KALETRA Oral solution Ref.[107473] Active ingredients: Lopinavir Lopinavir and Ritonavir Ritonavir

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. However, if it is judged necessary to resort to solid oral dosage form for children weighing less than 40 kg or with a BSA between 0.5 and 1.4 m² and able to swallow tablets, Kaletra 100 mg/25 mg tablets may be used. The adult dose of Kaletra tablets (400/100 mg twice daily) may be used in children 40 kg or greater or with a Body Surface Area (BSA)* greater than 1.4 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.

Total amounts of alcohol and propylene glycol from all medicines, including Kaletra oral solution, that are to be given to infants should be taken into account in order to avoid toxicity from these excipients (see section 4.4).

Dosage recommendation for paediatric patients aged from 14 days to 6 months:

^* 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.

^* weight based dosing recommendations are based on limited data
^** the volume (ml) of oral solution represents the average dose for the weight range

^* Body surface area can be calculated with the following equation
BSA (m²) = √ (Height (cm) X Weight (kg) / 3600)

Concomitant Therapy: Efavirenz or Nevirapine

The 230/57.5 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. The recommended dose of 533/133 mg or 6.5 ml twice daily should not be exceeded.

Children less than 14 days of age and premature neonates

Kaletra oral solution should not be administered to neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 42 weeks and a postnatal age of at least 14 days has been reached (see section 4.4).

Hepatic impairment

In HIV-infected patients with mild to moderate hepatic impairment, an increase of approximately 30% in lopinavir exposure has been observed but is not expected to be of clinical relevance (see section 5.2). No data are available in patients with severe hepatic impairment. Kaletra must not be given to these patients (see section 4.3).

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.

Method of administration

Kaletra is administered orally and should always be taken with food (see section 5.2). The dose should be administered using a calibrated 2 ml or 5 ml oral dosing syringe best corresponding to the volume prescribed.

To date, there is limited human experience of acute overdose with Kaletra.

Overdoses with Kaletra oral solution have been reported (including fatal outcome). The following events have been reported in association with unintended overdoses in preterm neonates: complete atrioventricular block, cardiomyopathy, lactic acidosis, and acute renal failure.

The adverse clinical signs observed in dogs included salivation, emesis and diarrhoea/abnormal stool. The signs of toxicity observed in mice, rats or dogs included decreased activity, ataxia, emaciation, dehydration and tremors.

There is no specific antidote for overdose with Kaletra. Treatment of overdose with Kaletra is to consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. If indicated, elimination of unabsorbed active substance is to be achieved by emesis or gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance. Since Kaletra is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substance.

However, dialysis can remove both alcohol and propylene glycol in the case of overdose with Kaletra oral solution.

2 years.

Store in a refrigerator (2°C-8°C).

In use storage: If kept outside of the refrigerator, do not store above 25C and discard any unused contents after 42 days (6 weeks). It is advised to write the date of removal from the refrigerator on the package.

Kaletra oral solution is supplied in amber coloured multiple-dose polyethylene terephthalate (PET)
bottles in a 60 ml size.

Two pack sizes are available for Kaletra oral solution:

• 120 ml (2 bottles x 60 ml) with 2 × 2 ml syringes with 0.1 ml graduations
  For volumes up to 2 ml. For larger volumes an alternative pack is available.
• 300 ml (5 bottles x 60 ml) with 5 × 5 ml syringes with 0.1 ml graduations
  For volumes greater than 2 ml. For smaller volumes an alternative pack is available.

No special requirements.