(mi nox' i dill)
P : Caution when used during pregnancy
|| See TERMINOLOGY & ABBREVIATIONS ||
Minoxidil tablets contain the powerful antihypertensive agent, minoxidil, which may produce serious adverse effects. It can cause pericardial effusion, occasionally progressing to tamponade, and angina pectoris may be exacerbated. Minoxidil should be reserved for hypertensive patients who do not respond adequately to maximum therapeutic doses of a diuretic and two other antihypertensive agents.
In experimental animals, minoxidil caused several kinds of myocardial lesions as well as other adverse cardiac effects.
Minoxidil must be administered under close supervision, usually concomitantly with therapeutic doses of a beta-adrenergic blocking agent to prevent tachycardia and increased myocardial workload. It must also usually be given with a diuretic, frequently one acting in the ascending limb of the loop of Henle, to prevent serious fluid accumulation. Patients with malignant hypertension and those already receiving guanethidine should be hospitalized when minoxidil is first administered so that they can be monitored to avoid too rapid, or large orthostatic, decreases in blood pressure.
Minoxidil is indicated for the treatment of severe hypertension.
It should not be used as the sole agent to initiate therapy. It is a peripheral vasodilator and should be given in conjunction with a diuretic, to control salt and water retention, and a beta-adrenergic blocking agent, or appropriate substitute, to control reflex tachycardia.
|Dosage & Administration||
Patients over 12 years and adults
The recommended starting dose is 5mg per day. If required, this dosage can later be increased up to 20 mg, and then to 40 mg daily (given as a single dose or in two divided doses). Dose increases should be made at increments of 5 mg to 10 mg minoxidil per day at intervals of three or more days. If a dose of 50 mg of minoxidil has been reached, the dose may be increased by 25 mg minoxidil per day to a maximum dose of 100 mg per day.
If the desired decrease of diastolic blood pressure exceeds 30 mmHg, dosage should be divided to two daily doses to keep daily blood pressure fluctuations as low as possible.
Dosage requirements may be lower in dialysis patients. Minoxidil is removed from the blood by dialysis, but its pharmacological action, once established is not reversed. Therefore haemodialysis patients should take minoxidil either after or at least two hours before dialysis.
Patients younger than 12 years of age
The use of minoxidil in children is restricted to children with severe hypertension associated with target organ damage where other treatment has failed. The data regarding the use of minoxidil in children is very limited, especially in infants. The dosage recommendations can only be considered as a rough guide to treatment at present as this is based on the publication of a few case reports and studies involving a small number of children. The starting dose used basing on these reports is 0.2mg/kg of minoxidil as a single or divided dose. Careful titration increasing in steps of 0.1 to 0.2 mg/kg/day at intervals of at least 3 days is essential. The effective dose range is 0.25 to 1.0 mg/kg/day. The maximum dose is 50mg/day.
Treatment of children with minoxidil should only be initiated under the close supervision of a specialist in hospital.
Rapid reduction of blood pressure: Under hospital monitoring conditions, rapid reduction of blood pressure can be achieved using continuous blood pressure monitoring and incremental doses of 5 mg every six hours.
Concomitant antihypertensive therapy: It is recommended that, where possible, antihypertensive therapy, other than a beta-adrenergic blocking agent and a diuretic be discontinued before minoxidil treatment is started. It is recognised that some antihypertensive agents should not be abruptly discontinued. These drugs should be gradually discontinued during the first week of minoxidil treatment.
Minoxidil causes sodium retention and if used alone can result in several hundred milli-equivalents of salt being retained together with a corresponding volume of water.
Therefore, in all patients who are not on dialysis, minoxidil must be given in conjunction with a diuretic in sufficient dosage to maintain salt and water balance. Examples of the daily dosages of diuretics commonly used when starting therapy with minoxidil include:
1. Hydrochlorothiazide (100 mg) - or other thiazides at equi-effective dosage.
2. Chlortalidone (100 mg).
3. Furosemide (80 mg).
If excessive water retention results in a weight gain of more than 3 pounds when a thiazide or chlortalidone is being used, diuretic therapy should be changed to furosemide, the dose of which may be increased in accordance with the patient's requirements. Diuretic dosage in children should be proportionally less in relation to weight.
Patients will require a sympathetic nervous system suppressant to limit a minoxidil-induced rise in heart rate. The preferred agent is a beta-blocker equivalent to an adult propranolol dosage of 80 - 160 mg/day. Higher doses may be required when pre-treated patients have an increase in heart rate exceeding 20 beats per minute or when simultaneous introduction causes an increase exceeding 10 beats per minute. When beta-blockers are contra-indicated, alternatives such as methyldopa may be used instead and should be started 24 hours prior to minoxidil.
Elderly patients: At present there are no extensive clinical studies with minoxidil in patients over age 65. There is data indicating that elevated systolic and diastolic pressures are important risk factors for cardiovascular disease in individuals over age 65. However, elderly patients may be sensitive to the blood pressure lowering effect of minoxidil and thus caution is urged in initiating therapy as orthostatic hypotension may occur. It is suggested that 2.5 mg per day be used as the initial starting dose in patients over 65 years of age.
May be taken with or without food.
|Overdosage||Symptoms: Hypotension, tachycardia, headache, nausea, dizziness, weakness syncope, warm flushed skin and palpitations; lethargy and ataxia (in children). Management: Trendelenburg positioning, vasoconstrictor or IV fluids may be used for hypotension; treatment is mainly supportive and symptomatic.|
Minoxidil is contra-indicated in patients with a phaeochromocytoma 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.
If used alone, minoxidil can cause a significant retention of salt and water leading to physical signs such as oedema, and to clinical deterioration of some patients with heart failure. Diuretic treatment alone, or in combination with restricted salt intake is, therefore, necessary for all patients taking minoxidil. The patient's bodyweight, fluid and electrolyte balance should be monitored for evidence of fluid retention.
Salt and water retention in excess of 1 to 1.5 kg may diminish the effectiveness of minoxidil. Patients should, therefore, be carefully instructed about compliance with diuretic therapy and a detailed record of body weight should be maintained.
The product should be used with particular attention to maintenance of salt and water balance in patients with renal impairment, but who are not on dialysis.
Renal failure or dialysis patients â€“ Those patients with renal failure or on haemodialysis may require smaller doses of minoxidil.
Patients who have had myocardial infarction should only be treated with minoxidil after a stable post-infarction state has been established.
Because minoxidil is a vasodilator, reflex tachycardia may occur and possibly angina pectoris may occur in patients at risk; it is recommended that minoxidil be used in combination with beta-adrenergic blocking agent or other sympathetic nervous system suppressants to blunt or prevent such a response.
Hypertrichosis occurs in most patients treated with minoxidil and all patients should be warned of this possibility before starting therapy. Most patients will experience an elongation, thickening and enhanced pigmentation of fine body hair. Usually these signs will emerge 3 to 6 weeks after starting treatment. They initially emerge in the face, and they may slightly subside with continued treatment. However, hypertrichosis was hardly or not at all tolerable in less than 10% of patients. Spontaneous reversal to the pre-treatment state can be expected one to six months after cessation of therapy.
Soon after starting minoxidil therapy approximately 60% of patients exhibit ECG alterations in the direction and magnitude of their T waves. Large changes may encroach on the ST segment, unaccompanied by evidence of ischaemia. These asymptomatic changes usually disappear with continuing minoxidil treatment. The ECG reverts to the pre-treatment state when minoxidil is discontinued.
Thrombocytopenia and leukopenia have been rarely reported.
Pericarditis, Pericardial Effusion and Tamponade â€“ Although there is no evidence of a causal relationship, there have been multiple reports of pericarditis occurring in association with minoxidil.
Pericardial effusion and occasionally tamponade, has been observed in about 3% - 5% of treated patients not on dialysis. While in many cases, the pericardial effusion is associated with other potential etiologies, there have been cases in which these potential causes of effusion were not present. Patients should be observed closely for any suggestion of a pericardial effusion and pericardiocentesis, or surgery may be required. If the effusion persists, withdrawal of minoxidil should be considered in light of other means of controlling the hypertension and the patient's clinical status.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
Children strictly require appropriate and individualised dosing of minoxidil, beta-blockers and diuretics. They should be under close specialist supervision in hospital. Caution is required when there is significant renal impairment. The development of peripheral oedema or any signs suggestive of congestive heart failure or of pericardial or pleural effusion should be carefully watched for. Renal function should be monitored. Body weight and urine output should be monitored.
Regular follow up must be ensured during treatment with minoxidil.
Before starting treatment parents and carers should be warned of the likely occurrence of hypertrichosis.
|Adverse Drug Reaction(s)||Reflex tachycardia, fluid retention (accompanied by wt gain, oedema, and sometimes deterioration of existing heart failure and changes in the ECG), hypertrichosis. Headache, nausea, gynaecomastia and breast tenderness, polymenorrhoea, skin rash, thrombocytopenia. Topical: Systemic effects may also occur; contact dermatitis, pruritus, local burning, flushing; changes in hair colour or texture.
Potentially Fatal: Ischaemic heart disease; pericardial effusion progressing to tamponade and death; angina pectoris may be aggravated or uncovered; pulmonary hypertension. Rebound hypertension (in patients with severe hypertension). Stevens-Johnson syndrome.
|Drug Interactions||Antihypertensive effect may be enhanced by other hypotensive drugs. Topical: Absorption may be increased with corticosteroids, retinoids, occlusive ointment bases.
Potentially Fatal: Severe orthostatic hypotension may occur with guanethidine. Please consult detailed drug interactions before prescribing.
|Food Interaction||Avoid natural licorice as it may aggravate fluid retention.|
|Use in Pregnancy
There is limited data from the use of minoxidil in pregnant women. Studies in animals have shown reproductive toxicity.
Minoxidil is not recommended during pregnancy and in women of childbearing potential not using contraception. Neonatal hirsutism has been reported following exposure of minoxidil during pregnancy.
Minoxidil has been reported to be excreted in human milk. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from minoxidil therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
There are no fertility data from the use of minoxidil in humans. In a fertility study with male and female rats, a dose-dependent reduction of the conception rate was found. The dose corresponded to one to five times the maximum dose used in humans to treat hypertension.
|Storage||Oral: Store at 20-25Â°C (68-77Â°F). Topical/Cutaneous: Store at 20-25Â°C (68-77Â°F).|
Mechanism of action
Minoxidil lowers the elevated systolic and diastolic blood pressure by decreasing peripheral vascular resistance via vasodilation. The smooth musculature of the resistance vessels must be regarded as the site of action for the relaxant effect of minoxidil. The active metabolite of minoxidil activates the ATP-modulated potassium (K+ATP) channel causing K+ efflux, hyperpolarization, and smooth muscle relaxation.
Sympathetic reflexes mediated by baroreceptors secondarily increase heart rate and myocardial contractility, thereby increasing cardiac output. In addition, the plasma renin activity is increased via sympathetic nervous system stimulation, which results in an increased angiotensin II concentration with subsequent increased aldosterone secretion. In this way, the renal sodium excretion is reduced and extracellular volume increased. The pulmonary artery pressure may occasionally increase after the administration of minoxidil alone, but it decreases with the recommended concomitant therapy (beta-blocker plus diuretic).
As severe hypertension requiring multi-drug therapy is uncommon in children, paediatric use of minoxidil was limited in the development programme and has remained so in published literature. Data available in children younger than 10 years of age is very limited; it involves approximately 40 patients, eight of whom were under one year of age.
Absorption and distribution
After oral administration in humans, at least 90% of minoxidil is absorbed in the gastrointestinal tract. Minoxidil is detected within 30 minutes in the plasma. Maximum plasma levels are reached 60 minutes after administration.
Based on results from a relative bioavailability study, tablet and oral solution formulations have similar values in area under the serum concentration-time curve (AUC), maximum serum concentration, time to reach maximum serum concentration (approximately 40 minutes), and the type of effect (antihypertensive). There is no accumulation following chronic administration of oral tablets compared with single dose.
Minoxidil is not bound to plasma proteins.
Minoxidil does not cross the blood-brain barrier.
At least 90% of the administered minoxidil is metabolized in the liver. The primary metabolite in humans is the minoxidil O-glucuronide. Some polar metabolites are also produced. The known metabolites have a weaker antihypertensive effect than the active ingredient itself.
In humans, minoxidil plasma concentrations decrease with an average half-life of approximately 4 hours. However, the duration of action is over several days.
Minoxidil and its metabolites are dialyzable.
The renal clearance of minoxidil corresponds to the glomerular filtration rate. No substantial changes in the glomerular filtration rate and the renal plasma flow could be detected under minoxidil.
No pharmacokinetic data regarding minoxidil in the paediatric population is currently available.
|ATC Classification||C02DC01 - minoxidil; Belongs to the class of pyrimidine derivative agents acting on arteriolar smooth muscle. Used in the treatment of hypertension.
D11AX01 - minoxidil; Belongs to the class of other dermatologicals. Used in the treatment of dermatological diseases.
|Brand Name||Manufacturer/Marketer||Composition||Dosage Form||Pack Size & Price|
|REGAIN 2%||Renata Limited||Minoxidil hydrochloride USP 20mg/ml||Topical Solution||60ml: 348.00 MRP|
|REGAIN 5%||Renata Limited||Minoxidil hydrochloride USP 50mg/ml||Topical Solution||60ml: 398.00 MRP|
|REGROW 2%||Techno Drugs||Minoxidil hydrochloride USP 20mg/ml||Topical Solution||60ml: 175.00 MRP|
|SPLENDORA 2%||Square Pharmaceuticals Ltd.||Minoxidil 2%||Topical Solution||60 ml : 501.50 MRP|
|SPLENDORA 5%||Square Pharmaceuticals Ltd.||Minoxidil 5%||Topical Solution||60 ml : 601.81 MRP|
|TRUGAIN 2%||Ziska Pharmaceuticals Ltd.||Minoxidil hydrochloride USP 20mg/ml||Topical Solution||60ml: 298.00 MRP|
|TRUGAIN 2% Spray||Ziska Pharmaceuticals Ltd.||Minoxidil hydrochloride USP 20mg/ml spray||Spray||60ml: 298.00 MRP|
|TRUGAIN 5%||Ziska Pharmaceuticals Ltd.||Minoxidil hydrochloride USP 50mg/ml||Topical Solution||60ml: 348.00 MRP|
|TRUGAIN 5% Spray||Ziska Pharmaceuticals Ltd.||Minoxidil hydrochloride USP 20mg/ml spray||Spray||60ml: 348.00 MRP|
|Xenogrow 2%||Incepta Pharmaceuticals Limited||Minoxidil 2%||Topical solution||1x1's:MRP 500 Tk|
|Xenogrow 5%||Incepta Pharmaceuticals Limited||Minoxidil 5%||Topical solution||1x1's:MRP 600 Tk|
Minoxidil may increase chest pain (angina) or cause other heart problems. It is important that you keep all appointments with your doctor so that you can be monitored for any symptoms or changes. If chest pain occurs or worsens while you are taking this medication, call your doctor immediately. Your doctor may prescribe other medicines as part of your minoxidil therapy. Do not stop taking these medications unless your doctor tells you to do so.
Why is this medication prescribed?
Minoxidil is used with other drugs to treat high blood pressure. It works by relaxing the blood vessels so that blood can flow more easily through the body.
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
How should this medicine be used?
Minoxidil comes as a tablet to take by mouth. It usually is taken once or twice a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take minoxidil exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Minoxidil controls high blood pressure but does not cure it. Continue to take minoxidil even if you feel well. Do not stop taking minoxidil without talking to your doctor.
What special precautions should I follow?
Before taking minoxidil,
- tell your doctor if you are allergic to minoxidil or any other drugs.
- tell your doctor what prescription and nonprescription medications you are taking, especially other medications for high blood pressure, diuretics ('water pills'), guanethidine, and vitamins.
- tell your doctor if you have or have ever had heart disease, a heart attack, pheochromocytoma, or kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking minoxidil, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking minoxidil.
- you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how it affects you.
- ask your doctor about the safe use of alcohol while you are taking minoxidil. Alcohol can make the side effects from minoxidil worse.
What special dietary instructions should I follow?
Your doctor may prescribe a low-salt or low-sodium diet. Follow these directions carefully.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Minoxidil may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
increase in size or darkness of fine body hair
If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING section, call your doctor immediately:
swollen ankles or feet
unexplained weight gain
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to this medicine.
Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Ref: U.S. National Library of Medicine.
This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.
|| See Brand Manufacturer's Prescribing Information |||| MINOXIDIL ||