Prezcobix

Dosage Forms & Strengths

darunavir/cobicistat

tablet

• 800mg/150mg

HIV Infection

Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type-1 (HIV-1) infection in treatment-naïve and treatment-experienced adults with no darunavir resistance-associated mutations

1 tablet (800 mg/150 mg) PO qDay with food

Dosage Modifications

CrCl <70 mL/min: Coadministration with tenofovir disoproxil fumarate (DF) is not recommended

Severe hepatic impairment: Not recommended

Dosing Considerations

Testing before initiating

• Creatinine clearance (CrCl): Before initiating, assess estimated CrCl because cobicistat decreases eCrCl owing to inhibition of tubular secretion of creatinine, without affecting actual renal glomerular function
• Coadministration with tenofovir DF: Assess eCrCl, urine glucose, and urine protein at baseline

Safety and efficacy not established

Instructions

Take once daily with food (improves absorption)

Prezcobix is a prescription medication used to treat human immunodeficiency virus (HIV) infection in adults.

It is a single product containing 2 medications: darunavir and cobicistat. Darunavir belongs to a group of drugs called protease inhibitors. It works by decreasing the amount of HIV in the blood. Cobicistat belongs to a group of drugs called pharmacokinetic enhancers. Cobicistat helps to keep darunavir in the body longer so that the medication will have a greater effect.

This medication comes in tablet form and is taken typically once a day, with food. Common side effects of Prezcobix include diarrhea, nausea, headache, abdominal pain and vomiting.

Prezcobix is part of the drug class:

• Antivirals for treatment of HIV infections, combinations

Before taking Prezcobix, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Prezcobix or to any of its ingredients
• have liver problems
• have kidney problems
• have high cholesterol
• have autoimmune conditions
• have or have had problems with your pancreas
• are pregnant or breastfeeding

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

You should not take this medicine if you are allergic to cobicistat or darunavir.

Some medicines can interact with cobicistat and darunavir and should not be used at the same time. Your doctor may need to change your treatment plan if you use any of the following drugs:

• alfuzosin;

• cisapride;

• colchicine;

• dronedarone;

• elbasvir and grazoprevir (Zepatier);

• ranolazine;

• rifampin;

• sildenafil (Revatio, for treating pulmonary arterial hypertension);

• St. John's wort;

• medicine to lower cholesterol--lovastatin, simvastatin;

• antipsychotic medicine--lurasidone, pimozide;

• oral sedatives--midazolam, triazolam;

• ergot medicines--dihydroergotamine, ergotamine, methylergonovine; or

• seizure medicine--carbamazepine, phenobarbital, phenytoin.

To make sure cobicistat and darunavir is safe for you, tell your doctor if you have ever had:

• liver disease (especially hepatitis B or C);

• kidney disease;

• a bleeding or blood clotting disorder such as hemophilia;

• an allergy to sulfa drugs;

• diabetes; or

• if you also take tenofovir or ritonavir.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of cobicistat and darunavir on the baby.

Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

Cobicistat and darunavir is not approved for use by anyone younger than 18 years old.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss;

• liver problems--upper stomach pain, vomiting, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning or redness in your eyes, tiredness, muscle or joint pain, skin sores, red or purple skin rash that spreads and causes blistering and peeling.

This medicine may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with cobicistat and darunavir. Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

• chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

• cold sores, sores on your genital or anal area;

• rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

• trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common side effects may include:

• nausea, vomiting, stomach pain, diarrhea;

• headache;

• rash; or

• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Darunavir and cobicistat combination is used together with other medicines to treat human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Darunavir and cobicistat combination will not cure or prevent HIV infection or AIDS. It helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay problems that are usually related to AIDS or HIV disease from occurring. This medicine will not keep you from spreading HIV to other people. People who receive this medicine may continue to have other problems usually related to AIDS or HIV disease.

This medicine is available only with your doctor's prescription.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a patient information leaflet. Read and follow these instructions carefully. Read it again each time you refill your prescription in case there is new information. You should talk to your doctor if you have any questions.

Do not change the dose or stop using this medicine without checking first with your doctor. When your supply of this medicine is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of this medicine.

If you are also using didanosine (Videx®), take it 1 hour before or 2 hours after taking Prezcobix®.

Darunavir and cobicistat contains a fixed amount of medicine in each tablet.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For treatment of HIV infection:
    • Adults—One tablet once a day with food. Each tablet contains 800 milligrams (mg) of darunavir and 150 mg of cobicistat.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose by more than 12 hours, skip that dose and take the next dose at the regular time.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Feeling very tired or weak.
• Change in body fat.
• Muscle or joint pain.
• Swollen gland.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• This medicine may help the immune system work. If you have an infection that you did not know you had, it may show up when you take Prezcobix. Tell your doctor right away if you notice any signs of infection like fever, sore throat, weakness, cough, or shortness of breath after you start this medicine.
• Very bad and sometimes deadly liver problems have happened with Prezcobix. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

Recommended Dosage

Prezcobix is a fixed-dose combination product containing 800 mg of darunavir and 150 mg of cobicistat. In treatment-naïve and treatment-experienced adults with no darunavir resistance-associated substitutions, the recommended dosage of Prezcobix is one tablet taken once daily orally with food. Administer Prezcobix in conjunction with other antiretroviral agents.

Testing Prior to Initiation of Prezcobix

HIV Genotypic Testing

HIV genotypic testing is recommended for antiretroviral treatment-experienced patients. However, when HIV genotypic testing is not feasible, Prezcobix can be used in protease inhibitor-naïve patients, but is not recommended in protease inhibitor-experienced patients.

Creatinine Clearance

Prior to starting Prezcobix, assess estimated creatinine clearance because cobicistat decreases estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function [see Warnings and Precautions (5.3)]. When co-administering Prezcobix with tenofovir disoproxil fumarate (tenofovir DF) assess estimated creatinine clearance, urine glucose, and urine protein at baseline [see Warnings and Precautions (5.4)].

Renal Impairment

Prezcobix co-administered with tenofovir DF is not recommended in patients who have an estimated creatinine clearance below 70 mL per minute [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].

Hepatic Impairment

Prezcobix is not recommended for use in patients with severe hepatic impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].