Minoxidil

You should not use minoxidil if you are allergic to it, or if you have:

• pheochromocytoma (tumor of the adrenal gland).

To make sure minoxidil is safe for you, tell your doctor if you have:

• congestive heart failure;

• angina (chest pain), or if you have recently had a heart attack;

• kidney disease (or if you are on dialysis);

• asthma;

• migraine headaches; or

• epilepsy or other seizure disorder.

It is not known whether this medicine will harm an unborn baby. However, a newborn baby could have excessive hair growth if the mother has taken minoxidil during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant.

Minoxidil can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Do not give this medicine to a child without medical advice.

You may need to limit or reduce the salt in your diet while taking minoxidil. Do not use potassium supplements or salt substitutes, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Ask your doctor or pharmacist before taking a cough or cold medicine that contains a decongestant such as phenylephrine.

Usual Adult Dose for Hypertension:

Initial dose: 5 mg orally once a day
Maintenance dose: 10 to 40 mg per day
Maximum dose: 100 mg per day

Comments:
-Daily doses can be increased to 10, 20, and then 40 mg in single or divided doses if needed for optimum blood pressure control.
-Doses should be titrated based on individual patient response; intervals between dose adjustments should be at least 3 days; adjustments can be made every 6 hours where more rapid management of hypertension is required if patient is carefully monitored.
-If supine diastolic pressure has been reduced less than 30 mmHg, administer only once a day; if supine diastolic pressure has been reduced more than 30 mmHg, the daily dosage should be given in 2 equally divided doses.

Use: For the treatment of hypertension that is symptomatic or associated with target organ damage not manageable with maximum therapeutic doses of a diuretic plus 2 other antihypertensive drugs; use in milder hypertension not recommended as benefit to risk ratio in such patients has not been defined

Usual Pediatric Dose for Hypertension:

Less than 12 years:
-Initial dose: 0.2 mg/kg orally once a day
-Maintenance 0.25 to 1 mg/kg/day
-Maximum dose: 50 mg per day

Comments:
-Doses may be increased in 50% to 100% increments until optimum blood pressure control is achieved.

Over 12 years:
-Initial dose: 5 mg orally once a day
-Maintenance dose: 10 to 40 mg per day
-Maximum dose: 100 mg per day

Comments:
-Daily doses can be increased to 10, 20, and then 40 mg in single or divided doses if needed for optimum blood pressure control.
-Doses should be titrated based on individual patient response; intervals between dose adjustments should be at least 3 days; adjustments can be made every 6 hours where more rapid management of hypertension is required if patient is carefully monitored.
-If supine diastolic pressure has been reduced less than 30 mmHg, administer only once a day; if supine diastolic pressure has been reduced more than 30 mmHg, the daily dosage should be given in 2 equally divided doses.

Use: For the treatment of hypertension that is symptomatic or associated with target organ damage not manageable with maximum therapeutic doses of a diuretic plus 2 other antihypertensive drugs; use in milder hypertension not recommended as benefit to risk ration in such patients has not been defined

Vasodilating agent.b

In the U.S.

• Loniten

Available Dosage Forms:

• Tablet

Therapeutic Class: Antihypertensive, Peripheral Vasodilator

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Fast or irregular heartbeat
• weight gain (rapid) of more than 5 pounds (2 pounds in children)

Less common

• Chest pain
• shortness of breath

Check with your doctor as soon as possible if any of the following side effects occur:

More common

• Bloating
• flushing or redness of skin
• swelling of feet or lower legs

Less common

• Numbness or tingling of hands, feet, or face

Rare

• Skin rash and itching

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Increase in hair growth, usually on face, arms, and back

Less common or rare

• Breast tenderness in males and females
• headache

minoxidil causes a temporary increase in hair growth in most people. Hair may grow longer and darker in both men and women. This may first be noticed on the face several weeks after you start taking minoxidil. Later, new hair growth may be noticed on the back, arms, legs, and scalp. Talk to your doctor about shaving or using a hair remover during this time. After treatment with minoxidil has ended, the hair will stop growing, although it may take several months for the new hair growth to go away.

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Minoxidil tablets contain Minoxidil, an antihypertensive peripheral vasodilator. Minoxidil occurs as a white to off-white, odorless, crystalline solid that is soluble in water to the extent of approximately 2 mg/mL, is readily soluble in propylene glycol or ethanol, and is almost insoluble in acetone, chloroform or ethyl acetate. The chemical name for Minoxidil is 2,4-pyrimidinediamine, 6-(1-piperidinyl)-, 3-oxide. The structural formula is represented at right:

  C9H15N50 MW 209.25

Minoxidil tablets for oral administration contain either 2.5 mg or 10 mg of Minoxidil. Inactive ingredients include colloidal silicon dioxide, corn starch, lactose anhydrous, magnesium stearate and microcrystalline cellulose.

1. General Precautions

(a)Monitor fluid and electrolyte balance and body weight(seeWARNINGS: Salt and Water Retention).

(b)Observe patients for signs and symptoms of pericardial effusion(seeWARNINGS: Pericarditis, Pericardial Effusion, and Tamponade).

(c)Use after myocardial infarction -Minoxidil tablets have not been used in patients who have had a myocardial infarction within the preceding month. It is possible that a reduction of arterial pressure with Minoxidil might further limit blood flow to the myocardium, although this might be compensated by decreased oxygen demand because of lower blood pressure.

(d)Hypersensitivity -Possible hypersensitivity to Minoxidil, manifested as a skin rash, has been seen in less than 1% of patients; whether the drug should be discontinued when this occurs depends on treatment alternatives.

(e)Renal failure or dialysis- Patients may require smaller doses of Minoxidil and should have close medical supervision to prevent exacerbation of renal failure or precipitation of cardiac failure.

2. Information for Patient

The patient should be fully aware of the importance of continuing all of his antihypertensive medications and of the nature of symptoms that would suggest fluid overload. A patient brochure has been prepared and is included with each Minoxidil package. The text of this brochure is reprinted at the end of the insert.

3. Laboratory Tests

Those laboratory tests which are abnormal at the time of initiation of Minoxidil therapy, such as urinalysis, renal function tests, EKG, chest x-ray, echocardiogram, etc., should be repeated at intervals to ascertain whether improvement or deterioration is occurring under Minoxidil therapy. Initially, such tests should be performed frequently, e.g., 1 to 3 month intervals; later as stabilization occurs, at intervals of 6 to 12 months.

4. Drug Interactions

See “Interaction with Guanethidine” under WARNINGS.

5. Carcinogenesis and Mutagenesis and Impairment of Fertility

Two-year carcinogenicity studies of Minoxidil have been conducted by the dermal and oral (dietary) routes of administration in mice and rats. There were no positive findings with the oral (dietary) route of administration in rats.

In the two-year dermal study in mice, an increased incidence of mammary adenomas and adenocarcinomas in the females at all dose levels (8, 25 and 80 mg/kg/day) was attributed to increased prolactin activity. Hyperprolactinemia is a well-known mechanism in the enhancement of mouse mammary tumors, but has not been associated with mammary tumorigenesis in women. Additionally, topical Minoxidil has not been shown to cause hyperprolactinemia in women on clinical trials. Absorption of Minoxidil through rodent skin is greater than would be experienced by patients treated topically with Minoxidil for hair loss. Dietary administration of Minoxidil to mice for up to 2 years was associated with an increased incidence of malignant lymphomas in females at all dose levels (10, 25 and 63 mg/kg/day) and an increased incidence of hepatic nodules in males (63 mg/kg/day). There was no effect of dietary Minoxidil on the incidence of malignant liver tumors.

In the two-year dermal study in rats there were significant increases in incidence of pheochromocytomas in males and females and preputial gland adenomas in males. Changes in incidence of neoplasms found to be increased in the dermal or oral carcinogenicity studies were typical of those expected in rodents treated with other hypotensive agents (adrenal pheochromocytomas in rats), treatment-related hormonal alterations (mammary carcinomas in female mice; preputial gland adenomas in male rats) or representative of normal variations within the range of historical incidence for rodent neoplasms (malignant lymphomas, liver nodules/adenomas in mice). Based on differences in absorption of Minoxidil and mechanisms of tumorigenesis in these rodent species, none of these changes were considered to be relevant to the safety of patients treated topically with Minoxidil for hair loss.

There was no evidence of epithelial hyperplasia or tumorigenesis at the sites of topical application of Minoxidil in either species in the 2-year dermal carcinogenesis studies. No evidence of carcinogenicity was detected in rats or rabbits treated topically with Minoxidil for one year. Topical Minoxidil (2% and 5%) did not significantly (p<0.05) reduce the latency period of UV light-initiated skin tumors in hairless mice, as compared to controls, in a 12-month photocarcinogenicity study.

Minoxidil was not mutagenic in the Salmonella (Ames) test, the DNA damage alkaline elution assay, the in vitro rat hepatocyte unscheduled DNA synthesis (UDS) assay, the rat bone marrow micronucleus assay, or the mouse bone marrow micronucleus assay. An equivocal result was recorded in an in vitro cytogenetic assay using Chinese hamster cells at long exposure times, but a similar assay using human lymphocytes was negative.

In a study in which male and female rats received one or five times the maximum recommended human oral antihypertensive dose of Minoxidil (multiples based on a 50 kg patient) there was a dose-dependent reduction in conception rate.

6. Pregnancy

TeratogenicEffects

Pregnancy Category C: Oral administration of Minoxidil has been associated with evidence of increased fetal resorption in rabbits, but not rats, when administered at five times the maximum recommended oral antihypertensive human dose. There was no evidence of teratogenic effects in rats and rabbits. Subcutaneous administration of Minoxidil to pregnant rats at 80 mg/kg/day was maternally toxic but not teratogenic. Higher subcutaneous doses produced evidence of developmental toxicity. There are no adequate and well controlled studies in pregnant women. Minoxidil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Neonatal hypertrichosis has been reported following exposure to Minoxidil during pregnancy.

7. Labor and Delivery

The effects on labor and delivery are unknown.

8. Nursing Mothers

There has been one report of Minoxidil excretion in the breast milk of a woman treated with 5 mg oral Minoxidil twice daily for hypertension. Because of the potential for adverse effects in nursing infants from Minoxidil absorption, Minoxidil should not be administered to a nursing woman.

9. Pediatric Use

Use in pediatric patients has been limited to date, particularly in infants. The recommendations under DOSAGE AND ADMINISTRATION can be considered only a rough guide at present and a careful titration is essential.

10. Geriatric Use

Clinical studies of Minoxidil tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

11. Unapproved Use

Use of Minoxidil tablets, in any formulation, to promote hair growth is not an approved indication. While clinical trials with ROGAINE® Topical Solution 2% demonstrated that formulation and dosage were safe and effective, the effects of extemporaneous formulations and dosages have not been shown to be safe or effective. Because systemic absorption of topically applied drug may occur and is dependent on vehicle and/or method of use, extemporaneous topical formulations made from Minoxidil should be considered to share in the full range of CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS listed in this insert. In addition, skin intolerance to drug and/or vehicle may occur.

Minoxidil TABLETS contain Minoxidil, a medicine for the treatment of high blood pressure in the patient who has not been controlled or is experiencing unacceptable side effects with other medications. It must usually be taken with other medicines.

Be absolutely sure to take all of your medicines for high blood pressure according to your doctor’s instructions. Do not stop taking Minoxidil unless your doctor tells you to. Do not give any of your medicine to other people.

It is important that you look for the warning signals of certain undesired effects of Minoxidil. Call your doctor if they occur. Your doctor will need to see you regularly while you are taking Minoxidil. Be sure to keep all your appointments or to arrange for new ones if you must miss one.

Do not hesitate to call your doctor if any discomforts or problems occur.

The information here is intended to help you take Minoxidil properly. It does not tell you all there is to know about Minoxidil. There is a more technical leaflet that you may request from the pharmacist; you may need your doctor’s help in understanding parts of that leaflet.

What is Minoxidil?

Minoxidil TABLETS contain Minoxidil which is a drug for lowering the blood pressure. It works by relaxing and enlarging certain small blood vessels so that blood flows through them more easily.

Why lower blood pressure?

Your doctor has prescribed Minoxidil to lower your blood pressure and protect vital parts of your body.

Uncontrolled blood pressure can cause stroke, heart failure, blindness, kidney failure, and heart attacks.

Most people with high blood pressure need to take medicines to treat it for their whole lives.

Who should take Minoxidil?

There are many people with high blood pressure, but most of them do not need Minoxidil.

Minoxidil is used ONLY when your doctor decides that:

• your high blood pressure is severe; • your high blood pressure is causing symptoms or damage to vital organs; and • other medicines did not work well enough or had very disturbing side effects.

Minoxidil should be taken only when a doctor prescribes it. Never give any of your Minoxidil TABLETS, or any other high blood pressure medicine, to a friend or relative.

Pregnancy: In some cases doctors may prescribe Minoxidil for women who are pregnant or who are planning to have children. However, its safe use in pregnancy has not been established. Laboratory animals had a reduced ability to become pregnant and a reduced survival of offspring while taking Minoxidil. If you are pregnant or are planning to become pregnant, be sure to tell your doctor.

How to take Minoxidil.

Usually, your doctor will prescribe two other medicines along with Minoxidil. These will help lower blood pressure and will help prevent undesired effect of Minoxidil.

Often, when a medicine like Minoxidil lowers blood pressure, your body tries to return the blood pressure to the original higher level. It does this by holding on to water and salt (so there will be more fluid to pump) and by making your heart beat faster. To prevent this, your doctor will usually prescribe a water tablet to remove the extra salt and water from your body (a diuretic: dye-u-RET-tic) and another medicine to slow your heart beat.

You must follow your doctor’s instructions exactly, taking all the prescribed medicines, in the right amounts, each day. These medicines will help keep your blood pressure down. The water tablet and heart beat medicine will help prevent the undesired effects of Minoxidil.

Minoxidil TABLETS come in two strengths (2½ milligrams and 10 milligrams) that are marked on each tablet. Pay close attention to the tablet markings to be sure you are taking the correct strength. Your doctor may prescribe half a tablet; the tablets are scored (partly cut on one side) so that you can easily break them.

When you first start taking Minoxidil, your doctor may need to see you often in order to adjust your dosage. Take all your medicine according to the schedule prescribed by your doctor. Do not skip any doses. If you should forget a dose of Minoxidil, wait until it is time for your next dose, then continue with your regular schedule. Remember: do not stop taking Minoxidil, or any of your other high blood pressure medicines, without checking with your doctor. Make sure that any doctor treating or examining you know that you are taking high blood pressure medicines, including Minoxidil.

WARNING SIGNALS

Even if you take all your medicines correctly, Minoxidil TABLETS may cause undesired effects. Some of these are serious and you should be on the lookout for them. If any of the following warning signals occur, you must call your doctor immediately:

  1. Increase in heart rate -You should measure your heart rate by counting your pulse rate while you are resting. If you have an increase of 20 beats or more a minute over your normal pulse, contact your doctor immediately. If you do not know how to take your pulse rate, ask your doctor. Also ask your doctor how often to check your pulse.   2. Rapid weight gain of more than 5 pounds -You should weigh yourself daily. If you quickly gain five or more pounds, or if there is any swelling or puffiness in the face, hands, ankles, or stomach area, this could be a sign that you are retaining body fluids. Your doctor may have to change your drugs or change the dose of your drugs. You may also need to reduce the amount of salt you eat. A smaller weight gain (2 to 3 pounds) often occurs when treatment is started. You may lose this extra weight with continued treatment.   3. Increased difficulty in breathing, especially when lying down. This too may be due to an increase of body fluids. It can also happen because your high blood pressure is getting worse. In either case, you might require treatment with other medicines.   4. New or worsening of pain in the chest, arm, or shoulder or signs of severe indigestion -These could be signs of serious heart problems.   5. Dizziness, lightheadedness or fainting -These can be signs of high blood pressure or they may be side effects from one of the medicines. Your doctor may need to change or adjust the dosage of the medicines you are taking.

OTHER UNDESIRED EFFECTS

Minoxidil TABLETS can cause other undesired effects such as nausea and/or vomiting that are annoying but not dangerous. Do not stop taking the drug because of these other undesired effects without talking to your doctor.

Hair growth: About 8 out of every 10 patients who have taken Minoxidil noticed that fine body hair grew darker or longer on certain parts of the body. This happened about 3 to 6 weeks after beginning treatment. The hair may first be noticed on the forehead and temples, between the eyebrows, or on the upper part of the cheeks. Later, hair may grow on the back, arms, legs or scalp. Although hair growth may not be noticeable to some patients, it often is bothersome in women and children. Unwanted hair can be controlled with a hair remover or by shaving. The extra hair is not permanent, it disappears within 1 to 6 months of stopping Minoxidil. Nevertheless, you should not stop taking Minoxidil without first talking to your doctor.

A few patients have developed a rash or breast tenderness while taking Minoxidil tablets, but this is unusual.

Distributed by:

Par Pharmaceutical Companies, Inc.

Chestnut Ridge, NY 10977 U.S.A.

Manufactured by:

Par Formulations Private Limited

1/58, Pudupakkam, Kelambakkam- 603 103.

Made in India

Mfg. Lic. No.: TN00002121

R10/15

Initial dose: 5 mg orally once a day
Maintenance dose: 10 to 40 mg per day
Maximum dose: 100 mg per day

Comments:
-Daily doses can be increased to 10, 20, and then 40 mg in single or divided doses if needed for optimum blood pressure control.
-Doses should be titrated based on individual patient response; intervals between dose adjustments should be at least 3 days; adjustments can be made every 6 hours where more rapid management of hypertension is required if patient is carefully monitored.
-If supine diastolic pressure has been reduced less than 30 mmHg, administer only once a day; if supine diastolic pressure has been reduced more than 30 mmHg, the daily dosage should be given in 2 equally divided doses.

Use: For the treatment of hypertension that is symptomatic or associated with target organ damage not manageable with maximum therapeutic doses of a diuretic plus 2 other antihypertensive drugs; use in milder hypertension not recommended as benefit to risk ratio in such patients has not been defined