Aptivus (Boehringer Ingelheim) - General Information
Aptivus (Boehringer Ingelheim) is a nonpeptidic protease inhibitor that targets the HIV protease. It is administered with ritonavir in combination therapy to treat HIV infections.
Pharmacology of Aptivus (Boehringer Ingelheim)
Aptivus (Boehringer Ingelheim) is a non-peptidic protease inhibitor (PI) of HIV. Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Aptivus (Boehringer Ingelheim) for patients
Patients should be informed that APTIVUS co-administered with 200 mg of ritonavir, has been associated with severe liver disease, including some deaths. Patients with signs or symptoms of clinical hepatitis should discontinue APTIVUS/ritonavir treatment and seek medical evaluation. Symptoms of hepatitis include fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly. Extra vigilance is needed for patients 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 tipranavir and 200 mg of ritonavir, and frequently throughout the duration of treatment. Patients with chronic hepatitis B or C co-infection or elevations in liver enzymes prior to treatment are at increased risk (approximately 2.5- fold) for developing further liver enzyme elevations or severe liver disease. Caution should be exercised when administering APTIVUS/ritonavir to patients with liver enzyme abnormalities or history of chronic liver disease. Increased liver function testing is warranted in these patients. APTIVUS should not be given to patients with moderate to severe liver disease.
Mild to moderate rash has been reported in HIV-infected men and women receiving APTIVUS/ritonavir.
Women receiving estrogen-based hormonal contraceptives should be instructed that additional or alternative contraceptive measures should be used during therapy with APTIVUS/ritonavir. There may be an increased risk of rash when APTIVUS is given with hormonal contraceptives.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.
Patients should be informed that APTIVUS must be co-administered with 200 mg ritonavir to ensure its therapeutic effect. Failure to correctly co-administer APTIVUS with ritonavir will result in reduced plasma levels of tipranavir that may be insufficient to achieve the desired antiviral effect.
Patients should be told that sustained decreases in plasma HIV-1 RNA have been associated with a reduced risk of progression to AIDS and death. Patients should remain under the care of a physician while using APTIVUS. Patients should be advised to take APTIVUS and other concomitant antiretroviral therapy every day as prescribed. APTIVUS, co-administered with ritonavir, must be given in combination with other antiretroviral drugs. Patients should not alter the dose or discontinue therapy without consulting with their doctor. If a dose of APTIVUS is missed, patients should take the dose as soon as possible and then return to their normal schedule. However, if a dose is skipped the patient should not double the next dose.
Patients should be informed that APTIVUS is not a cure for HIV-1 infection and that they may continue to develop opportunistic infections and other complications associated with HIV disease. The long-term effects of APTIVUS are unknown at this time. Patients should be told that there are currently no data demonstrating that therapy with APTIVUS can reduce the risk of transmitting HIV to others through sexual contact.
APTIVUS may interact with some drugs; therefore, patients should be advised to report to their health care provider the use of any other prescription, non-prescription medication or herbal products, particularly St. John’s wort.
APTIVUS should be taken with food to enhance absorption.
The Patient Package Insert provides written information for the patients, and should be dispensed with each new prescription and refill.
Aptivus (Boehringer Ingelheim) Interactions
Tipranavir administered with ritonavir can alter plasma exposure of other drugs and other drugs can alter plasma exposure of tipranavir and ritonavir.
Tipranavir co-administered with 200 mg of ritonavir at the recommended dosage 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 tipranavir/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 should be contraindicated. Co-administration with other CYP 3A substrates may require a dose adjustment or additional monitoring.Established and Other Potentially Significant Drug Interactions:
- Nucleoside reverse transcriptase inhibitors: Abacavir, Didanosine (EC), Zidovudine
- Protease inhibitors: Amprenavir, Lopinavir, Saquinavir
- Antifungals: Fluconazole, Itraconazole, Ketoconazole, Voriconazole
Aptivus (Boehringer Ingelheim) Contraindications
APTIVUS (tipranavir) is contraindicated in patients with known hypersensitivity to any of the ingredients of the product.
APTIVUS is contraindicated in patients with moderate and severe (Child-Pugh Class B and C, respectively) hepatic insufficiency.
Co-administration of APTIVUS with 200 mg of ritonavir with drugs that are highly dependent on CYP 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life- threatening events is contraindicated. These drugs are listed below.
Drugs that are Contraindicated with Tipranavir, Co-Administered with 200 mg of Ritonavir
- Antiarrhythmics - Amiodarone, bepridil, flecainide, propafenone, quinidine
- Antihistamines - Astemizole, terfenadine
- Ergot derivatives - Dihydroergotamine, ergonovine, ergotamine, methylergonovine
- GI motility agent - Cisapride
- Neuroleptic - Pimozide
- Sedatives/hypnotics - Midazolam, triazolam
Due to the need for co-administration of APTIVUS with 200 mg of ritonavir, please refer to ritonavir prescribing information for a description of ritonavir contraindications.
Additional information about Aptivus (Boehringer Ingelheim)
Aptivus (Boehringer Ingelheim) Indication: 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.
Mechanism Of Action: Aptivus (Boehringer Ingelheim) (TPV) is a non-peptidic HIV-1 protease inhibitor that inhibits the virus-specific processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Tipranavir
Drug Category: Anti-HIV Agents; HIV Protease Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Tipranavir: Aptivus (Boehringer Ingelheim);
Absorption: Absorption is limited, although no absolute quantification of absorption is available.
Toxicity (Overdose): Oral LD50 in rat is over 5,000 mg/kg. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.
Protein Binding: Extensive (> 99.9%), to both human serum albumin and α-1-acid glycoprotein.
Biotransformation: Hepatic. In vitro metabolism studies with human liver microsomes indicated that CYP 3A4 is the predominant CYP enzyme involved in tipranavir metabolism.
Half Life: 5-6 hours
Dosage Forms of Aptivus (Boehringer Ingelheim): Capsule Oral
Chemical IUPAC Name: N-[3-[(1R)-1-[(6R)-2-hydroxy-4-oxo-6-(2-phenylethyl)-6-propyl-5H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)pyridine-2-sulfonamide
Chemical Formula: C31H33F3N2O5S
Tipranavir on Wikipedia: http://en.wikipedia.org/wiki/Tipranavir
Organisms Affected: Human Immunodeficiency Virus