Koletra
Koletra - General Information
Koletra (ABT-378) is an antiretroviral of the protease inhibitor class. It is marketed by Abbott as Kaletra, a co-formulation with a sub-therapeutic dose of ritonavir, as a component of combination therapy to treat HIV/AIDS.
Pharmacology of Koletra
Koletra is an antiretroviral of the protease inhibitor class.
Koletra for patients
KALETRA®
(lopinavir/ritonavir) capsules
(lopinavir/ritonavir) oral solution
ALERT: Find out about medicines that should NOT be taken with
KALETRA. Please also read the section "MEDICINES YOU SHOULD NOT TAKE WITH KALETRA." Patient Information
KALETRA (kuh-LEE-tra)
Generic Name: lopinavir/ritonavir (lop-IN-uh-veer/rit-ON-uh-veer)
Read this leaflet carefully before you start taking KALETRA. Also, read it each time you get your KALETRA prescription refilled, in case something has changed. This information does not take the place of talking with your doctor when you start this medicine and at check ups. Ask your doctor if you have any questions about KALETRA.
Before taking your medicine, make sure you have received the correct medicine. Compare the name above with the name on your bottle and the appearance of your medicine with the description provided below. Contact your pharmacist immediately if you believe a dispensing error has occurred.
What is KALETRA and how does it work?
KALETRA is a combination of two medicines. They are lopinavir and ritonavir. KALETRA is a type of medicine called an HIV (human immunodeficiency virus) protease (PRO-tee-ase) inhibitor. KALETRA is always used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. KALETRA is for adults and for children age 6 months and older.
HIV infection destroys CD4 (T) cells, which are important to the immune system. After a large number of T cells are destroyed, acquired immune deficiency syndrome (AIDS) develops.
KALETRA blocks HIV protease, a chemical which is needed for HIV to multiply. KALETRA reduces the amount of HIV in your blood and increases the number of T cells. Reducing the amount of HIV in the blood reduces the chance of death or infections that happen when your immune system is weak (opportunistic infections).
Does KALETRA cure HIV or AIDS?
KALETRA does not cure HIV infection or AIDS. The long-term effects of KALETRA are not known at this time. People taking KALETRA may still get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.
Does KALETRA reduce the risk of passing HIV to others?
KALETRA does not reduce the risk of passing HIV to others through sexual contact or blood contamination. Continue to practice safe sex and do not use or share dirty needles.
How should I take KALETRA?
- You should stay under a doctor's care when taking KALETRA. Do not change your treatment or stop treatment without first talking with your doctor.
- You must take KALETRA every day exactly as your doctor prescribed it. The dose of KALETRA may be different for you than for other patients. Follow the directions from your doctor, exactly as written on the label.
- Dosing in adults (including children 12 years of age and older):
The usual dose for adults is 3 capsules (400/100 mg) or 5.0 mL of the oral solution twice a day (morning and night), in combination with other anti-HIV medicines.
The doctor may prescribe KALETRA as 6 capsules or 10.0 mL of oral solution (800/200 mg) once-daily in combination with other anti-HIV medicines for some patients who have not taken anti-HIV medications in the past.
- Dosing in children from 6 months to 12 years of age:
Children from 6 months to 12 years of age can also take KALETRA. The child's doctor will decide the right dose based on the child's weight. - Take KALETRA with food to help it work better.
- Do not change your dose or stop taking KALETRA without first talking with your doctor.
- When your KALETRA supply starts to run low, get more from your doctor orpharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to KALETRA and become harder to treat.
- Be sure to set up a schedule and follow it carefully.
- Only take medicine that has been prescribed specifically for you. Do not
give
KALETRA to others or take medicine prescribed for someone else.
What should I do if I miss a dose of KALETRA?
It is important that you do not miss any doses. If you miss a dose of KALETRA, take it as soon as possible and then take your next scheduled dose at its regular time. If it is almost time for your next dose, do not take the missed dose. Wait and take the next dose at the regular time. Do not double the next dose.
What happens if I take too much KALETRA?
If you suspect that you took more than the prescribed dose of this medicine, contact your local poison control center or emergency room immediately.
As with all prescription medicines, KALETRA should be kept out of the reach of young children. KALETRA liquid contains a large amount of alcohol. If a toddler or young child accidentally drinks more than the recommended dose of KALETRA, it could make him/her sick from too much alcohol. Contact your local poison control center or emergency room immediately if this happens.
Who should not take KALETRA?
Together with your doctor, you need to decide whether KALETRA is right for you.
- Do not take KALETRA if you are taking certain medicines. These could cause serious side effects that could cause death. Before you take KALETRA, you must tell your doctor about all the medicines you are taking or are planning to take. These include other prescription and non-prescription medicines and herbal supplements.
For more information about medicines you should not take with KALETRA, please read the section titled "MEDICINES YOU SHOULD NOT TAKE WITH KALETRA."
- Do not take KALETRA if you have an allergy to KALETRA or any of its ingredients, including ritonavir or lopinavir.
Can I take KALETRA with other medications?*
KALETRA may interact with other medicines, including those you take without a prescription. You must tell your doctor about all the medicines you are taking or planning to take before you take KALETRA.
KALETRA can be taken with acid reducing agents (such as omeprazole and ranitidine) with no dose adjustment.
MEDICINES YOU SHOULD NOT TAKE WITH KALETRA:
- Do not take the following medicines with KALETRA because they can cause
serious problems or death if taken with KALETRA.
- Dihydroergotamine, ergonovine, ergotamine and methylergonovine such as Cafergot®, Migranal® D.H.E. 45®, Ergotrate Maleate, Methergine, and others
- Halcion® (triazolam)
- Hismanal® (astemizole)
- Orap® (pimozide)
- Propulsid® (cisapride)
- Seldane® (terfenadine)
- Versed® (midazolam)
- Do not take KALETRA with rifampin, also known as Rimactane®, Rifadin®, Rifater®, or Rifamate®. Rifampin may lower the amount of KALETRA in your blood and make it less effective.
- Do not take KALETRA with St. John's wort (hypericum perforatum), an herbal product sold as a dietary supplement, or products containing St. John's wort. Talk with your doctor if you are taking or planning to take St. John's wort. Taking St. John's wort may decrease KALETRA levels and lead to increased viral load and possible resistance to KALETRA or cross-resistance to other anti-HIV medicines.
- Do not take KALETRA with the cholesterol-lowering medicines Mevacor® (lovastatin) or Zocor® (simvastatin) because of possible serious reactions. There is also an increased risk of drug interactions between KALETRA and Lipitor® (atorvastatin); talk to your doctor before you take any of these cholesterol-reducing medicines with KALETRA.
Medicines that require dosage adjustments:
It is possible that your doctor may need to increase or decrease the dose of other medicines when you are also taking KALETRA. Remember to tell your doctor all medicines you are taking or plan to take.
Before you take Viagra ® (sildenafil), Cialis® (tadalafil), or Levitra ® (vardenafil) with KALETRA, talk to your doctor about problems these two medicines can cause when taken together. You may get increased side effects of VIAGRA, CIALIS, or LEVITRA such as low blood pressure, vision changes, and penis erection lasting more than 4 hours. If an erection lasts longer than 4 hours, get medical help right away to avoid permanent damage to your penis. Your doctor can explain these symptoms to you.
- If you are taking oral contraceptives ("the pill") or the contraceptive patch to prevent pregnancy, you should use an additional or different type of contraception since KALETRA may reduce the effectiveness of oral or patch contraceptives.
- Efavirenz (Sustiva�), nevirapine (Viramune®), Agenerase (amprenavir) and Viracept (nelfinavir) may lower the amount of KALETRA in your blood. Your doctor may increase your dose of KALETRA if you are also taking efavirenz, nevirapine, amprenavir or nelfinavir. KALETRA should not be taken once-daily with these medicines.
- If you are taking Mycobutin® (rifabutin), your doctor will lower the dose of Mycobutin.
- A change in therapy should be considered if you are taking KALETRA with:
- Phenobarbital
- Phenytoin (Dilantin® and others)
- Carbamazepine (Tegretol® and others)
These medicines may lower the amount of KALETRA in your blood and make it less effective. KALETRA should not be taken once-daily with these medicines.
- If you are taking or before you begin using inhaled Flonase® (fluticasone propionate) talk to your doctor about problems these two medicines may cause when taken together. Your doctor may choose not to keep you on inhaled Flonase®.
- Other Special Considerations:
KALETRA oral solution contains alcohol. Talk with your doctor if you are taking or planning to take metronidazole or disulfiram. Severe nausea and vomiting can occur. - If you are taking both didanosine (Videx®) and KALETRA:
Didanosine (Videx®) should be taken one hour before or two hours after KALETRA.
What are the possible side effects of KALETRA?
- This list of side effects is not complete. If you have questions about side effects, ask your doctor, nurse, or pharmacist. You should report any new or continuing symptoms to your doctor right away. Your doctor may be able to help you manage these side effects.
- The most commonly reported side effects of moderate severity that are thought to be drug related are: abdominal pain, abnormal stools (bowel movements), diarrhea, feeling weak/tired, headache, and nausea. Children taking KALETRA may sometimes get a skin rash.
- Blood tests in patients taking KALETRA may show possible liver problems. People with liver disease such as Hepatitis B and Hepatitis C who take KALETRA may have worsening liver disease. Liver problems including death have occurred in patients taking KALETRA. In studies, it is unclear if KALETRA caused these liver problems because some patients had other illnesses or were taking other medicines.
- Some patients taking KALETRA can develop serious problems with their pancreas (pancreatitis), which may cause death. You have a higher chance of having pancreatitis if you have had it before. Tell your doctor if you have nausea, vomiting, or abdominal pain. These may be signs of pancreatitis.
- Some patients have large increases in triglycerides and cholesterol. The long- term chance of getting complications such as heart attacks or stroke due to increases in triglycerides and cholesterol caused by protease inhibitors is not known at this time.
- Diabetes and high blood sugar (hyperglycemia) occur in patients taking protease inhibitors such as KALETRA. Some patients had diabetes before starting protease inhibitors, others did not. Some patients need changes in their diabetes medicine. Others needed new diabetes medicine.
- Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the trunk. Loss of fat from the legs, arms and face may also happen. The cause and long term health effects of these conditions are not known at this time.
- Some patients with hemophilia have increased bleeding with protease inhibitors.
- There have been other side effects in patients taking KALETRA. However, these side effects may have been due to other medicines that patients were taking or to the illness itself. Some of these side effects can be serious.
What should I tell my doctor before taking KALETRA?
- If you are pregnant or planning to become pregnant: The effects of KALETRA on pregnant women or their unborn babies are not known.
- If you are breast-feeding: Do not breast-feed if you are taking KALETRA. You should not breast-feed if you have HIV. If you are a woman who has or will have a baby, talk with your doctor about the best way to feed your baby. You should be aware that if your baby does not already have HIV, there is a chance that HIV can be transmitted through breast- feeding.
- If you have liver problems: If you have liver problems or are infected with Hepatitis B or Hepatitis C, you should tell your doctor before taking KALETRA.
- If you have diabetes: Some people taking protease inhibitors develop new or more serious diabetes or high blood sugar. Tell your doctor if you have diabetes or an increase in thirst or frequent urination.
- If you have hemophilia: Patients taking KALETRA may have increased bleeding.
How do I store KALETRA?
- Keep KALETRA and all other medicines out of the reach of children.
- Refrigerated KALETRA capsules and oral solution remain stable until the expiration date printed on the label. If stored at room temperature up to 77°F (25°C), KALETRA capsules and oral solution should be used within 2 months.
- Avoid exposure to excessive heat.
Do not keep medicine that is out of date or that you no longer need. Be sure that if you throw any medicine away, it is out of the reach of children.
General advice about prescription medicines:
Talk to your doctor or other health care provider if you have any questions about this medicine or your condition. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. If you have any concerns about this medicine, ask your doctor. Your doctor or pharmacist can give you information about this medicine that was written for health care professionals. Do not use this medicine for a condition for which it was not prescribed. Do not share this medicine with other people.
* The brands listed are trademarks of their respective owners and are not trademarks of Abbott Laboratories. The makers of these brands are not affiliated with and do not endorse Abbott Laboratories or its products.
Koletra Interactions
KALETRA is an inhibitor of CYP3A (cytochrome P450 3A) both in vitro and in vivo. Co-administration of KALETRA and drugs primarily metabolized by CYP3A (e.g., dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants and PDE5 inhibitors) may result in increased plasma concentrations of the other drugs that could increase or prolong their therapeutic and adverse effects. 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 co-administered with KALETRA.
KALETRA does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 or CYP1A2 at clinically relevant concentrations.
KALETRA has been shown in vivo to induce its own metabolism and to increase the biotransformation of some drugs metabolized by cytochrome P450 enzymes and by glucuronidation.
KALETRA is metabolized by CYP3A. Co-administration of KALETRA and drugs that induce CYP3A may decrease lopinavir plasma concentrations and reduce its therapeutic effect. Although not noted with concurrent ketoconazole, co-administration of KALETRA and other drugs that inhibit CYP3A may increase lopinavir plasma concentrations.
Drugs that are contraindicated and not recommended for co-administration with KALETRA are included in Table 10. Drugs That Should Not Be Co-administered With KALETRA. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious events or loss of efficacy.
Table 10. Drugs That Should Not Be Co-administered With KALETRA
| Drug Class: Drug Name | Clinical Comment |
| Antihistamines: astemizole, terfenadine |
CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| Antimycobacterial: rifampin |
May lead to loss of virologic response and possible resistance to KALETRA or to the class of protease inhibitors or other co-administered antiretroviral agents.. |
| Ergot Derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine |
CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. |
| GI Motility Agent: cisapride |
CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| Herbal Products: St. John's wort (hypericum perforatum) |
May lead to loss of virologic response and possible resistance to KALETRA or to the class of protease inhibitors. |
| HMG-CoA Reductase Inhibitors: lovastatin, simvastatin |
Potential for serious reactions such as risk of myopathy including rhabdomyolysis. |
| Neuroleptic: pimozide |
CONTRAINDICATED due to the potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| Sedative/Hypnotics: midazolam, triazolam |
CONTRAINDICATED due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. |
Table 11. Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction See CLINICAL PHARMACOLOGY for Magnitude of Interaction � Table 3 and Table 4
| Concomitant Drug Class: Drug Name |
Effect on Concentration of lopinavir or Concomitant DrugHIV-Antiviral Agents |
Clinical Comment |
| HIV-Antiviral Agents | ||
| Non-nucleoside Reverse Transcriptase Inhibitors: efavirenz*, nevirapine* |
↓ Lopinavir | A dose increase of KALETRA to 533/133 mg (4 capsules or 6.5 mL) twice daily taken with food is recommended when used in combination with efavirenz or nevirapine. KALETRA should not be administered once-daily in combination with efavirenz or nevirapine. NOTE: Efavirenz and nevirapine induce the activity of CYP3A and thus have the potential to decrease plasma concentrations of other protease inhibitors when used in combination with KALETRA. |
| Non-nucleoside Reverse Transcriptase Inhibitor: delavirdine |
↑ Lopinavir | Appropriate doses of the combination with respect to safety and efficacy have not been established. |
| Nucleoside Reverse Transcriptase Inhibitor: didanosine |
It is recommended that didanosine be administered on an empty stomach; therefore, didanosine should be given one hour before or two hours after KALETRA (given with food). |
|
| Nucleoside Reverse Transcriptase Inhibitor: tenofovir |
↑ Tenofovir | KALETRA increases tenofovir concentrations. The mechanism of this interaction is unknown. Patients receiving KALETRA and tenofovir should be monitored for tenofovir-associated adverse events. |
| HIV-Protease Inhibitor: amprenavir* |
↑ Amprenavir (amprenavir 750 mg BID + KALETRA produces ↑ AUC, similar Cmax, ↑ Cmin, relative to amprenavir 1200 mg BID ↓ Lopinavir |
Increase KALETRA dose to 533/133 mg and decrease amprenavir dose to amprenavir 750 mg BID, when co-administered.. KALETRA should not be administered once-daily in combination with amprenavir. Appropriate doses of the combination of fosamprenavir and KALETRA have not been established. |
| HIV-Protease Inhibitor: fosamprenavir |
↓ Amprenavir ↓ Lopinavir |
An increased rate of adverse events has been observed with co-administration of these medications. Appropriate doses of the combinations with respect to safety and efficacy have not been established. |
| HIV-Protease Inhibitor: indinavir* |
↑ Indinavir (indinavir 600 mg BID + KALETRA produces similar AUC, ↓ Cmax, ↑ Cmin relative to indinavir 800 mg TID |
Decrease indinavir dose to 600 mg BID, when co- administered with KALETRA 400/100 mg BID . KALETRA once-daily has not been studied in combination with indinavir. |
| HIV-Protease Inhibitor: nelfinavir* |
↑ Nelfinavir (nelfinavir 1000 mg BID + KALETRA produces similar AUC, similar Cmax, ↑ Cmin relative to nelfinavir 1250 mg BID) ↑ M8 metabolite of nelfinavir ↓ Lopinavir |
Increase KALETRA dose to 533/133 mg and decrease nelfinavir dose to 1000 mg BID, when co- administered. KALETRA should not be administered once-daily in combination with nelfinavir. |
| HIV-Protease Inhibitor: saquinavir* |
↑ Saquinavir (saquinavir 800 mg BID + KALETRA produces ↑ AUC, ↑ Cmax, ↑ Cmin relative to saquinavir 1200 mg TID) |
Decrease saquinavir dose to 800 mg BID, when co- administered with KALETRA 400/100 mg BID . KALETRA once-daily has not been studied in combination with saquinavir. |
| HIV-Protease Inhibitor: tipranavir |
↓ Lopinavir AUC and Cmin | KALETRA should not be administered with tipranavir (500 mg twice-daily) co-administered with ritonavir (200 mg twice-daily). |
| HIV-Protease Inhibitor: ritonavir* |
↑ Lopinavir | Appropriate doses of additional ritonavir in combination with KALETRA with respect to safety and efficacy have not been established. |
| Other Agents | ||
| Antiarrhythmics: amiodarone, bepridil, lidocaine (systemic), and quinidine |
↑ Antiarrhythmics | Caution is warranted and therapeutic concentration monitoring is recommended for antiarrhythmics when co-administered with KALETRA, if available. |
| Anticoagulant: warfarin |
Concentrations of warfarin may be affected. It is recommended that INR (international normalized ratio) be monitored. |
|
| Anticonvulsants: carbamazepine, phenobarbital, phenytoin |
↓ Lopinavir | Use with caution. KALETRA may be less effective due to decreased lopinavir plasma concentrations in patients taking these agents concomitantly. KALETRA should not be administered once-daily in combination with carbamazepine, phenobarbital, or phenytoin. |
| Antidepressant: trazodone |
↑ Trazodone | Concomitant use of trazodone and KALETRA may increase concentrations of trazodone. Adverse events of nausea, dizziness, hypotension and syncope have been observed following co administration of trazodone and ritonavir. If trazodone is used with a CYP3A4 inhibitor such as ritonavir, the combination should be used with caution and a lower dose of trazodone should be considered. |
| Anti-infective: clarithromycin |
↑ Clarithromycin |
For patients with renal impairment, the following |
| Antifungals: ketoconazole*, itraconazole, voriconazole |
↑ Ketoconazole ↑ Itraconazole Voriconazole effect is unknown. |
High doses of ketoconazole or itraconazole (> 200 mg/day) are not recommended. Co- administration of voriconazole with KALETRA has not been studied. However,administration of voriconazole with ritonavir 400 mg every 12 hours decreased voriconazole steady-state AUC by an average of 82%. The effect of lower ritonavir doses on voriconazole is not known at this time. Until data are available, voriconazole should not be administered to patients receiving KALETRA. |
| Antimycobacterial: rifabutin* |
↑ Rifabutin and rifabutin metabolite |
Dosage reduction of rifabutin by at least 75% of the usual dose of 300 mg/day is recommended (i.e., a maximum dose of 150 mg every other day or three times per week). Increased monitoring for adverse events is warranted in patients receiving the combination. Further dosage reduction of rifabutin may be necessary. |
| Antimycobacterial: Rifampin |
↓ Lopinavir | May lead to loss of virologic response and possible resistance to KALETRA or to the class of protease inhibitors or other co-administered antiretroviral agents. A study evaluated combination of rifampin 600 mg QD, with KALETRA 800/200 mg BID or KALETRA 400/100 mg + ritonavir 300 mg BID. Pharmacokinetic and safety results from this study do not allow for a dose recommendation. Nine subjects (28%) experienced a ≥ grade 2 increase in ALT/AST, of which seven (21%) prematurely discontinued study per protocol. Based on the study design, it is not possible to determine whether the frequency or magnitude of the ALT/AST elevations observed is higher than what would be seen with rifampin alone.. |
| Antiparasitic: atovaquone |
↓ Atovaquone | Clinical significance is unknown; however, increase in atovaquone doses may be needed. |
| Calcium Channel Blockers, |
↑ Dihydropyridine calcium channel blockers |
Caution is warranted and clinical monitoring of patients is recommended. |
| Dihydropyridine: e.g.,felodipine, nifedipine, nicardipine Corticosteroid: Dexamethasone |
↓ Lopinavir | Use with caution. KALETRA may be less effective due to decreased lopinavir plasma concentrations in patients taking these agents concomitantly. |
| Disulfiram/metronidazole | KALETRA oral solution contains alcohol, which can produce disulfiram-like reactions when co- administered with disulfiram or other drugs that produce this reaction (e.g., metronidazole). |
|
| PDE5 inhibitors: sildenafil, tadalafil, vardenafil |
↑ Sildenafil ↑ Tadalafil ↑ Vardenafil |
Use sildenafil with caution at reduced doses of 25 mg every 48 hours with increased monitoring for adverse events. Use tadalafil with caution at reduced doses of 10 mg every 72 hours with increased monitoring for adverse events. Use vardenafil with caution at reduced doses of nomore than 2.5 mg every 72 hours with increased monitoring for adverse events. |
| HMG-CoA Reductase Inhibitors: atorvastatin* |
↑ Atorvastatin | Use lowest possible dose of atorvastatin with careful monitoring, or consider other HMG-CoA reductase inhibitors such as pravastatin or fluvastatin in combination with KALETRA. |
| Immunosuppressants: cyclosporine, tacrolimus, rapamycin |
↑ Immunosuppressants | Therapeutic concentration monitoring is recommended for immunosuppressant agents when co-administered with KALETRA. |
| Inhaled Steroid: fluticasone |
↑ Fluticasone | Concomitant use of fluticasone propionate and KALETRA may increase plasma concentrations of fluticasone propionate, resulting in significantly reduced serum cortisol concentrations. Co- administration of fluticasone propionate and KALETRA is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effect |
| Narcotic Analgesic: Methadone* |
↓ Methadone | Dosage of methadone may need to be increased when co-administered with KALETRA. |
| Oral Contraceptive: ethinyl estradiol* |
↓ Ethinyl estradiol | Because contraceptive steroid concentrations may be altered when KALETRA is co-administered with oral contraceptives or with the contraceptive patch, alternative methods of nonhormonal contraception are recommended. |
Other Drugs
Drug interaction studies reveal no clinically significant interaction between KALETRA and desipramine (CYP2D6 probe), pravastatin, stavudine, lamivudine, omeprazole or ranitidine.
Based on known metabolic profiles, clinically significant drug interactions are not expected between KALETRA and fluvastatin, dapsone, trimethoprim/sulfamethoxazole, azithromycin, erythromycin, or fluconazole.
Zidovudine and Abacavir: KALETRA induces glucuronidation; therefore, KALETRA has the potential to reduce zidovudine and abacavir plasma concentrations. The clinical significance of this potential interaction is unknown.
Koletra Contraindications
KALETRA is contraindicated in patients with known hypersensitivity to any of its ingredients, including ritonavir.
Co-administration of KALETRA 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 events. These drugs are listed in Table 9.
Table 9. Drugs That Are Contraindicated With KALETRA
| Drug Class | Drugs Within Class That Are Contraindicated With KALETRA |
| Antihistamines | Astemizole, Terfenadine |
| Ergot Derivatives | Dihydroergotamine, Ergonovine, Ergotamine, Methylergonovine |
| GI motility agent | Cisapride |
| Neuroleptic | Pimozide |
| Sedative/Hypnotics | Midazolam, Triazolam |
Additional information about Koletra
Koletra Indication: Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.
Mechanism Of Action: Koletra inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Drug Interactions: Not Available
Food Interactions: Take with food.
Avoid St.John's Wort.
Generic Name: Lopinavir
Synonyms: ABT-378; LPV
Drug Category: Anti-HIV Agents; HIV Protease Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Lopinavir: Aluviran; Koletra;
Absorption: Administered alone, lopinavir has insufficient bioavailability; however, like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of cytochrome P450 3A4.
Toxicity (Overdose): Although human experience of acute overdosage with lopinavir is limited, accidental ingestion of the product by a young child could result in significant alcohol-related toxicity and could approach the potential lethal dose of alcohol.
Protein Binding: Lopinavir is highly bound to plasma proteins (98-99%).
Biotransformation: Hepatic. Lopinavir is extensively metabolized by the hepatic cytochrome P450 system, almost exclusively by the CYP3A isozyme.
Half Life: Not Available
Dosage Forms of Koletra: Capsule Oral
Solution Oral
Chemical IUPAC Name: (2S)-N-[(2S,4S,5S)-5-[[2-(2,6-dimethylphenoxy)acetyl]amino]-4-hydroxy-1,6-di(phenyl)hexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
Chemical Formula: C37H48N4O5
Lopinavir on Wikipedia: https://en.wikipedia.org/wiki/Lopinavir
Organisms Affected: Human Immunodeficiency Virus
