Reydin 300 mg. FC tablets

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

Posology
Therapy should be initiated by a medical practitioner experienced in the management of HIV infection.
Adults: The dose of REYDIN is one tablet taken orally, once daily, without regard to food.
Paediatrics: REYDIN 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 REYDIN, was administered to patients with moderate to severe renal impairment (see section 4.3). The pharmacokinetics of tenofovir, as in REYDIN, have not been evaluated in non-haemodialysis patients with creatinine clearance < 50 mL/min; therefore, no dosing recommendations are available for these patients. REYDIN is not suitable for use in patients with renal impairment with creatinine clearance less than 50 mL/min. Rifampicin decreases the blood levels of dolutegravir. A supplementary dose of dolutegravir should be given to patients taking REYDIN.
Method of administration
REYDIN tablets are to be taken orally, once daily, without regard to food.

• REYDIN is contraindicated in patients with known hypersensitivity to dolutegravir, lamivudine, tenofovir disoproxil fumarate or any of the components of REYDIN.
• Uncontrolled renal failure (see section 4.4).
• Pregnancy and lactation (see section 4.6).
• Women of child-bearing age not using highly effective contraception.
• Concomitant use with adefovir dipivoxil.
• Co-administration with dofetilide and pilsicainide.
• Co-administration with didanosine.
• Co-administration with metformin.
• Patients younger than 18 years of age.
• Moderate and severe hepatic impairment.

Safety and efficacy of the individual active ingredients in various antiretroviral combination regimens with similar dosages as contained in REYDIN have been established in clinical studies for the treatment of HIV patients. However, safety and efficacy of the fixed-drug combination as in REYDIN for the treatment of HIV have not been established in clinical studies.
The complete patient information leaflets of the other medicines used in combination should be consulted before initiation of therapy.
Metabolic abnormalities
Combination antiretroviral therapy, including REYDIN has been associated with metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia and hyperlactataemia.
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The likelihood of interactions is low due to the limited metabolism as 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.
No medicine interaction studies have been conducted using REYDIN. As REYDIN contains tenofovir disoproxil fumarate and lamivudine, any interactions that have been identified with these individual medicines may occur with REYDIN.

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 REYDIN in women of childbearing potential to exclude inadvertent (unintentional) use of REYDIN during the first trimester of pregnancy. If a woman plans pregnancy, the benefits and risks of starting or continuing treatment with dolutegravir versus using another antiretroviral regimen should be discussed with her.
Pregnancy
REYDIN is contraindicated in pregnancy (see section 4.3). Use of dolutegravir during pregnancy was associated with a small increase in the prevalence of neural tube defects (0,19 %) compared to non-dolutegravir regimens (0,11 %). Most neural tube defects occur within the first 4 weeks of embryonic development after conception (approximately 6 weeks after the last menstrual period).

REYDIN cause dizziness, impaired concentration and/or drowsiness and 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 REYDIN affects them.

a. Summary of the safety profile
Studies revealed the most severe adverse reactions linked to dolutegravir treatment are hypersensitivity reactions that include rash and severe liver effects. The most common adverse reactions of dolutegravir are nausea (13 %), diarrhoea (18 %) and headache (13 %). Renal impairment, renal failure and proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to bone abnormalities (infrequently contributing to fractures) have been reported rarely in patients receiving tenofovir disoproxil. Monitoring of renal function is recommended for patients receiving REYDIN (see section 4.4).

If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary. 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 REYDIN. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. As REYDIN is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis. Lamivudine: Limited data are available on the consequences of ingestion of acute overdose in humans. If overdosage occurs the patient should be monitored, and palliative supportive treatment applied as required. Tenofovir disoproxil fumarate: If overdose occurs the patient must be monitored for evidence of toxicity and palliative supportive treatment be applied as necessary.