Lopinavir-Ritonavir

Lopinavir/Ritonavir is a prescription medicine used for the treatment of HIV-1 infection.

• Lopinavir/Ritonavir is available under the following different brand names: Kaletra

Adult dosage

Tablet

• 100mg/25mg
• 200mg/50mg

Oral solution

• (400mg/100mg)/5mL

HIV-1 Infection

• 400 mg/100 mg orally every 12 hours, OR
• 800 mg/200 mg orally once daily in patients with less than 3 lopinavir resistance-associated substitutions

Coadministration with efavirenz, nevirapine, fosamprenavir, or nelfinavir

• 500 mg/125 mg orally every 12 hours (i.e., 2 x 200 mg/50 mg + 100 mg/25 mg), OR
• Oral solution or capsules: 533 mg/133 mg orally every 12 hours (i.e., ~6.5 mL every 12 hours)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Lopinavir/Ritonavir include:

• nausea,
• vomiting, 
• diarrhea, or
• high cholesterol or triglycerides

Serious side effects of Lopinavir/Ritonavir include:

• signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat),
• signs of a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling)
• fast or pounding heartbeats, 
• fluttering in the chest, 
• shortness of breath, and
• sudden dizziness,
• signs of a kidney stone such as pain in your side or lower back, blood in your urine, painful or difficult urination;
• signs of high blood sugar such as increased thirst, increased urination, fruity breath odor, weight loss; or
• signs of liver or pancreas problems such as loss of appetite, upper stomach pain (that may spread to your back), nausea or vomiting, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes),
• signs of a new infection--fever, night sweats, swollen glands, cold sores, cough, wheezing, diarrhea, weight loss,
• trouble speaking or swallowing,
• problems with balance or eye movement, 
• weakness or prickly feeling, or
• swelling in your neck or throat (enlarged thyroid), 
• menstrual changes, and
• impotence

Rare side effects of Lopinavir/rRtonavir include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Lopinavir/ritonavir has severe interactions with at least 54 other drugs.
• Lopinavir/ritonavir has serious interactions with at least 286 other drugs.
• Lopinavir/ritonavir has moderate interactions with at least 478 other drugs.
• Lopinavir/ritonavir has minor interactions with at least 36 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Hypersensitivity to ritonavir, lopinavir
• Concomitant CYP3A4 inducers and/or major substrates
• Drugs that are contraindicated with lopinavir/ritonavir include alpha1-adrenoreceptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine, dronedarone), rifampin, lomitapide, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, ranolazine, pimozide, sildenafil (when used for PAH), midazolam, and triazolam, apalutamide, colchicine, elbasvir/grazoprevir

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Lopinavir/ritonavir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lopinavir/ritonavir?”

Cautions

• Pancreatitis reported; fatalities have occurred; suspend therapy as clinically appropriate
• Risk of immune reconstitution syndrome if used with HAART
• Hepatotoxicity reported; fatalities have occurred; monitor liver function before and during therapy, especially in patients with underlying hepatic disease, including hepatitis B and hepatitis C, or marked transaminase elevations
• Total cholesterol and triglycerides elevations may occur; monitor before therapy and periodically thereafter
• QT and PR interval prolongation and torsades de pointes have been reported rarely; do not use saquinavir/ritonavir with congenital or documented acquired QT prolongation (above 450 msec), refractory hypokalemia or magnesemia, and in combination with drugs that prolong QT interval
• Second and third-degree heart block reported; use with caution in patients with pre-existing conduction system disease, ischemic heart disease, cardiomyopathy, underlying structural heart disease, or when administering with other drugs that may prolong the PR interval
• Risks of fat redistribution, hemolytic anemia, hyperglycemia, hyperbilirubinemia if used in combination with other antiretroviral drugs
• Increased bleeding, including spontaneous skin hematomas and hemarthrosis reported in patients with hemophilia type A and B treated with protease inhibitors; A causal relationship between protease inhibitor therapy and these events has not been established
• 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; consider monitoring for hyperglycemia, new-onset diabetes mellitus, or an exacerbation of diabetes mellitus
• Adverse effects reported but casual link unclear includes new-onset or worsening of DM and bleeding problems
• Oral solution in newborns
  • Contains alcohol 42.4% and propylene glycol
  • Increased risk for toxicities (i.e., serious heart, kidney, or breathing problems) in premature babies or newborns because of decreased ability to eliminate propylene glycol
  • Postmarketing life-threatening cases of cardiac toxicity (including complete AV block, bradycardia, and cardiomyopathy), lactic acidosis, acute renal failure, CNS depression, and respiratory complications leading to death have been reported, predominantly in preterm neonates
  • Avoid oral solution in premature babies until PMA 42 weeks (i.e., 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 Kaletra 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

Pregnancy and Lactation

• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to therapy during pregnancy; physicians are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263
• Available data from the Antiretroviral Pregnancy Registry show no difference in risk of overall major birth defects compared to the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP); 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
• Newborn infants exposed in utero and then as neonates have an increased risk for congenital adrenal hyperplasia characterized by excessive production of 17-hydroxyprogesterone (17OHP) and above-normal levels of DHEA-S; Simon A, et al. JAMA 2011;306(1):11
• Contraception
• Therapy may reduce the efficacy of combined hormonal contraceptives; advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception
• Lactation
  • The 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 potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in the breastfed infant, instruct mothers not to breastfeed if they are receiving therapy.