Rivastigmine - Know How It Works

Overview:

As people became more aware of brain diseases that cause problems with memory and thinking, new medicines were being developed to fight these diseases. One of these medicines is called Rivastigmine, which was created in 1985. It is a medicine used to help control and treat memory and thinking problems in people with diseases like Alzheimer's. Medication for Alzheimer's disease is vital, although the advantages are limited. Medication is one of the aspects of caring for someone with Alzheimer's. Other therapies, activities, and support are also necessary to improve their quality of life. Rivastigmine belongs to a group of drugs that help improve communication between nerve cells in the brain. Rivastigmine received approval from the Food and Drug Administration (FDA) in 1997.

Drug Group:

Rivastigmine is a medicine that helps people with Alzheimer's and Parkinson's disease manage their memory and thinking problems. It falls into a group of drugs called cholinesterase inhibitors, which work to improve cognitive function in these conditions.

Available Doses and Dosage Forms:

Capsule:

• 1.5 milligram (mg).

• 3 mg.

• 4.5 mg.

• 6 mg.

Transdermal Patch:

• 4.6 mg/24 hour (hr).

• 9.5 mg/24 hr.

• 13.3 mg/ 24 hr.

For Patients

What Is Alzheimer’s Disease?

Alzheimer's is a brain disease causing memory loss and impairing daily tasks, with late-onset (common) and early-onset (rare) forms. Named after Dr. Alois Alzheimer, it involves abnormal brain clumps and cell connection loss, progressively affecting memory, language, reasoning, and social functions.

How Does Rivastigmine Work?

Acetylcholine is a chemical substance found in the brain that helps in nerve cell communication. But in Alzheimer's, this chemical is lower, and the nerve cells that use it are also lost. This leads to the worsening of symptoms. Drugs like Rivastigmine help to improve this situation. They do this by stopping an enzyme (a type of molecule) called acetylcholinesterase from breaking down acetylcholine in the brain. This results in more acetylcholine being available, which helps nerve cells communicate better. This might temporarily make some Alzheimer's symptoms get better or at least stay the same.

In the United Kingdom, the National Institute for Health and Care Excellence (NICE) advises which medications should be used in the National Health Service (NHS). NICE looks at Rivastigmine to make sure they are safe and work well. Rivastigmine helps increase a chemical in the brain that helps nerve cells communicate better.

What Is the Dosage of Rivastigmine?

1. For Alzheimer's:

• A person can take it as a pill, starting with a low dose of 1.5 mg twice a day and slowly increasing it to a maximum of 6 mg twice a day for maintenance.

• There's also a patch a person can wear, starting with a 4.6 mg patch that they can change daily.

• A person can increase to a 9.5 mg patch after 4 weeks and up to a 13.3 mg patch if needed. This is typically used for moderate to severe Alzheimer's.

2. For Parkinson's Dementia:

• Similarly, a person can take it as a pill, starting with 1.5 mg twice a day and increasing to a maximum of 6 mg twice a day.

• Patches are an option, too, starting with a 4.6 mg patch, and the person may increase it to 9.5 mg after 4 weeks and up to 13.3 mg if necessary.

How Is Rivastigmine Taken?

Rivastigmine is a medication used for Alzheimer's disease, and it comes in different forms:

Capsules to Swallow or a Liquid Solution to Drink:

• The patient is asked to take it twice daily, during morning and evening meals.

• When the patient starts taking it, they usually begin with a smaller dose of 3 mg (milligrams) a day, split into two doses.

• Over time, this dose can be increased every couple of weeks to between six and twelve mg daily. Most of the dose taken in a day is 12 mg.

Patches:

• These patches stick to the skin and slowly release the medication.

• They come in different strengths: 4.6 mg, 9.5 mg, or thirteen mg daily. The patches tend to have fewer side effects compared to the capsules.

• They are a good option for people who have trouble swallowing pills, and caregivers often find them helpful.

• Only one patch should be worn at a time. It should be put on different areas of the skin each time to avoid skin irritation.

What Are the Things to Inform the Doctor Before Taking the Rivastigmine?

Patients should inform their doctor if they have had:

• Asthma.

• Prostate enlargement.

• Ulcers.

• Heart rhythm issues.

• Seizures.

• Tremors.

• Heart/Lung problems.

• Kidney or Liver troubles.

What Are the Therapeutic Uses of Rivastigmine?

• Rivastigmine is a medication that helps with memory and thinking problems in people with Alzheimer's disease.

• It can not cure the disease, but it might make one remember things better, be more aware of their surroundings, and make daily tasks easier.

• Rivastigmine fixes the natural balance of chemicals in the brain that help with communication between nerve cells.

• It is like giving a little boost to the brain's messaging system to help it think and remember more clearly.

• Patients who took Rivastigmine performed about 30 percent better on memory tests than those who did not.

How Is Rivastigmine Administered?

• Rivastigmine comes in different forms: capsules to swallow, oral liquid, and patches to put on the skin.

• The capsules have different strengths, like 1.5 mg, three mg, 4.5 mg, and 6 mg.

• The liquid has two mg in each milliliter.

• The patches come in strengths of 4.6 mg, 9.5 mg, and 13.3 mg daily.

Doctors use Rivastigmine to help people with memory problems from Alzheimer's disease.

They use a test called the mini-mental state examination (MMSE) to see if Rivastigmine could work for a person. It might be a good option if the test scores are between twenty-four to twenty-six or ten to eleven.

• For the capsules, the dosing is as follows: Alzheimer's with mild to moderate memory problems should start with a low dose and slowly increase every two weeks with food.

• For the patches, the dosing is similar: Alzheimer's with mild to moderate memory problems should start with a low-strength patch and increase if needed. Alzheimer's with severe memory problems should start with a low-strength patch and increase if needed. If an individual stops treatment for over three days, they might need to start with a lower dose again. If the liver is not working well, their doctor might adjust the dose.

What Are the Side Effects of Taking Rivastigmine?

Cholinesterase inhibitors are medicines used for Alzheimer's disease, and they usually do not cause too many problems for most people. However, only some experience the same side effects, and if they do, the side effects might not last the same amount of time for everyone. The most common side effects of drugs are:

• Not feeling hungry.

• Feeling sick.

• Throwing up.

• Having diarrhea.

• Muscle cramps.

• Headaches.

• Feeling dizzy.

• Being tired.

• Having trouble sleeping.

These side effects might be less likely if an individual starts with a lower dose for about a month. It is essential to talk to the doctor or pharmacist if someone experiences any side effects. These drugs are not addictive, so one does not have to worry about addiction problems.

Dietary Considerations:

A person should take Rivastigmine with food for it to work effectively. It is typically taken twice a day, in the morning and evening, at consistent times. If a person uses the liquid form, use the provided dosing syringe to measure the dose.

Missed Dose:

If a person needs to remember to take a dose, they should take it as soon as they remember. But if the next dose is coming up soon, just skip the missed one and stick to the regular schedule. Do not take two doses to make up for the one the person missed. If they have missed doses for over three days, contact the doctor. They recommend going back to a lower dose.

Overdose:

Taking too much Rivastigmine can cause seizures or shock. Signs of shock include dilated pupils, irregular breathing, and a fast, weak pulse. An overdose may also result in severe nausea, vomiting, increased muscle weakness, excessive sweating, and a lot of saliva production. If this happens, seek immediate medical attention.

Managing Overdose:

• Overdose management approaches change over time, so it is best to contact a poison control center for the latest advice on any drug overdose.

• Rivastigmine has a short time in the bloodstream and moderately inhibits an enzyme for about eight to ten hours. If there is an overdose without symptoms, it is recommended to avoid taking more for the next twenty-four hours.

• If an overdose happens, general supportive care should be provided. Overdosing on drugs like Rivastigmine can lead to a cholinergic crisis with symptoms like severe nausea, vomiting, sweating, slow heart rate, low blood pressure, breathing problems, collapsing, and seizures. There might also be muscle weakness, potentially causing breathing issues and even death.

Storage:

Store the medication in a sealed container at room temperature, away from heat, dampness, and direct sunlight. Ensure it does not freeze. Keep it out of children's reach. Dispose of any expired or unneeded medicine as advised by the healthcare provider.

For Doctors

Indications:

• Rivastigmine is indicated for enhancing gait stability and reducing the risk of falls.

• In geriatric patients with preexisting cognitive impairments, Rivastigmine can aid in reducing postoperative delirium after surgery.

• It also offers cognitive improvement for individuals with dementia with Lewy bodies.

• Rivastigmine administration is associated with around 30 percent enhanced memory performance in comparison to non-users.

• Rivastigmine users experience alleviated anxiety levels and decreased instances of hallucinations and delusional perceptions.

Dose:

Individual patient dosages may vary. Adhere to the physician's instructions or label directions. Do not alter the dosage unless directed by the physician. The dose is contingent on the medication's potency, dosing frequency, time intervals between doses, and treatment duration relative to the medical condition.

For Oral Administration (Capsules or Solution):

For Alzheimer's treatment:

• Adults: Initiate at 1.5 milligrams (mg) administered twice daily. The physician may incrementally adjust the dose based on necessity and tolerance. Typically, the maximum dose does not exceed 6 mg twice daily.

• Children: Dosage is determined by the physician.

For Parkinson's Treatment:

• Adults: Commence with 1.5 milligrams (mg) taken twice daily. The physician may incrementally modify the dose based on necessity and tolerance. Usually, the maximum dose is 6 mg twice daily at most.

• Children: Dosage is determined by the physician.

Pharmacodynamics:

Rivastigmine is a reversible cholinesterase inhibitor that falls under the category of parasympathomimetic drugs. Alzheimer's disease is characterized by the early loss of cholinergic neurons in specific brain regions, resulting in reduced acetylcholine levels, which are linked to memory and cognitive impairments. The exact mechanism of how rivastigmine works is not fully understood, but it is thought to enhance cholinergic function by inhibiting the breakdown of acetylcholine through reversible cholinesterase inhibition. This increased acetylcholine concentration can help alleviate symptoms. However, as the disease progresses and fewer cholinergic neurons are functional, the effectiveness of rivastigmine may diminish.

Mechanism of Action:

In the brain, there are two types of enzymes that break down a neurotransmitter called acetylcholine. These enzymes are like scissors that slice acetylcholine into smaller fragments.

• One enzyme called acetylcholinesterase (AChE), is seen at special spots where nerve cells communicate.

• The other enzyme, called butyrylcholinesterase (BuChE), is found in different parts of the brain where it helps control acetylcholine activity.

As people get older, the activity of these enzymes increases. In diseases like Alzheimer's, this activity goes even higher than normal. The drug Rivastigmine can stick to both of these enzymes and stop them from breaking down acetylcholine. This leads to increased concentration of acetylcholine, which can be helpful for the brain's communication.

Pharmacokinetics:

Rivastigmine is a medication used for Alzheimer's disease. About 40 percent of the dose is absorbed into the body when a person takes it. It behaves as expected at lower doses, but its effects become less predictable at higher doses. For example, doubling the dose from three mg to six mg leads to a threefold increase in the amount of the medication in the body. The time it takes for half of the medication to be eliminated from the body is about 1.5 hours, with most of the breakdown products being removed through the urine.

• Absorption: When a person takes Rivastigmine, the body absorbs it rapidly and completely, with the highest concentration in the blood reached within about an hour. Taking it with food delays this absorption by about ninety minutes, but it also increases the overall amount of the medication in the system.

• Distribution: Rivastigmine is widely distributed throughout the body, including crossing into the brain, affecting brain fluid concentrations. It is moderately bound to blood proteins and distributed equally between blood and plasma at different concentrations.

• Metabolism: The body processes Rivastigmine quickly, primarily through the kidneys. After the medication is broken down, the main component is excreted in the urine, making up about 40 percent of the total dose. This process is not significantly influenced by certain enzymes in the liver that usually play a role in drug metabolism. Importantly, Rivastigmine does not appear to have significant interactions with other drugs that are processed by a specific enzyme group called cytochrome P450.

Toxicity:

Toxicity is anticipated to manifest similarly to poisoning caused by other carbamates and organophosphates, exhibiting a combination of muscarinic effects such as excessive salivation, tearing, urination, defecation, constricted pupils, increased bronchial secretions, and slowed heart rate, along with nicotinic effects including muscle weakness, muscle twitching, and paralysis.

Contraindications of Rivastigmine

Rivastigmine should not be used in the following circumstances:

• Individuals with a documented history of hypersensitivity reactions to Rivastigmine or similar medications are contraindicated from its use.

• Caution is advised for patients with severe adverse reactions to analogous medications.

• A history of severe adverse reactions to specific medications should also warrant caution when considering Rivastigmine administration.

• Patients with a history of significant skin reactions to transdermal patches should use Rivastigmine cautiously.

• Patients with specific medical conditions should exercise prudence when initiating Rivastigmine therapy.

• Children under eighteen years of age should avoid Rivastigmine.

• Special caution is warranted for those with cardiovascular comorbidities, bradycardia, respiratory disorders including asthma, peptic ulcers with bleeding, bleeding diathesis, or a history of seizures.

• Special consideration should be given to individuals with a body weight below 50 kg or 100 and ten pounds before prescribing Rivastigmine.

• Rivastigmine should be avoided in breastfeeding mothers.

Doctors must watch and evaluate before prescribing Rivastigmine to someone with these conditions.

Drug Interactions of Rivastigmine

• Interactions With Other Drugs:

  1. Rivastigmine is broken down mainly by enzymes called esterases. Major cytochrome P450 enzymes that process other drugs do not significantly affect it.

  2. There is no significant interaction between Rivastigmine and drugs like Digoxin, Warfarin, Diazepam, or Fluoxetine in healthy volunteers.

  3. Rivastigmine's metabolism is not greatly influenced by commonly used medications.

• Use With Other Types of Medications:

  1. Cholinesterase inhibitors like Rivastigmine could affect the activity of anticholinergic drugs.

  2. Combining cholinesterase inhibitors with certain neuromuscular blockers or cholinergic agonists might have a combined effect.

• Carcinogenesis, Mutagenesis, and Fertility:

  1. Rivastigmine did not cause cancer at doses up to 0.9 times the dose.

  2. Sometimes, Rivastigmine caused chromosomal changes, but it was not genotoxic.

  3. Rivastigmine is likely safe to use during pregnancy, but one should consult a physician before using it.

• Nursing and Pediatric Use:

  1. Rivastigmine has not been proven to be passed into human breast milk; however, it and Rivastigmine are not recommended for nursing mothers.

  2. Rivastigmine’s safety and effectiveness have not been properly tested in children for any condition.

Adverse Drug Effects of Rivastigmine

1. Problems that show up when someone starts taking the medicine or when the dose is increased to get the right amount in the body are:

• Vomiting is the main issues that can happen when using Rivastigmine are related to the stomach and digestion. The most common symptoms are feeling sick and throwing up. These problems usually appear when someone starts taking the medicine or increases the dose to get the right amount in the body. Symptoms can be reduced by slowly increasing the dose and taking the medicine with food if it is a pill.
• Trouble with movement.
• Sleeping problem.
• Muscle cramps.
• Feeling weak.

2. When the medicine is used for a long time, there could be effects on the brain and nervous system, although these are rare with Rivastigmine and more likely with a different medicine called Donepezil.

3. Using a patch to deliver Rivastigmine can be better for some people since it is less likely to cause nausea and vomiting. But, the patch can sometimes lead to skin problems like rashes. In rare cases, a serious allergic reaction can happen with the patch.

4. Compared to another medicine called Donepezil, using Rivastigmine for a long time might also increase the chances of passing away.

Special Considerations:

• During Pregnancy: If the patient is pregnant and considering Rivastigmine, the doctor should be cautious. The medication should be avoided during pregnancy unless it is really necessary.

• While Breastfeeding: If the patient is breastfeeding, it is not recommended to use Rivastigmine. Based on the drug's properties, it could transfer to babies through breast milk.