Darunavir and cobicistat

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medications that block activity of the enzyme CYP3A4 such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delaviridine (Rescriptor), and nefazadone
• medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), St John's wort, and nimodipine (Nimotop)
• Ergot derivatives such as dihydroergotamine, ergotamine, methylergonovine
• St. Johns Wort
• Alfuzosin (Uroxatrol)
• Ranolazine (Ranexa)
• Dronedarone (Multaq)
• Colchicine (Colcrys)
• Rifampin
• Lurasidone (Latuda) or Pimozide (Orap)

This is not a complete list of drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with darunavir/cobicistat including the following:

• Liver damage. Some people taking darunavir/cobicistat may develop liver problems which may be life-threatening. Your healthcare provider should do blood tests before and during your treatment. If you have chronic hepatitis B or C infection, your healthcare provider should check your blood tests more often because you have an increased chance of developing liver problems. Tell your doctor immediately if you notice signs and symptoms of liver problems such as:
  • Jaundice of the skin or eyes
  • Dark (tea colored) urine
  • Pale colored stools
  • Nausea
  • Vomiting
  • Loss of appetite
  • Pain
  • Aching
  • Sensitivity in the right upper quadrant of the stomach
• Severe skin reactions/rashes. Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. Call your doctor right away if you develop a rash. Stop taking darunavir/cobicistat and call your doctor right away if you develop any skin changes with symptoms below:
  • Fever
  • Tiredness
  • Muscle or joint pain
  • Blisters or skin lesions
  • Mouth sores or ulcers
  • Red or inflamed eye, like "pink eye"
• Kidney damage. Tell your healthcare provider right away if you have some or all of the following symptoms of kidney damage:
  • Black or bloody stools (feces)
  • Feeling confused or changes in mood
  • Changes in appetite
  • Pain in the lower back
  • Bruising easily or bleeding that has trouble stopping
  • Having seizures
  • Feeling extremely tired or fatigued
  • Irregular urination including little to no urination
  • Nausea
  • Vomiting
  • Swelling of the feet
• Increases in blood sugars (hyperglycemia). Some people who take protease inhibitors including darunavir/cobicistat can get high blood sugar, develop diabetes, or your diabetes can get worse Tell your healthcare provider right away if you have some or all of the following symptoms of hyperglycemia:
  • Feeling hungry soon after eating
  • Urinating (peeing) very often
  • Feeling thirsty often
  • Having frequent headaches
  • Feeling tired or fatigued
• Changes in the way the body stores fat. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). 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. Tell your healthcare provider right away if you have some or all of the following symptoms of changes in fat storage:
  • Having more abdominal obesity,
  • Noticing a arms and legs getting thinner
  • Accumulation of fat around the face (moon face)
  • Accumulation of fat at the bottom of the neck and the top of the back (buffalo hump)
• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after starting your HIV-1 medicine.
• Damage and inflammation of the pancreas (pancreatitis). Tell your healthcare provider right away if you have some or all of the following symptoms of inflammation of the pancreas:
  • Pain in your stomach or abdomen
  • Swelling in the stomach or abdominal area
  • Nausea
  • Vomiting
  • Fever
  • Fast heart rate
  • Unexpected weight loss
• Bleeding disorders. Some people with hemophilia have increased bleeding with protease inhibitors including darunavir/cobicistat. Tell your healthcare provider right away if you have some or all of the following symptoms of a bleeding disorder:
  • Bleeding that does not stop easily or takes a long time to stop
  • Black or bloody stools (feces)
  • Reddish urine or blood in urine
  • Bruising easily
  • Bruises that get bigger or bruises that do not go away

Do not take darunavir/cobicistat if you:

• Are allergic to darunavir, cobicistat, or to any of its ingredients 
• Are taking other medications that are known to interact with darunavir/cobicistat

• Store darunavir/cobicistat at room temperature.
• Keep this and all medicines out of the reach of children

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For darunavir and cobicistat, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to darunavir and cobicistat or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of darunavir and cobicistat combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of atazanavir and cobicistat combination in the elderly. However, elderly patients are more likely to have age-related liver problems, which may require caution for patients receiving darunavir and cobicistat.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking darunavir and cobicistat, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using darunavir and cobicistat with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Alfuzosin
• Astemizole
• Carbamazepine
• Cisapride
• Colchicine
• Conivaptan
• Crizotinib
• Dihydroergotamine
• Domperidone
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Dronedarone
• Eletriptan
• Eliglustat
• Eplerenone
• Ergonovine
• Ergotamine
• Fosphenytoin
• Grazoprevir
• Isavuconazonium Sulfate
• Ivabradine
• Lomitapide
• Lovastatin
• Lurasidone
• Maraviroc
• Methylergonovine
• Midazolam
• Naloxegol
• Pazopanib
• Phenobarbital
• Phenytoin
• Pimozide
• Primidone
• Ranolazine
• Rifampin
• Riociguat
• Romidepsin
• Sildenafil
• Silodosin
• Simvastatin
• St John's Wort
• Terfenadine
• Tolvaptan
• Triazolam
• Venetoclax

Using darunavir and cobicistat with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ado-Trastuzumab Emtansine
• Afatinib
• Alprazolam
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amprenavir
• Apixaban
• Aprepitant
• Aprobarbital
• Aripiprazole
• Atazanavir
• Atomoxetine
• Atorvastatin
• Avanafil
• Bedaquiline
• Betrixaban
• Boceprevir
• Bosentan
• Bosutinib
• Brigatinib
• Bromocriptine
• Budesonide
• Butabarbital
• Butalbital
• Cabazitaxel
• Cabozantinib
• Calcifediol
• Cariprazine
• Ceritinib
• Cilostazol
• Clarithromycin
• Clomipramine
• Cobimetinib
• Codeine
• Conivaptan
• Cyclophosphamide
• Cyclosporine
• Dabigatran Etexilate
• Dabrafenib
• Daclatasvir
• Dasabuvir
• Dasatinib
• Deflazacort
• Delamanid
• Delavirdine
• Desipramine
• Desogestrel
• Dexamethasone
• Dextromethorphan
• Diazepam
• Dibenzepin
• Didanosine
• Dienogest
• Digoxin
• Disopyramide
• Docetaxel
• Domperidone
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Drospirenone
• Duloxetine
• Efavirenz
• Eliglustat
• Elvitegravir
• Erlotinib
• Erythromycin
• Eslicarbazepine Acetate
• Estradiol Cypionate
• Estradiol Valerate
• Eszopiclone
• Ethinyl Estradiol
• Ethynodiol Diacetate
• Etonogestrel
• Etravirine
• Everolimus
• Fentanyl
• Flecainide
• Fluoxetine
• Fluticasone
• Fluvastatin
• Fosamprenavir
• Fosaprepitant
• Gestodene
• Haloperidol
• Hydrocortisone
• Ibrutinib
• Idelalisib
• Ifosfamide
• Iloperidone
• Imipramine
• Irinotecan
• Irinotecan Liposome
• Itraconazole
• Ivacaftor
• Ketoconazole
• Lapatinib
• Levomilnacipran
• Levonorgestrel
• Lidocaine
• Lofepramine
• Lopinavir
• Lumacaftor
• Macitentan
• Manidipine
• Medroxyprogesterone Acetate
• Melitracen
• Mephobarbital
• Mestranol
• Methadone
• Methohexital
• Mexiletine
• Midostaurin
• Mifepristone
• Modafinil
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Naloxegol
• Nelfinavir
• Netupitant
• Nevirapine
• Nifedipine
• Nilotinib
• Nimodipine
• Nisoldipine
• Norelgestromin
• Norethindrone
• Norgestimate
• Norgestrel
• Nortriptyline
• Olaparib
• Ombitasvir
• Ondansetron
• Opipramol
• Orlistat
• Oxcarbazepine
• Oxycodone
• Palbociclib
• Panobinostat
• Paritaprevir
• Pentobarbital
• Perphenazine
• Pimavanserin
• Piperaquine
• Pitavastatin
• Pixantrone
• Ponatinib
• Pravastatin
• Prednisolone
• Prednisone
• Primidone
• Propafenone
• Propranolol
• Protriptyline
• Quetiapine
• Quinidine
• Reboxetine
• Regorafenib
• Retapamulin
• Ribociclib
• Rifabutin
• Rifapentine
• Ritonavir
• Rivaroxaban
• Rosuvastatin
• Ruxolitinib
• Salmeterol
• Saquinavir
• Secobarbital
• Simeprevir
• Sirolimus
• Sunitinib
• Suvorexant
• Tacrolimus
• Tadalafil
• Tamoxifen
• Tamsulosin
• Telaprevir
• Telithromycin
• Temsirolimus
• Thiopental
• Thiotepa
• Tianeptine
• Ticagrelor
• Tipranavir
• Topotecan
• Toremifene
• Trabectedin
• Tramadol
• Trazodone
• Trimipramine
• Valbenazine
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vilazodone
• Vinblastine
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Vorapaxar
• Voriconazole
• Warfarin
• Zolpidem

Using darunavir and cobicistat with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aripiprazole Lauroxil
• Atazanavir
• Clarithromycin
• Cobicistat
• Darunavir
• Digoxin
• Indinavir
• Ketoconazole
• Nelfinavir
• Tenofovir Disoproxil Fumarate

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of darunavir and cobicistat. Make sure you tell your doctor if you have any other medical problems, especially:

• Diabetes or
• Fanconi syndrome (kidney disease), history of or
• Hemophilia (a bleeding problem) or
• Hyperglycemia (high blood sugar) or
• Kidney failure, history of or
• Liver disease (including hepatitis B or C) or
• Sulfa allergy—Use with caution. May make these conditions worse.

• Liver disease, severe—Use is not recommended in these patients.

• It is used to treat HIV infection.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take darunavir and cobicistat or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to darunavir and cobicistat. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

• Prezcobix

Coadministration with alfuzosin, carbamazepine, cisapride, colchicine (in patients with renal and/or hepatic impairment), dronedarone, elbasvir/grazoprevir, ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), lovastatin, lurasidone, oral midazolam, phenobarbital, phenytoin, pimozide, ranolazine, rifampin, sildenafil (for treatment of pulmonary arterial hypertension), simvastatin, St John's wort, triazolam

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to darunavir, cobicistat, or any component of the formulation; severe hepatic impairment (Child-Pugh class C). Coadministration with amiodarone, apixaban, lidocaine (systemic), quinidine, rivaroxaban, salmeterol, ticagrelor, astemizole (not available in Canada), bepridil (not available in Canada) or terfenadine (not available in Canada)

Frequency not always defined. Reactions reported with combination product: Also see individual agents.

1% to 10%:

Immunologic: Immune reconstitution syndrome