม่ใช่ยาเสพติด-มี ถ้าหยุดชะงักรักษาระยะสั้น (เช่น < 1 – 2 วัน) จำเป็น โดยทั่วไป แนะนำที่ ถูกยกเลิกตัวแทนทั้งหมดด้วยกัน โดยเฉพาะอย่างยิ่งถ้าถูกขัดจังหวะเนื่องจากความเป็นพิษร้ายแรง อย่างไรก็ตาม ถ้าถูกขัดจังหวะการรักษาระยะสั้นคาดในกรณีผ่าตัดวิชาเลือก pharmacokinetic คุณสมบัติและความต้องการอาหารเฉพาะยาเสพติดควร เมื่อระบบการปกครองด้วยประกอบด้วยยาเสพติด มีครึ่งชีวิตที่แตกต่าง การหยุดยาทั้งหมดพร้อมกันอาจส่งผลใน monotherapy ทำงานของยาที่มี half-life ยาวที่สุด ตัวอย่าง หลัง discontinuation ระยะเวลาการตรวจยาความเข้มข้นของอีฟาวิเรนซ์และ nevirapine ช่วงจาก < 1 สัปดาห์ > 3 สัปดาห์ หยุดยาทั้งหมดในระบบการปกครองประกอบด้วยตัวแทนเหล่านี้พร้อมกันอาจทำหน้าที่ monotherapy มี NNRTI และอาจเพิ่มความเสี่ยงของการกลายพันธุ์ NNRTI ทน ขัดจังหวะการรักษาระยะยาวแผนจะไม่แนะนำเนื่องจากเป็นเชื้อเอชไอวีโรคก้าวหน้า (เช่น คำนวณตรวจนับ CD4 ไวรัสฟื้นตัว อาการไวรัสเฉียบพลัน), พัฒนาลักษณะรองที่เกี่ยวข้องกับเอชไอวี หรือภาวะแทรกซ้อนรุนแรงไม่ใช่เอดส์ ยา ความเสี่ยงเพิ่มขึ้นการส่งเอชไอวี และความเสี่ยงเพิ่มขึ้นสำหรับการติดเชื้อฉวยโอกาส ถ้าต้องถูกยกเลิกการรักษา แนะนำผู้ป่วยในเสี่ยง และติดตามอย่างใกล้ชิดใด ๆ ทางคลินิก หรือความผิดปกติทางห้องปฏิบัติการ [46638] [42452]Coadministration ริโตนาเวียร์กับยาอื่นควรทำ ด้วยความระมัดระวังมากเนื่องจากการยับยั้งการมีศักยภาพของระบบเอนไซม์ CYP3A4 เฉพาะ การจัดการบางอย่าง nonsedating antihistamines, sedative hypnotics, antiarrhythmics และ ergot alkaloids จะรับริโตนาเวียร์อาจส่งผลร้ายแรง และอาจอายุส่วนปฏิกิริยาร้ายเนื่องห้ามเผาผลาญ และ ดังนั้น เพิ่มความเข้มข้นของยา coadministered ดูส่วนโต้ตอบสำหรับข้อมูลเฉพาะเพิ่มเติม [28315]Ritonavir should be used with caution in patients with pre-existing hepatic disease, liver enzyme abnormalities, jaundice, or hepatitis due to an increased risk for transaminase elevations during ritonavir therapy. Frequent monitoring of hepatic enzymes should be considered in these patients, especially during the first 3 months of therapy. Ritonavir should be used with caution in patients with moderate to severe hepatic impairment patients; dosage adjustment is not needed in patients with mild hepatic impairment. All patients presenting with HIV infection should be screened for hepatitis B virus (HBV) coinfection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts). HIV treatment guidelines recommend these patients receive an ARV regimen that contains tenofovir with either lamivudine or emtricitabine as a dual NRTI backbone. If tenofovir cannot be used, another agent with anti-HBV activity should be used in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection; avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, adefovir, entecavir, or telbivudine as the only active agent) as this may result in HIV and HBV resistant strains. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. For patients who refuse a fully suppressive ARV regimen, but still requires treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate .[28315] [47165] [46638] [38918]ผู้ป่วยที่ มีอาการขั้นสูงได้รับเอชไอวี (เอดส์) ได้ที่มีความเสี่ยงเพิ่มขึ้นสำหรับการพัฒนา hypertriglyceridemia และ pancreatitis ผู้ป่วยที่แสดงอาการหรือโรค pancreatitis ควรหยุดการรักษา ด้วยริโตนาเวียร์ ซอร์สไขมันและไขมันในเลือดสูงได้เป็น ผลข้างเคียงมากขึ้นรู้จักใช้ inhibitors รติเอส ไตรกลีเซอไรด์และไขมันทดสอบควรจะทำ ก่อนเริ่มริโตนาเวียร์ และ อย่างสม่ำเสมอในระหว่างการรักษา ผู้ป่วยที่ มี hypertriglyceridemia หรือ hypercholesterolemia ควรประเมินความเสี่ยงสำหรับเหตุการณ์หัวใจและหลอดเลือดและ pancreatitis ตามคำแนะนำของ CDC ถ้าผู้ป่วยพัฒนาไขมันในเลือดสูงในระหว่างการรักษากับผลรติเอส การแทรกแซงได้รวมถึงปรับเปลี่ยนอาหาร ใช้ไขมันลดตัวแทน หรือ discontinuation ของสารยับยั้งรติเอส Clinicians ควรทราบของการโต้ตอบยาที่อาจเกิดขึ้นระหว่างบางลดไขมันแทนริโตนาเวียร์ผู้ป่วยที่ มีเบาหวานหรือ hyperglycemia อาจ exacerbation ของสภาพของพวกเขาในระหว่างการรักษาริโตนาเวียร์ ผู้ป่วยบางส่วนอาจต้องการเริ่มต้นหรือปรับยาอินซูลินหรือตัวแทน hyperglycemic ปาก ควรติดตามผู้ป่วยอย่างใกล้ชิดสำหรับใหม่เริ่มมีอาการเบาหวาน โรคเบาหวาน ketoacidosis หรือ hyperglycemiaควรใช้ inhibitors รติเอสเช่นริโตนาเวียร์เดินในผู้ป่วย hemophilia A หรือ B เนื่องจากรายงานขาดตอนมีเลือดออกต้องบำบัด ด้วยการเติมปัจจัย VIII ในหลายกรณี รักษากับรติเอส inhibitors ถูกต่อ หรือเริ่มใหม่ ไม่การสร้างความสัมพันธ์ที่ไม่เป็นทางการTesting for HIV antimicrobial resistance is recommended in all antiretroviral treatment-naive patients at the time of HIV diagnosis, regardless of whether treatment will be initiated. Additionally, perform antimicrobial resistance testing prior to initiating or changing any HIV treatment regimen.[42452] [46638] Transmission of drug-resistant HIV strains has been both well documented and associated with suboptimal virologic response to initial antiretroviral therapy. In the US and Europe, recent studies suggest that 6—16% of transmitted virus will be resistant to at least one antiretroviral drug, with 3—5% exhibiting reduced susceptibility to more than one class of drugs; therefore, resistance testing at baseline can help optimize treatment and, thus, virologic response. In the absence of therapy, resistant viruses may decline over time to less than the detection limit of standard resistance tests, but may still increase the risk of treatment failure when therapy is eventually initiated. Thus, if therapy is deferred, resistance testing should still be performed during acute HIV infection with the genotypic resistance test result kept in the patient's medical record until it becomes clinically useful. Because of the possibility of acquisition of another drug-resistant virus before treatment initiation, repeat resistance testing at the time therapy is initiated would be prudent. Varying degrees of cross-resistance among protease inhibitors have been observed. Continued administration of ritonavir following loss of viral suppression may increase the likelihood of antimicrobial resistance to other protease inhibitors. In studies of indinavir with ritonavir, saquinavir, and amprenavir, the extent and spectrum of cross-resistance varied with the specific HIV mutational patterns observed; the degree of cross-resistance typically increased with the accumulation of resistance-associated amino acid substitutions. Within a panel of 29 viral isolates from indinavir-treated patients that exhibited measurable phenotypic resistance to indinavir, all were resistant to ritonavir and of the indinavir resistant HIV isolates, 63% showed resistance to saquinavir and 81% to amprenavir.[46638]The safety and effectiveness of ritonavir in neonates (i.e., those < 1 month of age) have not been established. Administering ritonavir oral solution to neonates before a postmenstrual age of 44 weeks (first day of the mother's last menstrual period to birth plus the time since birth) may result in significant alcohol and propylene glycol-related toxicities; use is not recommended. Premature neonates are especially at risk as they have a diminished ability to metabolize propylene glycol and ethanol may additionally competitively inhibit propylene glycol metabolism. If the benefits of using the oral solution in a neonate immediately after birth outweighs the potential risk, the manufacturer recommends monitoring for increases in serum osmolarity, serum creatinine, and for adverse events such as hyperosmolarity, lactic acidosis, renal toxicity, CNS depression (stupor, coma, apnea), seizures, hypotonia, cardiac arrhythmias (ECG changes), and hemolysis. In adolescents, children, and infants, the adverse events reported during clinical trials and post-marketing surveillance were similar to adults. When dosing and administering the oral solution to any pediatric patient, use caution to avoid an overdosage. The solution contains 43.2% (v/v) alcohol and 26.57% (w/v) propylene glycol; an accidental overdosage by a young child could result in significant propylene glycol or alcohol-related toxicities including death. For infants between the ages 1—6 months, health care providers are advised to calculate the total amounts of alcohol and propylene glycol from all medications that are being administered to patient.[28315] [47165]Antiretroviral therapy should be provided to all women during pregnancy, rega
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