Abbott confirms long-term commitment to HIV care with the planned development of new formulations

Abbott announced today that it plans to develop two new formulations of its HIV medicines, Kaletra (lopinavir/ritonavir) and Norvir (ritonavir), to offer new formulation options for people living with HIV-1. The company is currently investigating a new powder formulation of Norvir as well as a co-formulation of three HIV medicines – lopinavir, ritonavir and 3TC (lamivudine).

The Norvir powder formulation is planned to make it easier to store the medicine. The investigational fixed-dose combination of lopinavir, ritonavir and 3TC combines three established HIV medicines and could reduce the daily number of tablets a patient takes. Additionally, this tablet may offer a more cost-effective treatment option for patients. The fixed-dose combination, if developed and approved, would be designed to be taken in combination with one additional anti-HIV medicine.

Abbott is developing the new formulations with the ambition to make a contribution to the World Health Organization’s Treatment 2.0 strategy. This strategy includes providing treatment options to make the most of the resources available in those developing countries that carry the heaviest HIV burden.

“Abbott’s HIV research program confirms our continued commitment to develop and provide effective, quality HIV medicines for patients around the world,” said Scott C. Brun, M.D., divisional vice president, infectious disease development, Global Pharmaceutical Research and Development, Abbott. “Advances in HIV treatment formulations are critical as doctors and patients shift their goals from surviving HIV to living with HIV.”

Please see below for Use and Important Safety Information about Kaletra and Norvir.

Norvir Powder Formulation

Norvir is most often used in combination with other protease inhibitors as a pharmacokinetic enhancer to increase the blood levels of antiviral medicines that belong to the same group as Norvir (protease inhibitors).The investigational formulation of Norvir is planned to be a heat-stable powder that could be sprinkled over food or added to liquid. This planned formulation could be particularly important for delivering this HIV medicine to developing countries where refrigeration may not be an option. Norvir and another protease inhibitor are given with two additional medications as a daily combination regimen.

“When Abbott originally developed the liquid form of Norvir, we were limited to the technology that was available at the time,” said Brun. “We have developed improved formulation approaches that now allow us to explore a new formulation of Norvir that we hope will be better suited to the needs of HIV-infected children.”

New fixed-dose combination

The investigational fixed-dose combination of Kaletra and 3TC, given with an additional anti-HIV drug, has the potential to offer doctors and patients a simplified medicine that could reduce the number of prescriptions a patient receives and tablets a patient takes.

“Kaletra and 3TC have a long history of use in both the developed and developing worlds,” said Brun. “We are working to ensure that this co-formulation will be heat-stable, which would make it suitable to conditions in areas where storage options are limited.”

Abbott’s Commitment to HIV

Abbott has been a leader in HIV/AIDS research since the early years of the epidemic.

The company developed the first HIV diagnostic test more than 25 years ago. Norvir, one of the first protease inhibitors, was launched in 1995 as both a capsule and an oral solution, and remains an essential component of most protease inhibitor-based treatment regimens. And 10 years after its introduction, lopinavir/ritonavir remains a part of the most commonly used second-line treatment regimens in resource limited settings, according to the World Health Organization Price Reporting Mechanism.

In 1985, the company developed the first licensed test to detect HIV antibodies in the blood and remains a leader in HIV diagnostics. Abbott retroviral and hepatitis tests are used to screen more than half of the world’s donated blood supply. Abbott has developed two protease inhibitors for the treatment of HIV and a number of nutritionals, devices and diagnostics to help people living with HIV.

Expanding on its scientific contributions, Abbott and the Abbott Fund have invested more than $200 million in developing countries to improve the lives of people affected by HIV/AIDS through programs targeting critical areas of need, including strengthening healthcare systems, supporting children affected by HIV/AIDS and advancing HIV testing and treatment.

Globally, prescribing information varies. Refer to the individual country full prescribing information for complete information. For U.S. full Prescribing Information about Kaletra and Norvir, visit Kaletra.com and Norvir.com.

Information about KALETRA

Use

Kaletra is an antiretroviral medicine called a protease inhibitor used to help control human immunodeficiency virus (HIV). Kaletra is used by children 2 years of age or older and adults. Kaletra is used in combination with other antiretroviral medicines.

Kaletra does not cure HIV infection or AIDS and does not stop the risk of passing HIV to others. People taking Kaletra may still develop infections or other illnesses associated with HIV disease and AIDS.

Important Safety Information

Kaletra should not be taken by people who are allergic (hypersensitive) to lopinavir, ritonavir or any of the other ingredients of Kaletra or people who have severe liver problems.

Kaletra should not taken with any of the following medicines: astemizole, terfenadine, oral midazolam, triazolam, pimozide, cisapride, ergotamine, dihydroergotamine, ergonovine, and methylergonovine, amiodarone, lovastatin, simvastatin, vardenafil, sildenafil used to treat pulmonary arterial hypertension and products containing St. John’s Wort (Hypericum perforatum).

People must tell their doctor or pharmacist if they are taking or have recently taken any other medicines, including medicines obtained without prescription.

Kaletra must not be taken once daily in combination with efavirenz, nevirapine, nelfinavir, amprenavir, carbamazepine, phenobarbital, or phenytoin.

People must tell their doctor if they have/had:

• Haemophilia type A and B as Kaletra might increase the risk of bleeding.
• Diabetes as increased blood sugars has been reported in people receiving Kaletra.
• A history of liver problems as people with a history of liver disease, including chronic hepatitis B or C are at increased risk of severe and potentially fatal liver side effects.

People must tell their doctor if they experience:

• Nausea, vomiting, abdominal pain, difficulty breathing and severe weakness of the muscles in the legs and arms as these symptoms may indicate raised lactic acid levels.
• Thirst, frequent urination, blurred vision or weight loss as this may indicate raised sugar levels in the blood.
• Nausea, vomiting, abdominal pain as large increases in the amount of triglycerides (fats in the blood) have been considered a risk factor for pancreatitis (inflammation of the pancreas) and these symptoms may suggest this condition.
• Changes in body shape due to changes in fat distribution. These may include loss of fat from legs, arms and face, increased fat in the abdomen (belly) and other internal organs, breast enlargement and fatty lumps on the back of the neck (‘buffalo hump’). The cause and long-term health effects of these conditions are not known at this time.
• In some people with advanced HIV infection and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If people notice any symptoms of infection, their doctor should be informed immediately to seek necessary treatment.
• Joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement as some people taking these medicines may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression (reduction in the activity of the immune system), higher body mass index, among others, may be some of the many risk factors for developing this disease.
• Muscle pain, tenderness or weakness, particularly in combination with these medicines. On rare occasions these muscle disorders have been serious.
• Symptoms of dizziness, lightheadedness, fainting or sensation of abnormal heartbeats. Kaletra may cause changes in heart rhythm and electrical activity of the heart. These changes may be seen on an ECG (electrocardiogram).

People taking sildenafil or tadalafil and Kaletra together may be at risk of side effects such as low blood pressure, passing out, visual changes and penile erection lasting more than 4 hours. If an erection lasts longer than 4 hours, they should get medical help immediately to avoid permanent damage to their penis. Their doctor can explain these symptoms.

Women taking oral contraceptive or using a patch to prevent pregnancy should use an additional or different type of contraception since Kaletra may reduce the effectiveness of oral and patch contraceptives.

Pregnant or nursing mothers should not take Kaletra unless specifically directed by their doctor.

Kaletra should not be given to children younger than 2 years of age unless specifically directed by their doctor. Kaletra once daily has not been evaluated in pediatrics.

Very common (meaning affects more than 1 user in 10) side effects of Kaletra include diarrhoea, nausea and upper respiratory tract infection. This is not a complete list of reported side effects.

For more information about Kaletra, the local Summary of Product Characteristics should be consulted.

Information about Norvir

Use

Norvir is a protease inhibitor used to control HIV infection. Norvir is used in combination with other anti-HIV medicines (antiretrovirals) to control HIV infection in adults and children of 2 years of age and older.

Norvir can be used at full dose on its own, or at lower doses (called booster doses) with other medicines.

Norvir is not a cure for HIV infection or AIDS and does not lower the risk of passing HIV to others. People taking Norvir may still develop infections or other illnesses associated with HIV infection or AIDS.

Important Safety Information

Norvir should not be taken by people who are allergic (hypersensitive) to ritonavir or any of the other ingredients of Norvir or people who have severe liver disesase.

Norvir should not be taken with the following medicines: astemizole, terfenadine, amiodarone, bepridil, encainide, flecainide, propafenone, quinidine, dihydroergotamine, ergotamine, ergonovine, methylergonovine, clorazepate, diazepam, estazolam, flurazepam, triazolam or oral (taken by mouth) midazolam, clozapine, pimozide, pethidine, piroxicam, propoxyphene, cisapride rifabutin, voriconazole, simvastatin, lovastatin, alfuzosin, fusidic acid, sildenafil used to treat a lung disease called pulmonary arterial hypertension, and products containing St John’s wort (Hypericum perforatum).

People must tell their doctor or pharmacist if they are taking or have recently taken any other medicines, including medicines obtained without a prescription.

People must tell their doctor if they have/had:

• A history of liver disease.
• Hepatitis B or C and are being treated with a combination of antiretroviral agents, as they are at a greater risk of a severe and potentially life threatening reaction because of the effect on the liver. Regular blood tests may be required to check if the liver is working properly.
• Haemophilia, as there have been reports of increased bleeding in patients with haemophilia who are taking this type of medicine (protease inhibitors). The reason for this is not known.
• Additional medicine maybe needed to help blood clot (factor VIII), in order to control any bleeding.
• Erectile Dysfunction, as the medicines used to treat erectile dysfunction can cause hypotension and prolonged erection.
• Diabetes, as there have been reports of worsening of or the development of diabetes (diabetes mellitus) in some patients taking protease inhibitors.
• Kidney (renal) disease, since a doctor may need to check the dose of other medicines (such as protease inhibitors).

People must tell their doctor if they experience:

• Changes in the distribution of the fat on their body, or a build up or loss of body fat
• Diarrhoea or vomiting that is not improving (persistent), as this may reduce how well the medicines are working.
• Feeling sick (nausea), vomiting or have stomach pain, because these may be signs of inflammation of the pancreas (pancreatitis). Some patients taking Norvir can develop serious problems with their pancreas.
• Symptoms of infection – Some patients with advanced HIV infection (AIDS) who then start anti-HIV treatment may develop the symptoms of infections they have had in the past even if they didn’t know they had them. It is believed that this happens because the body’s immune response improves and helps the body to fight these infections.
• Joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty moving, as this may be a sign of a problem that can destroy bone (osteonecrosis). Some patients taking a number of antiretroviral medicines may develop this disease.
• Muscle pain, tenderness or weakness, particularly in combination with antiretroviral therapy including protease inhibitors and nucleoside analogues. On rare occasions these muscle disorders have been serious.
• Dizziness, lightheadedness, fainting spells or abnormal heartbeat. Some patients taking Norvir may experiences changes in the electrocardiogram (ECG). People must tell their doctor if they have a heart defect or conduction defect.
• If people have any other health concerns, they should discuss these with their doctor as soon as they can.

People must tell their doctor if they are taking any of the medicines listed below, as special care should be taken.

• Sildenafil, tadalafil, vardenafil for impotence (erectile dysfunction).
• The dose and/or frequency of use of these medicines may need to be reduced to avoid hypotension and prolonged erection. People must not take Norvir with sildenafil if they suffer from pulmonary arterial hypertension.
• Digoxin (heart medicine). Their doctor may need to adjust the dose of digoxin and monitor them while they are taking digoxin and Norvir in order to avoid heart problems.
• Hormonal contraceptives containing ethinyl oestradiol as Norvir may reduce the effectiveness of these medicines. It is recommended that a condom or other non-hormonal method of contraception is used instead. Women may also notice irregular uterine bleeding if they are taking this type of hormonal contraceptive with Norvir.
• Atorvastatin or rosuvastatin (for high cholesterol) as Norvir may raise the blood levels of these medicines. People must talk to their doctor before taking any cholesterol-reducing medicines with Norvir.
• Steriods (eg dexamethasone, fluticasone propionate, prednisolone) as Norvir may raise the blood levels of these medicines which may lead to Cushing’s syndrome (development of a rounded face) and reduce production of the hormone cortisol. The doctor may wish to reduce the steroid dose or monitor side effects more closely.
• Trazodone (a medicine for depression) as, unwanted effects like nausea, dizziness, low blood pressure and fainting can occur when taken with Norvir.
• Rifampicin and saquinavir (used for tuberculosis and HIV, respectively) as serious liver damage can occur when taken with Norvir.

It is not known if Norvir passes into breast milk. To avoid transmitting the infection, mothers with HIV should not breast feed their babies.

Norvir is not recommended in children below 2 years of age.

Very common side effects of Norvir are stomach ache, vomiting, diarrheoa, feeling sick (nausea), headache, a tingling sensation or numbness in the hands, feet or around the lips or mouth, feeling weak/tired, and a bad taste in the mouth.

For more information about Norvir, the local Summary of Product Characteristics should be consulted.