Teevir 300 mg, 600 mg, 200 mg FC tablets.

TEEVIR is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.

Therapy should be initiated by a medical practitioner experienced in the management of human immunodeficiency virus (HIV) infection.

Posology

Adults: The recommended dose of TEEVIR is one tablet taken orally once daily.

Method of administration: It is recommended that TEEVIR be swallowed whole with water. It is recommended that TEEVIR be taken on an empty stomach since food may increase efavirenz exposure and may lead to an increase in the frequency of adverse reactions. In order to improve the tolerability to efavirenz with respect to undesirable effects on the nervous system, bedtime dosing is recommended. It is anticipated that tenofovir exposure will be approximately 35 % lower following administration of TEEVIR on an empty stomach as compared to the individual component tenofovir disoproxil fumarate when taken with food. In virologically suppressed patients, the clinical relevance of this reduction can be expected to be limited. Further data on the clinical translation of the decrease in pharmacokinetic exposure is awaited.

Children and adolescents: TEEVIR is not recommended for use in children below 18 years of age due to lack of data on safety and efficacy.

Elderly: Insufficient numbers of elderly patients have been evaluated in clinical studies of the components of TEEVIR to determine whether they respond differently than younger patients. Caution should be exercised when prescribing TEEVIR to the elderly, keeping in mind the greater frequency of decreased hepatic or renal function in these patients.

Dose adjustment: If TEEVIR is co-administered with rifampicin, an additional 200 mg/day (800 mg total) of efavirenz is recommended.

Renal insufficiency: TEEVIR is not recommended for patients with moderate or severe renal impairment (creatinine clearance (CrCl) < 50 ml/min). Patients with moderate or severe renal impairment require dose interval adjustment of emtricitabine and tenofovir disoproxil fumarate that cannot be achieved with the combination tablet.

Hepatic impairment: The pharmacokinetics of TEEVIR have not been studied in patients with hepatic impairment. Patients with mild-to-moderate liver disease (Child-Pugh Grade A or B) may be treated with the normal recommended dose of TEEVIR. Patients should be monitored carefully for adverse reactions, especially nervous system symptoms related to efavirenz.

TEEVIR is contraindicated in patients with severe hepatic impairment.

It is important to take TEEVIR on a regular dosing schedule to avoid missing doses. Patients should be told that if they forget to take TEEVIR they should take the missed dose right away, unless it is less than 12 hours until the next dayu2019s dose. In this case, patients should be told not to take the missed dose and to take their next dose at the usual time.

• Hypersensitivity to TEEVIR or to any of the excipients.
• TEEVIR must not be used in patients with severe hepatic impairment.
• TEEVIR must not be administered concurrently with astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, or ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine), because competition for cytochrome P450 CYP3A4 by efavirenz could result in inhibition of metabolism and create the potential for serious and/or life-threatening undesirable effects (for example, cardiac dysrhythmias, prolonged sedation or respiratory depression).
• Herbal preparations containing St. Johnu2019s Wort (Hypericum perforatum) must not be used while taking TEEVIR due to the risk of decreased plasma concentrations and reduced clinical effects of TEEVIR.
• Efavirenz significantly decreases voriconazole plasma concentrations while voriconazole also significantly increases efavirenz plasma concentrations. Since TEEVIR is a fixed-dose combination product, the dose of efavirenz cannot be altered; therefore, voriconazole and TEEVIR must not be co-administered.
• TEEVIR must not be used in patients with moderate to severe renal impairment (creatine clearance < 50 ml/min) (see 4.4 Special warnings and precautions for use and 4.2 Posology and method of administration).
• TEEVIR must not be used during pregnancy and breast-feeding (see 4.6 Fertility, pregnancy and lactation).
• TEEVIR must not be used in patients younger than 18 years of age due to lack of safety and efficacy.
• TEEVIR must not be used concomitantly with medicinal products containing any of the components efavirenz, emtricitabine or tenofovir, or who concomitantly take other cytidine analogues, such as lamivudine and adefovir dipivoxil.

General: ALERT: Find out about medicines that should NOT be taken with TEEVIR or any of the active ingredients of TEEVIR (see 4.3 Contraindications, 4.5 Interaction with other medicinal products and other forms of interaction and 4.8 Undesirable effects).

Serious nervous system and psychiatric symptoms have been reported with efavirenz, one of the active ingredients in TEEVIR.

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, such as contained in TEEVIR, 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 TEEVIR 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 TEEVIR 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).

Patients with HIV and hepatitis B virus co-infection: It is recommended that all patients with HIV be tested for the presence of hepatitis B virus (HBV) before initiating antiretroviral therapy. TEEVIR is not indicated for the treatment of chronic HBV infection and the safety and efficacy of TEEVIR have not been established in patients co-infected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients after the discontinuation of emtricitabine (200 mg) and tenofovir disoproxil fumarate. Hepatic function should be closely monitored with both clinical and laboratory follow up for at least several months in patients who discontinue TEEVIR and are co-infected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Renal impairment: Emtricitabine and tenofovir, two of the active ingredients in TEEVIR are principally eliminated by the kidneys. Dosing interval adjustment of emtricitabine and tenofovir is recommended in all patients with creatinine clearance 30 u2013 49 ml/min. Since this is not possible with a fixed dose combination, TEEVIR should not be administered to patients with creatinine clearance < 50 ml/min or patients requiring haemodialysis (see 4.2 Posology and method of administration). 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 (see 4.8 Undesirable effects). The majority of these cases occurred in patients with underlying systemic or renal disease, or in patients taking nephrotoxic agents. However, some cases occurred in patients without identifiable risk factors. TEEVIR should be avoided with concurrent or recent use of a nephrotoxic agent. Patients at risk for, or with a history of, renal dysfunction and patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorous.

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 Graves' disease) have also been reported as IRIS reactions; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.

Osteonecrosis: Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported, particularly in patients with advanced HIV-disease and/or long-term exposure to combination antiretroviral therapy (cART). Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

Opportunistic infections: Patients receiving TEEVIR should be advised that they may continue to develop opportunistic infections and other complications of HIV infection, and therefore they should remain under close observation by healthcare professionals experienced in the treatment of patients with associated HIV disease. Regular monitoring of viral load and CD4 counts needs to be done.

The risk of HIV transmission to others: Patients should be advised that current antiretroviral therapy, including TEEVIR, does not prevent the risk of transmission of HIV to others through sexual contact or blood contamination. Appropriate precautions should continue to be employed.

Lactic acidosis/hyperlactataemia: Use of TEEVIR can result in potentially fatal lactic acidosis as a consequence of mitochondrial dysfunction. 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/u2113) and the serum bicarbonate and respond as follows:

• Lactate 2-5 mmol/u2113 with minimum symptoms: switch to agents that are less likely to cause lactic acidosis.
• Lactate 5-10 mmol/u2113 with symptoms and/or with reduced standard bicarbonate: Stop NRTIs and change treatment option. Once lactate has settled, use medicines that are less likely to cause lactic acidosis. Exclude other causes, (e.g. sepsis, uraemia, diabetic ketoacidosis, thyrotoxicosis and hyperthyroidism).
• Lactate > 10 mmol/u2113: STOP all therapy (80 % mortality).

The above lactate values may not be applicable to paediatric patients. Caution should be exercised when administering TEEVIR to patients with known risk factors for liver disease. Treatment with TEEVIR 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 fetus 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 sign and symptoms.

Pancreatitis: Pancreatitis has been observed in some patients receiving TEEVIR. Pancreatitis must be considered whenever a patient develops abdominal pain, nausea, vomiting or elevated biochemical markers. Discontinue use of TEEVIR until diagnosis of pancreatitis is excluded.

Patients with moderate to severe renal impairment: In patients with moderate to severe renal impairment, the terminal half-life of TEEVIR is increased due to decreased clearance. The dose of TEEVIR should therefore be adjusted (see 4.2 Posology and method of administration).

Liver disease: Use of TEEVIR can result in hepatomegaly due to nonalcoholic fatty liver disease (hepatic steatosis). The safety and efficacy of TEEVIR 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 preexisting 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: 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 TEEVIR 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. Discontinuation of TEEVIR therapy in patients coinfected with HIV and HBV may be associated with severe, acute exacerbations of hepatitis. If TEEVIR is discontinued in patients co-infected with HIV and HBV, these patients should be closely monitored for evidence of exacerbation of hepatitis. Where discontinuation of therapy with one of the components of TEEVIR is indicated or where dose modification is necessary, separate preparations of efavirenz, emtricitabine and tenofovir disoproxil fumarate are available. Please refer to the package inserts for these products. If therapy with TEEVIR is discontinued, consideration should be given to the long half-life of efavirenz and long intracellular half-lives of tenofovir and emtricitabine. Because of interpatient variability in these parameters and concerns regarding development of resistance, HIV treatment guidelines should be consulted, also taking into consideration the reason for discontinuation.

ALERT: Find out about medicines that should NOT be taken with TEEVIR (see 4.5 Interaction with other medicines and other forms of interaction). Since emtricitabine and tenofovir are primarily eliminated by the kidneys, co-administration of TEEVIR 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 adefovir dipivoxil, cidofovir, acyclovir, valaciclovir, ganciclovir and valganciclovir.

TEEVIR should not be co-administered with emtricitabine (200 mg), tenofovir or efavirenz. Due to similarities between emtricitabine and lamivudine, TEEVIR should not be co-administered with other medicines containing lamivudine, including lamivudine and zidovudine co-formulation, lamivudine for HIV, lamivudine for HBV, abacavir sulphate and lamivudine coformulation or abacavir sulphate, lamivudine and zidovudine co-formulation.

Bone effects: Tenofovir In a clinical study through 144 weeks, decreases from baseline in bone mineral density (BMD) were seen at the lumbar spine and hip in both treatment arms of the study. At week 144, there was a significantly greater mean percentage decrease from baseline in BMD at the lumbar spine in patients who received tenofovir + lamivudine + efavirenz compared with patients who received stavudine + lamivudine + efavirenz. Changes in BMD at the hip were similar between the two treatment groups. In both groups, the majority of the reduction in BMD occurred in the first 24 u2013 48 weeks of the study and this reduction was sustained through week 144. Twenty eight percent of tenofovir-treated patients versus 21 % of stavudine-treated patients lost at least 5 % of BMD at the spine or 7 % of BMD at the hip. Clinically relevant fractures (excluding fingers and toes) were reported in 4 patients in the tenofovir-group and 6 patients in the stavudine-group. In addition, there were significant increases in biochemical markers of bone metabolism (serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide and urinary N-telopeptide) in the tenofovir-group relative to the stavudine-group, suggesting increased bone turnover. Serum parathyroid hormone levels and 1,25 vitamin D levels were also higher in the tenofovir-group. Except for bone-specific alkaline phosphatase, these changes resulted in values that remained within the normal range. The effects of tenofovir-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. 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. If bone abnormalities are suspected then appropriate consultation should be obtained.

Pregnancy: Safety in pregnancy has not been established. There are no adequate or well-controlled studies of TEEVIR or its components in pregnant women. A small number of cases of neural tube defects, including meningomyelocele, have been reported but causality has not been established. Studies of efavirenz in animals have shown reproductive toxicity including marked teratogenic effects. TEEVIR should not be used during pregnancy. Women of childbearing potential should avoid pregnancy while receiving TEEVIR. Barrier contraception should always be used in combination with other methods of contraception (for example, oral or other hormonal contraceptives) while on therapy with TEEVIR. Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of TEEVIR is recommended. Women of childbearing potential should undergo pregnancy testing before initiation of TEEVIR.

Lactation: Studies in rats have demonstrated that efavirenz and tenofovir are excreted in milk; concentrations of efavirenz were much higher than those in maternal plasma. It is not known whether efavirenz, emtricitabine or tenofovir are excreted in human milk. Because of the potential for both HIV transmission and the potential for serious undesirable effects in breastfeeding infants, mothers should be instructed not to breast-feed if they are receiving TEEVIR.

Efavirenz, and therefore TEEVIR, may cause dizziness, impaired concentration, and/or drowsiness. Patients should be instructed that if they experience these symptoms, they should avoid potentially hazardous tasks, such as driving or operating machinery.

Side-effects EMTRICITABINE Blood and lymphatic system disorders Frequencies unknown: Neutropenia, anaemia Metabolism and nutrition disorders Frequencies unknown: Lactic acidosis, usually associated with severe hepatomegaly and steatosis, has been associated with nucleoside reverse transcriptase inhibitors. Hypertriglyceridaemia and hyperglycaemia. Nervous system disorders Frequent: Headache, asthenia Less frequent: Neuritis, paraesthesia and peripheral neuropathy and dizziness Psychiatric disorders Less frequent: Depressive disorders, sleep disturbances, abnormal dreams, insomnia Respiratory, thoracic and mediastinal disorders Frequent: Increased cough, rhinitis Gastrointestinal disorders Frequent: Nausea, diarrhoea Less frequent: Abdominal pain, dyspepsia and vomiting Hepatobiliary disorders Frequencies unknown: Raised liver enzyme concentrations and hyperbilirubinaemia Skin and subcutaneous tissue disorders Less frequent: Skin rashes (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash and allergic reaction) and skin discolouration, manifested by hyperpigmentation on the palms and/or soles. Musculoskeletal system disorders Less frequent: Arthralgia, myalgia Renal and urinary system disorders Frequent: Elevation of creatinine TENOFOVIR Blood and lymphatic system disorders Frequencies unknown: Neutropenia, haematuria Immune system disorders Frequencies unknown: Allergic reactions Metabolism and nutrition disorders Frequencies unknown: Lactic acidosis, usually associated with severe hepatomegaly and steatosis; also hypertriglyceridaemia, hyperglycaemia, hyperphosphataemia Nervous system disorders Frequent: Asthenia Less frequent: Anorexia Frequencies unknown: Headache, dizziness and peripheral neuropathy Psychiatric disorders Frequencies unknown: Depression, insomnia and anxiety Respiratory, thoracic and mediastinal disorders Frequencies unknown: Chest pain, pneumonia, dyspnoea Gastrointestinal disorders Frequent: Nausea, vomiting, diarrhoea Less frequent: Raised serum amylase concentrations, abdominal pain and flatulence Frequencies unknown: Pancreatitis and dyspepsia Hepatobiliary disorders Less frequent: Hepatotoxicity, including lactic acidosis Frequencies unknown: Raised liver enzymes and hepatitis Skin and subcutaneous tissue disorders Frequencies unknown: Skin rashes (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash and pustular rash) Musculoskeletal system disorders Frequent: decrease in bone mineral density Frequencies unknown: Back pain, myalgia, arthralgia Renal and urinary system disorders Frequencies unknown: Increased creatinine levels, nephritis, nephrogenic diabetes insipidus, renal impairment, acute renal failure and effects on the renal proximal tubules, including Fanconi syndrome and acute tubular necrosis General disorders and administrative site conditions Frequencies unknown: Fever, sweating and weight loss EFAVIRENZ Metabolism and nutritional system disorders Frequencies unknown: Weight gain and weight loss Nervous system disorders Frequent: Dizziness, impaired concentration, somnolence and headache Less frequent: Anorexia and hypoaesthesia Frequencies unknown: Abnormal co-ordination, ataxia, convulsions, paraesthesia, neuropathy, tremors, amnesia, increased appetite, confusion, impaired co-ordination, impotence, decreased libido, increased libido, neuralgia, peripheral neuropathy, speech disorder and vertigo Psychiatric disorders Frequent: Insomnia Less frequent: Abnormal dreams Frequencies unknown: Aggravated depression, agitation, anxiety, apathy, confusion, emotional lability, euphoria and hallucination Eye disorders Frequencies unknown: Abnormal vision Ear and labyrinth disorders Frequencies unknown: Tinnitus Cardiac disorders Frequencies unknown: Flushing Vascular disorders Frequencies unknown: Palpitations and tachycardia Respiratory system disorders Frequencies unknown: Asthma, sinusitis, dyspnoea and upper respiratory tract infections Gastrointestinal disorders Frequent: Nausea, vomiting and diarrhoea Less frequent: Dyspepsia and abdominal pain Frequencies unknown: Gastritis, gastro-enteritis, gastro-oesophageal reflux, constipation and malabsorption, taste perversion Hepatobiliary disorders Frequencies unknown: Hepatitis, hepatic enzyme increase and hepatic failure Skin and subcutaneous tissue disorders Frequent: Rash, pruritus and increased sweating Frequencies unknown: Acne, alopecia, eczema, folliculitis, seborrhea, skin exfoliation, urticaria, erythema multiforme, nail disorders, skin discolouration, Stevens-Johnson syndrome Musculoskeletal system disorders Frequencies unknown: Arthralgia, myalgia and myopathy General disorders and administrative site conditions Frequent: Fatigue and pain Frequencies unknown: Alcohol intolerance, allergic reaction, asthenia, hot flushes influenza-like symptoms, malaise, pain, syncope and redistribution/accumulation of body fat Laboratory abnormalities Raised liver enzyme values have occurred, particularly in patients with viral hepatitis. Raised serum cholesterol and triglyceride concentrations have been reported. Liver enzymes Elevations of AST and ALT to greater than five times the upper limit of the normal range were seen in patients treated with 600 mg of efavirenz. Elevations of GGT in patients receiving efavirenz may reflect enzyme induction not associated with liver toxicity (see 4.4 Special warnings and precautions for use). Lipids Increases in total cholesterol of 10 to 20 % have been observed in some uninfected volunteers receiving efavirenz. Increases in non-fasting total cholesterol and HDL of approximately 20 % and 25 %, respectively, were observed in patients treated with efavirenz + ZDV + STC and of approximately 40 % and 35 % in patients treated with efavirenz + IDV. The effects of efavirenz on triglycerides and LDL were not well characterised. The clinical significance of these findings is unknown toxicity (see 4.4 Special warnings and precautions for use). 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 to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

If overdose occurs the patient must be monitored for evidence of toxicity and standard supportive treatment supplied as necessary.

Emtricitabine: Limited clinical experience is available at doses higher than the therapeutic dose of emtricitabine (200 mg). 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: Limited clinical experience at doses higher than the therapeutic dose of tenofovir 300 mg is available. The effects of higher doses are not known. Tenofovir is efficiently removed by haemodialysis with an extraction coefficient of approximately 54 %. Following a single 300 mg dose of tenofovir, a four-hour haemodialysis session removed approximately 10 % of the administered tenofovir dose.

Efavirenz: Some patients accidentally taking 600 mg twice daily have reported increased nervous system symptoms and involuntary muscle contractions. Treatment of overdose with efavirenz should consist of general supportive measures, including monitoring of vital signs and observation of the patientu2019s clinical status. Administration of activated charcoal may be used to aid removal of unabsorbed medicine. There is no specific antidote for overdose with efavirenz. Since efavirenz is highly protein bound, dialysis is unlikely to significantly remove the medicine from the blood.