Emtricitabine, Tenofovir disoproxil and Rilpivirine interacts in the following cases:
Limited data from clinical studies support once daily dosing of emtricitabine/rilpivirine/tenofovir disoproxil in patients with mild renal impairment (creatinine clearance (CrCl) 50-80 mL/min). However, long-term safety data for the emtricitabine and tenofovir disoproxil have not been evaluated in patients with mild renal impairment. Therefore, in patients with mild renal impairment emtricitabine/rilpivirine/tenofovir disoproxil should only be used if the potential benefits of treatment outweigh the potential risks.
Emtricitabine/rilpivirine/tenofovir disoproxil combination is not recommended for patients with moderate or severe renal impairment (CrCl <50 mL/min). Patients with moderate or severe renal impairment require a dose interval adjustment of emtricitabine and tenofovir disoproxil that cannot be achieved with the combination tablet
There is limited information regarding the use of emtricitabine/rilpivirine/tenofovir disoproxil in patients with moderate hepatic impairment (Child-Pugh-Turcotte (CPT) Score B). No dose adjustment of emtricitabine/rilpivirine/tenofovir disoproxil is required in patients with moderate hepatic impairment. Emtricitabine/rilpivirine/tenofovir disoproxil combination should be used with caution in patients with moderate hepatic impairment.
Emtricitabine/rilpivirine/tenofovir disoproxil has not been studied in patients with severe hepatic impairment (CPT Score C). Therefore, emtricitabine/rilpivirine/tenofovir disoproxil is not recommended in patients with severe hepatic impairment.
There are no adequate and well-controlled studies of emtricitabine/rilpivirine/tenofovir disoproxil combination or its components in pregnant women. A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) indicate no malformative or foetal/neonatal toxicity of rilpivirine. Lower exposures of rilpivirine were observed during pregnancy; therefore viral load should be monitored closely. A large amount of data on pregnant women (more than 1,000 pregnancy outcomes) indicate no malformative nor foetal/neonatal toxicity associated with emtricitabine and tenofovir disoproxil.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity with the components of emtricitabine/rilpivirine/tenofovir disoproxil.
The use of emtricitabine/rilpivirine/tenofovir disoproxil may be considered during pregnancy, if necessary.
Emtricitabine and tenofovir disoproxil are excreted in human milk. It is not known whether rilpivirine is excreted in human milk. Rilpivirine is excreted in the milk of rats.
There is insufficient information on the effects of emtricitabine/rilpivirine/tenofovir disoproxil in newborns/infants.
Because of the potential for adverse reactions in breastfed infants, women should be instructed not to breast-feed if they are receiving emtricitabine/rilpivirine/tenofovir disoproxil.
In order to avoid transmission of HIV to the infant it is recommended that women living with HIV do not breast-feed their infants.
The use of emtricitabine/rilpivirine/tenofovir disoproxil must be accompanied by the use of effective contraception.
No human data on the effect of emtricitabine/rilpivirine/tenofovir disoproxil on fertility are available. Animal studies do not indicate harmful effects of emtricitabine, rilpivirine hydrochloride or tenofovir disoproxil on fertility.
Emtricitabine/rilpivirine/tenofovir disoproxil combination has no or negligible influence on the ability to drive and use machines. However, patients should be informed that fatigue, dizziness and somnolence have been reported during treatment with the components of emtricitabine/rilpivirine/tenofovir disoproxil. This should be considered when assessing a patient’s ability to drive or operate machinery.
The combination of emtricitabine, rilpivirine and tenofovir disoproxil has been studied as the component products in treatment-naïve patients (Phase III studies C209 and C215). The single-tablet regimen (STR), emtricitabine/rilpivirine/tenofovir disoproxil, has been studied in virologically suppressed patients who switched from a regimen containing a ritonavir-boosted PI (Phase III study GS-US-264-0106) or from efavirenz/emtricitabine/tenofovir disoproxil (Phase IIb study GS-US-264-0111). In treatment-naïve patients, the most frequently reported adverse reactions considered possibly or probably related to rilpivirine hydrochloride and emtricitabine/tenofovir disoproxil were nausea (9%), dizziness (8%), abnormal dreams (8%), headache (6%), diarrhoea (5%) and insomnia (5%) (pooled data from the Phase III clinical studies C209 and C215). In virologically suppressed patients switching to emtricitabine/rilpivirine/tenofovir disoproxil, the most frequently reported adverse reactions considered possibly or probably related to emtricitabine/rilpivirine/tenofovir disoproxil were fatigue (3%), diarrhoea (3%), nausea (2%) and insomnia (2%) (48 week data from the Phase III study GS-US-264-0106). The safety profile of emtricitabine and tenofovir disoproxil in these studies was consistent with the previous experience with these agents when each was administered with other antiretroviral agents.
In patients receiving tenofovir disoproxil, rare events of renal impairment, renal failure and uncommon events of proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to bone abnormalities (infrequently contributing to fractures) have been reported. Monitoring of renal function is recommended for patients receiving emtricitabine/rilpivirine/tenofovir disoproxil.
Discontinuation of emtricitabine/rilpivirine/tenofovir disoproxil therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis.
The adverse reactions considered at least possibly related to treatment with the components of emtricitabine/rilpivirine/tenofovir disoproxil from clinical study and post-marketing experience are listed in Table 2, below, by body system organ class and frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) or rare (≥1/10,000 to <1/1,000).
Table 2. Tabulated summary of adverse reactions to emtricitabine/rilpivirine/tenofovir disoproxil based on clinical study and post-marketing experience with emtricitabine/rilpivirine/tenofovir disoproxil and its individual components:
| Frequency | Adverse reaction |
|---|---|
| Blood and lymphatic system disorders | |
| Common: | neutropenia1, decreased white blood cell count2, decreased haemoglobin2, decreased platelet count2 |
| Uncommon: | anaemia1,4 |
| Immune system disorders | |
| Common: | allergic reaction1 |
| Uncommon: | immune reactivation syndrome |
| Metabolism and nutrition disorders | |
| Very common: | increased total cholesterol (fasted)2, increased LDL-cholesterol (fasted)2, hypophosphataemia3,5 |
| Common: | hypertriglyceridaemia1,2, hyperglycaemia1, decreased appetite2 |
| Uncommon: | hypokalaemia3,5 |
| Rare: | lactic acidosis3 |
| Psychiatric disorders | |
| Very common: | insomnia1,2 |
| Common: | depression2, depressed mood2, sleep disorders2, abnormal dreams1,2 |
| Nervous system disorders | |
| Very common: | headache1,2,3, dizziness1,2,3 |
| Common: | somnolence2 |
| Gastrointestinal disorders | |
| Very common: | increased pancreatic amylase2, vomiting1,2,3, diarrhoea1,3, nausea1,2,3 |
| Common: | elevated amylase including elevated pancreatic amylase1, elevated serum lipase1,2, abdominal pain1,2,3, abdominal discomfort2, abdominal distension3, dyspepsia1, flatulence3, dry mouth2 |
| Uncommon: | pancreatitis3 |
| Hepatobiliary disorders | |
| Very common: | increased transaminases (AST and/or ALT)1,2,3 |
| Common: | increased bilirubin1,2 |
| Rare: | hepatitis3, hepatic steatosis3 |
| Skin and subcutaneous tissue disorders | |
| Very common: | rash1,2,3 |
| Common: | vesiculobullous rash1, pustular rash1, urticaria1, skin discolouration (increased pigmentation)1,4, maculopapular rash1, pruritus1 |
| Uncommon: | angioedema1,3,6, severe skin reactions with systemic symptoms7 |
| Musculoskeletal and connective tissue disorders | |
| Very common: | elevated creatine kinase1 |
| Uncommon: rhabdomyolysis3,5, muscular weakness3,5 | |
| Rare: | osteomalacia (manifested as bone pain and infrequently contributing to fractures)3,5,8, myopathy3,5 |
| Renal and urinary disorders | |
| Uncommon: | proximal renal tubulopathy including Fanconi syndrome3, increased creatinine3, proteinuria3 |
| Rare: | renal failure (acute and chronic)3, acute tubular necrosis3, nephritis (including acute interstitial nephritis)3,8, nephrogenic diabetes insipidus3 |
| General disorders and administration site conditions | |
| Very common: | asthenia1,3 |
| Common: | pain1, fatigue2 |
1 Adverse reaction identified for emtricitabine.
2 Adverse reaction identified for rilpivirine hydrochloride.
3 Adverse reaction identified for tenofovir disoproxil.
4 Anaemia was common and skin discolouration (increased pigmentation) was very common when emtricitabine was administered to paediatric patients (see Paediatric population).
5 This adverse reaction may occur as a consequence of proximal renal tubulopathy. It is not considered to be causally associated with tenofovir disoproxil in the absence of this condition.
At 96 weeks in the pooled Phase III C209 and C215 studies of treatment-naïve patients, in the rilpivirine arm the mean change from baseline in total cholesterol (fasted) was 5 mg/dL, in high-density lipoprotein (HDL)-cholesterol (fasted) 4 mg/dL, in low density lipoprotein (LDL)-cholesterol (fasted) 1 mg/dL, and in triglycerides (fasted) -7 mg/dL. At 48 weeks in Phase III study GS-US-264-0106 of virologically suppressed patients switching to emtricitabine/rilpivirine/tenofovir disoproxil from a regimen containing a ritonavir-boosted PI, the mean change from baseline in total cholesterol (fasted) was -24 mg/dL, in HDL-cholesterol (fasted) -2 mg/dL, in LDL-cholesterol (fasted) -16 mg/dL, and in triglycerides (fasted) -64 mg/dL.
As emtricitabine/rilpivirine/tenofovir disoproxil may cause renal damage, monitoring of renal function is recommended. Proximal renal tubulopathy generally resolved or improved after tenofovir disoproxil discontinuation. However, in some patients, declines in CrCl did not completely resolve despite tenofovir disoproxil discontinuation. Patients at risk of renal impairment (such as patients with baseline renal risk factors, advanced HIV disease, or patients receiving concomitant nephrotoxic medications) are at increased risk of experiencing incomplete recovery of renal function despite tenofovir disoproxil discontinuation.
Cases of lactic acidosis have been reported with tenofovir disoproxil alone or in combination with other antiretrovirals. Patients with predisposing factors such as patients with decompensated liver disease, or patients receiving concomitant medications known to induce lactic acidosis are at increased risk of experiencing severe lactic acidosis during tenofovir disoproxil treatment, including fatal outcomes.
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy.
In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of this is unknown.
Severe skin reactions with systemic symptoms have been reported during post-marketing experience with emtricitabine/rilpivirine/tenofovir disoproxil, including rashes accompanied by fever, blisters, conjunctivitis, angioedema, elevated liver function tests, and/or eosinophilia.
Insufficient safety data are available for children under the age of 18 years. emtricitabine/rilpivirine/tenofovir disoproxil is not recommended in this population.
When emtricitabine was administered to paediatric patients, the following adverse reactions were observed more frequently in addition to the adverse reactions reported in adults: anaemia was common (9.5%) and skin discolouration (increased pigmentation) was very common (31.8%) in paediatric patients (see Tabulated summary of adverse reactions).
Emtricitabine/rilpivirine/tenofovir disoproxil has not been studied in patients over the age of 65 years. Elderly patients are more likely to have decreased renal function, therefore caution should be exercised when treating elderly patients with emtricitabine/rilpivirine/tenofovir disoproxil.
Since tenofovir disoproxil can cause renal toxicity, close monitoring of renal function is recommended in any patient with renal impairment treated with emtricitabine/rilpivirine/tenofovir disoproxil.
The adverse reaction profile of emtricitabine, rilpivirine hydrochloride and tenofovir disoproxil in patients co-infected with HIV/HBV or HIV/HCV was similar to that observed in patients infected with HIV without co-infection. However, as would be expected in this patient population, elevations in AST and ALT occurred more frequently than in the general HIV infected population.
In HIV infected patients co-infected with HBV, clinical and laboratory evidence of hepatitis have occurred after discontinuation of treatment.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
