Trelavue 50mg. 600mg. 300mg Tablet

TRELAVUE is indicated for the treatment of Human Immunodeficiency Virus (HIV) infection in adults and adolescents from 18 years of age, who are antiretroviral treatment-nau00efve or are infected with HIV without documented or clinically suspected resistance to any of the three antiretroviral agents in TRELAVUE.

TRELAVUE therapy should be initiated by a medical practitioner experienced in the management of HIV infection. TRELAVUE should not be administered to patients younger than 18 years. TRELAVUE can be taken with or without food. TRELAVUE is a fixed-dose tablet and should not be prescribed for patients requiring dosage adjustments, such as those with creatinine clearance less than 50 ml/min. Separate preparations of dolutegravir, abacavir or lamivudine should be administered in cases where discontinuation or dose adjustment is indicated. In these cases, the medical practitioner should refer to the individual product information for these medicinal products. Since the recommended dose of dolutegravir is 50 mg twice daily for patients with resistance to integrase inhibitors, the use of TRELAVUE is not recommended for patients with integrase inhibitor resistance. Populations: Adults and adolescents: The recommended dose of TRELAVUE in adults and adolescents weighing more than 40 kg is one tablet once daily. Elderly: There are limited data available on the use of dolutegravir, abacavir and lamivudine in patients aged 65 years and over. However, there is no evidence that elderly patients require a different dose than younger adult patients (see Pharmacokinetic properties u2013 Special Patient Populations). When treating elderly patients, consideration needs to be given to the greater frequency of decreased hepatic, renal and cardiac function, concomitant medicinal products or disease. Renal impairment: Whilst no dosage adjustment of dolutegravir or abacavir is necessary in patients with renal impairment, a dose reduction of lamivudine is required due to decreased clearance. Therefore, TRELAVUE should not be used in patients with a creatinine clearance less than 50 ml/min (see Pharmacokinetic properties u2013 Special Patient Populations and CONTRAINDICATIONS). Hepatic impairment: A dose reduction of abacavir may be required for patients with mild hepatic impairment (Child-Pugh grade A). As dose reduction is not possible with TRELAVUE, the separate preparations of dolutegravir, abacavir or lamivudine should be used when this is judged necessary. TRELAVUE is not recommended in patients with moderate and severe hepatic impairment (Child-Pugh grade B or C) (see Pharmacokinetic properties u2013 Special Patient Populations and CONTRAINDICATIONS).

TRELAVUE is contraindicated in patients with known hypersensitivity to dolutegravir, abacavir or lamivudine, or to any of the excipients. TRELAVUE is contraindicated in combination with dofetilide or pilsicainide. TRELAVUE is contraindicated for patients with moderate and severe hepatic impairment due to the abacavir component (see PHARMACOLOGICAL ACTION). TRELAVUE is contraindicated during pregnancy or in mothers who are breastfeeding their infants (see PREGNANCY AND LACTATION). TRELAVUE is contraindicated in patients with renal impairment with a creatinine clearance of < 50 ml/min due to the lamivudine component (see PHARMACOLOGICAL ACTION). Metformin is contraindicated in patients taking TRELAVUE.

Warnings relevant to dolutegravir, abacavir and lamivudine are included in this section. There are no additional warnings relevant to TRELAVUE. Hypersensitivity to abacavir u2013 refer to Boxed Warning. 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. 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 below), 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 sign and symptoms. Pancreatitis: Pancreatitis has been observed in some patients receiving TRELAVUE. Pancreatitis must be considered whenever a patient develops abdominal pain, nausea, vomiting or elevated biochemical markers. Discontinue use of TRELAVUE until diagnoses of pancreatitis is excluded. Hypersensitivity to dolutegravir: Hypersensitivity reactions have been reported with dolutegravir and were characterised by rash, constitutional findings and sometimes, organ dysfunction, including liver injury. Discontinue TRELAVUE immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, hepatitis, eosinophilia, angioedema). Clinical status including liver aminotransferases should be monitored and appropriate therapy initiated. Delay in stopping treatment with TRELAVUE after the onset of hypersensitivity may result in a life-threatening reaction. Lactic acidosis/severe hepatomegaly with steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of abacavir and lamivudine. A majority of these cases have been in women. Clinical features which may be indicative of the development of lactic acidosis include generalised weakness, anorexia, and sudden unexplained weight loss, gastrointestinal symptoms and respiratory symptoms (dyspnoea and tachypnoea). In patients with suspicious symptoms of biochemistry, measure the venous lactate level (normal 10 mmol/u2113: STOP all therapy (80 % mortality). Diagnosis of lactic acidosis is confirmed by demonstrating metabolic acidosis with an increased anion gap and raised lactate level. Therapy should be stopped in any patient with a raised lactate level. Blood for lactate assay should be heparinised and stored on ice. After recovery, NRTIs should be avoided. Seek expert advice on medicine selection. The above lactate values may not be applicable to paediatric patients. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of TRELAVUE alone or in combination. Caution should be exercised when administering TRELAVUE particularly to those with known risk factors for liver disease. Treatment with TRELAVUE should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis with or without hepatitis (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations). 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, elevated serum lipid and blood glucose levels have been observed either separately or together in some patients (see SIDE EFFECTS). Clinical examination should include evaluation for physical signs of fat redistribution. Consideration should be given to the measurement of serum lipids and blood glucose. Lipid disorders should be managed as clinically appropriate. Immune Reconstitution Syndrome: In HIV-infected patients with severe immune deficiency at the time of initiation of anti-retroviral therapy (ART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise 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 ART. Relevant examples are tuberculosis, cytomegalovirus retinitis, generalised and/or atypical focal mycobacterial infections and Pneumocystis jiroveci (P. carinii) pneumonia. Any inflammatory symptoms must be evaluated without delay and treatment initiated when necessary. Auto-immune disorders (such as Gravesu2019 disease, polymyositis and Guillain-Barre syndrome) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable and can occur many months after initiation of treatment and sometimes can be an atypical presentation. Liver chemistry elevations consistent with immune reconstitution syndrome were observed in some hepatitis B and/or C co-infected patients at the start of dolutegravir therapy. Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-infection (see Patients co-infected with hepatitis B virus (HBV) later in this section and SIDE EFFECTS). Patients co-infected with hepatitis B virus (HBV): Particular diligence should be applied in initiating or maintaining effective hepatitis B therapy when starting therapy with TRELAVUE in hepatitis B co-infected patients. Clinical study and marketed use of lamivudine, have shown that some patients with chronic HBV disease may experience clinical or laboratory evidence of recurrent hepatitis upon discontinuation of lamivudine, which may have more severe consequences in patients with decompensated liver disease. If TRELAVUE is discontinued in patients co-infected with HBV, periodic monitoring of both liver function tests and markers of HBV replication should be considered. Opportunistic infections: Patients receiving TRELAVUE may still develop opportunistic infections and other complications of HIV infection. Therefore patients should remain under close clinical observation by medical practitioners experienced in the treatment of these associated HIV diseases. Transmission of infection: Patients should be advised that antiretroviral therapy, including TRELAVUE, has not been proven to prevent the risk of transmission of HIV to others through sexual contact or blood contamination. Appropriate precautions should continue to be taken. Myocardial Infarction: In a prospective, observational, epidemiological study designed to investigate the rate of myocardial infarction in patients on combination antiretroviral therapy, the use of abacavir within the previous six months was correlated with an increased risk of myocardial infarction. As a precaution the underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir and action taken to minimise all modifiable risk factors (e.g. hypertension, hyperlipidaemia, diabetes mellitus and smoking).

Caution should be given to co-administering medications (prescription and non-prescription) that may change the exposure of dolutegravir, abacavir, lamivudine or medications that may have their exposure changed by TRELAVUE (see CONTRAINDICATIONS and INTERACTIONS). The co-administration of dolutegravir with etravirine (ETR) is not recommended unless the patient is also receiving concomitant atazanavir + ritonavir (ATV+RTV), lopinavir + ritonavir (LPV+RTV) or darunavir + ritonavir (DRV+RTV) (see INTERACTIONS). Dolutegravir should not be co-administered with polyvalent cation-containing antacids. Dolutegravir is recommended to be administered 2 hours before or 6 hours after these agents (see INTERACTIONS). TRELAVUE is recommended to be administered 2 hours before or 6 hours after taking calcium or iron supplements, or alternatively, administered with food (see INTERACTIONS). Metformin concentrations may be increased by TRELAVUE. Metformin is contraindicated in patients taking TRELAVUE (see CONTRAINDICATIONS). TRELAVUE should not be administered concurrently with other medicinal products containing any of the same active components (dolutegravir, abacavir, and/or lamivudine). Since the recommended dose of dolutegravir is 50 mg twice daily for patients taking efavirenz, nevirapine, rifampicin and tipranavir/ritonavir, the use of TRELAVUE is not recommended for patients taking these medicines (see INTERACTIONS).

TRELAVUE should not be used during pregnancy and lactation as teratogenicity has been observed in animal studies. The safe use of TRELAVUE in human pregnancy has not been established. Dolutegravir, lamivudine and abacavir were shown to cross the placenta in reproductive toxicity studies in animals. There have been reports of elevations in serum lactate levels, which may be due to mitochondrial dysfunction, in neonates and infants exposed in utero or peri-partum to nucleoside reverse transcriptase inhibitors (NRTIs) such as abacavir and lamivudine. The clinical relevance of transient elevations in serum lactate is unknown. There have also been reports of developmental delay, seizures and other neurological disease. Lactation: HIV infected women should not breastfeed their infants in order to avoid transmission of HIV. It is expected that abacavir and dolutegravir will be secreted into human milk. Lamivudine is excreted in human milk at similar concentrations to those found in serum. Therefore, mothers breastfeeding their infants should not use TRELAVUE.

There have been no studies to investigate the effect of TRELAVUE on driving performance or the ability to operate machinery. The clinical status of the patient and the adverse event profile of TRELAVUE should be borne in mind when considering the patient's ability to drive or operate machinery.

TRELAVUE contains dolutegravir, abacavir and lamivudine, therefore the adverse events associated with these may be expected. Hypersensitivity to abacavir (see also Boxed Warning). In clinical studies conducted before the introduction of screening for the HLA-B*5701 allele, approximately 5 % of subjects receiving abacavir developed a hypersensitivity reaction, which in some cases has proved fatal. This reaction is characterised by the appearance of symptoms indicating multi-organ/body-system involvement. Almost all patients developing hypersensitivity reactions will have fever and/or rash (usually maculopapular or urticarial) as part of the syndrome, however reactions have occurred without rash or fever. Symptoms can occur at any time while being treated with abacavir, 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. Those reported in at least 10 % of patients with a hypersensitivity reaction are in bold text. Skin and subcutaneous tissue disorders: rash (usually maculopapular or urticarial) Gastrointestinal disorders: nausea, vomiting, diarrhoea, abdominal pain, mouth ulceration Respiratory, thoracic and mediastinal disorders: dyspnoea, cough, sore throat, adult respiratory distress syndrome, respiratory failure General disorders and administrative site conditions: fever, fatigue, malaise, oedema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis Nervous system disorders: headache, paraesthesia Blood and the lymphatic system disorders: lymphopenia Hepato-biliary disorders: elevated liver function tests, hepatic failure Musculoskeletal connective tissue and bone disorders: myalgia, rarely myolysis, arthralgia, elevated creatine phosphokinase Renal and urinary disorders: elevated creatinine, renal failure. Some patients with hypersensitivity were initially thought to have respiratory disease (pneumonia, bronchitis, 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 a more severe hypersensitivity reaction or death. Therefore, the diagnosis of hypersensitivity reaction should be carefully considered for patients presenting with symptoms of these diseases. If hypersensitivity reaction cannot be ruled out, TRELAVUE, or any other medicinal product containing abacavir should not be restarted. The symptoms related to this hypersensitivity reaction worsen with continued therapy and usually resolve upon discontinuation of abacavir. Restarting abacavir following a hypersensitivity reaction results in a prompt return of symptoms within hours. This recurrence of the hypersensitivity reaction may be more severe than on initial presentation and may include life-threatening hypotension and death. Regardless of their HLA-B*5701 status, patients who develop this hypersensitivity reaction must discontinue TRELAVUE and must never be rechallenged with TRELAVUE, or any other medicinal product containing abacavir. There have been reports of hypersensitivity reactions following re-introduction of abacavir, where the interruption was preceded by a single key symptom of hypersensitivity (rash, fever, malaise/fatigue, gastrointestinal or a respiratory symptom). Hypersensitivity reactions have been reported in patients who have restarted therapy and who had no preceding symptoms of a hypersensitivity reaction. Many of the side effects listed occur commonly (nausea, vomiting, diarrhoea, fever, lethargy, rash) in patients with abacavir hypersensitivity. Therefore, patients with any of these symptoms should be carefully evaluated for the presence of this hypersensitivity reaction. If TRELAVUE has been discontinued in patients due to experiencing any one of these symptoms and a decision is made to restart abacavir, this must be done only under direct medical supervision (see Special considerations following an interruption of TRELAVUE therapy in Boxed Warning).

Symptoms and Signs: There is currently limited experience with overdosage in dolutegravir. Treatment: The patient should be treated symptomatically and supportively with appropriate monitoring as necessary. Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdose, although this has not been studied. It is not known whether abacavir can be removed by peritoneal dialysis or haemodialysis. As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.