Dovato Special Precautions

The special warnings and precautions relevant to dolutegravir and lamivudine are included in this section. There are no additional precautions and warnings relevant to DOVATO.
Hypersensitivity reactions: Hypersensitivity reactions have been reported with integrase inhibitors, including dolutegravir, and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including liver injury. Discontinue DOVATO and other suspect agents 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 DOVATO or other suspect agents 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 antiretroviral nucleoside analogues either alone or in combination, including 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).
Caution should be exercised when administering DOVATO particularly to those with known risk factors for liver disease. Treatment with DOVATO 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).
Serum lipids and blood glucose: Serum lipid and blood glucose levels may increase during antiretroviral therapy. Disease control and life style changes may also be contributing factors. 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 cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and Pneumocystis jiroveci pneumonia. Any inflammatory symptoms must be evaluated without delay and treatment initiated when necessary. Autoimmune disorders (such as Graves' 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) as follows).
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 DOVATO in hepatitis B co-infected patients.
Clinical trial 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 DOVATO 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 DOVATO or any other antiretroviral therapy may still develop opportunistic infections and other complications of HIV infection. Therefore, patients should remain under close clinical observation by physicians experienced in the treatment of these associated HIV diseases.
Transmission of infection: While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.
Drug Interactions: Caution should be given to co-administering medications (prescription and non-prescription) that may reduce the exposure of dolutegravir, lamivudine or medications that may have their exposure changed by DOVATO (see Interactions).
The recommended dose of dolutegravir is 50 mg twice daily when co-administered with rifampicin, carbamazepine, phenytoin, phenobarbital, St. John's wort, etravirine (without boosted protease inhibitors), efavirenz, nevirapine, or tipranavir/ritonavir (see Interactions).
Dolutegravir should not be co-administered with polyvalent cation-containing antacids. DOVATO is thus recommended to be administered 2 hours before or 6 hours after these agents (see Interactions).
DOVATO is recommended to be administered 2 hours before or 6 hours after taking calcium or iron supplements, or alternatively, administered with food (see Interactions).
Dolutegravir increased metformin concentrations. A dose adjustment of metformin should be considered when starting and stopping coadministration of DOVATO with metformin, to maintain glycaemic control (see Interactions).
Effects on Ability to Drive and Use Machines: There have been no studies to investigate the effect of DOVATO, on driving performance or the ability to operate machinery. A detrimental effect on such activities would not be anticipated given the pharmacology of these medicinal products. The clinical status of the patient and the adverse event profile of DOVATO should be borne in mind when considering the patient's ability to drive or operate machinery.