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Aptivus is a brand name for Tipranavir. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE APTIVUS, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected adults and pediatric patients weighing 36 kg or higher who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor (PI) [see Use in…
Verbatim from this product's FDA label. Tap a section to expand.
2 ) Pediatric patients (weighing 36 kg or higher): 500 mg APTIVUS, co-administered with 200 mg ritonavir twice daily. 1 ) Children should be assessed for their ability to swallow capsules before prescribing APTIVUS capsules. 1 ) Store unopened bottles of APTIVUS capsules in the refrigerator.
1 Dosage and Administration Overview APTIVUS must be co-administered with ritonavir to exert its therapeutic effect. 1) ] . 4) ] . 3) ] . APTIVUS is supplied as capsules. APTIVUS capsules must be swallowed whole and must not be opened or chewed.
Due to the need for co-administration of APTIVUS with ritonavir, please refer to the ritonavir prescribing information. 2 Recommended Dosage in Adults and Pediatric Patients Weighing 36 kg or Higher The recommended dosage in adults and pediatric patients weighing 36 kg or higher is 500 mg (two 250 mg capsules) of APTIVUS co-administered with 200 mg of ritonavir, twice daily.
6) ] Due to the need for co-administration of APTIVUS with ritonavir, please refer to ritonavir prescribing information for ritonavir-associated adverse reactions. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In adults the most frequent adverse reactions (incidence >4%) were diarrhea, nausea, pyrexia, vomiting, fatigue, headache, and abdominal pain. 1 ) In pediatric subjects the most frequent adverse reactions were generally similar to those seen in adults.
However, rash was more frequent in pediatric subjects than in adults. 2 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. gov/medwatch . 1 Clinical Trials in Adults APTIVUS, co-administered with ritonavir, has been studied in a total of 6308 HIV-1 positive adults as combination therapy in clinical studies.
Of these, 1299 treatment-experienced subjects received the dose of 500 mg/200 mg BID. 48 controlled clinical trials, have been treated for at least 48 weeks [ see Clinical Studies (14) ]. 48 in the APTIVUS/ritonavir arm, the most frequent adverse reactions were diarrhea, nausea, pyrexia, vomiting, fatigue, headache, and abdominal pain.
8% for the comparator arm subjects. 48, based on treatment-emergent clinical adverse reactions of moderate to severe intensity (Grades 2 - 4) in at least 2% of treatment-experienced subjects in either treatment group are summarized in Table 2 below.
48 in adults are summarized in Table 3 below. 1% at week 96 with APTIVUS/ritonavir. The risk of developing transaminase elevations is greater during the first year of therapy. 2 Clinical Trials in Pediatrics APTIVUS, co-administered with ritonavir, has been studied in a total of 135 HIV-1 infected pediatric subjects as combination therapy.
5 WARNINGS AND PRECAUTIONS Co-administration with Ritonavir: APTIVUS must be co-administered with ritonavir and food to achieve the desired antiviral effect. Failure to administer APTIVUS with ritonavir and food may result in a loss of efficacy of tipranavir.
1 ) Hepatic Impairment: Discontinue for signs and symptoms of clinical hepatitis or asymptomatic increases in ALT/AST >10 times ULN or asymptomatic increases in ALT/AST 5-10 times ULN with concomitant increases in total bilirubin. Monitor liver function tests prior to therapy and frequently thereafter.
2 ) Intracranial Hemorrhage/Platelet Aggregation and Coagulation: Use with caution in patients at risk for increased bleeding or who are receiving medications that increase the risk of bleeding. 5 ) The concomitant use of APTIVUS/ritonavir and certain other drugs may result in known or potentially significant drug interactions.
Consult the full prescribing information prior to and during treatment for potential drug interactions. 2 ) Rash: Discontinue and initiate appropriate treatment if severe skin reaction occurs or is suspected. 6 ) Use with caution in patients with a known sulfonamide allergy.
10 ), and elevated lipids. 11 ) Monitor cholesterol and triglycerides prior to therapy and periodically thereafter.
Hemophilia:
Spontaneous bleeding may occur, and additional factor VIII may be required. 1 Importance of Co-administration with Ritonavir APTIVUS must be co-administered with ritonavir and food to achieve the desired antiviral effect. Failure to administer APTIVUS with ritonavir and food may result in a loss of efficacy of tipranavir.
Please refer to the ritonavir prescribing information for additional information on precautionary measures. 2 Hepatic Impairment and Toxicity Clinical hepatitis and hepatic decompensation, including some fatalities, were reported with APTIVUS co-administered with 200 mg of ritonavir.
2) ]. 2) ]. Table 1 Drugs that are Contraindicated with APTIVUS Co-Administered with Ritonavir Drug Class Drugs within Class that are Contraindicated with APTIVUS Co-administered with Ritonavir Clinical Comments: Alpha 1-adrenoreceptor antagonist Alfuzosin Potentially increased alfuzosin concentrations can result in hypotension.
Antiarrhythmics Amiodarone, bepridil, flecainide, propafenone, quinidine Potential for serious and/or life-threatening reactions such as cardiac arrhythmias secondary to increases in plasma concentrations of antiarrhythmics. Antimycobacterials Rifampin May lead to loss of virologic response and possible resistance to APTIVUS or to the class of protease inhibitors or other co-administered antiretroviral agents.
Ergot derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine Potential for acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. GI motility agent Cisapride Potential for cardiac arrhythmias.
Herbal products St. John's wort (hypericum perforatum) May lead to loss of virologic response and possible resistance to APTIVUS or to the class of protease inhibitors. HMG CoA reductase inhibitors Lovastatin, simvastatin Potential for myopathy including rhabdomyolysis.
Antipsychotics Pimozide Potential for cardiac arrhythmias. Lurasidone Potential for serious and/or life-threatening reactions. PDE-5 inhibitors Sildenafil (Revatio) [for treatment of pulmonary arterial hypertension] A safe and effective dose has not been established when used with APTIVUS/ritonavir.
There is increased potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope). Sedatives/hypnotics Oral midazolam, triazolam Prolonged or increased sedation or respiratory depression.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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14 enrolled HIV-1 infected, treatment-experienced pediatric subjects (with the exception of 3 treatment-naïve subjects), with baseline HIV-1 RNA of at least 1500 copies/mL. 14) and 25 subjects were enrolled in other clinical studies including Expanded Access and Emergency Use Programs.
14 was similar to adults. 5%), was reported more frequently in pediatric subjects than in adults. 5%).
These have generally occurred in subjects with advanced HIV-1 disease taking multiple concomitant medications. A causal relationship to APTIVUS/ritonavir could not be established. Physicians and patients should be vigilant for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly.
Patients with signs or symptoms of clinical hepatitis should discontinue APTIVUS/ritonavir treatment and seek medical evaluation. All patients should be followed closely with clinical and laboratory monitoring, especially those with chronic hepatitis B or C co-infection, as these patients have an increased risk of hepatotoxicity.
Liver function tests should be performed prior to initiating therapy with APTIVUS/ritonavir, and frequently throughout the duration of treatment. If asymptomatic elevations in AST or ALT greater than 10 times the upper limit of normal occur, APTIVUS/ritonavir therapy should be discontinued.
5 times the upper limit of normal occur, APTIVUS/ritonavir therapy should be discontinued. Treatment-experienced patients with chronic hepatitis B or hepatitis C co-infection or elevated transaminases are at approximately 2-fold risk for developing Grade 3 or 4 transaminase elevations or hepatic decompensation.
9/100 PEY) receiving APTIVUS/ritonavir through week 48. 3% (21/100 PEY) experienced Grade 3 or 4 hepatic transaminase elevations while receiving APTIVUS/ritonavir 500 mg/200 mg through week 48. Tipranavir is principally metabolized by the liver.
3) ]. 3 Intracranial Hemorrhage APTIVUS, co-administered with 200 mg of ritonavir, has been associated with reports of both fatal and non-fatal intracranial hemorrhage (ICH). Many of these subjects had other medical conditions or were receiving concomitant medications that may have caused or contributed to these events.
No pattern of abnormal coagulation parameters has been observed in subjects in general, or preceding the development of ICH. Therefore, routine measurement of coagulation parameters is not currently indicated in the management of patients on APTIVUS.
4 Risk of Serious Adverse Reactions Due to Drug Interactions Initiation of APTIVUS/ritonavir, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving APTIVUS/ritonavir, may increase plasma concentrations of medications metabolized by CYP3A.
Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of APTIVUS/ritonavir, respectively.
These interactions may lead to:
Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications. Clinically significant adverse reactions from greater exposures of APTIVUS/ritonavir.
Loss of therapeutic effect of APTIVUS/ritonavir and possible development of resistance. See Table 4 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations [ see Drug Interactions (7) ].
Consider the potential for drug interactions prior to and during APTIVUS/ritonavir therapy; review concomitant medications during APTIVUS/ritonavir therapy; and monitor for the adverse reactions associated with the concomitant medications [ see Contraindications (4) and Drug Interactions (7) ].
5 Effects on Platelet Aggregation and Coagulation APTIVUS/ritonavir should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery or other medical conditions, or who are receiving medications known to increase the risk of bleeding such as antiplatelet agents and anticoagulants, or who are taking supplemental high doses of vitamin E.
In rats, tipranavir treatment alone induced dose-dependent changes in coagulation parameters, bleeding events and death. 2) ]. However, analyses of stored plasma from adult and pediatric subjects treated with APTIVUS capsules plus low-dose ritonavir showed no effect of APTIVUS/ritonavir on vitamin K-dependent coagulation factors (Factor II and Factor VII), Factor V, or on prothrombin or activated partial thromboplastin times.
In in vitro experiments, tipranavir was observed to inhibit human platelet aggregation at levels consistent with exposures observed in subjects receiving APTIVUS/ritonavir. 6 Rash Rash, including urticarial rash, maculopapular rash, and possible photosensitivity, has been reported in subjects receiving APTIVUS/ritonavir.
In some cases rash was accompanied by joint pain or stiffness, throat tightness, or generalized pruritus. In controlled adult clinical trials, rash (all grades, all causality) was observed in 10% of females and in 8% of males receiving APTIVUS/ritonavir through 48 weeks of treatment.
The median time to onset of rash was 53 days and the median duration of rash was 22 days. 5%. In an uncontrolled compassionate use program (n=3920), cases of rash, some of which were severe, accompanied by myalgia, fever, erythema, desquamation, and mucosal erosions were reported.
In the pediatric clinical trial, the frequency of rash (all grades, all causality) through 48 weeks of treatment was 21%. Overall, most of the pediatric subjects had mild rash and 5 (5%) had moderate rash. 9%. Discontinue and initiate appropriate treatment if severe skin rash develops.
7 Sulfa Allergy APTIVUS should be used with caution in patients with a known sulfonamide allergy. Tipranavir contains a sulfonamide moiety. The potential for cross-sensitivity between drugs in the sulfonamide class and APTIVUS is unknown.
8 Diabetes Mellitus/Hyperglycemia New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycemia have been reported during post-marketing surveillance in HIV-1 infected patients receiving protease inhibitor therapy.
Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases, diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases.
Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established. 9 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including APTIVUS.
During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia, tuberculosis, or reactivation of herpes simplex and herpes zoster), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment.
10 Fat Redistribution Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy.
The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established. 11 Elevated Lipids Treatment with APTIVUS co-administered with 200 mg of ritonavir has resulted in large increases in the concentration of total cholesterol and triglycerides [ see Adverse Reactions (6) ].
Triglyceride and cholesterol testing should be performed prior to initiating APTIVUS/ritonavir therapy and at periodic intervals during therapy. 2) ]. 12 Patients with Hemophilia There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis in patients with hemophilia type A and B treated with protease inhibitors.
In some patients additional Factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship between protease inhibitors and these events has not been established.
13 Resistance/Cross Resistance Because the potential for HIV-1 cross-resistance among protease inhibitors has not been fully explored in APTIVUS/ritonavir treated patients, it is unknown what effect therapy with APTIVUS will have on the activity of subsequently administered protease inhibitors.
Due to the need for co-administration of APTIVUS with ritonavir, please refer to the ritonavir prescribing information for a description of ritonavir contraindications. 4 , 7 )