Medical Editor: John P. Cunha, DO, FACOEP
What Is Aptivus?
Aptivus (tipranavir) is a protease inhibitor of HIV-1 used to treat HIV, which causes acquired immunodeficiency syndrome (AIDS). It is not a cure for HIV or AIDS.
What Are Side Effects of Aptivus?
Common side effects of Aptivus include:
- diarrhea,
- nausea,
- stomach pain,
- drowsiness,
- dizziness,
- headache,
- vomiting, or
- changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist)
Dosage for Aptivus
The recommended adult dose of Aptivus for adults is 500 mg (two 250 mg capsules or 5 mL oral solution) co-administered with 200 mg of ritonavir, twice daily.
What Drugs, Substances, or Supplements Interact with Aptivus?
Aptivus may interact with blood thinners, bosentan, colchicine, disulfiram, enfuvirtide, fluticasone, insulin or oral diabetes medications, itraconazole or ketoconazole, methadone, omeprazole, rifabutin, salmeterol, vitamin E, antidepressants, heart or blood pressure medications, cholesterol-lowering medicines, drugs that weaken the immune system, medication used to prevent blood clots, medicines to treat erectile dysfunction, other HIV /AIDS medicines, or seizure medications. Tell your doctor all medications and supplements you use.
Aptivus During Pregnancy and Breastfeeding
During pregnancy, Aptivus should be used only if prescribed. Because breast milk can transmit HIV; do not breastfeed.
Additional Information
Our Aptivus (tipranavir) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
A Timeline of the HIV/AIDS Pandemic See SlideshowGet emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Some people taking tipranavir with ritonavir have developed fatal medical problems including liver damage and bleeding in the brain. Stop taking this medicine and get emergency medical attention if you have:
- right-sided upper stomach pain, nausea, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
- unusual bleeding, sudden severe headache, problems with speech or vision.
Call your doctor at once if you have:
- severe skin rash, blistering, peeling, redness or sunburn;
- skin rash and also joint or muscle pain, fever, or tightness in your throat; or
- increased thirst, increased urination, hunger, dry mouth.
Tipranavir affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine). Tell your doctor if you have:
- signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss;
- trouble speaking or swallowing, problems with balance or eye movement, weakness or prickly feeling; or
- swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence.
Common side effects may include:
- nausea, vomiting, diarrhea, stomach pain;
- skin rash (especially in children);
- headache, fever, tired feeling; or
- changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
QUESTION
What is HIV? See AnswerSIDE EFFECTS
The following adverse reactions are described, in greater detail, in other sections:
- Hepatic Impairment and Toxicity [see WARNINGS AND PRECAUTIONS]
- Intracranial Hemorrhage [see WARNINGS AND PRECAUTIONS]
- Rash [see WARNINGS AND PRECAUTIONS]
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 [see Clinical Studies].
In 1182.12 and 1182.48 in the APTIVUS/ritonavir arm, the most frequent adverse reactions were diarrhea, nausea, pyrexia, vomiting, fatigue, headache, and abdominal pain. 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) |
| Gastrointestinal Disorders | ||
| 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) |
| General Disorders | ||
| Pyrexia | 7.5% (7.7) | 5.4% (8.2) |
| F atigue | 5.7% (5.9) | 5.6% (8.4) |
| Investigations | ||
| 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) |
| Psychiatric Disorders | ||
| 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
Gastrointestinal Disorders: abdominal distension, dyspepsia, flatulence, gastroesophageal reflux disease, pancreatitis
General Disorders: influenza-like illness, malaise
Hepatobiliary Disorders: hepatitis, hepatic failure, hyperbilirubinemia, cytolytic hepatitis, toxic hepatitis, hepatic steatosis
Immune System Disorders: hypersensitivity
Investigations: hepatic enzymes increased, liver function test abnormal, lipase increased
Metabolism and Nutrition Disorders: anorexia, decreased appetite, diabetes mellitus, facial wasting, hyperamylasemia, hypercholesterolemia, hyperglycemia, mitochondrial toxicity
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
Laboratory Abnormalities
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)
| Limit | Randomized, Controlled Clinical Trials 1182.12 and 1182.48 | ||
| Percentage of Patients (rate per 100 patient-exposure years) | |||
| APTIVUS/ritonavir (500/200 mg BID) + OBR (n=738) | Comparator PI/ritonavir + OBR* (n=724) | ||
| Hematology | |||
| 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) |
| Chemistry | |||
| Amylase | |||
| Grade 3 | >2.5 ULN | 5.7% (5.9) | 6.4% (10.4) |
| Grade 4 | >5 ULN | 0.3% (0.3) | 0.7% (1.1) |
| ALT | |||
| Grade 2 | >2.5-5 ULN | 14.9% (16.5) | 7.5% (12.4) |
| Grade 3 | >5-10 ULN | 5.6% (5.7) | 1.7% (2.6) |
| Grade 4 | >10 ULN | 4.1% (4.1) | 0.4% (0.7) |
| AST | |||
| Grade 2 | >2.5-5 ULN | 9.9% (10.5) | 8.0% (13.3) |
| Grade 3 | >5-10 ULN | 4.5% (4.6) | 1.4% (2.2) |
| Grade 4 | >10 ULN | 1.6% (1.6) | 0.4% (0.6) |
| ALT and/or AST | |||
| Grade 2-4 | >2.5 ULN | 26.0% (31.5) | 13.7% (23.8) |
| Cholesterol | |||
| 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) |
| Triglycerides | |||
| 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-naive 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.
Read the entire FDA prescribing information for Aptivus (Tipranavir)
© Aptivus Patient Information is supplied by Cerner Multum, Inc. and Aptivus Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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