Kaletra 200 mg/50 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Kaletra 200 mg/50 mg film-coated tablets

lopinavir/ritonavir

Read all of this leaflet carefully before you or your child start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you or your child only. Do not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you or your child experience any side effects, talk to your doctor or pharmacist, even if it is not one of the side effects listed in this leaflet. See section 4.

Contents of the leaflet

1. What Kaletra is and what it is used for
2. What you need to know before you or your child take Kaletra
3. How to take Kaletra
4. Possible side effects
5. How to store Kaletra
6. Contents of the pack and other information

1. What Kaletra is and what it is used for

• Your doctor has prescribed Kaletra to help control your human immunodeficiency virus (HIV) infection. This is possible because Kaletra works by preventing the infection from spreading rapidly.
• Kaletra is not a cure for HIV infection or AIDS.
• Kaletra is used in children aged 2 years and older, adolescents, and adults infected with HIV, the virus that causes AIDS.
• Kaletra contains the active substances lopinavir and ritonavir. Kaletra is an antiretroviral medicine belonging to the group of medicines called protease inhibitors.
• Kaletra is prescribed for use in combination with other antiviral medicines. Your doctor will inform you and decide which medicines are best for your case.

2. What you need to know before you or your child take Kaletra

Do not take Kaletra:

• if you are allergic to lopinavir, ritonavir, or any of the other ingredients of this medicine (listed in section 6);
• if you have severe liver problems.

Do not take Kaletra with any of the following medicines:

• astemizole or terfenadine (normally used to treat allergy symptoms – these medicines may not require a prescription);
• oral midazolam (taken by mouth), triazolam (used to relieve anxiety and/or sleep problems);
• pimozide (used to treat schizophrenia);
• quetiapine (used to treat schizophrenia, bipolar disorder, and major depressive disorder);
• lurasidone (used to treat depression);
• ranolazine (used to treat chronic chest pain [angina pectoris]);
• cisapride (used to relieve certain stomach problems);
• ergotamine, dihydroergotamine, ergonovina, methylergonovine (used to treat headaches);
• amiodarone, dronedarone (used to treat heart rhythm disorders);
• lovastatin, simvastatin (used to lower blood cholesterol);
• lomitapide (used to lower blood cholesterol);
• alfuzosin (used in men to treat symptoms of an enlarged prostate (benign prostatic hyperplasia (BPH));
• fusidic acid (used to treat skin infections caused by the bacterium Staphylococcus, such as impetigo and infected dermatitis). Fusidic acid is also used to treat long-term bone and joint infections under medical supervision (see section Other medicines and Kaletra);
• colchicine (a medicine used to treat gout). If you have liver or kidney problems (see section Other medicines and Kaletra);
• elbasvir/grazoprevir (used to treat chronic hepatitis C virus (HCV) infection);
• neratinib (used to treat breast cancer);
• avanafil or vardenafil (used to treat erectile dysfunction);
• sildenafil used for the treatment of pulmonary hypertension (high blood pressure in the pulmonary artery). Sildenafil may be used for erectile dysfunction under medical supervision (see section Other medicines and Kaletra);
• products containing St. John's wort (Hypericum perforatum).

For more information about other medicines that require special precautions, please refer to the list of medicines below included in “Other medicines and Kaletra”.

If you are currently taking any of these medicines, consult your doctor about whether it is necessary to change your treatment for other conditions or your antiretroviral therapy.

Warnings and precautions

Talk to your doctor or pharmacist before starting Kaletra.

Important information

• People taking Kaletra may still develop infections or other diseases associated with HIV and AIDS. Therefore, it is important that you remain under your doctor’s supervision while taking Kaletra.

Tell your doctor if you or your child have or have had:

• Haemophilia types A and B, as Kaletra may increase the risk of bleeding.
• Diabetes, as increased blood sugar levels have been reported in patients taking Kaletra.
• A history of liver problems, as patients with a history of liver disease, including chronic hepatitis B or C, have a higher risk of developing serious and potentially life-threatening liver side effects.

Tell your doctor if you or your child experience:

• Nausea, vomiting, abdominal pain, difficulty breathing, and severe muscle weakness in the arms and legs, as these may be symptoms of increased lactic acid levels.
• Thirst, frequent urination, blurred vision, or weight loss, as these may indicate high blood sugar levels.
• Nausea, vomiting, abdominal pain, as large increases in triglyceride levels (fats in the blood) are considered a risk factor for pancreatitis (inflammation of the pancreas), and the symptoms described may suggest this condition.
• In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections that were previously present without apparent symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition where the immune system attacks healthy body tissue) may also occur after starting medicines for HIV infection. Autoimmune disorders may appear several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving upward toward the trunk, palpitations, tremors, or hyperactivity, please inform your doctor immediately to receive necessary treatment.
• Joint stiffness, pain, and discomfort (especially in the hip, knee, and shoulder) and difficulty moving, as some patients taking these medicines may develop a bone disease called osteonecrosis (death of bone tissue due to loss of blood supply to the bone). Risk factors for developing this condition include duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression (reduced immune system activity), and high body mass index.
• Muscle pain, discomfort, or weakness, particularly when used in combination with these medicines. In rare cases, these muscle problems have been severe.
• Symptoms of dizziness, lightheadedness, fainting, or irregular heartbeat. Kaletra may cause changes in your heart rhythm and electrical activity. These changes may be seen on an ECG (electrocardiogram).

Other medicines and Kaletra

Tell your doctor or pharmacist if you or your child are taking, have recently taken, or might need to take any other medicines.

• antibiotics (e.g. rifampicin, rifabutin, clarithromycin);
• anticancer medicines (e.g. abemaciclib, afatinib, apalutamide, ceritinib, encorafenib, ibrutinib, venetoclax, most tyrosine kinase inhibitors such as dasatinib and nilotinib, and also vincristine and vinblastine);
• anticoagulants (e.g. dabigatran etexilate, edoxaban, rivaroxaban, warfarin);
• antidepressants (e.g. trazodone, bupropion);
• antiepileptic medicines (e.g. carbamazepine, phenytoin, phenobarbital, lamotrigine, and valproate);
• antifungal medicines (e.g. ketoconazole, itraconazole, voriconazole);
• medicines for gout (e.g. colchicine). You must not take Kaletra with colchicine if you have liver or kidney problems (see also “Do not take Kaletra” above);
• antituberculosis medicines (e.g. bedaquiline, delamanid);
• antiviral medicines used to treat chronic hepatitis C virus (HCV) infection in adults (e.g. glecaprevir/pibrentasvir, simeprevir, and sofosbuvir/velpatasvir/voxilaprevir);
• medicines for erectile dysfunction (e.g. sildenafil and tadalafil);
• fusidic acid used for long-term treatment of bone and joint infections (e.g. osteomyelitis);
• heart medicines including:
  • digoxin;
  • calcium channel blockers (e.g. felodipine, nifedipine, nicardipine);
  • medicines used to correct heart rhythm (e.g. bepridil, systemic lidocaine, quinidine);
• HIV CCR5 antagonists (e.g. maraviroc);
• HIV-1 integrase inhibitors (e.g. raltegravir);
• medicines used to treat low platelet count in blood (e.g. fostamatinib);
• levothyroxine (used to treat thyroid problems);
• medicines used to lower blood cholesterol (e.g. atorvastatin, lovastatin, rosuvastatin, or simvastatin);
• medicines used to treat asthma and other lung-related conditions such as chronic obstructive pulmonary disease (COPD) (e.g. salmeterol);
• medicines used to treat pulmonary arterial hypertension (high blood pressure in the pulmonary artery) (e.g. bosentan, riociguat, sildenafil, tadalafil);
• medicines that affect the immune system (e.g. cyclosporine, sirolimus (rapamycin), tacrolimus);
• medicines used to stop smoking (e.g. bupropion);
• painkillers (e.g. fentanyl);
• morphine-like medicines (e.g. methadone);
• non-nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g. efavirenz, nevirapine);
• oral contraceptives or contraceptive patches to prevent pregnancy (see section “Contraceptives” below);
• protease inhibitors (e.g. fosamprenavir, ritonavir, tipranavir);
• sedatives (e.g. injectable midazolam);
• steroids (e.g. budesonide, dexamethasone, fluticasone propionate, ethinylestradiol, triamcinolone).

For more information about other medicines you must not take while taking Kaletra, please refer to the list of medicines above included in “Do not take Kaletra with any of the following medicines”.

Tell your doctor or pharmacist if you or your child are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

Medicines for erectile dysfunction (e.g. avanafil, vardenafil, sildenafil, and tadalafil)

• Do not take Kaletra if you are currently taking avanafil or vardenafil.
• You must not take Kaletra together with sildenafil when used for the treatment of pulmonary hypertension (high blood pressure in the pulmonary artery) (see also the section above Do not take Kaletra).
• If you are taking sildenafil or tadalafil together with Kaletra, you may be at risk of adverse reactions such as low blood pressure, fainting, vision changes, and a penile erection lasting more than 4 hours. If an erection lasts more than 4 hours, you must seek immediate medical attention to avoid permanent penile damage. Your doctor can explain these symptoms to you.

Contraceptives

• If you are taking oral contraceptives or using contraceptive patches to prevent pregnancy, you should use an additional or different type of contraception (e.g. condom), as Kaletra may reduce the effectiveness of oral contraceptives and contraceptive patches.

Pregnancy and breastfeeding

• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor immediately before using this medicine.
• If you are breastfeeding or considering breastfeeding, you should consult your doctor as soon as possible.
• It is recommended that women living with HIV do not breastfeed their children, as there is a risk that the child could become infected with HIV through breast milk.

Driving and using machines

No specific studies have been conducted on the possible effects of Kaletra on the ability to drive and use machines. Do not drive or operate machinery if you experience any adverse effects (e.g. nausea) that could impair your ability to do so safely. Consult your doctor.

Kaletra contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially "sodium-free".

3. How to take Kaletra

Follow exactly the administration instructions for this medicine as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

How and when to take Kaletra

Use in adults

• The usual dose in adults is 400 mg/100 mg twice daily, e.g., every 12 hours, in combination with other anti-HIV medications. Adult patients who have not previously been treated with other antiviral medicines may also take Kaletra once daily at a dose of 800 mg/200 mg. Your doctor will tell you how many tablets or volume of oral solution you should take. If your doctor decides it is appropriate, adult patients who have previously been treated with other antiviral medicines may take Kaletra tablets once daily at a dose of 800 mg/200 mg.
• Kaletra must not be taken once daily with efavirenz, nevirapine, carbamazepine, phenobarbital, or phenytoin.
• Kaletra tablets may be taken with or without food.

Use in children

• For children, your doctor will determine the correct dose (number of tablets or volume of oral solution) based on the child's weight and height.
• Kaletra tablets may be taken with or without food.

Kaletra is also available as film-coated tablets 100 mg/25 mg. Kaletra oral solution is available for patients who cannot take tablets.

If you or your child have taken more Kaletra than you should

• If you realize you have taken more Kaletra than prescribed, inform your doctor immediately.
• If you cannot contact your doctor, go to the hospital.

If you or your child have forgotten to take Kaletra

If you are taking Kaletra twice daily

• If you realize you have missed a dose within 6 hours of your usual dosing time, take it as soon as possible and then continue with your normal dosing schedule, taking the next dose at the time prescribed by your doctor.

• If more than 6 hours have passed since your usual dosing time, do not take the missed dose. Take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you are taking Kaletra once daily

• If you realize you have missed a dose within 12 hours of your usual dosing time, take it as soon as possible and then continue with your normal dosing schedule at the time prescribed by your doctor.

• If more than 12 hours have passed since your usual dosing time, do not take the missed dose. Take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you or your child stop taking Kaletra

• Do not stop taking or change your daily dose of Kaletra without first consulting your doctor.
• Kaletra must be taken every day to help control HIV, regardless of how well you feel.
• Taking Kaletra as prescribed is the best way to delay the development of drug resistance.
• If an adverse reaction prevents you from taking Kaletra as directed, inform your doctor promptly.
• Always keep an adequate supply of Kaletra to avoid running out. When traveling or if you need to be hospitalized, ensure you have enough medication until you can obtain more.
• Continue taking this medicine until your doctor tells you otherwise.

4. Possible adverse effects

Like all medicines, Kaletra can cause adverse effects, although not everyone experiences them. It may be difficult to distinguish between adverse effects caused by Kaletra and those caused by other medicines taken at the same time, or those resulting from complications of HIV infection.

During HIV treatment, there may be an increase in weight and in blood glucose and lipid levels. This may be partly related to improved health and lifestyle, and in the case of blood lipids, sometimes to HIV medicines themselves. Your doctor will monitor these changes.

The following adverse effects have been reported by patients taking this medicine. You should inform your doctor promptly about these or any other symptoms. Seek medical advice if they persist or worsen.

Very common: may affect more than 1 in 10 people

• diarrhea;
• nausea;
• upper respiratory tract infection;

Common: may affect up to 1 in 10 people

• inflammation of the pancreas;
• vomiting, abdominal distension, pain in the upper and lower stomach area, transient flatulence, indigestion, decreased appetite, reflux from your stomach into your esophagus that may cause pain;
• Inform your doctor if you experience nausea, vomiting, or abdominal pain, as these may be symptoms of pancreatitis (inflammation of the pancreas).
• swelling or inflammation of the stomach, intestine, and colon;
• increased blood cholesterol levels, increased blood triglyceride levels (a type of fat), high blood pressure;
• reduced ability of the body to metabolize sugar as in diabetes mellitus, weight loss;
• low number of red blood cells, low number of white blood cells which are usually used to fight infections;
• rash, eczema, accumulation of greasy skin scales;
• dizziness, anxiety, difficulty sleeping;
• feeling tired, loss of strength and energy, headache including migraine;
• hemorrhoids;
• liver inflammation and increased liver enzymes;
• allergic reactions including hives and mouth inflammation;
• lower respiratory tract infection;
• enlargement of lymph nodes;
• impotence, abnormally heavy or prolonged menstrual flow, or absence of menstruation;
• muscle problems such as muscle weakness and spasms, joint, muscle, and back pain;
• damage to nerves of the peripheral nervous system;
• night sweats, itching, skin rash including raised bumps on the skin, skin infection, inflammation of the skin or hair pores, fluid accumulation in cells and tissues.

Uncommon: may affect up to 1 in 100 people

• abnormal dreams;
• loss or change in taste sensation;
• hair loss;
• an abnormality in your electrocardiogram (ECG) called atrioventricular block;
• accumulation of platelets in the arteries which may lead to heart attack and stroke;
• inflammation of blood vessels and capillaries;
• inflammation of the bile duct;
• uncontrollable shaking of the body;
• constipation;
• inflammation of veins related to a blood clot;
• dry mouth;
• inability to control sphincters;
• inflammation of the first section of the small intestine just after the stomach, wound or ulcer in the digestive tract, bleeding from the intestinal tract or rectum;
• red blood cells in the urine;
• yellowing of the skin or whites of the eyes (jaundice);
• fat deposits in the liver, increased liver size;
• testicular dysfunction;
• sudden flare-up of symptoms related to an inactive infection in your body (immune reconstitution);
• increased appetite;
• abnormally high level of bilirubin (a pigment produced by the breakdown of red blood cells) in the blood;
• decreased sexual desire;
• kidney inflammation;
• bone death caused by poor blood supply to the area;
• mouth sores or ulcers, inflammation of the stomach and intestine;
• kidney failure;
• breakdown of muscle fibers leading to the release of their contents (myoglobin) into the bloodstream;
• ringing, buzzing, or hissing sound in one or both ears;
• tremor;
• abnormal closure of one of the heart valves (tricuspid valve);
• vertigo (sensation of spinning);
• eye disorder, abnormal vision;
• weight gain.

Rare: may affect up to 1 in 1,000 people

• severe or potentially life-threatening skin rashes and blisters (Stevens-Johnson syndrome and erythema multiforme).

Frequency not known: cannot be estimated from available data

• kidney stones.

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effects not listed in this leaflet, inform your doctor or pharmacist.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Kaletra

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date is the last day of the month indicated.
• Store below 25°C.
• Do not use this medicine if you notice any change in colour.

How should I dispose of unused Kaletra?

Medicines should not be disposed of via wastewater drains or household waste.

Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Kaletra

The active substances are lopinavir and ritonavir.

Each tablet of Kaletra contains 200 mg of lopinavir and 50 mg of ritonavir.

The other components are:

Tablet

Copovidone, sorbitan laurate, colloidal anhydrous silica, sodium stearyl fumarate.

Coating

Hypromellose, titanium dioxide, macrogol 400 (polyethylene glycol 400), hydroxypropyl cellulose, talc, colloidal anhydrous silica, macrogol 3350 (polyethylene glycol 3350), iron oxide red E-172, polysorbate 80.

Appearance of the product and contents of the pack

Kaletra film-coated tablets are red, engraved with “AL” on one side.

Kaletra film-coated tablets are available in packs containing 120 tablets (1 plastic bottle with 120 tablets) and multipacks containing 3 plastic bottles, each containing 120 tablets (360 tablets).

Only certain pack sizes may be marketed.

Marketing Authorization Holder:

AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany

Manufacturer:

AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu

To request a copy of this leaflet in , , or as an