Safety

Complera (Emtricitabine, Rilpivirine, Tenofovir Disoproxil Fumarate) Tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

May 2015

Summary View

WARNINGS AND PRECAUTIONS

Skin and Hypersensitivity Reactions
  • Severe skin and hypersensitivity reactions have been reported during the postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries. During the Phase 3 clinical trials, treatment-related rashes with at least Grade 2 severity were reported in 1% of subjects receiving rilpivirine plus emtricitabine/tenofovir DF. Overall, most rashes were Grade 1 or 2 and occurred in the first four to six weeks of therapy [see Adverse Reactions (6.1 and 6.2)].
  • Discontinue COMPLERA immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis or eosinophilia. Clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated.

ADVERSE REACTIONS

Postmarketing Experience

Skin and Subcutaneous Tissue Disorders

  • Severe skin and hypersensitivity reactions including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

PATIENT COUNSELING INFORMATION

  • Patients should be informed that skin reactions ranging from mild to severe, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported with COMPLERA. Instruct patients to immediately stop taking COMPLERA and seek medical attention if they develop a rash associated with any of the following symptoms: fever, blisters, mucosal involvement, eye inflammation (conjunctivitis), severe allergic reaction causing swelling of the face, eyes, lips, mouth, tongue or throat which may lead to difficulty swallowing or breathing, and any signs and symptoms of liver problems, as they may be a sign of a more serious reaction. Patients should understand that if severe rash occurs, they will be closely monitored, laboratory tests will be performed and appropriate therapy will be initiated [See Warnings and Precautions (5.3)].

 

June 2014

Summary View

WARNINGS AND PRECAUTIONS

Coadministration with Other Products
  • Complera should not be administered with rilpivirine (Edurant) unless needed for dose adjustment (e.g., with rifabutin).

DRUG INTERACTIONS

  • Table 4 Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction:
  • (* Table 4- addition of rifabutin under Antimycobacterials )
Drugs with No Observed or Predicted Interactions with Complera
  • …No clinically significant drug interactions… Rilpivirine did not have a clinically significant effect on the pharmacokinetics of digoxin or metformin… 

PATIENT COUNSELING INFORMATION

  • For patients receiving rifabutin, an additional 25 mg tablet of rilpivirine (Edurant) once per day is recommended to be taken concomitantly with COMPLERA and with a meal for the duration of rifabutin coadministration.

Patient Information

  • If you take Complera, you should not take:
  • ….rilpivirine (Edurant), unless recommended by your healthcare provider and you are taking rifabutin (Mycobutin®)

Especially tell your healthcare provider if you take:

  • rifabutin (Mycobutin), a medicine to treat some bacterial infections. Talk to your doctor or pharmacist about the right amount of rilpivirine you should take. 

 

January 2013

Summary View

4 CONTRAINDICATIONS

  • added ..... proton pump inhibitors, such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole

5 WARNINGS AND PRECAUTIONS

5.5 Depressive Disorders
  • ... Suicidal ideation was reported in 4 subjects in each arm while suicide attempt was reported in 2 subjects in the rilpivirine arm...
5.6  Hepatotoxicity (new section added)
  • Hepatic adverse events have been reported in patients receiving a rilpivirine containing regimen. Patients with underlying hepatitis B or C, or marked elevations in serum liver biochemistries prior to treatment may be .....

6 ADVERSE REACTIONS

6.1 Adverse Reactions from Clinical Trials Experience
  • Studies C209 and C215 – Treatment-Emergent Adverse Drug Reactions
  • multiple section changes with data from week 96 pooled data
6.2 Postmarketing Experience
  • Rilpivirine: Renal and Urinary Disorders, nephrotic syndrome

8 USE IN SPECIFIC POPULATIONS

8. Nursing Mothers
  • Emtricitabine: Samples of breast milk obtained from five HIV-1 infected mothers show that emtricitabine is secreted in human milk. Breastfeeding infants whose mothers are being treated with emtricitabine may be at risk for developing viral resistance to emtricitabine. Other emtricitabine-associated risks in infants breastfed by mothers being treated with emtricitabine are unknown.
  • Rilpivirine: Studies in lactating rats and their offspring indicate that rilpivirine was present in rat milk. It is not known whether rilpivirine is secreted in human milk.
  • Tenofovir Disoproxil Fumarate: Samples of breast milk obtained from five HIV-1 infected mothers in the first post-partum week show that tenofovir is excreted in human milk. The impact of this exposure in breastfed infants is unknown.

17 PATIENT COUNSELING INFORMATION

Information for Patients
  • Patients should be advised not to breastfeed because at least two of the drugs contained in COMPLERA can be passed to the baby in breast milk. It is not known whether this could harm the baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in breast milk.
  • Patients should be informed that hepatotoxicity has been reported with COMPLERA [See Warnings and Precautions (5.6)].
  • COMPLERA should not be coadministered with ATRIPLA, Edurant,  EMTRIVA, STRIBILD, TRUVADA, or VIREAD; or with drugs containing lamivudine, including Combivir, Epivir or Epivir-HBV, Epzicom, or Trizivir; or with HEPSERA [See Warnings and Precautions (5.8)]. 

 

August 2012

Summary View

WARNINGS AND PRECAUTIONS

Immune Reconstitution Syndrome
  • Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Complera…
  • Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment.

 

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