KALETRA

Kaletra should be prescribed by physicians who are experienced in the treatment of HIV infection. Kaletra tablets must be swallowed whole and not chewed, broken or crushed. Posology Adults and adolescents The standard recommended dosage of Kaletra tablets is 400/100 mg (two 200/50 mg) tablets twice daily taken with or without food.

In adult patients, in cases where once-daily dosing is considered necessary for the management of the patient, Kaletra tablets may be administered as 800/200 mg (four 200/50 mg tablets) once daily with or without food. e. 8) compared to the recommended standard twice-daily dosing.

An oral solution is available to patients who have difficulty swallowing. Refer to the Summary of Product Characteristics for Kaletra oral solution for dosing instructions. 4 m2. 4 m2 and able to swallow tablets, refer to the dosing guideline tables below.

For children unable to swallow tablets, please refer to the Kaletra oral solution Summary of Product Characteristics. 1). Before prescribing Kaletra 100/25 mg tablets, infants and young children should be assessed for the ability to swallow intact tablets.

If a child is unable to reliably swallow a Kaletra tablet, Kaletra oral solution formulation should be prescribed. The following table contains dosing guidelines for Kaletra 100/25 mg tablets based on body weight and BSA. 4 4 tablets (400/100 mg) *weight based dosing recommendations are based on limited data If more convenient for patients, the Kaletra 200/50 mg tablets may also be considered alone or in combination with the Kaletra 100/25 mg tablet to achieve the recommended dose.

* Body surface area can be calculated with the following equation: BSA (m2) = √ (Height (cm) X Weight (kg) / 3600) Children less than 2 years of age The safety and efficacy of Kaletra in children aged less than 2 years have not been established.

2 but no recommendation on the posology can be made.

Concomitant Therapy:

Efavirenz or nevirapine The following table contains dosing guidelines for Kaletra 100/25 mg tablets based on BSA when used in combination with efavirenz or nevirapine in children. 4 5 tablets (500/125 mg) If more convenient for patients, the Kaletra 200/50 mg tablets may also be considered alone or in combination with the Kaletra 100/25 mg tablet to achieve the recommended dose.

a. Summary of the safety profile The safety of Kaletra has been investigated in over 2600 patients in Phase II-IV clinical trials, of which over 700 have received a dose of 800/200 mg (6 capsules or 4 tablets) once daily. Along with nucleoside reverse transcriptase inhibitors (NRTIs), in some studies, Kaletra was used in combination with efavirenz or nevirapine.

The most common adverse reactions related to Kaletra therapy during clinical trials were diarrhoea, nausea, vomiting, hypertriglyceridaemia and hypercholesterolemia. The risk of diarrhoea may be greater with once-daily dosing of Kaletra.

Diarrhoea, nausea and vomiting may occur at the beginning of the treatment while hypertriglyceridaemia and hypercholesterolemia may occur later. Treatment emergent adverse events led to premature study discontinuation for 7% of subjects from Phase II-IV studies.

It is important to note that cases of pancreatitis have been reported in patients receiving Kaletra, including those who developed hypertriglyceridaemia. 4). b. Tabulated list of adverse reactions Adverse reactions from clinical trials and post-marketing experience in adult and paediatric patients: The following events have been identified as adverse reactions.

The frequency category includes all reported events of moderate to severe intensity, regardless of the individual causality assessment. The adverse reactions are displayed by system organ class. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥1/10,000 to <1/1000) and not known (cannot be estimated from the available data).

4: pancreatitis and lipids c. g. 5). Increased creatine phosphokinase (CPK), myalgia, myositis, and rarely, rhabdomyolysis have been reported with protease inhibitors, particularly in combination with nucleoside reverse transcriptase inhibitors.

Patients with coexisting conditions Hepatic impairment The safety and efficacy of Kaletra has not been established in patients with significant underlying liver disorders. 3). Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.

In case of concomitant antiviral therapy for hepatitis B or C, please refer to the relevant product information for these medicinal products. Patients with pre-existing liver dysfunction including chronic hepatitis have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.

If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment should be considered. Elevated transaminases with or without elevated bilirubin levels have been reported in HIV-1 mono-infected and in individuals treated for post-exposure prophylaxis as early as 7 days after the initiation of lopinavir/ritonavir in conjunction with other antiretroviral agents.

In some cases the hepatic dysfunction was serious. Appropriate laboratory testing should be conducted prior to initiating therapy with lopinavir/ritonavir and close monitoring should be performed during treatment. Renal impairment Since the renal clearance of lopinavir and ritonavir is negligible, increased plasma concentrations are not expected in patients with renal impairment.

Because lopinavir and ritonavir are highly protein bound, it is unlikely that they will be significantly removed by haemodialysis or peritoneal dialysis. Haemophilia There have been reports of increased bleeding, including spontaneous skin haematomas and haemarthrosis in patients with haemophilia type A and B treated with protease inhibitors.

In some patients additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced if treatment had been discontinued. A causal relationship had been evoked, although the mechanism of action had not been elucidated.

1. Severe hepatic insufficiency. Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A. Kaletra should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life threatening events.

These medicinal products include:

Medicinal product class Medicinal products within class Rationale Concomitant medicinal product levels increased Alpha1-adrenoreceptor antagonist Alfuzosin Increased plasma concentrations of alfuzosin which may lead to severe hypotension.

5). 5). Antiarrhythmics Amiodarone, dronedarone Increased plasma concentrations of amiodarone and dronedarone. 5). Antibiotic Fusidic Acid Increased plasma concentrations of fusidic acid. 5). 5). Anticancer Venetoclax Increased plasma concentrations of venetoclax.

5). Anti-gout Colchicine Increased plasma concentrations of colchicine. 5). Antihistamines Astemizole, terfenadine Increased plasma concentrations of astemizole and terfenadine. 5). 5). Pimozide Increased plasma concentrations of pimozide.

5). Antipsychotics/ Neuroleptics Quetiapine Increased plasma concentrations of quetiapine which may lead to coma. 5). 5). GI motility agent Cisapride Increased plasma concentrations of cisapride. 5). 5). 5). 5). 5). 5) Sildenafil Contraindicated when used for the treatment of pulmonary arterial hypertension (PAH) only.

Increased plasma concentrations of sildenafil. Thereby, increasing the potential for sildenafil-associated adverse events (which include hypotension and syncope). 5 for co-administration of sildenafil in patients with erectile dysfunction.

5) Sedatives/hypnotics Oral midazolam, triazolam Increased plasma concentrations of oral midazolam and triazolam. Thereby, increasing the risk of extreme sedation and respiratory depression from these agents. For caution on parenterally administered midazolam, see section