| Summary
Kaletra is the brand name of a product
that contains two anti-HIV drugs called protease inhibitors lopinavir
and ritonavir. The most common side effects associated with the use of
Kaletra are diarrhoea, feeling weak or tired, nausea, vomiting and
frequent stools. Kaletra is licensed for the treatment of adults and
children older than six months who have HIV infection. Kaletra is
available in capsules and as a liquid.
What is Kaletra?
Kaletra is the brand name of two anti-HIV drugs ? lopinavir and
ritonavir (Norvir) ? that are sold together in one capsule or bottle.
These drugs are called protease inhibitors.
How does Kaletra work?
To explain how Kaletra works, we need to first tell you some information
about HIV. When HIV infects a cell, it takes control of that cell. HIV
then forces the cell to make many more copies of the virus. In order to
make these copies, the cell uses proteins called enzymes. When the
activity of these enzymes is reduced or blocked, production of HIV slows
or stops.
Kaletra contains two drugs, lopinavir and ritonavir, both of which
belong to a group of drugs called protease inhibitors. These drugs
affect an enzyme called protease which is used by HIV-infected cells to
make new viruses. Since lopinavir reduces or inhibits the activity of
this protease enzyme (hence the name "protease inhibitor), this
drug causes HIV-infected cells to produce fewer viruses.
The purpose of the small amount of ritonavir inside capsules of Kaletra
is to boost levels of lopinavir in the blood. Ritonavir also helps keep
lopinavir levels high for many hours. This is why Kaletra can be taken
twice daily instead of three times daily.
The protease inhibitor Kaletra is usually used in combination with at
least two other drugs from different classes, such as AZT and ddI (both
nucleoside analogues). Combinations such as this are called highly
active antiretroviral therapy, or HAART. For many people with HIV/AIDS (PHAs),
the use of HAART has increased their CD4+ cell counts and decreased the
amount of HIV in their blood (viral load). These beneficial effects help
to reduce a PHA's risk of developing a life-threatening infection.
Side effects
Common side effects experienced by users of Kaletra include the
following:
diarrhoea; frequent stools; feeling weak
or tired; headache; nausea; vomiting
Other possible side effects:
Women may experience heavier menstrual periods. Haemophiliacs may
experience unexpected episodes of bleeding, including bruising and
bleeding into joints. Over the long-term, use of protease inhibitors may
increase levels of sugar in the blood and also increase the risk of
developing diabetes. Although the risk of developing diabetes is low,
symptoms that may be related to diabetes increased thirst, increased
urination, unexplained weight loss, tiredness and dry, itchy skin should
be discussed with your doctor.
Warning
Painfully swollen pancreas gland pancreatitis has occurred in fewer than
1% of the 8,733 people who have received Kaletra in an expanded access
programme. In some of these cases, pancreatitis has been fatal.
According to the manufacturer of Kaletra, Abbott Laboratories,
pancreatitis should be considered if the following signs/symptoms occur:
nausea
vomiting
abdominal pain
and blood tests reveal high levels of the enzymes amylase and lipase in
the blood
Lipodystrophy syndrome
The HIV lipodystrophy syndrome is the name given to a range of symptoms
that may develop when people use HAART regimens, particularly ones that
contain a protease inhibitor. Signs/symptoms of lipodystrophy include:
The precise cause(s) of the lipodystrophy syndrome is not clear.
Moreover, there may be several syndromes occurring at the same time
in the same PHA. The role of protease inhibitors ? and other drugs in
lipodystrophy is also not clear. Researchers are studying the
lipodystrophy syndrome in an effort to find out what causes it and
how it can be managed.
Drug interactions
Like many drugs, lopinavir and ritonavir are broken down and
processed (metabolised) in the liver. The liver is able to
metabolize these drugs because it has a series of enzymes called
cytochrome p450. Taking Kaletra with another drug(s) that is also
metabolized by the same enzymes can affect levels of each drug in
the blood. As a result, levels of some drugs may increase, causing
side effects; or levels of some drugs may decrease, resulting in no
benefit from the drugs. Because of these interactions between
certain drugs, your doctor may do the following:
adjust your dose of Kaletra
adjust the dose of your other drugs
give you different drugs
The list of drug interactions and warnings in this fact sheet is not
exhaustive. Always consult your doctor and pharmacist about the
medications you are taking and possible interactions.
Warning
Kaletra should not be used with the following drugs:
- Heart drugs: Tambocor (flecainide), Rythmol
(propafenone)
- Antihistamines: Hismanal (astemizole), Seldane (terfenadine)
- Ergot drugs: Ergonovine, Ergomar
(ergotamine)
- Antibiotics: rifampin
- Gastrointestinal motility agents:
Prepulsid (Cisapride)
- Herbs: St. John's wort
- Anti-psychotics: Orap (pimozide)
- Sedatives/sleeping pills: Versed (midazolam), Halcion (triazolam)
- Lipid-lowering agents: lovastatin (Mevacor), simvastatin (Zocor).
The manufacturer suggests the use of other lipid-lowering agents
such as pravastatin (Pravachol) and fluvastatin (Lescol).
Here is a list of some drugs that can reduce levels of lopinavir in
the blood:
Non-nucleoside reverse transcriptase inhibitors:
efavirenz (Sustiva),
nevirapine (Viramune)
Anti-seizure drugs: carbamazepine (Tegretol), phenobarbital,
phenytoin (Dilantin)
Corticosteroids: dexamethasone (Decadron)
Kaletra can increase levels of the following drugs:
- Antibiotics: clarithromycin (Biaxin), rifabutin (Mycobutin)
- Antifungals: ketoconazole (Nizoral), itraconazole (Sporanox)
- Calcium channel blockers: nifedipine (Adalat), felodipine (Plendil,
Renedil), nicardipine (Cardene)
- Erectile dysfunction: Viagra (sildenafil)
- Immunosuppressive agents: cyclosporine (Neoral), Prograf (tacrolimus),
rapamycin (Sirolimus)
Kaletra can decrease levels of the following drugs:
- Narcotics: methadone
- Anti-parasite: Mepron (atovaquone)
- Oral contraceptives
Resistance and cross-resistance
Over time, as new copies of HIV are made in the body, the virus can
change its structure. These changes are called mutations and can
allow HIV to resist the effect of HAART. Combining Kaletra with at
least two other anti-HIV drugs delays the development of resistance
by HIV. To reduce the risk of developing resistance, all anti-HIV
drugs should be taken every day as prescribed. The strict schedule
for taking Kaletra is necessary because resistant virus can develop
if levels of lopinavir fall too low. This may happen if doses are
delayed or skipped.
When HIV becomes resistant to lopinavir it also becomes resistant to
several other protease inhibitors this effect is called cross
resistance including indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir).
Should HIV develop resistance to lopinavir, it is possible that the
following drugs could form treatment options: ritonavir with amprenavir
(Agenerase); ritonavir with saquinavir (Fortovase);
tipranavir (PNU 140690).
The purpose of ritonavir with the other protease inhibitors listed
above is to boost and maintain levels of the other protease
inhibitor (amprenavir or saquinavir). Ritonavir in these
formulations does not have antiviral activity. Its sole purpose in
these combinations is to boost and maintain the levels of the other
protease inhibitors.
Indication
In March 2001, Kaletra was approved for sale in Canada for the
treatment of adults and children over the age of six months with
HIV/AIDS. Although Kaletra is clearly a potent treatment when used
in combination with other anti-HIV drugs, the best point in the
course of HIV disease with which to use Kaletra is unclear. As well,
the issue of which protease inhibitor PHAs should use as a
first-line treatment is also not known.
Dosage
The recommended adult dose is 3 capsules or 5 mL taken twice daily
with food.
If you miss a dose of Kaletra, Abbott recommends that you take a
dose as soon as possible and then return to your normal schedule.
You should not take a double dose to make up for the missed dose. If
you keep forgetting to take Kaletra, talk to your doctor about this
problem.
Doctors prescribing Kaletra to adult PHAs who are also taking
nevirapine or efavirenz should consider increasing the dose of
Kaletra to 4 capsules or 6.5 mL twice daily with food, since these
drugs can reduce levels of lopinavir in the blood.
In children between the ages of six months and 12 years, the dose of
Kaletra is adjusted depending on the weight of the child.
Availability
Kaletra is available with a prescription. The manufacturer is
negotiating with Canada's provinces and territories to have Kaletra
paid for by their formularies.
This information was
provided by the Community AIDS Treatment Information Exchange (CATIE).
For more information, contact CATIE at 1-800-263-1638.
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