Chemical formula: C₈H₁₀FN₃O₃S Molecular mass: 247.043 g/mol
Emtricitabine interacts in the following cases:
Emtricitabine is eliminated by renal excretion and exposure to emtricitabine was significantly increased in patients with renal insufficiency. Dose or dose interval adjustment is required in all patients with creatinine clearance <30 ml/min.
The table below provides dose interval adjustment guidelines according to the degree of renal insufficiency. The safety and efficacy of the dose interval adjustments to every 72 or 96 hours in patients with creatinine clearance <30 ml/min have not been clinically evaluated. Therefore, clinical response to treatment and renal function should be closely monitored in these patients.
Dose interval guidelines adjusted according to creatinine clearance:
| \<>_.Creatinine Clearance (CLcr) (ml/min) | ||
| 15-29 | <15 (functionally anephric, requiring intermittent haemodialysis)* | |
| Recommended dose interval for 200 mg hard capsules | One 200 mg hard capsule every 72 hours | One 200 mg hard capsule every 96 hours |
| Recommended dose of emtricitabine 10 mg/mL oral solution every 24 hours | 80 mg (8 mL) | 60 mg (6 mL) |
* Assumes a 3h haemodialysis session three times a week commencing at least 12h after administration of the last dose of emtricitabine.
Patients with end-stage renal disease (ESRD) managed with other forms of dialysis such as ambulatory peritoneal dialysis have not been studied and no dose recommendations can be made.
Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine. There have been reports of mitochondrial dysfunction in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues; these have predominantly concerned treatment with regimens containing zidovudine. The main adverse reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipasemia). These events have often been transitory. Late onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are transient or permanent is currently unknown. These findings should be considered for any child exposed in utero to nucleos(t)ide analogues, who present with severe clinical findings of unknown etiology, particularly neurologic findings. These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
There is no clinical experience as yet on the co-administration of cytidine analogues. Consequently, the use of emtricitabine in combination with lamivudine for the treatment of HIV infection cannot be recommended at this time.
Emtricitabine is active in vitro against HBV. However, limited data are available on the efficacy and safety of emtricitabine (as a 200 mg hard capsule once daily) in patients who are co-infected with HIV and HBV. The use of emtricitabine in patients with chronic HBV induces the same mutation pattern in the YMDD motif observed with lamivudine therapy. The YMDD mutation confers resistance to both emtricitabine and lamivudine.
Patients co-infected with HIV and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with emtricitabine for evidence of exacerbations of hepatitis. Such exacerbations have been seen following discontinuation of emtricitabine treatment in HBV infected patients without concomitant HIV infection and have been detected primarily by serum alanine aminotransferase (ALT) elevations in addition to re-emergence of HBV DNA. In some of these patients, HBV reactivation was associated with more severe liver disease, including decompensation and liver failure. There is insufficient evidence to determine whether re-initiation of emtricitabine alters the course of post-treatment exacerbations of hepatitis. In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended since post-treatment exacerbations of hepatitis may lead to hepatic decompensation.
A moderate amount of data on pregnant women (between 300 and 1,000 pregnancy outcomes) indicate no malformations or foetal/neonatal toxicity associated with emtricitabine. Animal studies do not indicate reproductive toxicity. The use of emtricitabine may be considered during pregnancy, if necessary.
Emtricitabine has been shown to be excreted in human milk. There is insufficient information on the effects of emtricitabine in newborns/infants. Therefore emtricitabine should not be used during breast-feeding.
In order to avoid transmission of HIV to the infant it is recommended that women living with HIV do not breast-feed their infants.
No human data on the effect of emtricitabine are available. Animal studies do not indicate harmful effects of emtricitabine on fertility.
No studies on the effects on the ability to drive and use machines have been performed. However, patients should be informed that dizziness has been reported during treatment with emtricitabine.
In clinical trials of HIV infected adults, the most frequently occurring adverse reactions to emtricitabine were diarrhoea (14.0%), headache (10.2%), elevated creatine kinase (10.2%) and nausea (10.0%). In addition to the adverse reactions reported in adults, anaemia (9.5%) and skin discolouration (31.8%) occurred more frequently in clinical trials involving HIV infected paediatric patients.
Discontinuation of emtricitabine therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis.
Assessment of adverse reactions from clinical study data is based on experience in three studies in adults (n=1,479) and three paediatric studies (n=169). In the adult studies, 1,039 treatment-naïve and 440 treatment-experienced patients received emtricitabine (n=814) or comparator medicinal product (n=665) for 48 weeks in combination with other antiretroviral medicinal products.
The adverse reactions with suspected (at least possible) relationship to treatment in adults from clinical trial and post-marketing experience are listed 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) or uncommon (≥1/1,000 to <1/100).
Summary of adverse reactions associated with emtricitabine based on clinical study and post-marketing experience:
Common: neutropenia
Uncommon: anaemia2
Common: allergic reaction
Common: hypertriglyceridaemia, hyperglycaemia
Common: insomnia, abnormal dreams
Very common: headache
Common: dizziness
Very common: diarrhoea, nausea
Common: elevated amylase including elevated pancreatic amylase, elevated serum lipase, vomiting, abdominal pain, dyspepsia
Common: elevated serum aspartate aminotransferase (AST) and/or elevated serum alanine aminotransferase (ALT), hyperbilirubinaemia
Common: vesiculobullous rash, pustular rash, maculopapular rash, rash, pruritus, urticaria, skin discolouration (increased pigmentation)1,2
Uncommon: angioedema3
Very common: elevated creatine kinase
Common: pain, asthenia
1 See section Description of selected adverse reactions for more details.
2 Anaemia was common and skin discolouration (increased pigmentation) was very common when emtricitabine was administered to paediatric patients.
3 This adverse reaction, which was identified through post-marketing surveillance, was not observed in randomised controlled clinical trials in adults or paediatric HIV clinical trials of emtricitabine. The frequency category of uncommon was estimated from a statistical calculation based on the total number of patients exposed to emtricitabine in these clinical studies (n=1,563).
Skin discolouration, manifested by hyperpigmentation mainly on the palms and/or soles, was generally mild, asymptomatic and of little clinical significance. The mechanism is unknown.
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.
Assessment of adverse reactions in paediatric patients from clinical study data is based on experience in three paediatric studies (n=169) where treatment-naïve (n=123) and treatment-experienced (n=46) paediatric HIV infected patients aged 4 months to 18 years were treated with emtricitabine in combination with other antiretroviral agents.
In addition to the adverse reactions reported in adults, the following adverse reactions were observed more frequently in paediatric patients: anaemia was common (9.5%) and skin discolouration (increased pigmentation) was very common (31.8%) in paediatric patients.
Emtricitabine has not been studied in patients over the age of 65. Elderly patients are more likely to have decreased renal function, therefore caution should be exercised when treating elderly patients with emtricitabine.
Emtricitabine is eliminated by renal excretion and exposure to emtricitabine was significantly increased in patients with renal insufficiency. Dose or dose interval adjustment is required in all patients with creatinine clearance <30 ml/min.
The adverse reaction profile in patients co-infected with HBV is similar to that observed in patients infected with HIV without co-infection with HBV. 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, exacerbations of hepatitis may occur after discontinuation of treatment.
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