Kaletra

An innovative drug, produced by the British company Abbott Laboratories - Kaletra is a prothoretovirus substance for influencing HIV infection (human immunodeficiency virus).

[1], [2]

Indications Kaletra

The only indication for the use of the drug Kaletra is the treatment of HIV infection, by inhibiting the replication of the human immunodeficiency virus.

Release form

Form of release Kaletra - tablets, top covered with a special protective shell, which allows "deliver" the drug directly to the zone of their most effective work.

Kaletra contains two active substances with its dosage: lopinavir (0.2 mg) and ritonavir (0.05 mg).

Kaletra in the form of tablets is available in a vial of dense polyethylene. One bottle contains 120 units of the drug. The bottle with instructions for the use of the drug is packed in cardboard packaging.

Additional chemical compounds present in the drug are sorbitan laurate, sodium stearyl fumarate, copovidone K28, silicon dioxide colloid.

The film coating of the tablet has its own composition.

Pharmacodynamics

This medicine has a narrow specialization. The therapeutic features of Kaletra determine the pharmacodynamics of the two main active substances.

Lopinavir is an inhibitor of HIV-1 and HIV-2 protease, which provides antiviral pharmacodynamics of Kaletra. Inhibition of these proteases provides a disruption in the production of viral protein, leading to the formation and development of an underdeveloped retrovirus.

Ritonavir is a peptidomimetic, is an inhibitor of aspartyl-protease HIV-1 and HIV-2.

Metabolised in the liver.

There is no complete information on the cross-resistance of lopinavir and ritonavir to date, which requires additional studies.

[3], [4], [5], [6],

Pharmacokinetics

The pharmacokinetics of Kaletra are determined by the corresponding parameters of lopinavir and ritonavir. As clinical studies have shown, under the influence of CYP3A, lopinavir is almost 100% transformed into its metabolites. The presence of ritonavir inhibits the metabolism of lopinavir and leads to an increase in its concentration in the blood plasma, increasing the pharmacological effectiveness of the preparation Kaletra.

When applying the recommended dose of lopinavir / ritonavir (0.4 / 0.1 g) twice a day, the maximum concentration (C _max ) of lopinavir in the blood from 6.1 to 13.5 μg / ml is reached four hours after injection.

Single intake of the drug with lean food and fasting does not show a significant change in the level of absorption. When fed moderately fatty foods, the results of absorption of the drug improve.

Bioavailability of Kaletra is quite high and amounts to 99%. Lopinavir is predominantly associated with proteinaceous plasma structures such as albumins and alpha-1-acidic glycoproteins.

The drug is excreted from the body slowly enough. After eight days, the concentration of lopinavir is reduced by 10%, is derived in the main form of metabolites together with urine and more than 80% with fecal masses. About 2.2% of lopinavir is excreted unchanged in urine and 19.8% of them are with calves.

The clearance of lopinavir in the case of oral administration of the drug shows a level of 0.23 to 11.73 l / h.

[7], [8]

Dosing and administration

Kaletra tablets are taken orally. The way of application and the dose of the drug are prescribed by the attending physician individually, based on the patient's condition and the clinical picture of the disease. The effectiveness of the Kaletra drug does not depend on the time and amount of food taken. Tablets should not be bitten. It is recommended that they be swallowed whole.

In the ratio of lopinavir / ritonavir, the recommended starting dosage is the intake of two tableted forms, which corresponds 0.4 / 0.1 g (the concentration of the active active substances lopinavir / ritonavir of one tablet 0.2 / 0.05 g) twice daily throughout the day. Possible and the second schedule of admission - four tablets one-time.

For children who are already three years old, the drug in question is prescribed in several different dosages.

Kaletra dosage and dose schedule in standard adult dosages is allowed for prescribing to children whose weight exceeded the 35 kg mark and the body surface area (PPT) is at least 1.4 m ².

If the child has less weight, and his PPT falls within the limits of 0.6 m ² to 1.4 m ^{2, the} recommended dosage of the drug is 0.1 g + 0.025 g.

For children whose body surface area is less than 0.6 m ², or age is under three years old, Kaletra is used not in the form of tablets, but in the form of syrup. In this situation, the dose of the drug corresponds to a figure of 0.080 g + 0.020 g / ml.

The surface area of the body can be calculated quite easily and independently. To do this, the patient's height in centimeters should be multiplied by his body weight in kilograms and the resulting result divided by 3600.

PPT (m ² ) = (Height (cm) × Body weight (kg) / 3600)

[12], [13],

Use Kaletra during pregnancy

Use of antiviral drug Kaletra during pregnancy is not recommended by medics and pharmacists.

If there is a question of the need for antiretroviral therapy at a time when a young mother is breastfeeding her baby, the woman should stop breastfeeding.

Contraindications

Physicians denote such contraindications to the use of Kaletra:

1. Individual hypersensitivity of the patient's body to lopinavir and / or ritonavir, as well as to one or more additional substances of the drug.
2. Severe degree of hepatic dysfunction.
3. Age of a small patient up to three years of age.

With special care, it is necessary to introduce into the protocol of Kaletra's treatment those patients in whose anamnesis such diseases are present:

1. Cirrhosis of the liver.
2. Liver dysfunction of mild and moderate severity.
3. Hemophilia - blood coagulability.
4. Pancreatitis is an inflammation of the pancreas.
5. Viral hepatitis B and C.
6. Excess standards of liver enzymes.
7. Hypercholesterolemia.
8. Hypertriglyceridemia is an increased amount of triglycerides in the blood.
9. Venerable. The patient's elderly age is over 65 years.
10. Patients with heart problems.

[9],

Side effects Kaletra

Highly effective antiretroviral drug Kaletra, with oral administration can cause quite a lot of side effects:

1. Response of the digestive system:

• Appearance of symptoms of diarrhea.
• Nausea, which can induce vomitive reflex.
• Pain syndrome in the abdomen.
• Flatulence.
• Exacerbation of various diseases associated with the digestive tract: colitis, enterocolitis, hemorrhoids, hepatitis, gastroenteritis, steatosis of the liver, gastroesophageal reflux, hepatomegaly and a number of others that occur less frequently.

1. The reaction of the body's protective function is an allergic reaction of the body, conditioned by its symptoms:

• Hyperemia of the skin.
• Angioedema.
• Hives.
• Rash.
• Itching.
• Burning.

1. Reaction of the cardiovascular system:

• Increase in blood pressure.
• Less common are atherosclerosis, deep vein thrombosis, myocardial infarction, and a number of other disorders.

1. Neurological reaction:

• Headache.
• Sleep disturbance.
• The appearance of noise in the ears.
• Neuropathy, neuralgia.
• Dizziness.
• Appearance of a sense of anxiety.
• Visual impairment.

1. Reaction of the musculoskeletal system:

• Pain syndrome affecting the back area.
• Myalgia.

1. Reaction of the dermis and subcutaneous layers:

• Manifestation of various pathological changes of dermatological nature.

1. Endocrine system reaction:

• Impairment of appetite.
• Weight loss.
• Diabetes.
• Hypertriglyceridemia.
• Hypercholesterolemia (high cholesterol in the blood).

1. Reaction of excretory system:

• Renal dysfunction.

1. Reaction of the human reproduction system:

• Absence of menstruation during several menstrual cycles.
• Great loss of blood during menstruation.
• Erection dysfunction.

1. Response of the body's blood cells:

• Anemia is a condition caused by a scarcity of red blood cells.
• Lymphadenopathy is the reaction of the lymph nodes, expressed by their proliferation.

1. Deterioration of the general condition of a person:

• Frequent infections that affect the lower and upper respiratory tract.
• Infection of the dermis and subcutaneous fat.
• Furunculosis.
• Asthenia.
• Decrease in the general tone of the body.
• Deterioration of the results of laboratory studies.

[10], [11]

Overdose

An overdose of lopinavir and / or ritonavir - the active ingredients of an antiviral agent to influence HIV infection Kaletra - is not known due to the scarcity of facts and observations.

There is no effective antidote, and with the emergence of negative side symptoms symptomatic treatment is performed.

If necessary, disinfecting measures can be carried out: gastric lavage (allows removal of drug residues), as well as the use of sorbent (this can be ordinary activated charcoal).

Due to the fact that the active ingredients of the Kaletra preparation show a large percentage of the connections with plasma proteins, it is not advisable to use dialysis in the treatment of an overdose.

A number of warnings about taking:

1. Lopinavir and ritonavir are predominantly transformed into their metabolites in the liver, so if the liver function is disrupted, the standard dosage may need to be adjusted.
2. Against the backdrop of Kaletra's treatment, you need to cancel your trips while driving. If the work involves the need for a long time to maintain a high level of attention, it is worthwhile to raise the issue of a temporary transfer to another type of work.

[14], [15]

Interactions with other drugs

Most often the drug Kaletra is used in the complex treatment of HIV infection. Therefore, interactions with other Kaletra drugs are a prerequisite for the effectiveness of the entire medical complex.

 Joint use with zidovudine and abacavir, leads to a decrease in their concentration in the blood, which can lead to a deterioration in the effectiveness of the drug.

The reverse effect is observed when combined with tenofovir. The quantitative component in the blood plasma of the last pharmacological agent increases, causing symptoms of an overdose.

Simultaneous work with non-narcotic analgesics requires the medical staff to constantly monitor the patient's health condition, the emergence of secondary symptoms, as possible deterioration of the condition, down to respiratory depression.

With parallel application of HIV protease inhibitors, an increase in the activity of creatine phosphokinase is observed.

When Kaletra is used with nevirapine, there is a decrease in the quantitative index of lopinavir in the patient's blood, which weaken the effect of the antiviral drug under consideration.

It is strictly forbidden to take lopinavir and ritonavir together with efavirenzine and nevirapine together, as Kaletra's influence on retroviral structures is suppressed.

Delavirdine shows the activation of lopinavir and the increase in its quantitative presence in the blood plasma of the patient.

The combined use of Kaletra and anticoagulant drugs (eg, warfarin) increases the likelihood of bleeding.

Lopinavir and ritonavir, when combined in one treatment protocol, with amprenavir increased C _min (numerical presence in plasma) last. Their joint use is contraindicated during the day.

A similar clinical picture is also observed in the case of concurrent administration of Kaletra and nelfinavir. Doctors should not allow their joint application.

Dosages of drugs, inhibitors of the chemokine receptor CCR5 (eg, maraviroc), when taken together with lopinavir and ritonavir, should be reduced.

As shown by clinical observations, the quantitative component of saquinavir in the protocol of complex treatment should be reduced.

With the combined use of Kaletra and bocetrevir, physicians observe a decrease in the quantitative component of lopinavir and the second antiviral drug, which makes their joint application impossible.

Very carefully, it is necessary to introduce and adjust the dose of the drug under one therapeutic protocol of the antiviral drug in question and the drugs of the antidepressant group. The risk of developing side symptoms is great.

It is also not recommended to treat them when combined with antifungal medicines.

Against the background of treatment with Kaletra, oral contraceptive means should not be used, since there is a deterioration in the effective protection of the latter, which requires their replacement by other forms of contraceptive protection.

Storage conditions

Kaletra storage conditions require compliance with such items:

1. The place where lopinavir and ritonavir is supposed to be stored must be protected from exposure to direct sunlight.
2. The temperature regime of storage is allowed in the range from + 15 to + 30 degrees above zero.
3. It is necessary to contain an antiretroviral agent in places that are not accessible to adolescents and small children.

Shelf life

In this case, the shelf life of the drug Kaletra is four years.