Label: information for the user

Kaletra (80 mg + 20 mg)/ml oral solution

(lopinavir + ritonavir)

Read this label carefully before starting to take this medication, as it contains important information for you or your child.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you or your child and should not be given to others who may have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

1.What is Kaletra and how it is used

2.What you need to know before taking Kaletra or giving it to your child

3.How to take Kaletra

4.Possible adverse effects

5.Storage of Kaletra

6.Contents of the package and additional information

• Your doctor has prescribed Kaletra to help control your human immunodeficiency virus (HIV) infection. This is possible because Kaletra acts by preventing the infection from spreading rapidly.
• Kaletra is not a cure for HIV or AIDS infection.
• Kaletra is used in children aged 14 days and older, adolescents, and adults infected with HIV, the virus that causes AIDS.
• Kaletra contains the active ingredients lopinavir and ritonavir. Kaletra is an antiretroviral medication that belongs to the group of drugs known as protease inhibitors.
• Kaletra is prescribed for use in combination with other antiviral medications. Your doctor will inform you and decide which medications are best for your case.

Do not take Kaletra:

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

Do not take Kaletra with any of the following medications::

• astemizol or terfenadine (usually used to treat allergy symptoms – these medications may not require a prescription);
• midazolam oral (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]);
• cisapride (used to relieve certain stomach problems);
• ergotamine, dihydroergotamine, ergonovine, and methylergonovine (used to treat headaches);
• amiodarone, dronedarone (used to treat irregular heart rhythms);
• lovastatin, simvastatin (used to lower cholesterol in the blood);
• lomitapide (used to lower cholesterol in the blood);
• alfuzosin (used in men to treat symptoms of an enlarged prostate (benign prostatic hyperplasia (BPH));
• acid fusidic (used to treat skin infections caused by the Staphylococcus bacteria such as impetigo and infected dermatitis). Acid fusidic is also used to treat long-term bone and joint infections under medical supervision (see Kaletra use with other medications);
• colchicine (used to treat gout). If you have liver or kidney problems (see sectionOther medications and Kaletra);
• elbasvir/grazoprevir (used to treat chronic hepatitis C [HCV]);
• ombitasvir/paritaprevir/ritonavir with or without dasabuvir (used to treat chronic hepatitis C [HCV]);
• neratinib (used to treat breast cancer);
• avanafil or vardenafil (used to treat impotence);
• sildenafil used to treat pulmonary hypertension (high blood pressure in the pulmonary artery). Sildenafil may be used to treat erectile dysfunction under medical supervision (see sectionOther medications and Kaletra);
• products containing St. John's Wort (Hypericum perforatum).

For more information on other medications that require special precautions, see the list of medications included below in“Other medications and Kaletra”.

If you are currently taking any of these medications, consult your doctor to see if you need to change your treatment for other conditions or your antiretroviral treatment.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Kaletra.

Important information

• People taking Kaletra may still develop infections or other diseases associated with HIV and AIDS. Therefore, it is essential to remain under your doctor's supervision while taking Kaletra.
• Despite effective antiretroviral treatment reducing the risk of transmission, you may still transmit HIV to others while taking this medication. Consult your doctor about the necessary precautions to avoid infecting others.

Inform your doctor if you or your child have or have had

• Hemophiliatype A and B, as Kaletra may increase the risk of bleeding.
• Diabetesas there have been reports of increased blood sugar levels in patients taking Kaletra.
• History ofliver problems, as patients with a history of liver disease, including chronic hepatitis B or C, have a higher risk of severe and potentially life-threatening liver adverse effects.

Inform your doctor if you or your child experience

• Nausea, vomiting, abdominal pain, difficulty breathing, and severe muscle weakness in the legs and arms, as these may be symptoms of increased lactic acid levels.
• Thirst, frequent urination, blurred vision, or weight loss, as this 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 described symptoms may suggest this condition.
• In some patients with advanced HIV infection and a history of opportunistic infections, symptoms and signs of previous infections may appear shortly after starting antiretroviral treatment. It is believed that these symptoms are due to an improvement in the body's immune response, allowing it to fight off infections that were present without apparent symptoms.
• Additionally to opportunistic infections, you may also experience autoimmune disorders (a problem that occurs when the immune system attacks healthy body tissue) after starting treatment for your HIV infection. Autoimmune disorders may appear several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and rising to the trunk, palpitations, tremors, or hyperactivity, please inform your doctor immediately to seek necessary treatment.
• Stiffness in the joints, pain, and discomfort(especially in the hip, knee, and shoulder) and difficulty moving, as some patients taking these medications may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). Several risk factors for developing this disease include the duration of combined antiretroviral treatment, the use of corticosteroids, alcohol consumption, severe immunodepression (decreased activity of the immune system), and high body mass index.
• Muscle pain, discomfort, or weakness, particularly in combination with these medications. In rare cases, these muscle alterations have been severe.
• Symptoms of dizziness, dizziness, fainting, or abnormal heartbeats. Kaletra may cause changes in heart rhythm and cardiac electrical activity. These changes may be seen on an ECG (electrocardiogram).

Other medications and Kaletra

Inform your doctor or pharmacist if you or your child are taking, have taken recently, or may need to take any other medication.

• antibiotics (e.g. rifampicin, rifabutin, clarithromycin);
• anticancer medications (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. warfarin, rivaroxaban, vorapaxar);
• antidepressants (e.g. trazodone, bupropion);
• antiepileptic medications (e.g. carbamazepine, phenytoin, phenobarbital, lamotrigine, and valproate);
• antifungal medications (e.g. ketoconazole, itraconazole, voriconazole);
• gout medications (e.g. colchicine). You should not take Kaletra with colchicine if you have liver or kidney problems (see also “Do not take Kaletra” above);
• tuberculosis medications (e.g. bedaquiline, delamanid);
• antiviral medications used in the treatment of chronic hepatitis C (HCV) in adults (e.g. glecaprevir/pibrentasvir, simeprevir, and sofosbuvir/velpatasvir/voxilaprevir);
• erectile dysfunction medications (e.g. sildenafil and tadalafil);
• acid fusidic used in the treatment of long-term bone and joint infections (e.g. osteomyelitis);
• heart medications including:
• digoxin;
• calcium channel blockers (e.g. felodipine, nifedipine, nicardipine);
• medications used to correct heart rhythm (e.g.bepridil, lidocaine systemic, quinidine);
• CCR5 HIV antagonist (e.g. maraviroc)
• integrase inhibitor HIV-1 (e.g. raltegravir)
• levothyroxine (used to treat thyroid problems);
• medications used to lower cholesterol in the blood (e.g. atorvastatin, lovastatin, rosuvastatin, or simvastatin);
• medications used to treat asthma and other lung problems, such as chronic obstructive pulmonary disease (COPD) (e.g. salmeterol);
• medications used to treat pulmonary arterial hypertension (high blood pressure in the pulmonary artery) (e.g. bosentan, riociguat, sildenafil, tadalafil);
• medications that affect the immune system (e.g. cyclosporine, sirolimus (rapamycin), tacrolimus);
• smoking cessation medications (e.g. bupropion);
• analgesics (e.g. fentanyl);
• opioid-like medications (e.g. methadone);
• oral contraceptives or use of contraceptive patches to prevent pregnancy (see section “Contraceptives” below);
• protease inhibitors (e.g. fosamprenavir, indinavir, ritonavir, saquinavir, tipranavir);
• sedatives (e.g. midazolam injectable);
• steroids (e.g. budesonide, dexamethasone, fluticasone propionate, ethinylestradiol, triamcinolone);
• medications that interact with alcohol (e.g. disulfiram).

For more information on other medications that should not be taken while taking Kaletra, see the list of medications included above in “Do not take Kaletra with any of the following medications”.

Inform your doctor or pharmacist if you or your child are taking, have taken recently, or may need to take other medications, including those obtained without a prescription.

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

• Do not take Kaletraif you are currently taking avanafil or vardenafil.
• You should not take Kaletra with sildenafil when used to treat pulmonary arterial hypertension (high blood pressure in the pulmonary artery) (see also the section aboveDo not take Kaletra).
• If you are taking sildenafil or tadalafil and Kaletra together, you may have an increased risk of adverse reactions such as decreased blood pressure, fainting, changes in vision, and prolonged erection of the penis. If the erection of the penis lasts more than 4 hours, you should seek medical attention immediately to avoid permanent damage to the penis. Your doctor may explain these symptoms.

Contraceptives

• If you are taking oral contraceptives or a contraceptive patch 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 patches.
• Kaletra does not reduce the risk of HIV transmission to others. You should use appropriate precautions (e.g. using a condom) to prevent the transmission of the disease through sexual contact.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctorimmediatelybefore using this medication.
• If you are pregnant or breastfeeding, consult your doctor or pharmacist before taking this medication because it contains propylene glycol and alcohol. Pregnant women or breastfeeding mothers should not take Kaletra oral solution unless specifically recommended by their doctor.
• It is recommended that HIV-infected women not breastfeed their children as there is a possibility that the child may become infected with HIV through breast milk.

Driving and operating machinery

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

Kaletra contains 42% v/v of ethanol. The amount of alcohol in this medication may affect your ability to drive or operate machinery and may affect your judgment and reaction times.

Important information about some of the components of Kaletra

Kaletra contains 42% v/v of alcohol and 15% of propylene glycol p/v. Each milliliter of Kaletra oral solution contains 356.3 mg of alcohol and 152.7 mg of propylene glycol. Alcohol and propylene glycol are potentially harmful to those with liver disease, kidney disease, alcoholism, epilepsy, brain disease or damage, as well as to pregnant women and children. They may modify or increase the effects of other medications.

In the recommended adult doses of this medication, the estimated blood alcohol concentration in your body is approximately 0.002-0.01 g/dL. This is similar to an adult who has consumed4-22ml of beer or1-4ml of wine.

Other medications may also contain alcohol, and alcohol may be consumed in food and beverages. The combined effects may lead to increased blood alcohol levels and increased alcohol-related side effects.

This medication contains up to 0.8 g of fructose per dose when administered according to the recommended doses. This may not be suitable for individuals with hereditary fructose intolerance. Since there may be a possibility of undetected fructose intolerance, the medication should be administered to infants and children only after consulting with a doctor.

Kaletra contains glycerol, which is toxic in high doses. It may cause headaches and gastrointestinal discomfort and diarrhea.

Kaletra contains ricin oil polyoxyl 40 hydrogenated, which at high doses may cause nausea, vomiting, colic, and severe diarrhea. It should not be administered when there is intestinal obstruction.

Kaletra contains potassium as acesulfame potassium, which may be toxic in individuals with a low-potassium diet. High levels of potassium in the blood may cause stomach discomfort and diarrhea.

Kaletra contains sodium as saccharin sodium, sodium chloride, and sodium citrate, which may be toxic in individuals with a low-sodium diet.

Kaletra is recommended for use in adults and children 14 days of age and older who are infected with HIV.

Be careful when administering to children. The dose should be less than 5 ml twice a day in children who weigh less than 40 kg.

If you or your child is able to swallow tablets, Kaletra is also distributed as 200mg of lopinavir and 50mg of ritonavir in coated tablets and as 100mg of lopinavir and 25mg of ritonavir in coated tablets.

Take this medicine exactly as your doctor has told you. Consult your doctor or pharmacist if you have any doubts about how to take your medicine.

How and when to take Kaletra

For children 14 days and older and weighing up to 15 kg

• Your doctor will decide on the appropriate dose based on the child's height and weight.
• It is essential that all Kaletra oral solution doses are taken with food.
• Use the 2 ml oral dosing syringe provided to measure the dose.

For children weighing more than 15 kg

• Your doctor will decide on the correct dose based on the child's height and weight.
• It is essential that all Kaletra oral solution doses are taken with food.
• Use the 5 ml oral dosing syringe provided to measure the dose.

Use in adults

• The usual dose in adults is 5 ml of oral solution twice a day, e.g., every 12 hours, in combination with other HIV medications. Your doctor will recommend the amount of Kaletra you should take.
• It is essential that all Kaletra oral solution doses are taken with food.
• Use the 5 ml oral dosing syringe provided to measure the dose.

How to measure the correct dose?

• If the dose is up to 2 ml – use the 2 ml oral dosing syringe to prepare a dose.

• If the dose is between 2ml and 5ml – use the 5 ml oral dosing syringe to prepare a dose.

Check with your pharmacist that you have the correct size syringe. If you are unsure how to use the oral dosing syringe, consult your doctor, pharmacist, or nurse. They will tell you how to use it correctly.

Do not shake the bottle – this is because air bubbles may form that will affect how well you can measure the dose.

Open the child-resistant cap by pressing it with the palm of your hand and turning it in the opposite direction of the clock or in the direction of the arrow on the top of the cap. If you have trouble opening the bottle, consult your pharmacist.

Using the 2 ml oral dosing syringe

Using the 5 ml oral dosing syringe for doses over 2 ml

Replace the bottle cap after each dose.

After administering each dose of Kaletra, separate the plunger from the syringe body. Wash the plunger and syringe with soap and warm water as soon as possible; you can soak them in soapy water for up to 15 minutes. Rinse the syringe and plunger with clean water.

Put the plunger back into the syringe and prime and flush several times with tap water to clear it. Let the syringe dry completely before using it again.

Do not use the dosing syringes provided with Kaletra oral solution to administer any other medication that you or your child are taking.

If you or your child take more Kaletra than they should

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

If you or your child forget to take Kaletra

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

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

If you or your child stop taking Kaletra

• Do not stop taking or change your daily dose of Kaletra without consulting your doctor first.
• Kaletra must be taken twice a day to help control HIV, regardless of how you feel.
• Taking Kaletra as directed is the best way to delay the development of drug resistance.
• If an adverse reaction prevents you from taking Kaletra as directed, tell your doctor quickly.
• Always have a sufficient amount of Kaletra so you do not run out of medication. When traveling or in the hospital, ensure you have enough until you can get more.

Continuetaking this medicine until your doctor tells you to.

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

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

The following side effects have been reported by patients taking this medicine.You should inform your doctor quickly about these or any other symptoms. See your doctor 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:

• pancreatitis inflammation;
• vomiting, abdominal enlargement, upper and lower abdominal pain, temporary gas, indigestion, decreased appetite, reflux from the stomach to the esophagus that may cause pain;

- Inform your doctorif you experience nausea, vomiting, or abdominal pain, as they may be symptoms of pancreatitis (pancreatitis inflammation).

• swelling or inflammation of the stomach, intestines, and colon;
• increase in blood cholesterol levels, increase in triglyceride levels (a type of fat) in the blood, high blood pressure;
• decreased ability of the body to metabolize sugar, such as diabetes mellitus, weight loss;
• low red blood cell count, low white blood cell count that are usually used to fight infections;
• eruption, eczema, accumulation of greasy skin scales;
• dizziness, anxiety, difficulty sleeping;
• feeling of fatigue, loss of strength and energy, headache including migraine;
• hemorrhoids;
• liver inflammation and increased liver enzymes;
• allergic reactions including urticaria and inflammation in the mouth;
• lower respiratory tract infection;
• enlarged lymph nodes;
• impotence, abnormally heavy or prolonged menstrual flow or lack of menstruation;
• muscle problems such as muscle weakness and spasms, joint, muscle, and back pain;
• damage to the peripheral nervous system nerves;
• night sweats, itching, hives including raised skin bumps, skin infection, skin inflammation or capillary pore inflammation, fluid accumulation in cells and tissues.

Uncommon:may affect up to 1 in 100 people:

• abnormal dreams;
• loss or change of sense of taste;
• hair loss;
• an electrocardiogram (ECG) alteration called atrioventricular block;
• accumulation of platelets in arteries that may lead to heart attack and stroke;
• inflammation of blood vessels and capillaries;
• inflammation of the bile duct;
• uncontrollable body shaking;
• constipation;
• venous inflammation related to blood clotting;
• dry mouth;
• inability to control the sphincters;
• inflammation of the first section of the small intestine just after the stomach, wound or ulcer in the digestive tract, intestinal or rectal bleeding;
• red blood cells in the urine;
• yellowing of the skin or white of the eyes (jaundice);
• fat deposits in the liver, liver enlargement;
• testicular dysfunction;
• sudden reappearance of symptoms related to an inactive infection in your body (immune reconstitution);
• increased appetite;
• abnormal increase in bilirubin levels (a pigment produced by red blood cell breakdown) in the blood;
• decreased sexual desire;
• kidney inflammation;
• bone death caused by poor blood supply to the area;
• mouth or esophageal ulcers, stomach and intestinal inflammation;
• renal failure;
• muscle fiber rupture causing the release of its contents (myoglobin) into the bloodstream;
• sound in one ear or both ears, such as buzzing, ringing, or hissing;
• trembling;
• abnormal closure of one of the valves (tricuspid valve of the heart);
• dizziness (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 eruptions and blisters (Stevens-Johnson syndrome and erythema multiforme)

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.

• Do not use this medication after the expiration date that appears on the box after CAD. The expiration date is the last day of the month indicated.

How should I store Kaletra and for how long?

• Store in the refrigerator (between 2°C and 8°C).
• Storage during use: if kept out of the refrigerator, do not store at a temperature above 25°C and discard unused product after 42 days (6 weeks). It is recommended to note on the packaging the date when it was removed from the refrigerator.
• Store in the original packaging and place the bottle cap after each dose. Do not transfer to any other container.

How should I dispose of unused Kaletra?

Unused medications should not be flushed down the drain or thrown away. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Kaletra

The active principles are lopinavir and ritonavir.

Each ml of Kaletra oral solution contains 80 mg of lopinavir and 20 mg of ritonavir.

The other components are:

Etanol, corn syrup with high fructose, propylene glycol, purified water, glycerol, povidone, flavor Magnasweet-110 (ammonium glycirrate and glycerol mixture), vanilla flavor (contains p-hydroxybenzoic acid, p-hydrobenzaldehyde, vanillic acid, vanillin, heliotropine, ethyl vanillin), hydrogenated ricin oil polioxyil 40, cotton candy flavor (contains ethyl maltol, ethyl vanillin, acetoin, dihydrocoumarin, propylene glycol), potassium acesulfame, sodium saccharin, sodium chloride, peppermint oil, sodium citrate, citric acid, levomenthol.

Appearance of the product and contents of the package

Kaletra oral solution is presented in an amber bottle of 60 ml. Each ml of Kaletra contains 80 mg of lopinavir and 20 mg of ritonavir.

Two package sizes of Kaletra oral solution are available:

• 120ml (2bottles x 60ml) with 2 syringes of 2ml with graduations of 0.1ml.

For volumes up to 2 ml. For larger volumes, an alternative package is available.

• 300ml (5 bottles x60 ml) with 5 syringes of5ml with graduations of 0.1ml.

For volumes greater than 2 ml. For smaller volumes, an alternative package is available.

Marketing authorization holder:

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

Manufacturer:

Aesica QueenboroughLtd,Queenborough, Kent ME11 5EL, UK

AbbVie Logistics B.V., Zuiderzeelaan 53, 8017 JV Zwolle, Netherlands

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

For more information about this medicine, please contact the local representative of the marketing authorization holder.

Last update of this leaflet:

The detailed information about this medicine is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu