Lanograv. Telatri 144.5 mg FC tablet.

LANOGRAV is indicated for the treatment of HIV-1 infection in adults aged 18 years and older.

Therapy should be initiated by a medical practitioner experienced in the management of HIV infection.

Adults

The dose of LANOGRAV is one tablet taken orally, once daily, without regard to food.

Paediatrics: LANOGRAV is not recommended for use in patients younger than 18 years of age.

Dose adjustment for renal impairment: Significantly increased exposure occurred when tenofovir, as in LANOGRAV, was administered to patients with moderate to severe renal impairment (see section 4.3).

The pharmacokinetics of tenofovir, as in LANOGRAV, have not been evaluated in non-haemodialysis patients with creatinine clear (<80 ml/min); therefore, no dosing recommendations is available for these patients. LANOGRAV is not suitable for use in patients with renal impairment with creatinine clearance less than 80 ml/min. Rifampicin decreases the blood levels of dolutegravir. A supplementary dose of dolutegravir should be given to patients taking LANOGRAV. There is evidence that the concentration of isoniazid is increased by dolutegravir, as contained in LANOGRAV.

• LANOGRAV tablets are contra-indicated in patients with known hypersensitivity to lamivudine, tenofovir or dolutegravir or to any of the components of the tablets.
• Impairment of renal function.
• Concomitant use with adefovir dipivoxil.
• Co-administration with dofetilide and pilsicainide.
• Co-administration with didanosine.
• Co-administration with metformin.
• Moderate and severe hepatic impairment.

Safety and efficacy of the individual active ingredients in various antiretroviral combination regimens with similar dosages as contained in LANOGRAV have been established in clinical studies for the treatment of HIV patients. However, safety and efficacy of the fixed-drug combination as in LANOGRAV for the treatment of HIV have not been established in clinical studies.

The complete package inserts of the other medicines used in this combination should be consulted before initiation of therapy.

Metabolic abnormalities

Combination antiretroviral therapy, including LANOGRAV has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia.

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Lactic acidosis/severe hepatomegaly with steatosis: Lactic acidosis, usually associated with hepatic steatosis, including fatal cases, has been reported with the use of nucleoside analogues, such as in LANOGRAV. Early symptoms (symptomatic hyperlactataemia) include benign digestive symptoms (nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, weight loss, respiratory symptoms (rapid and/or deep breathing) or neurological symptoms (including motor weakness). Lactic acidosis has a high mortality and may be associated with pancreatitis, liver failure or renal failure. Lactic acidosis generally occurs after a few or several months of treatment. Treatment with nucleoside analogues should be discontinued in the setting of symptomatic hyperlactataemia and metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.

The likelihood of interactions is low due to the limited metabolism and plasma protein binding and almost complete renal clearance. Zidovudine plasma levels are not significantly altered when co-administered with lamivudine. Zidovudine has no effect on the pharmacokinetics of lamivudine. Lamivudine may inhibit the intracellular phosphorylation of zalcitabine when the two medicines are used concurrently. Lamivudine is therefore not recommended to be used in combination with zalcitabine. Administration of trimethoprim, a constituent of co-trimoxazole causes an increase in lamivudine plasma levels. However, unless the patient has renal impairment, no dosage adjustment of lamivudine is necessary. Lamivudine has no effect on the pharmacokinetics of co-trimoxazole. The possibility of interactions with other medicines administered concurrently should be considered, particularly when the main route is renal.

Women of childbearing potential should be counselled about the potential risk of neural tube defects with dolutegravir (see below), including consideration of using effective contraceptive measures.

Perform pregnancy testing before initiation of LANOGRAV in women of childbearing potential to exclude inadvertent (unintentional) use of LANOGRAV during the first trimester of pregnancy.

If a woman plans pregnancy, the benefits and the risks of starting or continuing treatment with dolutegravir versus using another antiretroviral regimen should be discussed with her.

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Breastfeeding: HIV infected women should not breast-feed their infants in order to avoid transmission of HIV or follow appropriate guidelines. Dolutegravir is excreted in human breast milk, and there is significant exposure to the neonate/infants due to slow elimination; the half-life of dolutegravir in the new born was 33 hr compared to 14 hr in the adults.

LANOGRAV may affect the ability to drive and use machines. Patients should ensure that they do not engage in driving or using machines until they know how LANOGRAV affects them.

Body System Lamivudine Tenofovir Disoproxil Fumarate Dolutegravir Blood and lymphatic systems disorders Less frequent: Neutropenia; anaemia, thrombocytopenia Frequency unknown: pure red cell aplasia Immune system disorders Frequency unknown: Autoimmune disorders (Gravesu2019 disease) (see section 4.4). Less frequent: Angioedema Less frequent: Allergic reaction, angioedema Less Frequent: Hypersensitivity; Immune Reconstitution syndrome

Tenofovir disoproxil fumarate: If overdose occurs the patient must be monitored for evidence of toxicity and palliative supportive treatment be applied as necessary. Tenofovir can be removed by haemodialysis; the median haemodialysis clearance of tenofovir is 134 ml/min. The elimination of tenofovir by peritoneal dialysis has not been studied.

Lamivudine: Limited data are available on the consequences of ingestion of acute overdoses in humans. If overdosage occurs the patient should be monitored, and palliative supportive treatment applied as required.

Dolutegravir: Management should be as clinically indicated or as recommended by the national poisons centre, where available. There is no specific treatment for an overdose of LANOGRAV. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.