Aptivus: Uses, Side Effects and Dosage

What is APTIVUS used for?

• APTIVUS is used to treat Human Immunodeficiency Virus (HIV) infection in adults. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).
• APTIVUS must be taken along with Norvir® (ritonavir).
• It is used in patients who have received treatment for their HIV infection in the past and whose HIV is resistant to more than one type of medicine that falls under the drug class protease inhibitor.

Since APTIVUS must be taken together with Norvir® (ritonavir), please also read the Patient Medication Information for Norvir® (ritonavir).

How does APTIVUS work?

HIV infection destroys CD4 (T) cells, which are important to the immune system. After a large number of T cells are destroyed, AIDS develops.

Serious Warnings and Precautions

• Patients taking APTIVUS together with Norvir^® (ritonavir) may develop bleeding in the brain that can cause death. Tell your doctor if you have any unusual or unexplained bleeding while you are receiving APTIVUS.
• Patients taking APTIVUS together with Norvir^® (ritonavir) may develop severe liver problems that can cause death. If you have chronic hepatitis B or C infection you have an increased chance of getting liver problems. Get immediate medical help if you get any of the following symptoms of liver problems: abdominal pain, dark urine or pale stool, loss of appetite, nausea, tiredness, vomiting, weakness or yellowing of your skin or eyes.

APTIVUS belongs to a class of medicines called protease inhibitors. It blocks HIV protease. This is an enzyme that is needed for HIV to multiply. APTIVUS reduces the amount of HIV in your blood. It also increases the number of T cells. Reducing the amount of HIV in the blood reduces the risk of death or infections that happen when your immune system is weak.

What are the ingredients in APTIVUS?

Medicinal ingredients: tipranavir

Non-medicinal ingredients: Cremophor^® EL (Polyoxyl 35 Castor Oil), ethanol, mono/diglycerides of caprylic/capric acid, propyl gallate, propylene glycol, purified water and trometamol.

Capsule shell: gelatin, iron oxide red, propylene glycol, purified water, ‘sorbitol special glycerin blend’ (d-sorbitol, 1,4-sorbitan, mannitol and glycerin) and titanium dioxide.

Black printing ink: ammonium hydroxide, ethylacetate, iron oxide black, isopropyl alcohol, Macrogol, polyvinyl acetate phthalate, propylene glycol, purified water and SDA 35 alcohol.

APTIVUS comes in the following dosage forms:

As capsules containing 250 mg tipranavir.

Do not use APTIVUS if:

• you are allergic to tipranavir or to any of the other ingredients in APTIVUS;
• you are allergic to a component of the APTIVUS container;
• you have moderate to severe liver problems;

• you are currently taking any of the following medications:

  • alfuzosin, used to treat benign prostatic hyperplasia;
  • amiodarone, used to treat abnormal heart rhythms;
  • colchicine, used to treat gout;
  • ergonovine, used to stop or treat bleeding that happens after a birth or an abortion;
  • dihydroergotamine and ergotamine, used to treat migraine headaches;
  • flecainide, used to prevent certain types of life-threatening irregular heartbeats;
  • lovastatin and simvastatin, used to lower cholesterol;
  • oral midazolam, used to treat anxiety;
  • pimozide, used to treat schizophrenia;
  • propafenone, used to control irregular heartbeats;
  • quetiapine, used to treat schizophrenia, bipolar and depressive disorder;
  • rifampin, used to treat tuberculosis;
  • sildenafil when used for pulmonary arterial hypertension (PAH);
  • St. John’s wort (Hypericum perforatum), used as a herbal product;
  • oral triazolam, used to treat insomnia;

  • fluticasone propionate (e.g. Flonase®, Flovent®, Advair®), used to treat allergies and

    • asthma;
  • trazodone (e.g. Desyrel®), used to treat depression;
  • omeprazole or esomeprazole, used to treat indigestion, heartburn and acid reflux.

Do not take APTIVUS if you have a rare hereditary condition of fructose intolerance as this product contains sorbitol.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take APTIVUS. Talk about any health conditions or problems you may have, including if you:

• are allergic to sulfa drugs;
• have liver problems, including infection with hepatitis B or C;
• have had hepatitis in the past or your liver enzyme tests have been abnormal;
• have hemophilia, have had or will have surgery, or other medical conditions that increase your chance of bleeding, or are taking medicines which increase your chance of bleeding (e.g. anticoagulants, antiplatelet medication, or vitamin E supplements): you may have an increased chance of bleeding while taking APTIVUS.

Other warnings you should know about:

Pregnancy:

Tell your doctor if you are pregnant or planning to become pregnant. It is not known if APTIVUS can harm your unborn baby. If you are pregnant, APTIVUS should only be taken after careful discussion with your doctor. Tell your doctor immediately if you become pregnant while you are taking APTIVUS.

Pregnancy Registry:

There is a pregnancy registry for women who take antiretroviral medicines like APTIVUS while they are pregnant. The purpose of this registry is to collect information about your health and the health of your baby. If you do become pregnant while taking APTIVUS, talk to your doctor about taking part in this registry.

Breastfeeding:

You should not breastfeed if you are taking APTIVUS. You should also not breastfeed a baby if you are infected with HIV. This is because you can pass HIV to your baby. If you breastfeed a baby they can get HIV from you.

Estrogens and Oral Contraception:

Talk to your doctor if you are taking estrogens for birth control or hormone replacement therapy. You are more likely to get a rash while taking APTIVUS. Tell your doctor if you get a rash since they might need to modify your treatment. APTIVUS makes birth control pills work less well. Talk to your doctor about other methods of birth control like condoms. Your doctor will monitor you for estrogen deficiency if you are taking estrogen for hormone replacement therapy.

Driving and using machines:

APTIVUS may make you tired, dizzy or sleepy. This may affect your ability to drive and use machines. Before driving or using machines, wait until you are feeling well again.

APTIVUS does not cure HIV infection or AIDS. People taking APTIVUS may still get infections or other conditions common in people with HIV. These include pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infection. These may require further evaluation and treatment. Therefore, it is very important that you stay under the care of your doctor while taking APTIVUS.

APTIVUS does not reduce the risk of passing HIV to others through sexual contact, sharing needles or being exposed to your blood. Always practice safe sex. Use condoms or other barrier methods to lower the chance of sexual contact with body fluids such as semen, vaginal secretions and blood. Never re-use or share needles. Ask your doctor if you have any questions about safe sex or how to prevent passing HIV to other people.

APTIVUS capsules contain ethanol. Talk to your doctor if you are pregnant or have liver disease or epilepsy. They will tell you if it is safe for you to take APTIVUS.

The use of APTIVUS/ritonavir with tadalafil, for the treatment of pulmonary arterial hypertension (PAH) is not recommended.

Levels are decreased for HIV protease inhibitors such as saquinavir, amprenavir, atazanavir and lopinavir. Fosamprenavir is expected to act the same way. The use of these inhibitors in combination with APTIVUS is not recommended. Your doctor needs to carefully consider whether to treat you with combinations of APTIVUS and these protease inhibitors.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines. The following medicines may require your healthcare provider either to monitor your therapy or to change the dose of either APTIVUS or the other medicine.

The following may interact with APTIVUS:

• bupropion (antidepressant), used to treat depression;
• bosentan, used to treat high blood pressure;
• etravirine, didanosine, rilpivirine and rifabutin, used to treat HIV;
• salmeterol, used to treat asthma and COPD;
• colchicine, used to treat gout;
• fluconazole, ketoconazole and itraconazole, used to treat fungal infections;
• clarithromycin, used to treat infections;
• selective serotonin reuptake inhibitors (SSRIs) and desipramine, used to treat depression;
• methadone, used to treat opioid dependence;
• meperidine, used to treat pain;
• theophylline, used to treat asthma;
• atorvastatin and rosuvastatin, used to lower cholesterol;
• antacids, used to relieve indigestion and heartburn;
• warfarin and other blood thinners, used to reduce blood clots;
• metronidazole, used to treat bacterial infections;
• tadalafil, used for the treatment of pulmonary arterial hypertension;
• carbamazepine, used to treat seizures, pain and bipolar disorder;
• phenobarbital or phenytoin, used to treat anxiety, insomnia and seizures;
• immunosuppressants (cyclosporine, tacrolimus, sirolimus), used to treat organ transplant rejection, rheumatoid arthritis and autoimmune disorders;
• vardenafil, used to treat erectile problems;
• saquinavir, amprenavir, atazanavir and lopinavir, used to treat HIV.

How to take APTIVUS:

• Take APTIVUS exactly as your doctor has told you to.
• You must always take APTIVUS together with Norvir® (ritonavir) at the same time.
• Read the Norvir® Patient Medication Information before taking APTIVUS with Norvir®.

• APTIVUS must be taken with food.

• Swallow capsules whole with water. Do not open or chew the capsules.
• Take APTIVUS along with any other anti-HIV-1 medicines that your doctor has told you to take.
• Stay under the care of your doctor during treatment with APTIVUS.
• Do not change your dose or stop taking APTIVUS without talking to your doctor.
• Make sure you never run out of APTIVUS. Get more from your doctor or pharmacy when your supply runs low. This is to ensure that you never run out of APTIVUS. If you do, the amount of HIV-1 virus in your blood may increase. The virus may then become resistant to APTIVUS and be harder to treat.
• Antacids and didanosine should be given as a separate dose after two hours.

Usual dose:

The usual dose is 500 mg (two 250 mg capsules) of APTIVUS, together with 200 mg (two 100 mg capsules) of ritonavir (Norvir^®), twice per day.

Overdose:

Missed Dose:

• It is important that you do not miss or skip doses of APTIVUS.
• If you miss a dose, take it as soon as you remember.
• Do not take a double dose to make up for a missed dose.
• If you are not sure what to do, call your doctor or pharmacist.

What are possible side effects from using APTIVUS?

These are not all the possible side effects you may have when taking APTIVUS. If you experience any side effects not listed here, tell your healthcare professional.

Side effects may include:

• Diarrhea, nausea, abdominal pain and vomiting.
• Tiredness.
• Sleepiness, dizziness.
• Headache.

Some patients taking APTIVUS have large increases in triglycerides and cholesterol (fat in the blood). The long-term chance of getting complications such as heart attacks or stroke due to these increases is not known. Taking APTIVUS can also cause other changes in your blood levels. Your doctor will perform blood tests while you are taking APTIVUS and will interpret the results.

Some people who take protease inhibitors like APTIVUS can get high blood sugar, develop diabetes or your diabetes can get worse. Some patients had diabetes before starting protease inhibitors, others did not. Some patients need changes in their diabetes medicine while others need new diabetes medicine.

Changes in body fat can happen in people who take HIV-1 medicines. The changes may include an increased amount of fat in the upper back and neck called a "buffalo hump", breast and in your abdomen. Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.

Changes in your immune system can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time, or it can also attack healthy body tissue.

These symptoms may develop at any time, sometimes months later after the start of HIV therapy.

Sometimes symptoms can be severe, so if you develop high temperature (fever), joint or muscle pain, redness, rash, swelling, or fatigue or any new symptoms contact your doctor right away.

Serious side effects and what to do about them

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Reporting Side Effects

Storage:

APTIVUS capsules should be stored at 2-8^oC (refrigerated). Once the bottle is opened, refrigeration of the capsules by the patient is not required if used within 60 days and stored at controlled room temperature 15-30^oC. You can write the date of opening the bottle on the label. Do not use after the expiration date stated on the bottle.

Keep out of reach and sight of children.

If you want more information about APTIVUS:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website: (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html; the manufacturer’s website (https://www.boehringer-ingelheim.ca), or by calling the manufacturer, Boehringer Ingelheim (Canada) Ltd. at 1-800-263-5103, extension 84633.

Last Revised: June 9, 2022