PAT-Darunavir: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

PAT-darunavir is an oral tablet used for the treatment of HIV (Human Immunodeficiency Virus) infection in adults and in children 6 years of age and older who have taken anti-HIV medicines in the past, when co-administered with ritonavir and other antiretroviral medications. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). PAT-darunavir is a type of anti-HIV medicine called a protease (PRO-tee-ase) inhibitor.

PAT-darunavir does not reduce the risk of passing HIV to others through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safer sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions, or blood. Never use or share dirty needles.

Ask your doctor if you have any questions on how to prevent passing HIV to other people.

What it does:

PAT-darunavir blocks HIV protease, an enzyme which is needed for HIV to multiply. When used with other anti-HIV medicines, PAT-darunavir can help to reduce the amount of HIV in your blood (called “viral load”) and increase your CD4+ (T) cell count. HIV infection destroys CD4+ (T) cells, which are important to the immune system. The immune system helps fight infection. Reducing the amount of HIV and increasing the CD4+ (T) cell count may improve your immune system.

PAT-darunavir is always taken with and at the same time as 100 mg of ritonavir (NORVIR^®), in combination with other anti-HIV medicines. PAT-darunavir should also be taken with food.

PAT-darunavir does not cure HIV infection or AIDS. At present, there is no cure for HIV infection. People taking PAT-darunavir may still develop infections or other conditions associated with HIV infection. Because of this, it is very important for you to remain under the care of a doctor.

When it should not be used:

Together with your doctor, you need to decide whether taking PAT-darunavir is right for you.

Do not take PAT-darunavir:

• if you are allergic to darunavir or any of the other ingredients in PAT-darunavir (see What the nonmedicinal ingredients are)
• if you are allergic to ritonavir (NORVIR^®)
• if you have severe liver disease

• if you take any of the following types of medicines because you could experience serious side effects:

  Type of Drug Examples of Generic

  Names (Brand Names) Alpha1-Adrenoreceptor

  Antagonists

  (to treat enlarged

  prostate)

  Antiarrhythmics

  (to treat abnormal

  heart rhythms)

  alfuzosin bepridil¹ lidocaine quinidine amiodarone (Cordarone^®) Antihistamines

  (to treat allergy

  symptoms)

  astemizole¹ terfenadine¹

  Antimycobacterials

  (to treat tuberculosis)

  rifampin (Rifadin^®, Rifater^®)

  Ergot Derivatives

  (to treat migraine and

  headaches)

  dihydroergotamine (Migranal^®)

  ergonovine ergotamine (Cafergot^®) methylergonovine Gastrointestinal

  Motility Agents

  (to treat some

  digestive conditions)

  cisapride¹

  Herbal products

  (to improve mood)

  St. John’s Wort

  HMG-CoA

  Reductase

  Inhibitors

  also known as statins

  (to lower cholesterol)

  lovastatin (Mevacor^®) simvastatin (Zocor^®)

  Neuroleptics

  (to treat psychiatric

  conditions)

  pimozide (Orap^®)

Type of Drug Examples of Generic

Names (Brand Names)

PDE-5 Inhibitor

(to treat pulmonary

arterial hypertension)

sildenafil (Revatio^®)

Sedatives/Hypnotics

(to treat trouble with

sleeping and/or

anxiety)

midazolam

triazolam (Halcion^®)

¹ Bepridil, astemizole, terfenadine and cisapride are no longer marketed in Canada.

What the medicinal ingredient is:

The active substance is darunavir.

Each 75 mg tablet contains 81.31 mg of darunavir ethanolate corresponding to 75 mg of darunavir.

Each 150 mg tablet contains 162.62 mg of darunavir ethanolate corresponding to 150 mg of darunavir.

Each 400 mg tablet contains 433.64 mg of darunavir ethanolate, corresponding to 400 mg of darunavir.

Each 600 mg tablet contains 650.46 mg of darunavir ethanolate, corresponding to 600 mg of darunavir.

Each 800 mg tablet contains 867.28 mg of darunavir ethanolate, corresponding to 800 mg of darunavir.

What the nonmedicinal ingredients are:

The other ingredients are colloidal anhydrous silica, crospovidone, magnesium stearate, and microcrystalline cellulose. The 800 mg tablet core also contains hypromellose. The tablet film coatings contain either OPADRY^® II White (polyethylene glycol, polyvinyl alcohol - partially hydrolyzed, talc, titanium dioxide) for the 75 and 150 mg tablets or OPADRY^® II Orange (polyethylene glycol, polyvinyl alcohol - partially hydrolyzed, titanium dioxide, talc, sunset yellow FCF aluminum lake) for the 400 and 600 mg tablets or OPADRY^® II Dark Red (polyethylene glycol, polyvinyl alcohol - partially hydrolyzed, titanium dioxide, talc, iron oxide red) for the 800 mg tablets.

What dosage forms it comes in:

75 mg tablets

150 mg tablets

400 mg tablets

600 mg tablets

800 mg tablets

WARNINGS AND PRECAUTIONS

BEFORE you use PAT-darunavir talk to your doctor or pharmacist if you:

• have diabetes. In general, anti-HIV medicines, such as PAT-darunavir, might increase sugar levels in the blood.
• have liver problems, including hepatitis B and/or C.

• have hemophilia. Anti-HIV medicines, such as

  PAT-darunavir, might increase the risk of bleeding.

• are pregnant or planning to become pregnant. It is not known if PAT-darunavir can harm your unborn baby. You and your doctor will need to decide if taking PAT-darunavir is right for you. If you take PAT-darunavir while you are pregnant, talk to your doctor about how you can be included in the Antiretroviral Pregnancy Registry.

• are breast-feeding. Do not breast-feed if you are taking PAT-darunavir. You should not breast-feed if you have HIV because of the chance of passing HIV to your baby. Talk with your doctor about the best way to feed your baby.
• are allergic to sulpha medications.

INTERACTIONS WITH THIS MEDICATION

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements, including St. John’s wort (Hypericum perforatum). PAT-darunavir and many other medicines can interact. Sometimes serious side effects will happen if PAT-darunavir is taken with certain other medicines (see “When it should not be used”).

PAT-darunavir should not be combined with phenobarbital, phenytoin, rifampin or St. John’s wort because the combination may significantly lower the amount of PAT-darunavir in your blood and reduce the effects of PAT-darunavir.

PAT-darunavir should not be combined with vardenafil, because you may be at increased risk of side effects of vardenafil such as low blood pressure, visual changes and penile erection lasting more than 4 hours.

Tell your doctor if you are taking estrogen-based contraceptives. PAT-darunavir might reduce the effectiveness of estrogen-based contraceptives (birth control). Therefore, alternative methods of non-hormonal contraception, such as a condom, are recommended.

Tell your doctor if you take other anti-HIV medicines (e.g. rilpivirine). PAT-darunavir can be combined with some other anti-HIV medicines while other combinations are not recommended.

Tell your doctor if you are taking any of the following medicines:

Type of Drug Examples of Generic

Names (Brand Names) Anticoagulants

(to prevent the clotting of red blood cells)

warfarin (Coumadin^®)

Anticonvulsants

(to treat epilepsy and prevent seizures)

Antigout

(to treat gout and familial Mediterranean fever)

carbamazepine

(Tegretol^®)

phenobarbital

phenytoin (Dilantin^®)

colchicine

Anti-infectives

(to treat bacterial

infections)

clarithromycin (Biaxin^®)

Antifungals

(to treat fungal infections)

ketoconazole (Nizoral^®) itraconazole (Sporanox^®) voriconazole (Vfend^®)

Antimycobacterials

(to treat bacterial

infections)

rifabutin (Mycobutin^®) rifampin (Rifadin^®, Rifater^®)

Calcium Channel

Blockers

(to treat heart disease)

felodipine

nifedipine (Adalat^®) nicardipine

Corticosteroids

(to treat inflammation or asthma)

Endothelial receptor Antagonist

(to treat pulmonary arterial hypertension)

dexamethasone

fluticasone propionate (Advair Diskus^®,

Cutivate^®, Flonase^®, Flovent Diskus^®)

bosentan (Tracleer^®)

HMG-CoA Reductase Inhibitors

(to lower cholesterol levels)

atorvastatin (Lipitor^®) lovastatin (Mevacor^®) pravastatin (Pravachol^®) simvastatin (Zocor^®) rosuvastatin (Crestor^®)

Immunosuppressants

(to prevent organ transplant rejection)

cyclosporine

(Sandimmune^®, Neoral^®) tacrolimus (Prograf^®) sirolimus (Rapamune^®)

Inhaled beta agonist

salmeterol (Advair^®)

Type of Drug Examples of Generic

Names (Brand Names) Narcotic Analgesics methadone buprenorphine/naloxone (Suboxone^TM)

NS3-4A Protease

Inhibitors:

(to treat Hepatitis C Virus

[HCV])

boceprevir (Victrelis™) telaprevir (Incivek™)

PDE-5 Inhibitors

(to treat erectile

dysfunction)

sildenafil (Viagra^®) vardenafil (Levitra^®) tadalafil (Cialis^®)

Selective Serotonin

Reuptake Inhibitors

(SSRIs)

(to treat depression,

anxiety, or panic disorder)

paroxetine (Paxil^®) sertraline (Zoloft^®)

Tell your doctor if you are taking any medicines that you obtained without a prescription.

This is not a complete list of medicines that you should tell your doctor that you are taking. Know and keep track of all the medicines you take and have a list of them with you. Show this list to all of your doctors and pharmacists any time you get a new medicine. Both your doctor and your pharmacist can tell you if you can take these other medicines with PAT-darunavir. Do not start any new medicines while you are taking PAT-darunavir without first talking with your doctor or pharmacist. You can ask your doctor or pharmacist for a list of medicines that can interact with PAT-darunavir.

PROPER USE OF THIS MEDICATION

Always use PAT-darunavir exactly as your doctor has told you. You must check with your doctor if you are not sure.

Usual dose:

Take PAT-darunavir tablets every day exactly as prescribed by your doctor. You must take ritonavir (NORVIR^®) at the same time as PAT-darunavir.

Adults:

• For adults who have never taken anti-HIV medicines the usual dose is 800 mg (two 400 mg tablets or one 800 mg tablet) of PAT-darunavir, together with 100 mg (one 100 mg capsule) of ritonavir (NORVIR^®), once daily every day.
• For adults who have taken anti-HIV medicines in the past, the dose is either 800 mg (two 400 mg tablets or one 800 mg tablet) of PAT-darunavir

together with 100 mg (one 100 mg capsule) of ritonavir (NORVIR^®), once daily every day OR 600 mg (one 600 mg tablet) of PAT-darunavir together with 100 mg (one 100 mg capsule) ritonavir (NORVIR^®), twice daily every day. Please discuss with your doctor which dose is right for you.

Children:

• For children at least 6 years of age weighing at least

  44 lbs (20 kg) who have taken anti-HIV medicines in the past, your child’s doctor will decide the right dose based on your child’s weight. Your child’s doctor will inform you exactly on how many PAT-darunavir tablets and how much ritonavir (NORVIR^®) (capsules or solution) your child should take. In case your child does not tolerate ritonavir oral solution, ask your child’s doctor for advice.

If you have questions about when to take PAT-darunavir and ritonavir (NORVIR^®), your doctor can help you decide which schedule works for you.

You should always take PAT-darunavir and ritonavir (NORVIR^®) together with food. The type of food is not important.

Continue taking PAT-darunavir and ritonavir (NORVIR^®) unless your doctor tells you to stop. Take the exact amount of PAT-darunavir and ritonavir (NORVIR^®) that your doctor tells you to take, right from the very start. To help make sure you will benefit from PAT-darunavir and ritonavir (NORVIR^®), you must not skip doses or interrupt therapy. If you don’t take PAT-darunavir and ritonavir (NORVIR^®) as prescribed, the beneficial effects of PAT-darunavir and ritonavir (NORVIR^®) may be reduced or even lost.

If you have also been prescribed enteric-coated didanosine as well as PAT-darunavir and ritonavir, take didanosine 2 hours before or after the PAT-darunavir/ritonavir combination.

Overdose:

In case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Missed dose:

Patients taking 800 mg of PAT-darunavir once daily: If you miss a dose of PAT-darunavir (two 400 mg tablets or one 800 mg tablet) or ritonavir (NORVIR^®) by more than 12 hours, wait and then take the next dose of PAT-darunavir (two 400 mg tablets or one 800 mg tablet) and ritonavir

(NORVIR^®) at the regularly scheduled time. If you miss a dose of PAT-darunavir (two 400 mg tablets or one 800 mg tablet) or ritonavir (NORVIR^®) by less than 12 hours, take your missed dose of PAT-darunavir (two 400 mg tablets or one 800 mg tablet) and ritonavir (NORVIR^®) immediately. Then take your next dose of PAT-darunavir (two 400 mg tablets or one 800 mg tablet) and ritonavir (NORVIR^®) at the regularly scheduled time.

Patients taking 600 mg of PAT-darunavir twice daily:

If you miss a dose of PAT-darunavir or ritonavir (NORVIR^®) by more than 6 hours, wait and then take the next dose of PAT-darunavir and ritonavir (NORVIR^®) at the regularly scheduled time. If you miss a dose of PAT-darunavir or ritonavir (NORVIR^®) by less than 6 hours, take your missed dose of PAT-darunavir and ritonavir (NORVIR^®) immediately. Then take your next dose of PAT-darunavir and ritonavir (NORVIR^®) at the regularly scheduled time.

If a dose of PAT-darunavir or ritonavir (NORVIR^®) is skipped, do not double the next dose. Do not take more or less than your prescribed dose of PAT-darunavir or ritonavir (NORVIR^®) at any one time.

Do not stop using PAT-darunavir without talking to your doctor first.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Like all prescription drugs, PAT-darunavir can cause side effects. The following is not a complete list of side effects reported with PAT-darunavir when taken either alone or with other anti-HIV medicines. Do not rely on this leaflet alone for information about side effects. Your doctor can discuss with you a more complete list of side effects.

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests prior to initiating PAT-darunavir. If you have chronic hepatitis B or C infection, your doctor should check your blood tests more often because you have an increased chance of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on your right side below your ribs.

Rash has been reported in 10.3% of patients receiving PAT-darunavir. In patients taking PAT-darunavir and raltegravir, rashes (generally mild or moderate) may

occur more frequently than in patients taking either drug separately. Contact your doctor immediately if you develop a rash. Your doctor will advise you whether your symptoms can be managed on therapy or whether PAT-darunavir should be stopped.

In some patients, PAT-darunavir has been reported to cause a severe or life-threatening rash. If you develop a severe rash (e.g. blisters, peeling skin) which may be accompanied with symptoms such as fever, fatigue, muscle aches and pain, and liver problems, immediately discontinue PAT-darunavir and contact your doctor.

Other relevant severe side effects reported at an uncommon or rare frequency were inflammation of the liver or pancreas, increased blood fat levels, diabetes, and changes in body fat.

The most common side effects include diarrhea, nausea, headache, abdominal pain and vomiting.

Some side effects are typical for anti-HIV medicines in the same family as PAT-darunavir. These are:

• high blood sugar (hyperglycemia) and diabetes.

  This can happen in patients taking PAT-darunavir or other protease inhibitor medicines. Some patients have diabetes before starting treatment with PAT-darunavir, which gets worse. Some patients get diabetes during treatment with PAT-darunavir. Some patients will need changes in their diabetes medicine. Some patients may need new diabetes medicine.

• increased bleeding in patients with hemophilia.

  This may happen in patients taking PAT-darunavir as it has been reported with other protease inhibitor medicines.

• changes in body fat. These changes can happen in

  patients taking anti-HIV medicines. The changes may include an increased amount of fat in the upper back and neck, breast, and around the back, chest, and stomach area. 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.

• increases in triglycerides and cholesterol (forms of

  fat that are found in your blood). Your doctor may order blood testing for you.

• development of pancreatitis (inflammation of the

  pancreas) with symptoms such as abdominal pain, nausea and vomiting. If you suffer these symptoms while taking PAT-darunavir, contact your doctor.

• immune reconstitution syndrome. In some patients

  with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is

  believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms.

  Tell your doctor promptly about these or any other unusual symptoms. If the condition persists or worsens, seek medical attention.

HOW TO STORE IT

Keep out of the reach and sight of children.

Store PAT-darunavir tablets at room temperature between 15-30°C. Ask your doctor or pharmacist if you have any questions about storing your tablets.

This medication is prescribed for your particular condition. Do not use it for any other condition or give it to anybody else. Keep PAT-darunavir and all of your medicines out of the reach of children. If you suspect that more than the prescribed dose of this medicine has been taken, contact your local poison control centre or emergency room immediately.

This leaflet provides a summary of information about PAT-darunavir. If you have any questions or concerns about either PAT-darunavir or HIV, talk to your doctor.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

• Report online at

  www.healthcanada.gc.ca/medeffect

• Call toll-free at 1-866-234-2345

• Complete a Canada Vigilance Reporting Form

  and:

  • Fax toll-free to 1-866-678-6789, or

  • Mail to: Canada Vigilance Program Health Canada

    Postal Locator 0701E Ottawa, ON K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found at: http://www.patriot-canada.ca or by contacting the sponsor, Janssen Inc., at: 1-800-567-3331 or 1-800-387-8781

Patriot, a Division of Janssen Inc.

Toronto, Ontario M3C 1L9

Last revised: November 30, 2012

All listed brand names are registered trademarks of their respective manufacturers.