Darunavir

Darunavir is a prescription medication used to treat the symptoms of HIV Infection. 

• Darunavir is available under the following different brand names: Prezista

Common side effects of Darunavir include:

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

Serious side effects of Darunavir 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,
• Skin rash (no matter how mild),
• Increased thirst,
• Increased urination,
• Dry mouth,
• Fruity breath odor,
• Loss of appetite,
• Upper stomach pain (that may spread to the back),
• Nausea,
• Vomiting,
• Fast heart rate,
• Dark urine,
• Yellowing of the skin or eyes (jaundice),
• Night sweats,
• Swollen glands,
• Cold sores,
• Cough,
• Wheezing,
• Diarrhoea,
• Weight loss,
• Trouble speaking or swallowing,
• Problems with balance or eye movement,
• Weakness,
• Prickly feeling,
• Swelling in the neck or throat (enlarged thyroid),
• Menstrual changes, and
• Impotence

Rare side effects of Darunavir 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 dosage

Tablet

• 75 mg
• 150 mg
• 400 mg
• 600 mg
• 800 mg

Oral suspension

• 100 mg/mL

HIV Infection

Adult dosage

• Treatment-naive or antiretroviral treatment-experienced (with no darunavir resistance-associated substitutions): 800 mg + ritonavir 100 mg orally once a day with food
• Treatment-experienced (with at least 1 DRV mutation) or genotyping not obtained: 600 mg + ritonavir 100 mg orally every 12 hours with food

Pregnant females

• Recommended: 600 mg + ritonavir 100 mg orally every 12hours with food
• 800 mg + ritonavir 100 mg orally once a day should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg + ritonavir 100 mg once a day regimen before pregnancy, are virologically suppressed (.e, HIV-1 RNA below 50 copies/mL), and in whom a change to the twice-daily regimen may compromise tolerability or compliance

Pediatric dosage

• Coadministered with ritonavir and in combination with other antiretroviral agents for HIV infection
• Below 3 years or below 10 kg: Safety and efficacy not established
• Must take with food
• Also, see Administration
• Treatment-naive or antiretroviral treatment-experienced (with no darunavir resistance-associated substitutions)
• NOTE: The HIV treatment guidelines differ from the prescribing information and recommend that once-daily darunavir dosing should NOT be used as initial therapy in children below 12 years; a switch to once-daily therapy may be considered in patients who have undetectable viral loads on twice-daily therapy to enhance ease of use and support compliance
• Weight 10 kg to below 15 kg
• Use oral suspension
  • Below 10 kg to above 11 kg: 350 mg (3.6 mL) * + ritonavir 64 mg (0.8 mL) orally every day
  • Above 11 kg to below 12 kg: 385 mg (4 mL) * + ritonavir 64 mg (0.8 mL) orally every day
  • Above 12 kg to below 13 kg: 420 mg (4.2 mL) + ritonavir 80 mg (1 mL) orally every day
  • Above 13 kg to below 14 kg: 455 mg (4.6 mL) * + ritonavir 80 mg (1 mL) orally every day
  • Above 14 kg to below 15 kg: 490 mg (5 mL) * + ritonavir 96 mg (1.2 ml) orally every day
  • *NOTE: Doses that were rounded up to the nearest measurable suspension dose
• Weight above 15 kg
  • Above 15 kg to below 30 kg: 600 mg + ritonavir 100 mg orally every day
  • Above 30 kg to below 40 kg: 675 mg + ritonavir 100 mg orally every day
  • Above 40 kg: 800 mg + ritonavir 100 mg orally every day
  • Antiretroviral treatment-experienced with at least 1 darunavir resistance-associated substitution
• Weight 10 kg to below 15 kg
• Use oral suspension
  • Above 10 kg to below 11 kg: 200 mg (2 mL) + ritonavir 32 mg (0.4 mL) orally two times a day
  • Above 11 kg to below 12 kg: 220 mg (2.2 mL) + ritonavir 40 mg (0.4 mL) orally two times a day
  • Above 12 kg to below 13 kg: 240 mg (2.4 mL) + ritonavir 32 mg (0.5 mL) orally two times a day
  • Above 13 kg to below 14 kg: 260 mg (2.6 mL) + ritonavir 40 mg (0.5 mL) orally two times a day
  • Above 14 kg to below 15 kg: 280 mg (2.8 mL) + ritonavir 48 mg (0.6 mL) orally two times a day
  • Weight above 15 kg
  • Above 15 kg to below 30 kg: 375 mg + ritonavir 48 mg orally two times a day
  • &ge:30 kg to below 40 kg: 450 mg + ritonavir 60 mg orally two times a day
  • Above 40 kg: 600 mg + ritonavir 100 mg orally two times a day

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 has severe interactions with at least 38 other drugs.
• Darunavir has serious interactions with at least 138 other drugs.
• Darunavir has moderate interactions with at least 308 other drugs.
• Darunavir has minor interactions with at least 43 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, or if you have health questions or concerns.

Contraindications

• Hypersensitivity
• Coadministration of darunavir/ritonavir
• Concomitant CYP3A4 substrates that are toxic in excess
• Concurrent strong CYP3A4 inducers (. g, St John's wort, rifampin)
• Alpha-1 antagonist: Alfuzosin
• Cardiovascular agents: Ranolazine, ivabradine, dronedarone
• Antigout: Colchicine (in patients with renal/and or hepatic impairment)
• Antimycobacterial: Rifampin
• Antipsychotics: Lurasidone, pimozide
• Ergot derivatives (. 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
• PDE-5 inhibitor: Sildenafil (used for the treatment of pulmonary arterial hypertension)
• Sedatives/hypnotics: PO midazolam, triazolam
• Opioid antagonist: Naloxegol

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Must be taken with ritonavir and food, since the dose is because darunavir is metabolized by CYP3A4 and ritonavir is a potent CYP3A4 inhibitor
• Severe skin reactions, accompanied by fever and/or elevations of transaminases reported (0.4%); Stevens-Johnson Syndrome (below 0.1%), toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis also reported
• Caution with elderly patients
• Caution with hepatic impairment (not recommended if severe)
• Contains a sulfa moiety; monitor patients with a known sulfonamide allergy
• Increase in total cholesterol and triglycerides reported, screen before therapy and throughout treatment
• Pancreatitis reported; use caution in patients at risk for pancreatitis (those with elevated triglycerides, history of pancreatitis, or advanced HIV disease
• Risk of immune reconstitution syndrome
• 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 antiretroviral therapy
• Patients may develop new-onset diabetes mellitus or hyperglycemia; initiation or dose adjustments of insulin or oral hypoglycemic agents may be required
• Patients with hemophilia may develop increased bleeding events
• Not for use in patients below 3 years of age; toxicity may occur
• Hepatoxicity
  • Risk of hepatotoxicity including drug-induced hepatitis: acute hepatitis, cytolytic hepatitis
  • Especially with pre-existing liver dysfunction (chronic hepatitis B or C)
  • Interrupt or discontinue treatment if new/worsening liver dysfunction develops

Pregnancy and Lactation

• The recommended dosage in pregnant patients is 600 mg taken with ritonavir 100 mg twice daily with food; darunavir 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on stable darunavir 800 mg with ritonavir 100 mg once daily regimen before pregnancy, are virologically suppressed (HIV-1 RNA less than 50 copies per mL), and in whom a change to twice daily darunavir 600 mg with ritonavir 100 mg may compromise tolerability or compliance
• 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)
• Use of darunavir may reduce the efficacy of combined hormonal contraceptives and the progestin-only pill; advise patients using combined hormonal contraceptives or the progestin-only pill to use an effective alternative contraceptive method or add a barrier method of contraception; for co-administration with drospirenone, clinical monitoring recommended due to potential for hyperkalemia
•  Lactation
  • The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV
  • There are no data on the presence of darunavir in human milk, the effects on the breastfed infant, or the effects on milk production; because of the potential for (1) HIV transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants) and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving darunavir