Buy Drugs Online:
Drugs Information:
Drugs List
Lopinavir and Ritonavir

Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: [1S - [R*(R*),3R*,4R*]] - N - [4 - [[2,6 - Dimethylphenoxy) - acetyl]amino] - 3 - hydroxy - 5 - phenyl - 1 - (phenylmethyl)pentyl]tetrahydro - ? - (1 - methylethyl) - 2 - oxo - 1(2H) - pyrimidineacetamide
Molecular Formula: C37H48N4O5C37H48N6O5S2
CAS Number: 192725-17-0
Brands: Kaletra

Special Alerts:

[Posted 03/08/2011] ISSUE: FDA notified healthcare professionals of serious health problems that have been reported in premature babies receiving lopinavir/ritonavir (Kaletra) oral solution. Lopinavir/ritonavir oral solution contains the ingredients alcohol and propylene glycol. Premature babies may be at increased risk for health problems because they have a decreased ability to eliminate propylene glycol; this could lead to adverse events such as serious heart, kidney, or breathing problems. Because the consequences of using lopinavir/ritonavir oral solution in babies immediately after birth can be severe or possibly fatal, the label is being revised to include a new warning.

BACKGROUND: Lopinavir/ritonavir oral solution is an antiviral medication used in combination with other antiretroviral drugs for the treatment of HIV-1 infection in pediatric patients 14 days of age (whether premature or full term) or older and in adults.

RECOMMENDATION: The use of lopinavir/ritonavir oral solution should be avoided in premature babies until 14 days after their due date, or in full-term babies younger than 14 days of age unless a healthcare professional believes that the benefit of using lopinavir/ritonavir oral solution to treat HIV infection immediately after birth outweighs the potential risks. In such cases, FDA strongly recommends monitoring for increases in serum osmolality, serum creatinine, and other signs of toxicity. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for lopinavir and ritonavir to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antiretroviral; fixed combination of 2 HIV protease inhibitors (lopinavir, ritonavir).1

Uses for Lopinavir and Ritonavir

Treatment of HIV Infection

Treatment of HIV infection in conjunction with other antiretrovirals.1

Administration of lopinavir/ritonavir in conjunction with other active antiretroviral agents associated with a greater likelihood of treatment response.1

Use of lopinavir/ritonavir should be guided by genotypic and phenotypic viral resistance testing and the individual’s prior antiretroviral treatment.1

Preferred PI for initial treatment regimens in adults.10

Twice-daily regimen is the preferred PI for initial therapy in pediatric patients.11

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with a risk for transmission of the virus.18 Used in conjunction with other antiretrovirals.18

Postexposure prophylaxis of HIV infection in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.15 Used in conjunction with other antiretrovirals.15

Lopinavir and Ritonavir Dosage and Administration

Administration

Oral Administration

Solution: Administer orally with food.1 Use calibrated dosing syringe.1

Tablets: Administer orally without regard to food.1 Tablets should be swallowed whole and should not be chewed, broken, or crushed.1

Solution is the preferred preparation for children with a body surface area <0.6 m2 and those unable to swallow tablets.1

Lopinavir/ritonavir oral solution is highly concentrated (contains 80 mg of lopinavir and 20 mg of ritonavir per mL).1 28 One death has occurred as a result of inadvertent overdosage of lopinavir/ritonavir oral solution.28 To avoid medication errors, use extra care in calculating the dose, transcribing the medication order, dispensing the prescription, and providing dosing instructions.28

Dosage

Available as fixed combination containing lopinavir and ritonavir; dosage expressed in terms of both drugs.1

For pediatric patients, base dosage on body surface area or body weight.1

Must be given in conjunction with other antiretrovirals.1 10 If used with certain didanosine preparations, adjustment of treatment regimen recommended.1 If used with efavirenz, fosamprenavir, nelfinavir, or nevirapine, dosage adjustments recommended.1 10 (See Specific Drugs under Interactions.)

Once-daily regimen may be used only in treatment-naive adults not receiving efavirenz, fosamprenavir, nelfinavir, or nevirapine.1 10 Once-daily regimen should not be used in treatment-experienced adults or patients receiving certain anticonvulsants (carbamazepine, phenobarbital, phenytoin).1

Once-daily regimen should not be used in pediatric patients.1 Twice-daily regimen recommended for adolescents.1 11

Pediatric Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Treatment of HIV Infection
Children ?18 Years of Age Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine
Oral

Infants 14 days to 6 months of age: The recommended dosage of the oral solution based on body surface area is lopinavir 300 mg/m2 and ritonavir 75 mg/m2 twice daily.1 Alternatively, the recommended dosage of the oral solution based on body weight is lopinavir 16 mg/kg and ritonavir 4 mg/kg twice daily.1 Dosage recommendations not available for concomitant use with efavirenz, fosamprenavir, nelfinavir, or nevirapine1

Children 6 months to 18 years of age: The recommended dosage of the oral solution based on body surface area is lopinavir 230 mg/m2 and ritonavir 57.5 mg/m2 twice daily.1 Alternatively, the recommended dosage of the oral solution based on body weight is lopinavir 12 mg/kg and ritonavir 3 mg/kg twice daily for those who weigh <15 kg and lopinavir 10 mg/kg and ritonavir 2.5 mg/kg twice daily for those who weigh ?15 kg.1

a: Two lopinavir/ritonavir tablets containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 4 tablets containing 100 mg of lopinavir and 25 mg of ritonavir.

Dosage of Lopinavir/Ritonavir for Treatment of HIV Infection in Children 6 Months to 18 Years of Age Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine1

Weight (kg)

Body Surface Area (m2)

Number of Lopinavir/Ritonavir Tablets containing 100 mg of lopinavir and 25 mg of ritonavir given twice daily

15 to 25

?0.6 to <0.9

2 tablets

>25 to 35

?0.9 to <1.4

3 tablets

>35

?1.4

4 tabletsa

Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine
Oral

Children 6 months to 18 years of age: The recommended dosage based on body surface area is lopinavir 300 mg/m2 and ritonavir 75 mg/m2 twice daily.1 Alternatively, the recommended dosage based on body weight is lopinavir 13 mg/kg and ritonavir 3.25 mg/kg twice daily for those who weigh <15 kg and lopinavir 11 mg/kg and ritonavir 2.75 mg/kg twice daily for those who weigh ?15 to 45 kg.1

a: Two lopinavir/ritonavir tablets containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 4 tablets containing 100 mg of lopinavir and 25 mg of ritonavir.

b: Two lopinavir/ritonavir tablets containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 4 tablets containing 100 mg of lopinavir and 25 mg of ritonavir. Three lopinavir/ritonavir tablets each containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 6 tablets each containing 100 mg of lopinavir and 25 mg of ritonavir.

Dosage of Lopinavir/Ritonavir for Treatment of HIV Infection in Children 6 Months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine1

Weight (kg)

Body Surface Area (m2)

Number of Lopinavir/Ritonavir Tablets containing 100 mg of lopinavir and 25 mg of ritonavir given twice daily

15 to 20

?0.6 to <0.8

2 tablets

>20 to 30

?0.8 to <1.2

3 tablets

>30 to 45

?1.2 to <1.7

4 tabletsa

>45

?1.7

4 or 6 tabletsb

Adults

Treatment of HIV Infection
Treatment-naive Adults Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine
Oral

Lopinavir 400 mg and ritonavir 100 mg (as 2 tablets containing 200 mg of lopinavir and 50 mg of ritonavir or 5 mL of oral solution) twice daily.1 10 20

Alternatively, lopinavir 800 mg and ritonavir 200 mg (as 4 tablets containing 200 mg of lopinavir and 50 mg of ritonavir or 10 mL of oral solution) once daily.1 10 20

Treatment-experienced Adults Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine
Oral

Lopinavir 400 mg and ritonavir 100 mg (as 2 tablets containing 200 mg of lopinavir and 50 mg of ritonavir or 5 mL of oral solution) twice daily.1 10 20

Once-daily regimen not recommended.1

Treatment-naive and Treatment-experienced Adults Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine
Oral

Lopinavir 500 mg and ritonavir 125 mg (as 2 tablets containing 200 mg of lopinavir and 50 mg of ritonavir and 1 tablet containing 100 mg of lopinavir and 25 mg of ritonavir) twice daily.1

Alternatively, lopinavir 533 mg and ritonavir 133 mg (6.7 mL of oral solution) twice daily.1

Once-daily regimen not recommended.1

Postexposure Prophylaxis of HIV
Occupational Exposure
Oral

Lopinavir 400 mg and ritonavir 100 mg twice daily.18 29

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.18

Nonoccupational Exposure
Oral

Lopinavir 400 mg and ritonavir 100 mg twice daily.15

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ?72 hours after exposure) and continue for 28 days.15

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection
Oral

Do not exceed adult dosage.1

Special Populations

Hepatic Impairment

Not studied to date in patients with severe hepatic impairment; dosage recommendations not available.1 10 (See Hepatic Impairment under Cautions.)

Renal Impairment

Renal clearance is negligible;1 dosage adjustments not necessary.10

Cautions for Lopinavir and Ritonavir

Contraindications

  • History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme) to lopinavir, ritonavir, or any ingredient in the formulation.1

  • Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., cisapride, ergot alkaloids, midazolam, pimozide, triazolam, lovastatin, simvastatin).1 (See Specific Drugs under Interactions.)

  • Concomitant use with drugs that are potent inducers of CYP3A; such use may result in decreased plasma concentrations of lopinavir, and possible loss of virologic response and development of resistance (e.g., rifampin, St. John’s wort [Hypericum perforatum]).1 (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

Interactions

Serious and/or life-threatening drug interactions, important drug interactions, or loss of virologic effect can occur with some drugs.1 (See Contraindications and Specific Drugs under Interactions.)

Pancreatitis

Pancreatitis (sometimes fatal) with or without marked elevations in triglycerides has occurred.1

Patients with advanced HIV disease may be at increased risk of elevated triglycerides and pancreatitis;1 those with a history of pancreatitis may be at increased risk for recurrence during lopinavir and ritonavir therapy.1

Consider pancreatitis in patients who develop abdominal pain, nausea, and vomiting or elevated serum amylase or lipase concentrations.1 Suspend lopinavir and ritonavir therapy, as well as other antiretroviral therapy, if clinically appropriate.1 (See Lipid Effects under Cautions.)

Hepatic Effects

Hepatic dysfunction (including some fatalities) reported; causal relationship not established.1 Generally has occurred in patients with advanced HIV infection receiving multiple concomitant drugs in the setting of chronic hepatitis or cirrhosis.1

Evaluate hepatic function prior to and during therapy.1 Consider increased AST/ALT monitoring in patients with hepatitis or cirrhosis, especially during the first several months of therapy.1

Hyperglycemic and Diabetogenic Effects

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of HIV protease inhibitors (PIs); diabetic ketoacidosis has occurred.1

Monitor blood glucose and initiate or adjust dosage of oral hypoglycemic agent or insulin as needed.1

General Precautions

HIV Resistance

Possibility of HIV-1 resistant to lopinavir and ritonavir and possible cross-resistance to other PIs.1 Effect of lopinavir therapy on subsequent therapy with other PIs under investigation.1

Hemophilia A and B

Spontaneous bleeding noted with PIs; causal relationship not established.1

Caution in patients with a history of hemophilia type A or B.1 Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.1

Cardiovascular Effects

Prolongation of the PR interval reported.1 Second- or third-degree AV block reported.1 Caution in patients with structural heart disease, cardiac conduction abnormalities, ischemic heart disease, or cardiomyopathies; these individuals may be at increased risk for cardiac conduction abnormalities.1 Caution if lopinavir/ritonavir is used with other drugs that prolong the PR interval (e.g., some ?-adrenergic blocking agents, digoxin, calcium-channel blockers, atazanavir), especially drugs metabolized by CYP3A4.1

Prolongation of the QT interval and torsades de pointes have occurred.1 Use with caution in patients who have or may develop prolongation of the QT interval (e.g., hypokalemia, congenital long QT syndrome, use of drugs known to prolong QT interval).1

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.1

Lipid Effects

Substantial increases in total serum cholesterol and triglyceride concentrations have occurred.1 Marked triglyceride elevations is a risk factor for pancreatitis.1 (See Pancreatitis under Cautions.)

Determine serum triglyceride and cholesterol concentrations prior to initiating therapy and monitor concentrations periodically; manage lipid disorders as clinically appropriate.1 (See HMG-CoA Reductase Inhibitors under Interactions.)

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.1

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling of Kaletra (the fixed combination of lopinavir and ritonavir) and Keppra (levetiracetam) may result in errors.13

To avoid medication errors when the oral solution is used, use care in the dose calculation, transcription of the order, and dispensing of the prescription.28

Specific Populations

Pregnancy

Category C.1

Antiretroviral Pregnancy Registry at 800-258-4263.1

Some experts state that lopinavir/ritonavir is the preferred PI for use in pregnant women.21 Specific dosage recommendations not available.21 Some experts recommend usual dosage throughout pregnancy with monitoring of virologic response and lopinavir concentrations; others recommend increasing dosage to 600 mg of lopinavir and 150 mg of ritonavir (as tablets) twice daily during third trimester.21 Pending further accumulation of data, once-daily regimen not recommended during pregnancy.21

Lactation

Lopinavir distributed into milk in rats; not known whether distributed into human milk.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 11

Pediatric Use

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Safety, efficacy, and pharmacokinetics not established in children <14 days of age.1

Once-daily regimen not evaluated in pediatric patients.1 Twice-daily regimen recommended in pediatric and adolescent patients.11

Significant alcohol-related toxicity may result if a young child accidentally ingests oral solution (contains 42.4% alcohol).1

Geriatric Use

Insufficient experience in those ?65 years of age to determine whether they respond differently than younger adults.1

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Hepatic Impairment

Use with caution since lopinavir plasma concentrations may be increased.1 Not evaluated in severe hepatic impairment.1

Risk of further transaminase elevations in patients with underlying hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or those with preexisting transaminase elevations.1 Carefully monitor liver function in these patients.1

Common Adverse Effects

Diarrhea, nausea, vomiting, headache, abdominal pain, asthenia, dyspepsia.1

Interactions for Lopinavir and Ritonavir

Lopinavir metabolized by CYP3A.1 Fixed combination of lopinavir and ritonavir inhibits CYP3A4.1 At clinically important concentrations, lopinavir does not inhibit CYP2D6, 2C9, 2C19, 2E1, 2B6, or 1A2.1

Fixed-combination of lopinavir and ritonavir induces glucuronidation.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A with possible alteration in metabolism of lopinavir, ritonavir, and/or other drug.1

Specific Drugs

Drug

Interaction

Comments

Abacavir

Possible decreased abacavir plasma concentrations1

Clinical importance unknown1

Antiarrhythmic agents (amiodarone, flecainide, systemic lidocaine, propafenone, quinidine)

Possible increased antiarrhythmic agent concentrations1

Cautious use with amiodarone, systemic lidocaine, or quinidine; monitor serum concentrations of antiarrhythmic if possible1

Some experts state concomitant use with flecainide or propafenone not recommended10

Anticoagulants, oral

Warfarin concentrations may be affected1

Monitor INR1

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Decreased lopinavir concentrations and possible decreased effectiveness of the antiretroviral;1 10 altered anticonvulsant concentrations10

Cautious use with carbamazepine, phenobarbital, and phenytoin; do not use lopinavir once-daily regimen1

Carbamazepine, phenobarbital, phenytoin: Some experts recommend considering use of an alternative anticonvulsant; if used, monitor plasma concentrations of the anticonvulsant and lopinavir10

Antifungals, azoles (itraconazole, ketoconazole, voriconazole)

Itraconazole: Increased antifungal concentrations1 10

Ketoconazole: Increased antifungal concentrations1 and decreased lopinavir AUC10

Fluconazole: Interaction not expected1

Voriconazole: Possible decreased antifungal concentrations10

Itraconazole: High itraconazole dosage (>200 mg daily) not recommended1 10 use with caution;1 10 monitor antifungal concentrations and toxicity10

Ketoconazole: High ketoconazole dosage (>200 mg daily) not recommended;1 10 use with caution10

Voriconazole: Concomitant use not recommended unless benefit outweighs risk1 10

Antimycobacterials, (rifabutin, rifampin, rifapentine)

Rifabutin: Increased rifabutin and rifabutin metabolite concentrations1 10

Rifampin: Substantially decreased lopinavir concentrations with possible loss of virologic response and increased risk of lopinavir resistance1

Rifabutin: Use usual lopinavir dosage but reduce rifabutin dosage to 150 mg every other day or 3 times weekly;1 10 further rifabutin dosage reductions may be necessary;1 monitor closely for adverse effects1

Rifampin: Concomitant use contraindicated1

Rifapentine: Concomitant use not recommended10

Atazanavir

Pharmacokinetic interaction unlikely10

In vitro evidence of additive antiretroviral effects1

Atovaquone

Possible decreased atovaquone concentrations;1 clinical importance unknown1

Consider need to increase atovaquone dosage1

Benzodiazepines

Pharmacokinetic interaction with midazolam or triazolam; potential for prolonged or increased sedation or respiratory depression1

Concomitant administration with oral midazolam expected to result in substantially higher concentrations of the benzodiazepine than concomitant administration with parenteral midazolam 1

Concomitant use with oral midazolam or triazolam contraindicated;1 10 some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation10

Bupropion

Possible decreased bupropion and hydroxybupropion (active metabolite) concentrations1

Monitor for response to bupropion1

Calcium-channel blocking agents

Possible increased concentrations of dihydropyridines (e.g., felodipine, nifedipine, nicardipine)1

Use concomitantly with caution; clinical monitoring recommended1

Cisapride

Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1 10

Corticosteroids (dexamethasone, fluticasone)

Fluticasone nasal spray/oral inhalation: Increased fluticasone concentrations with lopinavir and ritonavir resulting in decreased cortisol concentrations1

Dexamethasone: Decreased lopinavir concentrations1

Fluticasone nasal spray/oral inhalation: Concomitant use with lopinavir and ritonavir not recommended unless potential benefits outweigh risk of systemic corticosteroid adverse effects1

Dexamethasone: Use concomitantly with caution1

Co-trimoxazole

Interaction unlikely1

Dapsone

Interaction unlikely1

Darunavir

Decreased concentrations of darunavir; increased or no change in concentrations of lopinavir10 22

Concomitant use of ritonavir-boosted darunavir not recommended; appropriate dosages with respect to safety and efficacy not established10 22

Delavirdine

Possible increased lopinavir concentrations1 10

Appropriate dosages for concomitant use with respect to safety and efficacy not established1 10

Desipramine

Pharmacokinetic interaction unlikely1

Didanosine

Lopinavir and ritonavir oral solution: Conflicting administration instructions with regards to food1

Lopinavir and ritonavir oral solution: Administer didanosine (without food) 1 hour before or 2 hours after lopinavir (given with food)1

Lopinavir and ritonavir tablets: May be administered at the same time as didanosine1

Disulfiram

Possible disulfiram-like reaction with lopinavir and ritonavir oral solution because of alcohol content1

Efavirenz

Lopinavir 400 mg and ritonavir 100 mg twice daily with efavirenz 600 mg once daily: Decreased lopinavir plasma concentrations1

Lopinavir 600 mg and ritonavir 150 mg twice daily with efavirenz 600 mg once daily: Increased lopinavir concentrations relative to lopinavir 400 mg and ritonavir 100 mg twice daily (without efavirenz)1

Once-daily lopinavir regimen not recommended with efavirenz1 11 20

For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1

Manufacturer of lopinavir recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily1

For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)

Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)

Possible pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)1

Concomitant use contraindicated1 10

If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving lopinavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible11

Estrogens/Progestins

Hormonal contraceptives: Increased clearance of ethinyl estradiol contained in estrogen-based hormonal contraceptives1

Use alternative or additional nonhormonal contraceptive measures1 10

Etravirine

Increased concentrations of etravirine and decreased concentrations of lopinavir10 33

Limited data available on the safety of increased concentrations of etravirine; use with caution10 33

Some experts state that the usual dosages may be used10

Fosamprenavir

Decreased concentrations of amprenavir with fosamprenavir (with or without low-dose ritonavir); altered or no change in lopinavir concentrations1 10 26 27

Increased incidence of adverse effects reported1 10

In vitro evidence of additive antiretroviral effects1

Some experts state concomitant use of fosamprenavir not recommended since appropriate dosages not established10

Manufacturer of lopinavir states that concomitant use of ritonavir-boosted fosamprenavir and lopinavir/ritonavir not recommended because appropriate dosages not established1

For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1

Manufacturer of lopinavir recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily1

For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)

Histamine H2-receptor antagonists (ranitidine)

Ranitidine: No change in lopinavir/ritonavir concentrations1 10

HMG-CoA reductase inhibitors

Decreased clearance and increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis);1 10 interaction with fluvastatin not expected1

Concomitant use with lovastatin or simvastatin contraindicated1

If used with atorvastatin, use lowest possible atorvastatin dosage with careful monitoring1 10

If used with rosuvastatin, use lowest possible rosuvastatin dosage with careful monitoring;1 maximum recommended dosage of rosuvastatin is 10 mg once daily25

Consider using pravastatin or fluvastatin;1 10 dosage adjustment not necessary with pravastatin10

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1

Monitor concentrations of the immunosuppressive agent1

Indinavir

Pharmacokinetic interaction; increased indinavir concentrations and AUC1 10

In vitro evidence of additive antiretroviral effects1

Consider indinavir 600 mg twice daily with 400 mg of lopinavir and 100 mg of ritonavir twice daily;1 10 lopinavir once-daily regimen not studied in conjunction with indinavir1

Lamivudine

No clinically important interaction1

Lamotrigine

Decreased lamotrigine AUC; no change in lopinavir or ritonavir AUCs24

Macrolides

Clarithromycin: Increased clarithromycin concentrations1 10

Azithromycin or erythromycin: Interaction not expected1

Clarithromycin: If used concomitantly in patients with renal impairment, reduce clarithromycin dosage by 50% if Clcr 30–60 mL/minute or by 75% if Clcr <30 mL/minute1

Maraviroc

Increased maraviroc concentrations1 10 30

If used concomitantly with maraviroc, recommended dosage of maraviroc is 150 mg twice daily1 10 30

Methadone

Decreased methadone plasma concentrations and AUC;1 10 opiate withdrawal may occur10

Monitor closely for signs of opiate withdrawal;10 consider need to increase methadone dosage1 10

Metronidazole

Possible disulfiram-like reaction with lopinavir and ritonavir oral solution because of alcohol content1

Nelfinavir

Decreased lopinavir concentrations and increased nelfinavir concentrations1 10

Once-daily lopinavir regimen not recommended with nelfinavir1 20

Some experts state that appropriate dosages for concomitant use of nelfinavir and lopinavir not established10

For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1

Manufacturer of lopinavir recommends that adults receive i533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily1

For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)

Nevirapine

Decreased lopinavir concentrations1 10

Once-daily lopinavir regimen not recommended with nevirapine1 20

For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1

Manufacturer recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of oral solution) twice daily1 h

For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)

Pimozide

Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1 10

Proton-pump inhibitors (omeprazole)

Omeprazole: No change in lopinavir/ritonavir concentrations1 10

Ritonavir

Increased lopinavir concentrations1

Additional ritonavir not recommended with fixed combination of lopinavir and ritonavir1 10 ;

Saquinavir

Increased saquinavir concentrations1 10

In vitro evidence of additive antiretroviral effects1

Manufacturers and some experts recommend saquinavir 1 g twice daily with 400 mg of lopinavir and 100 mg of ritonavir twice daily;1 10 lopinavir once-daily regimen not studied in conjunction with saquinavir1

St. John’s wort (Hypericum perforatum)

Decreased lopinavir concentrations; possible loss of virologic response and increased risk of lopinavir resistance1

Concomitant use contraindicated1

Sildenafil

Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 10

Use caution and reduced sildenafil dosage (25 mg repeated no more frequently than every 48 hours);1 10 closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1 10

Stavudine

No clinically important interaction1

Tadalafil

Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 10

Use initial tadalafil dosage of 5 mg and do not exceed a single dose of 10 mg in 72 hours1 10

Tenofovir

Increased peak plasma concentration and AUC of tenofovir1 10 31

Clinical importance unknown10

Monitor for tenofovir toxicity;1 10 31 discontinue tenofovir if adverse effects occur31

Tipranavir

Decreased lopinavir concentrations1 10 17

In vitro evidence of additive antiretroviral effects1

Concomitant use not recommended; 1 10 appropriate dosage not established10

Trazodone

Possible increased trazodone concentrations; adverse effects (nausea, dizziness, hypotension, syncope) reported when trazodone and ritonavir used concomitantly1

Caution if trazodone used with lopinavir and ritonavir; consider decreased dosage of trazodone1

Valproic Acid

Increased lopinavir





Related Drugs Index:

  • , Buy Lopinavir and Ritonavir