What is Aptivus (tipranavir)?
Aptivus (tipranavir) is a non-peptidic protease inhibitor (PI) of HIV belonging to the class of 4-hydroxy-5,6-dihydro-2-pyrone sulfonamides, which is co-administered with 200 mg of ritonavir, and indicated for combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors.
Common side effects of Aptivus include:
Women taking birth control pills may get a skin rash. It may be hard to tell the difference between side effects caused by Aptivus, by the other medicines you are also taking, or by complications of HIV infection.
Serious side effects of Aptivus include:
- liver problems (including liver failure and death),
- increased bleeding in patients with hemophilia,
- diabetes and high blood sugar (hyperglycemia),
- increased blood fat (lipid) levels, and
- changes in body fat (which may include an increased amount of fat in the upper back and neck, breast, and around the back, chest, and stomach area, along with loss of fat from the legs, arms, and face).
Drug interactions of Aptivus co-administered with 200 mg of ritonavir include drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring.
Co-administration of Aptivus/ritonavir and drugs that induce CYP3A and/or P-gp may decrease tipranavir plasma concentrations. Coadministration of Aptivus/ritonavir and drugs that inhibit P-gp may increase tipranavir plasma concentrations.
There are no adequate and well-controlled studies in pregnant women for the treatment of HIV-1 infection. Aptivus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. To monitor maternal-fetal outcomes of pregnant women exposed to Aptivus, an Antiretroviral Pregnancy Registry has been established.
The Centers for Disease Control and Prevention recommends HIV-infected mothers do not breastfeed their infants to avoid risking postnatal transmission of HIV. Because of both the potential for HIV transmission and any possible adverse effects of tipranavir, breastfeeding is not recommended while using Aptivus.
What are the important side effects of Aptivus (tipranavir)?
Aptivus may cause serious side effects, including:
- Liver problems, including liver failure and death. Your doctor should do blood tests to monitor your liver function during treatment with Aptivus. Patients with liver diseases such as Hepatitis B and Hepatitis C may have worsening of their liver disease with Aptivus and should have more frequent monitoring blood tests.
- Rash. Mild to moderate rash, including flat or raised rashes or sensitivity to the sun, have been reported in approximately 10% of subjects receiving Aptivus. Some patients who developed rash also had joint pain or stiffness, throat tightness, or generalized itching.
- Increased bleeding in patients with hemophilia. This can happen in patients taking Aptivus or other protease inhibitor medicines.
- Diabetes and high blood sugar (hyperglycemia). This can happen in patients taking Aptivus or other protease inhibitor medicines. Some patients have diabetes before starting treatment with Aptivus which gets worse. Some patients get diabetes during treatment with Aptivus. Some patients will need changes in their diabetes medicine. Some patients will need new diabetes medicine.
- Increased blood fat (lipid) levels. Your doctor should do blood tests to monitor your blood fat (triglycerides and cholesterol) during treatment with Aptivus. Some patients taking Aptivus have large increases in triglycerides and cholesterol. The long-term chance of having a heart attack or stroke due to increases in blood fats caused by Aptivus is not known at this time.
- Changes in body fat. These changes have happened in patients taking Aptivus and other anti-HIV medicines. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen.
The cause and long-term health effects of these conditions are not known. The most common side effects include:
Women taking birth control pills may get a skin rash. It may be hard to tell the difference between side effects caused by Aptivus, by the other medicines you are also taking, or by the complications of HIV infection. For this reason, it is very important that you tell your doctor about any changes in your health.
You should report any new or continuing symptoms to your doctor right away. Your doctor may be able to help you manage these side effects. The list of side effects is not complete. Ask your doctor or pharmacist for more information.
Aptivus (tipranavir) side effects list for healthcare professionals
The following adverse reactions are described, in greater detail, in other sections:
- Hepatic Impairment and Toxicity
- Intracranial Hemorrhage
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.
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 patients received the dose of 500/200 mg BID. Nine hundred nine (909) adults, including 541 in the 1182.12 and 1182.48 controlled clinical trials, have been treated for at least 48 weeks.
In 1182.12 and 1182.48 in the Aptivus/ritonavir arm, the most frequent adverse reactions were:
The 48-Week Kaplan-Meier rates of adverse reactions leading to discontinuation were 13.3% for Aptivus/ritonavir-treated patients and 10.8% for the comparator arm patients.
Adverse reactions reported in the controlled clinical trials 1182.12 and 1182.48, 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.
Table 2: Adverse Reactions Reported in Randomized, Controlled Clinical Trials (1182.12 and 1182.48) 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 Groupa (48-week Analyses)
|Percentage of patients (rate per 100 patient-exposure years)|
|Aptivus/ritonavir (500/200 mg BID) + OBRc|
(n=749; 757.4 patient-exposure years)
|Comparator PI/ritonavirb + OBR|
(n=737; 503.9 patient-exposure years)
|Blood and Lymphatic Disorders|
|Anemia||3.3% (3.4)||2.3% (3.4)|
|Neutropenia||2.0% (2.0)||1.0% (1.4)|
|Diarrhea||15.0% (16.5)||13.4% (21.6)|
|Nausea||8.5% (9.0)||6.4% (9.7)|
|Vomiting||5.9% (6.0)||4.1% (6.1)|
|Abdominal pain||4.4% (4.5)||3.4% (5.1)|
|Abdominal pain upper||1.5% (1.5)||2.3% (3.4)|
|Pyrexia||7.5% (7.7)||5.4% (8.2)|
|Fatigue||5.7% (5.9)||5.6% (8.4)|
|Weight decreased||3.1% (3.1)||2.2% (3.2)|
|ALT increased||2.0% (2.0)||0.5% (0.8)|
|GGT increased||2.0% (2.0)||0.4% (0.6)|
|Metabolism and Nutrition Disorders|
|Hypertriglyceridemia||3.9% (4.0)||2.0% (3.0)|
|Hyperlipidemia||2.5% (2.6)||0.8% (1.2)|
|Dehydration||2.1% (2.1)||1.1% (1.6)|
|Musculoskeletal and Connective Tissue Disorders|
|Myalgia||2.3% (2.3)||1.8% (2.6)|
|Nervous System Disorders|
|Headache||5.2% (5.3)||4.2% (6.3)|
|Peripheral neuropathy||1.5% (1.5)||2.0% (3.0)|
|Insomnia||1.7% (1.7)||3.7% (5.5)|
|Respiratory, Thoracic and Mediastinal Disorders|
|Dyspnea||2.1% (2.1)||1.0% (1.4)|
|Skin and Subcutaneous Tissue Disorders|
|Rash||3.1% (3.1)||3.8% (5.7)|
|aExcludes laboratory abnormalities that were Adverse Events|
bComparator PI/ritonavir: lopinavir/ritonavir 400/100 mg BID, indinavir/ritonavir 800/100 mg BID, saquinavir/ritonavir 1000/100 mg BID, amprenavir/ritonavir 600/100 mg BID
cOptimized Background Regimen
Less Common Adverse Reactions
Other adverse reactions reported in <2% of adult patients (n=1474) treated with Aptivus/ritonavir 500/200 mg in Phase 2 and 3 clinical trials are listed below by body system:
Blood and Lymphatic System Disorders: thrombocytopenia
General Disorders: influenza-like illness, malaise
Immune System Disorders: hypersensitivity
Investigations: hepatic enzymes increased, liver function test abnormal, lipase increased
Musculoskeletal and Connective Tissue Disorders: muscle cramp
Nervous System Disorders: dizziness, intracranial hemorrhage, somnolence
Psychiatric Disorders: sleep disorder
Renal and Urinary Disorders: renal insufficiency
Skin and Subcutaneous System Disorders: exanthem, lipoatrophy, lipodystrophy acquired, lipohypertrophy, pruritus
Treatment-emergent laboratory abnormalities reported at 48 weeks in the controlled clinical trials 1182.12 and 1182.48 in adults are summarized in Table 3 below.
Table 3: Treatment-Emergent Laboratory Abnormalities Reported in ≥2% of Adult Patients (48-week Analyses)
|Randomized, Controlled Clinical Trials 1182.12 and 1182.48|
|Percentage of Patients (rate per 100 patient-exposure years)|
|Limit||Aptivus/ritonavir (500/200 mg|
BID) + OBR
|Comparator PI/ritonavir + OBR*|
|WBC count decrease|
|Grade 3||<2.0 x 103/μL||5.4% (5.6)||4.8% (7.7)|
|Grade 4||<1.0 x 103/μL||0.3% (0.3)||1.1% (1.7)|
|Grade 3||>2.5 x ULN||5.7% (5.9)||6.4% (10.4)|
|Grade 4||>5 x ULN||0.3% (0.3)||0.7% (1.1)|
|Grade 2||>2.5-5 x ULN||14.9% (16.5)||7.5% (12.4)|
|Grade 3||>5-10 x ULN||5.6% (5.7)||1.7% (2.6)|
|Grade 4||>10 x ULN||4.1% (4.1)||0.4% (0.7)|
|Grade 2||>2.5-5 x ULN||9.9% (10.5)||8.0% (13.3)|
|Grade 3||>5-10 x ULN||4.5% (4.6)||1.4% (2.2)|
|Grade 4||>10 x ULN||1.6% (1.6)||0.4% (0.6)|
|ALT and/or AST|
|Grade 2-4||>2.5 x ULN||26.0% (31.5)||13.7% (23.8)|
|Grade 2||>300 – 400 mg/dL||15.6% (17.7)||6.4% (10.5)|
|Grade 3||>400 – 500 mg/dL||3.3% (3.3)||0.3% (0.4)|
|Grade 4||>500 mg/dL||0.9% (1.0)||0.1% (0.2)|
|Grade 2||400 – 750 mg/dL||35.9% (49.9)||26.8% (51.0)|
|Grade 3||>750 – 1200 mg/dL||16.9% (19.4)||8.7% (14.6)|
|Grade 4||>1200 mg/dL||8.0% (8.4)||4.3% (7.0)|
|*Comparator PI/ritonavir: lopinavir/ritonavir 400/100 mg BID, indinavir/ritonavir 800/100 mg BID, saquinavir/ritonavir 1000/100 mg BID, amprenavir/ritonavir 600/100 mg BID|
In controlled clinical trials 1182.12 and 1182.48 extending up to 96 weeks, the proportion of patients who developed Grade 2-4 ALT and/or AST elevations increased from 26% at week 48 to 32.1% at week 96 with Aptivus/ritonavir. The risk of developing transaminase elevations is greater during the first year of therapy.
Clinical Trials In Pediatric Patients
Aptivus, co-administered with ritonavir, has been studied in a total of 135 HIV-1 infected pediatric patients age 2 through 18 years as combination therapy. This study enrolled HIV-1 infected, treatment-experienced pediatric patients (with the exception of 3 treatment-naïve patients), with baseline HIV-1 RNA of at least 1500 copies/mL. One hundred and ten (110) patients were enrolled in a randomized, open-label 48-week clinical trial (Study 1182.14) and 25 patients were enrolled in other clinical studies including Expanded Access and Emergency Use Programs.
The adverse reactions profile seen in Study 1182.14 was similar to adults. Pyrexia (6.4%), vomiting (5.5%), cough (5.5%), rash (5.5%), nausea (4.5%), and diarrhea (3.6%) were the most frequently reported adverse reactions (Grade 2-4, all causes) in pediatric patients. Rash was reported more frequently in pediatric patients than in adults.
The most common Grade 3-4 laboratory abnormalities were increases in CPK (11%), ALT (6.5%), and amylase (7.5%).
Due to previous reports of both fatal and non-fatal intracranial hemorrhage (ICH), an analysis of bleeding events was performed. At 48 weeks of treatment, the frequency of pediatric patients with any bleeding adverse reactions was 7.5%. No drug related serious bleeding adverse reaction was reported. The most frequent bleeding adverse reaction was epistaxis (3.7%). No other bleeding adverse reaction was reported in frequency of >1%. Additional trial follow-up through 100 weeks showed a cumulative 12% frequency of any bleeding adverse reaction.
What drugs interact with Aptivus (tipranavir)?
Potential For Aptivus/Ritonavir To Affect Other Drugs
Aptivus co-administered with ritonavir at the recommended dose is a net inhibitor of CYP 3A and may increase plasma concentrations of agents that are primarily metabolized by CYP 3A. Thus, co-administration of Aptivus/ritonavir with drugs highly dependent on CYP 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated. Co-administration with other CYP 3A substrates may require a dose adjustment or additional monitoring.
Clinically significant drug-drug interactions of Aptivus co-administered with ritonavir are summarized in Table 4 below.
A phenotypic cocktail study was conducted with 16 healthy volunteers to quantify the influence of 10 days of Aptivus/ritonavir capsule administration on the activity of hepatic CYP 1A2 (caffeine), 2C9 (warfarin), 2C19 (omeprazole), 2D6 (dextromethorphan) and the activity of intestinal and hepatic CYP 3A4/5 (midazolam) and Pglycoprotein (P-gp) (digoxin). This study determined the first-dose and steady-state effects of 500 mg of Aptivus co-administered with 200 mg of ritonavir twice daily in capsule form. Aptivus oral solution co-administered with ritonavir capsules demonstrated similar effects as Aptivus capsules co-administrated with ritonavir.
There was no net effect on CYP 2C9 or hepatic P-gp at first dose or steady state. There was no net effect after first dose on CYP 1A2, but there was moderate induction at steady state. There was modest inhibition of CYP 2C19 at the first dose, but there was marked induction at steady state. Potent inhibition of CYP 2D6 and both hepatic and intestinal CYP 3A4/5 activities were observed after first dose and steady state.
Intestinal and hepatic P-gp activity was assessed by administering oral and intravenous digoxin, respectively. The digoxin results indicate P-gp was inhibited after the first dose of Aptivus/ritonavir followed by induction of P-gp over time. Thus, it is difficult to predict the net effect of Aptivus administered with ritonavir on oral bioavailability and plasma concentrations of drugs that are dual substrates of CYP 3A and P-gp. The net effect will vary depending on the relative affinity of the coadministered drugs for CYP 3A and P-gp, and the extent of intestinal first-pass metabolism/efflux. An in vitro induction study in human hepatocytes showed an increase in UGT1A1 by tipranavir similar to that evoked by rifampin. The clinical consequences of this finding have not been established.
Potential For Other Drugs To Affect Tipranavir
Tipranavir is a CYP 3A substrate and a P-gp substrate. Co-administration of Aptivus/ritonavir and drugs that induce CYP 3A and/or P-gp may decrease tipranavir plasma concentrations. Co-administration of Aptivus/ritonavir and drugs that inhibit P-gp may increase tipranavir plasma concentrations. Co-administration of Aptivus/ritonavir with drugs that inhibit CYP 3A may not further increase tipranavir plasma concentrations, because the level of metabolites is low following steadystate administration of Aptivus/ritonavir 500/200 mg twice daily.
Clinically significant drug-drug interactions of Aptivus co-administered with ritonavir are summarized in Table 4 below.
Table 4: Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen May be Recommended Based on Drug
Interaction Studies or Predicted Interaction
|Concomitant Drug Class:
|Effect on Concentration of Tipranavir or
|HIV-1 Antiviral Agents|
|Enfuvirtide||↑ Tipranavir||At steady state, tipranavir trough concentrations were approximately 45% higher in patients co-administered enfuvirtide in the Phase 3 trials. The mechanism for this increase is not known. Dose adjustments are not recommended.|
|Non-Nucleoside Reverse Transcriptase Inhibitors:|
|Etravirine||↓ Etravirine||Aptivus/ritonavir when coadministered with etravirine may cause a significant decrease in the plasma concentrations of etravirine and loss of therapeutic effect of etravirine. Etravirine and Aptivus/ritonavir should not be coadministered.|
|Rilpivirine||The use of rilpivirine co-administered with Aptivus/ritonavir has not been studied.||Concomitant use of rilpivirine with Aptivus/ritonavir may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). Rilpivirine is not expected to affect the plasma concentrations of Aptivus/ritonavir.|
|Nucleoside Reverse Transcriptase Inhibitors:|
|Abacavir||↓ Abacavir AUC by approximately 40%||Clinical relevance of reduction in abacavir levels not established.
Dose adjustment of abacavir cannot be recommended at this time.
|Didanosine (EC)||↓ Didanosine||Clinical relevance of reduction in didanosine levels not established.
For optimal absorption, didanosine should be separated from Aptivus/ritonavir dosing by at least 2 hours.
|Zidovudine||↓ Zidovudine AUC by approximately 35%.
ZDV glucuronide concentrations were unaltered.
|Clinical relevance of reduction in zidovudine levels not established.
Dose adjustment of zidovudine cannot be recommended at this time.
|Protease Inhibitors (co-administered with 200 mg of ritonavir):|
|Fosamprenavir||↓ Amprenavir||Combining a protease inhibitor with Aptivus/ritonavir is not recommended.|
|Protease Inhibitors (co-administered with 100 mg of ritonavir):|
|Virus Integrase Strand Transfer Inhibitors:|
|Raltegravir||↓ Raltegravir||Aptivus/ritonavir reduces plasma concentrations of raltegravir.
Since comparable efficacy was observed for this combination in phase 3 studies, dose adjustment is not recommended.
|Agents for Opportunistic Infections|
|↑ Tipranavir, ↔ Fluconazole||Fluconazole increases tipranavir concentrations but dose adjustments are not needed. Fluconazole doses >200 mg/day are not recommended.|
|↑ Itraconazole (not studied)
↑ Ketoconazole (not studied)
|Based on theoretical considerations itraconazole and ketoconazole should be used with caution. High doses (>200 mg/day) are not recommended.|
|↕ Voriconazole (not studied)||Due to multiple enzymes involved with voriconazole metabolism, it is difficult to predict the interaction.|
↓ 14-hydroxy-clarithromycin metabolite
|No dose adjustment of Aptivus or clarithromycin for patients with normal renal function is necessary.|
|For patients with renal impairment the following dosage adjustments
should be considered:
|Rifabutin||Tipranavir not changed, ↑Rifabutin
|Single dose study. Dosage reductions of rifabutin by 75% are
recommended (e.g., 150 mg every other day). Increased monitoring
for adverse events in patients receiving the combination is warranted.
Further dosage reduction may be necessary.
|Other Agents Commonly Used|
|↓ Tipranavir||Caution should be used when prescribing carbamazepine, phenobarbital and/or phenytoin. Aptivus may be less effective due to decreased tipranavir plasma concentration in patients taking these agents concomitantly.|
|Valproic Acid||↓ Valproic Acid||Caution should be used when prescribing valproic acid. Valproic acid may be less effective due to decreased valproic acid plasma concentration in patients taking Aptivus concomitantly.|
|Trazodone||↑ Trazodone||Concomitant use of trazodone and Aptivus/ritonavir may increase plasma concentrations of trazodone. Adverse events of nausea, dizziness, hypotension, and syncope have been observed following coadministration of trazodone and ritonavir. If trazodone is used with a CYP 3A4 inhibitor such as Aptivus/ritonavir, the combination should be used with caution and a lower dose of trazodone should be considered.|
|Desipramine||Combination with Aptivus/ritonavir not
|Dosage reduction and concentration monitoring of desipramine is recommended.|
|Selective Serotonin-Reuptake Inhibitors:||Combination with Aptivus/ritonavir not studied||Antidepressants have a wide therapeutic index, but doses may need to be adjusted upon initiation of Aptivus/ritonavir therapy.|
|Colchicine||↑ Colchicine||In patients with renal or hepatic impairment, coadministration of colchicine in patients on Aptivus/ritonavir is contraindicated.|
|In combination with Aptivus/ritonavir, the following dosage adjustments are recommended in patients with normal renal and hepatic function:|
|Treatment of gout flares: Co-administration of colchicine in patients on Aptivus/ritonavir:|
|Prophylaxis of gout flares: Co-administration of colchicine in patients on Aptivus/ritonavir:|
|Treatment of familial Mediterranean fever (FMF): Co-administration of colchicine in patients on Aptivus/ritonavir:|
|Quetiapine||↑ Quetiapine||Initiation of Aptivus with ritonavir in patients taking quetiapine:
Consider alternative antiretroviral therapy to avoid increases in quetiapine exposures. If coadministration is necessary, reduce the quetiapine dose to 1/6 of the current dose and monitor for quetiapineassociated adverse reactions. Refer to the quetiapine prescribing information for recommendations on adverse reaction monitoring. Initiation of quetiapine in patients taking Aptivus with ritonavir:
Refer to the quetiapine prescribing information for initial dosing and titration of quetiapine.
|Parenterally administered midazolam||↑ Midazolam||Midazolam is extensively metabolized by CYP 3A4. Increases in the concentration of midazolam are expected to be significantly higher with oral than parenteral administration. Therefore, Aptivus should not be given with orally administered midazolam. If Aptivus is co-administered with parenteral midazolam, close clinical monitoring for respiratory depression and/or prolonged sedation should be exercised and dosage adjustments should be considered.|
|Aptivus/ritonavir did not result in changes in the clinical efficacy of buprenorphine/naloxone. Compared to historical controls tipranavir Cmin was decreased approximately 40% with this combination. Dose adjustments cannot be recommended.|
|Calcium Channel Blockers:|
|Combination with Aptivus/ritonavir not studied. Cannot predict effect of TPV/ritonavir on calcium channel blockers that are dual substrates of CYP3A and P-gp due to conflicting effect of TPV/ritonavir on CYP3A and P-gp.||Caution is warranted and clinical monitoring of patients is recommended.|
↑ Felodipine (CYP3A substrate but not Pgp substrate)
↕ Nisoldipine (CYP3A substrate but not clear whether it is a P-gp substrate)
|Disulfiram/Metronidazole||Combination with TPV/ritonavir not studied||Aptivus capsules contain alcohol that can produce disulfiram-like reactions when co-administered with disulfiram or other drugs which produce this reaction (e.g., metronidazole).|
|Endothelin receptor antagonists||Co-administration of bosentan in patients on Aptivus/ritonavir:|
|Bosentan||↑ Bosentan||In patients who have been receiving Aptivus/ritonavir for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability.|
|Co-administration of Aptivus/ritonavir in patients on bosentan:|
|Discontinue use of bosentan at least 36 hours prior to initiation of Aptivus/ritonavir.|
|After at least 10 days following the initiation of Aptivus/ritonavir, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability.|
|HMG-CoA Reductase Inhibitors:|
↓ Hydroxy-atorvastatin metabolites
|Avoid co-administration with atorvastatin.|
|Hypoglycemics:||Combination with Aptivus/ritonavir not studied||Careful glucose monitoring is warranted.|
|↔ Glimepiride (CYP 2C9)
↔ Glipizide (CYP 2C9)
↔ Glyburide (CYP 2C9)
↕ Pioglitazone (CYP 2C8 and CYP 3A4)
↕ Repaglinide (CYP 2C8 and CYP 3A4)
↔ Tolbutamide (CYP 2C9)
|The effect of TPV/ritonavir on CYP 2C8
substrate is not known.
|Combination with Aptivus/ritonavir not
studied. Cannot predict effect of
TPV/ritonavir on immunosuppressants due
to conflicting effect of TPV/ritonavir on
CYP 3A and P-gp.
|Increased frequency of monitoring of plasma levels of immunosuppressant drugs is recommended.|
|Inhaled beta agonist:|
|Salmeterol||↑ Salmeterol||Concurrent administration of Aptivus/ritonavir is not recommended.
The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.
|Fluticasone||↑ Fluticasone||Concomitant use of fluticasone propionate and Aptivus/ritonavir may increase plasma concentrations of fluticasone propionate, resulting in significantly reduced serum cortisol concentrations. Coadministration of fluticasone propionate and Aptivus/ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.|
|Meperidine||Combinations with Aptivus/ritonavir not
↓ Meperidine, ↑ Normeperidine
|Dosage increase and long-term use of meperidine are not recommended due to increased concentrations of the metabolite normeperidine which has both analgesic activity and CNS stimulant activity (e.g., seizures).|
↓ S-Methadone, ↓ R-Methadone
|Dosage of methadone may need to be increased when co-administered with Aptivus and 200 mg of ritonavir.|
|Ethinyl estradiol||↓ Ethinyl estradiol concentrations by 50%||Alternative methods of nonhormonal contraception should be used when estrogen based oral contraceptives are co-administered with Aptivus and 200 mg of ritonavir. Patients using estrogens as hormone replacement therapy should be clinically monitored for signs of estrogen deficiency. Women using estrogens may have an increased risk of non-serious rash.|
|Proton Pump Inhibitors:|
|Omeprazole||↓ Omeprazole, ↔ Tipranavir||Dosage of omeprazole may need to be increased when co-administered with Aptivus and ritonavir.|
|Only the combination of tadalafil with Aptivus/ritonavir has been studied (at doses used for treatment of erectile dysfunction).||Co-administration with Aptivus/ritonavir may result in an increase in PDE-5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism.|
|↑ Sildenafil (not studied)
↑ Tadalafil with first dose Aptivus/ritonavir
↔ Tadalafil at Aptivus/ritonavir steadystate
↑ Vardenafil (not studied)
|Use of PDE-5 inhibitors for pulmonary arterial hypertension (PAH):|
|Co-administration of tadalafil (Adcirca) in patients on Aptivus/ritonavir:|
|In patients receiving Aptivus/ritonavir for at least one week, start Adcirca at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.|
|Co-administration of Aptivus/ritonavir in patients on tadalafil (Adcirca):|
|Avoid use of tadalafil (Adcirca) during the initiation of Aptivus/ritonavir. Stop Adcirca at least 24 hours prior to starting Aptivus/ritonavir. After at least one week following the initiation of Aptivus/ritonavir, resume Adcirca at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.|
|Use of PDE-5 inhibitors for erectile dysfunction:|
|Concomitant use of PDE-5 inhibitors with Aptivus/ritonavir should
be used with caution and in no case should the starting dose of:
|Warfarin||↔ S-Warfarin||Frequent INR (international normalized ratio) monitoring upon
initiation of Aptivus/ritonavir therapy.
|↑ increase, ↓ decrease, ↔ no change, ↕ unable to predict|
Aptivus (tipranavir) is a non-peptidic protease inhibitor (PI) of HIV belonging to the class of 4-hydroxy-5,6-dihydro-2-pyrone sulfonamides, which is co-administered with 200 mg of ritonavir, and indicated for combination antiretroviral treatment of HIV-1 infected adult patients with evidence of viral replication, who are highly treatment-experienced or have HIV-1 strains resistant to multiple protease inhibitors. Common side effects of Aptivus include diarrhea, nausea, vomiting, stomach pain, tiredness and headache. Women taking birth control pills may get a skin rash. It may be hard to tell the difference between side effects caused by Aptivus, by the other medicines you are also taking, or by complications of HIV infection. There are no adequate and well-controlled studies in pregnant women for the treatment of HIV-1 infection. Aptivus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of both the potential for HIV transmission and any possible adverse effects of tipranavir, breastfeeding is not recommended while using Aptivus.
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Now, more than ever, you should know about HIV/AIDS, especially its causes, symptoms treatments, and complications. Take the...
Picture of HIV/AIDS
Acronym for the Human Immunodeficiency Virus, the cause of AIDS (acquired immunodeficiency syndrome). See a picture of HIV/AIDS...
Picture of HIV-associated Dementia (HAD)
A 40-year-old woman diagnosed with HIV presented with confusion and decline in memory. See a picture of HIV-associated Dementia...
Related Disease Conditions
HIV Early Signs and Stages
HIV (human immunodeficiency virus) weakens your immune system. Some people with HIV don’t have any symptoms, but those that do may experience mononucleosis-like or flu-like symptoms. There are 3 stages of HIV.
HIV and AIDS
Second Source article from WebMD
Human Immunodeficiency Virus (HIV)
HIV (human immunodeficiency virus) infection left untreated causes AIDS (acquired immunodeficiency syndrome). The human immunodeficiency virus (HIV) is a type of virus called a retrovirus, which can infect humans when it comes in contact with tissues that line the vagina, anal area, mouth, or eyes, or through a break in the skin. HIV infection is generally a slowly progressive disease in which the virus is present throughout the body at all stages of the disease. Three stages of HIV infection have been described. The initial stage of infection (primary infection), which occurs within weeks of acquiring the virus, often is characterized by the flu- or mono-like illness that generally resolves within weeks. The stage of chronic asymptomatic infection (meaning a long duration of infection without symptoms) lasts an average of eight to 10 years without treatment. The stage of symptomatic infection, in which the body's immune (or defense) system has been suppressed and complications have developed, is called the acquired immunodeficiency syndrome (AIDS). The symptoms are caused by the complications of AIDS, which include one or more unusual infections or cancers, severe loss of weight, and intellectual deterioration (called dementia). When HIV grows (that is, by reproducing itself), it acquires the ability to change (mutate) its own structure. These mutations enable the virus to become resistant to previously effective drug therapy. The goals of drug therapy are to prevent damage to the immune system by the HIV virus and to halt or delay the progress of the infection to symptomatic disease. Therapy for HIV includes combinations of drugs that decrease the growth of the virus to such an extent that the treatment prevents or markedly delays the development of viral resistance to the drugs. The best combination of drugs for HIV are those that effectively suppress viral replication in the blood and also are well tolerated and simple to take so that people can take the medications consistently without missing doses.
HIV vs. AIDS
Human immunodeficiency virus causes HIV infection. Acquired immunodeficiency syndrome (AIDS) is a condition that results after HIV has extensively damaged a person's immune system. Risk factors for HIV and AIDS include use of contaminated needles or syringes, unprotected sex, STDs, receiving a blood transfusion prior to 1985 in the United States, having many sex partners, and transmission from a mother to her child.
HIV Medications List and Drug Charts
The ultimate goal of HIV treatment is getting the viral load down below detectable levels. As long as those viral load and antibody levels are below a proscribed range, people with HIV can stave off AIDS and other serious symptoms. Antiviral treatment options usually include combinations of two NRTIs, often referred to as "nucs," and a third drug, typically being a boosted protease inhibitor, a NNRTI, often called "non-nucs," and integrase strand transfer inhibitors.
HIV/AIDS Infection Transmission and Prevention
HIV (human immunodeficiency virus) is spread through contact with genital fluids or blood of an infected person. The spread of HIV can occur when these secretions come in contact with tissues such as those lining the vagina, anal area, mouth, eyes (the mucus membranes), or with a break in the skin, such as from a cut or puncture by a needle.
HIV/AIDS Testing: Diagnosis and Monitoring
HIV/AIDS diagnosis and monitoring have come a long way from the days when a diagnosis was a death sentence. Crucial parts of the effective treatment regimens developed in the last 40 years are consistent monitoring of the viral load (the amount of virus in the blood), and the immune cell count, which function as biological markers of the disease’s progression. Doctors also must test for drug resistance.
HIV/AIDS Facts: What Is HIV?
HIV (human immunodeficiency virus) is the precursor infection to AIDS (acquired immunodeficiency syndrome). HIV is transmitted through blood and genital secretions; most people get it through sexual contact or sharing needles for illegal IV drug use. HIV can be controlled by a strict drug regimen, but left unchecked, it leads to AIDS. In AIDS, the immune system collapses and the body falls prey to secondary, opportunistic infections and cancers that typically kill the person.
What Are the Side Effects of HIV Medications?
It’s important to know the potential side effects of all the drugs you take to control your HIV infection, as well as potential drug interactions. All of the NNRTIs (nonnucleoside analogue reverse transcriptase inhibitors), for example, are associated with important drug-drug interactions so they must be used with caution in patients on other medications. Learn more about the side effects of the drugs in standard treatment regimens.
When should you start HIV medication?
Nearly everyone who is infected with HIV (human immunodeficiency virus) should start antiviral medication therapy as soon as they are diagnosed. Older guidelines recommended delaying treatment to help reduce the potential for drug side effects and viral resistance to treatment. Current thinking theorizes that early treatment may preserve more of the body's immune function.
Treatment & Diagnosis
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Medications & Supplements
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.