Amprenavir is an antiviral drug used to treat the Human Immunodeficiency Virus (HIV) infection.
This drug was approved by the Food and Drug Administration (FDA) in 1999 and is available as capsules or oral solutions.
The drug is sold under the brand name Agenerase.
Amprenavir was discontinued in 2007.
However, a prodrug version of the same, called Fosamprenavir, is available now.
A prodrug is a substance that is converted into an active drug form in the body after the person consumes it. Sometimes when the actual drug is poorly absorbed or leads to severe side effects, a prodrug form of the same is developed.
The prodrug is created to ensure maximal absorption by the target cells and bring down the risk of adverse effects.
In this case, Fosamprenavir, on administration, is metabolized into amprenavir and directly targets the virus.
No. You will need a prescription to be able to buy the drug.
Amprenavir belongs to a class of drugs called protease inhibitors. Protease is a type of enzyme that the virus makes.
This HIV-1 protease enzyme makes the virus infectious and, as a result, harmful.
Protease inhibitors attach themselves to the virus’s protease and prevent it from functioning. As a result, the virus remains infectious.
An adult will need 1200 mg of the drug twice a day, and the drug is available in the form of 50 mg or 150 mg capsules.
Some of the common side effects of amprenavir are:
About 27% of people may develop skin rashes and itchy skin when amprenavir is administered.
In addition, a severe skin condition called Stevens-Johnson Syndrome (losing the outer layer of the skin) may occur in 1% of people using the drug.
16% of people who use amprenavir may also experience psychiatric disorders, including mood swings and depression.
Amprenavir oral solution can lead to the following side effects:
Like other protease inhibitors, Amprenavir may lead to increased cholesterol levels, insulin resistance, and worsening diabetes.
Yes, protease inhibitors are safe to use under the guidance of a healthcare provider. However, make sure to talk to your doctor about your existing health conditions and the drugs you use to prevent the risk of side effects.
Amprenavir may interact with other drugs and lead to changes in drug efficacy or worsening of the adverse effects. Therefore, notify your doctor if you use amprenavir along with the following medications.
The SLCO1B1 gene (Solute Carrier Organic anion transporter family member 1B1 gene) provides instructions for producing the organic anion transporting polypeptide 1B1 (OATP1B1) protein.
This protein transports drugs, toxins, hormones, and other substances from the blood to the liver for elimination.
rs4149056 is a Single Nucleotide Polymorphism (SNP) in the SLCO1B1 gene.
In people with HIV infection, the CC and CT types of this SNP may lead to reduced blood amprenavir levels.
In contrast, TT type may lead to increased blood amprenavir levels.
However, this association was only found in people of European descent.
Low levels of amprenavir may not be sufficient to fight HIV effectively, while high drug levels may lead to an increased risk of developing adverse side effects.
Knowing specific gene changes can help plan the right drug dosage to maintain optimal drug levels in the body.
|CC||Decreased blood amprenavir levels in people of European descent with HIV|
|CT||Decreased blood amprenavir levels in people of European descent with HIV|
|TT||Increased blood amprenavir levels in people of European descent with HIV|
Studies in animals show that usage of amprenavir during pregnancy may be associated with an increased risk of abortion and low birth weight in babies.
Talk to your doctor and weigh the benefits and risks of using amprenavir if you are pregnant.
Animal studies also show that amprenavir is secreted in the milk of lactating animals. This is not confirmed in humans, though.
Hence, talk to your doctor and understand the risks of the same.
Doctors generally don’t recommend mothers with HIV to breastfeed because of the risk of postnatal transmission of the virus from the mother to the baby.
People with existing liver conditions must use amprenavir with caution.
The Child-Pugh score is an assessment to determine the extent of liver damage.
People with a Child-Pugh score of 5-8 should bring down amprenavir dosage to 450 mg/twice a day.
Those with a score of 9-12 should decrease the dosage to 300 mg/twice a day.
The oral amprenavir solution contains high amounts of propylene glycol. This colorless liquid is harmful in large doses.
Doctors recommend patients choose the capsules over the oral solution for this reason.
Also, the oral solution is not recommended for pediatric patients below four and the elderly.
Studies show that a high-fat diet may decrease the absorption of amprenavir. Therefore, patients are advised to monitor their fat intake while on the drug.
Certain hormonal birth control pills can interfere with amprenavir and reduce its efficacy. Talk to your doctor if you are on birth control pills and are prescribed amprenavir.
If you think you have overdosed on Amprenavir, make sure you call 911 or visit the nearest Emergency Room right away.
Genetic testing will help find out if you have SLCO1B1 gene changes. This can help plan the right dosage of amprenavir, preventing both lowered drug efficacy and drug overdose.
Amphetamine is a central nervous system (CNS) stimulator used to treat medical conditions like Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy.
CNS stimulators affect the chemicals in the brain and cause hyperactivity and impulse control.
ADHD is a complex psychological disorder caused by genetic and non-genetic factors.
It is the most common neurodevelopmental disorder occurring in childhood.
Children with ADHD have trouble paying attention, controlling impulsive behaviors, and being overly active.
Aside from its medical uses, Amphetamine is also a habit-forming (highly addictive) substance with a long history of abuse.
Apart from a few brands, Amphetamine is not recommended for children below the age of three years.
Today, Amphetamine is also being used for treating obesity, depression, and chronic pain, although off-label.
Amphetamine is a CNS stimulant that increases the amount of neurotransmitters (chemical messengers) like dopamine, norepinephrine, and serotonin in the synapse via different mechanisms.
A synapse is a small gap between two nerve cells where transmission of electrical impulses occurs.
Amphetamine enters the nerve cell at the synapse by diffusion and is taken up by transporter molecules at the synapse.
Once inside the nerve cell, Amphetamine disrupts the electrochemical gradients required for standard impulse transmission.
Amphetamine also inhibits the metabolism of monoamine neurotransmitters (chemical modifications that monoamine transmitters undergo) by inhibiting Monoamine Oxidase (MAO) enzymes.
MAO inhibitors are responsible for degrading neurotransmitters. So, if Amphetamine inhibits MAO, the quantity of specific neurotransmitters increases.
Though Amphetamine is safe when taken legally and in doses strictly prescribed by the doctor, some people may experience mild to severe side effects on taking it.
These side effects may be physical or psychological.
Physical side effects of Amphetamine include:
Psychological side effects of taking Amphetamine may include:
Some studies have also shown that when Amphetamine is used to treat ADHD in children, it can retard or slow down growth.
Some minor effects have also been observed in the cardiovascular system, including increased heart rate and blood pressure.
However, more research is required to confirm this.
When Amphetamine is taken at higher doses or through routes not prescribed by a doctor, the risk of adverse effects increases.
Taking excess Amphetamine increases dopamine levels in the brain.
Overuse or abuse of Amphetamine may lead to:
People who take Amphetamine for recreational purposes may also experience withdrawal symptoms like depression and sleep disturbances when they stop taking the drug.
Many drugs, nutritional supplements, and herbal supplements may interact with Amphetamine.
Therefore, you must always inform your doctor about medications or supplements you are currently taking.
Drug interactions may change how drugs work and increase the risk of adverse reactions.
Some drugs that interaction with Amphetamine are:
Monoamine Oxidase Inhibitors of MAO inhibitors are a class of drugs used to treat depression.
Taking MAO inhibitors with Amphetamine may cause serious and possibly fatal drug interactions.
Therefore, you must avoid taking Amphetamine with MAO inhibitors like isocarboxazid, linezolid, metaxalone, methylene blue, etc.
You must also avoid taking MAO inhibitors for two weeks before taking Amphetamine.
Speak to your doctor to know when you should stop taking MAO inhibitors before starting on Amphetamine.
If you are taking drugs like methadone, dextromethorphan, or methylenedioxymethamphetamine (also called ecstasy) that increase serotonin production, taking Amphetamine can lead to serotonin syndrome or toxicity.
Amphetamine is similar to dextroamphetamine or lisdexamfetamine.
To avoid adverse effects or overdose, you must not take these medications together.
Amphetamine may interfere with routine lab tests like blood, urine analysis, and brain scan for Parkinson’s disease and give false results.
So, you must inform your doctor if you are taking Amphetamine before undergoing these tests.
The CYP2D6 gene gives instructions for the production of Cytochrome P450 Family 2 Subfamily D Member 6 enzyme.
The CYP2D6 enzyme plays a vital role in the metabolism of most psychostimulants (drugs that can stimulate the central nervous system), including Amphetamines.
Over 100 forms of the CYP2D6 gene have been identified.
They are classified as normal function, decreased function, or no function.
Though most people carry two copies of the CYP2D6, a few people might have more than two copies.
Individuals who carry one decreased function allele and one no function allele of the CYP2D6 are called intermediate metabolizers of Amphetamine.
Individuals who have two no-function alleles of the gene are called poor metabolizers of the drug.
A majority of people carry two normal function alleles of the CYP2D6 and are normal metabolizers of Amphetamine.
The DRD2 gene gives instructions for producing the Dopamine Receptor D2 subtype.
A particular mutation or abnormal change in this gene may cause myoclonus dystonia whereas other mutations may cause schizophrenia.
The DRD2 is also called the ‘pleasure-seeking gene due to its association with addictions.
People with the A1 type of the DRD2 gene are more prone to addictions of various kinds, including Amphetamine drug addiciton.
Some medical conditions can make it unsafe to take Amphetamine. Inform your doctor about any medical conditions that you may have, particularly:
If you have a history of sensitivity or allergy to Amphetamine, you must avoid taking the drug.
If you have a history of drug abuse or addictions, you must not take Amphetamine and inform your doctor about the same.
Inform your doctor if you are pregnant or are planning a pregnancy. Taking Amphetamine during pregnancy may cause premature birth, low birth weight of the baby, or withdrawal symptoms in the newborn.
Since Amphetamine can pass into breast milk and harm your baby, you must inform your doctor if you are breastfeeding before taking the drug.
Genetic testing helps your doctor understand how a particular drug may affect you. It can also help them determine the appropriate dosage for you based on your medical history, medications you are taking, and history of addictions.
Before taking Amphetamine, genetic testing for the CYP2D6 and DRD2 genes may be helpful to determine how you will metabolize the drug without causing side effects.
Pharmacogenomics, sometimes called as pharmacogenetics, is the study of how genes affect a person’s response to drugs. It is a combination of two fields - pharmacology (the science of drugs) and genomics (the study of genes and their functions).
Just like how genes determine our eye color, height, etc. they also partly influence how our body responds to drugs. Some chemical changes in these genes can elicit unwanted side effects upon drug consumption.
The long-term goal of pharmacogenomic research is to design drugs best suited for each person, in order to avoid these undesirable side effects.
Genes influence multiple steps involved in your response to drugs. They include:
Drug Receptors: Some drugs require a type of protein called the receptors, to which they bind and get activated. Your genes can influence the number and effectiveness of these receptors.
Example: T-DM1 is a drug used to treat breast cancer. This drug works by attaching to a receptor called the HER-2 receptor. However, not all breast cancer cells express this receptor. So, this drug may not be effective for all individuals with breast cancer.
Drug Uptake: Certain drugs are activated only after they are taken into the cells and tissues. If your genetic makeup leads to reduced uptake of the drug, it may accumulate in other parts of the body.
Example: Statins are a class of drugs commonly used to treat high cholesterol levels. For the drug to work, it must be transported to and taken up by the liver efficiently. SLCO1B1 gene influences this process. A change in this gene results in a reduced transport of statins to the liver. This can result in statin buildup in muscles resulting in pain and weakness.
Drug breakdown/metabolism: If your genetic makeup results in a faster breakdown of drugs, it gets clear from the body faster. This may warrant an increased dosage of the drug or a different drug. On the other hand, if your drug metabolism is slow, it stays in your body for a longer period. In this case, a lower dosage may do the work.
Example: Amitriptyline is an antidepressant drug. Two genes, namely, CYP2D6 and CYP2C19, are involved in its metabolism. If you carry a change that slows down or boosts the metabolism, you may need to alter the drug dosage accordingly.
Patients can respond differently to the same medicine.
Commonly used drugs to treat some medical conditions need not be effective for everyone. Some examples are:
- Antidepressants drugs (SSRIs) are ineffective in as many as 38% of patients who are prescribed these drugs
- Asthma drugs are ineffective in as many as 40% of patients who are prescribed these drugs
- Diabetes drugs are ineffective in as many as 43% of patients who are prescribed these drugs
- Arthritis drugs are ineffective in as many as 50% of patients who are prescribed these drugs
- Alzheimer’s drugs are ineffective in as many as 70% of patients who are prescribed these drugs
- Cancer drugs are ineffective in as many as 75% of patients who are prescribed these drugs
- Cardiac Arrhythmias drugs are ineffective in as many as 40% of patients who are prescribed these drugs
Source: Brian B Spear, Margo Heath-Chiozzi, Jeffrey Huff, Clinical application of pharmacogenetics, Trends in Molecular Medicine, Volume 7, Issue 5, 2001, Pages 201-204, ISSN 1471-4914, https://doi.org/10.1016/S1471-4914(01)01986-4.
The purpose of pharmacogenomic testing is to find out if a medication is right for you. A pharmacogenomic test will help in knowing:
Efficacy - Whether a medication may be an effective treatment for you.
Dosage - What is the best dose for you for specific medications.
Toxicity - Whether you could have serious side effects from a medication.
CYP enzymes or the Cytochrome P450 enzymes are the major drug-metabolizing enzymes in the body. The P450 enzymes contain a protein called heme (iron-containing compound) and are commonly present in hepatocytes (cells of the liver). This is why drugs are mostly broken down or metabolized in the liver.
From a clinical perspective, the most commonly tested CYPs are:
Changes in CYP enzymes can influence the metabolism and clearance of drugs.
The CYP450 Test categorizes individuals into one of the four known metabolic profiles, called “predicted phenotypes.”
What are the limitations of a CYP test?
- Pharmacogenomic research is still in its infancy. Therefore, tests are available only for certain drugs.
- Any change in medication will require a new CYP test - this is because different enzymes are responsible for metabolizing different drugs
- The test reveals how genes affect the drugs and not what the drug does to the body (for example, we cannot determine how the drugs change certain receptors in the brain to alleviate the symptoms)
- Some drugs are metabolized and cleared by more than one CYP enzyme. For example, antidepressant drugs like the SSRIs (Selective Serotonin Reuptake Inhibitor) are metabolized by serotonin receptor molecules as well. This can limit the predictive value of the test.
Who should take the PGx test ?
If you answer yes to any of the below questions, you are an ideal candidate for a PGx test.
1. Are you currently taking four or more medications monthly?
2. Have you or anyone in your family ever been hospitalized for taking medication?
3. Have you or anyone in your family ever felt ill after taking a new medication?
4. Has your doctor changed your dose of medication due to a lack of response or a reaction to the medication?
5. Do you take your prescribed medication, and you still aren’t feeling better?
6. Are you taking or is your doctor considering prescribing to you pain medicine, tamoxifen, or Plavix?
7. Do you take herbal supplements regularly in addition to your medication?