Enfuvirtid
When ATH:
J05AX07
Pharmacological action
Fusion inhibitor (confluence). Specific binding to the glycoprotein gp41 of HIV-1 is cell and inhibiting its structural rearrangement, blocks the penetration virus into cells. It does not require intracellular activation. Antiviral activity due to the interaction with the other seven times repeated patterns in the natural gp41 HR1 on the virus surface
Pharmacokinetics
After a single s / c administration to the anterior abdominal wall at a dose of enfuvirtide 90 mg Cmax - 4.59 ± 1.5 pg / 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 at a dose 90 mg - 2.6-3.4 ug / ml. Vd After i / v administration 90 mg - 5.5 ± 1.1 L. Plasma protein binding – 92% (mainly to albumin and, less – with an acidic α1-glycoprotein).
It is a peptide, subjected to amino acid catabolism, its constituent, with their subsequent utilization in the body. It does not inhibit CYP isoenzymes system. 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 of a dose of enfuvirtide 90 mg T1/2 - 3.8 ± 0.6, clearance - 1.7 ± 0.4 l / h.
Testimony
HIV-1 (in combination with other antiretroviral agents).
Dosage regimen
Enter n / a in the shoulder area, anterior thigh or abdominal wall. Dose set individually, depending on the age and weight of the patient. No dose adjustment for patients with CC more 35 ml / min does not require.
Side effect
From the central and peripheral nervous system: headache, perifericheskaya neuropathy, dizziness, taste disturbance, insomnia, depression, alarm, nightmares, irritability, gipesteziya, impaired concentration, tremor.
The respiratory system: cough, sore throat, sinusitis, folliculitis, pneumonia, respiratory distress syndrome.
Dermatological reactions: itch, night sweat, xerosis, increased sweating, seborrheic dermatitis, эritema, acne, herpes simplex, skin papilloma.
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, glomerulonephritis.
From the digestive system: nausea, pain in the upper abdomen, constipation, diarrhea, pancreatitis, decreased appetite, anorexia, candidiasis of the oral mucosa, nausea, vomiting, increase in liver transaminases.
From the senses: conjunctivitis, vertigo, otitis.
Allergic reactions: skin rash, itch, fever, chills, tremor, decrease in blood pressure, primary immune complex reaction.
Local reactions: pain, discomfort at the injection site, packing, эritema, node, cyst, itch, ecchymosis; rarely – abscess and cellulitis.
Other: weakness, weight loss, asthenia, flu-like symptoms, lymphadenopathy, flu; changes in laboratory parameters (most 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.
Contraindications
Lactation (breast-feeding), hypersensitivity to enfuvirtide.
Pregnancy and lactation
Not recommended during pregnancy except, when the potential benefits of treatment to the mother outweighs the potential risk to the fetus.
It is not known whether enfuvirtide is allocated with breast milk in humans. If necessary, use during lactation should stop breastfeeding.
IN experimental studies enfuvirtide has not shown mutagenic and clastogenic properties 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.
Cautions
Only applicable in combination with other antiretroviral agents.
If you suspect a systemic allergic reaction should discontinue treatment and examine the patient. Do not renew the treatment after the onset of systemic reactions, possibly associated with taking enfuvirtide. Risk factors, which may determine the development or severity of the allergic reaction is not installed.
The therapy was an increase in the incidence of bacterial pneumonia, which in some cases were fatal. Risk factors for pneumonia included low initial CD4-lymphocyte number, high viral load, / in the administration of the drug, 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.
Effects on ability to drive vehicles and management mechanisms
Not applicable effect on the ability to drive vehicles and operate machinery, but consider the side effects, arising during therapy.
Drug Interactions
Studies of enfuvirtide in combination with other antiviral agents different 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.
