Nivalin 5mg/ml

Nivalin 5mg/ml® ER and Nivalin 5mg/ml® are indicated for the treatment of mild to moderate dementia of the Alzheimer's type.

Nivalin 5mg/ml is used to treat mild to moderate dementia (memory loss and mental changes) that is a sign of Alzheimer's disease. Nivalin 5mg/ml will not cure Alzheimer's disease, and it will not stop the disease from getting worse. However, Nivalin 5mg/ml can improve the thinking ability in some patients with Alzheimer's disease.

In Alzheimer's disease, many chemical changes take place in the brain. One of the earliest and biggest changes is that there is less of a chemical called acetylcholine (ACh). ACh helps the brain to work properly. Nivalin 5mg/ml slows the breakdown of ACh, so it can build up and have a greater effect. However, as Alzheimer's disease gets worse, there will be less and less ACh, so Nivalin 5mg/ml may not work as well.

Nivalin 5mg/ml is available only with your doctor's prescription.

Nivalin 5mg/ml® ER Extended-Release Capsules

Nivalin 5mg/ml® ER extended-release capsules should be administered once daily in the morning, preferably with food.

The recommended starting dosage of Nivalin 5mg/ml® ER is 8 mg/day. The dosage should be increased to the initial maintenance dose of 16 mg/day after a minimum of 4 weeks. A further increase to 24 mg/day should be attempted after a minimum of 4 weeks at 16 mg/day. Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.

The dosage of Nivalin 5mg/ml® ER shown to be effective in a controlled clinical trial is 16–24 mg/day.

Patients currently being treated with Nivalin 5mg/ml® tablets or oral solution can convert to Nivalin 5mg/ml® ER (extended-release capsules) by taking their last dose of Nivalin 5mg/ml® tablets or oral solution in the evening and starting Nivalin 5mg/ml® ER once daily treatment the next morning. Converting from Nivalin 5mg/ml® to Nivalin 5mg/ml® ER should occur at the same total daily dosage.

Nivalin 5mg/ml® Immediate-Release Tablets and

Oral Solution

The dosage of Nivalin 5mg/ml® tablets shown to be effective in controlled clinical trials is 16–32 mg/day given as twice daily dosing. As the dosage of 32 mg/day is less well tolerated than lower dosages and does not provide increased effectiveness, the recommended dosage range is 16–24 mg/day given twice daily. The dosage of 24 mg/day did not provide a statistically significant greater clinical benefit than 16 mg/day. It is possible, however, that a daily dosage of 24 mg of Nivalin 5mg/ml® might provide additional benefit for some patients.

The recommended starting dosage of Nivalin 5mg/ml® tablets and oral solution is 4 mg twice a day (8 mg/day). The dosage should be increased to the initial maintenance dosage of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day).

Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.

Nivalin 5mg/ml® tablets and oral solution should be administered twice a day, preferably with morning and evening meals.

Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for more than three days, the patient should be restarted at the lowest dosage and the dosage escalated to the current dose.

The abrupt withdrawal of Nivalin 5mg/ml® ER and Nivalin 5mg/ml® in those patients who had been receiving dosages in the effective range was not associated with an increased frequency of adverse events in comparison with those continuing to receive the same dosages of that drug. The beneficial effects of Nivalin 5mg/ml® ER and Nivalin 5mg/ml® are lost, however, when the drug is discontinued.

Dosage in Patients with Hepatic Impairment

In patients with moderate hepatic impairment (Child-Pugh score of 7–9), the dosage should generally not exceed 16 mg/day. The use of Nivalin 5mg/ml® ER and Nivalin 5mg/ml® in patients with severe hepatic impairment (Child-Pugh score of 10–15) is not recommended.

Dosage in Patients with Renal Impairment

In patients with creatinine clearance of 9 to 59 mL/min, the dosage should generally not exceed 16 mg/day. In patients with creatinine clearance less than 9 mL/min, the use of Nivalin 5mg/ml® ER and Nivalin 5mg/ml® is not recommended.

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What is the most important information I should know about Nivalin 5mg/ml?

Before taking Nivalin 5mg/ml, tell your doctor if you have urination problems, heart disease, a heart rhythm disorder, stomach ulcers or bleeding, a seizure disorder, kidney disease, liver disease, or asthma.

Stop using Nivalin 5mg/ml and call your doctor at once if you have chest pain, slow heart rate, blood in your stools, coughing up blood, decreased urination, weakness, confusion, extreme thirst, or hot, dry skin.

There are many other drugs that can interact with Nivalin 5mg/ml. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

If you need surgery, tell the surgeon ahead of time that you are using Nivalin 5mg/ml. You may need to stop using the medicine for a short time.

If you have stopped taking Nivalin 5mg/ml for any reason, talk with your doctor before you start taking it again. You may need to restart the medication at a lower dose.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Use Nivalin 5mg/ml solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• A patient information instruction sheet is available with Nivalin 5mg/ml solution. Talk to your pharmacist if you have questions about this information.
• Take Nivalin 5mg/ml solution by mouth with morning and evening meals, unless otherwise directed by your doctor.
• Use the measuring device that comes with Nivalin 5mg/ml solution to measure your dose. Ask your pharmacist for help if you are unsure of how to measure your dose.
• After you have measured the dose, empty all of the medicine into 3 to 4 oz (100 mL) of any nonalcoholic drink. Stir well, then drink the mixture right away.
• After use, rinse the measuring device. This is done by inserting it into a glass of water, pulling the plunger out, and then pushing the plunger back in to remove the water.
• Drinking extra fluids while you are taking Nivalin 5mg/ml solution is recommended. Check with your doctor for instructions.
• Take Nivalin 5mg/ml solution on a regular schedule to get the most benefit from it.
• Taking Nivalin 5mg/ml solution at the same time each day will help you remember to take it.
• Continue to take Nivalin 5mg/ml solution even if you feel well. Do not miss any doses.
• If you miss a dose of Nivalin 5mg/ml solution, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once. Contact your doctor if you miss several doses of Nivalin 5mg/ml solution. Your doctor may need to restart your medicine at a lower dose to avoid side effects.

Ask your health care provider any questions you may have about how to use Nivalin 5mg/ml solution.

Nivalin 5mg/ml is used to treat mild to moderate confusion (dementia) related to Alzheimer's disease. It does not cure Alzheimer's disease, but it may improve memory, awareness, and the ability to perform daily functions. This medication works by restoring the balance of certain natural substances (neurotransmitters) in the brain.

How to use Nivalin 5mg/ml

Take this medication by mouth with food, usually twice daily with the morning and evening meals, or as directed by your doctor. Drink plenty of fluids with this medication unless instructed otherwise. To lower your risk of side effects, your dosage will be gradually increased to your target dose. Your dosage is based on your medical condition and response to therapy. Do not take more than the maximum recommended dose of 24 milligrams per day.

If you are using the liquid form of this drug, read the manufacturer's instruction sheet that comes with the bottle. Follow the directions exactly. Use the measuring device that comes with the product to measure out your dose. Mix your dose of medication in about 4 ounces (120 milliliters) of nonalcoholic beverage, stir, and drink the entire mixture. Ask your pharmacist about any information that is unclear.

If you stop taking Nivalin 5mg/ml for longer than 3 days, your doctor may direct you to restart this medication at a low dose and gradually increase your dose to reduce your risk of side effects. Carefully follow your doctor's instructions.

Use this medication regularly in order to get the most benefit from it. Do not stop taking it or increase the dosage unless your doctor instructs you to do so.

It may take at least 4 weeks of continued use before the full benefit of this drug takes effect.

Inform your doctor if your condition worsens.

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What other drugs will affect Nivalin 5mg/ml?

Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anticholinergic drugs (e.g., atropine, diphenhydramine, scopolamine, tolterodine), aspirin (high doses used for arthritis), cholinergic drugs (e.g., bethanechol), cholinesterase inhibitors (e.g., neostigmine), long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, naproxen), drugs affecting liver enzymes that remove Nivalin 5mg/ml from your body (such as azole antifungals including ketoconazole, amitriptyline, SSRI antidepressants including paroxetine, quinidine).

Also report the use of heart drugs (those that decrease heart rate or block AV impulse conduction) such as: beta-blockers (e.g., metoprolol, propranolol), calcium channel blockers (e.g., diltiazem, verapamil), digoxin.

Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (NSAIDs such as aspirin, ibuprofen, or naproxen) which, if taken together with Nivalin 5mg/ml, may increase your risk for stomach/intestinal bleeding. Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day), should be continued. Consult your doctor or pharmacist for more details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

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What are the possible side effects of Nivalin 5mg/ml?

Serious adverse reactions are discussed in more detail in the following sections of the labeling:

• Serious skin reactions
• Cardiovascular Conditions
• Gastrointestinal Conditions
• Genitourinary Conditions
• Neurological Conditions
• Pulmonary Conditions
• Deaths in subjects with mild cognitive impairment (MCI)

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reactions in Nivalin 5mg/ml-treated patients from double-blind clinical trials (≥5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite.

The most common adverse reactions associated with discontinuation (≥1%) in Nivalin 5mg/ml-treated patients from double-blind clinical trials were nausea (6.2%), vomiting (3.3%), decreased appetite (1.5%), and dizziness (1.3%).

The safety of the extended-release capsule and immediate-release tablet formulations of Nivalin 5mg/ml was evaluated in 3956 Nivalin 5mg/ml-treated patients who participated in 8 placebo-controlled clinical studies and 1454 subjects in 5 open-label clinical studies with mild to moderate dementia of the Alzheimer's type. In clinical studies, the safety profile of once-daily treatment with extended-release Nivalin 5mg/ml was similar in frequency and nature to that seen with tablets. The information presented in this section was derived from pooled double-blind studies and from pooled open-label data.

Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials

Table 1 lists the adverse reactions reported in ≥1% of Nivalin 5mg/ml-treated patients in 8 placebo-controlled, double-blind clinical trials.

The majority of these adverse reactions occurred during the dose-escalation period. In those patients who experienced the most frequent adverse reaction, nausea, the median duration of the nausea was 5–7 days.

Other Adverse Reactions Observed in Clinical Trials of Nivalin 5mg/ml

The following adverse reactions occurred in <1% of all Nivalin 5mg/ml-treated patients (N=3956) in the above double-blind, placebo-controlled clinical trial data sets. In addition, the following also includes all adverse reactions reported at any frequency rate in patients (N=1454) who participated in open-label studies. Adverse reactions listed in Table 1 above were not included below:

Metabolism and Nutrition Disorders: Dehydration

Nervous System Disorders: Dysgeusia, Hypersomnia, Paresthesia

Eye Disorders: Blurred vision

Cardiac Disorders: First degree atrioventricular block, Palpitations, Sinus bradycardia, Supraventricular extrasystoles

Vascular Disorders: Flushing, Hypotension

Gastrointestinal Disorders: Retching

Skin and Subcutaneous Tissue Disorders: Hyperhidrosis

Musculoskeletal and Connective Tissue Disorders: Muscular weakness

Discontinuations Due to Adverse Reactions

In the 8 placebo-controlled studies of adults, 418 (10.6%) Nivalin 5mg/ml-treated patients (N=3956) and 56 (2.2%) placebo patients (N=2546) discontinued due to an adverse reaction. Those events with an incidence of ≥0.5% in the Nivalin 5mg/ml-treated patients included nausea (245, 6.2%), vomiting (129, 3.3%), decreased appetite (60, 1.5%), dizziness (50, 1.3%), diarrhea (31, 0.8%), headache (29, 0.7%), and decreased weight (26, 0.7%). The only event with an incidence of ≥0.5% in placebo patients was nausea (17, 0.7%).

In the 5 open-label studies, 103 (7.1%) patients (N=1454) discontinued due to an adverse reaction. Those events with an incidence of ≥0.5% included nausea (43, 3.0%), vomiting (23, 1.6%), decreased appetite (13, 0.9%), headache (12, 0.8%), decreased weight (9, 0.6%), dizziness (8, 0.6%), and diarrhea (7, 0.5%).

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of Nivalin 5mg/ml® ER and Nivalin 5mg/ml®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency:

Immune System Disorders: Hypersensitivity

Psychiatric Disorders: Hallucinations

Nervous System Disorders: Seizures

Ear and Labyrinth Disorders: Tinnitus

Vascular Disorders: Hypertension

Hepatobiliary Disorders: Hepatitis, Increased hepatic enzyme

Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome, Acute generalized exanthematous pustulosis, Erythema multiforme

A benzazepine derived from norbelladine. It is found in galanthus and other amaryllidaceae. Nivalin 5mg/ml is a cholinesterase inhibitor that has been used to reverse the muscular effects of gallamine triethiodide and tubocurarine, and has been studied as a treatment for Alzheimer's disease and other central nervous system disorders. [PubChem]