Darunavir-Cobicistat

Darunavir-Cobicistat is a combination medication used for the treatment of HIV-1 Infection

• Darunavir-Cobicistat is available under the following different brand names: Prezcobix

Common side effects of Darunavir-Cobicistat include:

• Nausea,
• Vomiting,
• Stomach pain,
• Diarrhea,
• Headache,
• Rash, and
• Changes in the shape or location of body fat (especially in the arms, legs, face, neck, breast, and waist)

Serious side effects of Darunavir-Cobicistat include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Fever,
• Sore throat,
• Burning in the eyes,
• Skin pain,
• Red or purple skin rash that spreads and causes blistering and peeling,
• Increased thirst,
• Increased urination,
• Dry mouth,
• Fruity breath odor,
• Headache,
• Blurred vision,
• Upper stomach pain,
• Vomiting,
• Loss of appetite,
• Dark urine,
• Clay-colored stools,
• Yellowing of the skin or eyes (jaundice),
• Night sweats,
• Swollen glands,
• Cold sores,
• Cough,
• Wheezing,
• Diarrhea,
• Weight loss,
• Stomach pain,
• Tiredness,
• Itching,
• Skin redness,
• Trouble speaking or swallowing,
• Problems with balance or eye movement,
• Weakness,
• Prickly feeling,
• Swelling in your neck or throat (enlarged thyroid),
• Menstrual changes, and
• Impotence

Rare side effects of Darunavir-Cobicistat include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage 

Tablet

• 800 mg/150 mg

HIV-1 Infection

Adult dosage

• 1 tablet (800 mg/150 mg) orally once a day with food

Pediatric dosage

• Children below 40 kg: Safety and efficacy not established.
• Children 40 kg and above: 1 tablet (800 mg/150 mg) orally once a day with food

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Darunavir-Cobicistat has severe interactions with at least 59 other drugs.
• Darunavir-Cobicistat has serious interactions with at least 215 other drugs.
• Darunavir-Cobicistat has moderate interactions with at least 394 other drugs.
• Darunavir-Cobicistat has minor interactions with at least 48 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Coadministration with alfuzosin, dronedarone, ivabradine, ranolazine, naloxegol
• CYP inducers (rifampin, St. John’s wort), cisapride, pimozide, lurasidone, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine)
• HMG-CoA reductase inhibitors (lomitapide, lovastatin, simvastatin)
• PDE5 inhibitors (long-term administration [. g, sildenafil as Revatio for PAH]), triazolam, midazolam, anticonvulsants (carbamazepine, phenobarbital, phenytoin)
• Hepatitis C direct-acting antiviral (elbasvir/grazoprevir)
• Colchicine (in patients with renal/and or hepatic impairment)
• CYP3A4 substrates with a narrow therapeutic index

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Darunavir-Cobicistat?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Darunavir-Cobicistat?”

Cautions

• Hepatotoxicity reported; monitor liver enzymes at baseline and during treatment; consider interrupting or discontinuing treatment with evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms [. g, fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly])
• Severe skin reactions accompanied by fever and/or elevations of transaminases; Stevens-Johnson syndrome rarely; mild-to-moderate rash reported to occur within first 4 weeks of treatment and resolved with continued dosing.
• Assess eCrCl before initiating therapy; cobicistat decreases estimated creatinine clearance without affecting actual renal glomerular function by inhibiting the tubular secretion of creatinine.
• Sulfa allergy: Darunavir contains sulfa moiety; monitor patients with a known sulfonamide allergy.
• New-onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia reported during postmarketing surveillance in HIV-infected patients receiving protease inhibitors.
• Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been observed in patients receiving ARTs.
• Increased bleeding, including spontaneous skin hematomas and hemarthrosis, was reported in patients with hemophilia type A and B treated with HIV protease inhibitors.
• Not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy
• Immune reconstitution
  • Reported during the initial phase of combination ART treatment.
  • Patients whose immune systems become active may develop an inflammatory reaction to indolent or residual opportunistic infections (. g, Mycobacterium avium infection, CMV, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
  • Autoimmune disorders (. g, Graves’ disease, polymyositis, Guillan-Barre syndrome, autoimmune hepatitis) were also reported.
• Renal impairment
  • Renal impairment, including cases of acute renal failure and Fanconi syndrome, was reported when cobicistat was used in an ART regimen that contained tenofovir DF.
  • Document urine glucose and urine protein at baseline and perform routine monitoring of eCrCl, urine glucose, and urine protein during treatment.
  • Coadministration of Darunavir-Cobicistat plus tenofovir DF in combination with concomitant or recent use of a nephrotoxic agent is not recommended.
• Drug interaction overview
  • Also see Contraindications and Drug Interaction Checker
  • When evaluated separately, darunavir and cobicistat both inhibited CYP3A and CYP2D6.
  • Cobicistat inhibits the following transporters: P-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3
  • Drugs that are metabolized by CYP3A and CYP2D6, or are substrates of the transporters P-gp, BCRP, OATP1B1, or OATP1B3, may show increased systemic exposure if coadministered with Darunavir-Cobicistat.
• ART agents that are not recommended
  • Not recommended in combination with other ART drugs that require pharmacokinetic boosting (ie, another protease inhibitor or elvitegravir)
  • Dosing recommendations for such combinations not established; coadministration may result in decreased plasma concentrations of ART agents, leading to loss of therapeutic effect and development of resistance.
  • Darunavir-Cobicistat is not recommended in combination with products containing the individual components (darunavir and cobicistat) or with ritonavir.

Pregnancy and Lactation

Not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy

• A study evaluating the pharmacokinetics of antiretrovirals during pregnancy demonstrated substantially lower exposures of darunavir and cobicistat in the second and third trimesters compared to the post-partum period.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to therapy during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
• Prospective pregnancy data from APR are not sufficient to adequately assess the risk of birth defects or miscarriage; available data from APR show no statistically significant difference in the overall risk of major birth defects for darunavir and cobicistat compared with the background rate for major birth defects of 2.7% in a U.S. reference population of Metropolitan Atlanta Congenital Defects Program (MACDP)
• Contraception
  • Consider additional or alternative (non-hormonal) forms of contraception when estrogen-containing contraceptives are co-administered; for co-administration with drospirenone, clinical monitoring is recommended due to the potential for hyperkalemia; no data are available to make recommendations on co-administration with other hormonal contraceptives.
• Lactation
  • There are no data on the presence of darunavir or cobicistat in human milk, its effects on the breastfed infant, or milk production; darunavir and cobicistat are secreted into the milk of lactating rats; because of the potential for (1) HIV trans therapy. (in HIV- negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in breastfed infants, instruct mothers not to breastfeed if receiving therapy