Complera is a combination of non-nucleoside, nucleoside, and nucleotide reverse transcriptase inhibitors.

• It s used in the treatment of HIV-1 infection in the following patients  :

  • As a complete regimen in adult

  • pediatric patients >35 kg as initial therapy in antiretroviral treatment-naive patients with HIV-1 RNA  having less than 100,000 copies/mL at the start of therapy

  • virologically suppressed (HIV-1 RNA <50 copies/mL) patients who are on a stable antiretroviral regimen for ≥6 months with no treatment failure or substitutions due to fumarate resistance to emtricitabine, rilpivirine, or tenofovir disoproxil fumarate in order to replace their current antiretroviral treatment regimen.

Complera dose in Adults

Complera dose in the treatment of HIV-1 infection:

• One tablet once daily is given orally

• Missed dose:

  • If ≤12 hours, take the dose as soon as possible
  • if >12 hours, then resume at the next regularly scheduled time.

• Dosage adjustment for concomitant therapy with rifabutin:

  • One tablet once daily is given plus rilpivirine 25 mg

Complera dose in Childrens

Complera dosage in the treatment of HIV-1 infection:

• Children and Adolescents weighing ≥35 kg:

  • One tablet (emtricitabine 200 mg, rilpivirine 25 mg, tenofovir disoproxil fumarate 300 mg) once daily is given

• Dosing adjustment for concomitant therapy with rifabutin:

  • Children and Adolescents weighing ≥35 kg:

    • One tablet (emtricitabine 200 mg, rilpivirine 25 mg, tenofovir disoproxil fumarate 300 mg) once daily is given plus an additional rilpivirine 25 mg once daily

Complera pregnancy Category: Insufficient Data

• This fixed-dose combination is recommended by the Health and Human Services' (HHS) Perinatal HIV Guidelines as an alternative to follow HIV-infected pregnant women.
• Who are antiretroviral-naive
• People who have received antiretroviral treatment (ART) in the previous but are starting again
• Patients who need a new ART regimen because of poor tolerance or poor viral response to the current regimen
• People who aren't yet pregnant, but are trying to conceive.
• If the combination is effective in suppressing viral infections and tolerated well, females may become pregnant. However, it is best to monitor them more frequently.
• Pretreatment HIV RNA >=100,000.0 copies/mL, or CD4 cell count >=200./mm should be avoided.
• Complera is a combination of emtricitabine and rilpivirine. It can be used during lactation.
• Emtricitabine and tenofovir disoproxil fumarate is usually present in breast milk.
• It is unknown if breast milk contains rilpivirine or not.

Complera dose in kidney disease:

• CrCl ≥50 mL/minute:

  • No dosage adjustments required.

• CrCl <50 mL/minute:

  • Use not advised.

• ESRD requiring dialysis:

  • Use not advised.

Complera dose in Liver disease:

• Mild to moderate impairment (Child-Pugh class A or B):

  • No dosage adjustments required.

• Severe impairment (Child-Pugh class C):

  • There are no dosage adjustments given in the manufacturer's labeling (has not been studied).

Common Side Effects of Complera (Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate) Include:

• Endocrine & Metabolic:

  • Increased Serum Cholesterol
  • Increased LDL Cholesterol

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

Less Common Side Effects of Complera (Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate) Include:

• Central Nervous System:

  • Depression
  • Headache
  • Insomnia
  • Abnormal Dreams
  • Dizziness

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Adrenocortical Insufficiency
  • Increased Serum Triglycerides

• Gastrointestinal:

  • Nausea

• Hepatic:

  • Increased Serum Bilirubin

• Renal:

  • Increased Serum Creatinine

Rare side effects of Complera

• Central Nervous System:

  • Anxiety
  • Drowsiness
  • Fatigue
  • Sleep Disorder

• Gastrointestinal:

  • Abdominal Distress
  • Abdominal Pain
  • Cholecystitis
  • Cholelithiasis
  • Decreased Appetite
  • Diarrhea
  • Vomiting

• Renal:

  • Glomerulonephritis (Membranous and Mesangioproliferative)
  • Nephrolithiasis

Contraindication to Complera (Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate) Include:

• Concurrent use of carbamazepine, systemic dexamethasone (>1 dose), proton pump inhibitors (PPIs) (eg, dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole),oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, and/or St John's wort.
• Hypersensitivity to emtricitabine or rilpivirine, tenofovir dioproxil fumarate, or any component of the formulation.

Warnings and precautions

• Cardiac effects:

  • The QTc interval in the electrocardiogram has been extended by taking supratherapeutic doses of rilpivirine (75mg once daily, 300mg once daily).
  • Take care when you are taking drugs that have a high risk of torsades, de pointes.

• Reduced bone mineral density

  • Tenofovir disoproxil fusarate has been shown to decrease bone mineral density in HIV-1-infected adults, and increase bone metabolism markers.
  • Infected children with HIV-1 have also seen a decrease in bone mineral density.
  • Adult and pediatric patients with a history or other risk factors for osteoporosis or bone loss should be monitored for their bone density.
  • All patients should receive vitamin D and calcium supplementation

• Depressive disorders:

  • Rilpivirine may cause depression, mood changes and major depression.
  • It can also lead to depression, mood swings, depression, dysphoria, major depressive disorder, depression, suicidal thoughts and suicide attempts.
  • Patients with severe depression symptoms should be evaluated immediately and the risk-benefit ratio of continuing combination therapy reevaluated.

• Hepatotoxicity:

  • Hepatotoxicity has been seen with rilpivirine-containing regimens.
  • Patients with hepatitis B/C or elevated baseline liver function tests are at higher risk
  • Patients with elevated baseline liver function or hepatitis C or B before treatment start and periodically throughout therapy should monitor their liver function.
  • Patients with no pre-existing hepatic diseases or risk factors for hepatic illness should be evaluated.

• Hypersensitivity

  • There have been cases of severe hypersensitivity and skin reactions, including blisters or hepatitis, eosinophilia, fever, eosinophilia or hepatitis, mucosal involvement and conjunctivitis.
  • Some skin reactions could be accompanied by constitutional symptoms (eg fever).
  • Some skin reactions can be linked to organ dysfunction (eg, hepatic se biochemistry elevations).
  • Keep an eye on laboratory and clinical parameters. Stop if severe hypersensitivity or skin rash occurs.

• Immune reconstitution syndrome:

  • Patients may also develop an immune reconstitution syndrome, which is an inflammation response to an indolent, residual opportunistic HIV infection.
  • This can occur during initial HIV treatment, activation of autoimmune disorders (eg Graves disease or GBS), or later in therapy.
  • Additional evaluation and treatment may be necessary.

• Hepatomegaly and lactic acidosis:

  • The use of nucleoside analogues alone or in combination, with antiretrovirals, has been associated with severe hepatomegaly and lactic acidosis, which can sometimes be fatal.
  • If a patient develops laboratory or clinical findings that suggest lactic acidosis, or hepatotoxicity, withhold treatment. Marked transaminase elevation can/may not be associated with hepatomegaly or steatosis.

• Osteomalacia, renal dysfunction

  • Tenofovir disoproxil fumarate can cause osteomalacia with proximal renal tubulopathy.
  • We have seen bone pain, extremity pain and muscle pain.
  • Patients at high risk of renal dysfunction should seek treatment for osteomalacia and hypophosphatemia if they have persistent or worsening muscle or bone symptoms.

• Toxicity in the renal system:

  • It can lead to renal toxicity (acute kidney failure or Fanconi syndrome).
  • Use caution with any concurrent or recent nephrotoxic treatment (including multiple NSAID or high-dose NSAID)
  • Acute renal failure has seen in HIV-infected patients with risk factors for renal impairment who were on a stable tenofovir disoproxil fumarate regimen to which a high dose or multiple NSAID therapy was added.
  • Consider alternatives to NSAIDs in patients using tenofovir disoproxil fumarate and at risk for renal impairment.
  • Before starting therapy, monitor serum creatinine, estimated CrCl and urine protein. Also, monitor urine glucose as needed during therapy.
  • Patients with chronic kidney disease should monitor their serum phosphorus.
  • The IDSA recommends that HIV-infected patients with a decrease in GFR should stop taking tenofovir and replace it with antiretroviral treatment. This is especially true if there are proximal tubular dysfunctions (eg, euglycemic, increased urinary Phosphorus excretion, hypophosphatemia, and proteinuria [new onset] or worsening).

• Chronic Hepatitis B: [US-Boxed Warning]

  • It is not known if HIV-1 and HBV coinfections are safe and effective.
  • After discontinuation of antiretroviral treatment, acute and severe HBV exacerbations have been observed.
  • It is not recommended for chronic hepatitis B.
  • Patients with HIV-1 or HBV should be closely monitored for at least three months. If necessary, stop the therapy.
  • Anti-hepatitis B therapy may be necessary if appropriate in patients with advanced liver disease or cirrhosis. Posttreatment exacerbation could lead to liver failure or hepatic decompensation.
  • Before starting treatment, all HIV-positive patients should be tested for HBV.

• Renal impairment

  • Patients with CrCl levels below 50 mL/minute are not recommended to use this medication.

Monitor:

• CBC with differential and reticulocyte count
• creatine kinase
• CD4 count
• HIV RNA plasma levels
• serum phosphorus (chronic kidney disease patients), serum creatinine, estimated creatine clearance
• urine glucose, urine protein (before initiation and as clinically indicated during therapy)
• hepatic function tests
• bone density (patients with a history of bone fracture or have risk factors for bone loss)
• fever, skin reactions, and/or hypersensitivity reactions
• testing for HBV is recommended before initiation of antiretroviral therapy
• weight (children).
• If used as therapy replacement in virologically suppressed patients meeting criteria, additional HIV-1 RNA and regimen tolerability monitoring is advised to assess potential virologic failure or rebound.
• Patients with HIV and HBV coinfection should be monitored for several months after tenofovir discontinuation.

How to Administer Complera (Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate)?

• Administer with food.
• A protein drink is not a substitute for food.

Mechanism of action of Complera (Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate):

• It is a mixture of nucleoside, non-nucleoside and nucleotide reverse transcriptionase inhibitors.
• Rilpivirine is a binder to reverse transcriptase. It does not require intracellular Phosphorylation for antiviral activity.
• Emtricitabine is a cytosine analog while tenofovir disoproxil fumarate (TDF) is an analog of adenosine 5'-monophosphate.
• Each drug inhibits HIV viral replication by interfering with HIV viral RNA dependent DNA Polymerase activities.

International Brands of Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate:

• Complera
• Eviplera

Complera (Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate) Brands in Pakistan:

Rilpivirine, emtricitabine, and tenofovir disoproxil fumarate are not available in Pakistan (as a single pill combination).