Arlansa pills 100mg, 56pcs

Composition

of 1 tab. : Active ingredients:  narlaprevir-100 mg; Excipients: Copovidone (Plasdone S-630) – 100 mg, microcrystalline cellulose-52 mg, sodium lauryl sulfate-15 mg, croscarmellose sodium-30 mg, colloidal silicon dioxide-1.5 mg, magnesium stearate-1.5 mg

Pharmacological action

An antiviral agent, an NS3 inhibitor of the hepatitis C virus serine protease. Narlaprevir has an inhibitory effect by covalent but reversible binding to the serine active site of the hepatitis C virus protease via a ketoamide functional group. Thus, narlaprevir inhibits the virus ‘ polyprotein processing and prevents its replication in infected host cells.

When studying antiviral activity in cell culture, it was shown that the inhibition constant (Ki) of narlaprevir for NS3 protease genotype 1b is 7 nM. Narlaprevir is also active against genotypes 1a,2a,3a, and 4 (Ki=0.7 nM,3 nM,7 nM, and 16 nM, respectively). In the bicistrone replicon system of genotype 1b, the values of narlaprevir IC50 and ic90are 20 nM and 40 nM, respectively. In the genotype 1a replicon system, the IC₉₀of narlaprevir is 140 nM. In the presence of 50% human serum, the IC50 of narlaprevir in replicon 1b increases to 720 nM.

When conducting biochemical tests and study replicon demonstrated cross-resistance to narrativer when mutations of resistance encountered in the application of other ketoamide protease inhibitors of hepatitis C virus Activity of alapraia moderately reduced with the following basic virus mutations associated with resistance to other protease inhibitors of hepatitis C virus: V36M (Ki= 12 nm, IC₅₀ for replicon = 430 nm, IC₉₀ = 940 nm), V170A (Ki= 30 nm, IC₅₀ = 300 nm, IC₉₀ = 900 nm) T 54 A (Ki= 40 nm, IC₅₀ = 400 nm, IC₉₀ = 700 nm). The activity of narlaprevir is significantly reduced against mutations at loci 155 (R155K) and 156 (A156S/T). The multiplicity of resistance increases in double mutations is approximately equivalent to the sum of indicators for individual mutations (i. e., the relationship is multiplicative, not additive). Narlaprevir is fully active against the D168V mutation.

Indications

Treatment of chronic viral hepatitis C caused by genotype 1 virus in patients over 18 years of age with compensated liver damage, in combination with ritonavir, peginterferon alfa and ribavirin, who have not previously received antiviral therapy with peginterferon alfa and ribavirin, or in whom previous two-component treatment with peginterferon alfa and ribavirin was ineffective.

Narlaprevir is not used as monotherapy.

Contraindications

Severe neutropenia (neutrophil count

Since narlaprevir should only be used in combination with ritonavir, peginterferon alfa and ribavirin, appropriate contraindications to the use of these drugs should be considered.

Side effects

Adverse reactions observed during treatment with narlaprevir in combination with ritonavir, peginterferon alfa and ribavirin

Infectious and parasitic diseases:  infrequently: pharyngitis, herpes virus infection

From the hematopoietic system:  very often-a decrease in the concentration of hemoglobin; often-anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia.

From the immune system:  infrequently – hypersensitivity.

From the endocrine system:  infrequently – hypothyroidism.

From the side of metabolism:  often-decreased appetite, weight loss, hyperuricemia; infrequently-hypertriglyceridemia.

From the side of the psyche:  infrequently – sleep disorder, insomnia, decreased interest.

Nervous system disorders:  often – headache, dysgeusia; infrequently-drowsiness, dizziness.

From the side of the visual organ:  infrequently-eye pain.

From the cardiovascular system:  infrequently-tachycardia, arterial hypertension.

Respiratory system disorders:  often-cough; infrequently-tachypnea.

From the digestive system:  often – nausea, diarrhea; infrequently-upper abdominal pain, dry mouth, unusual feces, vomiting, abdominal discomfort, cheilitis, gastroesophageal reflux, bleeding gums, anal itching, anal fissure, proctalgia.

Liver and biliary tract disorders:  often – hyperbilirubinemia, increased GGT activity; infrequently-increased AST, alkaline phosphatase activity.

Skin and subcutaneous tissue disorders:  often – pruritus, alopecia, urticaria, rash (papular, macular); infrequently-xeroderma, dry skin, dermatitis, eczema, hyperhidrosis, rash.

From the musculoskeletal system: often-myalgia, arthralgia; infrequently-back pain, pain in the extremity.

From the urinary system:  infrequently – hemaglobinuria, proteinuria.

From the side of the reproductive system:  infrequently-bartholinitis.

General reactions:  very often – asthenia; often-flu-like condition, chills, pyrexia, fatigue, pain; infrequently-hyperthermia.

Interaction

Narlaprevir is a substrate and weak inhibitor of the CYP3A4 isoenzyme. In addition, ritonavir, a mandatory component of therapy with narlaprevir, is a potent inhibitor of the CYP3A4 isoenzyme, so when used together with drugs that are substrates, inhibitors and/or inducers of the CYP3A4 isoenzyme, it is possible to change the concentration of both narlaprevir and ritonavir, as well as concomitant drugs.

It has been shown that taking narlaprevir at therapeutic doses in combination with ritonavir does not lead to prolongation of the QTc interval. However, at doses many times higher than the therapeutic dose, narlaprevir in combination with ritonavir may prolong the QTc interval. Therefore, narlaprevir should be used with caution in patients taking concomitant medications that prolong the QT interval.

Since narlaprevir is used in combination with ritonavir, peginterferon alfa and ribavirin, possible drug interactions of concomitant therapy with each of the components of narlaprevir therapy should be considered.

How to take, course of use and dosage

Narlaprevir should be used in combination therapy with other antiviral drugs (ritonavir, peginterferon alfa and ribavirin). Narlaprevir with ritonavir in combination with peginterferon alfa and ribavirin should be used according to a special scheme.

In combination therapy, a single dose of narlaprevir is 200 mg

. The frequency of use and duration of use are determined in accordance with the treatment regimen.

Reducing the dose of narlaprevir and / or ritonavir during therapy is not allowed. If narlaprevir is discontinued due to the development of adverse reactions or an inadequate virological response, the resumption of narlaprevir therapy is not allowed.

During the entire treatment period, it is recommended to monitor the indicators of general, biochemical blood analysis, as well as the level of viral load.

Special instructions

Since narlaprevir is only used in combination with ritonavir, peginterferon alfa, and ribavirin, warnings for the use of these medications should be considered.

Narlaprevir should not be used as monotherapy

Co-use with medications that prolong the QT interval requires careful monitoring of ECG parameters.

It should be used with caution in cases of neutropenia, anemia.

During the entire treatment period, it is recommended to monitor the indicators of general and biochemical blood tests, as well as the level of viral load.

In case of development of adverse reactions potentially associated with peginterferon alfa or ribavirin, and requiring dose adjustment or suspension of therapy with any of these drugs, it is necessary to follow the instructions set out in the instructions for use of the relevant drug.

Influence on the ability to drive vehicles and mechanisms

Due to the possibility of fatigue or drowsiness during combination therapy with narlaprevir, ritonavir, peginterferon alfa and ribavirin, it is not recommended to drive a car and/or complex equipment.

Active ingredient

Narlaprevir

Conditions of release from pharmacies

By prescription

Dosage form

Tablets