Ritonavir

720.96

720.94

208-127-9

O3J8G9O825

760369|693184

DTXSID1048627

C1609

White to light tan powder

J05AE03|J05AR10|J05AP53|J - Antiinfectives for systemic use

29341000

202

3.9

white to beige

1.239±0.06 g/cm3(Predicted)

120-122°C

947.0±65.0 °C(Predicted)

2℃

1.600

Practically insoluble in water;DMSO: soluble 10mg/mL (clear solution, warmed)

-20°C Freezer

1.1X10-27 mm Hg @ 25 deg C /Estimated/

Henry's Law constant = 2.7X10-33 atm-cu m/mol @ 25 °C /Estimated/

Hydroxyl radical reaction rate constant = 9.7X10-11 cu cm/molec-sec @ 25 °C /Estimated/

UN 1648 3 / PGII

3

36/38-20/21/22-41

26-37/39-36/37-39

XA5310000

Xi,Xn

P261-P280-P301 + P312 + P330

H302 + H312 + H332

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl ritonavir, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H302+H312+H332 (41.49%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P312, P322, P330, P337+P313, P363, P405, and P501|Aggregated GHS information provided by 94 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice. Oral LD value in rats is >2500 mg/kg. Adverse effects of ritonavir may arise from drug-drug interactions. Other effects include hepatotoxicity, pancreatitis, and allergic reactions/hypersensitivity.

In large randomized controlled trials, serum aminotransferase elevations more than 5 times the upper limit of normal (ULN) occurred in 1% to 2% of Viekira Pak treated patients. Interestingly, this rate was lower than occurred with placebo therapy (3% to 7%). The elevations were generally asymptomatic and short lived, resolving with or without dose modification and requiring drug discontinuation in approximately 1% of patients. Despite the frequency of serum enzyme elevations during therapy, clinically apparent liver injury was rarely reported in preregistration studies. However, since the general availability of Viekira Pak in the United States and during years of clinical use elsewhere, occasional instances of marked serum aminotransferase elevations with symptoms and mild jaundice have been reported, although not described in the published literature. Furthermore, some patients with chronic hepatitis C and advanced cirrhosis have developed sudden hepatic decompensation during therapy with D-O-P/r. Similar episodes have been described in patients receiving other oral antiviral combinations such as sofosbuvir with daclatasvir, ledipasvir or simeprevir. Thus, this phenomenon may be unrelated to a specific agent, but rather common to all potent antiviral therapies for hepatitis C and perhaps is a paradoxical response to sudden clearance of HCV. Alternatively, these episodes may be spontaneous, coincidental and unrelated to the antiviral therapy. Trials of these therapies in patients with cirrhosis have not been placebo controlled so that the rate of spontaneous hepatic decompensation in patients with cirrhosis due to hepatitis C is not well defined. Whatever the reason, the occurrence of decompensation in up to 10% of patients with cirrhosis undergoing potent antiviral therapy makes prospective monitoring advisable and prompt discontinuation of treatment if evidence of hepatic failure supervenes.|Some degree of serum aminotransferase elevations occurs in a high proportion of patients taking ritonavir containing antiretroviral regimens. Moderate-to severe elevations in serum aminotransferase levels (>5 times the upper limit of normal) are found in up to 15% of patients treated with full doses of ritonavir and are more common in patients with HIV-HCV coinfection. With low “booster” doses, ritonavir does not appear to increase the frequency or severity of serum enzyme elevations, and those that occur are usually asymptomatic and self-limited, resolving even with continuation of ritonavir. Clinically apparent liver injury from full doses of ritonavir has been reported, but hepatotoxicity from low dose ritonavir has not been clearly linked to acute liver injury. In many situations, the liver injury is difficult to attribute to ritonavir because it is used in combination with higher doses of other protease inhibitors. HIV protease inhibitors have been associated with acute liver injury arising 1 to 8 weeks after onset, with variable patterns of liver enzyme elevation, from hepatocellular to cholestatic. Immunoallergic features (rash, fever, eosinophilia) are uncommon as is autoantibody formation. Ritonavir in combination with saquinavir has also been associated with a rapid onset (1 to 4 days) acute hepatic injury in patients who are taking rifampin and perhaps other agents that affect CYP 450 activity, such as phenobarbital. Finally, initiation of ritonavir based highly active antiretroviral therapy can lead to exacerbation of an underlying chronic hepatitis B or C in coinfected individuals, typically arising 2 to 12 months after starting therapy and associated with a hepatocellular pattern of serum enzyme elevations and increases followed by falls in serum levels of hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA. Ritonavir therapy has not been clearly linked to lactic acidosis and acute fatty liver that is reported in association with several nucleoside analogue reverse transcriptase inhibitors.

These medications /amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, dihydroergotamine, encainide, ergotamine, flecainide, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin or terfenadine/ should not be administered concurrently with ritonavir; concurrent administration with ritonavir is likely to produce a large increase in the plasma concentrations of these medications, which may increase the risk of arrhythmias, hematologic abnormalities, seizures, or other potentially serious adverse effects.|In one study, concurrent administration /with clarithromycin/ increased the AUC of clarithromycin by 77% and the peak plasma concentration by 31%; dosing does not need to be adjusted in patients with normal renal function; however, for patients with a creatinine clearance of 30 to 60 ml/minute (0.5 to 1 ml/second), the dose of clarithromycin should be reduced by 50%, and for patients with a creatinine clearance of less than 30 ml/minute (0.5 ml/second), the dose of clarithromycin should be reduced by 75%.|These medications /clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, or zolpidem/ should not be administered concurrently with ritonavir; concurrent administration with ritonavir is likely to produce a large increase in the plasma concentrations of these medications, which may produce extreme sedation and respiratory depression.|In one study, concurrent administration /with estrogen-containing oral contraceptive/ decreased the AUC of ethinyl estradiol by 40%; an oral contraceptive with a higher estrogen content or an alternative method of contraception should be considered.|For more Interactions (Complete) data for RITONAVIR (14 total), please visit the HSDB record page.

Ritonavir is highly protein-bound in plasma (~98-99%), primarily to albumin and alpha-1 acid glycoprotein over the standard concentration range.

Indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.|FDA Label|Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV 1 infected patients (adults and children of 2 years of age and older).|Kaletra is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infected adults, adolescents and children aged from 14 days and older.The choice of Kaletra to treat protease inhibitor experienced HIV-1 infected patients should be based on individual viral resistance testing and treatment history of patients.|Lopinavir/ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infected adults, adolescents and children above the age of 2 years.The choice of lopinavir/ritonavir to treat protease inhibitor experienced HIV-1 infected patients should be based on individual viral resistance testing and treatment history of patients.|Viekirax is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.For hepatitis C virus (HCV) genotype specific activity.|Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1-infected patients (adults and children of two years of age and older).|Treatment of human immunodeficiency virus (HIV-1) infection|Treatment of chronic hepatitis C

Viekira Pak is a combination of oral antiviral agents that is used to treat chronic hepatitis C, genotype 1. This combination has been associated with a low rate of serum enzyme elevations during therapy, and has been reported to cause rare cases of clinically apparent liver injury with jaundice and may result in hepatic decompensation in some patients with preexisting cirrhosis.|Ritonavir is an antiretroviral protease inhibitor that is widely used in combination with other protease inhibitors in the therapy and prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Ritonavir can cause transient and usually asymptomatic elevations in serum aminotransferase levels and, rarely, can lead to clinically apparent acute liver injury. In HBV or HCV coinfected patients, highly active antiretroviral therapy with ritonavir may result of an exacerbation of the underlying chronic hepatitis B or C.

Hepatitis C Agents|Antiviral Agents

Ritonavir is indicated in combination with nucleoside analogs or as monotherapy for the treatment of HIV infection or AIDS. /Included in US product labeling/|Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult. The objective of this study was to investigate a liquid coformulation of lopinavir/ritonavir, in combination with reverse transcriptase inhibitors, in HIV-infected children. One hundred antiretroviral (ARV)-naive and ARV-experienced, nonnucleoside reverse transcriptase inhibitor-naive children between 6 months and 12 years of age participated in this Phase I/II, open label, multicenter trial. Subjects initially received either 230/57.5 mg/sq m or 300/75 mg/sq m lopinavir/ritonavir twice daily; ARV-naive subjects also received stavudine and lamivudine, whereas ARV-experienced subjects also received nevirapine and one or two nucleoside reverse transcriptase inhibitors. Lopinavir/ritonavir pharmacokinetics, safety and efficacy were evaluated. All subjects were escalated to the 300/75 mg/sq m twice daily dose based on results from an interim pharmacokinetic and safety evaluation. The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine. Overall 79% of subjects had HIV RNA levels <400 copies/mL at Week 48 (intent-to-treat: missing = failure). Mean increases in absolute and relative (percent) CD4 counts from baseline to Week 48 were observed in both ARV-naive subjects (404 cells/cu mm; 10.3%) and ARV-experienced subjects (284 cells/cu mm; 5.9%). Only one subject prematurely discontinued the study because of a study drug-related adverse event. The liquid coformulation of lopinavir/ritonavir demonstrated durable antiviral activity and was safe and well-tolerated after 48 weeks of treatment in HIV-infected children.

The most frequent adverse effects associated with ritonavir therapy involve the GI tract. In one clinical study in HIV-infected patients, nausea occurred in 25.6%, vomiting in 13.7%, diarrhea in 15.4%, taste perversion in 11.1%, abdominal pain in 6%, local throat irritation in 1.7%, anorexia in 1.7%, and flatulence in 0.9% of patients who received ritonavir monotherapy. In clinical studies in patients with HIV infection who received ritonavir in conjunction with nucleoside antiretroviral therapy or ritonavir in conjunction with saquinavir, nausea occurred in 18.4-46.6%, vomiting in 7.1-23.3%, diarrhea in 22.7-25%, taste perversion in 5-17.2%, anorexia in 4.3-8.6%, abdominal pain in 2.1-8.3%, local throat irritation in 0.9-2.8%, and flatulence in 1.7-3.5% of patients. Constipation, dyspepsia, or fecal incontinence occurred in 0.2-3.4, 0.7-5.9, or 2.8%, respectively, of patients receiving ritonavir with other antiretroviral agents; these effects were not reported in patients receiving ritonavir monotherapy. Many adverse GI effects reported with ritonavir are transient; vomiting persists for an average of 1 week, nausea for 2-3 weeks, and diarrhea for 5 weeks.|Adverse GI effects reported in less than 2% of patients receiving ritonavir alone or in conjunction with other antiretroviral agents include abnormal stools, bloody diarrhea, cheilitis, cholangitis, colitis, dry mouth, dysphagia, enlarged abdomen, eructation, esophageal ulcer, esophagitis, gastritis, gastroenteritis, GI disorder, GI hemorrhage, gingivitis,ileus, melena, mouth ulcer, pseudomembranous colitis, rectal disorder, rectal hemorrhage, sialadenitis, stomatitis, taste loss, tenesmus, thirst, tongue edema, and ulcerative colitis.|Peripheral paresthesia occurred in 6% and paresthesia or circumoral paresthesia occurred in 2.6-3.4% of patients with HIV infection receiving ritonavir monotherapy in one clinical study (study 245). In clinical studies in patients receiving ritonavir in conjunction with nucleoside antiretroviral therapy (studies 245 and 247) or in conjunction with saquinavir (study 462), peripheral paresthesia was reported in 55.7%, paresthesia in 2.1-5.2%, and circumoral paresthesia in 5.2-6.7% of patients. Asthenia occurred in 10.3% of patients receiving ritonavir monotherapy and in 15.3-28.4% of patients receiving ritonavir with other antiretroviral agents. Many of these adverse effects are transient; peripheral paresthesia persists for an average of 34 weeks and circumoral paresthesia and asthenia persist for 35 weeks.|Dizziness, insomnia, or somnolence have been reported in 2.6% of patients receiving ritonavir monotherapy and in 3.9-8.5, 2-3.4, or 2.4-2.6%, respectively, of patients receiving ritonavir with other antiretroviral agents. Headache, depression, or abnormal thinking were reported in 4.3-7.8, 1.7-7.1, or 0.7-2.6%, respectively, of patients receiving ritonavir in conjunction with other antiretroviral agents. Anxiety or confusion were reported in up to 2.1% of patients receiving ritonavir with other antiretroviral agents.|For more Drug Warnings (Complete) data for RITONAVIR (34 total), please visit the HSDB record page.

In patients treated with ritonavir, viral replication in the presence of drug selects for progressive accumulation of drug-resistance mutations. The first ritonavir resistance mutation is usually at protease codon 82. Additional mutations associated with increasing resistance occur at codons 20, 32, 46, 54, 63, 71, 84, and 90. High-level resistance requires multiple mutations.

Ritonavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Ritonavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Modern protease inhibitors require the use of low-dose ritonavir to boost pharmacokinetic exposure through inhibition of metabolism via the cytochrome P450 3A4 enzyme pathway.

Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly. (See all compounds classified as HIV Protease Inhibitors.)|Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A. (See all compounds classified as Cytochrome P-450 CYP3A Inhibitors.)

The absolute bioavailability of ritonavir has not been determined. Following oral administration, peak concentrations are reached after approximately 2 hours and 4 hours (T_max) after dosing under fasting and non-fasting conditions, respectively. It should be noted that ritonavir capsules and tablets are not considered bioequivalent.|Ritonavir is primarily eliminated in the feces. Following oral administration of a single 600mg dose of radiolabeled ritonavir, approximately 11.3 ± 2.8% of the dose was excreted into the urine, of which 3.5 ± 1.8% was unchanged parent drug. The same study found that 86.4 ± 2.9% of the dose was excreted in the feces, of which 33.8 ± 10.8% was unchanged parent drug.|The estimated volume of distribution of ritonavir is 0.41 ± 0.25 L/kg.|The apparent oral clearance at steady-state is 8.8 ± 3.2 L/h. Renal clearance is minimal and estimated to be <0.1 L/h.|Ritonavir and its metabolites are eliminated from the body predominantly in the feces (86% of unchanged drug and metabolites), with minor urinary elimination (11%, mostly metabolites).|Absorption of ritonavir is only slightly affected by diet, and this is somewhat dependent on the formulation. The overall absorption of ritonavir from the capsule formulation may increase by 15% when taken with meals. ... There is greater than sixfold variability in drug trough concentrations among patients given 600 mg of ritonavir every 12 hours.|The extent of oral absorption is high and is not affected by food. Within the clinical concentration range, ritonavir is approximately 98 to 99% bound to plasma proteins, including albumin and alpha 1-acid glycoprotein. Cerebrospinal fluid (CSF) drug concentrations are low in relation to total plasma concentration. However, parallel decreases in the viral burden have been observed in the plasma, CSF and other tissues. ... About 34% and 3.5% of a 600 mg dose is excreted as unchanged drug in the feces and urine, respectively. The clinically relevant t1/2 beta is about 3 to 5 hours. Because of autoinduction, plasma concentrations generally reach steady state 2 weeks after the start of administration. The pharmacokinetics of ritonavir are relatively linear after multiple doses, with apparent oral clearance averaging 7 to 9 L/hr.|Ritonavir is excreted principally in the feces, both as unchanged drug and metabolites. Following oral administration of 600 mg of radiolabeled ritonavir as the oral solution, 86.4% of the dose is excreted in feces (33.8% as unchanged drug) and 11.3% of the dose is excreted in urine (3.5% as unchanged drug).|For more Absorption, Distribution and Excretion (Complete) data for RITONAVIR (6 total), please visit the HSDB record page.

Ritonavir circulates in the plasma predominantly as unchanged drug. Five metabolites have been identified. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite in low plasma concentrations and retains similar antiviral activity to unchanged ritonavir. The cytochrome P450 enzymes CYP3A and CYP2D6 are the enzymes primarily involved in the metabolism of ritonavir.|... Ritonavir is primarily metabolised by cytochrome P450 (CYP) 3A isozymes and, to a lesser extent, by CYP2D6. Four major oxidative metabolites have been identified in humans, but are unlikely to contribute to the antiviral effect. ...|Five ritonavir metabolites have been identified in human urine and feces. The isopropylthiazole oxidation metabolite (M2) appears to be the major metabolite. M2 (but not other metabolites) has antiviral activity similar to that of ritonavir; however, only very low concentrations of this metabolite are present in plasma. Other metabolites identified in in vitro studies include a decarbamoylated metabolite (M1) and a product of N-dealkylation at the urea terminus (M11).

The approximate half-life of ritonavir is 3-5 hours.|The clinically relevant t1/2 beta is about 3 to 5 hours.

Ritonavic inhibits the HIV viral proteinase enzyme that normally cleaves the structural and replicative proteins that arise from major HIV genes, such as *gag* and *pol*. *Gag* encodes proteins involved in the core and the nucleocapsid, while *pol* encodes the the HIV reverse transcriptase, ribonuclease H, integrase, and protease. The *pol*-encoded proteins are initially translated in the form of a larger precursoe polypeptide, *gag-pol*, and needs to be cleaved by HIV protease to form other complement proteins. Ritonavir prevents the cleavage of the *gag-pol* polyprotein, which results in noninfectious, immature viral particles. Ritonavir is a potent inhibitor of cytochrome P450 CYP3A4 isoenzyme present both in the intestinal tract and liver. It is a type II ligand that perfectly fits into the CYP3A4 active site cavity and irreversibly binds to the heme iron via the thiazole nitrogen, which decreases the redox potential of the protein and precludes its reduction with the redox partner, cytochrome P450 reductase. Ritonavir may also play a role in limiting cellular transport and efflux of other protease inhibitors via the P-glycoprotein and MRP efflux channels.|Unlike nucleoside antiretroviral agents, the antiviral activity of ritonavir does not depend on intracellular conversion to an active metabolite. Ritonavir and other HIV protease inhibitors (e.g., amprenavir, indinavir, lopinavir, nelfinavir, saquinavir) act at a different stage of the HIV replication cycle than nucleoside and nonnucleoside reverse transcriptase inhibitors, and results of in vitro studies indicate that the antiretroviral effects of HIV protease inhibitors and some nucleoside or nonnucleoside antiretroviral agents may be additive or synergistic.|Ritonavir is a selective, competitive, reversible inhibitor of HIV protease. HIV protease, an aspartic endopeptidase that functions as a homodimer, plays an essential role in the HIV replication cycle and the formation of infectious virus. During HIV replication, HIV protease cleaves viral polypeptide products of the gag and gag-pol genes (i.e., p55 and p160) to form structural proteins of the virion core (i.e., p17, p24, p9, and p7) and essential viral enzymes (i.e., reverse transcriptase, integrase, and protease). By interfering with the formation of these essential proteins and enzymes, ritonavir blocks maturation of the virus and causes formation of nonfunctional, immature, noninfectious virions. Ritonavir is active in both acutely and chronically infected cells since it targets the HIV replication cycle after translation and before assembly. Thus, the drug is active in chronically infected cells (e.g., monocytes and macrophages) that generally are not affected by nucleoside reverse transcriptase inhibitors (e.g., didanosine, lamivudine, stavudine, zalcitabine, zidovudine). Ritonavir does not affect early stages of the HIV replication cycle; however, the drug interferes with production of infectious HIV and limits further infectious spread of the virus.|While the complete mechanisms of antiviral activity of ritonavir have not been fully elucidated, ritonavir apparently inhibits replication of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and 2 (HIV-2), by interfering with HIV protease. The drug, therefore, exerts a virustatic effect against retroviruses by acting as an HIV protease inhibitor.

To enhance elimination: Administration of activated charcoal. Monitoring: Monitoring of vital signs and observation of the clinical status of the patient. Supportive care: Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/|Treatment of overdose: To decrease absorption: Patients may benefit from treatment with activated charcoal. Monitoring: Patient's vital signs should be monitored. Supportive care: Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.|Maintain an open airway and assist ventilation if needed. Treat coma, seizures, hypotension or anaphylaxis if they occur. replace fluid losses resulting from gastroenteritis with intravenous crystalloids. Maintain steady urine flow with intravenous fluids to alleviate crystalluria and reverse renal dysfunction. Treat lactic acidosis with judicious doses of sodium bicarbonate and by withdrawal of the offending drug. There are no specific antidotes for these agents. Administer activated charcoal.

/HUMAN EXPOSURE STUDIES/ Overdosage of ritonavir would be expected to produce manifestations that are principally extensions of the adverse reactions reported with the drug. Paresthesia occurred in one patient who ingested 1.5 g of ritonavir daily for 2 days; this adverse effect resolved once the ritonavir dosage was decreased. Renal failure with eosinophilia has occurred in association with an overdosage of ritonavir.|/HUMAN EXPOSURE STUDIES/ Hepatic coma, hepatitis, hepatomegaly, hepatosplenomegaly, or liver damage have been reported in less than 2% of patients receiving ritonavir in clinical studies. There have been postmarketing reports of hepatic dysfunction, including some fatalities, in patients receiving ritonavir. These generally occurred in patients receiving multiple drugs and/or with advanced AIDS.|/HUMAN EXPOSURE STUDIES/ Adverse hematologic effects reported in less than 2% of patients receiving ritonavir alone or with other antiretroviral agents include anemia, ecchymosis, leukopenia, lymphadenopathy, lymphocytosis, myeloproliferative disorder, and thrombocytopenia.|/HUMAN EXPOSURE STUDIES/ Pancreatitis, including some fatalities, has been reported in patients receiving ritonavir, including some patients who developed hypertriglyceridemia. Pancreatitis has been reported in less than 2% of patients receiving ritonavir in clinical studies. Fatal pancreatitis has been reported in a few patients receiving didanosine, stavudine, and an HIV protease inhibitor (i.e., indinavir, nelfinavir). Pancreatorenal syndrome consisting of acute pancreatitis in conjunction with acute renal failure has been reported in at least one patient receiving a multiple-drug regimen that included ritonavir; this syndrome also has been reported rarely in patients receiving regimens that did not include ritonavir.|For more Human Toxicity Excerpts (Complete) data for RITONAVIR (9 total), please visit the HSDB record page.

ABT 538

Oral: Capsules, liquid-filled, 100 mg, Norvir Softgel (with alcohol and polyoxyl 35 castor oil), Abbott; Solution 80 mg/ml, Norvir (with alcohol polyoxyl 35 castor oil, and propylene glycol), Abbott

Human drugs -> Ritonavir Mylan -> EMA Drug Category|Antivirals for systemic use -> Human pharmacotherapeutic group|Human drugs -> Kaletra -> EMA Drug Category|Antivirals for systemic use, Protease inhibitors -> Human pharmacotherapeutic group|Human drugs -> Lopinavir/Ritonavir Mylan -> EMA Drug Category|Human drugs -> Viekirax -> EMA Drug Category|Human drugs -> Norvir -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients