Note: This document contains side effect information about tipranavir. Some dosage forms listed on this page may not apply to the brand name Aptivus.

Summary

Common side effects of Aptivus include: hypercholesterolemia and hypertriglyceridemia. Continue reading for a comprehensive list of adverse effects.

Applies to tipranavir: oral capsule liquid filled.

Serious side effects of Aptivus

Along with its needed effects, tipranavir (the active ingredient contained in Aptivus) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tipranavir:

Less common

• Bleeding gums
• confusion
• cough producing mucus
• coughing up blood
• difficulty with breathing or swallowing
• dizziness
• fever
• general feeling of tiredness or weakness
• headache
• increased menstrual flow or vaginal bleeding
• loss of appetite
• nausea or vomiting
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red or black, tarry, or light-colored stools
• red or dark brown urine
• sudden severe weakness
• tightness in the chest
• unusual bleeding
• upper right abdominal or stomach pain
• yellow eyes and skin

Other side effects of Aptivus

Some side effects of tipranavir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Diarrhea

Less common

• Abdominal or stomach pain
• cough
• discouragement
• fat redistribution
• feeling sad or empty
• irritability
• lack of appetite
• lack or loss of strength
• loss of interest or pleasure
• rash
• trouble concentrating
• trouble sleeping

For Healthcare Professionals

Applies to tipranavir: oral capsule, oral solution.

General

The most frequent side effects reported in clinical trials with this drug (plus ritonavir) were diarrhea/loose stools, nausea, fatigue, headache, vomiting, pyrexia, abdominal pain, and hyperlipidemia. Therapy was discontinued due to side effects in 13.3% of patients using tipranavir (the active ingredient contained in Aptivus) ritonavir and 10.8% of patients using the comparator.

The manufacturer product information for ritonavir should be consulted.^[Ref]

Metabolic

Very common (10% or more): Elevated triglycerides (up to 35.9%), elevated cholesterol (up to 15.6%)

Common (1% to 10%): Hypertriglyceridemia, hyperlipidemia, dehydration, decreased appetite

Uncommon (0.1% to 1%): Anorexia, diabetes mellitus, hyperamylasemia, hypercholesterolemia, hyperglycemia

Frequency not reported: Mitochondrial toxicity, porphyria cutanea tarda

Antiretroviral therapy:

-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased blood lipid levels, increased glucose levels

Protease inhibitor therapy:

-Postmarketing reports: New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, diabetic ketoacidosis^[Ref]

Elevated triglycerides (grade 2 [400 to 750 mg/dL]: 35.9%; grade 3 [greater than 750 to 1200 mg/dL]: 16.9%; grade 4 [greater than 1200 mg/dL]: 8%) and cholesterol (grade 2 [greater than 300 to 400 mg/dL]: 15.6%; grade 3 [greater than 400 to 500 mg/dL]: 3.3%; grade 4 [greater than 500 mg/dL]: 0.9%) have been reported at 48 weeks in controlled trials.^[Ref]

Hepatic

Grade 2 to 4 ALT and/or AST elevations (greater than 2.5 times the upper limit of normal [2.5 x ULN]: 26%), ALT elevations (grade 2 [greater than 2.5 to 5 x ULN]: 14.9%; grade 3 [greater than 5 to 10 x ULN]: 5.6%; grade 4 [greater than 10 x ULN]: 4.1%), and AST elevations (grade 2: 9.9%; grade 3: 4.5%; grade 4: 1.6%) have been reported at 48 weeks in controlled trials. In controlled clinical trials continued up to 96 weeks, 32.1% of patients developed grade 2 to 4 ALT and/or AST elevations.

Grade 3 and 4 hepatic transaminase elevations were reported in 10.3% of therapy-experienced patients in 2 large studies and in 20.3% of therapy-naive patients in 1 study; the studies were through 48 weeks. Elevated ALT or AST at baseline and hepatitis B or C coinfection were risk factors for such elevations in the 2 large studies; most patients were able to continue therapy with this drug (plus ritonavir).

Clinical hepatitis and hepatic decompensation (including some fatalities) have been reported with this drug (plus ritonavir); generally in patients with advanced HIV-1 disease taking multiple concomitant medications.

Significant liver toxicity has been reported with this drug (plus ritonavir). In at least 2 clinical trials, the frequency of transaminase elevations was significantly increased with this drug (plus ritonavir) compared to the comparator.^[Ref]

Very common (10% or more): Elevated ALT and/or AST (up to 32.1%), increased hepatic transaminases (up to 20.3%), elevated ALT (up to 14.9%)

Common (1% to 10%): Elevated AST, elevated GGT

Uncommon (0.1% to 1%): Increased hepatic enzymes, cytolytic hepatitis, abnormal liver function tests, hepatitis, toxic hepatitis, hepatic steatosis

Rare (less than 0.1%): Hepatic failure (including fatalities), hyperbilirubinemia

Frequency not reported: Clinical hepatitis, hepatic decompensation, liver toxicity, hepatic impairment^[Ref]

Gastrointestinal

Very common (10% or more): Diarrhea (15%), nausea

Common (1% to 10%): Vomiting, elevated amylase, abdominal pain, upper abdominal pain, abdominal distension, dyspepsia, flatulence, elevated lipase

Uncommon (0.1% to 1%): Gastroesophageal reflux disease, pancreatitis^[Ref]

Elevated amylase (grade 3 [greater than 2.5 x ULN]: 5.7%; grade 4 [greater than 5 x ULN]: 0.3%) has been reported at 48 weeks in controlled trials.^[Ref]

Dermatologic

Common (1% to 10%): Rash (including with joint pain/stiffness, throat tightness, generalized pruritus, myalgia, fever, erythema, desquamation, mucosal erosions), pruritus

Uncommon (0.1% to 1%): Exanthem, lipoatrophy, lipohypertrophy, acquired lipodystrophy

Rare (less than 0.1%): Facial wasting

Frequency not reported: Urticarial rash, maculopapular rash, photosensitivity (possible), rash (with joint pain/stiffness, throat tightness, generalized pruritus^[Ref]

Rash (including urticarial rash, maculopapular rash, and possible photosensitivity) has been reported in 8% of males and 10% of females using this drug (plus ritonavir) through 48 weeks of therapy. The time to onset and duration of rash averaged 53 and 22 days, respectively. Some cases of rash occurred in conjunction with joint pain or stiffness, throat tightness, and generalized pruritus. Cases of rash (some severe) with myalgia, fever, erythema, desquamation, and mucosal erosions have been reported. Rash has been reported more often in pediatric patients than in adults.^[Ref]

Hematologic

Decreased WBC count (grade 3 [less than 2000/mcL]: 5.4%; grade 4 [less than 1000/mcL]: 0.3%) has been reported at 48 weeks in controlled trials.

Increased bleeding (including spontaneous skin hematomas and hemarthrosis) in patients with hemophilia type A and B has been associated with protease inhibitors. In many of the reported cases, treatment with protease inhibitors was continued or restarted and some patients required additional factor VIII. A causal relationship between protease inhibitor therapy and these episodes has not been established.^[Ref]

Common (1% to 10%): Decreased WBC counts, anemia, neutropenia

Uncommon (0.1% to 1%): Thrombocytopenia

Frequency not reported: Bleeding event (not otherwise specified)

Protease inhibitor therapy:

-Frequency not reported: Increased bleeding (including spontaneous skin hematomas, hemarthrosis) in hemophiliacs^[Ref]

Musculoskeletal

Common (1% to 10%): Myalgia

Uncommon (0.1% to 1%): Muscle spasms

Frequency not reported: Muscle cramps, elevated creatine phosphokinase (CPK)

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis

Protease inhibitor therapy:

-Rare (less than 0.1%): Rhabdomyolysis

-Frequency not reported: Increased CPK, myalgia, myositis^[Ref]

Nervous system

Cases of fatal and nonfatal intracranial hemorrhage have been reported with this drug (plus ritonavir). Many of the patients had other medical conditions or were using concomitant medications that may have contributed to or caused these events. No pattern of abnormal hematologic or coagulation parameters was observed in patients in general or preceding development of intracranial hemorrhage.

An increased risk of intracranial hemorrhage was previously observed in patients with advanced HIV disease/AIDS, such as those treated in clinical trials with this drug.^[Ref]

Common (1% to 10%): Headache, peripheral neuropathy

Uncommon (0.1% to 1%): Dizziness, somnolence, intracranial hemorrhage

Frequency not reported: Cerebrovascular accident^[Ref]

Other

Common (1% to 10%): Pyrexia, fatigue, decreased weight

Uncommon (0.1% to 1%): Influenza-like illness, malaise

Frequency not reported: Asthenia, reactivation of herpes simplex, reactivation of varicella zoster, sepsis

Antiretroviral therapy:

-Frequency not reported: Increased weight^[Ref]

Psychiatric

Common (1% to 10%): Insomnia

Uncommon (0.1% to 1%): Sleep disorder

Frequency not reported: Depression^[Ref]

Respiratory

Common (1% to 10%): Dyspnea

Frequency not reported: Bronchitis, cough, nasopharyngitis, upper respiratory tract infection, pneumonia, epistaxis^[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity reactions^[Ref]

Renal

Uncommon (0.1% to 1%): Renal failure

Frequency not reported: Renal insufficiency^[Ref]

Immunologic

Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)^[Ref]