Truvada (Page 2 of 10)

4 CONTRAINDICATIONS

TRUVADA for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status [see Warnings and Precautions (5.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Severe Acute Exacerbation of Hepatitis B in Individuals with HBV Infection

All individuals should be tested for the presence of chronic hepatitis B virus (HBV) before or when initiating TRUVADA [see Dosage and Administration (2.1)].

Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in HBV-infected individuals who have discontinued TRUVADA. Individuals infected with HBV who discontinue TRUVADA should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, anti-hepatitis B therapy may be warranted, especially in individuals with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure. HBV-uninfected individuals should be offered vaccination.

5.2 Comprehensive Management to Reduce the Risk of Sexually Transmitted Infections, Including HIV-1, and Development of HIV-1 Resistance When TRUVADA Is Used for HIV-1 PrEP

Use TRUVADA for HIV-1 PrEP to reduce the risk of HIV-1 infection as part of a comprehensive prevention strategy that includes other prevention measures, including adherence to daily administration and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). The time from initiation of TRUVADA for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.

Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including but not limited to condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network.

Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use, knowledge of partner(s)’ HIV-1 status, including viral suppression status, regular testing for STIs that can facilitate HIV-1 transmission). Inform uninfected individuals about and support their efforts in reducing sexual risk behavior.

Use TRUVADA to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-negative. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only TRUVADA, because TRUVADA alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology (12.4)]; therefore, care should be taken to minimize the risk of initiating or continuing TRUVADA before confirming the individual is HIV-1 negative.

  • Some HIV-1 tests only detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating TRUVADA for HIV-1 PrEP, ask seronegative individuals about recent (in past month) potential exposure events (e.g., condomless sex or condom breaking during sex with a partner of unknown HIV-1 status or unknown viremic status, or a recent STI), and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash).
  • If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection.

While using TRUVADA for HIV-1 PrEP, HIV-1 testing should be repeated at least every 3 months, and upon diagnosis of any other STIs.

  • If an HIV-1 test indicates possible HIV-1 infection, or if symptoms consistent with acute HIV-1 infection develop following a potential exposure event, convert the HIV-1 PrEP regimen to an HIV treatment regimen until negative infection status is confirmed using a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection.

Counsel HIV-1 uninfected individuals to strictly adhere to the once daily TRUVADA dosing schedule. The effectiveness of TRUVADA in reducing the risk of acquiring HIV-1 is strongly correlated with adherence, as demonstrated by measurable drug levels in clinical trials of TRUVADA for HIV-1 PrEP. Some individuals, such as adolescents, may benefit from more frequent visits and counseling to support adherence [see Use in Specific Populations (8.4), Microbiology (12.4), and Clinical Studies (14.3 and 14.4)].

5.3 New Onset or Worsening Renal Impairment

Emtricitabine and tenofovir are principally eliminated by the kidney. Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported with the use of TDF, a component of TRUVADA [see Adverse Reactions (6.2)].

Prior to initiation and during use of TRUVADA, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all individuals. In individuals with chronic kidney disease, also assess serum phosphorus.

TRUVADA should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs [NSAIDs]) [see Drug Interactions (7.1)]. Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in HIV-infected patients with risk factors for renal dysfunction who appeared stable on TDF. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction.

Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in individuals at risk of renal dysfunction.

Treatment of HIV-1 Infection

Dosing interval adjustment of TRUVADA and close monitoring of renal function are recommended in all patients with estimated creatinine clearance 30–49 mL/min [see Dosage and Administration (2.6)]. No safety or efficacy data are available in patients with renal impairment who received TRUVADA using these dosing guidelines, so the potential benefit of TRUVADA therapy should be assessed against the potential risk of renal toxicity. TRUVADA is not recommended in patients with estimated creatinine clearance below 30 mL/min or patients requiring hemodialysis.

HIV-1 PrEP

TRUVADA for HIV-1 PrEP is not recommended in uninfected individuals with estimated creatinine clearance less than 60 mL/min. If a decrease in estimated creatinine clearance is observed while using TRUVADA for HIV-1 PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use [see Dosage and Administration (2.6)].

5.4 Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in HIV-1 infected patients treated with combination antiretroviral therapy, including TRUVADA. During the initial phase of combination antiretroviral treatment, HIV-1 infected patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) 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.

5.5 Bone Loss and Mineralization Defects

Bone Mineral Density

In clinical trials in HIV-1 infected adults and in a clinical trial of HIV-1 uninfected individuals, TDF (a component of TRUVADA) was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggesting increased bone turnover relative to comparators [see Adverse Reactions (6.1)]. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher in subjects receiving TDF.

Clinical trials evaluating TDF in pediatric and adolescent subjects were conducted. Under normal circumstances, BMD increases rapidly in pediatric patients. In HIV-1 infected subjects aged 2 years to less than 18 years, bone effects were similar to those observed in adult subjects and suggest increased bone turnover. Total body BMD gain was less in the TDF-treated HIV-1 infected pediatric subjects as compared to the control groups. Similar trends were observed in adolescent subjects aged 12 years to less than 18 years treated for chronic hepatitis B. In all pediatric trials, skeletal growth (height) appeared to be unaffected.

The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. Assessment of BMD should be considered for adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial. If bone abnormalities are suspected, appropriate consultation should be obtained.

Mineralization Defects

Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with TDF use [see Adverse Reactions (6.1)]. Arthralgia and muscle pain or weakness have also been reported in cases of proximal renal tubulopathy. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms while receiving TDF-containing products [see Warnings and Precautions (5.3)].

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