Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
PACKAGE INSERT FOR HETEMCIT  
SCHEDULING STATUS: S4  
PROPRIETARY NAME (AND DOSAGE FORM):  
HETEMCIT (Film-coated tablet)  
WARNING:  
LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, INCLUDING FATAL  
CASES, HAVE BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES ALONE  
OR IN COMBINATION WITH OTHER ANTIRETROVIRALS (SEE WARNINGS AND SPECIAL  
PRECAUTIONS).  
HETEMCIT IS NOT INDICATED FOR THE TREATMENT OF CHRONIC HEPATITIS B VIRUS  
(HBV) INFECTION. IN PATIENTS WHO ARE CO-INFECTED WITH HBV AND HAVE  
DISCONTINUED HETEMCIT, SEVERE ACUTE EXACERBATIONS OF HEPATITIS B HAVE  
BEEN REPORTED.  
IN PATIENTS CO-INFECTED WITH HBV, HEPATIC FUNCTION SHOULD BE MONITORED  
CLOSELY WITH BOTH CLINICAL AND LABORATORY FOLLOW-UP FOR AT LEAST  
SEVERAL MONTHS AFTER HETEMCIT IS DISCONTINUED. IF APPROPRIATE, INITIATION  
OF ANTI-HEPATITIS B THERAPY MAY BE WARRANTED (SEE WARNINGS AND SPECIAL  
PRECAUTIONS).  
HETEMCIT USED FOR PRE-EXPOSURE PROPHYLAXIS (PrEP) INDICATION, MUST ONLY  
BE PRESCRIBED TO INDIVIDUALS CONFIRMED TO BE HIV-NEGATIVE IMMEDIATELY  
PRIOR TO INITIATING AND PERIODICALLY (AT LEAST ONCE EVERY 3 MONTHS)  
DURING USE. RESISTANT HIV-1 VARIANTS HAVE BEEN IDENTIFIED WITH THE USE OF  
HETEMCIT FOR THE PRE-EXPOSURE PROPHYLAXIS (PrEP) INDICATION FOLLOWING  
UNDETECTED ACUTE HIV-1 INFECTION. DO NOT INITIATE HETEMCIT FOR A PRE  
EXPOSURE PROPHYLAXIS (PrEP) INDICATION IF SIGNS OR SYMPTOMS OF ACUTE HIV  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
INFECTION ARE PRESENT UNLESS NEGATIVE INFECTION STATUS IS CONFIRMED (SEE  
WARNINGS AND SPECIAL PRECAUTIONS).  
COMPOSITION:  
Each film-coated tablet contains: 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate.  
List of excipients: croscarmellose sodium, magnesium stearate, microcrystalline cellulose,  
pregelatinized starch and Opadry II Blue (coating agent).  
Opadry II Blue 32K10849 contains lactose monohydrate, HPMC 2910 / hypromellose 15cP,  
titanium dioxide, triacetin, FD & C blue #2/ indigo carmine aluminium lake.  
Contains sugar: lactose monohydrate  
PHARMACOLOGICAL CLASSIFICATION:  
20.2.8 Antimicrobial (chemotherapeutic) agents. Antiviral agents  
PHARMACOLOGICAL ACTION:  
HETEMCIT is a combination of 2 antiretroviral agents, viz. emtricitabine and tenofovir disoproxil  
fumarate which are nucleoside reverse transcriptase inhibitors (NRTI’s).  
Pharmacodynamic properties:  
Emtricitabine: Emtricitabine is a cytosine analogue. Emtricitabine enters the cells by passive  
diffusion and is phosphorylated to its active metabolite, emtricitabine 5’-triphosphate. The intracellular  
triphosphate acts as a competitive inhibitor of reverse transcriptase and is incorporated into HIV DNA  
to cause chain termination. Emtricitabine has a low affinity for human DNA polymerase.  
Tenofovir disoproxil fumarate: Tenofovir is a derivative of adenosine 5’ – monophosphate lacking  
a complete ribose ring. Tenofovir disoproxil fumarate is rapidly hydrolysed to tenofovir, and then  
undergoes phosphorylation by cellular kinases to form tenofovir diphosphate, the active metabolite.  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
Tenofovir diphosphate is a competitive inhibitor of viral reverse transcriptase by competing with the  
natural substrate deoxyadenosine 5’-triphosphate. It is incorporated into HIV DNA to cause chain  
termination due to its incomplete ribose ring. Although tenofovir diphosphate has a broad spectrum  
of activity against viral DNA polymerases, it has low affinity for human DNA polymerases - α, β and  
y.  
Resistance and cross-resistance:  
Emtricitabine: High level resistance to emtricitabine occurs with the mutation of methionine to valine  
substitution at codon 184(M184V).This same mutation occurs with lamivudine, although this appears  
to occur less frequently with emtricitabine. The M184V mutation restores zidovudine susceptibility to  
zidovudine-resistant HIV and also partially restores tenofovir susceptibility to tenofovir-resistant HIV  
harbouring the K65R mutation. The K65R mutation confers resistance to emtricitabine and other  
cytosine analogues.  
Tenofovir disoproxil fumarate: Viral replication in the presence of suboptimal concentrations of  
tenofovir can select for mutations that confer resistance. A single substitution at codon 65 of reverse  
transcriptase K65R results in specific resistance to tenofovir, reducing in vitro sensitivity 3 to 4 fold.  
In patients harbouring HIV isolates with high-level resistance (M41L, L120W) to zidovudine or  
stavudine, sensitivity to tenofovir and virologic efficacy are also reduced. Only partial resistance to  
tenofovir is apparent in HIV variants that are resistant to zidovudine. Susceptibility in tenofovir-  
resistant HIV harbouring the K65R mutation is partially restored in M18V mutations associated with  
lamivudine or emtricitabine.  
In initial clinical studies, the K65R mutation was reported in only 2 to 3 % of patients treated with  
tenofovir, and was not usually associated with treatment failure. Treatment failure in tenofovir-  
containing regimens is most likely associated with genotypic resistance to other medicines in the  
regimen.  
Pharmacokinetic properties:  
Emtricitabine:  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
Absorption: Emtricitabine has an oral bioavailability of 93 % and is rapidly absorbed. The AUC is not  
affected by food, while Cmax is reduced by food, emtricitabine can however be taken without regard  
to food.  
Protein binding: Emtricitabine is not significantly bound to plasma proteins.  
Elimination: Emtricitabine is excreted primarily unchanged in the urine, undergoing glomerular  
filtration and tubular secretion. Relative to other nucleoside analogues, emtricitabine has a slow  
systemic clearance and a long elimination half-life of 8 to 10 hours. In addition the estimated half-life  
of the intracellular triphosphate is very long (up to 39 hours) therefore affording the rationale for a  
once-daily dosing of this agent.  
Tenofovir disoproxil fumarate:  
Absorption: The oral bioavailability of tenofovir disoproxil fumarate is 25 %. The oral bioavailability is  
increased to 39 % following intake with a high-fat meal, but  
it can be taken without regard to food.  
Protein binding: Plasma protein binding of tenofovir is not significant.  
Elimination: The plasma elimination half-life of tenofovir is 14 to 17 hours; the intracellular elimination  
half-life of tenofovir triphosphate is 11 to 49 hours. This is the reason once-daily dosing is possible.  
Tenofovir is eliminated by both glomerular filtration and active tubular secretion; 70 to 80 % of  
tenofovir is eliminated unchanged in the urine. In patients with renal insufficiency, doses should be  
decreased.  
INDICATIONS:  
•
•
HETEMCIT is indicated for the treatment of HIV-1 infection in adults, in combination with  
other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or  
protease inhibitors).  
HETEMCIT is indicated in combination with safer sex practices for pre-exposure  
prophylaxis (PrEP) in proven HIV-1 uninfected adults to reduce the risk of sexually  
acquired HIV-1 in adults at high risk, provided maximum treatment compliance can be  
monitored.  
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Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
CONTRAINDICATIONS:  
HETEMCIT is contraindicated in patients with previously demonstrated hypersensitivity to any of  
the compounds of HETEMCIT.  
•
•
•
Pregnancy and lactation.  
Creatinine CL < 60 ml/min when used for PrEP.  
Creatinine CL < 50 ml/min when used for treatment of HIV-1.  
HETEMCIT should not be co-administered with other tenofovir-containing products, or with other  
emtricitabine-containing products. HETEMCIT should not be administered with lamivudine-  
containing products due to similarities between emtricitabine and lamivudine.  
HETEMCIT should not be used for Pre-Exposure Prophylaxis (PrEP) in individuals with unknown or  
positive HIV-1 status.  
HETEMCIT should not be used for PrEP in individuals not fully committed to full treatment  
compliance.  
WARNINGS AND SPECIAL PRECAUTIONS:  
•
•
•
There are no study results demonstrating the effect of HETEMCIT on clinical progression of  
HIV-1.  
It is not recommended that HETEMCIT be used as a component of a triple nucleoside  
regimen.  
Individuals should be warned that full compliance with treatment is  
essential to the efficacy in preventing HIV-1 transmission and should be fully informed  
about the use of other preventative measures including barrier contraception (condoms).  
Individuals not fully committed or trusted to be treatment-compliant should not use  
HETEMCIT for HIV-1 transmission prophylaxis.  
Lactic acidosis/severe hepatomegaly with steatosis  
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Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported  
with the use of nucleoside analogues such as HETEMCIT alone or in combination with other  
antiretrovirals. This is caused by mitochondrial dysfunction. A majority of these cases have been in  
women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should  
be exercised when administering nucleoside analogues such as HETEMCIT to any patient with  
known risk factors for liver disease; however, cases have also been reported in patients with no  
known risk factors. Treatment with HETEMCIT should be suspended in any patient who develops  
clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may  
include hepatomegaly and steatosis even in the absence of marked transaminase elevations).  
Clinical features are non-specific, and include nausea, vomiting, abdominal pain, dyspnoea, fatigue  
and weight loss. In patients with suspicious symptoms or biochemistry, measure the venous lactate  
level (normal < 2 mmol/l) and the serum bicarbonate and respond as follows:  
•
Lactate 2 to 5 mmol/l with minimum symptoms: Switch to medicines  
that are less likely to cause lactic acidosis.  
•
Lactate 5 to 10 mmol/l with symptoms and/or with reduced standard bicarbonate: Stop  
HETEMCIT and change treatment option. Once lactate has settled, use medicines that are  
less likely to cause lactic acidosis. Exclude other causes (e.g. sepsis, uraemia, diabetic  
ketoacidosis, thyrotoxicosis and hyperthyroidism).  
•
Lactate > 10 mmol/l: STOP all therapy (80 % mortality).  
The above lactate values may not be applicable to paediatric patients. Caution should be exercised  
when administering HETEMCIT to patients with known risk factors for liver disease.  
Treatment with HETEMCIT should be suspended in any patient who develops clinical or laboratory  
findings suggestive of lactic acidosis or hepatotoxicity.  
Pancreatitis  
Pancreatitis has been observed in some patients receiving HETEMCIT.  
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Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
Pancreatitis must be considered whenever a patient develops abdominal pain, nausea, vomiting or  
elevated biochemical markers. Discontinue use of HETEMCIT until diagnosis of pancreatitis is  
excluded.  
Liver disease  
Use of HETEMCIT can result in hepatomegaly due to non-alcoholic fatty liver disease (hepatic  
steatosis). The safety and efficacy of HETEMCIT has not been established in patients with  
significant underlying liver disorders/diseases. Patients with pre-existing liver dysfunction including  
chronic active hepatitis have an increased frequency of liver function abnormalities during  
combination antiretroviral therapy and should be monitored. If there is evidence of worsening liver  
disease in such patients, temporary or permanent discontinuation of treatment must be considered.  
Mitochondrial dysfunction  
Nucleoside and nucleotide analogues such as HETEMCIT have been demonstrated in vitro and in  
vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial  
dysfunction in HIV negative infants exposed in utero and/or post-natally to nucleoside analogues.  
Apart from lactic acidosis/hyperlactataemia (see above), other manifestations of mitochondrial  
dysfunction include haematological disorders (anaemia, neutropenia), and peripheral neuropathy.  
Some late-onset neurological disorders have been reported (hypertonia, convulsion, abnormal  
behaviour). It is not known whether the neurological disorders are transient or permanent. Any  
foetus exposed in utero to nucleoside and nucleotide analogues, even HIV negative  
infants/children, should have clinical and laboratory follow-up and should be fully investigated for  
possible mitochondrial dysfunction in case of relevant signs and symptoms.  
Patients with HIV and Hepatitis B or C Virus co-infection  
Patients with chronic hepatitis B or C and treated with antiretroviral therapy such as HETEMCIT,  
are at an increased risk for severe and potentially fatal hepatic adverse reactions. Patients co-  
infected with HBV to discontinue HETEMCIT, should be closely monitored with both clinical and  
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Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
laboratory follow-up after stopping treatment. Medical practitioners should refer to current HIV  
treatment guidelines for the optimal management of HIV infection in patients co-infected with  
hepatitis B virus (HBV). HETEMCIT is not indicated for the treatment of chronic HBV infection and  
the safety and efficacy of HETEMCIT have not been established in patients co-infected with HBV  
and HIV.  
In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant  
package inserts for these medicines. In patients with advanced liver disease or cirrhosis, treatment  
discontinuation is not recommended since post-treatment exacerbation of hepatitis may lead to  
hepatic decompensation.  
Discontinuation of HETEMCIT therapy in patients co-infected with HIV and HBV may be associated  
with severe, acute exacerbations of hepatitis which may lead to liver decompensation and liver  
failure.  
It is recommended that all patients with HIV be tested for the presence of chronic hepatitis B virus  
(HBV) before initiating HETEMCIT therapy. Hepatic function should be monitored closely with both  
clinical and laboratory follow-up for at least several months in patients who are co-infected with HIV  
and HBV and discontinue HETEMCIT. If appropriate, initiation of anti-hepatitis B therapy may be  
warranted.  
Renal impairment  
HETEMCIT is mainly eliminated by the kidney.  
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury  
with severe hypophosphatemia), has been reported in association with the use of tenofovir  
disoproxil fumarate (see CONTRAINDICATIONS).  
It is recommended that creatinine clearance be calculated in all patients prior  
to initiating therapy and as clinically appropriate during therapy with HETEMCIT. Routine  
monitoring of calculated creatinine clearance and serum phosphorus should be performed in  
patients at risk for renal impairment (see CONTRAINDICATIONS).  
HETEMCIT should be avoided with concurrent or recent use of a nephrotoxic medicine.  
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Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
HETEMCIT should not be administered to patients with creatinine clearance below 50 ml/min or  
patients requiring haemodialysis or for pre-exposure prophylaxis in patients with creatinine  
clearance below 60 ml/min (see CONTRAINDICATIONS).  
If a decrease in creatinine clearance is observed in uninfected individuals while using HETEMCIT  
for PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use  
(see CONTRAINDICATIONS).  
Interactions  
HETEMCIT is a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate.  
HETEMCIT should not be co-administered with other medicines containing emtricitabine or  
tenofovir (see CONTRAINDICATIONS).  
Due to similarities between emtricitabine and lamivudine, HETEMCIT should not be co-  
administered with other medicines containing lamivudine, including lamivudine and zidovudine co-  
formulation, lamivudine for HIV, lamivudine for HBV, abacavir sulfate and lamivudine co-formulation  
or abacavir sulfate, lamivudine and zidovudine co-formulation (see CONTRAINDICATIONS).  
Co-administration of didanosine buffered tablet formulation with HETEMCIT should be under fasted  
conditions (see INTERACTIONS).  
Co-administration of HETEMCIT and didanosine should be undertaken with  
caution and patients receiving this combination should be monitored closely for didanosine-  
associated adverse events. Didanosine should be discontinued in patients who develop  
didanosine-associated adverse events (see SIDE EFFECTS).  
Patients receiving atazanavir and lopinavir/ritonavir and HETEMCIT should be monitored for  
HETEMCIT-associated adverse events. HETEMCIT should be discontinued in patients who  
develop HETEMCIT-associated adverse events (see SIDE EFFECTS)  
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Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
Tenofovir decreases the AUC and Cmin of atazanavir (see INTERACTIONS). When co-administered  
with HETEMCIT, it is recommended that atazanavir 300 mg is given with ritonavir 100 mg.  
Atazanavir without ritonavir should not be co-administered with HETEMCIT.  
Since emtricitabine and tenofovir are primarily eliminated by the kidneys, co-administration of  
HETEMCIT with medicines that reduce renal function or compete for active tubular secretion may  
increase serum concentrations of emtricitabine, tenofovir, and/or other renally eliminated medicines  
(see INTERACTIONS). Some examples include, but are not limited to adefovir dipivoxil, cidofovir,  
aciclovir, valaciclovir, ganciclovir and valganciclovir.  
Lipodystrophy and metabolic abnormalities  
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement  
(buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid  
appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and  
long term consequences of these events are currently unknown. A causal relationship has not been  
established.  
Clinical examination should include evaluation for physical signs of fat redistribution. Patients with  
evidence of lipodystrophy should have a thorough cardiovascular risk assessment.  
Immune reconstitution inflammatory syndrome  
Immune reconstitution inflammatory syndrome (IRIS) is an immunopathological response resulting  
from the rapid restoration of pathogen-specific immune responses to pre-existing antigens  
combined with immune dysregulation, which occurs shortly after starting combination Anti-  
Retroviral Therapy (cART). Typically such reaction presents by paradoxical deterioration of  
opportunistic infections being treated or with unmasking of an asymptomatic opportunistic disease,  
often with an atypical inflammatory presentation. IRIS usually develops within the first three months  
of initiation of ART and occurs more commonly in patients with low CD4 counts. Common  
examples of IRIS reactions to opportunistic diseases are pulmonary tuberculosis, cytomegalovirus  
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Product proprietary name: HETEMCIT  
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retinitis, Pneumocystis jirovecii pneumonia (PCP), cryptococcal meningitis and other forms of  
tuberculosis and atypical myco-bacterial infections. Appropriate treatment of the opportunistic  
disease should be instituted or continued and ART continued. Inflammatory manifestations  
generally subside after a few weeks. Severe cases may respond to glucocorticoids, but there is  
only limited evidence for this in patients with tuberculosis IRIS.  
Autoimmune disorders (such as Graves' disease) have also been reported as IRIS reactions;  
however, the reported time to onset is more variable and these events can occur many months  
after initiation of treatment.  
Osteonecrosis  
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol  
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have  
been reported, particularly in patients with advanced HIV-disease and/or long-term exposure to  
combination antiretroviral therapy (cART). Patients should be advised to seek medical advice if  
they experience joint aches and pain, joint stiffness or difficulty in movement.  
Bone mineral density  
During therapy with HETEMCIT assessment of bone mineral density (BMD) should be considered  
for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or  
bone loss. The effect of supplementation with calcium and vitamin D was not studied. If bone  
abnormalities are suspected then appropriate consultation should be obtained. Bone mineral  
density monitoring should be considered for HIV infected patients who have a history of pathologic  
bone fracture or are at risk for osteopenia. Tenofovir combination therapy is associated with  
decreased bone mineral density.  
In clinical trials of HIV-1 uninfected individuals, decreases in BMD were also observed. In a pre-  
exposure trial of men having sex with men (MSM), a sub study of 503 subjects found mean  
changes from baseline in BMD ranging from -0,4 % to -1,0 % across total hip, spine, femoral neck,  
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and trochanter in the HETEMCIT group compared with the placebo group. Bone fractures were  
reported in 1,7 % of the HETEMCIT group compared with 1,4 % in the placebo group. No  
correlation between BMD and fractures was noted. A pre-exposure study in heterosexual couples  
where one of the partners was HIV-1 infected, found similar fracture rates between treatment and  
placebo groups (0,8 % and 0,6 %, respectively). No BMD evaluations were conducted during this  
trial.  
Cases of osteomalacia (associated with proximal renal tubulopathy) have been reported in  
association with the use of tenofovir DF, such as HETEMCIT (see SIDE EFFECTS).  
Opportunistic infections  
Patients receiving HETEMCIT should be advised that they may continue to develop opportunistic  
infections and other complications of HIV infection, and therefore they should remain under close  
observation by healthcare professionals experienced in the treatment of patients with associated  
HIV disease. Regular monitoring of viral load and CD4 counts needs to be done.  
The risk of HIV transmission to others  
Patients should be advised that current antiretroviral therapy, including HETEMCIT, does not  
prevent the risk of transmission of HIV-1 to others through sexual contact or blood contamination.  
Appropriate precautions should continue to be employed.  
Comprehensive management to reduce the risk of acquiring HIV-1  
Use HETEMCIT for pre-exposure prophylaxis only as part of a comprehensive prevention strategy  
that includes other prevention measures, such as safer sex practices, because HETEMCIT is not  
always effective in preventing the acquisition of HIV-1.  
•
Counsel uninfected individuals about safer sex practices that include consistent and correct  
use of condoms, knowledge of their HIV-1 status and that of their partner(s), and regular  
testing for other sexually  
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transmitted infections that can facilitate HIV-1 transmission (such a syphilis and  
gonorrhoea).  
•
Inform uninfected individuals about and support their efforts in reducing  
sexual risk behaviour.  
Use of HETEMCIT 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 HETEMCIT, because HETEMCIT alone does not constitute a  
complete treatment regimen for HIV-1 treatment. Therefore, care should be taken to avoid  
HETEMCIT exposure in HIV-infected individuals (see CONTRAINDICATIONS).  
•
Many HIV-1 tests, such as rapid tests, detect anti-HIV antibodies and may not  
identify HIV-1 during the acute stage of infection. Prior to initiating HETEMCIT for a  
PrEP indication, evaluate seronegative individuals for current or recent signs or  
symptoms consistent with acute viral infections (e.g. fever, fatigue, myalgia, skin  
rash, etc.) and ask about potential exposure events (e.g. unprotected sex, or condom  
broken during sex with an HIV-1 infected partner) that may have occurred within the  
last month.  
•
If clinical symptoms consistent with acute viral infection are present and recent (< 1  
month) exposures are suspected, delay starting PrEP for at least one month and  
reconfirm HIV-1 status or  
use an approved test as an aid in the diagnosis of HIV-1 infection,  
including acute or primary HIV-1 infection.  
•
While using HETEMCIT for a PrEP indication, HIV-1 screening tests should be  
repeated at least once every 3 months. If symptoms consistent with acute HIV-1  
infection develop following a potential exposure event, PrEP should be discontinued  
until negative infection status is confirmed using an approved test as an aid in the  
diagnosis of HIV-1, including acute or primary HIV-1 infection.  
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Counsel uninfected individuals to strictly adhere to the recommended HETEMCIT dosing schedule.  
The effectiveness of HETEMCIT in reducing the risk of acquiring HIV-1 is strongly correlated with  
adherence as demonstrated by measurable drug levels in clinical trials.  
Early virologic failure  
Clinical trials in HIV-1 infected patients have demonstrated that certain regimens that only contain  
three nucleoside reverse transcriptase inhibitors (NRTIs) are generally less effective than regimens  
containing two NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor or  
a HIV-1 protease inhibitor. In particular, early virological failure and high rates of resistance  
substitutions have been reported.  
Triple nucleoside regimens should therefore be used with caution. Patients on a therapy utilising a  
triple nucleoside-only regimen should be carefully monitored and considered for treatment  
modification.  
Paediatric use  
Safety and effectiveness in paediatric patients have not been established.  
Geriatric use  
Clinical studies of emtricitabine (200 mg) or tenofovir DF did not include sufficient numbers of  
subjects aged 65 and over to determine whether they respond differently from younger subjects. In  
general, dose selection for the elderly patients should be cautious, keeping in mind the greater  
frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other  
drug therapy.  
Lactose warning  
HETEMCIT contains lactose monohydrate. Patients with rare hereditary problems of galactose  
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this  
medicine.  
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Effects on ability to drive and use machines  
No studies on the effects of either tenofovir disoproxil fumarate or emtricitabine on the ability to  
drive and use machines have been performed. However dizziness has been reported during  
treatment with both tenofovir disoproxil fumarate and emtricitabine.  
INTERACTIONS:  
Studies have shown the potential for CYP450 mediated interactions involving emtricitabine and  
tenofovir with other medicinal products is low.  
•
HETEMCIT is primarily excreted by the kidneys by a combination of glomerular filtration  
and active tubular secretion. No interactions due to competition for renal excretion have  
been observed; however; co-administration of HETEMCIT with medicines that are  
eliminated by active tubular secretion may increase concentrations of emtricitabine and/or  
tenofovir.  
The serum concentration of those agents eliminated by active tubular  
secretion or HETEMCIT may be increased.  
•
Any interactions that have been identified with emtricitabine and tenofovir individually may  
occur with HETEMCIT. As HETEMCIT is a combination product of emtricitabine and  
tenofovir, it should not be co-administered with either tenofovir or emtricitabine individually.  
The interactions listed below should not be considered exhaustive but  
are representative of the classes of medicines where caution should be  
exercised.  
•
•
Famciclovir and stavudine: no clinically significant medicine interactions have been  
observed when emtricitabine was used in combination with these agents.  
Lamivudine or products containing lamivudine: should not be co-administered due to  
similarities between emtricitabine and lamivudine. Furthermore the Cmax of lamivudine is  
decreased with tenofovir co-administration.  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
•
Indinavir: no clinically significant medicine interactions have been observed with  
emtricitabine; however concurrent administration of indinavir and tenofovir resulted in an  
increase of tenofovir Cmax and a decrease in indinavir Cmax.  
•
•
Abacavir: co-administration of abacavir and tenofovir resulted in an increase of Cmax of  
abacavir.  
Atazanavir: concurrent use of atazanavir and HETEMCIT may result in increased  
concentration of tenofovir and a decrease in the AUC and Cmin of atazanavir. It is  
recommended that atazanavir not administered with HETEMCIT.  
Lopinavir/ritonavir: an increase in tenofovir concentration has been demonstrated with  
co-administration of lopinavir/ritonavir. Patients should be monitored for emtricitabine or  
tenofovir associated adverse events and discontinued in those patients who develop these  
adverse events.  
•
•
Didanosine: concurrent use of didanosine and HETEMCIT should be undertaken with  
caution as didanosine concentrations are increased significantly. The adverse events  
associated with didanosine, including pancreatitis and neuropathy could therefore be  
potentiated. Patients must be closely monitored for these adverse events and dose  
adjustments may be required.  
Acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir or valganciclovir: concurrent  
administration of HETEMCIT and these agents or agents that are renally eliminated may increase  
serum concentrations of emtricitabine, tenofovir or the concurrently administered agent due to  
competition for this elimination pathway.  
PREGNANCY AND LACTATION:  
Pregnancy: Safety in pregnancy has not been established, as adequate and well-controlled  
studies have not been done in pregnant women.  
Lactation: HIV-infected mothers should not breast-feed their infants, to avoid risking  
postnatal transmission of HIV. Studies in rats have demonstrated that tenofovir is secreted in  
milk. It is not known whether tenofovir is excreted in human milk, it is not known if emtricitabine is  
Initial K.B  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
excreted in human milk. Because of both the potential for HIV transmission and the potential for  
serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if  
they receiving HETEMCIT.  
DOSAGE AND DIRECTIONS FOR USE:  
Adults:  
The recommended dose is one tablet of HETEMCIT (emtricitabine 200 mg and tenofovir 300 mg)  
taken once daily, with or without food.  
PrEP in HIV-1 uninfected adults: One tablet once daily with or without food; do not use if CrCl  
<60 ml/min (see CONTRAINDICATIONS).  
Paediatric use:  
Safety and efficacy in patients less than 18 years of age have not been established.  
Dose Adjustment for Renal Impairment:  
Significantly increased exposure occurred when emtricitabine (200 mg) or tenofovir were  
administered to patients with moderate to severe renal impairment (see CONTRAINDICATIONS).  
SIDE EFFECTS:  
Emtricitabine and Tenofovir Disoproxil Fumarate  
Frequencies are defined as follows: very common ≥ 10 %; common ≥ 1 % and < 10 %; uncommon  
≥ 0,1 % and < 1 %; rare ≥ 0,01 % and < 0,1 %; very rare < 0,01 %.  
Blood and the lymphatic system disorders  
Common: Neutropenia  
The following side effects have been reported but frequencies are unknown: Anaemia  
Immune system disorders  
Common: Allergic reaction, including angioedema  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
Metabolism and nutrition disorders  
Common: Hypertriglyceridemia, hyperglycaemia  
The following side effects have been reported but frequencies are unknown: Hypophosphataemia,  
lactic acidosis, hypokalaemia  
Psychiatric disorders  
Common: Insomnia, abnormal dreams  
Nervous system disorders  
Very common: Dizziness, headache  
Respiratory, thoracic and mediastinal disorders  
Common: Dyspnoea  
Gastrointestinal disorders  
Very common: Diarrhoea, nausea, vomiting  
Common: Flatulence, dyspepsia, abdominal pain, amylase elevation, lipase elevation  
The following side effects have been reported but frequencies are unknown: Pancreatitis  
Hepato-biliary disorders  
Common: Hyperbilirubinemia, increased liver enzymes (including increased AST, increased ALT  
and/or gamma GT)  
The following side effects have been reported but frequencies are unknown: Hepatitis, hepatic  
steatosis  
Skin and subcutaneous tissue disorders  
Common: Rash event (rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular  
rash), skin discoloration  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
Musculoskeletal, connective tissue and bone disorders  
Very common: Creatine kinase elevation  
The following side effects have been reported but frequencies are unknown: Myopathy,  
osteomalacia (both associated with proximal renal tubulopathy), rhabdomyolysis, muscular  
weakness  
Renal and urinary disorders  
The following side effects have been reported but frequencies are unknown: Increased creatinine,  
renal insufficiency, renal failure, acute renal failure, Fanconi syndrome, proximal tubulopathy,  
nephrogenic diabetes insipidus, proteinuria, acute tubular necrosis, polyuria, interstitial nephritis  
(including acute cases)  
General disorders and administrative site conditions  
Common: Pain, asthenia  
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:  
There is limited clinical experience of acute over dosage with HETEMCIT. Contact a poison control  
centre for further management of overdose or unintentional ingestion.  
Treatment of an overdose is essentially symptomatic and supportive.  
Patients must be monitored for toxicity and standard supportive measures must be applied.  
To enhance elimination of emtricitabine and tenofovir, haemodialysis is used.  
IDENTIFICATION:  
HETEMCIT: Blue, capsule shaped, film-coated tablets, debossed with 'H' on one side and '124' on  
the other side.  
PRESENTATION:  
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Applicant/PHRC: Hetero Drugs SA (Pty) Ltd  
Product proprietary name: HETEMCIT  
Dosage form and strength: Film-coated tablet; emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg  
HETEMCIT is packed in round white HDPE containers, with desiccant and closed with a white, child  
resistant cap/Continuous thread cap with pulp liner, in packs of 28’s, 30’s or 56’s or 60’s tablets.  
STORAGE INSTRUCTIONS:  
Store at or below 30 ºC in tightly closed containers.  
Protect from light and moisture. Keep in the original container.  
KEEP OUT OF REACH OF CHILDREN  
REGISTRATION NUMBER:  
47/20.2.8/0232  
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE  
OF REGISTRATION:  
Hetero Drugs South Africa (Pty) Ltd.,  
Waterfall Corporate Campus,  
Building 2, First Floor,  
74 Waterfall Drive, Midrand, 2066  
DATE OF PUBLICATION OF THE PACKAGE INSERT:  
29 September 2017  
DATE OF REVISION OF THE TEXT  
31 July 2022  
Initial K.B  
20/06/2022  
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