Kaletra

Kaletra should be prescribed by physicians who are experienced in the treatment of HIV infection. Posology Adults and adolescents The recommended dosage of Kaletra is 5 ml of oral solution (400/100 mg) twice daily taken with food. Paediatric population aged from 14 days and older The oral solution formulation is the recommended option for the most accurate dosing in children based on body surface area or body weight.

4 m2 and able to swallow tablets, Kaletra 100 mg/25 mg tablets may be used. 4 m2. Kaletra tablets are administered orally and must be swallowed whole and not chewed, broken or crushed. Please refer to the Kaletra 100 mg/25 mg film-coated tablets Summary of Product Characteristics.

4). 75 ml/m2) Given twice daily with food *Body surface area can be calculated with the following equation BSA (m2) =  (Height (cm) X Weight (kg) / 3600) It is recommended that Kaletra not be administered in combination with efavirenz or nevirapine in patients less than 6 months of age.

Dosage recommendation for paediatric patients older than 6 months to less than 18 years Without Concomitant Efavirenz or Nevirapine The following tables contain dosing guidelines for Kaletra oral solution based on body weight and BSA.

5 mg/m2 dosage might be insufficient in some children when co-administered with nevirapine or efavirenz. An increase of the dose of Kaletra to 300/75 mg/m2 is needed in these patients. 5 ml twice daily should not be exceeded. 4). 2). No data are available in patients with severe hepatic impairment.

3). 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.

2). The dose should be administered using a calibrated 2 ml or 5 ml oral dosing syringe best corresponding to the volume prescribed.

27 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. 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 29 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: 5 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). 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). 6 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). 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