Stavudine

At Stavudine it is a nucleoside reverse transcriptase inhibitor. It is used to treat HIV infections.

What is stavudine?

The active ingredient stavudine is used to treat HIV diseases such as AIDS. It is administered as part of an antiretroviral combination therapy. Stavudine is a component of the nucleoside reverse transcriptase inhibitors (NRTIs).

The synthesis of stavudine took place in 1966 by the American chemist Jerome Phillip Horwitz (1919-2012). However, it was not until the mid-1990s that the agent was used in Europe. It is produced by the US pharmaceutical company Bristol-Myers Squibb (BMS).

At the present time, however, stavudine is rarely used in western industrialized countries. The reason for this is the poor tolerance of the drug. However, its administration can sometimes be useful in the case of special mutation combinations as part of salvage therapy.Stavudine is offered under the trade name Zerit®.

Pharmacological effect

Stavudine is classified as a nucleoside reverse transcriptase inhibitor. This means that the drug has an inhibitory effect on the enzyme reverse transcriptase. The enzyme is extremely important for the HI viruses to overwrite the viral RNA in human DNA, which allows the pathogens to multiply.

Stavudine is also one of the so-called prodrugs. The drug is an active ingredient precursor that does not yet have any effect against viruses. It is only within the body that the substance is converted into the actually effective medicinal substance.

This has the property of inhibiting reverse transcriptase, so that the HI viruses resident in the body can no longer multiply. This effect in turn reduces the amount of virus in the organism. At the same time, the number of special white blood cells, which include CD-4 positive T lymphocytes, may increase. This effect can strengthen the body's defense system.

One of the disadvantages of stavudine is that the HI viruses often quickly become insensitive to the active substance. The reason for this is the pronounced adaptability and changeability of the HI virus. For this reason, stavudine is always used in combination therapy and is administered with several other drugs.

Once stavudine has reached the infected body cell and has been absorbed by it, the substance is converted into an active metabolite, which then blocks the enzyme reverse transcriptase.

The oral bioavailability of stavudine is quite high at around 90 percent. A simultaneous consumption of food hardly has a negative effect on the active ingredient. The plasma half-life of stavudine is approximately 1.5 hours.

Medical application & use

Stavudine is used to treat HIV infections such as AIDS. The active ingredient strengthens the human immune system and combats the immunodeficiency disease or at least delays its onset. A cure of AIDS is not possible with stavudine. However, the drug has a positive effect on the life expectancy and quality of life of the patient.

However, stavudine is only used when all other treatment options are unsuccessful. The reason for this is the strong side effects of the drug. For this reason, the anti-AIDS agent should only be given for a short time.

Stavudine is taken in the form of hard capsules, which have a dose of 30 to 40 milligrams. The recommended dosage is twice 30 milligrams for patients weighing less than 60 kilograms and twice 40 milligrams for patients weighing more than 60 kilograms. The capsules should be taken on an empty stomach 60 minutes before meals.

Risks & side effects

Taking stavudine often results in undesirable side effects. The most common symptoms are pain or numbness in the hands and feet, tingling, chest pain, headache, chills, fever, general malaise, diarrhea, nausea, vomiting, the breakdown of fatty tissue on the limbs, back pain and an increased susceptibility to infection.

Other common side effects are sleep problems, inflammation of the pancreas, constipation, benign skin tumors, impaired performance, redistribution of body fat, slight liver dysfunction, pain in muscles and joints, hives, rashes on the skin, itching, hyperacidity of the body, anxiety and depression . Sometimes those affected may also suffer from anemia, enlarged mammary glands, blood disorders in the bone marrow, jaundice or an inflamed liver.

A problem with AIDS patients is that the side effects of the drug are often difficult to distinguish from their disease-related symptoms. In addition, the side effects can also result from the combination therapy, so that an exact trigger cannot be assigned.

The extent of the undesirable side effects is also influenced by the dose and the duration of therapy. By lowering the dose it is sometimes possible to reduce serious side effects. Occasionally, switching to another reverse transcriptase inhibitor is also helpful.

In the early stages of stavudine treatment, AIDS patients often suffer from deterioration in their health. The reason for this is the reaction of the stronger immune system to the pathogens that are in the body. In such cases, doctors speak of an immune reactivation syndrome. However, if the patient reacts positively to the drug, the symptoms of the disease improve significantly after a few weeks.

If there is hypersensitivity to stavudine, the drug must not be administered. The same applies to inflammation of the pancreas and severe kidney dysfunction.

Stavudine should only be used during pregnancy if the doctor carefully weighs the benefits and risks of the treatment beforehand. Animal experiments have shown harmful effects on the child.