Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
PROPOSED PROFESSIONAL INFORMATION FOR TABEX  
SCHEDULING STATUS  
S4  
1 NAME OF THE MEDICINE  
TABEX 600 mg, 200 mg and 300 mg (film coated tablets)  
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 ANTI-RETROVIRALS.  
TABEX IS NOT INDICATED FOR THE TREATMENT OF CHRONIC HEPATITIS B  
VIRUS (HBV) INFECTION AND THE SAFETY AND EFFICACY OF TABEX HAVE  
NOT BEEN ESTABLISHED IN PATIENTS CO-INFECTED WITH HBV AND HIV.  
SEVERE ACUTE EXACERBATIONS OF HEPATITIS B HAVE BEEN REPORTED  
IN PATIENTS  
WHO HAVE DISCONTINUED EMTRICITABINE OR TENOFOVIR, WHICH ARE  
COMPONENTS OF TABEX. HEPATIC FUNCTION SHOULD BE MONITORED  
CLOSELY WITH BOTH CLINICAL AND LABORATORY FOLLOW-UP FOR ATLEAST  
SEVERAL MONTHS IN PATIENTS WHO ARE CO-INFECTED WITH HIV AND  
HBV AND DISCONTINUE TABEX. IF APPROPRIATE, INITIATION OF  
ANTI-HEPATITIS B THERAPY MAY BE WARRANTED.  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each film coated tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of tenofovir disoproxil  
(which is equivalent to 245 mg of tenofovir).  
TABEX is sugar free.  
This medicine contains 12 mg Sodium Lauryl Sulphate per tablet, essentially ‘sodium-free’.  
For full list of excipients, see section 6.1.  
Initials K.B  
May 2022  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
3 PHARMACEUTICAL FORM  
Film coated tablets, pink coloured, capsule shaped, debossed with “H” on one side and “128” on the other side.  
4 CLINICAL PARTICULARS  
4.1 Therapeutic indications  
TABEX is indicated for use alone as a complete regimen or in combination with other anti-retroviral medicines for the  
treatment of HIV-1 infection in adults.  
4.2 Posology and method of administration  
Posology  
Adults  
The dose of TABEX is one tablet once daily taken orally on an empty stomach. Dosing at bedtime may improve the  
tolerability of nervous system symptoms.  
Special populations  
Patients weighing less than 40 kg and presenting with long-term neuropsychiatric effects  
A dose reduction and therapeutic drug monitoring of efavirenz should be considered in patients weighing less than 40  
kg and presenting with long-term neuropsychiatric effects such as ataxia, encephalopathy, hyper- somnolence and  
coma. As a dose reduction of efavirenz, only, is not possible with TABEX, these patients should be treated with  
separate formulations of the active ingredients.  
Elderly  
TABEX should be administered with caution to elderly patients (see Section 4.4).  
Renal impairment  
Because TABEX is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment  
such as those with moderate or severe renal impairment (creatinine clearance less than 50 ml/min) (see Sections 4.4  
and 5.2).  
Initials K.B  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Hepatic impairment  
The pharmacokinetics of TABEX have not been studied in patients with hepatic impairment. TABEX is  
contraindicated in patients with severe hepatic impairment (see Section 4.3).  
Paediatric population  
TABEX is not recommended for use in patients under 18 years of age (see Section 5.2).  
Method of Administration  
TABEX tablets should be swallowed whole with water.  
TABEX is a coated tablet. It should not be chewed or broken.  
4.3 Contraindications  
•
Hypersensitivity to efavirenz, emtricitabine or tenofovir disoproxil or any of the ingredients of TABEX,  
including the excipients.  
•
TABEX should not be administered concurrently with astemizole, bepridil, cisapride, midazolam,  
pimozide, triazolam or ergot derivatives because competition for CYP3A4 by efavirenz could result in  
inhibition of metabolism of these medicines and create the potential for serious and/or life-threatening  
adverse events (e.g. cardiac dysrhythmias, prolonged sedation or respiratory depression). TABEX should  
not be administered concurrently with voriconazole because efavirenz significantly decreases  
voriconazole plasma concentrations (see Section 4.5).  
•
TABEX is contraindicated in patients with moderate to severe renal impairment [Creatinine Clearance less  
than 50 ml/min (see Sections 4.4 and 5.2).  
•
•
TABEX is contraindicated in patients with severe hepatic impairment.  
TABEX is contraindicated in patients with a history of previous liver injury/failure with efavirenz containing  
antiretroviral treatment (ARV).  
•
Pregnancy and lactation (see Section 4.6).  
4.4 Special warnings and precautions for use  
Initials K.B  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Lactic Acidosis/Severe Hepatomegaly with Steatosis  
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. 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 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 TABEX 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).  
Routine testing of serum lactate levels in asymptomatic patients on antiretroviral is not recommended. Measurement  
of serum lactate levels is recommended only for patients presenting with clinical signs or symptoms consistent with  
lactic acidosis  
Lactate 2 to 5 mmol/L: monitor regularly and be alert tor clinical signs.  
Lactate 5 to 10 mmol/L without symptoms: monitor closely.  
Lactate 5 to 10 mmol/L with symptoms: STOP all therapy. Exclude other causes (e.g. sepsis, uraemia, diabetic  
ketoacidosis, thyrotoxicosis, lymphoma).  
Lactate greater than or equal to 10 mmol/L: STOP all therapy (80 % mortality in case studies).  
Patients Co-infected with HIV and HBV  
It is recommended that all patients with HIV be tested for the presence of chronic HBV before initiating anti-retroviral  
therapy. TABEX is not indicated for the treatment of chronic HBV infection and the safety and efficacy of TABEX  
have not been established in patients co-infected with HBV and HIV. Severe acute exacerbations of hepatitis B have  
been reported in patients who are co-infected with HBV and HIV and have discontinued emtricitabine or tenofovir DF.  
In some of these patients treated with emtricitabine, the exacerbations of hepatitis B were associated with liver  
decompensation and liver failure. 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 TABEX. If  
appropriate, initiation of anti-hepatitis B therapy may be warranted.  
Co-administration with Related Medicines  
Initials K.B  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Related medicines not for co-administration with TABEX include emtricitabine, tenofovir DF, emtricitabine / tenofovir  
DF and efavirenz, which contain the same active components as TABEX. Due to similarities between emtricitabine  
and lamivudine, TABEX should not be co-administered with medicines containing lamivudine, including lamivudine /  
zidovudine, lamivudine, abacavir sulphate / lamivudine or abacavir sulphate / lamivudine / zidovudine.  
Medicine Interactions (see Section 4.5)  
Concomitant use of TABEX and St. John's Wort (Hypericum perforatum) or St. John's Wort-containing products is not  
recommended. Co-administration of NNRTIs, including efavirenz, with St. John's Wort is expected to substantially  
decrease NNRTI concentrations and may result in suboptimal levels of efavirenz and lead to loss of virologic  
response and possible resistance to efavirenz or to the class of NNRTIs.  
Co-administration of TABEX and didanosine is not recommended since exposure to didanosine is significantly  
increased following co-administration with tenofovir disoproxil that may increase the risk of didanosine-related  
adverse reactions (see Section 4.5). Rarely, pancreatitis and lactic acidosis, sometimes fatal have been reported.  
Co-administration of TABEX and sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir is not recommended  
since plasma concentrations of velpatasvir and voxilaprevir are expected to decrease following co-administration with  
efavirenz leading to reduced therapeutic effect of sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir (see  
Section 4.5).  
Psychiatric Symptoms  
Serious psychiatric adverse experiences have been reported in patients treated with efavirenz (see Section 4.8).  
Nervous System Symptoms  
Patients receiving TABEX should be alerted to the potential for additive central nervous system effects when TABEX  
is used concomitantly with alcohol or psycho-active medicines (see Section 4.5).  
Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or  
drowsiness should avoid potentially hazardous tasks such as driving or operating machinery (see Section 4.7).  
Initials K.B  
May 2022  
Page 5 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Neurotoxicity  
Efavirenz, as contained in TABEX may cause long-term neuropsychiatric effects. Severe reversible ataxia often with  
signs of encephalopathy, associated with supra-therapeutic efavirenz concentrations were reported in underweight  
women (less than 40 kg) who were probably slow metabolisers. Cases of efavirenz-induced hyper-somnolence  
resulting in coma and death and brain histology demonstrated by vacuolar axonopathy were reported. Lower doses of  
efavirenz and therapeutic drug monitoring should be considered in patients with body weight of less than 40 kg and  
patients presenting with severe and prolonged neuropsychiatric manifestations. As a dose reduction of efavirenz,  
only, is not possible with TABEX, such patients should be treated with separate formulations of the active ingredients.  
Liver failure  
There is some evidence that efavirenz is associated with three clinical pathological patterns of drug induced liver  
failure in HIV positive patients of which the sub massive necrosis histological pattern seems to be associated with a  
high morbidity/mortality risk and may present many months after therapy has been initiated or even stopped. Risk  
factors include younger age, CD4+ counts ≥ 350 cells/μL and female gender.  
Patients on TABEX or efavirenz containing antiretroviral treatment (ART) should be regularly monitored for jaundice  
(including a laboratory bilirubin and liver enzymes) and bleeding tendencies.  
Early detection and treatment of the liver failure and the immediate discontinuation of TABEX or efavirenz containing  
medicines should be stressed. Patients who discontinued treatment with TABEX should be followed up for  
symptoms/signs of liver failure for up to 12 months.  
TABEX is not recommended in patients with moderate hepatic impairment because there are insufficient data to  
determine whether dose adjustments are required. TABEX is contraindicated in patients with severe hepatic  
impairment (see Section 4.3).  
The safety and efficacy of TABEX in patients with both HIV and hepatitis 8 virus infection have not been established.  
Initials K.B  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Renal Impairment (see Section 4.2)  
Emtricitabine and tenofovir are principally eliminated by the kidney, however efavirenz is not. Since TABEX is a  
combination product and the dose of the individual components cannot be altered, patients with creatinine clearance  
less than 50 ml/min should not receive TABEX.  
140- age x mass(kg)  
CrCl (ml/min) =  
72 x serum creatinine (mg/dl)  
* For females multiply the GFR by 0,85  
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe  
hypophosphataemia), has been reported in association with the use of tenofovir DF (see Section 4.8).  
It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy and as clinically  
appropriate during therapy with TABEX. Routine monitoring of calculated creatinine clearance and serum phosphorus  
should be performed in patients at risk for renal impairment.  
TABEX should be avoided with concurrent or recent use of a nephrotoxic medicine.  
Reproductive Risk Potential  
Efavirenz may cause foetal harm when administered during the first trimester to a pregnant woman. Pregnancy  
should be avoided in women receiving TABEX. Barrier contraception should always be used in combination with  
other methods of contraception (e.g. oral or other hormonal contraceptives). Women of childbearing potential should  
undergo pregnancy testing before initiation of TABEX. If this medicine is used during the first trimester of pregnancy,  
or if the patient becomes pregnant while taking this medicine, the patient should be apprised of the potential harm to  
the foetus (see Section 4.6).  
Paediatric Use  
TABEX is not recommended for patients < 18 years of age as safety and efficacy have not been established.  
Geriatric Use  
Initials K.B  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Dose selection for the elderly patients should be cautious, due to the greater frequency of decreased hepatic, renal or  
cardiac function and of concomitant disease or other medicine therapy (see Section 4.2).  
Skin Rash  
Mild to moderate rash has been reported in patients treated with efavirenz and usually resolves with continued  
therapy. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of  
rash. TABEX can be reinitiated in patients interrupting therapy because of rash. TABEX should be discontinued in  
patients developing severe rash associated with blistering, desquamation, mucosal involvement or fever (see Section  
4.8).  
Liver Enzymes  
In patients with known or suspected history of hepatitis B or C infection and in patients treated with other medications  
associated with liver toxicity, monitoring of liver enzymes is recommended (see Section 4.4). Patients Co-infected  
with HIV and HBV). In patients with persistent elevations of serum transaminases to greater than five times the upper  
limit of the normal range, the benefit of continued therapy with TABEX needs to be weighed against the unknown  
risks of significant liver toxicity (see Section 4.8).  
Because of the extensive cytochrome P450 mediated metabolism of efavirenz and limited clinical experience in  
patients with hepatic impairment, caution should be exercised in administering TABEX to these patients.  
Bone Effects  
Cases of osteomalacia (associated with proximal renal tubulopathy) have been reported in association with the use of  
tenofovir (see Section 4.8).  
Bone monitoring should be considered for HIV infected patients who have a history of pathologic bone fracture or are  
at risk for osteopenia. Although the effect of supplementation with calcium and vitamin D was not studied, such  
supplementation may be beneficial for all patients.  
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol; consumption, severe  
Initials K.B  
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Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
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.  
Convulsions  
Convulsions have been observed in patients receiving efavirenz, generally in the presence of known medical history  
of seizures. Caution must be taken in any patient with a history of seizures.  
Patients who are receiving concomitant anticonvulsant medications primarily metabolised by the liver, such as  
phenytoin and phenobarbital, may require periodic monitoring of plasma levels (see Section 4.5).  
Lipodystrophy and metabolic abnormalities  
Combination antiretroviral therapy has been associated with the redistribution/accumulation of body fat, including  
central obesity, dorso-cervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement,  
and elevated serum lipid and glucose levels in HIV patients.  
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 tuberculosis, cytomegalovirus retinitis, and cryptococcal meningitis.  
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 Grave’s disease) have  
Initials K.B  
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Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
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.  
Opportunistic infections  
Patients receiving TABEX 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  
experiences 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 TABEX, does not prevent the risk of  
transmission of HIV to others through sexual contact or blood contamination. Appropriate precautions should continue  
to be employed.  
Mitochondrial dysfunction  
Nucleoside and nucleotide analogues 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. The main adverse events reported are haematological disorders  
(anaemia, neutropenia) and metabolic disorders (hyperlactataemia, hyperlipidaemia). These events are often  
transitory. Some late-onset neurological disorders have been reported (hypertonia, convulsion, abnormal behaviour).  
Whether the neurological disorders are transient or permanent is not known. Any child exposed in utero to nucleoside  
and nucleotide analogues, even HIV negative children, should have clinical and laboratory follow-up and should be  
fully investigated for possible mitochondrial dysfunction in case of relevant sign and symptoms (see Section 4.8).  
QTc Prolongation  
QTc prolongation has been observed with the use of efavirenz (see Sections 4.5 and 5.2). For patients at increased  
risk of Torsade de Pointes or who are receiving drugs with a known risk for Torsade de Pointes, consider alternatives  
to TABEX.  
Initials K.B  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Weight and metabolic parameters  
An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes  
may in part be linked to disease control and life-style. For lipids, there is in some cases evidence for a treatment  
effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring of  
blood lipids and glucose reference is made to established HIV treatment guidelines. Lipid disorders should be  
managed as clinically appropriate.  
Oral contraceptives  
The potential interaction of efavirenz with oral contraceptives such as ethinyl estradiol has not been fully  
characterized. A reliable method of barrier contraception should be used in addition to oral contraceptives (see  
Section 4.5).  
4.5 Interaction with other medicines and other forms of interaction  
Efavirenz: Efavirenz has been shown in vivo to induce CYP3A4. Other compounds that are substrates of CYP3A4  
may have decreased plasma concentrations when co-administered with efavirenz. In vitro studies have demonstrated  
that efavirenz inhibits 2C9, 2C19 and 3A4 isozymes in the range of observed efavirenz plasma concentrations. Co-  
administration of efavirenz with medicines primarily metabolised by these isozymes may result in altered plasma  
concentrations of the co-administered medicine. Therefore, appropriate dose adjustments may be necessary for  
these medicines.  
Medicines which induce CYP3A4 activity (e.g. phenobarbital, rifampicin, rifabutin) would be expected to increase the  
clearance of efavirenz resulting in lowered plasma concentrations.  
Efavirenz exposure may be increased when given with grapefruit juice which inhibits CYP3A4 or CYP2B6 activity.  
Emtricitabine and tenofovir disoproxil fumarate: Since emtricitabine and tenofovir are primarily eliminated by the  
kidneys, co-administration of TABEX 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.  
Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valaciclovir and  
Initials K.B  
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Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
valganciclovir.  
Co-administration of tenofovir 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 (for didanosine dosing adjustment  
recommendations, see Table 2). Suppression of CD4 cell counts has been observed in patients receiving tenofovir  
DF with didanosine at a dose of 400 mg daily.  
Atazanavir and lopinavir/ritonavir have been shown to increase tenofovir concentrations. The mechanism of this  
interaction is unknown. Higher tenofovir concentrations could potentiate tenofovir-associated adverse events,  
including renal disorders. Patients receiving either atazanavir or lopinavir/ritonavir with tenofovir DF should be  
monitored for tenofovir-associated adverse events. TABEX should be discontinued in patients who develop tenofovir-  
associated adverse events (for atazanavir dosing adjustment recommendations, see Table 2).  
Other important medicine interaction information for TABEX is summarised Tables 1 and 2. The medicine  
interactions described are based on studies conducted with efavirenz, emtricitabine or tenofovir DF as individual  
medicines or are potential medicine interactions; no medicine interaction studies have been conducted using TABEX.  
The tables include potentially significant interactions, but are not all inclusive.  
Table 1  
Medicines that are Contraindicated or not recommended for use with TABEX (see Section 4.3)  
Medicine  
Clinical Comment / Contraindicated  
Efavirenz significantly decreases voriconazole plasma concentrations  
and co-administration may decrease the therapeutic effectiveness of  
voriconazole. Voriconazole significantly increases efavirenz plasma  
concentrations, which may increase the risk of efavirenz-associated  
side effects.  
Antifungal: voriconazole  
Potential for serious and/or life-threatening reactions such as cardiac  
dysrhythmias.  
Antihistamine: astemizole  
Anti-migraine: ergot  
derivatives  
Potential for serious and/or life-threatening reactions such as acute  
ergot toxicity characterised by peripheral vasospasm and ischaemia  
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Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
(dihydroergotamine,  
ergonovine, ergotamine)  
Anti-retrovirals: efavirenz,  
emtricitabine, tenofovir DF,  
lamivudine  
of the extremities and other tissues.  
Not for use with TABEX because the active ingredients,  
emtricitabine, tenofovir, emtricitabine/tenofovir and efavirenz are  
components of TABEX. Lamivudine is similar to emtricitabine.  
Potential for serious and/or life-threatening reactions such as  
prolonged or increased sedation or respiratory depression.  
Potential for serious and/or life-threatening reactions such as cardiac  
dysrhythmias.  
Benzodiazepines:  
midazolam, triazolam  
Calcium channel blocker.  
bepridil  
Gl motility medicine:  
cisapride  
Potential for serious and/or life-threatening reactions such as cardiac  
dysrhythmias.  
Potential for serious and/or life-threatening reactions such as cardiac  
dysrhythmias.  
Neuroleptic: pimozide  
NOT RECOMMENDED: Expected to substantially decrease plasma  
levels of efavirenz; has not been studied in combination with  
efavirenz.  
St. John's Wort (Hypericum  
perforatum)  
Table 2  
Established and Other Potentially Significant Medicine Interactions:  
Alteration in Dose or Regimen May Be Recommended Based on Medicine Interaction Studies or Predicted  
Interaction  
1 This table is not all inclusive  
Concomitant Medicine  
Effect  
Clinical Comment  
Anti-retroviral medicines  
↓amprenavir  
concentration  
↓fosamprenavir  
concentration  
Efavirenz has the potential to decrease serum  
concentrations of amprenavir  
Protease inhibitor: Amprenavir  
Protease inhibitor:  
Fosamprenavir (unboosted): Appropriate doses of  
fosamprenavir and TABEX with respect to safety  
and efficacy have not been established.  
Fosamprenavir calcium  
Fosamprenavir/ritonavir: An additional 100 mg/day  
(300 mg total) of ritonavir is recommended when  
TABEX is administered with fosamprenavir/ritonavir  
daily. No change in the ritonavir dose is required  
when TABEX is administered with fosamprenavir  
plus ritonavir twice daily.  
Protease inhibitor: Atazanavir  
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↓atazanavir  
Plasma  
concentrations  
of  
atazanavir  
were  
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Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
concentration  
↑tenofovir  
decreased by both efavirenz and tenofovir.  
Sufficient data are not available to make a dosing  
concentration  
recommendation  
for  
atazanavir  
or  
atazanavir/ritonavir with TABEX. Therefore, co-  
administration of TABEX and atazanavir is not  
recommended  
decreased atazanavir concentrations.  
The optimal dose of indinavir, when given in  
combination with efavirenz, is not known.  
due  
to  
concerns  
regarding  
Protease inhibitor: Indinavir  
↓indinavir  
concentration  
Increasing the indinavir dose to 1 000 mg every 8  
hours does not compensate for the increased  
indinavir metabolism due to efavirenz.  
Protease inhibitor:  
lopinavir/ritonavir  
↓lopinavir  
A dose increase of lopinavir/ritonavir to 600/150 mg  
(3 tablets) twice daily may be considered when used  
in combination with efavirenz in treatment-  
experienced patients where decreased susceptibility  
to lopinavir is clinically suspected (by treatment  
history of laboratory evidence). Patients should be  
monitored for tenofovir-associated adverse events.  
TABEX should be discontinued in patients who  
develop tenofovir-associated adverse events.  
concentration  
↑tenofovir  
concentration  
Protease inhibitor: Ritonavir  
↑ritonavir  
When ritonavir 500 mg every 12 hours was co-  
administered with efavirenz 600 mg once daily, the  
combination was associated with a higher frequency  
of adverse clinical experiences (e.g. dizziness,  
nausea, paraesthesia) and laboratory abnormalities  
(elevated liver enzymes). Monitoring of liver  
enzymes is recommended when TABEX is used in  
combination with ritonavir.  
concentration  
↑efavirenz  
concentration  
Protease inhibitor: Saquinavir  
↓saquinavir  
Should not be used as sole protease inhibitor in  
combination with TABEX.  
concentration  
↑didanosine  
concentration  
NRTI:  
Higher didanosine concentrations could potentiate  
didanosine-associated adverse events, including  
pancreatitis and neuropathy. In adults weighing  
more than 60 kg, the didanosine dose should be  
reduced to 250 mg if co-administered with TABEX.  
Data are not available to recommend a dose  
adjustment of didanosine for patients weighing less  
Didanosine  
Initials K.B  
May 2022  
Page 14 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
than 60 kg. When co-administered, TABEX and  
didanosine may be taken under fasted conditions or  
with a light meal (less than 400 kcal, 20 % fat). Co-  
administration of didanosine buffered formulation  
with TABEX should be under fasted conditions. Co-  
administration of TABEX and didanosine should be  
taken with caution and patients receiving this  
combination should be monitored closely for  
didanosine-associated  
adverse  
events.  
For  
additional information, please consult the didanosine  
professional information.  
Other medicines  
Anticoagulant: Warfarin  
↑or↓ warfarin  
Plasma concentrations and effects potentially  
increased or decreased by efavirenz.  
concentration  
Anticonvulsants:  
Carbamazepine  
↓ carbamazepine There are insufficient data to make a dose  
concentration  
↓efavirenz  
recommendation for TABEX.  
Alternative anticonvulsant treatment should be used.  
concentration  
↓anticonvulsant  
concentration  
↓efavirenz  
Phenytoin, phenobarbitone  
Potential for reduction in anticonvulsant and/or  
efavirenz plasma levels; periodic monitoring of  
anticonvulsant plasma levels should be conducted.  
concentration  
↓sertraline  
Antidepressant: Sertraline  
Antifungals: Itraconazole  
Increases in sertraline dose should be guided by  
clinical response.  
concentration  
↓itraconazole  
concentration  
Since no dose recommendation for itraconazole can  
be made, alternative antifungal treatment should be  
considered.  
↓hydroxy-  
Ketoconazole  
itraconazole  
concentration  
↓ketoconazole  
concentration  
↓clarithromycin  
concentration  
↑14-OH  
Medicine interaction studies with TABEX and  
ketoconazole have not been conducted. Efavirenz  
has the potential to decrease plasma concentrations  
of ketoconazole.  
Anti-infective: Clarithromycin  
Clinical  
significance  
unknown.  
In  
uninfected  
volunteers, 46 % developed rash while receiving  
efavirenz and clarithromycin. No dose adjustment of  
TABEX is recommended when given with  
clarithromycin. Alternatives to clarithromycin, such  
as azithromycin, should be considered. Other  
metabolite  
concentration  
Initials K.B  
May 2022  
Page 15 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
macrolide antibiotics, such as erythromycin, have  
not been studied in combination with TABEX.  
Antimycobacterial: Rifabutin  
Antimycobacterial: Rifampicin  
↓rifabutin  
Increase daily dose of rifabutin by 50 %. Consider  
doubling the rifabutin dose in regimens where  
rifabutin is given 2 or 3 times a week.  
concentration  
↓efavirenz  
Clinical  
significance  
of  
reduced  
efavirenz  
concentration  
concentration is unknown. Dosing recommendations  
for concomitant use of TABEX and rifampicin have  
not been established.  
Calcium channel blockers:  
Diltiazem  
↓diltiazem  
Diltiazem dose adjustments should be guided by  
clinical response (refer to the complete professional  
information for diltiazem). No dose adjustment of  
TABEX is necessary when administered with  
diltiazem.  
concentration  
↓desacetyl  
diltiazem  
concentration  
Others  
↓N-monodes-  
methyl diltiazem  
concentration  
No data are available on the potential interactions of  
efavirenz with other calcium channel blockers that  
are substrates of the CYP3A4 enzyme. The  
(e.g. felodipine, nicardipine,  
nifedipine, verapamil)  
↓calcium channel potential  
blocker  
exists  
for  
reduction  
in  
plasma  
concentrations of the calcium channel blocker. Dose  
adjustments should be guided by clinical response  
(refer to the complete professional information for  
the calcium channel blocker).  
HMG-CoA reductase inhibitors: ↓atorvastatin  
Plasma concentrations of atorvastatin, pravastatin  
and simvastatin decreased with efavirenz. Consult  
the complete professional information for the HMG-  
Atorvastatin Pravastatin  
Simvastatin  
concentration  
↓pravastatin  
concentration  
↓simvastatin  
concentration  
↓methadone  
concentration  
CoA  
reductase  
inhibitor  
for  
guidance  
on  
individualising the dose.  
Narcotic analgesic:  
Methadone  
Co-administration of efavirenz in HIV-infected  
individuals with a history of injection medicine use  
resulted in decreased plasma levels of methadone  
and signs of opiate withdrawal. Methadone dose  
was increased by a mean of 22 % to alleviate  
withdrawal symptoms. Patients should be monitored  
for signs of withdrawal and their methadone dose  
increased as required to alleviate withdrawal  
symptoms.  
Initials K.B  
May 2022  
Page 16 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Oral contraceptive: Ethinyl  
oestradiol  
↑ethinyl oestradiol Clinical significance unknown. Because the potential  
concentration  
interaction of efavirenz with oral contraceptives has  
not been fully characterised, a reliable method of  
barrier contraception should be used in addition to  
oral contraceptives.  
Efavirenz Assay Interference  
Cannabinoid Test Interaction: Efavirenz does not bind to cannabinoid receptors. False-positive urine cannabinoid  
test results have been observed in non-HIV-infected volunteers receiving efavirenz when the Microgenics Cedia DAU  
Multi-Level THC assay was used for screening. Negative results were obtained when more specific confirmatory  
testing was performed with gas chromatography/mass spectrometry. For more information, please consult the  
efavirenz professional information.  
Other Interactions  
Efavirenz  
Medicine interaction studies were performed with efavirenz and other medicines likely to be co-administered or  
medicines commonly used as probes for pharmacokinetic interaction. There was no clinically significant interaction  
observed between efavirenz and zidovudine, lamivudine, azithromycin, fluconazole, lorazepam, cetirizine or  
paroxetine. Single doses of famotidine or an aluminium and magnesium antacid with simethicone had no effects on  
efavirenz exposures.  
Emtricitabine and tenofovir disoproxil fumarate  
No clinically significant medicine interactions have been observed between emtricitabine and famciclovir, indinavir,  
stavudine, tenofovir and zidovudine. Similarly, no clinically significant medicine interactions have been observed  
between tenofovir and abacavir, adefovir, dipivoxil, efavirenz, emtricitabine, indinavir, lamivudine, lopinavir/ritonavir,  
methadone, nelfinavir, oral contraceptives, ribavirin and saquinavir/ritonavir in studies conducted in healthy  
volunteers.  
Following multiple dosing to HIV-negative subjects receiving either chronic methadone maintenance therapy, oral  
contraceptives or single doses of ribavirin, steady-state tenofovir pharmacokinetics were similar to those observed in  
previous studies, indicating a lack of clinically significant medicine interactions between these medicines and  
Initials K.B  
May 2022  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
tenofovir.  
4.6 Fertility, pregnancy and lactation  
Women of childbearing potential / Contraception in males and females  
Pregnancy should be avoided in women receiving TABEX. Women of childbearing potential should undergo  
pregnancy testing before initiation of TABEX. Barrier contraception should always be used in combination with  
other methods of contraception (for example, oral or other hormonal contraceptives) while on therapy with TABEX.  
Because of the long half-life of efavirenz, the use of adequate contraceptive measures for 12 weeks after  
discontinuation of TABEX is recommended (see Section 5.2).  
Pregnancy  
TABEX should not be used in pregnancy (see Section 4.3).  
Efavirenz is teratogenic and may cause foetal harm when administered during the first trimester of pregnancy.  
There have been reports of congenital abnormalities including neural tube defects and meningomeroceal in babies  
exposed in utero to efavirenz during the first trimester of pregnancy.  
If a patient becomes pregnant while taking TABEX the patient (and partner) should be counselled and informed  
about the potential harm to the foetus. The possibility of termination of pregnancy should be considered and  
discussed with both patients if there is already evidence of severe harm to the foetus. If termination is unavoidable  
the patient should be treated with an alternative medicine, known to be safe or safer for use in pregnancy. If no  
safe or safer alternative is available, cannot be tolerated, has failed or is contraindicated, both partners should be  
counselled and written consent preferable to both partners be obtained to continue treatment with TABEX.  
If a patient is to be treated with TABEX, pregnancy should be excluded 24 hours prior to initiation of treatment.  
Breastfeeding  
It is recommended that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission  
of HIV. Because of both the potential for HIV transmission and the potential for serious adverse reactions in  
Initials K.B  
May 2022  
Page 18 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
breastfed infants, mothers should be instructed not to breastfeed if they are receiving TABEX.  
Fertility  
Human data on the effect of TABEX on fertility are not available.  
4.7 Effects on ability to drive and use machines  
Dizziness, impaired concentration and drowsiness have been reported during treatment with the individual  
components of TABEX. If the patient experiences any of these symptoms while taking TABEX, he/she should be  
advised not to drive or use any tools or machines (see Section 4.8).  
4.8 Undesirable effects  
a. Summary of safety profile  
For additional safety information about efavirenz, emtricitabine or tenofovir in combination with other anti-retroviral  
medicines, consult the professional informations for these products.  
Severe skin reactions such as Stevens-Johnson syndrome and erythema multiforme, neuropsychiatric adverse  
reactions (including severe depression, death by suicide, psychosis-like behaviour, seizures), severe hepatic events,  
pancreatitis and lactic acidosis (sometimes fatal) have been reported.  
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 also been reported.  
Monitoring of renal function is recommended for patients receiving TABEX (see Section 4.4).  
Discontinuation of TABEX therapy in patients co-infected with HIV and HBV may be associated with severe acute  
exacerbations of hepatitis (see Section 4.4).  
The administration of TABEX with food may increase efavirenz exposure and may lead to an increase in the  
frequency of adverse reactions (see Sections 4.4 and 5.2).  
Initials K.B  
May 2022  
Page 19 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
b. Listing of adverse reactions  
EFAVIRENZ  
Infections and Infestations  
Frequent:  
Folliculitis  
Immune system disorders  
Less frequent:  
Allergic reactions  
Immune reconstitution syndrome  
Frequency unknown:  
Metabolism and nutrition disorders  
Less frequent:  
Anorexia, hypercholesterolaemia, hypertriglyceridaemia  
Frequency unknown:  
Redistribution/accumulation of body fat (see Section 4.4), alcohol intolerance  
increased appetite  
Psychiatric disorders  
Frequent:  
Insomnia  
Less frequent:  
Agitation, stupor, depression, anxiety, hallucination, euphoria, abnormal  
thinking, apathy, aggressive reactions, emotional lability, mania, psychosis,  
suicide  
Frequency unknown:  
Paranoia, neurosis, delusions, aggravated depression  
Nervous system disorders  
Frequent:  
Dizziness, headache, drowsiness  
Less frequent:  
Taste perversion, abnormal dreams, confusion, impaired concentration,  
somnolence, amnesia, migraine headaches, neuralgia, peripheral neuropathy,  
speech disorder, abnormal co-ordination, ataxia, convulsions, hypoaesthesia,  
paraesthesia, neuropathy, tremor  
Eye disorders  
Initials K.B  
May 2022  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Frequency unknown:  
Abnormal vision  
Ear and labyrinth disorders  
Frequency unknown:  
Tinnitus  
Cardiac disorders  
Frequency unknown:  
Palpitations  
Vascular disorders  
Less frequent:  
Flushing or hot flushes, syncope  
Respiratory, thoracic and mediastinal disorders  
Frequency unknown:  
Dyspnoea, asthma, sinusitis, upper respiratory tract infections  
Gastrointestinal disorders  
Frequent:  
Nausea  
Less frequent:  
Frequency unknown:  
Dyspepsia, abdominal pain, abdominal coordination, vomiting, diarrhoea  
Constipation, malabsorption, gastritis, gastroenteritis, gastro-oesophageal reflux  
Hepato-biliary disorders  
Less frequent:  
Hepatitis  
Hepatic failure  
Frequency unknown:  
Skin and subcutaneous tissue disorders  
Frequent:  
Rash pruritus, increased sweating, alopecia, eczema, skin exfoliation, urticaria,  
flushing, erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome  
Acne, seborrhoea, nail disorders, skin discolouration  
Less frequent:  
Musculoskeletal, connective tissue and bone disorders  
Initials K.B  
May 2022  
Page 21 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Less frequent:  
Frequency unknown:  
Arthralgia, myalgia  
Myopathy  
Reproductive system and breast disorders  
Frequency unknown:  
Gynaecomastia, impotence, decreased libido, increased libido  
General disorders and administrative site conditions  
Frequent:  
Fatigue  
Less frequent:  
Frequency unknown:  
Malaise  
Pain, influenza-like symptoms, asthenia  
Investigations  
Frequent:  
Weight increase and weight decrease  
Increased hepatic enzyme  
Frequency unknown:  
EMTRICITABINE  
Blood and the lymphatic system disorders  
Frequent:  
Neutropenia  
Less frequent:  
Anaemia, hyperbilirubinaemia, hepatitis  
Immune system disorders  
Frequent:  
Allergic reaction  
Angioedema  
Frequency unknown:  
Metabolism and nutrition disorders  
Frequent:  
Hypertriglyceridaemia, hyperglycaemia  
Frequency unknown:  
Accumulation and redistribution of body fat, including breast enlargement,  
central obesity, cushingoid appearance, dorsocervical fat enlargement (buffalo  
hump), facial wasting and peripheral wasting  
Initials K.B  
May 2022  
Page 22 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Psychiatric disorders  
Frequent:  
Insomnia  
Nervous system disorders  
Frequent:  
Abnormal dreams, dizziness, headache  
Gastrointestinal disorders  
Frequent:  
Nausea, diarrhoea  
Abdominal pain, dyspepsia, vomiting  
Less frequent:  
Skin and subcutaneous tissue disorders  
Frequent:  
Skin discolouration (increased pigmentation)  
Vesiculobullous rash, pustular rash, maculopapular rash, rash, pruritus, urticaria  
Less frequent:  
General disorders and administrative site conditions  
Less frequent:  
Asthenia, pain  
Investigations  
Frequent:  
Blood creatine phosphokinase increased  
Less frequent:  
Increased serum amylase concentrations including elevated pancreatic  
amylase, elevated serum lipase  
TENOFOVIR DISOPROXIL FUMARATE  
Infections and Infestations  
Frequency unknown:  
Pneumonia  
Blood and the lymphatic system disorders  
Initials K.B  
May 2022  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Frequency unknown:  
Neutropenia  
Immune system disorders  
Frequency unknown: Allergic reaction, angioedema, immune reconstitution syndrome  
Metabolism and nutrition disorders  
Frequent  
Hypophosphataemia  
Less frequent:  
Including fatal cases, usually associated with severe hepatomegaly and  
steatosis, anorexia, pancreatitis  
Frequency unknown:  
Accumulation and redistribution of body fat, including breast enlargement,  
central obesity, cushingoid appearance, dorsocervical fat enlargement (buffalo  
hump), facial wasting, and, peripheral wasting, hypertriglyceridaemia,  
hyperglycaemia, hypokalaemia, Lactic acidosis  
Psychiatric disorders  
Frequent:  
Anxiety, insomnia, depression  
Nervous system disorders  
Frequent:  
Dizziness  
Headache, peripheral neuropathy, convulsions  
Frequency unknown:  
Gastrointestinal disorders  
Frequent:  
Nausea, vomiting, diarrhoea  
Less frequent:  
Frequency unknown:  
Abdominal pain, flatulence  
Dyspepsia  
Hepato-biliary disorders  
Less frequent:  
Hepatotoxicity  
Hepatitis, hepatic steatosis  
Frequency unknown:  
Initials K.B  
May 2022  
Page 24 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Skin and subcutaneous tissue disorders  
Frequent  
Skin rashes  
Sweating  
Frequency unknown:  
Musculoskeletal, connective tissue and bone disorders  
Frequency unknown: Myopathy, osteomalacia (both associated with proximal renal tubulopathy),  
muscular weakness, myalgia, arthralgia, osteonecrosis  
Renal and urinary disorders  
Frequency unknown: Renal insufficiency, renal failure, acute renal failure, Fanconi syndrome,  
proximal tubulopathy, proteinuria, increased creatinine, acute tubular necrosis,  
nephrogenic diabetes insipidus, polyuria, interstitial nephritis (including acute  
cases)  
General disorders and administrative site conditions  
Frequent:  
Asthenia, fatigue  
Frequency unknown:  
Fever, pain, back pain, chest pain  
Investigations  
Frequency unknown:  
Increased serum amylase concentrations, increased hepatic enzymes, weight  
decreased  
c) Description of selected adverse reactions  
Efavirenz: The most significant adverse events observed in patients treated with efavirenz are nervous system  
symptoms (see Section 4.4, nervous system symptoms), psychiatric symptoms (see Section 4.4, psychiatric  
symptoms) and rash (see Section 4.4, skin rash).  
Pancreatitis has been reported, although a causal relationship with efavirenz has not been established.  
Asymptomatic increases in serum amylase levels have been observed.  
Initials K.B  
May 2022  
Page 25 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Emtricitabine and tenofovir disoproxil fumarate: Adverse events that occurred in at least 5 % of patients receiving  
emtricitabine or tenofovir with other anti-retroviral medicines include anxiety, arthralgia, increased cough, dyspepsia,  
fever, myalgia, pain, abdominal pain, back pain, paraesthesia, peripheral neuropathy (including peripheral neuritis  
and neuropathy), pneumonia, rhinitis and rash event (including rash, pruritus, maculopapular rash, urticaria,  
vesiculobullous rash, pustular rash and allergic reaction).  
Skin discolouration has been reported with higher frequency among emtricitabine treated patients. Skin  
discolouration, manifested by hyper-pigmentation on the palms and/or soles was generally mild and  
asymptomatic. The mechanism and clinical significance are unknown.  
d) Paediatric population  
Insufficient safety data are available for children below 18 years of age. TABEX is not recommended in this  
population (see Section 4.2).  
e) Other special population  
Elderly: TABEX has not been studied in patients over the age of 65. Elderly patients are more likely to have  
decreased hepatic or renal function, therefore caution should be exercised when treating elderly patients with TABEX  
(see Section 4.2).  
Patients with renal impairment: Since tenofovir disoproxil can cause renal toxicity, close monitoring of renal  
function is recommended in any patient with mild renal impairment treated with TABEX (see Sections 4.2, 4.4 and  
5.2).  
HIV/HBV or HCV co-infected patients:  
The adverse reaction profile of efavirenz, emtricitabine 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.  
Initials K.B  
May 2022  
Page 26 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Exacerbations of hepatitis after discontinuation of treatment: In HIV infected patients co-infected with HBV,  
clinical and laboratory evidence of hepatitis may occur after discontinuation of treatment (see Section 4.4).  
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued  
monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected  
adverse reactions via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s  
publications: https://www.sahpra.org.za/publications/Index/8 or to the Holder of certificate of registration through  
the mail: pvg.cdma@heterogroups.com .  
4.9 Overdose  
If overdose occurs, the patient should be monitored for evidence of toxicity, including monitoring of vital signs and  
observation of the patient’s clinical status; standard supportive treatment should then be applied as necessary.  
Administration of activated charcoal may be used to aid removal of unabsorbed efavirenz. Haemodialysis can  
remove both emtricitabine and tenofovir DF (refer to detailed information below), but is unlikely to significantly  
remove efavirenz from the blood.  
Efavirenz: Increased nervous system symptoms. Involuntary muscle contractions were reported.  
Emtricitabine: Haemodialysis treatment removes approximately 30 % of the emtricitabine dose over a 3-hour  
dialysis period starting within 1,5 hours of emtricitabine dosing (blood flow rate of 400 ml/min and a dialysate flow  
rate of 600 ml/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.  
Tenofovir disoproxil fumarate: Tenofovir is efficiently removed by haemodialysis with an extraction coefficient of  
approximately 54 %. Following a single 300 mg dose of tenofovir DF, a 4-hour haemodialysis session removed  
approximately 10 % of the administered tenofovir dose.  
PHARMACOLOGICAL PROPERTIES  
5.1 Pharmacodynamic properties:  
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Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
A 20.2.8 Antiviral agents  
TABEX is a fixed dose combination tablet containing efavirenz, emtricitabine and tenofovir disoproxil fumarate.  
Efavirenz is a non-nucleoside reverse transcriptase inhibitor; emtricitabine is a synthetic nucleoside analogue of  
cytidine, and tenofovir DF is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analogue  
of adenosine 5′-monophosphate.  
Mechanism of action:  
Efavirenz: Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. Efavirenz activity is  
mediated predominantly by non-competitive inhibition of HIV-1 reverse transcriptase (RT). HIV-2 RT and human  
cellular DNA polymerases , β, , and are not inhibited by efavirenz.  
Emtricitabine: Emtricitabine, a synthetic nucleoside analogue of cytidine, is phosphorylated by cellular enzymes to  
form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 RT by competing with  
the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in  
chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerase , β, ε- and  
mitochondrial DNA polymerase .  
Tenofovir disoproxil fumarate: Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analogue  
of adenosine monophosphate. Tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to  
tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate  
inhibits the activity of HIV-1 RT by competing with the natural substrate deoxyadenosine 5'-triphosphate and after  
incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA  
polymerases , β and mitochondrial DNA polymerase .  
Antiviral Activity  
Efavirenz, emtricitabine and tenofovir disoproxil fumarate: Synergistic antiviral effects were observed in  
combination studies evaluating the antiviral activity in cell cultures of emtricitabine and efavirenz together, efavirenz  
and tenofovir together and emtricitabine and tenofovir together.  
Initials K.B  
May 2022  
Page 28 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Medicine Resistance  
Efavirenz, emtricitabine, and tenofovir disoproxil fumarate: HIV-1 isolates with reduced susceptibility to the  
combination of emtricitabine and tenofovir have been selected in cell culture and in clinical studies. Genotypic  
analysis of these isolates identified the M184V/I and/or K65R amino acid substitutions in the viral RT.  
Cross-resistance  
Efavirenz, emtricitabine and tenofovir disoproxil fumarate: Cross-resistance has been recognised among  
NNRTIs. Cross resistance has also been recognised among certain NRTIs. The M184V/I and/or K65R substitutions  
selected in cell cultures by the combination of emtricitabine and tenofovir are also observed in some HIV-1 isolates  
from subjects failing treatment with tenofovir in combination with either lamivudine or emtricitabine, and either  
abacavir or didanosine. Therefore, cross-resistance among these medicines may occur in patients whose virus  
harbours either or both of these amino acid substitutions (see Section 4.4).  
5.2 Pharmacokinetic properties  
Efavirenz:  
Absorption  
In HIV-infected patients time-to-time peak plasma concentrations were approximately 3 to 5 hours and steady-state  
plasma concentrations are reached in 6 to 10 days. At a dose of efavirenz 600 mg once daily, steady-state Cmax was  
12,9 ± 3,7 μM (mean ± SD), Cmin was 5,6 ± 3,2 μM, and AUC was 184 ± 73 μM•hr.  
Distribution  
Efavirenz is highly bound (approximately 99,5 to 99,75 %) to human plasma proteins, predominantly albumin.  
Biotransformation  
In vitro studies suggest CYP3A4 and CYP2B6 are the major isozymes responsible for efavirenz metabolism.  
Efavirenz has been shown to induce P450 enzymes, resulting in induction of its own metabolism. Efavirenz has a  
terminal half-life of 52 to 76 hours after single doses and 40 to 55 hours after multiple doses.  
Elimination  
Following administration of 14C-labelled efavirenz, 14 to 34 % of the dose is recovered in the urine (mostly as  
metabolites) and 16 to 61 % is recovered in faeces (mostly as parent medicine)  
Initials K.B  
May 2022  
Page 29 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Emtricitabine:  
Absorption  
Emtricitabine is rapidly absorbed after oral administration with peak plasma concentrations occurring at 1 to 2 hours  
post-dose. Following multiple dose oral administration of emtricitabine, the steady-state plasma emtricitabine Cmax  
was 1,8 ± 0,7 μg/ml (mean ± SD) and the AUC over a 24-hour dosing interval was 10,0 ± 3,1 μg•hr/ml. The mean  
steady state plasma trough concentration at 24 hours post-dose was 0,09 μg/ml. The mean absolute bioavailability of  
emtricitabine was 93 %.  
Distribution  
In vitro binding of emtricitabine to human plasma proteins is less than 4 % and is independent of concentration over  
the range of 0,02 to 200 μg/ml.  
Biotransformation  
Following administration of radio-labelled emtricitabine, approximately 86 % is recovered in the urine and 13 % is  
recovered as metabolites.  
Elimination  
The metabolites of emtricitabine include 3'-sulfoxide diastereomers and their glucuronic acid conjugate. Emtricitabine  
is eliminated by a combination of glomerular filtration and active tubular secretion with a renal clearance in adults with  
normal renal function of 213 ± 89 ml/min (mean ± SD). Following a single oral dose, the plasma emtricitabine half-life  
is approximately 10 hours.  
Tenofovir disoproxil fumarate:  
Following oral administration of a single 300 mg dose of tenofovir DF to HIV-1 infected patients in the fasted state,  
maximum serum concentrations (Cmax) were achieved in 1,0 ± 0,4 hours (mean ± SD) and Cmax and AUC values were  
296 ± 90 ng/ml and 2 287 ± 685 ng•hr/ml, respectively. The oral bioavailability of tenofovir from tenofovir DF in fasted  
patients is approximately 25 %. In vitro binding of tenofovir to human plasma proteins is < 0,7 % and is independent  
of concentration over the range of 0,01 to 25 μg/ml. Approximately 70 to 80 % of the intravenous dose of tenofovir is  
recovered as unchanged medicine in the urine. Tenofovir is eliminated by a combination of glomerular filtration and  
active tubular secretion with a renal clearance in adults with normal renal function of 243 ± 33 ml/min (mean ± SD).  
Following a single oral dose, the terminal elimination half-life of tenofovir is approximately 17 hours.  
Initials K.B  
May 2022  
Page 30 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Effects of Food on Oral Absorption  
TABEX has not been evaluated in the presence of food. Administration of efavirenz tablets with a high fat meal  
increased the mean AUC and Cmax of efavirenz by 28 % and 79 %, respectively, compared to administration in the  
fasted state. Compared to fasted administration, dosing of tenofovir DF and emtricitabine in combination with either a  
high fat meal or a light meal increased the mean AUC and Cmax of tenofovir by 35 % and 15 %, respectively, without  
affecting emtricitabine exposures (see Sections 4.9, 4.8 and 4.4).  
Special populations  
Race  
Efavirenz: The pharmacokinetics of efavirenz in patients appear to be similar among the racial groups studied.  
Emtricitabine: No pharmacokinetic differences due to race have been identified following the administration of  
emtricitabine.  
Tenofovir disoproxil fumarate: There were insufficient numbers from racial and ethnic groups other than Caucasian  
to adequately determine potential pharmacokinetic differences among these populations following the administration  
of tenofovir DF.  
Gender  
Efavirenz, emtricitabine and tenofovir disoproxil fumarate:  
Efavirenz, emtricitabine and tenofovir pharmacokinetics are similar in male and female patients.  
Paediatric and Geriatric Patients  
Pharmacokinetic studies have not been performed in paediatric patients (less than 18 years) and the elderly (more  
than 65 years)  
Patients with Impaired Renal Function  
Efavirenz: The pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however,  
less than 1 % of efavirenz is excreted unchanged in the urine, so the impact of renal impairment on efavirenz should  
be minimal.  
Initials K.B  
May 2022  
Page 31 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Emtricitabine and tenofovir disoproxil fumarate: The pharmacokinetics of emtricitabine and tenofovir are altered in  
patients with renal impairment. In patients with creatinine clearance less than 50 ml/min, Cmax and AUC10-∞ of  
emtricitabine and tenofovir were increased (see Sections 4.3 and 4.4).  
Patients with Hepatic Impairment  
Efavirenz: The pharmacokinetics of efavirenz have not been adequately studied in patients with hepatic impairment  
(see Sections 4.4 and 4.8).  
Emtricitabine: The pharmacokinetics of emtricitabine have not been adequately studied in patients with hepatic  
impairment; however, emtricitabine is not significantly metabolised by liver enzymes, so the impact of liver impairment  
should be limited.  
Tenofovir disoproxil fumarate: There were no substantial alterations in tenofovir pharmacokinetics in patients  
with hepatic impairment compared with unimpaired patients.  
5.3 Preclinical safety data  
Not Applicable  
Environmental Risk Assessment  
The environmental exposure of the active substance and metabolites are expected to be very limited. The use of  
efavirenz, emtricitabine and tenofovir disoproxil fumarate film coated tablets 600 mg / 200 mg / 300 mg is not  
considered warranting any environmental concerns or requiring any special product labelling.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
•
•
•
•
•
Croscarmellose sodium  
microcrystalline cellulose  
sodium lauryl sulphate  
hydroxypropyl cellulose  
magnesium stearate  
Film coating:  
Initials K.B  
May 2022  
Page 32 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
Opadry II pink 85F94172 consists of polyvinyl alcohol-part hydrolysed, titanium dioxide, macrogol/PEG 3350, talc,  
iron oxide red, iron oxide black  
6.2 Incompatibilities  
Not applicable  
6.3 Shelf life  
36 months  
6.4 Special precautions for storage  
Store at or below 30 °C.  
Keep the container tightly closed.  
Protect from light and moisture.  
Keep the tablets in the HDPE bottle until required for use.  
Keep the HDPE bottle in the outer carton.  
6.5 Nature and contents of container  
•
•
•
•
28’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 28 film coated  
tablets.  
30’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 30 film coated  
tablets.  
60’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 60 film coated  
tablets.  
84’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 84 film coated  
tablets.  
Initials K.B  
May 2022  
Page 33 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
•
•
•
•
90’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 90 film coated  
tablets.  
120’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 120 film coated  
tablets.  
180’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 180 film coated  
tablets.  
500’s Count HDPE container: White opaque high density polyethylene (HDPE) container with a desiccant  
canister 2 g silica gel enclosed with a child-resistant plastic cap with a pulp liner, containing 500 film coated  
tablets.  
HDPE bottle is enclosed in an outer carton box.  
Not all pack sizes may be marketed.  
6.6 Special precautions for disposal and other handling  
No special requirements  
7 HOLDER OF CERTIFICATE OF REGISTRATION  
Hetero Drugs South Africa (Pty) Ltd  
Waterfall Corporate Campus, Building 2,  
First Floor, 74 waterfall Drive,  
Midrand,2066  
Initials K.B  
May 2022  
Page 34 of 35  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: TABEX  
Dosage form and strength: Film coated tablets; 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of  
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir)  
8 REGISTRATION NUMBER(S)  
51/20.2.8/0201  
9 DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION  
05 May 2020  
10 DATE OF REVISION OF THE TEXT  
27 May 2022  
Initials K.B  
May 2022  
Page 35 of 35