Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
PROFESSIONAL INFORMATION  
SCHEDULING STATUS  
S4  
1 NAME OF THE MEDICINE  
Hetacav Oral Solution 20 mg/ml (ORAL SOLUTION)  
WARNING:  
Hypersensitivity: approximately 4 % of subjects receiving Hetacav Oral Solution 20 mg/ml develop a  
hypersensitivity reaction which in rare cases is fatal.  
Description:  
The symptoms of this hypersensitivity reaction can occur at any time during treatment with Hetacav Oral  
Solution 20 mg/ml, but usually appear within the first six weeks of initiation of treatment (median time to onset  
11 days). This is characterised by the presence of symptoms illustrative of multi-organ/body-system  
involvement. Most patients have fever and/or rash as part of the syndrome. Other symptoms include  
gastrointestinal indicators (nausea, vomiting, diarrhoea, and abdominal pain), rash and fatigue or malaise,  
myalgia, arthralgia, oedema, paraesthesia, and respiratory signs and symptoms such as dyspnoea, sore throat,  
cough, and abnormal chest X-ray findings (predominantly infiltrates, which can be localised).  
The symptoms worsen with continued therapy and can be life-threatening. These symptoms usually resolve  
upon discontinuation of Hetacav Oral Solution 20 mg/ml.  
Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitive reaction. Prior to  
initiating therapy with Hetacav Oral Solution 20 mg/ml screening for HLA-B*5701 allele is recommended, this  
approach has been found to decrease the risk of hypersensitivity reaction.  
Management:  
To avoid a delay in diagnosis and minimise the risk of a life-threatening hypersensitivity reaction, Hetacav Oral  
Solution 20 mg/ml should be permanently discontinued if hypersensitivity cannot be ruled out, even when  
other diagnoses are possible (respiratory diseases, flu-like illness, gastroenteritis or reactions to other  
Nov 2021  
Initial:………………….  
Page 1 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
medicines). Hetacav Oral Solution 20 mg/ml, or any other medicine containing abacavir, should not be  
restarted.  
Special considerations following an interruption of Hetacav Oral Solution 20 mg/ml therapy:  
If therapy with Hetacav Oral Solution 20 mg/ml has been discontinued and restarting therapy is under  
consideration, the reason for discontinuation should be evaluated to ensure that the patient did not have  
symptoms of a hypersensitivity reaction. Patients who have stopped Hetacav Oral Solution 20 mg/ml due to  
possible adverse reactions or illness should be advised to contact their doctor before restarting. If  
hypersensitivity cannot be ruled out Hetacav Oral Solution 20 mg/ml or any other medicine containing  
abacavir should not be restarted.  
If a decision is made to restart Hetacav Oral Solution 20 mg/ml, this should be done only under direct medical  
supervision.  
Infrequently, hypersensitivity reactions have been reported in patients who have restarted therapy, and who  
had no preceding symptoms of a hypersensitivity reaction. If a decision is made to restart Hetacav Oral  
Solution 20 mg/ml, this must be done only if medical care can be accessed readily by the patient or others.  
Essential patient information:  
Prescribers must ensure that patients are fully informed regarding the following information on the  
hypersensitivity reaction:  
Patients must be made aware of the possibility of a hypersensitivity reaction to abacavir that may result in a  
life-threatening reaction or death:  
•
Patients developing signs or symptoms possibly linked with a hypersensitivity reaction MUST  
CONTACT their doctor IMMEDIATELY.  
•
Patients who are hypersensitive to abacavir should be reminded that they must never take Hetacav  
Oral Solution 20 mg/ml or any other medicinal product containing abacavir again.  
Nov 2021  
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Page 2 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
In order to avoid restarting Hetacav Oral Solution 20 mg/ml, patients who have experienced a hypersensitivity  
reaction should be asked to return the remaining Hetacav Oral Solution 20 mg/ml to the pharmacy.  
Patients who have stopped Hetacav Oral Solution 20 mg/ml for any reason, and particularly due to possible  
adverse reactions or illness, must be advised to contact their doctor before restarting.  
Each patient should be reminded to read the package insert included in the Hetacav Oral Solution 20 mg/ml  
pack.  
2 QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir.  
Hetacav Oral Solution 20 mg/ml contains sugar (sorbitol and saccharine sodium).  
‘for full list of excipients, see section 6.1’.  
3 PHARMACEUTICAL FORM  
Clear to opalescent, yellowish, and strawberry banana flavoured liquid.  
4 CLINICAL PARTICULARS  
4.1 Therapeutic indications  
Hetacav Oral Solution 20 mg/ml is indicated in antiretroviral combination therapy for the treatment of  
Human Immunodeficiency Virus (HIV) infected adults and children.  
4.2 Posology and method of administration  
Adults and adolescents over 12 years:  
The recommended dosage of Hetacav Oral Solution 20 mg/ml is 600 mg daily. This may be dministered  
as either 300 mg twice daily or 600mg once daily.  
Children from three months to 12 years:  
The recommended dosage is 8 mg/kg twice daily up to a maximum of 600 mg daily.  
Children less than three months:  
There are no data available on the use of Hetacav Oral Solution 20 mg/ml in this age group.  
Nov 2021  
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Page 3 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Method of administration  
Hetacav Oral Solution 20 mg/ml can be taken with or without food.  
4.3 Contraindications  
Hetacav Oral Solution 20 mg/ml is contra-indicated:  
•
•
•
•
•
in patients with known hypersensitivity to abacavir or any ingredient of the formulation  
administration of abacavir with alcohol  
in patients with a hereditary fructose intolerance  
in patients with liver function impairment  
during pregnancy and lactation.  
4.4 Special warnings and precautions for use  
Hypersensitivity reaction:  
Serious and sometimes fatal hypersensitivity reactions have been associated with Hetacav Oral Solution  
20 mg/ml and other abacavir-containing products. Patients who carry the HLA-B*5701 allele are at high  
risk for experiencing a hypersensitive reaction. Prior to initiating therapy with Hetacav Oral Solution 20  
mg/ml screening for HLA-B*5701 allele is recommended, this approach has been found to decrease the  
risk of hypersensitivity reaction. For HLA-B*5701 positive patients, treatment with abacavir containing  
regimen is not recommended and should be considered when no other therapeutic option is available based  
on treatment history and resistance testing. HLA-B*5701 negative patients may develop hypersensitivity.  
Important information on signs and symptoms of hypersensitivity, as well as clinical management, is  
presented below:  
Signs and Symptoms of Hypersensitivity:  
Nov 2021  
Initial:………………….  
Page 4 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterised by a sign or symptom  
in 2 or more of the following groups.  
Group 1: Fever  
Group 2: Rash  
Group 3: Gastrointestinal (including nausea, vomiting, diarrhoea, or abdominal pain)  
Group 4: Constitutional (including generalised malaise, fatigue, or achiness)  
Group 5: Respiratory (including dyspnoea, cough, or pharyngitis).  
Hypersensitivity to abacavir following the presentation of a single sign or symptom has been reported  
infrequently. Other less common signs and symptoms of hypersensitivity include lethargy, myolysis,  
oedema, abnormal chest x-ray findings (predominantly infiltrates, which can be localised), and  
paraesthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome,  
respiratory failure, and death have occurred in association with hypersensitivity reactions.  
Clinical Management of Hypersensitivity:  
Discontinue Hetacav Oral Solution 20 mg/ml as soon as a hypersensitivity reaction is suspected. To  
minimise the risk of a life-threatening hypersensitivity reaction, permanently discontinue Hetacav Oral  
Solution 20 mg/ml if hypersensitivity cannot be ruled out, even when other diagnoses are possible (e.g.,  
acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza;gastroenteritis;  
or reactions to other medications).  
Following a hypersensitivity reaction to abacavir, NEVER restart  
Hetacav Oral Solution 20 mg/ml or any other abacavir-containing product because more severe  
symptoms can occur within hours and may include life-threatening hypotension and death.  
Lactic acidosis / hyperlactataemia:  
Nov 2021  
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Page 5 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Use of Hetacav Oral Solution 20 mg/ml can result in potentially fatal lactic acidosis as a consequence of.  
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 2-5 mmol/ℓ with minimum symptoms: switch to agents that are less likely to cause lactic acidosis.  
- Lactate 5-10 mmol/ℓ with symptoms and/or with reduced standard bicarbonate: Stop NRTIs andchange  
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 Hetacav Oral Solution 20 mg/ml  
to patients with known risk factors for liver disease. Treatment with Hetacav Oral Solution 20 mg/ml should  
be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or  
hepatotoxicity.  
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. 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.  
Nov 2021  
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Page 6 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Lactic Acidosis/Severe Hepatomegaly with Steatosis:  
Lactic acidosis/severe hepatomegaly with steatosis, including fatal cases, have been reported with the use  
Hetacav Oral Solution 20 mg/ml, 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. Caution  
should be exercised when administering Hetacav Oral Solution 20 mg/ml to any patient, and particularly  
to those with known risk factors for liver disease. Treatment with Hetacav Oral Solution 20 mg/ml should  
be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or  
hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked  
transaminase elevations).  
Immune Reconstitution Inflammatory Syndrome (IRIS):  
In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral  
therapy (cART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may rise  
and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been  
observed within the first few weeks or months of initiation of CART.  
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterium infections and  
Pneumocystis jerovicii (carinii) pneumonia. Any inflammatory symptoms should be evaluated and treatment  
instituted when necessary.  
Auto-immune disorders (such as Graves’ disease) have also been reported to occur in the setting of  
immune reactivation; however, the reported time to onset is more variable and these events can occur  
many months after initiation of treatment.  
Fat redistribution:  
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo  
hump), peripheral wasting, facial wasting, breast enlargement, elevated serum lipid and blood glucose  
levels have been observed either separately or together in some patients receiving combination  
antiretroviral therapy (see section 4.8).  
Nov 2021  
Initial:………………….  
Page 7 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Clinical evaluation should include evaluation for physical signs of fat redistribution. Consideration should  
be given to measurement of serum lipids and blood glucose. Lipid disorders should be managed as clinically  
appropriate.  
Myocardial Infarction:  
Observational studies have shown an association between myocardial infarction and the use of Hetacav  
Oral Solution 20 mg/ml. As a precaution, the underlying risk of coronary heart disease should be  
considered when prescribing antiretroviral therapies, including abacavir as in Hetacav Oral Solution 20  
mg/ml, and action taken to minimise all modifiable risk factors (e.g., hypertension, hyperlipidaemia,  
diabetes mellitus, smoking).  
Pancreatitis:  
Pancreatitis has been observed in some patients receiving Hetacav Oral Solution 20 mg/ml. Pancreatitis  
must be considered whenever a patient develops abdominal pain, nausea, vomiting or elevated biochemical  
markers. Discontinue use of Hetacav Oral Solution 20 mg/ml until diagnosis of pancreatitis is excluded.  
Liver disease:  
Use of Hetacav Oral Solution 20 mg/ml can result in hepatomegaly due to non-alcoholic fatty liver disease  
(hepatic steatosis). The safety and efficacy of Hetacav Oral Solution 20 mg/ml has not been established  
in patients with significant underlying liver disorders/diseases. In case of concomitant antiviral therapy for  
hepatitis B or C, please also consult the relevant package inserts for these medicines. 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.  
Patients with HIV and hepatitis B or C virus co-infection:  
Nov 2021  
Initial:………………….  
Page 8 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Patients with chronic hepatitis B or C and treated with antiretroviral therapy are at an increased risk for  
severe and potentially fatal hepatic adverse reactions. 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). In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant  
package inserts for these medicines.  
Patients co-infected with HIV and HBV who discontinue Hetacav Oral Solution 20 mg/ml should be closely  
monitored with both clinical and laboratory follow-up after stopping treatment. In patients with advanced  
liver disease or cirrhosis, treatment discontinuation - is not recommended since post treatment exacerbation  
of hepatitis may lead to hepatic decompensation.  
Osteonecrosis:  
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption,  
severe immune suppression, 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.  
Opportunistic infections:  
Patients receiving Hetacav Oral Solution 20 mg/ml 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 medical practitioners experienced in treatment of patients with associated HIV  
disease.  
The risk of HIV transmission to others:  
Patients should be advised that current antiretroviral therapy, including Hetacav Oral Solution 20 mg/ml  
has not been proven to prevent the risk of transmission of HIV to others through sexual contact or blood  
contamination. Appropriate precaution should continue to be employed.  
Nov 2021  
Initial:………………….  
Page 9 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Hetacav Oral Solution 20 mg/ml contains sorbitol and may have a laxative effect. Patients with rare  
hereditary problems of sorbitol intolerance should not take Hetacav Oral Solution 20 mg/ml.  
4.5 Interaction with other medicines and other forms of interaction  
Abacavir shows no potential to inhibit metabolism mediated by the cytochrome P450 3A4 enzyme. There  
is little potential for drug interactions with antiretroviral protease inhibitors and other medicines metabolised  
by major P450 enzymes. There are no clinically significant interactions between abacavir, zidovudine, and  
lamivudine.  
Ethanol: The metabolism of abacavir is altered by concomitant ethanol resulting in an increase in AUC of  
abacavir of about 41 %. No dose reduction of abacavir is necessary. Abacavir has no effect on the  
metabolism of ethanol.  
Methadone: In a pharmacokinetic study, co-administration of 600 mg abacavir twice daily with methadone  
showed a 35 % reduction in abacavir Cmax and a one-hour delay in Tmax but the AUC was unchanged. The  
changes in abacavir pharmacokinetics are not considered clinically relevant. In this study abacavir  
increased the mean methadone systemic clearance by 22 %. This change is not considered clinically  
relevant for the majority of patients, however occasionally methadone re-titration may be required.  
Retinoids: Retinoid compounds such as isotretinoin are eliminated via alcohol dehydrogenase. Interaction  
with abacavir is possible but has not been studied.  
4.6 Fertility, pregnancy and lactation  
Pregnancy:  
The safe use of Hetacav Oral Solution 20 mg/ml in human pregnancy has not been established.  
Breastfeeding:  
Nov 2021  
Initial:………………….  
Page 10 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Abacavir and its metabolites are secreted into the milk of lactating rats. It is expected that these will also  
be secreted into human milk, although this has not been confirmed. There is no data available on the safety  
of Hetacav Oral Solution 20 mg/ml when administered to babies less than three months old. It is therefore  
recommended that mothers do not breastfeed their babies while receiving treatment with Hetacav Oral  
Solution 20 mg/ml.  
4.7 Effects on ability to drive and use machines  
No studies on the effects on ability to drive and use machines have been performed.  
4.8 Undesirable effects  
Hypersensitivity: approximately 4 % of subjects receiving Hetacav Oral Solution 20 mg/ml develop  
a hypersensitivity reaction which in rare cases is fatal. The symptoms of this hypersensitivity reaction  
can occur at any time during treatment with Hetacav Oral Solution 20 mg/ml, but usually appear  
within the first six weeks of initiation of treatment (median time to onset 11 days).  
The signs and symptoms of this hypersensitivity reaction are listed below:  
Skin: rash (usually maculopapular or urticarial)  
Gastrointestinal tract: nausea, vomiting, diarrhoea, abdominal pain and mouth ulceration.  
Respiratory tract: dyspnoea, sore throat, cough or pharyngitis, respiratory failure.  
Miscellaneous: fever, fatigue, malaise, oedema, lymphadenopathy, hypotension, conjunctivitis,  
anaphylaxis  
Neurological/psychiatry: headache, paraesthesia  
Haematological: lymphopenia  
Liver/pancreas: elevated liver function tests, hepatic failure  
Musculoskeletal: myalgia, myolysis, arthralgia, elevated creatine phosphokinase  
Urology: elevated creatinine, renal failure  
Nov 2021  
Initial:………………….  
Page 11 of 17  
Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Some patients with hypersensitivity reactions were initially thought to have respiratory disease (pneumonia,  
bronchitis, and pharyngitis), a flu-like illness, gastroenteritis or reactions to other medications.  
This delay in diagnosis of hypersensitivity has resulted in abacavir being continued or re-introduced, leading  
to more severe hypersensitivity reactions or death. Therefore, the diagnosis of hypersensitivity reactions  
should be carefully considered for patients presenting with symptoms of these diseases.  
In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis  
of clinical decision-making. Even in the absence of the HLA-B*5701 allele, it is important to permanently  
discontinue abacavir and not re-challenge with abacavir if a hypersensitivity reaction cannot be ruled out  
on clinical grounds, due to the potential for a severe or even fatal reaction.  
The following adverse effects have been reported while taking  
Hetacav Oral Solution 20 mg/ml:  
SYSTEM ORGAN CLASS  
Blood and lymphatic Less frequent  
system disorders  
Endocrine disorders  
Metabolism and nutrition Frequent  
FREQUENCY  
ADVERSE REACTION  
Anaemia, immune reactivation syndrome,  
neutropenia  
Less frequent  
Elevated creatine phosphokinase  
anorexia  
disorders  
Frequency unknown  
elevated blood glucose and triglyceride  
concentrations, redistribution/accumulation of  
body  
hypertrigyceridaemia, hypercholesterolaemia,  
insulin resistance, hyperglycaemia,  
hyperlactaemia, hyperlipidemia, myalgia,  
fat  
(see  
section  
4.4),  
myositis, rhabdomyolysis and elevated liver  
enzymes.  
Psychiatric disorders  
Frequent  
depressive disorders, dreams/sleep disorders  
Nov 2021  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Less frequent  
Frequent  
anxiety  
Nervous system disorders  
headache, insomnia, convulsions, hypotonia  
ear/nose/throat infections, viral respiratory  
infections pneumonia  
Respiratory, thoracic and Less frequent  
mediastinal disorders  
Gastrointestinal disorders  
Frequent  
nausea, vomiting and diarrhoea  
pancreatitis  
Less frequent  
Skin  
and  
subcutaneous Frequent  
rash (without systemic symptoms)  
tissue disorders  
Less frequent  
erythema  
multiforme,  
Stevens-Johnson  
syndrome and toxic epidermal necrolysis.  
Lethargy, fatigue, fever  
General  
disorders  
and Frequent  
site  
administration  
conditions  
Less frequent  
abnormal behavior  
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of Hetacav Oral Solution 20 mg/ml is  
important. It allows continued monitoring of the benefit/risk balance of the Hetacav Oral Solution 20  
mg/ml. Healthcare professionals are asked to report any suspected adverse to report any suspected  
adverse reactions to SAHPRA 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  
The effects of higher doses are not known. If over dosage occurs the patient should be monitored for  
evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary.  
Nov 2021  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
5 PHARMACILOGICAL PROPERTIES  
5.1 Pharmacodynamic properties  
A 20.2.8 Antiviral agents  
Abacavir is a nucleoside analogue reverse transcriptase inhibitor.  
It is a selective inhibitor of HIV-1 and HIV-2, including HIV-1 isolates with reduced susceptibility to  
zidovudine, lamivudine, zalcitabine, didanosine or nevirapine. Abacavir is metabolised intracelullarly to the  
active moiety, carbovir 5’- triphosphate (TP).  
Abacavir’s mechanism of action in relation to HIV is inhibition of the HIV reverse transcriptase enzyme, an  
event that results in chain termination and interruption of the viral replication cycle.  
5.2 Pharmacokinetic properties  
Absorption  
Abacavir is well absorbed following oral administration. The absolute bioavailability of oral abacavir in adults  
is about 83 %. Following oral administration, the mean time (Tmax) to maximal serum concentrations of  
abacavir is about 1,0 hour.  
Distribution  
The apparent volume of distribution is about 0,8 ℓ/kg, indicating that abacavir penetrates freely into body  
tissues. Studies in HIV infected patients have shown good penetration of abacavir into the cerebrospinal  
fluid (CSF), with a CSF to plasma AUC ratio of between 30 to 44 %.  
Biotransformation  
Abacavir is principally metabolised by the liver with less than 2 % of the administered dose being renally  
excreted, unchanged. The main pathways of metabolism are by alcohol dehydrogenase and by  
glucuronidation to produce the 5’-carboxylic acid and 5’-glucuronide which account for about 66 % of the  
dose in the urine.  
Elimination  
Nov 2021  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
The mean half-life of abacavir is about 1,5 hours. Elimination of abacavir is via hepatic metabolism with  
ensuing excretion of metabolites primarily in the urine. The metabolites and unchanged abacavir account  
for about 83 % of the administered abacavir dose in the urine, the remainder is eliminated in the faeces.  
Pharmacokinetics in special populations:  
Elderly:  
When treating elderly patients, consideration needs to be given to the greater frequency of decreased  
hepatic, renal and cardiac function, and concomitant disease or other medicine therapy.  
Renal impairment:  
Abacavir is mainly metabolised by the liver, with approximately 2 % of abacavir excreted unchanged in the  
urine. The pharmacokinetics of abacavir in patients with end-stage renal disease is similar to patients with  
normal renal function. Therefore, there is no dosage reduction required in patients with renal impairment.  
Paediatric population  
Abacavir’s overall pharmacokinetic parameters in children are comparable to adults. There is insufficient  
safety data to recommend the use of abacavir in infants less than three months old.  
6 PHARMACEUTICAL PARTICULARS  
6.1 List of excipients  
•
•
•
•
•
•
•
Abacavir sulphate  
Noncrystalizing sorbitol solution  
Sodium citrate  
MethyI paraben  
Propyl paraben  
Propylene glycol  
Citric acid, Anhydrous  
Nov 2021  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
•
•
•
Saccharin Sodium  
NA & Strawberry FL wild TP  
Banana FlavorART  
6.2 Incompatibilities  
N/A  
6.3 Shelf life  
24 months  
6.4 Special precautions or storage  
Store at or below 25 °C.  
Keep the HDPE container well closed and protect from moisture.  
Do not refrigerate.  
KEEP OUT OF REACH OF CHILDREN  
6.5 Nature and contents of container  
250 ml white opaque HDPE bottles with white, opaque polypropylene child resistant plastic caps with pulp  
liners cap. The bottle contains 240 ml (20 mg/ml abacavir) of solution. Bottle is enclosed in an outer  
cardboard box with a 20 ml dosing syringe is included inside the box.  
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,  
Nov 2021  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd  
Product proprietary name: HETACAV Oral Solution 20 mg/ml  
Dosage form and strength: Each 1 ml contains abacavir sulphate equivalent to 20 mg of abacavir  
Building 2, First Floor,  
74 Waterfall Drive,  
Midrand, 2066  
8 REGISTRATION NUMBER  
48/20.2.8/0342  
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION  
29 July 2016  
10 DATE OF REVISION OF THE TEXT  
09 November 2021  
Nov 2021  
Initial:………………….  
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