INVERSINE® (Mecamylamine HCl) is a potent, oral antihypertension agent and ganglion blocker, and is a secondary amine. It is N,2,3,3-tetramethyl-bicyclo (2.2.1] heptan- 2 -amine hydrochloride. Its empirical formula is C₁₁H₂₁N • HCI and its structural formula is:

It is a white, odorless, or practically odorless, crystalline powder, is highly stable, soluble in water and has a molecular weight of 203.75.

INVERSINE is supplied as tablets for oral use, each containing 2.5 mg mecamylamine HCI. Inactive ingredients are acacia, calcium phosphate, D&C Yellow 10, FD&C Yellow 6, lactose, magnesium stearate, starch, and talc.

Last updated on RxList: 12/2/2008

For the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension.

Therapy is usually started with one 2.5 mg tablet of INVERSINE twice a day. This initial dosage should be modified by increments of one 2.5 mg tablet at intervals of not less than 2 days until the desired blood pressure response occurs (the criterion being a dosage just under that which causes signs of mild postural hypotension).

The average total daily dosage of INVERSINE is 25 mg, usually in three divided doses. However, as little as 2.5 mg daily may be sufficient to control hypertension in some patients. A range of two to four or even more doses may be required in severe cases when smooth control is difficult to obtain. In severe or urgent cases, larger increments at smaller intervals may be needed. Partial tolerance may develop in certain patients, requiring an increase in the daily dosage of INVERSINE.

Administration of INVERSINE after meals may cause a more gradual absorption and smoother control of excessively high blood pressure. The timing of doses in relation to meals should be consistent. Since the blood pressure response to antihypertensive drugs is increased in the early morning, the larger dose should be given at noontime and perhaps in the evening. The morning dose, as a rule, should be relatively small and in some instances may even be omitted.

The initial regulation of dosage should be determined by blood pressure readings in the erect position at the time of maximal effect of the drug, as well as by other signs and symptoms of orthostatic hypotension.

The effective maintenance dosage should be regulated by blood pressure readings in the erect position and by limitation of dosage to that which causes slight faintness or dizziness in this position. If the patient or a relative can use a sphygmomanometer, instructions may be given to reduce or omit a dose if readings fall below a designated level or if faintness or lightheadedness occurs. However, no change should be instituted without the knowledge of the physician.

Close supervision and education of the patient, as well as critical adjustment of dosage, are essential to successful therapy.

Other Antihypertensive Agents

When INVERSINE is given with other antihypertensive drugs, the dosage of these other agents, as well as that of INVERSINE, should be reduced to avoid excessive hypotension. However, thiazides should be continued in their usual dosage, while that of INVERSINE is decreased by at least 50 percent.

Tablets INVERSINE, 2.5 mg, are slightly yellow, round compressed tablets, coded LBS01. They are supplied as follows:

NDC 17205-0626-1 in bottles of 100.

Storage Condition

Store at 25°C (77°F); excursions permitted to 15-30°(59-86°F)

(see USP Controlled Room (Temperature)

Manufactured by: Siegfried CMS Ltd., Zofingen, Switzerland for Targacept, Inc., Wmston-Salem, NC 27101. FDA revision date: 10/18/2002

Last updated on RxList: 12/2/2008

The following adverse reactions have been reported and within each category are listed in order of decreasing severity.

Gastrointestinal: Ileus, constipation (sometimes preceded by small, frequent liquid stools), vomiting, nausea, anorexia glossitis and dryness of mouth.

Cardiovascular: Orthostatic dizziness and syncope, postural hypotension.

Nervous System/Psychiatric: Convulsions, choreiform movements, mental aberrations, tremor, and paresthesias (see WARNINGS).

Respiratory:Interstitial pulmonary edema and fibrosis.

Urogenital:Urinary retention, impotence, decreased libido.

Special Senses: Blurred vision, dilated pupils.

Miscellaneous: Weakness, fatigue, sedation.

Patients receiving antibiotics and sulfonamides generally should not be treated with ganglion blockers.

The action of INVERSINE may be potentiated by anesthesia, other anti hypertensive drugs and alcohol.

Last updated on RxList: 12/2/2008

Mecamylamine, a secondary amine, readily penetrates into the brain and thus may produce central nervous system effects. Tremor, choreiform movements, mental aberrations, and convulsions may occur rarely. These have occurred most often when large doses of INVERSINE were used, especially in patients with cerebral or renal insufficiency.

When ganglion blockers or other potent anti hypertensive drugs are discontinued suddenly, hypertensive levels return. In patients with malignant hypertension and others, this may occur abruptly and may cause fatal cerebral vascular accidents or acute congestive heart failure. When INVERSINE is withdrawn, this should be done gradually and other anti hypertensive therapy usually must be substituted. On the other hand, the effects of INVERSINE sometimes may last from hours to days after therapy is discontinued.

General

The patient's condition should be evaluated carefully, particularly as to renal and cardiovascular function. When renal, cerebral, or coronary blood flow is deficient, any additional impairment, which might result from added hypotension, must be avoided. The use of INVERSINE in patients with marked cerebral and coronary arteriosclerosis or after a recent cerebral accident requires caution.

The action of INVERSINE may be potentiated by . excessive heat, fever, infection, hemorrhage, pregnancy, anesthesia, surgery, vigorous exercise, other anti hypertensive drugs, alcohol, and salt depletion as a result of diminished intake or increased excretion due to diarrhea, vomiting, excessive sweating, or diuretics.

During therapy with INVERSINE, sodium intake should not be restricted but, if necessary, the dosage of the ganglion blocker must be adjusted.

Since urinary retention may occur in patients on ganglion blockers, caution is required in patients with prostatic hypertrophy, bladder neck obstruction, and urethral stricture.

Frequent loose bowel movements with abdominal distention and decreased borborygmi may be the first signs of paralytic ileus. If these are present, INVERSINE should be discontinued immediately and remedial steps taken.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the effects upon fertility, mutagenic or carcinogenic potential of INVERSINE.

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with INVERSINE. It is not known whether INVERSINE can cause fetal harm when given to a pregnant woman or can affect reproductive capacity. INVERSINE should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Because of the potential for serious adverse reactions in nursing infants from INVERSINE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Last updated on RxList: 12/2/2008

Signs of overdosage include: hypotension (which may progress to peripheral vascular collapse), postural hypotension, nausea, vomiting, diarrhea, constipation paralytic ileus, urinary retention, dizziness, anxiety, dry mouth, mydriasis, blurred vision, or palpitations. A rise in intraocular pressure may occur.

Pressor amines may be used to counteract excessive hypotension. Since patients being treated with ganglion blockers are more than normally reactive to pressor amines small doses of the latter are recommended to avoid excessive response.

The oral LD₅₀ of mecamylamine in the mouse is 92 mg/kg.

INVERSINE should not be used in mild, moderate, labile hypertension and may prove unsuitable in uncooperative patients. It is contraindicated in coronary insufficiency or recent myocardial infarction.

INVERSINE should be given with great discretion, if at all, when renal insufficiency is manifested by a rising or elevated BUN. The drug is contraindicated in uremia. Patients receiving antibiotics and sulfonamides should generally not be treated with ganglion blockers. Other contraindications are glaucoma, organic pyloric stenosis or hypersensitivity to the product

Last updated on RxList: 12/2/2008

Mecamylamine reduces blood pressure in both normotensive and hypertensive individuals. It has a gradual onset of action (1/2 to 2 hours) and a long-lasting effect (usually 6 to 12 hours or more). A small oral dosage often produces a smooth and predictable reduction of blood pressure. Although this anti hypertensive effect is predominantly orthostatic, the supine blood pressure is also significantly reduced.

Pharmacokinetics and Metabolism

Mecamylamine is almost completely absorbed from the gastrointestinal tract, resulting in consistent lowering of blood pressure in most patients with hypertensive cardiovascular disease. Mecamylamine is excreted slowly in the urine in the unchanged form. The rate of its renal elimination is influenced markedly by urinary pH. Alkalinization of the urine reduces, and acidification promotes, renal excretion of mecamylamine.

Mecamylamine crosses the blood-brain and placental barriers.

Last updated on RxList: 12/2/2008

INVERSINE may cause dizziness, lightheadedness, or fainting, especially when rising from a lying or sitting position. This effect may be increased by alcoholic beverages, exercise, or during hot weather. Getting up slowly may help alleviate such a reaction.

Last updated on RxList: 12/2/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

MECAMYLAMINE - ORAL

(MECK-uh-MILL-uh-meen)

COMMON BRAND NAME(S): Inversine

USES: This medication is used to treat moderately severe to severe high blood pressure. It can also be used in sudden high blood pressure emergencies (malignant hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. Mecamylamine belongs to a class of drugs known as ganglion blockers. It works by relaxing blood vessels so blood can flow more easily.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to help people stop smoking.

HOW TO USE: Take this medication by mouth after meals, usually 2 to 3 times daily or as directed by your doctor. If you take this medication 2 times a day, take it in the afternoon (e.g., after lunch) and in the evening (e.g., after dinner). If you take this medication 3 times a day, the manufacturer recommends that you take a smaller dose in the morning.

The dosage is based on your medical condition and response to treatment.

If your doctor has directed you to use this medication on a schedule, take it regularly in order to get the most benefit from it. To help you remember, take it at the same times each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

Do not suddenly stop taking this medication without consulting your doctor. Your condition may become worse (rarely fatal) when the drug is suddenly stopped. Your dose may need to be gradually decreased.

For the treatment of moderately severe high blood pressure, it may take up to 12 hours before you get the full benefit of this drug.

Tell your doctor if your condition worsens (e.g., your routine blood pressure readings increase).

When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

SIDE EFFECTS: Dizziness, lightheadedness, blurred vision, constipation, difficulty urinating, decreased sexual ability/interest, and dry mouth may occur as your body adjusts to the medication. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Hot weather, exercise, or alcohol may increase dizziness and lightheadedness while taking this medication. To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: seizures, shaking, uncontrolled movements of the face/hands/arms/legs, mental/mood changes.

If you develop frequent diarrhea with severe stomach/abdominal discomfort and/or bloating while taking this medication, seek immediate medical attention.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking mecamylamine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: mild/moderate/rapidly changing high blood pressure, heart problems (coronary insufficiency or recent heart attack), a certain kidney condition (uremia), a certain eye condition (glaucoma), a certain stomach condition (organic pyloric stenosis).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: a certain kidney disease (renal insufficiency), stroke, heart problems (e.g., heart attack, coronary arteriosclerosis), a certain prostate problem (prostatic hypertrophy), bladder problems (bladder neck obstruction, urethral stricture), fever, infection, severe/prolonged diarrhea, vomiting, sweating, bleeding, loss of salt.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy or cause blurred vision. Use caution while driving, using machinery, or taking part in any other activity that requires alertness and clear vision. Avoid alcoholic beverages.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects, especially dizziness.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because very serious interactions may occur: ambenonium.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting mecamylamine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antibiotics, sulfonamide drugs (e.g., sulfisoxazole, sulfamethizole, sulfasalazine).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, nonsteroidal anti-inflammatory drugs-NSAIDs such as ibuprofen for pain/fever reduction) because they may contain ingredients that could increase your blood pressure. Ask your pharmacist about using those products safely.

Low-dose aspirin should be continued if it has been prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day). 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.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: fainting, severe weakness, severe/sudden nausea and vomiting, seizures, hallucinations, rapid/irregular heartbeat.

NOTES: Do not share this medication with others.

Talk with your doctor about making changes to your lifestyle that may increase the effectiveness of this medication (e.g., stress reduction programs, exercise, and dietary changes).

Laboratory and/or medical tests may need to be performed to monitor your progress or check for side effects. Consult your doctor for more details.

Have your blood pressure checked regularly while taking this medication. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.