Tipranavir is an active pharmaceutical ingredient in the Protease Inhibitors group (J05AE). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
USOfficial regulatory label· revised June 18, 2025[1]
4) ] . This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of APTIVUS/ritonavir of 48 weeks duration in treatment-experienced adults and one open-label 48-week study in pediatric patients. The adult studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
2) ]. 4) and Clinical Studies (14) ]. 4) ]. 4) ]. 2) ]. 2) ]. The drug-drug interaction potential of APTIVUS/ritonavir when co-administered with other drugs must be considered prior to and during APTIVUS/ritonavir use [ see Contraindications (4) and Drug Interactions (7) ].
5) ]. There are no study results demonstrating the effect of APTIVUS/ritonavir on clinical progression of HIV-1. APTIVUS, a protease inhibitor, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected adult 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 ( 1 ) Do not use APTIVUS/ritonavir in treatment-naïve patients ( 1 )
EUEuropean Union· EMA
1 product
Uses
EUOfficial regulatory label· revised April 23, 2026[2]
3 m2 or weight ≥ 36 kg and with virus resistant to multiple protease inhibitors. Aptivus should only be used as part of an active combination antiretroviral regimen in patients with no other therapeutic options. In deciding to initiate treatment with Aptivus, co-administered with low dose ritonavir, careful consideration should be given to the treatment history of the individual patient and the patterns of mutations associated with different agents.
Genotypic or phenotypic testing (when available) and treatment history should guide the use of Aptivus. 1).
How to take
Drug interactions
Known interactions involving Tipranavir. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 300. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]FDA DailyMed · 08982e49-d2eb-4b… · revised June 18, 2025 [PDF]
[2]European Medicines Agency · EMEA/H/C/000631 · revised April 23, 2026
[3]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
How to take
USOfficial regulatory label· revised June 18, 2025[1]
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.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 68 reports total. [3]
USOfficial regulatory label· Adverse reactions· revised June 18, 2025[1]
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.
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%).
USOfficial regulatory label· Warnings and precautions· revised June 18, 2025[1]
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.
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.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised June 18, 2025[1]
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.
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 )
This is not medical advice. Consult a qualified healthcare professional.
EUOfficial regulatory label· revised April 23, 2026[2]
Aptivus must always be given with low dose ritonavir as a pharmacokinetic enhancer, and in combination with other antiretroviral medicinal products. The Summary of Product Characteristics of ritonavir must therefore be consulted prior to initiation of therapy with Aptivus (especially as regards the contraindications, warnings and undesirable effects sections).
Aptivus should be prescribed by physicians who are experienced in the treatment of HIV-1 infection. 4 for precautionary measures in adolescents). 3 Body surface area (BSA) can be calculated as follows: Mosteller Formula: 𝐵𝑆𝐴 (𝑚²) = √𝐻𝑒𝑖𝑔ℎ𝑡 (𝑐𝑚) × 𝑊𝑡 (𝑘𝑔) 3600 Doses of ritonavir lower than 200 mg twice daily should not be used as they might alter the efficacy profile of the combination.
1) close monitoring of virologic response and tolerance is particularly warranted in this patient group. Missed dose Patients should be advised of the need to take Aptivus and ritonavir every day as prescribed. If a dose is missed by more than 5 hours, the patient should be instructed to wait and then to take the next dose of Aptivus and ritonavir at the regularly scheduled time.
If a dose is missed by less than 5 hours, the patient should be instructed to take the missed dose immediately, and then to take the next dose of Aptivus and ritonavir at the regularly scheduled time. 2). 4). Liver impairment Tipranavir is metabolised by the hepatic system.
Liver impairment could therefore result in an increase of tipranavir exposure and a worsening of its safety profile. Therefore, Aptivus should be used with caution, and with increased monitoring frequency, in patients with mild hepatic impairment (Child- Pugh Class A).
2). 2). Paediatric population The safety and efficacy of Aptivus capsules in children has not been established below 12 years of age. 2 but no recommendation on a posology can be made. Also, appropriate dose adjustments for children under 12 years cannot be achieved with Aptivus capsules.
Aptivus capsules should not be used in paediatric patients less than 12 years of age as there are no clinical data supporting the use of capsules in this paediatric subset. Method of administration Oral use. 2). Aptivus soft capsules must be swallowed whole and must not be opened or chewed.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
EUOfficial regulatory label· Adverse reactions· revised April 23, 2026[2]
Summary of the safety profile Amongst the most common adverse reactions reported for Aptivus were gastrointestinal complaints such as diarrhoea and nausea as well as hyperlipidaemia. The most serious adverse reactions include hepatic impairment and liver toxicity.
4). Aptivus co-administered with low dose ritonavir, has been associated with reports of significant liver toxicity. In Phase III RESIST trials, the frequency of transaminase elevations was significantly increased in the tipranavir with ritonavir arm compared to the comparator arm.
4). Limited data are currently available for the use of Aptivus, co-administered with low dose ritonavir, in patients co-infected with hepatitis B or C. Aptivus should therefore be used with caution in patients co-infected with hepatitis B or C.
Aptivus should be used in this patient population only if the potential benefit outweighs the potential risk, and with increased clinical and laboratory monitoring. Tabulated summary of adverse reactions Assessment of adverse reactions from HIV-1 clinical study data is based on experience in all Phase II and III trials in adults treated with the 500 mg tipranavir with 200 mg ritonavir dose twice daily (n = 1 397) and are listed below by system organ class and frequency according to the following categories: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000) 25 Tabulated summary of adverse reactions associated with Aptivus based on clinical studies and post- marketing experience: Blood and lymphatic system disorders uncommon neutropenia, anaemia, thrombocytopenia Immune system disorders uncommon hypersensitivity Metabolism and nutrition disorders common hypertriglyceridaemia, hyperlipidaemia uncommon anorexia, decreased appetite, weight decreased, hyperamylasaemia, hypercholesterolaemia, diabetes mellitus, hyperglycaemia rare dehydration Psychiatric disorders uncommon insomnia, sleep disorder Nervous system disorders common headache uncommon dizziness, neuropathy peripheral, somnolence rare intracranial haemorrhage* Respiratory, thoracic and mediastinal disorders uncommon dyspnoea Gastrointestinal disorders very common diarrhoea, nausea common vomiting, flatulence, abdominal pain, abdominal distension, dyspepsia uncommon gastrooesophageal reflux disease, pancreatitis rare lipase increased Hepatobiliary disorders uncommon hepatic enzyme increased (ALAT, ASAT), cytolytic hepatitis, liver function test abnormal (ALAT, ASAT), hepatitis toxic rare hepatic failure (including fatal outcome), hepatitis, hepatic steatosis, hyperbilirubinaemia Skin and subcutaneous tissue disorders common rash uncommon pruritus, exanthem Musculoskeletal and connective tissue disorders uncommon myalgia, muscle spasms Renal and urinary disorders uncommon renal failure General disorders and administration site conditions common fatigue uncommon pyrexia, influenza like illness, malaise * see section Description of selected adverse reactions “Bleeding” for source of information Description of selected adverse reactions The following clinical safety features (hepatotoxicity, hyperlipidaemia, bleeding events, rash) were seen at higher frequency among tipranavir with ritonavir treated patients when compared with the comparator arm treated patients in the RESIST trials, or have been observed with tipranavir with ritonavir administration.
The clinical significance of these observations has not been fully explored. 4%, respectively). Multivariate analyses showed that baseline ALAT or ASAT above DAIDS Grade 1 and 26 co-infection with hepatitis B or C were risk factors for these elevations.
Most patients were able to continue treatment with tipranavir with ritonavir. 4) Hyperlipidaemia Grade 3 or 4 elevations of triglycerides occurred more frequently in the tipranavir with ritonavir arm compared with the comparator arm.
6% in the comparator arm. Bleeding This adverse reaction was identified through post-marketing surveillance but not observed in randomised controlled clinical trials (n = 6 300). 80). 12). There was no pattern for the bleeding events and no difference between treatment groups in coagulation parameters.
The significance of this finding is being further monitored. Fatal and non-fatal intracranial haemorrhage (ICH) have been reported in patients receiving tipranavir, many of whom had other medical conditions or were receiving concomitant medicinal products that may have caused or contributed to these events.
However, in some cases the role of tipranavir cannot be excluded. No pattern of abnormal haematological or coagulation parameters has been observed in patients 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.
An increased risk of ICH has previously been observed in patients with advanced HIV disease/AIDS such as those treated in the Aptivus clinical trials. Rash An interaction study in women between tipranavir, co-administered with low dose ritonavir, and ethinyl oestradiol/norethindrone demonstrated […]
EUOfficial regulatory label· Warnings and precautions· revised April 23, 2026[2]
2). Failure to correctly co-administer tipranavir with ritonavir will result in reduced plasma levels of tipranavir that may be insufficient to achieve the desired antiviral effect. Patients should be instructed accordingly. Aptivus is not a cure for HIV-1 infection or AIDS.
Patients receiving Aptivus or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV-1 infection. Liver disease Aptivus is contraindicated in patients with moderate or severe (Child-Pugh Class B or C) hepatic insufficiency.
Limited data are currently available for the use of Aptivus, co-administered with low dose ritonavir, in patients co-infected with hepatitis B or C. Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reaction.
Aptivus should be used in this patient population only if the potential benefit outweighs the potential risk, and with increased clinical and laboratory monitoring. In the case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant Summary of Product Characteristics for these medicinal products.
Patients with mild hepatic impairment (Child-Pugh Class A) should be closely monitored. Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver function abnormalities during combination therapy and should be monitored according to standard practice.
Aptivus with ritonavir should be discontinued once signs of worsening liver function occur in patients with pre-existing liver disease. Aptivus co-administered with low dose ritonavir, has been associated with reports of clinical hepatitis and hepatic decompensation, including some fatalities.
These have generally occurred in patients with advanced HIV disease taking multiple concomitant medicinal products. Caution should be exercised when administering Aptivus to patients with liver enzyme abnormalities or with a history of hepatitis.
Increased ALAT/ASAT monitoring should be considered in these patients. 5 Aptivus therapy should not be initiated in patients with pre-treatment ASAT or ALAT greater than 5 times the Upper Limit Normal (ULN) until baseline ASAT/ALAT is stabilised at less than 5X ULN, unless the potential benefit justifies the potential risk.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
EUOfficial regulatory label· Contraindications· revised April 23, 2026[2]
1. Patients with moderate or severe (Child-Pugh B or C) hepatic impairment. 5). 5). Co-administration of Aptivus with low dose ritonavir, with active substances that are highly dependent on CYP3A for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
5). Also the use of the alpha-1 adrenoceptor antagonist alfuzosin, and sildenafil when used for the treatment of pulmonary arterial hypertension. 5). 5).
This is not medical advice. Consult a qualified healthcare professional.
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.
Aptivus therapy should be discontinued in patients experiencing ASAT or ALAT elevations greater than 10X ULN, or developing signs or symptoms of clinical hepatitis during therapy. If another cause is identified (eg acute hepatitis A, B or C virus, gallbladder disease, other medicinal products), then rechallenge with Aptivus may be considered when ASAT/ALAT have returned to the patient’s baseline levels.
Liver monitoring Monitoring of hepatic tests should be done prior to initiation of therapy, after two, four and then every four weeks until 24 weeks, and then every eight to twelve weeks thereafter. e. prior to initiation of therapy, every two weeks during the first three months of treatment, then monthly until 48 weeks, and then every eight to twelve weeks thereafter) is warranted when Aptivus and low dose ritonavir are administered to patients with elevated ASAT and ALAT levels, mild hepatic impairment, chronic hepatitis B or C, or other underlying liver disease.
Treatment-naïve patients In a study performed in antiretroviral naïve adult patients, tipranavir 500 mg with ritonavir 200 mg twice daily, as compared to lopinavir/ritonavir, was associated with an excess in the occurrence of significant (grade 3 and 4) transaminase elevations without any advantage in terms of efficacy (trend towards a lower efficacy).
The study was prematurely stopped after 60 weeks. 2). Renal impairment Since the renal clearance of tipranavir is negligible, increased plasma concentrations are not expected in patients with renal impairment. Haemophilia There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis in patients with haemophilia 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 has been evoked, although the mechanism of action had not been elucidated.
Haemophiliac patients should therefore be made aware of the possibility of increased bleeding. 80). 12). There was no pattern for the bleeding events and no difference between treatment groups in coagulation parameters. The significance of this finding is being further monitored.
Fatal and non-fatal intracranial haemorrhages (ICH) have been reported in patients receiving Aptivus, many of whom had other medical conditions or were receiving concomitant medicinal products that may have caused or contributed to these events.
However, in some cases the role of Aptivus cannot be excluded. No pattern of abnormal haematological or coagulation parameters has been observed in patients 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.
An increased risk of ICH has previously been observed in patients with advanced HIV disease/AIDS such as those treated in the Aptivus clinical trials. In in vitro experiments, tipranavir was observed to inhibit human platelet aggregation at levels consistent with […]