The mean change in estimated glomerular filtration rate (GFR) by Cockcroft-Gault at week 24 was -4.4 mL/min for the Complera arm and 0.1 mL/min for the protease-based regimen (p<0.001). Resistance mutations were observed in two patients in the Complera switch arm and one in the protease inhibitor arm.

Complera Important Product Safety Information and Indication

WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of Complera, in combination with other antiretrovirals.

Complera is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of Complera have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HBV and HIV-1 and have discontinued Emtriva or Viread, which are components of Complera. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue Complera. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

CONTRAINDICATIONS

Complera should not be co-administered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to Complera or to the class of NNRTIs:
  • the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
  • the antimycobacterials rifabutin, rifampin, rifapentine
  • proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
  • the glucocorticoid systemic dexamethasone (more than a single dose)
  • St John’s wort (Hypericum perforatum)

WARNINGS AND PRECAUTIONS
  • New onset or worsening renal impairmentRenal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of tenofovir disoproxil fumarate. Assess creatinine clearance (CrCl) before initiating treatment with Complera. Monitor CrCl and serum phosphorus in patients at risk for renal impairment, including patients who have previously experienced renal events while receiving Hepsera ® (adefovir dipivoxil). Avoid administering Complera with concurrent or recent use of nephrotoxic drugs. Patients with CrCl below 50 mL per minute should not receive Complera.
  • Drug InteractionsComplera should be used with caution when given with drugs that may reduce the exposure of rilpivirine.Complera should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.
  • Depressive DisordersThe adverse reaction depressive disorders (depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, suicidal ideation) has been reported with rilpivirine. During the Phase 3 trials (N = 1,368), the incidence of depressive disorders (regardless of causality, severity) reported among rilpivirine (N = 686) or efavirenz (N = 682) was 8% and 6%, respectively. Most events were mild or moderate in severity. The incidence of Grade 3 and 4 depressive disorders (regardless of causality) was 1% for both rilpivirine and efavirenz. The incidence of discontinuation due to depressive disorders among rilpivirine or efavirenz was 1% in each arm. Suicide attempt was reported in 2 subjects in the rilpivirine arm while suicide ideation was reported in 1 subject in the rilpivirine arm and in 3 subjects in the efavirenz arm. Patients with severe depressive symptoms should seek immediate medical evaluation to assess the possibility that the symptoms are related to Complera, and if so, to determine whether the risks of continued therapy outweigh the benefits.
  • Decreases in bone mineral densityBone mineral density (BMD) monitoring should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of tenofovir disoproxil fumarate.
  • Co-administration with other productsComplera should not be administered concurrently with other medicinal products containing any of the same active components, emtricitabine, rilpivirine, or tenofovir disoproxil fumarate (Emtriva, Edurant, Viread, Truvada, Atripla), with medicinal products containing lamivudine (Epivir, Epivir-HBV, Epzicom, Combivir, Trizivir), or with adefovir dipivoxil (Hepsera).
  • Fat redistributionRedistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.
  • Immune reconstitution syndromeImmune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of Complera. Further evaluation and treatment may be necessary.

ADVERSE REACTIONS

The most common adverse drug reactions to rilpivirine (incidence greater than or equal to 2%, Grades 2-4) were insomnia and headache.

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