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  • Kaletra
    / AbbVie


    Active Ingredient *
    Lopinavir 100 mg, 200 mg, 80 mg/ml
    Ritonavir 25 mg, 50 mg, 20 mg/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    60 X 100/25 mg

    partial basket chart 4874 11259

    Film Coated Tablets

    120 X 200/50 mg

    partial basket chart 70141 11262

    Solution

    60 ml X 80/20 mg/ml

    partial basket chart 56828 11180

    Related information


    Dosage

    General Administration Recommendations: KALETRA tablets may be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed. KALETRA oral solution must be taken with food.
    Because KALETRA oral solution contains ethanol, it is not recommended for use with polyurethane feeding tubes due to potential incompatibility.
    KALETRA can be given in once daily or twice daily dosing regimen: Tablets 400/100 mg (given as two 200/50 mg tablets) twice-daily with or without food. Oral solution 400/100 mg (5 ml) twice-daily taken with food. Tablets 800/200 mg (given as four 200/50 mg tablets) once-daily taken with or without food. Oral solution 800/200 mg (10 mL) once-daily taken with food.
    Once daily administration of this drug  is not recommended in:  
    – Adult patients with three or more of the following lopinavir resistance-associated substitutions: L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V.
    – In combination with carbamazepine, phenobarbital, or phenytoin.
    –  In combination with efavirenz, nevirapine, or nelfinavir.
    – In pediatric patients younger than 18 years of age.
    – In pregnant women.
    The dose of KALETRA must be increased when administered in combination with efavirenz, nevirapine or nelfinavir as following:
    Recommended Dosage in Adults- KALETRA Twice Daily Regimen: 200 mg/50 mg Tablets and 100 mg/25 mg Tablets: 500 mg/125 mg (2 tablets of 200 mg/50 mg + 1 tablet of 100 mg/25 mg) twice daily.
    80 mg/20 mg per mL Oral Solution: 520 mg/130 mg (6.5 mL) twice daily.
    Pediatric Patients: Kaletra Oral Solution is intended for pediatric patients > 6 months of age. KALETRA tablets and oral solution are not recommended for once daily in pediatric patients younger than 18 years of age. The dose of the oral solution should be administered using a calibrated dosing syringe.
    KALETRA 100/25 mg tablets should be considered only in children who have reliably demonstrated the ability to swallow the intact tablet.
    KALETRA oral solution contains 42.4 % (v/v) ethanol and 15.3 % (w/v) propylene glycol.
    Pediatric Dosage Calculations: Calculate the appropriate dose of KALETRA for each individual pediatric patient based on body weight (kg) or body surface area (BSA) to avoid underdosing or exceeding the recommended adult dose – See prescribing information for full details.
    ORAL SOLUTION
    Oral Solution Dosage Recommendation in Pediatric Patients 6 Months to Less Than 18 Years:
    Please refer to table 4 at doctor’s leaflet.
    KALETRA administered in combination with efavirenz, nevirapine, or nelfinavir in patients younger than 6 months of age is not recommended. Total dose of KALETRA oral solution in pediatric patients should not exceed the recommended adult daily dose of 400/100 mg (5mL) twice daily.
    Concomitant Therapy with Efavirenz, Nevirapine, or Nelfinavir: Please refer to table 6 at doctor’s leaflet for dosing recommendations using oral solution.
    TABLETS
    Tablet Dosage Recommendation in Pediatric Patients Older than 6 Months to Less than 18 Years: 
    Please refer to table 5 at doctor’s leaflet.
    Concomitant Therapy with Efavirenz, Nevirapine, or Nelfinavir: Please refer to table 7 at doctor’s leaflet for dosing recommendations using tablets.
    Dosage Recommendations in Pregnancy: Administer 400/100 mg of KALETRA twice daily in pregnant patients with no documented lopinavirassociated
    resistance substitutions.
    – Once daily KALETRA dosing is not recommended in pregnancy.
    – There are insufficient data to recommend dosing in pregnant women with any documented lopinavirassociated resistance substitutions.
    – No dosage adjustment of KALETRA is required for patients during the postpartum period.
    – Avoid use of KALETRA oral solution in pregnant women.
    See prescribing information for full details.


    Indications

    In combination with other antiretroviral agents for the treatment of HIV-1 infection.
    The following points should be considered when initiating therapy with KALETRA:
    – The use of other active agents with KALETRA is associated with a greater likelihood of treatment response.
    – Genotypic or phenotypic testing and/or treatment history should guide the use of KALETRA. The number of baseline lopinavir resistance-associated substitutions affects the virologic response to KALETRA.


    Contra-Indications

    – Patients with previously demonstrated clinically significant hypersensitivity(e.g., toxic epidermal necrolysis,Stevens-Johnson syndrome, erythema multiforme) to any of its ingredients, including ritonavir.
    – Co-administration of this drug is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions.
    ◦ Alpha 1- Adrenoreceptor Antagonist : alfuzosin
    ◦ Antianginal: ranolazine
    ◦ Antiarrhythmic: dronedarone
    ◦ Anti-gout: colchicine
    ◦ Antipsychotics: lurasidone, pimozide
    ◦ Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine
    ◦ GI Motility Agent: cisapride
    ◦ Hepatitis C direct acting antiviral: elbasvir/grazoprevir
    ◦ HMG-CoA Reductase Inhibitors: lovastatin, simvastatin
    ◦ Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide
    ◦ PDE5 Inhibitor: sildenafil when used for the treatment of pulmonary arterial hypertension
    ◦ Sedative/Hypnotics: triazolam, orally administered midazolam
    – Co-administration of this drug is contraindicated with potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance.
    ◦ Antimycobacterial: rifampin
    ◦ Herbal Products: St. John’s Wort (hypericum perforatum)


    Special Precautions

    Risk of Serious Adverse Reactions Due to Drug Interactions: This drug is a CYP3A inhibitor. Initiating treatment with this drug in patients receiving medications metabolized by CYP3A or initiating medications metabolized by CYP3A in patients already maintained on this drug may result in increased plasma concentrations of concomitant medications. Higher plasma concentrations of concomitant medications can result in increased or prolonged therapeutic or adverse effects, potentially leading to severe, life-threatening or fatal events.
    Toxicity in Preterm Neonates: Oral solution contains the excipients alcohol (42.4% v/v) and propylene glycol (15.3% w/v). When administered concomitantly with propylene glycol, ethanol competitively inhibits the metabolism of propylene glycol, which may lead to elevated concentrations. Preterm neonates may be at increased risk of propylene glycol-associated adverse events due to diminished ability to metabolize propylene glycol, thereby leading to accumulation and potential adverse events.
    Pancreatitis: Pancreatitis has been observed in patients receiving this drug therapy, including those who developed marked triglyceride elevations. In some cases, fatalities have been observed.
    Hepatotoxicity: Patients with underlying hepatitis B or C or marked elevations in transaminase prior to treatment may be at increased risk for developing or worsening of transaminase elevations or hepatic decompensation with use of this drug.
    Diabetes Mellitus/Hyperglycemia: New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during post-marketing surveillance in HIV-1 infected patients receiving protease inhibitor therapy.
    Interval Prolongation: Lopinavir/ritonavir prolongs the PR interval in some patients. Cases of second or third degree atrioventricular block have been reported. This formulation should be used with caution in patients with underlying structural heart disease, pre-existing conduction system abnormalities, ischemic heart disease or cardio-myopathies, as these patients may be at increased risk for developing cardiac conduction abnormalities.
    QT Interval Prolongation: Postmarketing cases of QT interval prolongation and torsade de pointes have been reported although causality of this drug could not be established.
    Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including this drug. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, CMV, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis) which may necessitate further evaluation and treatment.
    Fat Redistribution: Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
    Lipid Elevations: Treatment with this drug has resulted in large increases in the concentration of total cholesterol and triglycerides.
    Patients with Hemophilia: Increased bleeding, including spontaneous skin hematomas and hemarthrosis have been reported in patients with hemophilia type A and B treated with protease inhibitors. In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. A causal relationship between protease inhibitor therapy and these events has not been established.
    See prescribing information for full details.  


    Side Effects

    Commonly reported adverse reactions to KALETRA included diarrhea, nausea, vomiting, hypertriglyceridemia and hypercholesterolemia. Diarrhea, nausea and vomiting may occur at the beginning of the treatment while hypertriglyceridemia and hypercholesterolemia may occur later.
    See prescribing information for full details.


    Drug interactions

    Potential for KALETRA to Affect Other Drugs: Lopinavir/ritonavir is an inhibitor of CYP3A and may increase plasma concentrations of agents that are primarily metabolized by CYP3A. Agents that are extensively metabolized by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in AUC (> 3-fold) when coadministered with KALETRA. Thus, co-administration of KALETRA with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or lifethreatening events is contraindicated. Co-administration with other CYP3A substrates may require a dose adjustment or additional monitoring – See prescribing information for full details.
    Additionally, KALETRA induces glucuronidation.
    Published data suggest that lopinavir is an inhibitor of OATP1B1.
    Potential for Other Drugs to Affect Lopinavir: Lopinavir/ritonavir is a CYP3A substrate; therefore, drugs that induce CYP3A may decrease lopinavir plasma concentrations and reduce KALETRA’s therapeutic effect. Although not observed in the KALETRA/ketoconazole drug interaction study, co-dministration of KALETRA and other drugs that inhibit CYP3A may increase lopinavir plasma concentrations.
    Drugs with No Observed or Predicted Interactions with KALETRA: Drug interaction or clinical studies reveal no clinically significant interaction between KALETRA and desipramine (CYP2D6 probe), etravirine, pitavastatin, pravastatin, stavudine, lamivudine, omeprazole, raltegravir, ranitidine, or rilpivirine.
    Based on known metabolic profiles, clinically significant drug interactions are not expected between KALETRA and dapsone, trimethoprim/sulfamethoxazole, azithromycin, erythromycin, or fluconazole.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: Available data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects compared to the background rate for major birth defects in the general population. No treatment-related malformations were observed when lopinavir in combination with ritonavir was
    administered to pregnant rats or rabbits; however embryonic and fetal developmental toxicities occurred in rats administered maternally toxic doses.
    LactationThe Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1. Because of the potential for: 1) HIV transmission (in HIV-negative infants), 2) developing viral resistance (in HIV- positive infants), and 3)
    adverse reactions in the breastfed infant, instruct mothers not to breastfeed if they are receiving KALETRA.
    See prescribing information for full details.                        


    Overdose

    Overdoses with oral solution have been reported. One of these reports described fatal cardiogenic shock in a 2.1 kg infant who received a single dose of 6.5 mL of  oral solution(520 mg lopinavir, approximately 10-fold above the recommended lopinavir dose) nine days prior. The following events have been reported in association with unintended overdoses in preterm neonates: complete AV block, cardiomyopathy, lactic acidosis, and acute renal failure. Healthcare professionals should be aware that oral solution is highly concentrated and therefore, should pay special attention to accurate calculation of the dose of this drug transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors and overdose. This is especially important for infants and young children.
    Oral solution contains 42.4% alcohol (v/v) and 15.3% propylene glycol (w/v). Ingestion of the product over the recommended dose by an infant or a young child could result in significant toxicity and could potentially be lethal. Human experience of acute overdose with this drug is limited. Treatment of overdose with should consist 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. If indicated, elimination of unabsorbed drug should be achieved gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed drug. Since Lopinavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the drug. However, dialysis can remove both alcohol and propylene glycol in the case of overdose with oral solution.
    See prescribing information for full details.  


    Important notes

    Oral solution contains 42.4% (v/v) alcohol and 15.3% (w/v) propylene glycol. Special attention should be given to accurate calculation of the dose of this drug. See prescribing information for full details.
    Before/after meal: Oral solution should be taken with food; tablets may be taken with or without food.
    Storage: Store oral solution at 2°-8°C until dispensed. Avoid exposure to excessive heat. For patient use, refrigerated. Oral solution remains stable until the expiration date printed on the label. If stored at room temperature up to 25°C oral solution should be used within 42 days.
    Tablets: Store below 25°C.


    Manufacturer
    AbbVie Deutschland GmbH & Co. KG., Germany
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