FUZEON
(enfuvirtide) for Injection
FUZEON (enfuvirtide) is an inhibitor of the fusion of HIV-1 with CD4+ cells. 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 C204H301N51O64, and the molecular weight is 4492. It has the following primary amino acid sequence:
CH3CO-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-NH2 and the following structural formula:
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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.
Last updated on RxList: 7/9/2009
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.
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.
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 on body weight. Weight should be monitored periodically and the FUZEON dose adjusted accordingly.
Table 7: Pediatric Dosing Guidelines
| Weight | Dose per bid Injection (mg/dose) | Injection Volume (90 mg enfuvirtide per mL) | |
| Kilograms (kg) | Pounds (lbs) | ||
| 11.0 to 15.5 | 24 to 34 | 27 | 0.3 mL |
| 15.6 to 20.0 | > 34 to 44 | 36 | 0.4 mL |
| 20.1 to 24.5 | > 44 to 54 | 45 | 0.5 mL |
| 24.6 to 29.0 | > 54 to 64 | 54 | 0.6 mL |
| 29.1 to 33.5 | > 64 to 74 | 63 | 0.7 mL |
| 33.6 to 38.0 | > 74 to 84 | 72 | 0.8 mL |
| 38.1 to 42.5 | > 84 to 94 | 81 | 0.9 mL |
| ≥ 42.6 | > 94 | 90 | 1.0 mL |
For more detailed instructions, see FUZEON Injection Instructions.
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.
FUZEON (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).
Store at 25ºC (77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature].
Reconstituted solution should be stored under refrigeration at 2º to 8ºC (36º to 46ºF) and used within 24 hours.
FUZEON has been jointly developed by Trimeris, Inc. and Hoffmann-La Roche Inc. FUZEON is manufactured by Hoffmann-La Roche Inc. Distributed by: Roche Laboratories Inc. 340 Kingsland Street, Nutley, New Jersey 07110-1199. Licensed from: Trimeris, Inc. www.trimeris.com. Revised December 2008.
Last updated on RxList: 7/9/2009
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.
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.
Table 4: Summary of Individual Signs/Symptoms Characterizing
Local Injection Site Reactions to Enfuvirtide in Studies T20-301 and T20-302
Combined (% of Subjects) Through 48 Weeks
| N=663 | |||
| Event Category | Any Severity Grade | % of Patients with Grade 3 Reactions | % of Patients with Grade 4 Reactions |
| Pain/Discomforta | 96% | 11% | 0% |
| Induration | 90% | 39% > 25 but < 50 mm |
18% ≥ 50 mm |
| Erythema | 91% | 22% > 50 but < 85 mm |
10% ≥ 85 mm |
| Nodules and Cysts | 80% | 23% > 3 cm average diameter |
0.2% draining |
| Pruritusb | 65% | 3% | NA |
| Ecchymosis | 52% | 5% > 3 but ≤ 5 cm |
2% > 5 cm |
| aGrade 3 = severe pain requiring prescription non-topical
analgesics or limiting usual activities. Grade 4 = severe pain requiring hospitalization or prolongation of hospitalization, resulting in death, or persistent or significant disability/incapacity, or life-threatening, or medically significant. bGrade 3 = refractory to topical treatment or requiring oral or parenteral treatment; Grade 4 = not applicable. |
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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 (see PRECAUTIONS).
Systemic hypersensitivity reactions have been attributed to FUZEON ( ≤ 1%) and in some cases have recurred upon re-challenge (see WARNINGS).
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.
Table 5: Rates of Treatment-Emergent Adverse Events* ( ≥ Grade
2) Reported in ≥ 2 % of Patients Treated with FUZEON** (Pooled Studies
T20-301/T20-302 at 48 Weeks)
| Adverse Event (by System Organ Class) | FUZEON + Back-ground Regimen (N=663) |
FUZEON + Back-ground Regimen (N=663) |
Background Regimen (N=334) |
| 663 patients total | 557 total patient-years | 162 total patient-years | |
| % frequency | rate/100 patient-years | rate/100 patient-years | |
| Weight Decreased | 6.6% | 7.9 | 6.2 |
| Sinusitis | 6.0% | 7.2 | 4.9 |
| Abdominal Pain | 3.9% | 4.7 | 3.7 |
| Cough | 3.9% | 4.7 | 2.5 |
| Herpes Simplex | 3.5% | 4.1 | 3.7 |
| Appetite Decreased | 3.2% | 3.8 | 2.5 |
| Pancreatitis | 3.0% | 3.6 | 2.5 |
| Pain in Limb | 2.9% | 3.4 | 3.1 |
| Pneumonia (see text below) | 2.7% | 3.2 | 0.6 |
| Myalgia | 2.7% | 3.2 | 1.2 |
| Influenza-Like Illness | 2.4% | 2.9 | 1.9 |
| Folliculitis | 2.4% | 2.9 | 2.5 |
| Anorexia | 2.3% | 2.7 | 1.9 |
| Dry Mouth | 2.1% | 2.5 | 1.9 |
| Conjunctivitis | 2.0% | 2.3 | 1.9 |
| *Excludes Injection Site Reactions **Events listed occurred more frequently in patients treated with FUZEON (based on rates/100 patient-years). |
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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 CD4+ lymphocyte 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 (see WARNINGS).
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
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.
Table 6: Treatment-Emergent Laboratory Abnormalities in ≥ 2%
of Patients Receiving FUZEON* (Pooled Studies T20-301 and T20-302 at 48 Weeks)
| Laboratory Parameters | Grading | FUZEON + Back-ground Regimen (N=663) |
FUZEON + Back-ground Regimen (N=663) |
Background Regimen (N=334) |
| 663 patients total | 557 total patient-years | 162 total patient-years | ||
| % frequency | rate/100 patient-years | rate/100 patient-years | ||
| Eosinophilia | ||||
| 1-2 X ULN (0.7 x 109/L) | 0.7-1.4 x 109/L | 9.1% | 10.8 | 3.7 |
| > 2 X ULN (0.7 x 109/L) | > 1.4 x 109/L | 1.8% | 2.2 | 1.8 |
| ALT | ||||
| Grade 3 | > 5-10 x ULN | 4.1% | 4.8 | 4.3 |
| Grade 4 | > 10 x ULN | 1.2% | 1.4 | 1.2 |
| Creatine Phosphokinase (U/L) | ||||
| Grade 3 | > 5-10 x ULN | 6.9% | 8.3 | 8.0 |
| Grade 4 | > 10 x ULN | 2.6% | 3.1 | 8.6 |
| *Events listed occurred more frequently in patients treated with FUZEON (based on rates/100 patient-years). | ||||
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.
Results from in vitro and in vivo studies suggest that enfuvirtide is unlikely to have significant drug interactions with concomitantly administered drugs metabolized by CYP450 enzymes (see CLINICAL PHARMACOLOGY).
No drug interactions with other antiretroviral medications have been identified that would warrant alteration of either the enfuvirtide dose or the dose of the other antiretroviral medication.
Last updated on RxList: 7/9/2009
The majority of patients (98%) receiving FUZEON in the Phase 3 clinical trials had at least one local injection site reaction; ISRs occurred throughout treatment with FUZEON. Manifestations may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis (see ADVERSE REACTIONS). Reactions are often present at more than one injection site. Patients must be familiar with the FUZEON Injection Instructions in order to know how to inject FUZEON appropriately and how to monitor carefully for signs or symptoms of cellulitis or local infection.
An increased rate of bacterial pneumonia was observed in subjects treated with FUZEON in the Phase 3 clinical trials compared to the control arm (see ADVERSE REACTIONS). It is unclear if the increased incidence of pneumonia is 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. Risk factors for pneumonia included low initial CD4+ cell count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease (see ADVERSE REACTIONS).
Systemic hypersensitivity reactions have been associated with FUZEON therapy and may recur on re-challenge. Hypersensitivity reactions have occurred in < 1% of patients studied and have included combinations of: rash, fever, nausea and vomiting, chills, rigors, hypotension, and/or elevated serum liver transaminases. Other adverse events that may be immune mediated and have been reported in subjects receiving FUZEON include primary immune complex reaction, respiratory distress, glomerulonephritis, and Guillain-Barre syndrome. Patients developing signs and symptoms suggestive of a systemic hypersensitivity reaction should discontinue FUZEON and should seek medical evaluation immediately. Therapy with FUZEON should not be restarted following systemic signs and symptoms consistent with a hypersensitivity reaction. Risk factors that may predict the occurrence or severity of hypersensitivity to FUZEON have not been identified (see ADVERSE REACTIONS).
There is a theoretical risk that FUZEON use may lead to the production of anti-enfuvirtide antibodies which cross react with HIV gp41. This could result in a false positive HIV test with an ELISA assay; a confirmatory western blot test would be expected to be negative. FUZEON has not been studied in non-HIV infected individuals.
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including FUZEON. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP] or tuberculosis), which may necessitate further evaluation and treatment.
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 (see ADVERSE REACTIONS) have occurred with use of the Biojector 2000 needle-free device for administration of FUZEON. Patients receiving anticoagulants or persons with hemophilia, or other coagulation disorders, may have a higher risk of post-injection bleeding.
To assure safe and effective use of FUZEON, the following information and instructions should be given to patients:
Patients should be advised that no studies have been conducted on the ability to drive or operate machinery while taking FUZEON. If patients experience dizziness while taking FUZEON, they should be advised to talk to their healthcare provider before driving or operating machinery.
Long-term animal carcinogenicity studies of enfuvirtide have not been conducted.
Enfuvirtide was neither mutagenic nor clastogenic in a series of in vivo and in vitro assays including the Ames bacterial reverse mutation assay, a mammalian cell forward gene mutation assay in AS52 Chinese Hamster ovary cells or an in vivo mouse micronucleus assay.
Enfuvirtide produced no adverse effects on fertility in male or female rats at doses up to 1.6 times the maximum recommended adult human daily dose on a m2 basis.
Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 27 times and 3.2 times the adult human dose on a m2 basis. The animal studies revealed no evidence of harm to the fetus from enfuvirtide. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
To monitor maternal-fetal outcomes of pregnant women exposed to FUZEON and other antiretroviral drugs, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
The Centers for Disease Control and Prevention recommends that HIV-infected mothers not breast-feed their infants to avoid the risk of postnatal transmission of HIV. It is not known whether enfuvirtide is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving FUZEON.
Studies where radio-labeled 3H-enfuvirtide was administered to lactating rats indicated that radioactivity was present in the milk. It is not known whether the radioactivity in the milk was from radio-labeled enfuvirtide or from radio-labeled metabolites of enfuvirtide (ie, amino acids and peptide fragments).
The safety and pharmacokinetics of FUZEON have not been established in pediatric subjects below 6 years of age; limited efficacy data is available in pediatric subjects 6 years of age and older.
Sixty-three HIV-1 infected pediatric subjects ages 5 through 16 years have received FUZEON in two open-label, single-arm clinical trials. Adverse experiences, including ISRs, were similar to those observed in adult patients.
Study T20-204 was an open-label, multicenter trial that evaluated the safety and antiviral activity of FUZEON in treatment-experienced pediatric subjects. Eleven subjects from 6 to 12 years were enrolled (median age of 9 years). Median baseline CD4+ cell count was 495 cells/µL and the median baseline HIV-1 RNA was 4.6 log10 copies/mL.
Ten of the 11 study subjects completed 48 weeks of chronic therapy. At week 48, 6/11 (55%) subjects had ≥ 1 log10 decline in HIV-1 RNA and 4/11 (36%) subjects were below 400 copies/mL of HIV-1 RNA. The median changes from baseline (for the As Treated population) in HIV-1 RNA and CD4+ cell count were -1.48 log10 copies/mL and +122 cells/µL, respectively.
Study T20-310 was an open-label, multicenter trial that evaluated the pharmacokinetics, safety, and antiviral activity of FUZEON in treatment-experienced pediatric subjects and adolescents. Fifty-two subjects from 5 through 16 years were enrolled (median age of 12 years). Median baseline CD4+ cell count was 117 cells/µL and the median baseline HIV-1 RNA was 5.0 log10 copies/mL.
Thirty-two of the 52 study subjects completed 48 weeks of chronic therapy. At week 48, 17/52 (33%) of subjects had ≥ 1 log10 decline in HIV-1 RNA, 11/52 (21%) of subjects were below 400 copies/mL of HIV-1 RNA and 5/52 (10%) were below 50 copies/mL. The median changes from baseline (for the As Treated population) in HIV-1 RNA and CD4+ cell count were -1.17 log10 copies/mL and +106 cells/µL, respectively.
Clinical studies of FUZEON did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Last updated on RxList: 7/9/2009
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.
FUZEON is contraindicated in patients with known hypersensitivity to FUZEON or any of its components (see WARNINGS).
Last updated on RxList: 7/9/2009
Enfuvirtide interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes. Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes.
The in vitro antiviral activity of enfuvirtide was assessed by infecting different CD4+ cell types with laboratory and clinical isolates of HIV-1. The IC50 values for baseline clinical isolates ranged from 0.089 to 107 nM (0.4 to 480 ng/mL) by the cMAGI assay (n=130) and from 1.56 to 1680 nM (7 to 7530 ng/mL) by a recombinant phenotypic entry assay (n=627). Enfuvirtide was similarly active in vitro against clades A, AE, C, D, E, F, and G (range 5.1 to 10.5 nM), and R5, X4, and dual tropic viruses. Enfuvirtide has no activity against HIV-2.
Enfuvirtide exhibited additive to synergistic effects in cell culture assays when combined with individual members of various antiretroviral classes, including lamivudine, zidovudine, indinavir, nelfinavir, and efavirenz.
HIV-1 isolates with reduced susceptibility to enfuvirtide have been selected in vitro. Genotypic analysis of the in vitro-selected resistant isolates showed mutations that resulted in amino acid substitutions at the enfuvirtide binding HR1 domain positions 36 to 38 of the HIV-1 envelope glycoprotein gp41. Phenotypic analysis of site-directed mutants in positions 36 to 38 in an HIV-1 molecular clone showed a 5-fold to 684-fold decrease in susceptibility to enfuvirtide.
In clinical trials, HIV-1 isolates with reduced susceptibility to enfuvirtide have been recovered from subjects failing a FUZEON containing regimen. Posttreatment HIV-1 virus from 277 subjects experiencing protocol defined virological failure at 48 weeks exhibited a median decrease in susceptibility to enfuvirtide of 33.4-fold (range 0.4-6318-fold) relative to their respective baseline virus. Of these, 249 had decreases in susceptibility to enfuvirtide of greater than 4-fold and all but 3 of those 249 exhibited genotypic changes in the codons encoding gp41 HR1 domain amino acids 36 to 45. Substitutions in this region were observed with decreasing frequency at amino acid positions 38, 43, 36, 40, 42, and 45.
HIV-1 clinical isolates resistant to nucleoside analogue reverse transcriptase inhibitors (NRTI), non-nucleoside analogue reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI) were susceptible to enfuvirtide in cell culture.
The pharmacokinetic properties of enfuvirtide were evaluated in HIV-1 infected adult and pediatric patients.
Following a 90-mg single subcutaneous injection of FUZEON into the abdomen in 12 HIV-1 infected subjects, the mean (±SD) Cmax was 4.59 ± 1.5 µg/mL, AUC was 55.8 ± 12.1 µg•h/mL and the median Tmax was 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 Cmax was 5.0 ± 1.7 µg/mL, Ctrough was 3.3 ± 1.6 µg/mL, AUC0-12h was 48.7 ± 19.1 µg•h/mL, and the median Tmax was 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.
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 µg/mL. It is bound predominantly to albumin and to a lower extent to a-1 acid glycoprotein.
The CSF levels of enfuvirtide (measured from 2 hours to 18 hours after administration of enfuvirtide) in 4 HIV-infected subjects were below the limit of quantification (0.025 µg/mL).
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.
Formal pharmacokinetic studies of enfuvirtide have not been conducted in patients with hepatic impairment.
Analysis of plasma concentration data from subjects in clinical trials indicated that the clearance of enfuvirtide is not affected in patients with creatinine clearance greater than 35 mL/min. The results of a renal impairment study indicate clearance of enfuvirtide was reduced by 38% in patients with severe renal impairment (CL = 11 – 35 mL/min; n = 4) and by 14 - 28% in patients with end-stage renal disease maintained on dialysis (n = 8) compared to patients with normal renal function (CL > 80 mL/min; n = 8). Hemodialysis did not significantly alter enfuvirtide clearance.
No dose adjustment is recommended for patients with impaired renal function.
Analysis of plasma concentration data from subjects in clinical trials indicated that the clearance of enfuvirtide is 20% lower in females than males after adjusting for body weight.
Enfuvirtide clearance decreases with decreased body weight irrespective of gender. Relative to the clearance of a 70-kg male, a 40-kg male will have 20% lower clearance and a 110-kg male will have a 26% higher clearance. Relative to a 70-kg male, a 40-kg female will have a 36% lower clearance and a 110-kg female will have the same clearance.
No dose adjustment is recommended for weight or gender.
Analysis of plasma concentration data from subjects in clinical trials indicated that the clearance of enfuvirtide was not different in Blacks compared to Caucasians. Other pharmacokinetic studies suggest no difference between Asians and Caucasians after adjusting for body weight.
The pharmacokinetics of enfuvirtide have been studied in 23 pediatric subjects aged 6 through 16 years at a dose of 2 mg/kg. Enfuvirtide pharmacokinetics were determined in the presence of concomitant medications including antiretroviral agents. A dose of 2 mg/kg bid (maximum 90 mg bid) provided enfuvirtide plasma concentrations similar to those obtained in adult patients receiving 90 mg bid.
In the 23 pediatric subjects receiving the 2 mg/kg bid dose, the mean ±SD steady-state AUC was 56.3 ± 22.3 µg•h/mL, Cmax was 6.3 ± 2.4 µg/mL, Ctrough was 3.1 ± 1.5 µg/mL, and apparent clearance was 40 ± 17 mL/h/kg.
The pharmacokinetics of enfuvirtide have not been studied in patients over 65 years of age.
Based on the results from an in vitro human microsomal study, enfuvirtide is not an inhibitor of CYP450 enzymes. In an in vivo human metabolism study (N=12), FUZEON at the recommended dose of 90 mg bid did not alter the metabolism of CYP3A4, CYP2D6, CYP1A2, CYP2C19 or CYP2E1 substrates.
As indicated in Table 1, pharmacokinetic interaction studies were conducted between FUZEON and the following drugs: ritonavir, saquinavir/ritonavir, and rifampin.
Table 1: Effect of Ritonavir, Saquinavir/Ritonavir, and Rifampin
on the Steady-State Pharmacokinetics of Enfuvirtide (90 mg bid)*
| Coadministered Drug | Dose of Coadministered Drug | N | % Change of Enfuvirtide Pharmacokinetic Parameters†x (90% CI) | ||
| Cmax | AUC | Ctrough | |||
| Ritonavir | 200 mg, q12h, 4 days | 12 | ↑24 (↑9 to ↑41) |
↑22 (↑8 to ↑37) |
↑14 (↑2 to ↑28) |
| Saquinavir/ Ritonavir | 1000/100 mg, q12h, 4 days | 12 | ⇔ | ↑14 (↑5 to ↑24) |
↑26 (↑17 to ↑35) |
| Rifampin | 600 mg, qd, 10 days | 12 | ⇔ | ⇔ | ↓15 (↓22 to ↓7) |
| * All studies were performed in HIV-1+ subjects using a sequential
crossover design. † ↑= Increase; ↓ = Decrease; ⇔ = No Effect (↑ or ↓ < 10%) x No interactions were clinically significant. |
|||||
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.
Table 2: T20-301 and T20-302 Pooled Subject Demographics
| FUZEON+Background Regimen | Background Regimen | |
| N=663 | N=334 | |
| Sex | ||
| Male | 90% | 90% |
| Female | 10% | 10% |
| Race | ||
| White | 89% | 89% |
| Black | 8% | 7% |
| Mean Age (yr) (range) | 42 (16-67) |
43 (24-82) |
| Median Baseline HIV-1 RNA (log10 copies/mL) (range) | 5.2 (3.5-6.7) |
5.1 (3.7-7.1) |
| Median Baseline CD4+ Cell Count (cells/mm3) (range) | 89 (1-994) |
97 (1-847) |
The disposition and efficacy outcomes of studies T20-301 and T20-302 are shown in Table 3.
Table 3: Outcomes at Week 48 (Pooled Studies T20-301 and
T20-302)
| Outcomes | FUZEON + Background Regimen 90 mg bid N=663 | Background Regimen N=334 |
|
| Virological Responder (at least 1 log10 below baseline) | 304 (46%) | 61 (18%) | |
| Virological Non-responder: • Switch |
0 | 220 (66%) | |
| • Completed 48 weeks randomized regimen* | 191 (29%) | 12 (4%) | |
| Continued Background Regimen (N=112) |
Switched to FUZEON (N=220) |
||
| Discontinued due to insufficient treatmentresponse# | 37 (5%) | 13 (12%) | 22 (10%) |
| Discontinued due to adverse reactions/intercurrent illness/labs | 46 (7%) | 9 (8%) | 13 (6%) |
| Deaths | 15 (2%) | 5 (4%) | 2 (1%) |
| Discontinued due to injection: | |||
| • Injection site reactions | 27 (4%) | NA | 10 (5%) |
| • Difficulty with injecting Fuzeon## | 18 (3%) | NA | 2 (1%) |
| Discontinued due to other reasons† | 25 (4%) | 14 (13%) | 6 (3%) |
| *Includes never responded, rebound, and missing RNA data. #Includes study discontinuation for virological failure and insufficient response as per the judgment of the investigator. ##Includes difficulties with injection, such as injection fatigue and inconvenience. †Includes lost to follow-up, treatment refusal, and non-compliance. |
|||
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 log10 below baseline.
The mean log change in HIV-1 RNA from baseline was -1.4 log10 copies/mL in subjects receiving FUZEON+background and -0.5 in those receiving background alone. The mean change in CD4+ cell count from baseline to week 48 was +91 cells/mm3 in the FUZEON+background arm and +45 cells/mm3 in 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 CD4+ cell count, baseline HIV-1 RNA, number of prior ARVs or number of active ARVs in the background regimen.
Last updated on RxList: 7/9/2009
FUZEON
(few'-zee-on)
Generic Name: enfuvirtide (en-few'-ver-tide) for Injection
WHAT IS FUZEON?
DOES FUZEON CURE HIV AND AIDS?
DOES FUZEON LOWER THE CHANCE OF PASSING HIV TO OTHER PEOPLE?
WHO SHOULD NOT USE FUZEON?
HOW SHOULD I USE FUZEON?
WHAT SHOULD I AVOID WHILE USING FUZEON?
WHAT ARE THE POSSIBLE SIDE EFFECTS OF FUZEON?
HOW IS FUZEON STORED?
GENERAL INFORMATION ABOUT THE SAFE AND EFFECTIVE USE OF FUZEON
WHAT ARE THE INGREDIENTS IN FUZEON?
WHERE CAN I GET MORE INFORMATION ABOUT FUZEON?
CHANGES SINCE THE LAST VERSION OF THIS LEAFLET
This leaflet contains important information for patients and their caregivers about FUZEON. Please read this leaflet and FUZEON Injection Instructions carefully before you start using FUZEON. Always read the section “Changes since the last version of this leaflet” at the end of this leaflet each time you get your FUZEON prescription refilled. There may be new important information about the use of FUZEON.
This information does not take the place of talking with your healthcare provider about your medical conditions or treatment.
What is FUZEON?
FUZEON is a medicine called an HIV (human immunodeficiency virus) fusion inhibitor. FUZEON is always used with other anti-HIV medicines to treat adults and children ages 6 years and older with HIV infection.
FUZEON blocks HIV's ability to infect healthy CD4 cells. When used with other anti-HIV medicines, FUZEON can reduce the amount of HIV in the blood and increase the number of CD4 cells. This may keep your immune system healthy, so it can help fight infection.
Does FUZEON cure HIV and AIDS?
FUZEON does not cure HIV infection or AIDS. People taking FUZEON may still get opportunistic infections or other conditions that can happen with HIV infection. For these reasons it is very important that you remain under the care of your healthcare provider while taking FUZEON.
Does FUZEON lower the chance of passing HIV to other people?
FUZEON does not lower your chance of passing HIV to other people through unprotected sex, sharing needles or being exposed to your blood. For your own health and the health of others, it is important to continue to practice safer sex. Use a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with semen, vaginal secretions or blood. Never use dirty needles or share needles. Ask your healthcare provider if you have any questions about safer sex or how to prevent passing HIV to other people.
Who should not use FUZEON?
Do not use FUZEON if you are allergic to any of the ingredients in FUZEON. See the end of this leaflet for a list of ingredients in FUZEON.
Tell your healthcare provider:
FUZEON does not affect other anti-HIV medicines or the medicine rifampin (also known as rifampicin, Rifadin or Rimactane ). You can take FUZEON at the same times or at different times than your other anti-HIV medicines.
How should I use FUZEON?
Before you use FUZEON, make sure you understand all of the information in this leaflet and the FUZEON Injection Instructions that come with your medicine. You or your caregiver should be trained by a healthcare provider before injecting it. If you do not
understand all the information or are having a hard time mixing or injecting FUZEON, talk with your healthcare provider.
What should I avoid while using FUZEON?
What are the possible side effects of FUZEON?
Injection site reactions
FUZEON causes injection site reactions. Almost all people get injection site reactions with FUZEON. Reactions are usually mild to moderate but occasionally may be severe. Reactions on the skin where FUZEON is injected include:
These reactions generally happen within the first week of FUZEON treatment and usually happen again as you keep using FUZEON. A reaction at one skin injection site usually lasts for less than 7 days.
Injection site reactions may be worse when injections are given again in the same place on the body or when the injection is given deeper than it should be (for example, into the muscle).
If you are worried about the reaction you are having, call your healthcare provider to help you decide if you need medical care. If the injection site reaction you are having is severe, call your healthcare provider right away. If you have an injection site reaction, you can discuss with your healthcare provider ways to help the symptoms.
An injection site can get infected. It is important to follow the FUZEON Injection Instructions that come with your medicine to lower your chances of getting an injection site infection. Call your healthcare provider right away if there are signs of infection at the injection site such as oozing, increasing heat, swelling, redness or pain.
Injection using Biojector® 2000
Shooting nerve pain and tingling lasting up to 6 months from injecting close to large nerves or near joints, and bruising and/or collections of blood under the skin have been reported with use of the Biojector 2000 needle-free device to inject FUZEON. If you are taking any blood thinners, or have hemophilia or any other bleeding disorder, you may be at higher risk of bruising or bleeding after using the Biojector.
Patients with HIV get bacterial pneumonia more often than patients without HIV. Patients taking FUZEON with other HIV medicines may get bacterial pneumonia more often than patients not receiving FUZEON. It is unclear if this is related to the use of FUZEON. You should contact your healthcare provider right away if you have a cough, fever or trouble breathing. Patients are more likely to get bacterial pneumonia if they had a low number of CD4 cells, increased amount of HIV in the blood, intravenous (injected into the vein) drug use, smoking or had experienced lung disease in the past. It is unclear if pneumonia is related to FUZEON.
Allergic reactions
FUZEON can cause serious allergic reactions. Symptoms of a serious allergic reaction with FUZEON can include:
Call your healthcare provider right away if you get any of these symptoms.
Other side effects
The following side effects were seen more often in patients using FUZEON with their other anti-HIV medicines than in patients not using FUZEON with their other anti-HIV medicines:
These are not all the side effects of FUZEON. For more information, ask your healthcare provider or pharmacist.
If you have questions about side effects, ask your healthcare provider. Report any new or continuing symptoms to your healthcare provider. Your healthcare provider will tell you what to do and may be able to help you with these side effects.
How is FUZEON stored?
FUZEON vials not mixed with sterile water can be stored at room temperature (59° to 86°F). FUZEON should be refrigerated if it cannot be stored at room temperature.
The Sterile Water for Injection (diluent) may be stored at room temperature (59° to 86°F).
After FUZEON has been mixed with the sterile water, the vial can be stored in a refrigerator for up to 24 hours.
Do not use FUZEON or sterile water after the expiration date on the vials. Do not keep FUZEON that is out of date or that you no longer need.
If you have more questions about how to store FUZEON, ask your healthcare provider or pharmacist or call 1-877-4FUZEON.
General information about the safe and effective use of FUZEON
Medicines are sometimes prescribed for conditions not mentioned in patient information leaflets. Do not use FUZEON for a condition for which it was not prescribed. Do not give FUZEON to other people, even if they have the same symptoms you have. It may harm them. Keep FUZEON and all medicines out of the reach of children.
This leaflet summarizes the most important information about FUZEON. If you would like more information, talk with your healthcare provider or see the section, “Where can I get more information about FUZEON?” in this leaflet. You can ask your healthcare provider or pharmacist for information about FUZEON that is written for health professionals.
What are the ingredients in FUZEON?
Active Ingredient: enfuvirtide
Inactive Ingredients: Mannitol, sodium carbonate, sodium hydroxide, and hydrochloric acid.
FUZEON comes packaged as a Convenience Kit containing the following:
Call your healthcare provider or pharmacist if you need more supplies.
Where can I get more information about FUZEON?
The best source for more information about FUZEON is your healthcare provider. More information about FUZEON can be found at www.FUZEON.com and 1-877-4FUZEON (1-877-438-9366).
Changes since the last version of this leaflet
Clarification of appropriate injection sites for FUZEON and addition of side effects when injecting with Biojector 2000 needle-free device.
Last updated on RxList: 7/9/2009
IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.
ENFUVIRTIDE - INJECTION
(en-FEW-ver-tide)
COMMON BRAND NAME(S): Fuzeon
USES: This medication is used in combination with other anti-HIV drugs to treat HIV (Human Immunodeficiency Virus) infection.
It works by blocking the HIV virus' ability to infect healthy immune cells (CD4 cells).
This medication does not cure HIV. Patients treated with this medication may continue to acquire "opportunistic" infections associated with HIV. This product also does not prevent the spread of HIV to others through sexual contact, blood, or sharing of needles.
HOW TO USE: Learn how to prepare and inject this drug and review the patient information leaflet and the injection instructions leaflet. If any of the information is unclear, consult your doctor or pharmacist.
Inject this medication under the skin (subcutaneously) usually twice daily into the upper arm, thigh, or abdomen. Do not inject into the buttock or near the elbow, knee or groin. Rotate injection sites with each shot. Do not inject in or near bumps from past injections. Also, do not inject into moles, scars, bruises, or your belly button.
Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid.
Learn how to store and discard needles and medical supplies safely. Consult your pharmacist.
It is very important to continue using this medication (and other anti-HIV medications) exactly as prescribed by your doctor. Do not skip any doses.
If you have a very serious allergic reaction to enfuvirtide, do not use it again (see Side Effects section).
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor immediately if any of these serious side effects occur: anxiety, muscle pain, numbness/tingling/shooting nerve pain near injection site, signs of injection site infection (such as oozing, warmth, persistent pain and redness).
Tell your doctor immediately if any of these unlikely but serious side effects occur: abdominal pain, loss of appetite, cough with fever, rapid breathing, shortness of breath, night sweats, vision/eye changes.
An allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, trouble breathing, fever, chills, nausea/vomiting.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.
PRECAUTIONS: Before using enfuvirtide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.
Before using this medication, tell your doctor or pharmacist your medical history, especially of: bleeding problems (e.g., hemophilia, coagulopathy), smoking, IV drug abuse, lung disease.
This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.
It is not known whether this drug passes into breast milk. Because breast milk can transmit HIV, do not breast-feed.
Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: "blood thinners" (e.g., warfarin, heparin, enoxaparin).
This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.
NOTES: Do not share this medication with others.
Laboratory and/or medical tests (e.g., blood test, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is within 2 hours of the next dose, skip the missed dose and resume your usual dosing schedule. It is important not to miss doses of this drug.
STORAGE: Store unmixed drug at room temperature at 77 degrees F (25 degrees C). Brief storage between 59 and 86 degrees F (15-30 degrees C) is permitted. Inject the mixed drug immediately. If you are unable to use it right away, the mixed drug should be refrigerated between 36 and 46 degrees F (2-8 degrees C) and used within 24 hours. Do not store in the bathroom. Keep all medicines away from children and pets.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854- 1166 (USA) or 1-800-668-1507 (Canada).
Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.
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.
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