Cobicistat / Darunavir Ethanolate

Cobicistat/darunavir ethanolate is an HIV-1 antiviral combination used as part of a multi-drug HIV treatment regimen.

• Prezcobix (film-coated tablet, 800 mg/150 mg) treats HIV-1 in adults and pediatric patients weighing at least 40 kg — both those new to treatment and those who have been treated before — provided the virus has no darunavir resistance mutations
• Prezcobix (film-coated tablet, 675 mg/150 mg) treats HIV-1 in pediatric patients weighing at least 25 kg to less than 40 kg with no darunavir resistance mutations
• Prezcobix Ped (tablet for oral suspension, 600 mg/90 mg) treats HIV-1 in pediatric patients 3 years of age and older weighing at least 15 kg to less than 25 kg with no darunavir resistance mutations
• All products must always be used in combination with other antiretroviral (HIV) medicines — they are never used alone

This combination works through two complementary mechanisms. Darunavir is an HIV-1 protease inhibitor — it blocks a key enzyme the virus uses to assemble mature, infectious viral particles. Without working protease, HIV cannot produce new copies that can infect other cells. Cobicistat acts as a pharmacokinetic booster: it inhibits a liver enzyme (CYP3A) that would normally break darunavir down, keeping blood levels of darunavir high enough to suppress the virus throughout the day.

Because both components are processed through the same CYP3A enzyme pathway, this combination interacts with a large number of other medicines — either raising or lowering their levels in the blood. This is why a careful medication review before and during treatment is essential.

All forms of Prezcobix and Prezcobix Ped are taken once daily by mouth with food. The specific tablet strength is determined by the patient's body weight, so always follow your prescriber's dosing instructions exactly.

• Prezcobix 800 mg/150 mg tablet: for adults and patients weighing at least 40 kg — swallowed whole once daily with food
• Prezcobix 675 mg/150 mg tablet: for patients weighing 25 kg to less than 40 kg — may be split in half if needed to help swallowing, but both pieces must be taken immediately
• Prezcobix Ped 600 mg/90 mg tablet for oral suspension: for patients 3 years and older weighing 15 kg to less than 25 kg — must be dissolved in water and taken immediately with food; never swallow whole

If you miss a dose, follow your prescriber or pharmacist's guidance — do not double up without asking first.

The most commonly reported side effects of darunavir, a component of Prezcobix and Prezcobix Ped, are:

• Diarrhea
• Nausea
• Skin rash (often mild to moderate and most common in the first four weeks)
• Headache
• Stomach (abdominal) pain
• Vomiting

Serious reactions requiring prompt medical attention include severe liver injury (watch for jaundice, dark urine, or severe fatigue), serious skin reactions such as Stevens-Johnson Syndrome (blistering, peeling, or widespread rash), and new or worsening kidney problems especially when taken with tenofovir DF.

• Liver injury: Drug-induced hepatitis and serious liver damage, including some deaths, have been reported — most often in people with pre-existing hepatitis B or C. Liver function must be monitored before and during treatment.
• Severe skin reactions: Conditions such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, and DRESS (drug rash with eosinophilia and systemic symptoms) have occurred. Stop the medicine immediately if severe rash or blistering develops.
• Kidney effects: Cobicistat causes a measurable rise in serum creatinine (a kidney marker) that does not reflect actual kidney damage — but real kidney injury can occur if this medicine is combined with tenofovir DF, particularly in patients with underlying kidney problems.
• Drug interactions: This combination inhibits important drug-processing enzymes and transporters, meaning it can raise or lower levels of many other medicines to dangerous levels. Review all medications before starting.
• Not for use in pregnancy: Drug levels drop substantially during the second and third trimesters, risking treatment failure. An alternative regimen is strongly recommended for pregnant individuals.
• Blood sugar changes: New or worsening diabetes and high blood sugar have been reported with HIV protease inhibitor therapy.
• Body fat changes: Fat redistribution (such as increased belly fat or loss of fat in the face or limbs) has been observed with antiretroviral therapy.

Cobicistat/darunavir has a wide range of significant drug interactions — always tell every prescriber and pharmacist you take it. Key interactions include:

• Completely contraindicated (must not be combined): St. John's Wort, rifampin, certain seizure medicines (carbamazepine, phenobarbital, phenytoin), the heart medicines dronedarone, ivabradine, and ranolazine, the sleep drugs oral midazolam and triazolam, the cholesterol drugs lovastatin and simvastatin, the antipsychotics lurasidone and pimozide, and sildenafil when used for pulmonary arterial hypertension
• Blood thinners (warfarin, apixaban, rivaroxaban, dabigatran, edoxaban): levels may increase — dose adjustments or close monitoring required
• Antifungals (itraconazole, ketoconazole, voriconazole): mutual elevation of drug levels — monitoring needed
• Certain antibiotics (clarithromycin, erythromycin, telithromycin): levels of both the antibiotic and darunavir/cobicistat may rise — consider alternatives
• Cancer medicines (vincristine, vinblastine, dasatinib, nilotinib): increased exposure — dose adjustments may be needed
• Antidepressants (SSRIs, tricyclics, trazodone): levels may be affected — careful dose titration needed
• Other HIV boosters or protease inhibitors: should not be combined with ritonavir, elvitegravir, or any other pharmacokinetic booster
• Colchicine (gout medicine): contraindicated in patients with kidney or liver impairment; strict dose limits apply in others

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Tell your doctor if you have any liver disease, including hepatitis B or C — you are at higher risk for serious liver problems
• Tell your doctor about any known allergy to sulfonamide drugs — darunavir contains a sulfonamide chemical group
• Tell your doctor about kidney disease, especially if you also take tenofovir DF
• Tell your doctor about hemophilia — HIV protease inhibitors have been associated with increased bleeding episodes
• Not recommended during pregnancy — drug levels drop significantly in the second and third trimesters, which can lead to treatment failure
• Breastfeeding is not recommended while taking this medicine
• Not appropriate for children younger than 3 years or weighing less than 15 kg
• Provide a complete list of all medicines, vitamins, and supplements you take — this combination interacts with a very large number of drugs
• HIV genotypic testing (checking which mutations your virus carries) is recommended for patients who have been on HIV treatment before starting this medicine
• Your doctor will check your kidney function (creatinine clearance) before you start, because cobicistat affects how creatinine is measured

There is limited human experience with overdose of Prezcobix or Prezcobix Ped. There is no specific antidote. If an overdose is suspected, supportive care — including monitoring of vital signs and clinical status — is the main approach.

Because both darunavir and cobicistat bind tightly to blood proteins, dialysis is unlikely to remove a meaningful amount of the drug from the body. Contact a poison control center or emergency services immediately if an overdose is suspected.

Cobicistat can cause a rise in the blood marker serum creatinine — not because it damages the kidneys, but because it blocks the kidney's active secretion of creatinine (a normal process for removing waste) without affecting actual kidney filtration (glomerular function). This effect appears within days of starting treatment and reverses after stopping. Your doctor needs to know this when interpreting lab results.

Studies of cobicistat at higher-than-recommended doses showed a modest prolongation of the PR interval (a measure of electrical conduction in the heart), though no significant effect on the QT interval was detected. The heart effects of darunavir combined specifically with cobicistat have not been fully evaluated together.

After taking Prezcobix or Prezcobix Ped with food, darunavir reaches its peak blood concentration in about 4 to 4.5 hours, and cobicistat peaks in about 4 to 5 hours. Food has a major effect on darunavir absorption — taking it without food can reduce drug levels substantially, which is why it must always be taken with a meal. Darunavir is about 95% bound to blood proteins and is primarily broken down by the CYP3A liver enzyme; cobicistat inhibits this enzyme, which is what keeps darunavir levels high enough to work.

Cobicistat itself is 97–98% protein-bound and is metabolized by CYP3A (and to a lesser extent CYP2D6). After a single dose of darunavir given with a booster, most of the drug is eliminated through the feces and a smaller portion through the urine.

of PREZCOBIX tablets: Store at 20 °C to 25 °C (between 68 °F to 77 °F); with excursions permitted to 15 °C to 30 °C (59 °F to 86 °F) . of PREZCOBIX PED tablets for oral suspension: Store in the original container in order to protect from light.