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

Significant inhibition of CYP3A4, increased concentration and effectiveness of concomitant antiretroviral agents (booster effect); enhancement of the effect of other protease inhibitors by inhibiting cytochrome P450 isoenzymes: CYP3A> CYP2D6> CYP2C9, CYP2C19 >> CYP2A6, CYP1A2, CYP2E1 (series of decrease in affinity).

Inhibition of HIV protease inhibits rupture of the gag-pol bond of the polyprotein, which leads to the formation of an immature and unable to infect the virus. Ritonavir has a selective affinity for the HIV protease and shows little activity with respect to aspartyl protease of a human.

The in vitro data indicate that ritonavir is active against all types of HIV tested on various primary and transformed human cell lines.

Pharmacokinetics:

F 65-75% (increase with admission with fatty foods by 15%). VD 0.41 ± 0.25 l / kg.Relationship with plasma proteins 98-99%. Biotransformation with the formation of active metabolite M2 occurs in the liver (CYP3A4, CYP2D6). Typical is the induction of its own metabolism. The half-life of 3-5 hours Cl 2.1 ± 0.8 ml / min (increased in children, decreased with cirrhosis of the liver). Is eliminated with the feces (86%, 34% of them in unmodified form) and kidney (11% of them in unmodified form at 3.5-4%).

Indications:

Treatment of HIV infection.

ICD-10

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

Contraindications:

Hypersensitivity to ritonavir.

Simultaneous use with amiodarone, astemizole, itraconazole, ketoconazole, bepridilum, cisapride, bupropion, clozapine, dihydroergotamine, ergotamine, enkainide, flecainide, meperidine, nimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, terfenadine, sodium clorazepate, flurazepam, diazepam, estazolam, midazolam, triazolam, zolpidem, alprazolam.

Carefully:

Use with caution in patients with liver disease.

During the treatment period, it is necessary to regularly monitor the liver function in patients with a previous increase in the level of liver enzymes and in hepatitis, as well as long-term treatment and in elderly patients.

Pregnancy and lactation:

Recommendations FDA category B.

Adequate and well-controlled studies in humans are not conducted. In animals, an insignificant increase in the incidence of cryptorchidism, the resorption of fruits and their small size. There is no information on the penetration into breast milk. HIV patients do not breast-feed.

Dosing and Administration:

When administered to adults - 600 mg 2 times / day. To reduce the side effect on the first day, you can use 300 mg 2 times / day, followed by a gradual increase in the dose of 100 mg until the recommended dose.

In children it is recommended to use in combination with antiviral analogues of nucleosides. The recommended dose is 400 mg / m2 2 times / day. Determination of the dose for children is recommended to be carried out according to a special nomogram table.

Side effects:

From the digestive system: often - anorexia, nausea, vomiting, diarrhea, dry mouth, ulcerative lesions of the oral mucosa, eructations, flatulence, impaired functional liver tests; an increase in liver and digestive enzymes.

From the side of the central nervous system and the peripheral nervous system: often - fear, insomnia, paresthesia around the mouth and on the periphery, dizziness, drowsiness.

From the respiratory system: possible laryngitis, cough, pharyngitis.

On the part of the hematopoiesis system: reduction of hemoglobin, decrease in hematocrit, decrease in the number of erythrocytes, decrease in the number of leukocytes, a decrease in the number of neutrophils, an increase in the number of eosinophils.

From the side of metabolism: increased uric acid, hyperlipidemia, weight loss, decreased potassium, increased triglycerides.

Dermatological reactions: skin rash, itching, increased sweating.

Other: expansion of peripheral vessels, myalgia.

Overdose:Not studied.

Interaction:

Amiodarone, dihydroergotamine, lovastatin, methylergonovine, midazolam, pimozide, propafenone, simvastatin, trazolam, flecainide, quinidine, cisapride, ergonovine, ergotamine, Hypericum perforatum (Hypericum perforatum) - increase in their concentration with the development of severe side effects. Do not use at the same time!

Atovaquon, warfarin, дивалпроекс, lamotrigine, phenytoin - careful monitoring of treatment is necessary.

Atorvastatin, bupropoin, verapamil, dexamethasone, diazepam, disopyramide, diltiazem, dronabinol, estazolam, zolpidem, carbamazepine, clonazepam, clorazepate, lidocaine, mexiletine, methamphetamine, metoprolol, nefazodone, nefidipin, perphenazine, prednisone, propoxyphene, risperidone, sirolimus, tacrolimus, timolol, thioridazine, Tamadol, flurazepam, quinine, ciclosporin, ethosuximide, selective serotonin reuptake inhibitors, tricyclic antidepressants - monitoring of joint therapy; should reduce the dose of these funds.

Didanosine, oral contraceptives containing ethinyl estradiol, methadone, theophylline - reduction of their concentration and effectiveness; Do not use at the same time or you need to change the dose regimen, carry out pharmacotherapeutic monitoring.

Disulfiram, metronidazole - development of disulfiram-like reactions in connection with the content of ethanol in the ritonavir drug form.

Desipramine, indinavir, clarithromycin, ketoconazole, meperedin, rifabutin, saquinavir (in low doses), sildenafil - increase in their concentration (or metabolites); should reduce the dose.

Rifampicin is a decrease in the concentration and effect of ritonavir.

Special instructions:

HIV-1 protease substrate analogue, hydroxyethylamine derivative.

It should be used only as a booster to enhance the effect of indinavir,lopinavir or saquinavir and in combination with two other antiretroviral agents.

Instructions

Ritonavir (Ritonavirum)