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AURO-RITONAVIR is a brand name for Ritonavir, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Verbatim from this product's HC label. Tap a section to expand.
). Pharmacodynamics Ritonavir was administered orally to mice or rats at doses of 5 to 50 mg/kg to determine potential effects on various neuropharmacological endpoints. In mice, ritonavir had no meaningful effect on rotarod performance, ethanol-induced sleep time or pentobarbital-induced sleep time.
In rats, no effect was observed on spontaneous motor activity or rotarod performance. Ritonavir produced no pharmacologically significant effects on heart rate or blood pressure when administered orally to unanesthetized rats at doses of 20 or 50 mg/kg.
The compound was also infused intravenously in a vehicle consisting of 20% ethanol and 15% propylene glycol in 5% dextrose water to pentobarbital-anesthetized dogs instrumented to measure various cardiovascular parameters. 11 mcg/mL.
Although the vehicle itself produced hemodynamic changes consistent with cardiac depression, ritonavir produced no consistent additional effects on systemic or pulmonary pressures or resistance, central venous pressure, cardiac output, left ventricular dP/dt or end-diastolic pressure.
Ritonavir had no effect on isolated guinea pig ileum basal tone or on carbachol-induced contractions. Auro-Ritonavir (Product Monograph) Page 53 of 63 Acute Toxicity Ritonavir has a low order of acute toxicity in rodents by oral route but is more toxic when given intravenously.
The difference is probably due to the fact that the acute toxicity produced by ritonavir is more related to plasma Cmax than AUC values, and Cmax is most likely considerably higher following intravenous injection. When given orally in a vehicle of propylene glycol and ethyl alcohol (95:5, v/v) containing 2 molar equivalents of p-toluene sulfonic acid monohydrate, the median lethal dose (LD50) generally exceeds the limited dose of 2500 mg/kg for both mice and rats.
Toxic signs for both species consisted of decreased activity, ataxia, dyspnea, squinting, prostration, and tremors. When administered intravenously, the approximately lethal dose (ALD) ranged from 35 to 80 mg/kg for both species. Signs of toxicity included decreased activity, ataxia, dyspnea, exophthalmos, and clonic convulsions.
Sub-chronic Toxicity Rat Ritonavir has been studied in rats at study durations for 1-month (0, 15, 50 and 150/100 mg/kg/day), 13- weeks (0, 25, 75, and 175/125 mg/kg/day) and 6-months (0, 25, 75, and 175/125 mg/kg/day). Consistent findings across all studies included treatment-related clinical signs consisting of decreased activity, emaciation, hunched posture, weakness, and rough hair coat along with some indications of ataxia, lower body weight and food consumption at higher dosages.
Target organs of toxicity were liver, eye (retina), kidney and thyroid. Hepatic changes include multinucleated hepatocytes, single cell necrosis, histiocytic granulomas and chronic pericholangitis. Changes in laboratory parameters consistent with these findings were observed in serum for ALT, AST, GGT, ALP, total bilirubin, and cholesterol.
and 9 DRUG INTERACTIONS for co-administration of sildenafil in patients with erectile dysfunction. c. See Table 6 for parenterally administered midazolam. Oral formulation of midazolam is not marketed in Canada. d. See Table 6 for co-administration of the maintenance dose of venetoclax.
3 Serious Warnings and Precautions Box Serious Warnings and Precautions • Pancreatitis should be considered if clinical symptoms (nausea, vomiting, abdominal pain) or abnormalities in laboratory values (such as increased serum lipase or amylase values) suggestive of Auro-Ritonavir (Product Monograph) Page 7 of 63 pancreatitis should occur.
Patients who exhibit these signs or symptoms should be evaluated and Auro-Ritonavir therapy should be discontinued if a diagnosis of pancreatitis is made (see 7 WARNINGS AND PRECAUTIONS). • Co-administration of ritonavir with certain non-sedating antihistamines, sedative hypnotics, or antiarrhythmics may result in potentially serious and/or life-threatening adverse events due to possible effects of ritonavir on the hepatic metabolism of certain drugs (see 2 CONTRAINDICATIONS and 9 DRUG INTERACTIONS).
1 Serious Drug Interactions. 1 Dosing Considerations Patients should be aware that frequently observed adverse events, such as mild to moderate gastrointestinal disturbances and paresthesias, may diminish as therapy is continued. In addition, patients initiating combination regimens with ritonavir and other antiretroviral agents may improve gastrointestinal tolerance by initiating Auro-Ritonavir alone and subsequently adding the other antiretroviral agents before completing 2 weeks of Auro-Ritonavir monotherapy.
The long-term effects of dose escalation on efficacy have not been established. Dose reduction of Auro-Ritonavir is necessary when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir.
When Auro-Ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information and clinical study information of that protease inhibitor. 2 Recommended Dose and Dosage Adjustment Adult Patients The recommended dose of Auro-Ritonavir is 600 mg (6 tablets) twice daily orally and should be taken with a meal.
and 9 DRUG INTERACTIONS). 1 Serious Drug Interactions. 1 Dosing Considerations Patients should be aware that frequently observed adverse events, such as mild to moderate gastrointestinal disturbances and paresthesias, may diminish as therapy is continued.
In addition, patients initiating combination regimens with ritonavir and other antiretroviral agents may improve gastrointestinal tolerance by initiating Auro-Ritonavir alone and subsequently adding the other antiretroviral agents before completing 2 weeks of Auro-Ritonavir monotherapy.
The long-term effects of dose escalation on efficacy have not been established. Dose reduction of Auro-Ritonavir is necessary when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir.
When Auro-Ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information and clinical study information of that protease inhibitor. 2 Recommended Dose and Dosage Adjustment Adult Patients The recommended dose of Auro-Ritonavir is 600 mg (6 tablets) twice daily orally and should be taken with a meal.
Auro-Ritonavir tablets should be swallowed whole with water and not chewed, broken, or crushed. Some patients experience nausea upon initiation of 600 mg twice daily dosing. Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels.
Auro-Ritonavir should be started at no less than 300 mg twice daily and increased by 100 mg twice daily increments up to 600 mg twice daily. The titration period should not exceed 14 days. Pediatric Patients (2 to 16 years of age) Auro-Ritonavir should be used in combination with other antiretroviral agents.
3 Reconstitution Not applicable. 4 Administration Auro-Ritonavir is administered orally. 5 Missed Dose If a dose of this medication has been missed, it should be taken as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Retinal changes included observation of pale choroidal vasculature, with hypertrophy and cytoplasmic granularity in the retinal pigment epithelium, with reduced or absent photoreceptor outer segments. Electroretinograms (ERGs) revealed decreases in A- and B–wave amplitudes, with primary findings associated with rods.
Recovery was not observed following treatment discontinuation. Mild epithelial hypertrophy in the thyroid gland was associated with increased TSH and lower T4. Kidney changes were consisted of tubular degeneration and were only observed in the 6-month study.
9 mcg·h/mL in female rats (approximately 1/25th of the expected human exposure of 150 mcg·h/mL from a dose of 600 mg twice daily). Dog Ritonavir has been studied in dogs at study durations for 1-month (0, 10, 50 and 200 mg/kg/day), 13- weeks (0, 10, 50, and 200/100 mg/kg/day) and 6-months (0, 10, 50 and 125 mg/kg/day).
Consistent findings across all studies included treatment-related clinical signs consisting of emesis and abnormal Auro-Ritonavir (Product Monograph) Page 54 of 63 stool/diarrhea; at higher dosages decreased activity, ataxia, weakness, tremor, and posture difficulties were observed along with decreased body weight and food intake.
Target organs of toxicity were liver and thymus. Due to pronounced clinical adversity and moribundity the high dosage was reduced from 200 to 100 mg/kg/day in the 13-week study. Hepatic changes included histopathological findings of hydropic degeneration, with pericholangitis, biliary hyperplasia, fibrosis becoming evident as the dose duration increased.
Associated changes in serum markers included ALT, ALLP, GGT, and bile acids. Decreased thymic weight and atrophy were observed at the highest dosages. The no-toxic effect dosage was dependent on the test formulation used and ranged from 10 to 50 mg/kg/day that corresponded to systemic exposure of 18 to 25 mcg·h/mL (approximately one-seventh of the expected human exposure of 150 mcg·h/mL).
However, it is important to note that histopathological changes in liver were only observed in a single female dog at the highest dosage (125 mg/kg/day) at a plasma drug exposure of 482 mcg·h/mL. Carcinogenicity Carcinogenicity studies with ritonavir have been conducted in mice and rats.
In male mice, at dosage levels of 50, 100, or 200 mg/kg/day, there was a dose dependent increase in the incidence of both adenomas and combined adenomas and carcinomas in the liver. 3-fold for males that of exposure in humans with the recommended therapeutic dose (600 mg twice daily).
There were no carcinogenic effects seen in females at the dosages tested. 6- fold for the females […]
Auro-Ritonavir tablets should be swallowed whole with water and not chewed, broken, or crushed. Some patients experience nausea upon initiation of 600 mg twice daily dosing. Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels.
Auro-Ritonavir should be started at no less than 300 mg twice daily and increased by 100 mg twice daily increments up to 600 mg twice daily. The titration period should not exceed 14 days. Pediatric Patients (2 to 16 years of age) Auro-Ritonavir should be used in combination with other antiretroviral agents.
3 Reconstitution Not applicable. 4 Administration Auro-Ritonavir is administered orally. 5 Missed Dose If a dose of this medication has been missed, it should be taken as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule.
Do not double doses. 5 Overdosage Acute Overdosage Human Overdose Experience Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for 2 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. Management of Overdosage Administration of activated charcoal may be used to aid in removal of unabsorbed drug. Treatment of overdose with Auro-Ritonavir consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
There is no specific antidote for overdose with Auro- Ritonavir. Since ritonavir is extensively metabolized by the liver and is highly protein-bound, dialysis is unlikely to be beneficial in significant removal of the drug. For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764- 7669).
6 Dosage forms, Strengths, Composition and Packaging Table 2 - Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form/Strength/Composition Non-medicinal Ingredients Auro-Ritonavir (Product Monograph) Page 9 of 63 oral film-coated tablets/100 mg The film coat, Aquarius Prime BAP 118010 white Contains: Hypromellose 2910, titanium dioxide, talc, polyethylene glycol and polysorbate.
The tablet core contains:
Calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, copovidone, maize starch, mannitol, microcrystalline cellulose, silicified microcrystalline cellulose (prosolv SMCC 50), silicified microcrystalline cellulose (prosolv SMCC 90), powdered cellulose, sodium stearyl fumarate and sorbitan laurate.
Auro-Ritonavir is available as 100 mg film-coated tablets. Auro-Ritonavir tablets are White to off-white, film-coated, ovaloid tablets, debossed with ‘I’ on one side and ‘100’ on other side. Available in HDPE bottles of 30, 60 and 90 Tablets and Blister Pack of 8x10's 7 Warnings and Precautions Please see 3 WARNINGS AND PRECAUTIONS BOX.
Drug-Drug Interactions When Auro-Ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information of that protease inhibitor including Warning and Precautions. Ritonavir is an inhibitor of cytochrome P450 3A (CYP3A) both in vitro and in vivo.
Ritonavir also inhibits CYP2D6 in vitro, but to a lesser extent than CYP3A. Initiation of Auro-Ritonavir, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients […]
Do not double doses. 5 Overdosage Acute Overdosage Human Overdose Experience Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for 2 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. Management of Overdosage Administration of activated charcoal may be used to aid in removal of unabsorbed drug. Treatment of overdose with Auro-Ritonavir consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
There is no specific antidote for overdose with Auro- Ritonavir. Since ritonavir is extensively metabolized by the liver and is highly protein-bound, dialysis is unlikely to be beneficial in significant removal of the drug. For the most recent information in the management of a suspected drug overdose, contact your regional poison control centre or Health Canada’s toll-free number, 1-844 POISON-X (1-844-764- 7669).
6 Dosage forms, Strengths, Composition and Packaging Table 2 - Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form/Strength/Composition Non-medicinal Ingredients Auro-Ritonavir (Product Monograph) Page 9 of 63 oral film-coated tablets/100 mg The film coat, Aquarius Prime BAP 118010 white Contains: Hypromellose 2910, titanium dioxide, talc, polyethylene glycol and polysorbate.
The tablet core contains:
Calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, copovidone, maize starch, mannitol, microcrystalline cellulose, silicified microcrystalline cellulose (prosolv SMCC 50), silicified microcrystalline cellulose (prosolv SMCC 90), powdered cellulose, sodium stearyl fumarate and sorbitan laurate.
Auro-Ritonavir is available as 100 mg film-coated tablets. Auro-Ritonavir tablets are White to off-white, film-coated, ovaloid tablets, debossed with ‘I’ on one side and ‘100’ on other side. Available in HDPE bottles of 30, 60 and 90 Tablets and Blister Pack of 8x10's 7 Warnings and Precautions Please see 3 WARNINGS AND PRECAUTIONS BOX.
Drug-Drug Interactions When Auro-Ritonavir is used as a pharmacokinetic enhancer with other protease inhibitors, see the full prescribing information of that protease inhibitor including Warning and Precautions. Ritonavir is an inhibitor of cytochrome P450 3A (CYP3A) both in vitro and in vivo.
Ritonavir also inhibits CYP2D6 in vitro, but to a lesser extent than CYP3A. Initiation of Auro-Ritonavir, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A or initiation of medications metabolized by CYP3A in patients already receiving Auro-Ritonavir, may increase plasma concentrations of medications metabolized by CYP3A.
Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of Auro-Ritonavir, respectively. These interactions may lead to: • Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications.
• Clinically significant adverse reactions from greater exposures of ritonavir. • Loss of therapeutic effect of ritonavir and possible development of resistance. Due to inhibition of CYP3A by ritonavir, co-administration of ritonavir with quetiapine may result in increased quetiapine concentrations.
Serious and life-threatening quetiapine-related adverse reactions have been reported with CYP3A inhibitors. Auro-Ritonavir should not be used in combination with Auro-Ritonavir (Product Monograph) Page 10 of 63 quetiapine. Monitoring and dose reduction may be required if necessary (see Table 6).
See Table 6 for steps to prevent or manage these possible and known significant drug […]