Ritonavir

Ritonavir is an antiretroviral agent belongs to the group of known as protease inhibitors, but ritonavir has improved oral bioavailability compared with other protease inhibitors. Ritonavir is used either alone, or in combination with nucleoside reverse transcriptase inhibitor, for the treatment of progressive or advanced HIV infection.

Brands
Adult Dose
Dose: 600 mg
Single Dose: 600 (600)
Frequency: 12 hourly
Route: PO
Instructions:
Neonatal
Paedriatic
Characteristics
. The Molecular Weight of Ritonavir is 720.90.
Contraindications
Ritonavir
Effects
The severe or irreversible adverse effects of Ritonavir, which give rise to further complications include Orthostatic hypotension, Vasodilation, Syncope, Myalgia, Renal insufficiency.The symptomatic adverse reactions produced by Ritonavir are more or less tolerable and if they become severe, they can be treated symptomatically, these include Dizziness, Headache, Fatigue, Diarrhea, Pruritus, Skin RashX, Taste disturbance, Asthenia, Nausea and vomiting.
Indications
Ritonavir is primarily indicated in conditions like Chronic lymphocytic leukaemia, HIV infection, Schizophrenia and other psychoses.
Interactions
Ritonavir is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAbacavirAfatinibritonavir may increase the level of afatinibuse alternative or reduce dose.Amiodarone (HCl)Ritonavir may decrease the metabolism, via CYP isoenzymes, of Amiodarone thus increase its plasma concentration resulting in prolong QT interval and ventricular arrhythmias.MajorThis combination is contraindicated.Amlodipine (Besylate)Increased plasma concentration of Amlodipine when given with antivirals (e.g Ritonavir).ArtesunateConcurrent use may increase artesunate serum concentrations . AstemizoleRitonavir increases the plasma concentration of astemizole by inhibiting its metabolism. Increased plasma level may lead to prolongation of QT interval, ventricular arrythmia, cardiac arrest and sudden death.MajorCoadministration of these agents is considered contraindicated. Loratidine, fexofenadine and cetirizine are considered more safer alternatives.BosentanPlasma concentration of Bosentan possibly increased by Ritonavir.MajorCanagliflozinco administration may decrease the efficacy of canagliflozinincrease dose to 300mg once dailyCarbamazepineCoadministration decreases the plasma level of ritonavir due to cabamazepine induction of CYP450 3A4 which also metabolizes ritonavir.ModerateCare must be taken during coadministration and carbamazepine serum level must be closely monitored.CisaprideRitonavir increases the plasma concentration of cisapride by inhibiting its metabolic clearence. Increased level of cisapide results in prolongation of QT interval on ECG, ventricular arrythmia, cardiac arrest and sudden death.MajorCoadministration should be avoided.ClarithromycinRitonavir increases the plasma concentration of clarithromycin by inhibiting CYP450 3A4, an enzyme responsible for metabolic conversion of clarithromycin to 14-hydroxyclarithromycin. ModerateDose of clarithromycin should be reduced upto 50% in patient with moderate renal impairment and upto 75% with severe renal impairment.Clorazepate (K)ClozapineRitonavir decreases the plasma concentration of clozapine by enhances its hepatic metabolism.MinorDose of clozapine should be adjusted accordingly.conjugated Estrogens/Bazedoxifenemay increase the exposure of conjugated estrogensmonitor closelyCyclosporin ADeflazacortDesipramine (HCl)DexamethasoneDextropropoxypheneDidanosineDigoxinRitonavir may increase the serum concentration of Digoxin. ModerateMonitor for increased effects of digoxin if Ritonavir is initiated/dose increased, and for decreased effects if Ritonavir is discontinued/dose decreased. Dihydroergotamine (Mesylate)DisulfiramDolutegravirdecrease level of dolutegravirdose adjustment recommendedErgotamine (Tartrate)ErlotinibThis CYP3A4 inhibitor increases levels/toxicity of erlotinibErythromycinRitonavir increases plasma concentration of erythromycin by inhibiting CYP450 3A4 thus prolong QT interval which leads to ventricular arrhythmias.MajorErythromycin and ritonavir coadministration should be avoided.Estrogens ConjugatedFlecainide (Acetate)FluconazoleFluconazole responsible for CYP450 3A4 inhibition can cause slight increase in ritonavir plasma concentration.MinorNo such measures should be taken in coadministration of these drugs.Fluoxetine (HCl)HaloperidolCoadministration increases the plasma concentration by decreasing clearance due to competitive inhibition of CYP4502D6.ModerateDose adjustment as well as clinical and laboratory monitoring should be done.IndacaterolStrong inhibitors of CYP3A4 may increase levels of indacaterol.monitor closely for adverse eventItraconazoleKetoconazoleCo-admistration increases the plasma concentration of ketoconazzole by inhibiting ritonavir metabolism.ritonavir increases Cmax and AUC of ketoconazole upto 55%.ModerateTo avoid excessive plasma drug levels ketoconazole should not exceed to 200mg/day.co-administration increases risk of hepatotoxicity,impairment of testosterone and cortisol productionLinagliptinRitonavir increases AUC and Cmax of Linagliptin two to three foldsMacitentanRitonavir approximately doublemacitentan exposureAvoid concomitant use of macitentan with strong CYP3A4 inhibitorsMethadoneMetronidazoleMidazolamOxycodonePethidine (HCl)PhenobarbitonePhenytoin (Na)Prednisolone and PrednisoneProgesteronePropafenone (HCl)QuinidineRifabutinRifampicinRivaroxabanHIV protease Inhibitor , it may increase plasma concentration of Rivaroxaban, lead to BleedingNot indicatedRosuvastatinRitonav irsignificantly increased rosuvastatin exposure. Iin patients taking a combination of Ritonavir the dose of Rosuvastatin should be limited to 10 mg once daily. SalmeterolConcurrent use may potentiate the risk of cardiovascular adverse events.SaquinavirSunitinibMay increases sunitinib concentrations.TacrolimusTadalafilRitonavir (500 mg or 600 mg twice daily at steady state), an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil 20-mg single-dose exposure (AUC) by 32% with a 30% reduction in Cmax, relative to the values for tadalafil 20 mg alone. Tenofovir DisoproxilRitonavir has been shown to increase tenofovir concentrations.TerfenadineTheophyllineTriazolamVemurafenibRitonavir inhibit P-gp, glucuronidation and CYP3A4, and increases plasma concentration of Vemurafenib.VORICONAZOLERitonavir may decrease the serum concentration of voriconazole by increasing its metabolism. Concomitant therapy with high dose ritonavir is contraindicated. Vortioxetineincreases the level of vortioxetineuse alternative or reduce dose ofvortioxetune by 50%Zolpidem (Tartrate) These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.
Interfrence
Risks
If prescribing authority justifies the benefits of the drug against the possible damages he/she should reevaluate them and consult the reference material and previous studies.
Storage
Caps, Oral Soln, Store in a well closed container. Refrigeration is recommended.
Warnings
Caution is required in diabetic patient, patients with hemophilia who may experienced increased bleeding. It should be used with caution and possible dose reduction is needed in hepatic impairment. Adequate hydration is recommended to avoid any risk of nephrolithiasis. Monotoring is required in case of renal impairment.
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