Dolutegravir-Rilpivirine

Dolutegravir-Rilpivirine is a combination medication used as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to dolutegravir or rilpivirine.

• Dolutegravir-Rilpivirine is available under the following different brand names: Juluca

Common side effects of Dolutegravir-Rilpivirine include:

• diarrhea
• nausea
• headache

Serious side effects of Dolutegravir-Rilpivirine include: 

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• fever
• general ill feeling
• extreme tiredness
• mouth sores
• redness or swelling in the eyes
• blistering or peeling skin
• thoughts about suicide or self-harm
• anxiety
• sadness
• feeling hopeless
• nausea
• vomiting
• loss of appetite
• right-sided upper stomach pain
• dark urine
• clay-colored stools
• yellowing of the skin or eyes (jaundice)
• night sweats
• swollen glands
• cold sores
• cough
• wheezing
• diarrhea
• 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
• impotence

Rare side effects of Dolutegravir-Rilpivirine include:

• none 

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

• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
• 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.

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 the FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 50 mg/25 mg
• Equivalent to 52.6 mg dolutegravir sodium/27.5 mg rilpivirine hydrochloride

HIV Infection

Adult dosage

• HIV-1 RNA less than 50 copies/mL on a stable ART regimen for 6 months and more: 1 tablet (dolutegravir 50 mg/rilpivirine 25 mg) orally once daily

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, healthcare provider, or pharmacist first.

• Dolutegravir-Rilpivirine has severe interactions with the following drugs:
  • carbamazepine
  • dexamethasone
  • dexlansoprazole
  • dofetilide
  • efavirenz
• Dolutegravir-Rilpivirine has serious interactions with 51 other drugs
• Dolutegravir-Rilpivirine has moderate interactions with 152 other drugs
• Dolutegravir-Rilpivirine has minor interactions with the following drugs:
  • chloroquine
  • crizotinib

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 the products you use. 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

• Documented hypersensitivity to dolutegravir or rilpivirine
• Concomitant use with other drugs
• Dofetilide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, dexamethasone, St. John’s wort, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dolutegravir-Rilpivirine?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dolutegravir-Rilpivirine?”

Cautions

Depressive disorders (including depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, and suicidal ideation) have been associated with rilpivirine

May 18, 2018: The FDA issued a safety alert regarding the potential risk of neural tube birth defects (see Pregnancy)

• Hepatotoxicity
  • Hepatic adverse events were reported in patients receiving a dolutegravir- or rilpivirine-containing regimen; patients with underlying hepatitis B or C or marked elevations in transaminases before treatment may be at increased risk for worsening or development of transaminase elevations
  • Drug-induced liver injury leading to acute liver failure has been reported with dolutegravir-containing products; monitor for hepatotoxicity
• Skin and hypersensitivity reactions
  • Hypersensitivity reactions (eg, rash, constitutional findings, and sometimes organ dysfunction, including liver injury) have been reported
  • Severe skin and hypersensitivity reactions have been reported during postmarketing experience, including cases of drug reaction with eosinophilia and systemic symptoms, with rilpivirine-containing regimens
  • Discontinue treatment immediately if signs or symptoms of severe skin or hypersensitivity reactions develop 
• Drug interactions overview
  • Concomitant use of Dolutegravir-Rilpivirine and other drugs may result in known or potentially significant drug interactions, loss of therapeutic effect of Dolutegravir-Rilpivirine, possible development of resistance, or possible increases in toxicities of Dolutegravir-Rilpivirine
  • Because Dolutegravir-Rilpivirine is a complete regimen, coadministration with other antiretroviral medications is not recommended
  • Dolutegravir inhibits the renal organic cation transporters (OCT)2 and multidrug and toxin extrusion transporter (MATE)1; thus, it may increase plasma concentrations of drugs eliminated via OCT2 or MATE1 (eg, dofetilide and metformin)
  • Potential for other drugs to affect dolutegravir
    • Dolutegravir is metabolized by uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 with some contribution from CYP3A; dolutegravir is also a substrate of UGT1A3, UGT1A9, breast cancer resistance protein (BCRP), and p-glycoprotein (P-gp) in vitro
    • Drugs that induce those enzymes and transporters may decrease dolutegravir plasma concentrations and reduce the therapeutic effect of dolutegravir
    • Coadministration of dolutegravir and other drugs that inhibit these enzymes may increase dolutegravir plasma concentrations
  • Potential for other drugs to affect rilpivirine
    • Drugs that induce or inhibit CYP3A may affect the clearance of rilpivirine
    • Coadministration with CYP3A4 inducers may decrease plasma concentrations of rilpivirine and result in loss of virologic response and possible resistance to rilpivirine OR to non-nucleoside reverse transcriptase inhibitors (NNRTIs)
    • Coadministration with CYP3A4 inhibitors may increase plasma concentrations of rilpivirine
    • Coadministration with drugs that increase gastric pH may decrease plasma concentrations of rilpivirine and result in loss of virologic response and possible resistance to rilpivirine or NNRTIs
    • In healthy subjects, rilpivirine 75 mg orally once daily (3 times Dolutegravir-Rilpivirine dose) and 300 mg orally once daily (12 times Dolutegravir-Rilpivirine dose) have been shown to prolong the QTc interval; consider alternatives to Dolutegravir-Rilpivirine when coadministered with a drug with a known risk of torsade de pointes

Pregnancy and Lactation

Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

Dolutegravir has been shown to cross the placenta; data from a birth outcome surveillance study has identified an increased risk of neural tube defects when dolutegravir, a component of the drug combination, is administered at the time of conception compared with non-dolutegravir-containing antiretroviral regimens

As defects related to the closure of the neural tube occur from conception through the first 6 weeks of gestation, embryos exposed to dolutegravir from the time of conception through the first 6 weeks of gestation are at potential risk

In addition, 2 of 5 birth defects (encephalocele and iniencephaly), which have been observed with dolutegravir use, although often termed neural tube defects, may occur post-neural tube closure, the period of which may be later than 6 weeks of gestation, but within the first trimester

Due to a limited understanding of types of reported neural tube defects associated with dolutegravir use and because the date of conception may not be determined with precision, an alternative treatment should be considered at the time of conception through the first trimester of pregnancy

Initiation of therapy is not recommended in women actively trying to become pregnant unless there is no suitable alternative

In individuals of childbearing potential currently on therapy who are actively trying to become pregnant, or if pregnancy is confirmed in the first trimester, assess the risks and benefits of continuing therapy versus switching to another antiretroviral regimen and consider switching to an alternative regimen

Advise pregnant women of the potential risk of embryo exposure to drugs from the time of conception through the first trimester of pregnancy; a benefit-risk assessment should consider factors such as the feasibility of switching, tolerability, ability to maintain viral suppression, and risk of transmission to the infant against the risk of neural tube defects

• Potential risk of neural tube birth defects
  • Serious cases of neural tube birth defects involving the brain, spine, and spinal cord were reported in babies born to women treated with dolutegravir
• Recommendations
  • Patients should not discontinue dolutegravir without consulting a healthcare professional because stopping your medicine can cause the HIV infection to worsen
  • Pregnant women stopping dolutegravir-containing regimen without switching to alternative HIV medicines could cause the amount of virus to increase and spread HIV to your baby
  • Healthcare providers should weigh the benefits and the risks of dolutegravir when prescribing antiretroviral medicines to women of childbearing age; consider alternative antiretroviral medicines; discuss the relative risks and benefits of appropriate alternative antiretroviral therapies
  • Women of childbearing age who decide to take a dolutegravir-containing regimen should consistently use effective birth control (contraception) while on HIV treatment; women should discuss with their healthcare professionals an effective birth control method to use while taking a dolutegravir-containing regimen
  • Perform pregnancy testing before initiating a dolutegravir-containing regimen in women of childbearing age to exclude pregnancy
• Lactation
  • The CDC does not recommend that HIV-1-infected mothers in the US breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection
  • Dolutegravir and lamivudine are present in human milk; there is no information on the effects of the drug components on the breastfed infant or the effects on milk production
  • When administered to lactating rats, dolutegravir and rilpivirine were present in milk
  • Because of the potential for HIV-1 transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving therapy