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

Clinical and pharmacological group: & nbsp

Means for the treatment of HIV infection

Included in the formulation

Invirase®

pills inwards

Hoffmann-La Roche Ltd. Switzerland

Interfast®

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FARMASINTEZ, JSC (Irkutsk) Russia

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

VED

АТХ:

J.05.A.E. Protease Inhibitors

J.05.A.E.01 Saquinavir

Pharmacodynamics:

Promotes the formation of inactive virus particles that are unable to infect new cells. Competitively inhibits the protease of HIV, thereby disrupting the cleavage of the Gag-pol polypeptide by viral proteins - reverse transcriptase, proteases and integrases.

Pharmacokinetics:

Bioavailability is 4% for hard gelatin capsules and 13% for soft gelatin capsules; when taken with fatty food bioavailability increases by 600%. The volume of distribution is 10 l / kg - the main amount of the drug is in the tissues of the body, and not in the blood plasma. Relationship with plasma proteins 98%. Biotransformation in the liver (CYP3A4). The half-life is 7-12 hours. Cl 19 ± 2.3 ml / min. Eliminated with feces (more than 95%) and urine (less than 3%).

Indications:

HIV infection:

- as part of combination therapy in combination with antiretroviral agents;

- in the expressed stage of HIV infection with CD4 counts no more than 300 in 1 μl;

- monotherapy of patients with intolerance to nucleoside analogues.

ICD-10

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

I.B20-B24.B23.8 The disease caused by HIV, with manifestations of other specified states

I.B20-B24.B23.2 The disease caused by HIV, with manifestations of hematological and immunological disorders, not classified elsewhere

I.B20-B24.B23.1 The disease caused by HIV, with manifestations of (persistent) generalized lymphadenopathy

I.B20-B24.B22.7 The disease caused by HIV, with manifestations of multiple diseases classified elsewhere

I.B20-B24.B22.2 The disease caused by HIV, with manifestations of debilitating syndrome

I.B20-B24.B22.1 The disease caused by HIV, with manifestations of lymphatic interstitial pneumonitis

I.B20-B24.B22.0 The disease caused by HIV, with manifestations of encephalopathy

I.B20-B24.B21.9 The disease caused by HIV, with manifestations of unspecified malignant neoplasms

I.B20-B24.B21.8 The disease caused by HIV, with manifestations of other malignant neoplasms

I.B20-B24.B21.7 The disease caused by HIV, with manifestations of multiple malignant neoplasms

I.B20-B24.B21.3 The disease caused by HIV, with manifestations of other malignant neoplasms of lymphatic, hematopoietic and related tissues

I.B20-B24.B21.2 The disease caused by HIV, with manifestations of other non-Hodgkin's lymphomas

I.B20-B24.B21.1 The disease caused by HIV, with manifestations of Burkitt's lymphoma

I.B20-B24.B21.0 The disease caused by HIV, with manifestations of Kaposi's sarcoma

I.B20-B24.B20.9 The disease caused by HIV, with manifestations of unspecified infectious and parasitic diseases

I.B20-B24.B20.8 The disease caused by HIV, with manifestations of other infectious and parasitic diseases

I.B20-B24.B20.7 The disease caused by HIV, with manifestations of multiple infections

I.B20-B24.B20.6 The disease caused by HIV, with manifestations of pneumonia caused by Pneumocystis carinii

I.B20-B24.B20.5 The disease caused by HIV, with manifestations of other mycoses

I.B20-B24.B20.4 The disease caused by HIV, with manifestations of candidiasis

I.B20-B24.B20.3 The disease caused by HIV, with manifestations of other viral infections

I.B20-B24.B20.2 The disease caused by HIV, with manifestations of cytomegalovirus disease

I.B20-B24.B20.1 The disease caused by HIV, with manifestations of other bacterial infections

I.B20-B24.B20.0 The disease caused by HIV, with manifestations of mycobacterial infection

Contraindications:Hypersensitivity.

Carefully:

With severe liver damage (possibly an increase in plasma concentration), severe renal failure. Age to 16 and over 65 years of age (safety and efficacy in these age groups are not defined).

Pregnancy and lactation:

Action category for the fetus by FDA - AT

Adequate and well-controlled studies in humans are not conducted. Application in animals does not lead to impaired development of the fetus. There is no information on the penetration into breast milk.

Dosing and Administration:

Inside (not later than 2 hours after meals), 600 mg 3 times a day. Dosing is less than 1800 mg /day Not recommended.

Invirase: inside 600 mg 3 times a day (no later than 2 hours after ingestion) in combination with 0.75 mg of zalcitabine and / or 200 mg of zidovudine (total daily dose of saquinavir 1.8 g, zalcitabine 2.2 g, zidovudine 0.6 g).

Fortorthase: when used in combination with nucleoside analogues - inside by 1200 mg 3 times a day.

When combined with other protease inhibitors, the dose can be reduced if necessary.

Side effects:

From the nervous system and sensory organs: headache (8%), peripheral neuropathy (8%), paresthesia (6%),numbness in the limbs (5%), dizziness (2%), depression (≥ 2%), fatigue (≥ 2%), asthenia syndrome (≥ 2%), mental confusion, drowsiness, ataxia, seizures, suicide attempt.

From the cardiovascular system and blood: hypertension, hypotension, cyanosis, syncope, thrombophlebitis, hemolytic anemia, thrombocytopenia, neutropenia.

On the part of the digestive system: diarrhea (17%), nausea (8%), ulcerative stomatitis (6%), abdominal discomfort (4%), vomiting (3%), abdominal pain (3%), flatulence (2%), cheilitis, dysphagia , dyspepsia (≥ 5%), constipation (≥ 2%), intestinal obstruction, hepatitis, jaundice, portal hypertension.

From the side of metabolism: hyperglycemia, diabetes mellitus, ketoacidosis, obesity, dehydration.

From the genitourinary system: nephrolithiasis.

From the skin: skin rashes (5%), pruritus (3%), dermatitis, erythema, warts, Stevens - Johnson.

Other: ossalgiya, myalgia (≥ 2%), xerophthalmia, fever, elevated transaminases and creatin phosphokinase.

With combined therapy (optional):

- with zalcitabine: insomnia, vomiting, anorexia, hypoglycemia.

- with zidovudine: hot flashes, skin pigmentation, euphoria,insomnia, irritability, dry mouth, anorexia, intestinal hypermotorism, fecal discoloration, glossitis, laryngitis, urination disorder, myeloid leukemia.

- with zalcitabine and zidovudine: insomnia, decreased intelligence, irritability, euphoria, impaired vision and gustatory sensations, mucous membrane damage, glossitis, pharyngitis, shortness of breath, appetite disorder, pancreatitis, sweating.

Overdose:

Only one case of a dose of 8000 mg was studied. 2 hours later, vomiting was caused in the patient, no negative effects were noted.

Interaction:

Combination with zalcitabine and / or zidovudine does not affect their absorption, metabolism, excretion and toxicity profile.

Simultaneous reception with ranitidine while eating increases AUC by 67% compared to that when taken only with food. Inhibitors of the enzyme CYP3A4 (clarithromycin, ketoconazole, fluconazole, itraconazole, miconazole, grapefruit juice) increase the concentration in the plasma, without affecting the half-life.

Inductors of hepatic enzymes (rifampicin, rifabutin, phenobarbital, phenytoin, carbamazepine, dexamethasone) reduce concentration and activity.

It can increase plasma concentrations and toxicity of other compounds that are a substrate for CYP3A4 (nifedipine, verapamil, diltiazem, dapsone, clindamycin, quinidine, ergot alkaloids). Simultaneous reception of benzodiazepines metabolized by CYP3A4 (midazolam, triazolam), may be accompanied by prolongation of sedation.

Increases (mutually) AUC and Cmax of ritonavir, nevirapine, indinavir, nelfinavir, clarithromycin, terfenadine.

Special instructions:

HIV does not heal, against the background of treatment, there may be AIDS-associated diseases - opportunistic infections, etc. There are no data on the impact of treatment on the risk of HIV transmission.

Instructions

Saquinavir (Saquinavirum)