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Lopinavir / Ritonavir

Pronunciation: loe-PIN-a-vir/rit-OH-na-vir
Class: Protease inhibitor combination

Trade Names

Kaletra
- Tablets, oral lopinavir 100 mg/ritonavir 25 mg
- Tablets, oral lopinavir 200 mg/ritonavir 50 mg
- Solution, oral lopinavir 80 mg/ritonavir 20 mg per mL

Pharmacology

Lopinavir inhibits HIV protease, the enzyme required to form functional proteins in HIV-infected patients. Ritonavir inhibits the CYP3A4–mediated metabolism of lopinavir, increasing lopinavir plasma concentrations.

Slideshow: Flashback: FDA Drug Approvals 2013

Indications and Usage

Treatment of HIV-1 infection in combination with other antiviral agents.

Contraindications

Coadministration with drugs that are highly dependent on CYP3A for Cl; coadministration with potent CYP3A inducers; coadministration with alfuzosin, cisapride, dihydroergotamine, ergonovine, ergotamine, lovastatin, methylergonovine, oral midazolam, pimozide, rifampin, or sildenafil when used for pulmonary arterial hypertension, simvastatin, St. John's wort, or triazolam; hypersensitivity to any of the ingredients.

Dosage and Administration

HIV Infection Adults

PO lopinavir 400 mg/ritonavir 100 mg twice daily or lopinavir 800 mg/ritonavir 200 mg once daily in patients with less than 3 lopinavir resistance-associated substitutions.

Children 6 mo to 18 y of age PO Tablets

For children weighing 15 to 25 kg, lopinavir 200 mg/ritonavir 50 mg twice daily; 26 to 35 kg, lopinavir 300 mg/ritonavir 75 mg twice daily; more than 35 kg, lopinavir 400 mg/ritonavir 100 mg twice daily (max, lopinavir 400 mg/ritonavir 100 mg twice daily).

Oral solution

Based on BSA, lopinavir 230 mg/ritonavir 57.5 mg/m 2 twice daily with food. Based on body weight: children weighing less than 15 kg, lopinavir 12 mg/ritonavir 3 mg/kg twice daily with food; 15 to 40 kg, lopinavir 10 mg/ritonavir 2.5 mg/kg twice daily with food (max, lopinavir 400 mg/ritonavir 100 mg twice daily).

Children 14 days to 6 mo of age

PO lopinavir 300 mg/ritonavir 75 mg/m 2 or lopinavir 16 mg/ritonavir 4 mg/kg twice daily.

Concomitant Therapy With Efavirenz, (Fos)amprenavir, Nelfinavir, or Nevirapine
Adults PO Tablets

Lopinavir 500 mg/ritonavir 125 mg twice daily.

Solution

Lopinavir 533 mg/ritonavir 133 mg twice daily with food.

Children 6 mo to 18 y of age PO Tablets

For children weighing 15 to 20 kg, lopinavir 200 mg/ritonavir 50 mg twice daily; more than 20 to 30 kg, lopinavir 300 mg/ritonavir 75 mg twice daily; more than 30 to 45 kg, lopinavir 400 mg/ritonavir 100 mg twice daily; more than 45 kg, lopinavir 500 mg/ritonavir 125 mg twice daily (max, lopinavir 500 mg/ritonavir 125 mg twice daily).

Oral solution

Based on BSA, lopinavir 300 mg/ritonavir 75 mg/m 2 twice daily with food. Based on body weight: children weighing less than 15 kg, lopinavir 13 mg/ritonavir 3.25 mg/kg twice daily with food; 15 to 45 kg, lopinavir 11 mg/ritonavir 2.75 mg/kg twice daily with food (max, lopinavir 533 mg/ritonavir 133 mg twice daily).

General Advice

  • Lopinavir/ritonavir oral solution must be taken with food; tablets may be taken with or without food.
  • Once-daily administration of lopinavir/ritonavir is not recommended in children younger than 18 y.
  • Instruct patients to swallow tablets whole, and not to chew, break, or crush.
  • Do not administer lopinavir/ritonavir as a once-daily regimen in combination with efavirenz, (fos)amprenavir, nelfinavir, or nevirapine, or in patients taking carbamazepine, phenobarbital, or phenytoin.
  • When possible, administer child dose using a calibrated dosing syringe.
  • If the solution is used, the volume needed can be determined as follows: Volume of lopinavir/ritonavir solution (mL) = Administered lopinavir dose (mg) ÷ 80 (mg/mL).
  • Oral solution should not be administered to neonates before a postmenstrual age (first day of the mother's last menstrual period to birth plus the time elapsed after birth) of 42 wk and a postnatal age of at least 14 days has been attained.
  • Oral solution contains alcohol and propylene glycol; the total amount given to children 14 days to 6 mo of age should be taken into account to avoid toxicity from these excipients.

Storage/Stability

Store oral solution between 36° and 46°F until dispensed. Avoid excessive heat. Under refrigeration, the oral solution is stable until the expiration date. If stored at 77°F, use within 2 mo.

Store tablets between 59° and 86°F. Avoid exposure to high humidity.

Drug Interactions

Abacavir, atovaquone, bupropion, (fos)amprenavir, lamotrigine, methadone, olanzapine, phenytoin, theophylline, zidovudine

Levels of these agents may be reduced, decreasing the efficacy. Monitor the clinical response of the patient and adjust the dose of these agents as needed.

Aldesleukin

Lopinavir concentrations may be elevated, increasing the pharmacologic and adverse reactions. Monitor the clinical response of the patient when one of these agents is started or stopped. Adjust the lopinavir/ritonavir dose as needed.

Antiarrhythmics (eg, amiodarone, bepridil, lidocaine [systemic], quinidine)

Caution is warranted and therapeutic concentration monitoring (if available) is recommended for antiarrhythmics when coadministered with lopinavir/ritonavir.

Aripiprazole

Aripiprazole plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Consider reducing the aripiprazole dose by 50% when used in combination with lopinavir/ritonavir.

Atorvastatin, beta-blockers (eg, metoprolol), buspirone, calcium channel blockers (eg, amlodipine), cilostazol, cyclosporine, desipramine, digoxin, dronabinol, erlotinib, eszopiclone, methamphetamine, nefazodone, phenothiazines (eg, perphenazine), protease inhibitors (eg, nelfinavir), quetiapine, quinine, rapamycin, risperidone, rosuvastatin, tacrolimus, tenofovir, trazodone, tyrosine kinase receptor inhibitors (eg, dasatinib)

Levels of these agents may be elevated, increasing the pharmacologic and adverse reactions. Use with caution and monitor the patient and drug concentrations (when available). A dose reduction in these agents may be needed.

Azole antifungals (eg, itraconazole, ketoconazole, voriconazole)

Ketoconazole and itraconazole levels may be increased. High dosages of ketoconazole or itraconazole (greater than 200 mg/day) are not recommended. Voriconazole levels may be decreased when coadministered with ritonavir; therefore, voriconazole coadministered with ritonavir is contraindicated. Plasma ritonavir concentrations may be elevated, increasing the risk of toxicity. Consider using an alternative antifungal agent.

Benzodiazepines (eg, alprazolam, flurazepam), buprenorphine, fentanyl, zolpidem

Plasma levels of these agents, including parenteral midazolam, may be increased. Closely monitor for respiratory depression and prolonged sedation. Adjust the dose of these agents as needed. Coadministration of oral midazolam or triazolam and lopinavir/ritonavir is contraindicated.

Bosentan

Bosentan plasma concentrations may be elevated, increasing the pharmacologic effect and risk of adverse reactions. Discontinue bosentan at least 36 hours prior to starting lopinavir/ritonavir therapy. Bosentan 62.5 mg once daily or every other day can be resumed 10 days or more after starting lopinavir/ritonavir.

Cabazitaxel

Cabazitaxel plasma concentrations may be elevated, increasing the risk of adverse reactions. Avoid coadministration.

Carbamazepine, phenobarbital, phenytoin, protease inhibitors (amprenavir, fosamprenavir, tipranavir)

Lopinavir concentrations may be reduced, decreasing efficacy. Monitor the clinical response of the patient when one of these agents is started or stopped. Adjust the lopinavir/ritonavir dose as needed. Avoid coadministration of tipranavir and lopinavir/ritonavir.

Cat's claw ( Uncaria tomentosa )

Ritonavir plasma concentrations may be elevated, increasing the risk of toxicity. Advise patients receiving lopinavir/ritonavir to avoid use of the herbal product cat's claw.

Cisapride, conivaptan, dronedarone, eplerenone, ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin), meperidine, midazolam (oral), pimozide, propoxyphene, ranolazine, rifampin, St. John's wort, tolvaptan, triazolam

Contraindicated because of potentially serious or life-threatening reactions or loss of virologic response.

Clarithromycin

Ritonavir and clarithromycin plasma levels may be increased. For patients with renal impairment, consider the following dosage adjustments: for patients with CrCl 30 to 60 mL/min, reduce the dose of clarithromycin by 50%; for patients with CrCl less than 30 mL/min, reduce the dose of clarithromycin by 75%.

Colchicine

Colchicine plasma concentrations may be elevated, increasing the risk of toxicity. Coadministration of colchicine and lopinavir/ritonavir is contraindicated in patients with hepatic or renal function impairment. In patients with healthy renal and hepatic function, coadminister lopinavir/ritonavir and colchicine with caution, using a max colchicine dosage of 0.3 mg twice daily. Carefully monitor for colchicine-related adverse reactions.

Contraceptives, hormonal (eg, ethinyl estradiol)

Loss of hormonal contraceptive effectiveness, possibly leading to unintended pregnancy, may occur. Use alternative or additional nonhormonal contraceptive measures when estrogen-based oral contraceptives or the contraceptive patch and lopinavir/ritonavir are coadministered.

Corticosteroids (eg, dexamethasone, fluticasone propionate [inhaled], prednisone, triamcinolone)

Lopinavir/ritonavir may be less effective when coadministered with corticosteroids because of decreased lopinavir plasma concentrations. Corticosteroid plasma concentrations may be elevated, increasing the pharmacologic and toxic effects (eg, Cushing syndrome with secondary adrenal insufficiency). Coadministration of inhaled fluticasone and lopinavir/ritonavir is not recommended unless the potential benefit outweighs the risk of adverse reactions. Use the lowest effective dose of triamcinolone when coadministered with lopinavir/ritonavir. Close clinical monitoring for signs and symptoms of adrenal suppression and Cushing syndrome is recommended.

Darunavir

Darunavir plasma concentrations may be reduced, decreasing the pharmacologic effects. Lopinavir/ritonavir plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Coadministration is not recommended.

Deferasirox

Deferasirox plasma concentrations may be reduced, decreasing the pharmacologic effect. If coadministration cannot be avoided, consider an initial dosage of deferasirox 30 mg/kg/day. Adjust the deferasirox dosages according to serum ferritin concentrations and clinical response.

Didanosine

Because didanosine should be given on an empty stomach and lopinavir/ritonavir oral solution should be taken with food, give didanosine 1 h before or 2 h after lopinavir/ritonavir oral solution.

Disulfiram, metronidazole

A disulfiram-like reaction may occur when coadministered with the lopinavir/ritonavir oral solution, which contains alcohol. Avoid lopinavir/ritonavir solution in patients taking disulfiram or metronidazole.

Docetaxel

Plasma concentrations and pharmacologic effects of docetaxel may be increased. Use of lopinavir/ritonavir with docetaxel may increase the risk of neutropenia. If coadministration cannot be avoided, close clinical and laboratory monitoring are indicated. A docetaxel dosage reduction may be needed.

Eletriptan

Plasma concentrations and pharmacologic effects of eletriptan may be increased by lopinavir/ritonavir. Do not use eletriptan within 72 h of lopinavir/ritonavir.

Erythromycin

Erythromycin plasma concentration may be elevated, increasing the risk of sudden death from cardiac causes. Avoid concurrent use of erythromycin and lopinavir/ritonavir.

Evening primrose

Ritonavir plasma concentrations may be elevated, increasing the risk of toxicity. Advise patients receiving lopinavir/ritonavir to avoid use of the herbal product evening primrose.

Food

Relative to fasting, administration of oral solution with a moderate- or high-fat meal increased lopinavir AUC and C max . To enhance bioavailability and minimize pharmacokinetic variability, administer the oral solution with food.

Garlic

Plasma concentrations and pharmacologic activity of lopinavir/ritonavir may be decreased by garlic, reducing the efficacy. Avoid coadministration of garlic and lopinavir/ritonavir. If combination use cannot be avoided, closely monitor for signs of therapeutic failure of lopinavir/ritonavir.

Grapefruit

Grapefruit juice may increase the plasma concentrations of lopinavir/ritonavir. If grapefruit juice cannot be avoided, closely monitor the clinical response of the patient and adjust the lopinavir/ritonavir dose as needed.

Iloperidone

Iloperidone plasma concentrations and pharmacologic effects may be increased. Reduce the dose of iloperidone by one-half when coadministered with lopinavir/ritonavir. If therapy with lopinavir/ritonavir is discontinued, increase the dose of iloperidone to the original dose.

Indinavir

Indinavir plasma levels may be elevated, increasing the pharmacologic and adverse reactions. Decrease indinavir dosage to 600 mg twice daily when coadministered with lopinavir 400 mg/ritonavir 100 mg twice daily.

Irinotecan

Irinotecan plasma levels may be elevated, increasing the pharmacologic effects and risk of toxicity (eg, diarrhea, neutropenia). Closely monitor for irinotecan toxicity.

Ixabepilone

Ixabepilone plasma levels may be elevated, increasing the pharmacologic and adverse reactions. If coadministration cannot be avoided, consider a reduction in ixabepilone dose. Consult the package labeling for ixabepilone for the specific recommendations.

Levothyroxine

Thyroxine serum concentrations may be increased or decreased. Monitor thyroid function status when lopinavir/ritonavir is started or stopped. Adjust the levothyroxine dose as needed.

Maraviroc

Maraviroc plasma concentrations may be increased. When coadministered with lopinavir/ritonavir, patients should receive maraviroc 150 mg twice daily.

mTOR inhibitors (eg, everolimus, temsirolimus)

mTOR plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. If coadministration of lopinavir/ritonavir is necessary, monitor the clinical response of the patient and adjust the mTOR dose as needed.

Muscarinic receptor antagonists (eg, darifenacin, fesoterodine, solifenacin, tolterodine)

Muscarinic receptor antagonist plasma concentrations may be increased by lopinavir/ritonavir. When lopinavir/ritonavir is coadministered, the dose of darifenacin should not exceed 7.5 mg daily, the dose of fesoterodine should not exceed 4 mg daily, the dose of solifenacin should not exceed 5 mg daily, and the dose of tolterodine should not exceed 2 mg daily.

Nelfinavir

Lopinavir concentrations may be reduced, decreasing the efficacy. Consider a dosage increase of lopinavir/ritonavir in treatment-experienced patients when decreased susceptibility to lopinavir is clinically suspected. Nelfinavir concentrations may be increased. Do not administer lopinavir/ritonavir once daily in combination with nelfinavir.

Nilotinib

Plasma concentrations and pharmacologic effects of nilotinib may be increased, including life-threatening cardiac arrhythmias. If coadministration cannot be avoided, closely monitor for adverse reactions, including QT prolongation. Nilotinib dosage adjustments may be needed when lopinavir/ritonavir is started or stopped.

NNRTIs (eg, delavirdine, efavirenz, nevirapine)

Lopinavir and ritonavir plasma concentrations and clinical efficacy may be reduced when coadministered with efavirenz and nevirapine. Consider a dosage increase of lopinavir/ritonavir when used in combination with efavirenz or nevirapine. Delavirdine may increase lopinavir and ritonavir concentrations. Appropriate doses of this combination have not been established.

Phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil)

Coadministration of lopinavir/ritonavir with sildenafil is contraindicated when used for the treatment of pulmonary arterial hypertension. When used for erectile dysfunction, coadminister with caution and increase monitoring for adverse reactions. In patients receiving lopinavir/ritonavir, the phosphodiesterase type 5 dosage should not exceed the following: sildenafil 25 mg every 48 h, tadalafil 10 mg every 72 h, or vardenafil 2.5 mg every 72 h.

QT prolonging drugs (eg, antiarrhythmic agents [amiodarone], cisapride, pimozide)

Postmarketing cases of QT interval prolongation and torsade de pointes have been reported, although causality of lopinavir/ritonavir could not be established. An additive effect of lopinavir/ritonavir with other drugs that prolong the QT interval cannot be excluded.

Quinazolines (eg, alfuzosin, silodosin, tamsulosin)

Quinazoline plasma concentrations may be elevated. Coadministration of alfuzosin or silodosin and ritonavir is contraindicated. Similarly, tamsulosin should not be coadministered with lopinavir/ritonavir.

Rifamycins (rifabutin, rifampin, rifapentine)

Coadministration may lead to loss of virologic response and possible resistance to lopinavir/ritonavir, or to the class of protease inhibitors or other coadministered antiretroviral agents when administered with rifampin. Ritonavir may elevate serum rifabutin concentrations; therefore, dosage reduction of rifabutin by at least 75% of the usual dosage of 300 mg/day is recommended (ie, a max dosage of 150 mg every other day or 3 times per wk). Monitor for adverse reactions. Coadministration with rifampin is contraindicated.

Romidepsin

Romidepsin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions (including QT prolongation). If coadministration cannot be avoided, close clinical, laboratory, and ECG monitoring are indicated. Adjust the romidepsin dose as needed.

Salmeterol

The risk of CV adverse reactions associated with salmeterol, including QT prolongation, palpitation, and sinus tachycardia may be increased. Coadministration is not recommended.

SSRIs (eg, fluoxetine, paroxetine)

The AUC of ritonavir may be increased. SSRI levels may be increased. Serotonin syndrome may occur; closely monitor for adverse reactions. A dose decrease may be needed. Lopinavir/ritonavir decreased plasma levels of paroxetine with coadministration. Guide any dose adjustment by clinical effect.

Vinblastine, vincristine

Vinblastine or vincristine concentrations may be elevated, increasing the risk of adverse reactions. Consider temporarily withholding lopinavir/ritonavir in patients who develop hematologic or GI side effects. If lopinavir/ritonavir must be withheld for a prolonged period, consider initiating a revised regimen that does not include a CYP3A or P-glycoprotein inhibitor.

Warfarin

Because warfarin concentrations may be altered, monitor INR when starting or stopping lopinavir/ritonavir. Adjust the warfarin dose as needed.

Adverse Reactions

Cardiovascular

Vasodilation (3%); hypertension (2%); angina pectoris, atrial fibrillation, AV block, cerebral infarct, deep vein thrombosis, MI, palpitation, postural hypotension, thrombophlebitis, tricuspid valve incompetence, varicose vein, vasculitis (less than 2%); bradyarrhythmias, first-degree AV block, QTc interval prolongation, second-degree AV block, third-degree AV block, torsades de pointes (postmarketing).

CNS

Asthenia (9%); headache (6%); depression, insomnia (3%); decreased libido, paraesthesia (2%); abnormal dreams, abnormal thinking, affect lability, agitation, amnesia, anxiety, apathy, ataxia, balance disorder, confusion, convulsion, disorientation, dizziness, dyskinesia, encephalopathy, extrapyramidal syndrome, facial palsy, fatigue, hypertonia, malaise, migraine, mood swings, nervousness, peripheral neuropathy, somnolence, tremor, vertigo (less than 2%).

Dermatologic

Rash (12%); acne, allergic dermatitis, alopecia, benign neoplasm of the skin, cellulitis, dermatitis acneiform, dry skin, eczema, exfoliative dermatitis, face swelling, folliculitis, furuncle, idiopathic capillaritis, maculopapular rash, nail disorder, pruritus, seborrhea, skin discoloration, skin hypertrophy, skin striae, skin ulcer, sweating (less than 2%); erythema multiforme, Stevens-Johnson syndrome (postmarketing).

EENT

Ageusia, eye disorder, hyperacusis, otitis media, tinnitus, visual disturbance (less than 2%).

Endocrine

Cushing syndrome, diabetes mellitus, hypothyroidism (less than 2%).

GI

Diarrhea (60%); dysgeusia (22%); vomiting (21%); nausea (16%); abdominal pain (11%); dyspepsia (6%); flatulence (4%); anorexia, dysphagia, upper abdominal pain (2%); abdominal discomfort, abdominal distension, cholangitis, constipation, decreased appetite, dry mouth, duodenitis, enteritis, enterocolitis, eructation, esophagitis, fecal incontinence, gastric disorder, gastric ulcer, gastritis, gastroenteritis, gastroesophageal reflux disease, hemorrhagic enterocolitis, hemorrhoids, increased appetite, lower abdominal pain, mouth ulceration, pancreatitis, periodontitis, rectal hemorrhage, sialadenitis, stomach discomfort, stomatitis (less than 2%).

Genitourinary

Hypogonadism (2%); breast enlargement, ejaculation disorder, erectile dysfunction, gynecomastia, hematuria, menorrhagia, nephritis, nephrolithiasis, perineal abscess, renal disorder, urine abnormality, urine odor abnormal (less than 2%).

Hematologic-Lymphatic

Anemia, leukopenia, lymphadenopathy, neutropenia, splenomegaly (less than 2%).

Hepatic

Cholecystitis, cytolytic hepatitis, hepatic steatosis, hepatitis, hepatomegaly, jaundice, liver tenderness (less than 2%).

Hypersensitivity

Drug hypersensitivity, hypersensitivity (less than 2%).

Lab Tests

Increased total cholesterol (39%); increased triglycerides (36%); increased GGT (29%); increased ALT (11%); increased AST (10%); increased amylase (8%); decreased neutrophils, increased CPK, increased glucose, increased lipase, increased uric acid (5%); decreased platelet count (4%); decreased CrCl, decreased sodium, increased sodium, increased total bilirubin (3%); decreased Hgb, decreased inorganic phosphorous (2%).

Metabolic-Nutritional

Weight decreased (3%); decreased glucose tolerance, dehydration, edema, facial edema, hypovitaminosis, lactic acidosis, lipomatosis, obesity, peripheral edema, weight increased (less than 2%).

Musculoskeletal

Myalgia (2%); arthralgia, arthropathy, back pain, muscular weakness, osteoarthritis, osteonecrosis, pain in extremity (less than 2%).

Respiratory

Bronchitis (2%); asthma, bronchopneumonia, cough, dyspnea, pharyngitis, pulmonary edema, rhinitis, sinusitis (less than 2%).

Miscellaneous

Chills, pyrexia (2%); bacterial infection, chest pain, cyst, drug level increased, hypertrophy, immune reconstitution syndrome, influenza, lipoma, neoplasm, viral infection (less than 2%); accumulation/redistribution of body fat (postmarketing).

Precautions

Monitor

Assess serum transaminases and cholesterol and triglyceride levels before starting therapy and periodically during therapy. Consider increased AST/ALT monitoring in patients with underlying chronic hepatitis or cirrhosis, especially during the first several months of therapy. Monitor blood glucose before starting therapy and periodically during therapy.


Pregnancy

Category C .

Lactation

HIV-infected mothers should not breast-feed infants.

Children

Safety and efficacy have not been established in children younger than 14 days.

Elderly

Select dose with caution, reflecting greater frequency of cardiac, hepatic, or renal function impairment, and of comorbidity.

Hepatic Function

Use with caution; decreased lopinavir/ritonavir Cl may occur.

Cross-resistance

Various degrees of cross-resistance among protease inhibitors have been observed.

Diabetes mellitus

New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia have been reported.

Fat redistribution

Redistribution and accumulation of body fat has been observed.

Hemophilia

Increased bleeding, including spontaneous skin hematomas and hemarthrosis, has been reported in patients with hemophilia type A and B treated with protease inhibitors.

Hepatotoxicity

Patients with underlying hepatitis B or C or marked transaminase elevations prior to treatment may be at increased risk of development or worsening of transaminase elevations or hepatic decompensation.

Immune reconstitution syndrome

Has been reported in patients receiving combination antiretroviral therapy, including lopinavir/ritonavir.

Lipid elevations

Treatment has resulted in large increases in total cholesterol and triglycerides.

Pancreatitis

Fatalities have been associated with use.

Preterm neonate toxicity

The lopinavir/ritonavir oral solution contains the excipients alcohol and propylene glycol, which may place preterm neonates at an increased risk of propylene glycol–associated adverse reactions. Life-threatening cases of cardiac toxicity, lactic acidosis, acute renal failure, CNS depression, and respiratory complications leading to death have been reported.

PR interval prolongation

PR interval may be prolonged in some patients; cases of second- and third-degree heart block have been reported. Use with caution in patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, or cardiomyopathies.

QT prolongation

QT interval prolongation and torsades de pointes have been reported. Avoid use in patients with congenital long QT syndrome, those with hypokalemia, and with other drugs that prolong the QT interval.

Overdosage

Symptoms

Fatal cardiogenic shock in an infant; complete AV block, cardiomyopathy, lactic acidosis, and acute renal failure in preterm neonates.

Patient Information

  • Advise patient to review the Medication Guide before starting therapy and with each refill.
  • Advise patients and/or their health care providers to pay special attention to accurate administration of their dose to minimize the risk of accidental overdose or underdose of lopinavir/ritonavir.
  • Instruct caregivers to inform their health care provider if their children's weight changes to ensure that the child's lopinavir/ritonavir dose is correct.
  • Instruct patients to take the prescribed dose of lopinavir/ritonavir as directed and to set up a daily routine in order to do so.
  • Instruct patients to take the tablets with or without food; the oral solution should be taken with food to enhance absorption.
  • Inform patients that sustained decreases in plasma HIV-1 RNA have been associated with a reduced risk of progression to AIDS and death. Instruct patients to remain under the care of a health care provider while using lopinavir/ritonavir.
  • Advise patients to take lopinavir/ritonavir and other concomitant antiretroviral therapy every day as prescribed; lopinavir/ritonavir must always be used in combination with other antiretroviral drugs. Instruct patients not to alter the dose or discontinue therapy without consulting their health care provider. If a dose is missed, instruct the patient to take the dose as soon as possible and then return to their normal schedule. However, if a dose is skipped, instruct the patient not to double the next dose.
  • Inform patients that lopinavir/ritonavir is not a cure for HIV-1 infection and that they may continue to develop opportunistic infections and other complications associated with HIV-1 disease. The long-term effects of lopinavir/ritonavir are unknown at this time. There are currently no data demonstrating that therapy with lopinavir/ritonavir can reduce the risk of transmitting HIV-1 to others through sexual contact, sharing needles, or being exposed to blood. For their health and the health of others, it is important that they always practice safer sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with any body fluids, such as semen, vaginal secretions, or blood. Advise patients never to reuse or share needles.
  • Lopinavir/ritonavir may interact with some drugs; therefore, advise patients to report to their health care provider the use of any other prescription or nonprescription medication or herbal product, particularly St. John's wort.
  • Lopinavir/ritonavir tablets can be taken at the same time as didanosine without food. Instruct patients taking didanosine to take didanosine 1 h before or 2 h after lopinavir/ritonavir oral solution.
  • Advise patients receiving sildenafil, tadalafil, or vardenafil that they may be at an increased risk of associated adverse reactions, including hypotension, visual changes, and sustained erection, and to promptly report any symptoms to their health care provider. Instruct patients to seek medical assistance immediately if they develop a sustained penile erection lasting more than 4 h while taking lopinavir/ritonavir and a phosphodiesterase type 5 inhibitor.
  • Instruct patients receiving estrogen-based hormonal contraceptives to use additional or alternate contraceptive measures during therapy.
  • If they are taking or before they begin using salmeterol or salmeterol with fluticasone and lopinavir/ritonavir, advise patients to talk to their health care provider about problems these medications may cause when taken together.
  • Advise patients to contact their health care provider if they develop a rash while taking lopinavir/ritonavir.
  • Advise patients that appropriate liver function testing will be conducted prior to initiating and during therapy with lopinavir/ritonavir. Advise patients that their liver function tests will need to be monitored closely, especially during the first several months of lopinavir/ritonavir treatment; instruct patients to notify their health care provider if they develop the signs and symptoms of worsening liver disease, including loss of appetite, abdominal pain, jaundice, and itchy skin.
  • Advise patients to notify their health care provider if they develop the signs and symptoms of diabetes mellitus, including frequent urination, excessive thirst, extreme hunger, unusual weight loss, and/or an increased blood sugar, while taking lopinavir/ritonavir because they may require a change in their diabetes treatment or new treatment.
  • Instruct patients to consult their health care provider if they experience symptoms such as dizziness, light-headedness, abnormal heart rhythm, or loss of consciousness.
  • Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy, including protease inhibitors, and that the cause and long-term health effects of these conditions are not known at this time.
  • Inform patients that there may be a greater chance of developing diarrhea with the once-daily regimen compared with the twice-daily regimen.

Copyright © 2009 Wolters Kluwer Health.

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