Linked Life Data

Fuzeon (Kit)

Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1614

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dailymed-drugs:1614rdfs:labelFuzeon (Kit)lld:dailymed
dailymed-drugs:1614dailymed-instance:dosageAdults: The recommended dose of FUZEON is 90 mg (1 mL) twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site, and only where there is no current injection site reaction from an earlier dose. FUZEON should not be injected near any anatomical areas where large nerves course close to the skin, such as near the elbow, knee, groin or the inferior or medial section of the buttocks, skin abnormalities, including directly over a blood vessel, into moles, scar tissue, bruises, or near the navel, surgical scars, tattoos or burn sites. Additional detailed information regarding the administration of FUZEON is described in the FUZEON Injection Instructions.<br/>Pediatric Patients: Insufficient data are available to establish a dose recommendation of FUZEON in pediatric patients below the age of 6 years. In pediatric patients 6 years through 16 years of age, the recommended dosage of FUZEON is 2 mg/kg twice daily up to a maximum dose of 90 mg twice daily injected subcutaneously into the upper arm, anterior thigh or abdomen. Each injection should be given at a site different from the preceding injection site and only where there is no current injection site reaction from an earlier dose. FUZEON should not be injected into moles, scar tissue, bruises or the navel. Table 7 contains dosing guidelines for FUZEON based onbody weight. Weight should be monitored periodically and the FUZEON dose adjusted accordingly.<br/>Directions for Use: For more detailed instructions, see FUZEON Injection Instructions.<br/>Subcutaneous Administration: FUZEON must only be reconstituted with 1.1 mL of Sterile Water for Injection. After adding sterile water, the vial should be gently tapped for 10 seconds and then gently rolled between the hands to avoid foaming and to ensure all particles of drug are in contact with the liquid and no drug remains on the vial wall. The vial should then be allowed to stand until the powder goes completely into solution, which could take up to 45 minutes. Reconstitution time can be reduced by gently rolling the vial between the hands until the product is completely dissolved. Before the solution is withdrawn for administration, the vial should be inspected visually to ensure that the contents are fully dissolved in solution, and that the solution is clear, colorless and without bubbles or particulate matter. If the FUZEON is foamy or jelled, allow more time for it to dissolve. If there is evidence of particulate matter, the vial must not be used and should be returned to the pharmacy. FUZEON contains no preservatives. Once reconstituted, FUZEON should be injected immediately or kept refrigerated in the original vial until use. Reconstituted FUZEON must be used within 24 hours. The subsequent dose of FUZEON can be reconstituted in advance and must be stored in the refrigerator in the original vial and used within 24 hours. Refrigerated reconstituted solution should be brought to room temperature before injection and the vial should be inspected visually again to ensure that the contents are fully dissolved in solution and that the solution is clear, colorless, and without bubbles or particulate matter. The reconstituted solution should be injected subcutaneously in the upper arm, abdomen or anterior thigh. The injection should be given at a site different from the preceding injection site and only where there is no current injection site reaction. Also, do not inject near any anatomical areas where large nerves course close to the skin, such as near the elbow, knee, groin or the inferior or medial sections of the buttocks, skin abnormalities, including directly over a blood vessel, into moles, scar tissue, bruises, or near the navel, surgical scars, tattoos or burn sites. A vial is suitable for single use only; unused portions must be discarded (see FUZEON Injection Instructions). Patients should contact their healthcare provider for any questions regarding the administration of FUZEON. Information about the self-administration of FUZEON may also be obtained by calling the toll-free number 1-877-4-FUZEON (1-877-438-9366) or at the FUZEON website, www.FUZEON.com. Patients should be taught to recognize the signs and symptoms of injection site reactions and instructed when to contact their healthcare provider about these reactions.lld:dailymed
dailymed-drugs:1614dailymed-instance:descripti...FUZEON (enfuvirtide) is an inhibitor of the fusion of HIV-1 with CD4cells. Enfuvirtide is a linear 36-amino acid synthetic peptide with the N-terminus acetylated and the C-terminus is a carboxamide. It is composed of naturally occurring L-amino acid residues. Enfuvirtide is a white to off-white amorphous solid. It has negligible solubility in pure water and the solubility increases in aqueous buffers (pH 7.5) to 85-142 g/100 mL. The empirical formula of enfuvirtide is CHNO, and the molecular weight is 4492. It has the following primary amino acid sequence: CHCO-Tyr-Thr-Ser-Leu-Ile-His-Ser-Leu-Ile-Glu-Glu-Ser-Gln-Asn-Gln-Gln-Glu-Lys-Asn-Glu-Gln-Glu-Leu-Leu-Glu-Leu-Asp-Lys-Trp-Ala-Ser-Leu-Trp-Asn-Trp-Phe-NHand the following structural formula: The drug product, FUZEON (enfuvirtide) for Injection, is a white to off-white, sterile, lyophilized powder. Each single-use vial contains 108 mg of enfuvirtide for the delivery of 90 mg. Prior to subcutaneous administration, the contents of the vial are reconstituted with 1.1 mL of Sterile Water for Injection giving a volume of approximately 1.2 mL to provide the delivery of 1 mL of the solution. Each 1 mL of the reconstituted solution contains approximately 90 mg of enfuvirtide with approximate amounts of the following excipients: 22.55 mg of mannitol, 2.39 mg of sodium carbonate (anhydrous), and sodium hydroxide and hydrochloric acid for pH adjustment as needed. The reconstituted solution has an approximate pH of 9.0.lld:dailymed
dailymed-drugs:1614dailymed-instance:clinicalP...Pharmacokinetics: The pharmacokinetic properties of enfuvirtide were evaluated in HIV-1 infected adult and pediatric patients.<br/>Absorption: Following a 90-mg single subcutaneous injection of FUZEON into the abdomen in 12 HIV-1 infected subjects, the mean (��SD) Cwas 4.59��1.5��g/mL, AUC was 55.8��12.1��g���h/mL and the median Twas 8 hours (ranged from 3 to 12 h). The absolute bioavailability (using a 90-mg intravenous dose as a reference) was 84.3%��15.5%. Following 90-mg bid dosing of FUZEON subcutaneously in combination with other antiretroviral agents in 11 HIV-1 infected subjects, the mean (��SD) steady-state Cwas 5.0��1.7��g/mL, Cwas 3.3��1.6��g/mL, AUCwas 48.7��19.1��g���h/mL, and the median Twas 4 hours (ranged from 4 to 8 h). Absorption of the 90-mg dose was comparable when injected into the subcutaneous tissue of the abdomen, thigh or arm.<br/>Distribution: The mean (��SD) steady-state volume of distribution after intravenous administration of a 90-mg dose of FUZEON (N=12) was 5.5��1.1 L. Enfuvirtide is approximately 92% bound to plasma proteins in HIV-infected plasma over a concentration range of 2 to 10��g/mL. It is bound predominantly to albumin and to a lower extent to��-1 acid glycoprotein.<br/>Metabolism/Elimination: As a peptide, enfuvirtide is expected to undergo catabolism to its constituent amino acids, with subsequent recycling of the amino acids in the body pool. Mass balance studies to determine elimination pathway(s) of enfuvirtide have not been performed in humans. In vitro studies with human microsomes and hepatocytes indicate that enfuvirtide undergoes hydrolysis to form a deamidated metabolite at the C-terminal phenylalanine residue, M3. The hydrolysis reaction is not NADPH dependent. The M3 metabolite is detected in human plasma following administration of enfuvirtide, with an AUC ranging from 2.4% to 15% of the enfuvirtide AUC. Following a 90-mg single subcutaneous dose of enfuvirtide (N=12) the mean��SD elimination half-life of enfuvirtide is 3.8��0.6 h and the mean��SD apparent clearance was 24.8��4.1 mL/h/kg. Following 90-mg bid dosing of FUZEON subcutaneously in combination with other antiretroviral agents in 11 HIV-1 infected subjects, the mean��SD apparent clearance was 30.6��10.6 mL/h/kg.<br/>Special Populations:<br/>Drug Interactions:lld:dailymed
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dailymed-drugs:1614dailymed-instance:contraind...FUZEON is contraindicated in patients with known hypersensitivity to FUZEON or any of its components .lld:dailymed
dailymed-drugs:1614dailymed-instance:supplyFUZEON (enfuvirtide) for Injection is a white to off-white, sterile, lyophilized powder and it is packaged in a single-use clear glass vial containing 108 mg of enfuvirtide for the delivery of approximately 90 mg/1 mL when reconstituted with 1.1 mL of Sterile Water for Injection. FUZEON is available in a Convenience Kit containing 60 single-use vials of FUZEON (90 mg strength), 60 vials (2 cartons of 30 each) of Sterile Water for Injection (1.1 mL per vial), 60 reconstitution syringes (3 cc), 60 administration syringes (1 cc), alcohol wipes, Package Insert, Patient Package Insert, and Injection Instruction Guide (NDC 0004-0380-39).<br/>Storage Conditions: Store at 25��C (77��F); excursions permitted to 15��to 30��C (59��to 86��F) [see USP Controlled Room Temperature]. Reconstituted solution should be stored under refrigeration at 2��to 8��C (36��to 46��F) and used within 24 hours. Roche and FUZEON are trademarks of Hoffmann-La Roche Inc. Biojector is a trademark of Bioject Medical Technologies, Inc. FUZEON has been jointly developed by Trimeris, Inc. and Hoffmann-La Roche Inc. FUZEON is manufactured by Hoffmann-La Roche Inc.lld:dailymed
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dailymed-drugs:1614dailymed-instance:overdosag...There are no reports of human experience of acute overdose with FUZEON. The highest dose administered to 12 subjects in a clinical trial was 180 mg as a single dose subcutaneously. There is no specific antidote for overdose with FUZEON. Treatment of overdose should consist of general supportive measures.lld:dailymed
dailymed-drugs:1614dailymed-instance:genericMe...enfuvirtidelld:dailymed
dailymed-drugs:1614dailymed-instance:fullNameFuzeon (Kit)lld:dailymed
dailymed-drugs:1614dailymed-instance:adverseRe...The overall safety profile of FUZEON is based on 2131 subjects who received at least 1 dose of FUZEON during various clinical trials. This includes 2051 adults, 658 of whom received the recommended dose for greater than 48 weeks, and 63 pediatric subjects. Assessment of treatment-emergent adverse events is based on the pooled data from the two Phase 3 studies T20-301 and T20-302.<br/>Local Injection Site Reactions: Local injection site reactions were the most frequent adverse events associated with the use of FUZEON. In Phase 3 clinical studies (T20-301 and T20-302), 98% of subjects had at least one local injection site reaction (ISR). A total of 7% of subjects discontinued treatment with FUZEON because of ISRs (4%) or difficulties with injecting FUZEON (3%) such as injection fatigue and inconvenience. Eighty-five percent of subjects experienced their first ISR during the initial week of treatment; ISRs continued to occur throughout treatment with FUZEON. For most subjects the severity of signs and symptoms associated with ISRs did not change during the 48 weeks of treatment. The majority of ISRs were associated with erythema, induration, the presence of nodules or cysts, and mild to moderate pain at the injection site (Table 4). In addition, the average duration of individual ISRs was between three and seven days in 41% of subjects and more than seven days in 24% of subjects. Also, the numbers of ISRs per subject at any one time was between six to 14 ISRs in 26% of subjects and more than 14 ISRs in 1.3% of subjects. Infection at the injection site (including abscess and cellulitis) was reported in 1.7% of adult subjects.<br/>Biojector 2000 Needle-Free Device: Adverse events associated with the use of the Biojector 2000 needle-free device for administration of FUZEON have included: nerve pain (neuralgia and/or paresthesia) lasting up to 6 months associated with administration at anatomical sites where large nerves course close to the skin, bruising and hematomas .<br/>Other Adverse Events: Systemic hypersensitivity reactions have been attributed to FUZEON (���1%) and in some cases have recurred upon re-challenge . In the T20-301 and T20-302 studies, after study week 8, patients on background alone who met protocol defined criteria for virological failure were permitted to revise their background regimens and add FUZEON. Exposure on FUZEON+background was 557 patient-years, and to background alone 162 patient-years. Due to this difference in exposure, safety results are expressed as the number of patients with an adverse event per 100 patient-years of exposure. For FUZEON+background, adverse events are also displayed by percent of subjects. The events most frequently reported in subjects receiving FUZEON+background regimen, excluding injection site reactions, were diarrhea (38 per 100 patient-years or 31.7%), nausea (27 per 100 patient-years or 22.8%), and fatigue (24 per 100 patient-years or 20.2%). These events were also commonly observed in subjects that received background regimen alone: diarrhea (73 per 100 patient-years), nausea (50 per 100 patient-years), and fatigue (38 per 100 patient-years). Treatment-emergent adverse events, regardless of causality and excluding ISRs, from Phase 3 studies are summarized for adult subjects, in Table 5. Any Grade 2 or above events occurring at���2 percent of subjects and at a higher rate in subjects treated with FUZEON are summarized in Table 5; events that occurred at a higher rate in the control arms are not displayed. Rates of adverse events for patients who switched to FUZEON after virological failure were similar. The incidence of pneumonia was 2.7% or 3.2 events/100 patient-years in subjects receiving FUZEON+background regimen. On analysis of all diagnoses of pneumonia (pneumonia, bacterial pneumonia, bronchopneumonia, and related terms) in the Phase 3 clinical trials, an increased rate of bacterial pneumonia was observed in subjects treated with FUZEON compared to the control arm (6.9%, 6.7 pneumonia events per 100 patient-years versus 0.6 events per 100 patient-years, respectively). Approximately half of the study subjects with pneumonia required hospitalization. Three subject deaths in the FUZEON arm were attributed to pneumonia; all three had serious concomitant AIDS-related illnesses that contributed to their deaths. Risk factors for pneumonia included low initial CD4lymphocyte count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease. It is unclear if the increased incidence of pneumonia was related to FUZEON use. However, because of this, finding patients with HIV infection should be carefully monitored for signs and symptoms of pneumonia, especially if they have underlying conditions which may predispose them to pneumonia .<br/>Less Common Events: The following adverse events have been reported in 1 or more subjects; however, a causal relationship to FUZEON has not been established. Immune System Disorders: worsening abacavir hypersensitivity reaction Renal and Urinary Disorders: glomerulonephritis; tubular necrosis; renal insufficiency; renal failure (including fatal cases) Blood and Lymphatic Disorders: thrombocytopenia; neutropenia; fever; lymphadenopathy Endocrine and Metabolic: hyperglycemia Infections: sepsis; herpes simplex Nervous System Disorders: taste disturbance; Guillain-Barre syndrome (fatal); sixth nerve palsy; peripheral neuropathy Cardiac Disorders: unstable angina pectoris Gastrointestinal Disorders: constipation; abdominal pain upper General: asthenia Hepatobiliary Disorders: toxic hepatitis; hepatic steatosis Investigations: increased amylase; increased lipase; increased AST; increased GGT; increased triglycerides Psychiatric Disorders: insomnia; depression; anxiety; suicide attempt Respiratory, Thoracic, and Mediastinal Disorders: pneumopathy; respiratory distress; cough Skin and Subcutaneous Tissue Disorders: pruritus<br/>Laboratory Abnormalities: Table 6 shows the treatment-emergent laboratory abnormalities that occurred in at least 2 subjects per 100 patient-years and more frequently in those receiving FUZEON+background regimen than background regimen alone from studies T20-301 and T20-302.<br/>Adverse Events in Pediatric Patients: FUZEON has been studied in 63 pediatric subjects 5 through 16 years of age with duration of FUZEON exposure ranging from 1 dose to 134 weeks. Adverse experiences seen during clinical trials were similar to those observed in adult subjects, although infections at site of injection (cellulitis or abscess) were more frequent in adolescents than in adults, with 4 events occurring in 3 of 28 (11%) subjects.lld:dailymed
dailymed-drugs:1614dailymed-instance:indicatio...FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. This indication is based on results from two controlled studies of 48 weeks duration. Subjects enrolled were treatment-experienced adults; many had advanced disease. There are no studies of FUZEON in antiretroviral naive patients.<br/>Description of Clinical Studies:<br/>Studies in Antiretroviral Experienced Patients: Studies T20-301 and T20-302 were randomized, controlled, open-label, multicenter trials in HIV-1 infected subjects. Subjects were required to have either (1) viremia despite 3 to 6 months prior therapy with a nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI) or (2) viremia and documented resistance or intolerance to at least one member in each of the NRTI, NNRTI, and PI classes. All subjects received an individualized background regimen consisting of 3 to 5 antiretroviral agents selected on the basis of the subject's prior treatment history and baseline genotypic and phenotypic viral resistance measurements. Subjects were then randomized at a 2:1 ratio to FUZEON 90 mg bid with background regimen or background regimen alone. After week 8, patients on either treatment arm who met protocol defined criteria for virological failure were permitted to revise their background regimens; those on background regimen alone were also permitted to add FUZEON. Demographic characteristics for studies T20-301 and T20-302 are shown in Table 2. Subjects had prior exposure to a median of 12 antiretrovirals for a median of 7 years. The disposition and efficacy outcomes of studies T20-301 and T20-302 are shown in Table 3. At 48 weeks, 154 (23%) of subjects in the FUZEON+background regimen and 27 (8%) in the background regimen alone had HIV RNA levels<50 copies/mL, and 225 (34%) of subjects receiving FUZEON+background regimen had HIV RNA levels<400 copies/mL compared to 44 (13%) in the background regimen alone. Subjects achieving HIV RNA levels<50 copies/mL were included in the<400 copies/mL category and both categories were incorporated in the overall virologic responder category of achieving HIV RNA at least 1 logbelow baseline. The mean log change in HIV-1 RNA from baseline was -1.4 logcopies/mL in subjects receiving FUZEON+background and -0.5 in those receiving background alone. The mean change in CD4cell count from baseline to week 48 was +91 cells/mmin the FUZEON+background arm and +45 cells/mmin the background alone arm. Subjects in the FUZEON+background arm achieved a better virologic and immunologic outcome than subjects in the background alone arm across all subgroups based on baseline CD4cell count, baseline HIV-1 RNA, number of prior ARVs or number of active ARVs in the background regimen.lld:dailymed
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