Active material: Enfuvirtid
When ATH: J05AX07
CCF: Viricide, active against HIV
When CSF: 09.01.04.03
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)
DOSAGE FORM, COMPOSITION AND PACKAGING
Valium for solution to the p/to the injections white or white with a slightly yellowish brown color; the recovered solution transparent, colorless or slightly yellow.
|1 ml ready-r-ra||1 fl.|
|enfuvirtide||90 mg||108 mg|
[Ring] anhydrous sodium carbonate,, mannitol, Sodium hydroxide, hydrochloric acid.
Solvent: water d / and – 1.1 ml.
Glass Bottles (60) together with the solvent (fl. 60 PC.) – packs cardboard.
Fusion inhibitor (confluence). Specific binding to the glycoprotein gp41 of HIV-1 is cell and inhibiting its structural rearrangement, blocking the penetration of virus into the cell. It does not require intracellular activation. Antiviral activity due to interaction with others. seven times a recurring plot HR1 in gp41 on the surface of the virus.
After a single p/to the introduction in the region of the anterior abdominal wall 90 mg Cmax enfuvirtide-4.59 ± 1.5 µg/ml, AUC - 55.8 ± 12.1 mcg x h / ml, absolute bioavailability - 84.3 ± 15.5%. When s / to the introduction of a range of doses 45-180 bioavailability is proportional to the input mg dose. Absorption does not depend on the site of administration. CSS introduction 90 mg - 2.6-3.4 ug / ml.
The volume of distribution after in/introductions 90 mg - 5.5 ± 1.1 L. Contact proteins – 92% (mainly to albumin and, less – with Alpha1-acid glikoproteinom).
It is a peptide, subjected to amino acid catabolism, its constituent, with their subsequent utilization in the body.
Not ingibiruet enzymes cytochrome CYP450 family.
In vitro hydrolysis of the amide group of the C-terminal amino acid phenylalanine leads to the formation of deamidated metabolite, and the formation of this metabolite is not dependent on NADPH. Metabolite found in plasma following administration of enfuvirtide with AUC 2.4-15% from enfuvirtide AUC.
After p/to the introduction 90 mg enfuvirtide T1/2-3.8 ± 0.4 h, clearance - 1.7 ± 0.4 l / h.
Pharmacokinetics of enfuvirtide in patients with hepatic and renal insufficiency was not studied, as well as in patients over the age of 65 years. Clearance enfuvirtide does not change in patients with KK above 35 ml/ml.
Clearance of enfuvirtide on 20% below in women, than in men and increases with increasing body weight, regardless of gender (on 20% higher in patients with body weight 100 kg, and 20% lower in patients with body weight 40 kg, regarding patient comparison with body weight 70 kg), that is not clinically significant.
Children 3-16 years on assignment to dose 2 mg / kg 2 once a day (no more 90 mg 2 once a day) enfuvirtide concentration in plasma is similar to that of adult patients, receiving drug dose 90 mg 2 once a day. In children 5-16 years, receiving enfuvirtide dose 2 mg / kg 2 once a day, AUC-51.4 ± 14.2 µg x h/ml, Cmax-5.81 ± 2.35 µg/ml and Smin wvedeniami-2.82 ± 1.46 µg/ml.
HIV-1 (in combination with other. mentioned HP).
Pregnancy, childhood (to 6 years).
P/to the shoulder area, anterior thigh or abdominal wall. You must change each subsequent injections.
Adult – 90 mg 2 once a day.
Children 6-16 years – 2 mg / kg 2 once a day. The maximum dose – 90 mg 2 once a day.
Doses, input 2 times a day and the corresponding amount of solution, featured in paediatric practice depending on body mass index: 11-15.5 kg- 27 mg (0.3 ml), 15.6-20 kg- 36 mg (0.4 ml), 20.1-24.5 kg- 45 mg (0.5 ml), 24.6-29 kg- 54 mg (0.6 ml), 29.1-33.5 kg- 63 mg (0.7 ml), 33.6-38 kg- 72 mg (0.8 ml), 38.1-42.5 kg 81 mg (0.9 ml), more 42.6 kg- 90 mg (1 ml).
No dose adjustment for patients with CC more 35 ml / min does not require.
Liofilizirovanny powder to be diluted with sterile water for injection to get solution.
Local reactions: pain, discomfort at the injection site, packing, эritema, node, cyst, itch, ecchymosis. Rarely (1.5%) – abscess and cellulitis.
Noted no less than 2 adult patients on 100 patients-years, receiving combined treatment with an optimized antiretroviral therapy basic.
From the nervous system: headache, perifericheskaya neuropathy, dizziness, taste disturbance, insomnia, depression, alarm, nightmares, irritability, gipesteziya, impaired concentration, tremor.
The respiratory system: cough, sore throat.
For the skin: itch, night sweat, xerosis, increased sweating, seborrheic dermatitis, эritema, acne.
On the part of the musculoskeletal system: myalgia, arthralgia, backache, pain in the limbs, muscle spasms.
From the urinary system: concretions in the kidneys, hematuria.
From the digestive system: nausea, pain in the upper abdomen, constipation, diarrhea, pancreatitis.
From the senses: conjunctivitis, vertigo.
Allergic reactions: skin rash, itch, fever, nausea, vomiting, chills, tremor, arsnizhenie HELL, activity increase “hepatic” transaminases, primary immune complex reaction, respiratory distress syndrome, glomerulonephritis.
Other: weakness, weight loss, decreased appetite, anorexia, asthenia, flu-like symptoms, lymphadenopathy.
Infection: candidiasis of oral mucosa, herpes simplex, skin papilloma, flu, sinusitis, folliculitis, otitis, pneumonia.
Laboratory findings (changes were observed more frequently in patients, treated with combination therapy with enfuvirtide optimized base antiretroviral therapy, compared to patients, receive only the basic optimized antiretroviral therapy): eozinofilija, increased ALT, CPK, decrease in Hb.
No overdose information. Maximum imposed dose – 180 mg once p/. Side effects, other than arising with the introduction of the recommended dose, not marked.
Treatment: symptomatic. No specific antidote.
Clinically significant pharmacokinetic interactions between jenfuvirtidom and HP, of metabolism involving enzymes CYP450 family, not installed.
The introduction of the drug Fuzeon, in combination with ritonavir, sakvinavirom and rifampicin do not lead to clinically significant farmakokineticski interactions.
Enfuvirtide is not being forced out of their protein-binding sakvinavirom, nelfinavirom, lopinavir, EFV, nevirapine, amprenavir, itraconazole, Midazolam or warfarin.
Does not replace warfarin, midazolam, amprenavir or jefavirenz in their field associate with protein.
Study of enfuvirtide in combination with other. antiviral means various classes (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors), including as zidovudine, lamivudine, Nelfinavir, indinavir and эfavirenz, They showed the presence of the additive to synergistic effects and the lack of antagonism. Relationship between sensitivity of HIV-1 to jenfurvitidu in vitro and inhibition of HIV-1 replication in humans has not been established. Due to various target enzymes and is expected due to the activity of enfuvirtide in HIV strains, resistant to others. classes of antiviral drugs, HIV isolates, resistant to jenfuvirtidu must remain sensitive to the nukleozidnym reverse transcriptase inhibitors, nenukleozidnym reverse transcriptase inhibitors and protease inhibitors.
Do not mix with others. PM, with the exception of the supplied diluent (Water for Injection).
Data on the efficacy of the drug in children older than 3 years limited.
Appointed only in combination with other. mentioned HP. Patients with symptoms of alleged systemic allergic reaction should discontinue treatment and immediately undergo medical examination. Do not renew the treatment after the onset of systemic reactions, perhaps related to the admission of the drug. Risk factors, which may determine the development or severity of the allergic reaction is not installed.
When drug therapy is marked by increased frequency of occurrence of bacterial pneumonia (6.6 patients with pneumonia compared with 0.6 on 100 patients in groups, treated with combination therapy jenfuvirtidom and the optimized underlying seropositive and only optimized basic therapy, respectively; the analysis included pneumonia and related phenomena), which in some cases were fatal. Frequency of pneumonia in therapy jenfuvirtidom was similar to that in the general population of patients (literature data), but it was less than in the control group. Link of pneumonia with drug therapy is not installed. Risk factors for pneumonia included low initial CD4-lymphocyte number, high viral load, in/in the introduction of the HP, smoking and lung disease in history. It is necessary to carefully monitor the emergence of symptoms of infection, especially, if there are risk factors for developing pneumonia.
The most frequent side effects were reactions at the injection (98%). But canceling therapy required only 4% patients. The vast majority of local reactions (85%) mild to moderate severity, observed during the first week of treatment and does not restrict normal activities. The severity of pain and discomfort while continuing treatment did not increase. The number of local lesions, observed when there is a planned visit to a doctor during clinical studies, was less than 5 in 72% patients with such phenomena. The introduction of drug entities, uninfected HIV-1 (eg, After carrying out prevention) can cause anti-enfuvirtide antibodies, with swing quantization with HIV gp41, that can lead to lozhnopolozhitel'nomu HIV-test when conducting ELISA test for HIV-antibodies.
Enfuvirtide has not provided tertogennogo action in research, carried out on animals (rats and rabbits), dose in 8.9 times the human therapeutic. Study on the application of the drug in pregnant women have not been carried out. Use during pregnancy should be avoided, unless the potential benefit of therapy for the mother does not exceed the potential risk to the fetus.
It is not known whether the drug is secreted in breast milk in humans,. Breast-feeding should be stopped prior to the start of therapy, incl. and in order to avoid HIV transmission to the child.
Jefuvirtid not mutagenic and clastogenic properties in a series of tests in vivo and in vitro; It had no effect on fertility in male and female rats at doses, superior in 0.7, 2.5 and 8.3 times the maximum recommended daily dose for humans and calculated in mg / kg s / c.
There is no evidence of the influence of the drug on the ability to drive and operate moving mechanisms, However, you must take into consideration the side effects, occur when a drug.
Divorced product stored in the refrigerator (2-8 degrees c) and use within 24 no. Before the introduction of the ready solution from the fridge is brought to room temperature (eg, hold in hand for about 5 m) and check whether the contents of bottle dissolved. The recovered solution does not use, If it contains the mechanical inclusion.