Ritonavir oral solution

Norvir oral solution is available for oral administration as 80 mg/mL ritonavir in a peppermint- and caramel-flavored vehicle. Each 8-ounce bottle contains 19.2 g ritonavir. Norvir oral solution also contains ethanol, water, polyoxyl 

35 castor oil, propylene glycol, anhydrous citric acid to adjust pH, saccharin sodium, peppermint oil, creamy caramel flavoring, and FD C yellow no. 6. 

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Drugs that should not be combined due to overlapping toxi-cities include amprenavir oral solution plus ritonavir oral solution, atazanavir plus indinavir (due to enhanced hyperbilirubinemia), and any combination of didanosine, stavudine, and zalcitabine. Emtricitabine and lamivudine should not be combined because of their similar chemical structures, and antagonism can result when lamivudine is combined with zalcitabine, or stavudine is combined with zidovudine. 

If possible, take with food. Patients may improve the taste of ritonavir oral solution by mixing with chocolate milk or enteral nutritional therapy liquids (eg, Ensure, Advera) within 1 hour of dosing. The effects of antacids on the absorption of ritonavir have not been studied. 

Oral solution Concomitant use of amprenavir oral solution and ritonavir oral solution is not recommended because the large amount of propylene glycol in amprenavir oral solution and ethanol in ritonavir oral solution may compete for the same metabolic pathway for elimination. 

Children (6 months to 12 years of age) The recommended dosage of lopinavir/ritonavir oral solution is 12/3 mg/kg for those weighing 7 to less than 15 kg and 10/2.5 mg/kg for those 15 to 40 kg (approximately equivalent to 230/57.5 mg/m ) twice daily with food, up to a maximum dose of 400/100 mg in children greater than 40 kg (5 mL or 3 capsules, or 2 tablets) twice daily. It is preferred that the prescriber calculate the appropriate milligram dose for each individual child 12 years of age and younger and determine the corresponding volume of solution or number of capsules or tablets. 

Similar labeling language also in the labeling of INVIRASE (Roche Laboratories) (saquinavir mesylate) capsules, December 2003 KALETRA (Abbott) (lopinavir/ritonavir) capsules, (lopinavir/ritonavir) oral solution, February 2004 and LEXIVA (GlaxoSmithKline) (fosamprenavir calcium) tablets. May 2004. 

Fosamprenavir PI2 1400 mg bid or 700 mg bid with ritonavir 100 bid or 1400 mg daily with ritonavir 100-200 mg daily. Adjust dose in hepatic insufficiency Separate dosing from antacids by 2 h. Avoid concurrent high-fat meals Diarrhea, nausea, vomiting, hypertriglyceridemia, rash, headache, perioral paresthesias, t liver enzymes See footnote 4 for contraindicated medications. Do not administer with lopinavir/ritonavir or in severe hepatic insufficiency. Also avoid cimetidine, disulfiram, metronidazole, vitamin E, ritonavir oral solution, and alcohol when using the oral solution... 

DISULFIRAM ANTIVIRALS-PROTEASE INHIBITORS t risk of disulfiram reaction with ritonavir (with or without lopinavir) Ritonavir and lopinavir/ritonavir oral solutions contain 43% alcohol Warn patients. Consider using capsule preparations as an alternative... 

An optimum dosage for concurrent use has not been established. A dose increase of lopinavir/ritonavir oral solution to 533/133 mg twice daily (dose rounded to 6.5 mL) or 600/150 mg twice daily may be needed if amprenavir is given. Avoid once daily regimens. ... 

Children The recommended dosage of ritonavir is 400 mg/m twice daily by mouth and should not exceed 600 mg twice daily. Start ritonavir at 250 mg/m and increase at 2- to 3-day intervals by 50 mg/m twice daily. Administer oral solution dose using a calibrated dosing syringe. 

Administration - Lopinavir/ritonavir tablets may be taken with or without food capsules and oral solution must be taken with food. Tablets should be swallowed whole and not chewed, broken, or crushed. 

KALETRA (Abbott) (lopinavir/ ritonavir) capsules or oral solution February 2004 labeling... 

Lopinavir/ritonavir PI/PI2 400 mg/100 mg bid or 800 mg/200 mg daily. May need dose adjustment in hepatic insufficiency Take with food. Separate dosing from ddl by 1 h. Store capsules and solution in refrigerator Diarrhea, abdominal pain, nausea, hypertriglyceridemia, headache, t liver enzymes, See footnote 4 for contraindicated medications. Also avoid fosamprenavir. Avoid disulfiram and metronidazole with oral solution... 

Ritonavir PI2 600 mg bid Take with food. Separate dosing with ddl by 2 h. Dose-escalate from 300 mg bid over 1-2 weeks to improve tolerance. Refrigerate capsules but not oral solution Nausea, diarrhea, paresthesias, hepatitis See footnote 4 for contraindicated medications... 

Kaletra oral solution is available for oral administration as 80 mg lopinavir and 20 mg ritonavir per milliliter with the following inactive ingredients acesulfame potassium, alcohol, artificial cotton candy flavor, citric acid, glycerin, high fructose com symp, Magnasweet-110 flavor, men-... 

Subsequently, studies have shown that M3 can be administered successfully in a tablet form rather than by an oral solution. Also, two drug interaction clinical trials of M3, in combination with the approved HIV drugs ritonavir and atazanavir. 

Soft gelatin Oleic acid capsule 133.3 mg Polyoxyl 35 lopinavir and castor oil 33.3 mg ritonavir (Cremophor EL) Oral solution Propylene glycol... 

Ethanol 2.1 ml, b.i.d. Kaletra Oral Solution (Lopinavir and Ritonavir)... 

Ritonavir, an HIV protease inhibitor with peptidelike structure, has an intrinsic water solubility of l.Opg/ml. Norvir is a thermodynamically stable solution formulation containing 100 mg of ritonavir dissolved in a mixture of oleic acid, Cremophor EL, ethanol, and the antioxidant butylated hydroxytoluene (BHT), and filled into soft gelatin capsules. However, Norvir is being replaced by Kaletra oral solution and soft gelatin capsule, which is a combination of 133.3 mg of lopinavir and 33.3 mg ritonavir dissolved in a mixture of oleic acid, polyoxyl 35 castor oil (Cremophor EL), and propylene glycol. The water-insoluble HIV protease inhibitor, saquinavir, is solubilized by a mixture of Vitamin E and medium-chain mono- and diglycerides in 200 mg Fortovase soft gelatin capsules. 

Ritonavir is solubilized in a cosolvent mixture of propylene glycol, ethanol, water, the surfactant Cremophor EL, and peppermint oil to 80 mg/ml in the Norvir oral solution. A similar cosolvent mixture of propylene glycol, 42% ethanol, water, glycerin, the surfactant Cremophor RH 40, and peppermint oil is used to cosolubilize ritonavir to 20 mg/ml and lopinavir, a non-ionizable water-insoluble HIV protease inhibitor, to 80 mg/ml in the Kaletra oral solution. The dose of Kaletra Oral Solution is up to 5 ml twice daily, which is 2.1 ml of ethanol per dose representing the estimated maximum amount of ethanol administered orally per dose. 

Quatenary Gremophor EL, propylene glycol, ethanol, peppermint oil, water Norvir oral solution (Ritonavir)... 

Propylene glycol, 42% ethanol, glycerin, Gremophor RH 40, peppermint oil, water. 11.9% Ethanol, dl-Q -tocopherol, corn oil-mono-di-triglycerides, Gremophor RH 40, propylene glycol. Kaletra oral solution (Lopinavir and ritonavir) Neoral oral solution (Cyclosporin A)... 

Ritonavir is formulated as both Norvir soft gelatin capsules and Norvir oral solution, which contains 80 mg/mL of ritonavir solubilized in a mixture of cremophor EL, propylene glycol, 42% ethanol, water, and peppermint oil. The pediatric dose of ritonavir is 250—450 mg/m or up to a maximum of 600 mg (7.5 mL) twice daily. The total amount of ethanol administered in conjunction with a daily adult dose of ritonavir as the oral solution... 

Lopinavir and ritonavir are co-formulated as both Kaletra soft gelatin capsules and Kaletra oral solution. Kaletra fixed-dose combination oral solution contains 80 mg/mL of lopinavir and 20 mg/mL of ritonavir solubilized in propylene glycol, 42% ethanol, water, glycerin, cremophor RH 40 and peppermint oil. Kaletra oral solution is packaged in a 160-mL multi-dose container and should be stored refrigerated at 2-8°C or at room temperature for no more than two months. Kaletra oral solution has been available in the UK since 2001 and is also available in the USA. 

Absorption of ritonavir is rapid and is only slightly affected by food, depending on the formulation. The overall absorption of ritonavir from the capsule formulation increases by 13% when the capsule is taken with meals, but the bioavailability of the oral solution decreases by 7%. Interindividual variability in pharmacokinetics is high, with a greater than sixfold variability in trough concentrations among patients given 600 mg ritonavir every 12 hours. 

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