Minoxidil 10mg Information
Minoxidil 10mg (Minoxidil)
Minoxidil 10mg (Minoxidil) Description
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.
CHN0 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.
Minoxidil 10mg (Minoxidil) Clinical Pharmacology
Minoxidil is an orally effective direct acting peripheral vasodilator that reduces elevated systolic and diastolic blood pressure by decreasing peripheral vascular resistance. Microcirculatory blood flow in animals is enhanced or maintained in all systemic vascular beds. In man, forearm and renal vascular resistance decline; forearm blood flow increases while renal blood flow and glomerular filtration rate are preserved.
Because it causes peripheral vasodilation, minoxidil elicits a number of predictable reactions. Reduction of peripheral arteriolar resistance and the associated fall in blood pressure trigger sympathetic, vagal inhibitory, and renal homeostatic mechanisms, including an increase in renin secretion, that lead to increased cardiac rate and output and salt and water retention. These adverse effects can usually be minimized by concomitant administration of a diuretic and a beta-adrenergic blocking agent or other sympathetic nervous system suppressant.
Minoxidil does not interfere with vasomotor reflexes and therefore does not produce orthostatic hypotension. The drug does not enter the central nervous system in experimental animals in significant amounts, and it does not affect CNS function in man.
The extent and time-course of blood pressure reduction by minoxidil do not correspond closely to its concentration in plasma. After an effective single oral dose, blood pressure usually starts to decline within one-half hour, reaches a minimum between 2 and 3 hours and recovers at an arithmetically linear rate of about 30%/day. The total duration of effect is approximately 75 hours. When minoxidil is administered chronically, once or twice a day, the time required to achieve maximum effect on blood pressure with a given daily dose is inversely related to the size of the dose. Thus, maximum effect is achieved on 10 mg/day within 7 days, on 20 mg/day within 5 days, and on 40 mg/day within 3 days.
The blood pressure response to minoxidil is linearly related to the logarithm of the dose administered. The slope of this log-linear dose-response relationship is proportional to the extent of hypertension and approaches zero at a supine diastolic blood pressure of approximately 85 mmHg.
When used in severely hypertensive patients resistant to other therapy, frequently with an accompanying diuretic and beta-blocker, minoxidil tablets usually decreased the blood pressure and reversed encephalopathy and retinopathy.
Minoxidil produces several cardiac lesions in animals. Some are characteristic of agents that cause tachycardia and diastolic hypotension (beta-agonists like isoproterenol, arterial dilators like hydralazine) while others are produced by a narrower range of agents with arterial dilating properties. The significance of these lesions for humans is not clear, as they have not been recognized in patients treated with oral minoxidil at systemically active doses, despite formal review of over 150 autopsies of treated patients.
a. Papillary muscle/subendocardial necrosis
The most characteristic lesion of minoxidil, seen in rat, dog, and minipig (but not monkeys) is focal necrosis of the papillary muscle and subendocardial areas of the left ventricle. These lesions appear rapidly, within a few days of treatment with doses of 0.5 mg to 10 mg/kg/day in the dog and minipig, and are not progressive, although they leave residual scars. They are similar to lesions produced by other peripheral arterial dilators, by theobromine, and by beta-adrenergic receptor agonists such as isoproterenol, epinephrine, and albuterol. The lesions are thought to reflect ischemia provoked by increased oxygen demand (tachycardia, increased cardiac output) and relative decrease in coronary flow (decreased diastolic pressure and decreased time in diastole) caused by the vasodilatory effects of these agents coupled with reflex or directly induced tachycardia.
b. Hemorrhagic lesions
After acute oral minoxidil treatment (0.5 mg to 10 mg/kg/day) in dogs and mini-pigs, hemorrhagic lesions are seen in many parts of the heart, mainly in the epicardium, endocardium, and walls of small coronary arteries and arterioles. In minipigs the lesions occur primarily in the left atrium while in dogs they are most prominent in the right atrium, frequently appearing as grossly visible hemorrhagic lesions. With exposure of 1 to 20 mg/kg/day in the dog for 30 days or longer, there is replacement of myocardial cells by proliferating fibroblasts and angioblasts, hemorrhage and hemosiderin accumulation. These lesions can be produced by topical minoxidil administration that gives systemic absorption of 0.5 to 1 mg/kg/day. Other peripheral dilators, including an experimental agent, nicorandil and theobromine have produced similar lesions.
c. Epicarditis
A less fully studied lesion is local epicarditis, seen in dogs after 2 days of oral minoxidil. More recently, chronic proliferative epicarditis was observed in dogs treated topically twice a day for 90 days. In a one year oral dog study, serosanguineous pericardial fluid was seen.
d. Hypertrophy and Dilation
Oral and topical studies in rats, dogs, monkeys (oral only), and rabbits (dermal only) show cardiac hypertrophy and dilation. This is presumed to represent the consequences of prolonged fluid overload; there is preliminary evidence in monkeys that diuretics partly reverse these effects.
Autopsies of over 150 patients who died of various causes after receiving minoxidil for hypertension have not revealed the characteristic hemorrhagic (especially atrial) lesions seen in dogs and minipigs. While areas of papillary muscle and subendocardial necrosis were occasionally seen, they occurred in the presence of known pre-existing coronary artery disease and were also seen in patients never exposed to minoxidil in another series using similar, but not identical autopsy methods.
Minoxidil 10mg (Minoxidil) Indications And Usage
Because of the potential for serious adverse effects, minoxidil tablets are indicated only in the treatment of hypertension that is symptomatic or associated with target organ damage and is not manageable with maximum therapeutic doses of diuretic plus two other antihypertensive drugs. At the present time use in milder degrees of hypertension is not recommended because the benefit-risk relationship in such patients has not been defined.
Minoxidil reduced supine diastolic blood pressure by 20 mmHg or to 90 mmHg or less in approximately 75% of patients, most of whom had hypertension that could not be controlled by other drugs.
Minoxidil 10mg (Minoxidil) Contraindications
Minoxidil tablets are contraindicated in pheochromocytoma, because it may stimulate secretion of catecholamines from the tumor through its antihypertensive action. Minoxidil is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.
Minoxidil 10mg (Minoxidil) Warnings
In patients with very severe blood pressure elevation, too rapid control of blood pressure, especially with intravenous agents, can precipitate syncope, cerebrovascular accidents, myocardial infarction and ischemia of special sense organs with resulting decrease or loss of vision or hearing. Patients with compromised circulation or cryoglobulinemia may also suffer ischemic episodes of the affected organs. Although such events have not been unequivocally associated with minoxidil use, total experience is limited at present.
Any patient with malignant hypertension should have initial treatment with minoxidil carried out in a hospital setting, both to assure that blood pressure is falling and to assure that it is not falling more rapidly than intended.
Minoxidil 10mg (Minoxidil) Precautions
(a)(see ).
(b)(see ).
(c)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)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)patients may require smaller doses of minoxidil and should have close medical supervision to prevent exacerbation of renal failure or precipitation of cardiac failure.
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
Minoxidil was not mutagenic in the (Ames) test, the DNA damage alkaline elution assay, the 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 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 to 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.
Teratogenic Effects
Minoxidil 10mg (Minoxidil) Adverse Reactions
Allergic - Rashes have been reported, including rare reports of bullous eruptions, and Stevens-Johnson Syndrome.
Minoxidil 10mg (Minoxidil) Overdosage
There have been only a few instances of deliberate or accidental overdosage with minoxidil tablets. One patient recovered after taking 50 mg of minoxidil together with 500 mg of a barbiturate. When exaggerated hypotension is encountered, it is most likely to occur in association with residual sympathetic nervous system blockade from previous therapy (guanethidine-like effects or alpha-adrenergic blockage), which prevents the usual compensatory maintenance of blood pressure. Intravenous administration of normal saline will help to maintain blood pressure and facilitate urine formation in these patients. Sympathomimetic drugs such as norepinephrine or epinephrine should be avoided because of their excessive cardiac stimulating action. Phenylephrine, angiotensin II, vasopressin, and dopamine all reverse hypotension due to minoxidil, but should only be used if underperfusion of a vital organ is evident.
Radioimmunoassay can be performed to determine the concentration of minoxidil in the blood. At the maximum adult dose of 100 mg/day, peak blood levels of 1641 ng/mL and 2441 ng/mL were observed in two patients, respectively. Due to patient-to-patient variation in blood levels, it is difficult to establish an overdosage warning level. In general, a substantial increase above 2000 ng/mL should be regarded as overdosage, unless the physician is aware that the patient has taken no more than the maximum dose.
Oral LDin rats has ranged from 1321 to 3492 mg/kg; in mice, 2456 to 2648 mg/kg.
Minoxidil 10mg (Minoxidil) Dosage And Administration
If beta-blockers are contraindicated, methyldopa (250 mg to 750 mg, b.i.d.) may be used instead. Methyldopa must be given for at least 24 hours before starting therapy with minoxidil because of the delay in the onset of methyldopa’s action. Limited clinical experience indicates that clonidine may also be used to prevent tachycardia induced by minoxidil; the usual dosage is 0.1 mg to 0.2 mg twice daily.
Sympathetic nervous system suppressants may not completely prevent an increase in heart rate due to minoxidil but usually do prevent tachycardia. Typically, patients receiving a beta-blocker prior to initiation of therapy with minoxidil have a bradycardia and can be expected to have an increase in heart rate toward normal when minoxidil is added. When treatment with minoxidil and beta-blocker or other sympathetic nervous system suppressant are begun simultaneously, their opposing cardiac effects usually nullify each other, leading to little change in heart rate.
Minoxidil 10mg (Minoxidil) How Supplied
2.5 mg: white, round, bisected tablets, debossed “Par 256” on one side and “Minoxidil 2 1/2” on the other side, supplied in unit dose package of 100 (10x10) NDC NDC 68084-204-01.
10 mg: white, round, bisected tablets, debossed “Par 257” on one side and “Minoxidil 10” on the other side, supplied in unit dose package of 100 (10x10) NDC NDC 68084-205-01
Store at controlled room temperature 20°-25°C (68°-77°F) [See USP].
Minoxidil 10mg (Minoxidil) Patient Information
MINOXIDIL TABLETS 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.
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.
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.
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.
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:
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.
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.
MINOXIDIL TABLETS come in two strengths (2 1/2 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. Make sure that any doctor treating or examining you know that you are taking high blood pressure medicines, including MINOXIDIL.
Minoxidil 10mg (Minoxidil) Principal Display Panel .mg Tablets
Minoxidil 10mg (Minoxidil) Principal Display Panel Mg Tablets
