Stavudine is a nucleoside reverse transcriptase inhibitor. It is used to treat HIV infection.
What is stavudine?
The active ingredient stavudine is used to treat HIV diseases such as AIDS. Its administration takes place as part of combination antiretroviral therapy. Stavudine is a component of nucleoside reverse transcriptase inhibitors (NRTIs). The synthesis of stavudine took place as early as 1966 by the American chemist Jerome Phillip Horwitz (1919-2012). However, it took until the mid-1990s for the drug to be used in Europe. It is manufactured by the U.S. pharmaceutical company Bristol-Myers Squibb (BMS). Today, however, stavudine is hardly ever used in western industrialized countries. The reason for this is the poor tolerability of the drug. However, its administration can sometimes be useful for special mutation combinations as part of a salvage therapy. Stavudine is offered under the trade name Zerit.
Pharmacologic Action
Stavudine is classified as a nucleoside reverse transcriptase inhibitor. This means that the drug has an inhibitory effect on the enzyme reverse transcriptase. This enzyme is extremely important for the HI viruses in order to transcribe the viral RNA into human DNA, which enables the pathogens to multiply. Stavudine is also one of the so-called prodrugs. The drug is a precursor of an active ingredient that does not itself have any effect against viruses. It is only within the body that the substance is converted into the drug that is actually effective. This has the property of inhibiting reverse transcriptase, as a result of which the HI viruses resident in the body cannot reproduce any further. This effect, in turn, results in the reduction of the amount of viruses in the organism. At the same time, the number of special white blood cells, which include CD-4 positive T lymphocytes, can increase. This effect helps to 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 mutability of the HI virus. For this reason, stavudine is always used as part of a combination therapy and is administered with several other drugs. Once stavudine has reached and been absorbed by the infected body cell, the substance is converted into an active metabolite that subsequently blocks the enzyme reverse transcriptase. The oral bioavailability of stavudine is quite high at approximately 90 percent. Concomitant ingestion of food has little negative effect on the active ingredient. The plasma half-life of stavudine is approximately 1.5 hours.
Medicinal use and application
Stavudine is used to treat HIV infections such as AIDS. In doing so, the active ingredient strengthens the human immune system and fights the immunodeficiency disease or at least delays its onset. Stavudine cannot cure AIDS. However, the drug has a positive effect on the patient’s life expectancy and quality of life. 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 drug should only be administered for a short period of time. Stavudine is taken in the form of hard capsules, which have a dose of 30 to 40 milligrams. The recommended dosage is two times 30 milligrams for patients weighing less than 60 kilograms and two times 40 milligrams for patients weighing more than 60 kilograms. The capsules should be taken on an empty stomach 60 minutes before meals.
Risks and side effects
It is not uncommon for taking stavudine to result in unwanted side effects. The most common are pain or numbness in the hands and feet, tingling, chest pain, headache, chills, fever, general malaise, diarrhea, nausea, vomiting, breakdown of fatty tissue in the limbs, back pain, and increased susceptibility to infection.Other common side effects include sleep problems, pancreatitis, constipation, benign skin growths, limitations in performance, redistribution of body fat, mild liver dysfunction, pain in muscles and joints, hives, rashes on the skin, itching, hyperacidity of the body, anxiety and depression. Sometimes sufferers may also have anemia, enlarged mammary glands, bone marrow hematopoiesis disorders, jaundice, or an inflamed liver. One problem with AIDS patients is that it is often difficult to distinguish the side effects of the drug from their disease-related symptoms. In addition, the side effects may also result from the combination therapy, making it impossible to assign an exact trigger. The extent of the unpleasant side effects is also influenced by the dose and the duration of therapy. By lowering the dose, it is sometimes possible to reduce severe side effects. Occasionally, switching to another reverse transcriptase inhibitor is also helpful. In the initial stages of stavudine treatment, it is not uncommon for AIDS patients to suffer a deterioration in their health. The reason for this is the reaction of the stronger immune system to the pathogens that are present in the body. In such cases, physicians speak of an immune reactivation syndrome. However, if the patient reacts positively to the medication, the symptoms of the disease improve considerably 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 may only be used during pregnancy if the doctor has carefully weighed up the benefits and risks of the treatment beforehand. Animal studies showed harmful effects on the child.
