Overdose : מינון יתר

9 OVERDOSAGE
Overdoses with KALETRA oral solution have been reported. One of these reports described fatal cardiogenic shock in a 2.1 kg infant who received a single dose of 6.5 mL of KALETRA oral solution (520 mg lopinavir, approximately 10-fold above the recommended lopinavir dose) nine days prior. The following events have been reported in association with unintended overdoses in preterm neonates: complete AV block, cardiomyopathy, lactic acidosis, and acute renal failure [see Warnings and Precautions (5.2)].
Healthcare professionals should be aware that KALETRA oral solution is highly concentrated and therefore, should pay special attention to accurate calculation of the dose of KALETRA, transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors and overdose. This is especially important for infants and young children.
KALETRA oral solution contains approximately 42 % (v/v) ethanol and approximately 15 % (w/v) propylene glycol. Ingestion of the product over the recommended dose by an infant or a young child could result in significant toxicity and could potentially be lethal.
Human experience of acute overdosage with KALETRA is limited. Treatment of overdose with KALETRA should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with KALETRA. If indicated, elimination of unabsorbed drug should be achieved by gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed drug. Since lopinavir is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the drug. However, dialysis can remove both ethanol and propylene glycol in the case of overdose with KALETRA oral solution.


10 DESCRIPTION
KALETRA is a co-formulation of lopinavir and ritonavir. Lopinavir is an inhibitor of the HIV-1 protease.
As co-formulated in KALETRA, ritonavir inhibits the CYP3A-mediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir.
Lopinavir is chemically designated as [1S-[1R*,(R*), 3R*, 4R*]]-N-[4-[[(2,6- dimethylphenoxy)acetyl]amino]-3-hydroxy-5-phenyl-1-(phenylmethyl)pentyl]tetrahydro-alpha-(1- methylethyl)-2-oxo-1(2H)-pyrimidineacetamide. Its molecular formula is C37H48N4O5, and its molecular weight is 628.80. Lopinavir is a white to light tan powder. It is freely soluble in methanol and ethanol, soluble in isopropanol and practically insoluble in water. Lopinavir has the following structural formula: 


Ritonavir is chemically designated as 10-hydroxy-2-methyl-5-(1-methylethyl)-1- [2-(1-methylethyl)-4- thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12-tetraazatridecan-13-oic acid, 5-thiazolylmethyl ester, [5S-(5R*,8R*,10R*,11R*)]. Its molecular formula is C37H48N6O5S2, and its molecular weight is 720.95.
Ritonavir is a white to light tan powder. It is freely soluble in methanol and ethanol, soluble in isopropanol and practically insoluble in water. Ritonavir has the following structural formula: 


KALETRA tablets are available for oral administration in two strengths: 
•   Red tablets containing 200 mg of lopinavir and 50 mg of ritonavir •   Pale yellow tablets containing 100 mg of lopinavir and 25 mg of ritonavir.


The Red, 200 mg lopinavir and 50 mg ritonavir, tablets contain the following inactive ingredients: Copovidone, Sorbitan laurate, Colloidal anhydrous silica, Hypromellose, Sodium stearyl fumarate, Titanium dioxide, Macrogols type 400, Hydroxypropyl cellulose, Red ferric oxide E172, Talc, Macrogol type 3350 and polysorbate 80.


The pale yellow, 100 mg lopinavir and 25 mg ritonavir, tablets contain the following inactive ingredients: Copovidone, Sorbitan laurate, Colloidal anhydrous silica, Sodium stearyl fumarate, Polyvinyl alcohol, Titanium dioxide, Macrogol type 3350, Talc and Yellow ferric oxide E172.


KALETRA oral solution is available for oral administration as 80 mg lopinavir and 20 mg ritonavir per milliliter with the following inactive ingredients: Dehydrated Alcohol, Corn syrup high fructose, Propylene glycol ,Purified water, Glycerol, Povidone, Flavor Magnasweet, Flavour vanilla natural & artificial, Flavour cotton candy artificial, Polyoxyl 40 hydrogenated castor oil, Saccharin sodium, Acesulfame potassium, Sodium chloride, Oil peppermint, Sodium citrate, Anhydrous citric acid and Levomenthol.
KALETRA oral solution contains approximately 42 %(v/v) ethanol and approximately 15 % (w/v) propylene glycol.