Enfuvirtide - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Means for the treatment of HIV infection

Included in the formulation

Fuzeon®

lyophilizate PC

Hoffmann-La Roche Ltd. Switzerland

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

J.05.A.X.07 Enfuvirtide

Pharmacodynamics:Fusion inhibitor (fusion). Specifically binding to the HIV-1 gp41 glycoprotein outside the cell and inhibiting its structural rearrangement, blocks the penetration of the virus into the cell. Does not require intracellular activation. Antiviral activity is due to interaction with another seven-fold repetitive site of HR1 in natural gp41 on the surface of the virus.

Pharmacokinetics:

After a single subcutaneous injection into the anterior abdominal wall of enfuvirtide at a dose of 90 mg, the maximum concentration is 4.59 ± 1.5 μg / ml, AUC is 55.8 ± 12.1 μg x h / ml, absolute bioavailability is 84.3 ± 15.5%. When administered subcutaneously in the dose range of 45-180 mg, bioavailability is proportional to the dose administered. Absorption does not depend on the place of administration. The equilibrium concentration at a dose of 90 mg is 2.6-3.4 μg / ml. The volume of distribution after intravenous administration of 90 mg is 5.5 ± 1.1 L. Binding to plasma proteins - 92% (mainly with albumin and to a lesser extent - with acid α₁glycoprotein).

Being a peptide, it is subjected to catabolism to the amino acids that make up its composition, followed by their utilization in the body. Does not inhibit the isoenzymes of the CYP system. In vitro hydrolysis of the amide group of the C-terminus of the amino acid phenylalanine leads to the formation of a deamidated metabolite and the formation of this metabolite is independent of NADPH. Metabolite is detected in the plasma after the introduction of enfuvirtide with an AUC of 2.4-15% of the AUC of enfuvirtide.

After subcutaneous administration of enfuvirtide in a dose of 90 mg, the half-life period is 3.8 ± 0.6 hours, the clearance is 1.7 ± 0.4 l / h.

Indications:

HIV-1 (in combination with other antiretroviral agents).

ICD-10

I.B20-B24.B24 Disease caused by human immunodeficiency virus [HIV], unspecified

Contraindications:

Lactation (breastfeeding), increased sensitivity to enfuvirtide.

Carefully:

Pregnancy, children's age (up to 6 years). Intravenous drug administration, low CD4 count⁺lymphocytes, high viral load, lung diseases in the anamnesis, smoking.

Pregnancy and lactation:

Recommendations for FDA - Category B. Qualitative and well-controlled studies on humans have not been conducted. It is not recommended to use during pregnancy, except when the potential benefit of therapy for the mother exceeds the possible risk to the fetus.

It is not known whether enfuvirtide with human breast milk.If it is necessary to use lactation, breastfeeding should be discontinued.

Dosing and Administration:

Subcutaneously in the shoulder region, the front surface of the thigh or the anterior abdominal wall. It is necessary to change the location of each subsequent injection.

Adults - 90 mg 2 times a day.

Children 6-16 years - 2 mg / kg 2 times a day. The maximum dose is 90 mg 2 times a day.

Dosages administered 2 times a day and the corresponding volume of solution recommended in pediatric practice, depending on the body weight: 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 than 42.6 kg 90 mg ( 1 ml).

Correction of the dose for patients with a creatinine clearance of more than 35 ml / min is not required.

Lyophilized powder should be diluted with sterile water for injection to obtain a solution.

Side effects:

Local reactions: pain, discomfort at the injection site, compaction, erythema, node, cyst, itching, ecchymosis. Rarely (1.5%) is an abscess and phlegmon.

From the side nervous system: headache, peripheral neuropathy, dizziness, impaired taste, insomnia, depression, anxiety, nightmares, irritability, hypoesthesia, impaired concentration, tremor.

From the side respiratory system: cough, sore throat.

From the side skin integument: itching, night sweats, dry skin, excessive sweating, seborrheic eczema, erythema, acne.

From the side musculoskeletal system: myalgia, arthralgia, back pain, pain in the limbs, muscle spasms.

From the side urinary system: concrements in the kidneys, hematuria.

From the side digestive system: nausea, pain in the upper abdomen, constipation, diarrhea, pancreatitis.

From the side sense organs: conjunctivitis, vertigo.

Allergic reactions: skin rash, itching, fever, nausea, vomiting, chills, tremors, decreased blood pressure, increased activity of hepatic transaminases, primary reaction of immune complexes, respiratory distress syndrome, glomerulonephritis.

Other: weakness, weight loss, decreased appetite, anorexia, asthenia, flu-like syndrome, lymphadenopathy.

Infections: candidiasis of the oral mucosa, herpes simplex, skin papilloma, influenza, sinusitis, folliculitis, otitis media, pneumonia.

Laboratory indicators (changes were observed more often in patients who received combined therapy with enfuvirtide with optimized baseline antiretroviral therapy, compared with patients who received anti-receiving only optimized basic antiretroviral therapy): eosinophilia, increased activity of ALT, creatine phosphokinase, decreased hemoglobin.

Overdose:

There is no information about an overdose. The maximum administered dose is 180 mg once subcutaneously. Side-effects, other than those that occur when a recommended dose is administered, are not noted.

Treatment: symptomatic. There is no specific antidote.

Interaction:

Do not mix with other drugs, except for the supplied solvent (water for injections).

Studies of enfuvirtide in combination with other antiviral agents of various classes (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors), including zidovudine, lamivudine, nelfinavir, indinavir and efavirenz, showed the presence of additive to synergistic effects and the absence of antagonism.

Special instructions:

Applied only in combination with other antiretroviral agents.

If suspected of a systemic allergic reaction, discontinue treatment and examine the patient.Do not resume treatment after the occurrence of systemic reactions, possibly associated with the use of enfuvirtide. Risk factors that may predetermine the development or severity of an allergic reaction are not established.

Against the background of therapy, there was an increased incidence of bacterial pneumonia, which in some cases was fatal. Risk factors for the development of pneumonia include a low baseline number of CD4-lymphocytes, a high viral load, intravenous medication, smoking and a history of lung disease. It is necessary to carefully monitor the appearance of symptoms of infection, especially if there are risk factors for the development of pneumonia.

The influence on the ability to drive vehicles and work with mechanisms has not been established, however, it is necessary to take into account the adverse reactions that occur in the background of therapy.

Instructions

Enfuvirtide (Enfuvirtidum)