Darunavir-Cobicistat-Emtricitabine-Tenofovir AF

Darunavir-Cobicistat-Emtricitabine-Tenofovir AF is a combination medication used for the treatment of HIV Infection. 

• Darunavir-Cobicistat-Emtricitabine-Tenofovir AF is available under the following different brand names: Symtuza.

Common side effects of Darunavir-Cobicistat-Emtricitabine-Tenofovir AF include:

• Nausea,
• Upper stomach,
• Diarrhea,
• Gas,
• Headache,
• Tiredness, and
• Rash

Serious side effects of Darunavir-Cobicistat-Emtricitabine-Tenofovir AF include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Fever,
• Sore throat,
• Burning eyes,
• Skin pain,
• Red or purple skin rash with blistering and peeling,
• Increased thirst,
• Increased urination,
• Little or no urination,
• Unusual muscle pain,
• Trouble breathing,
• Stomach pain,
• Vomiting,
• Irregular heart rate,
• Dizziness,
• Feeling cold,
• Weakness,
• Tiredness,
• Swelling around the midsection,
• Right-sided upper stomach pain,
• Loss of appetite,
• Dark urine,
• Clay-colored stools,
• Yellowing of the skin or eyes (jaundice),
• Night sweats,
• Swollen glands,
• Cold sores,
• Wheezing,
• Diarrhea,
• Weight loss,
• Trouble speaking or swallowing,
• Problems with balance or eye movement,
• Prickly feeling,
• Swelling in the neck or throat (enlarged thyroid),
• Menstrual changes, and
• Impotence

Rare side effects of Darunavir-Cobicistat-Emtricitabine-Tenofovir AF 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

Darunavir-Cobicistat-Emtricitabine-Tenofovir AF

Tablet

• 800 mg/150 mg/200 mg/10 mg

HIV Infection

Adult dosage

• 1 tablet (i.e., darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir AF 10 mg) orally once a day

Pediatric dosage

• Children below 40 kg: Safety and efficacy not established.
• Children 40 kg and above: 1 tablet (i.e., darunavir 800 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir AF 10 mg) orally once a day
• Darunavir is not recommended in children aged below 3 years because of toxicity and mortality observed in juvenile rats dosed with darunavir.

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-Emtricitabine-Tenofovir AF has severe interactions with at least 29 other drugs.
• Darunavir-Cobicistat-Emtricitabine-Tenofovir AF has serious interactions with at least 196 other drugs.
• Darunavir-Cobicistat-Emtricitabine-Tenofovir AF has moderate interactions with at least 467 other drugs.
• Darunavir-Cobicistat-Emtricitabine-Tenofovir AF has minor interactions with at least 34 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 of the following drugs due to the potential for serious and/or life-threatening events or loss of therapeutic effect:
• Alpha 1-adrenoreceptor antagonist: Alfuzosin
• Anticonvulsants: Carbamazepine, phenobarbital, phenytoin
• Anti-gout: Colchicine, in patients with renal and/or hepatic impairment
• Antimycobacterial: Rifampin
• Antipsychotics: Lurasidone, pimozide
• Cardiac disorders: Dronedarone, ivabradine, ranolazine
• Ergot derivative (. g, dihydroergotamine, ergotamine, methylergonovine)
• GI motility agent: Cisapride
• Herbal product: St. John’s wort (Hypericum perforatum)
• Hepatitis C direct-acting antiviral: Elbasvir/grazoprevir
• Lipid modifying agents: Lomitapide, lovastatin, simvastatin.
• Opioid Antagonist: Naloxegol
• PDE-5 inhibitor: Sildenafil for treatment of pulmonary arterial hypertension
• Sedatives/hypnotics: Midazolam PO, triazolam
• 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-Emtricitabine-Tenofovir AF?”

Long-Term Effects

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

Cautions

• Severe, acute exacerbation of hepatitis B in patients co-infected with HBV and HIV-1 reported (see Black Box Warnings and Dosing Considerations); test HIV-1 patients for the presence of chronic hepatitis B virus before initiating therapy.
• Drug-induced hepatitis (. g, acute hepatitis, cytolytic hepatitis) reported in clinical trials with darunavir; patients with preexisting liver dysfunction, including chronic active hepatitis B or C, are at increased risk for liver function abnormalities, including severe hepatic adverse reactions.
• Rare reports of severe skin reactions, accompanied by fever and/or elevations of transaminases; Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have been reported.
• Immune reconstitution syndrome was reported in patients treated with combination antiretroviral therapy; autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) were reported.
• Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), reported with the use of tenofovir prodrugs.
• Darunavir contains a sulfonamide moiety; monitor patients with a known sulfonamide allergy after initiation.
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, were reported with the use of nucleoside analogs, including emtricitabine.
• New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia reported during postmarketing surveillance in HIV-infected patients receiving HIV protease inhibitor therapy.
• Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, observed in patients receiving ARTs.
• Reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis in patients with hemophilia type A and B treated with HIV protease inhibitors.
• Drug interaction overview
  • Also see Contraindications.
  • Symtuza is a complete regimen for HIV-1 infection, and coadministration with other ARTs is not recommended.
  • May interact with many drugs; therefore, inform patients of the potential serious drug interactions and that some drugs are contraindicated, while other drugs may require a dosage adjustment.
  • CYP3A4 inhibitors or inducers
    • Darunavir is metabolized by CYP3A.
    • Cobicistat is metabolized by CYP3A and, to a minor extent, by CYP2D6.
    • Coadministration of drugs that induce CYP3A activity is expected to increase the clearance of darunavir and cobicistat, resulting in lower plasma concentrations, which may lead to loss of therapeutic effect and development of resistance.
    • Coadministration drugs that inhibit CYP3A may result in increased plasma concentrations of darunavir and cobicistat.
    • Potential for other drugs to affect Symtuza.
  • Tenofovir AF is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3
    • Drugs that strongly affect P-gp activity may lead to changes in tenofovir AF absorption.
    • Drugs that induce P-gp activity are expected to decrease the absorption of tenofovir AF, resulting in decreased plasma concentrations of tenofovir AF, which may lead to loss of the therapeutic effect of Symtuza and development of resistance.
    • Coadministration of Symtuza with drugs that inhibit P-gp may increase the absorption and plasma concentrations of tenofovir AF.
  • Drugs affecting renal function.
    • Emtricitabine and tenofovir are primarily excreted by the kidneys via glomerular filtration and active tubular secretion.
    • Coadministration of Symtuza with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and other eliminated drugs, and may increase the risk of adverse effects.
    • Examples of drugs that are eliminated by active tubular secretion include but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, and high-dose or multiple NSAIDs.

Pregnancy and Lactation

• Not recommended during pregnancy because of substantially lower exposures of darunavir and cobicistat during pregnancy
• Do not initiate Symtuza in pregnant women; switch to an alternant regimen for women who become pregnant during therapy.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARTs during pregnancy; clinicians are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
• Lactation
  • The CDC recommends that HIV-infected mothers in the United States not breastfeed their infants to avoid risking postnatal HIV-1 infection transmission.