Вирасепт

Uses

Вирасепт is used for the treatment of HIV infection when antiretroviral therapy is warranted

Вирасепт is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection

How Вирасепт works

Вирасепт inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

Dosage

Вирасепт dosage

Adults: The recommended dose is 1250 mg (five 250 mg tablets) twice daily or 750 mg (three 250 mg tablets) three times daily. Вирасепт should be taken with a meal. Antiviral activity is enhanced when Вирасепт is administered in combination with nucleoside analogues. Therefore, it is recommended that Вирасепт should be used in combination with nucleoside analogues.

Paediatric patients (2-13 years): The recommended oral dose of Вирасепт for paediatric patients 2 to 13 years of age is 20-30 mg/kg per dose, three times daily with a meal.

Side Effects

The safety of Вирасепт was studied in over 1500 patients who received drug either alone or in combination with nucleoside analogues. The majority of adverse events were of mild intensity. The most frequently reported adverse event among patients receiving Вирасепт was diarrhoea, which was generally of mild to moderate intensity. Adverse events occurring in less than 2% of patients receiving Вирасепт in all phase II/III clinical trials and considered at least possibly related or of unknown relationship to treatment and of at least moderate severity are listed below.

General: Abdominal pain, accidental injury, allergic reaction, asthenia, back pain, fever, headache, malaise, pain and redistribution/accumulation of body fat.

Digestive system: Anorexia, dyspepsia, epigastric pain, gastrointestinal bleeding, hepatitis, mouth ulceration, pancreatitis and vomiting.

Haemic/Lymphatic system: Anaemia, leukopenia and thrombocytopenia.

Metabolic/Nutritional: Increase in alkaline phosphate, amylase, creatinine phosphokinase, lactic dehydrogenase, SGOT, SGPT and g glutamyl transpeptidase, hyperlipaemia, hyperuricaemia, hyperglycaemia, hypoglycaemia, dehydration and liver function tests abnormal.

Musculoskeletal system: Arthralgia, arthritis, cramps, myalgia, myasthenia and myopathy.

Nervous system: Anxiety, depression, dizziness, emotional lability, hyperkinesia, insomnia, migraine, paraesthesia, seizures, sleep disorder, somnolence and suicide ideation.

Respiratory system: Dyspnoea, pharyngitis, rhinitis and sinusitis.

Skin/Appendages: Dermatitis, folliculitis, fungal dermatitis, maculopapular rash, pruitus, sweating, and urticaria.

Ophthalmic: Acute iritis and eye disorder.

Urogenital system: Kidney calculas, sexual dysfunction.

Toxicity

Oral LD₅₀ is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.

Precaution

Вирасепт should not be administered concurrently with Terfenadine, Astemizole, Cisapride, Triazolam, Midazolam, Ergot derivatives, Amiodarone or Quinidine because Вирасепт may affect the hepatic metabolism of these drugs and create potential for serious and/or life-threatening adverse events. New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycaemia have been reported during post-marketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycaemic agents for treatment of these events. In some cases diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycaemia persisted in some cases.

General: Вирасепт is principally metabolised by the liver. Therefore, caution should be exercised when administering this drug to patients with hepatic impairment.

Haemophilia: There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis, in patients with haemophilia type A and B treated with protease inhibitors. In some patients, additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. A causal relationship has not been established.

Interaction

Reduced levels/effects with antacids, phenobarbital, carbamazepine, aminoglutethimide, phenytoin, rifampicin, nafcillin, nevirapine, omeprazole, nevirapine. Increased serum levels/effects with azole antifungal agents, cimetidine, efavirenz. Increased serum levels/effects of azithromycin, calcium channel blockers, clarithromycin, corticosteroids (e.g. fluticasone), mirtazapine, nateglinide, nefazodone, ciclosporin, sirolimus, tacrolimus, venlafaxine, eplerinone, fentanyl, atorvastatin, phosphodiesterase-5 (PDE-5) inhibitors, rifabutin, trazodone, TCAs. Reduced serum levels/effects of hormonal contraceptives, methadone, theophylline derivatives.

Food Interaction

• Take with food. Food increases exposure and decreases pharmacokinetic variability.

Вирасепт Cholesterol interaction

[Moderate] Hyperlipidemia has been observed in 10% of patients receiving ritonavir during clinical trials.

Increases of 30% to 40% from baseline have been reported for total cholesterol and 200% to 300% or more for triglycerides.

These effects have also been reported during postmarketing experience with other protease inhibitors (PIs) but may be the most dramatic with ritonavir.

The clinical significance of these elevations is unclear.

Severe hyperlipidemia is known to sometimes cause pancreatitis.

In addition, some patients have reportedly developed symptomatic atherosclerosis and coronary artery disease after initiating PI treatment.

Patients with preexisting hyperlipidemia may require closer monitoring during PI therapy, and adjustments made accordingly in their lipid-lowering regimen.

PI therapy should be administered cautiously in patients with coronary artery disease or a history of ischemic heart disease.

Вирасепт Drug Interaction

Major: methylprednisolone, omeprazole, oxycodoneModerate: doxorubicin, loratadine / pseudoephedrine, indinavir, ritonavir, finasteride, dulaglutideMinor: famotidineUnknown: contained in alcoholic beverages , aspirin, lamivudine / zidovudine, ibuprofen, rabies vaccine, human diploid cell, carfilzomib, cisplatin, sulfamethoxazole / trimethoprim, filgrastim

Вирасепт Disease Interaction

Major: hemophiliaModerate: liver disease, PKU, hyperglycemia, hyperlipidemia

Volume of Distribution

• 2 to 7 L/kg

Elimination Route

Well absorbed following oral administration.

Half Life

3.5 - 5 hours

Elimination Route

The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1–2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.

Pregnancy & Breastfeeding use

Pregnancy Category B. There are no adequate and well controlled studies in pregnant women.

Lactation: The US Public Health Service Centers for Disease Control and Prevention advises HIV-infected women not to breast-feed to avoid postnatal transmission of HIV to a child.

Contraindication

Вирасепт is contraindicated in patients with clinically significant hypersensitivity to any of its components. Co-administration of Avifix is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening adverse events

Special Warning

Paediatric use: The safety, effectiveness and pharmacokinetics of Вирасепт have not been evaluated in paediatric patients below the age of 2 years.

Storage Condition

Store at 15-30° C

Innovators Monograph

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