To be sold by retail on the prescription of Cardiologist only
Midodrine Hydrochloride Tablets 5 mg /10 mg
WARNING: BECAUSE MIDODRINE CAN CAUSE MARKED ELEVATION OF SUPINE BLOOD PRESSURE, IT SHOULD BE USED IN PATIENTS WHOSE LIVES ARE CONSIDERABLY IMPAIRED DESPITE STANDARD CLINICAL CARE. THE INDICATION FOR USE OF MIDODRINE IN THE TREATMENT OF SYMPTOMATIC ORTHOSTATIC HYPOTENSION IS BASED PRIMARILY ON A CHANGE IN A SURROGATE MARKER OF EFFECTIVENESS, AN INCREASE IN SYSTOLIC BLOOD PRESSURE MEASURED ONE MINUTE AFTER STANDING, A SURROGATE MARKER CONSIDERED LIKELY TO CORRESPOND TO A CLINICAL BENEFIT. AT PRESENT, HOWEVER, CLINICAL BENEFITS OF MIDODRINE, PRINCIPALLY IMPROVED ABILITY TO CARRY OUT ACTIVITIES OF DAILY LIVING, HAVE NOT BEEN VERIFIED.
CIPMIDO Tablets 5 mg
Each uncoated tablet contains:
Midodrine Hydrochloride ……..5 mg
CIPMIDO Tablets 10 mg
Each Uncoated tablet contains:
Midodrine Hydrochloride…….10 mg
Dosage form: Solid dosage form; oral, uncoated tablets.
Strengths: 5 mg and 10 mg
Midodrine Hydrochloride Tablet is indicated in the treatment of symptomatic orthostatic hypotension.
5.2Posology and Method of Administration
Initial dose: 2.5 mg three times a day. Depending on results of supine and standing blood pressure recordings, this dose can be increased weekly up to a dose of 10 mg three times a day. This is the normal maintenance dosage. A careful evaluation of the response to treatment and of the overall balance of the expected benefits and risks needs to be undertaken before any dose increase and advice to continue therapy for long periods. The last daily dose should be taken at least 4 hours before bedtime in order to prevent supine hypertension (see also section 5.4)
Midodrine Hydrochloride tablets may be taken with food. (see section 6.3).
Midodrine Hydrochloride is contraindicated in patients with the following conditions/diseases:
- Severe organic heart disease (e.g. bradycardia, ischaemic heart disease, heart attack, congestive heart failure, cardiac conduction disturbances or aortic aneurysm).
- Serious obliterative blood vessel disease, cerebro-vascular occlusions and vessel spasms
- Acute kidney disease
- Severe renal impairment (creatinine clearance of less than 30 ml/min.)
- Serious prostate disorder (e.g. Hypertrophy of the prostate gland)
- Urinary retention
- Proliferative diabetic retinopathy
- Narrow angle glaucoma
- Hypersensitivity to the active substance or to any of the excipients listed in (see section 9.1).
5.4Special Warnings and Precautions for Use
Severe orthostatic hypotension with supine hypertension
Regular monitoring of supine and standing blood pressure is necessary due to the risk of hypertension in the supine position, e.g. at night. Patients should be told to report symptoms of supine hypertension immediately such as chest pain, palpitations, shortness of breath, headache and blurred vision, and should be monitored closely for these side effects by the treating doctor. Supine hypertension may often be controlled by an adjustment to the dose. If hypertension occurs in the supine position and does not respond to a reduction of the dosage, treatment with midodrine hydrochloride must be stopped.
The time of administration of the drug is important in this context: Avoid administration in the evenings. The last daily dose should be taken at least 4 hours before bedtime in order to prevent supine hypertension. The risk of supine hypertension occurring during the night can be reduced by elevating the head. Patients should be monitored for possible secondary events on hypertension.
Severe disturbances of the autonomic nervous system
In patients suffering from a severe disturbance of the autonomic nervous system, administration of midodrine hydrochloride may lead to a further reduction of blood pressure in the standing position. If this is the case, further treatment with midodrine hydrochloride should be stopped.
Caution must be observed in patients with atherosclerotic disease especially with symptoms of intestinal angina or claudication of the legs.
Caution is advised in patients with prostate disorders. Use of the drug may cause urinary retention.
Renal and Hepatic function
Midodrine hydrochloride is contraindicated in patients with acute renal impairment or severe renal impairment. It is advised always to monitor the blood pressure and renal function in patients before start of long-term treatment with midodrine hydrochloride. Treatment with midodrine hydrochloride has not been studied in patients with liver impairment. It is therefore recommended to evaluate the renal and hepatic parameters before starting treatment with midodrine hydrochloride and on continuous basis.
Slowing of the heart rate may occur after midodrine administration, due to vagal reflex. Caution is advised when midodrine is used concomitantly with cardiac glycosides (such as digitalis preparations) and other agents that directly or indirectly reduce heart rate. Patients should be monitored for signs or symptoms suggesting bradycardia.
Potential effect of midodrine hydrochloride on other drugs
Midodrine hydrochloride is an inhibitor of CYP2D6 and may affect the metabolism of other drugs. This may be of clinical relevance for active substances that are mainly metabolized by CYP2D6, e.g. tricyclic antidepressants, beta blockers, selective serotonin reuptake inhibitors (SSRI), antiarrhythmics (including class 1A, 1B and 1C) and monoamine oxidase inhibitors (MAO-inhibitors) type B, especially if the active substance also has a narrow therapeutic index.
Potential pharmacokinetic interactions
The potential for pharmacokinetic interaction is limited as the metabolic pathways do not involve cytochrome P450 enzymes. However, decreased clearance of medicinal products metabolised by CYP2D6 (e.g. promethazine) has been reported. (see also section 6.3).
Potential effect of other drugs on midodrine hydrochloride
No studies to evaluate the effect of other drugs on the pharmacokinetics of midodrine hydrochloride or the active metabolite desglymidodrine have been conducted. In vitro data indicate that desglymidodrine is a substrate of CYP2D6.Concomitant administration of drugs that inhibit this enzyme (e.g. quinidine, paroxetine, fluoxetine and bupropion) may cause increased plasma levels of desglymidodrine with a potential risk of increased adverse events.
Sympathomimetics and other vasopressor agents
Concomitant treatment with sympathomimetics and other vasoconstrictive substances such as reserpine, guanethidine, tricyclic antidepressants, antihistamines, thyroid hormones and MAO-inhibitors, including over-the-counter remedies should be avoided as a pronounced increase in blood pressure may occur.
As with other specific α-adrenergic agonists, the effect of midodrine hydrochloride is blocked by a-adrenergic antagonists such as prazosin and phentolamine. Monitoring is recommended if midodrine hydrochloride is combined with other drugs that directly or indirectly reduce the heart rate.
Simultaneous use of digitalis preparations is not recommended, since the bradycardia which occurs as a result of the use of midodrine hydrochloride is then potentiated and heart block may occur.
Patients being treated with midodrine hydrochloride in combination with mineralocorticoids or glucocorticoids (e.g. fludrocortisone) may be at increased risk of glaucoma/increased intraocular pressure, and should be carefully monitored. Midodrine hydrochloride may enhance or potentiate the hypertensive effects of possible blood pressure raising effect of corticosteroid preparations.
Heart rate reducing drugs
Monitoring is recommended if midodrine hydrochloride is combined with other drugs that directly or indirectly reduce the heart rate.
Falsely elevated plasma metanephrine
Patients taking midodrine hydrochloride may have falsely elevated plasma metanephrine as a result of analytical interference when measured by HILIC-based HPLC-MS/MS. This potential for interference should be considered in cases where patients taking midodrine hydrochloride require biochemical investigation for potential phaeochromocytomas and paragangliomas.
5.6Use in Special Populations
There is limited data on dosing in the elderly and no specific studies have been performed addressing a possible dose-reduction in the elderly population. Cautious dose titration is recommended.
Patients with Renal impairment
No specific studies have been performed addressing a possible dose-reduction in patients with renal insufficiency. Generally, midodrine is contraindicated in patients with acute renal impairment and severe renal impairment. (see also section 5.3).
Patients with Hepatic impairment
No specific studies have been performed in this patient population. (see also section 5.4).
The safety and efficacy of midodrine hydrochloride in children has not been established. No data are available.
There are no data on the use of midodrine hydrochloride in pregnant women. Studies in animals have shown reproductive toxicity at maternally toxic doses. Midodrine hydrochloride tablets are not recommended during pregnancy and in woman of childbearing potential not using contraception.
It is unknown whether midodrine hydrochloride and its metabolites are excreted in the breast milk. A risk to newborns/infants cannot be excluded. Midodrine hydrochloride tablets should not be used during breast-feeding.
Animal studies are insufficient with respect to the assessment of fertility.
5.7Effects on Ability to Drive and Use Machines
Midodrine hydrochloride tablets have negligible influence on the ability to drive or use machines. However, patients who experience dizziness or light-headedness while receiving midodrine hydrochloride tablets should refrain from driving or operating machinery.
Summary of safety profile
The most frequent and very common adverse reactions related to Midodrine hydrochloride therapy are piloerection, dysuria and pruritus of the scalp. Events of supine hypertension have been reported during midodrine hydrochloride treatment, the degree of which is dose dependent.
Tabulated list of adverse reactions
The frequency groupings follow this convention: Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).
(>1/100, < 1/10)
(> 1/1000, < 1/100)
Frequency not known (cannot be estimated from available data)
Sleep disorders Insomnia
Nervous system disorders
Paraesthesia Paraesthesia of the scalp
Supine hypertension (dose dependent effect)
Abdominal pain Vomiting
Abnormal hepatic function
Raised liver enzymes
Skin and subcutaneous tissue disorders
(goosebumps) Pruritus of the scalp
Pruritus Chills, flushing, skin rash
Renal and urinary disorders
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. If your patient experiences any side-effects, write to firstname.lastname@example.org. You can also report side effects directly via the National Pharmacovigilance Program of India by calling on 1800 180 3024 or you can report to Cipla Ltd. on 1800 267 7779.
By reporting side effects, you can help provide more information on the safety of this product.
Overdose symptoms are those seen as undesirable effects, in particular hypertension, piloerection (goosebumps), and sensation of coldness, bradycardia (reflex-bradycardia) and urinary retention.
Besides basic life-support measures recommended general treatment based on the pharmacology of the drug includes induced emesis and administration of alpha-sympatholytic agent (e.g., nitroprusside, phentolamine, nitroglycerin). Bradycardia and bradycardic conduction defects can be counteracted by atropine. The active metabolite desglymidodrine is dialyzable.
Pharmacotherapeutic group: Cardiac Therapy, Adrenergic and dopaminergic agents
ATC-code: C01C A17.
6.1Mechanism of Action
Midodrine hydrochloride is the rapidly absorbed pro-drug of the pharmacologically active constituent desglymidodrine. Desglymidodrine is a sympathomimetic agent with a direct and selective effect on the peripheral α1-adrenergic receptors. This α1-stimulative effect induces vasoconstriction of the venous system (causing a reduction in venous pooling). The α1-adrenergic effects of desglymidodrine are almost wholly attributable to the (-) enantiomer of desglymidodrine. After taking midodrine hydrochloride, which is a racemic mixture ,(+) desglymidodrine is also present, though this contributes almost nothing to the desired effect.
Desglymidodrine increases the peripheral arterial resistance, resulting in an increase of the arterial blood pressure.
Only limited data is available on the long-term effects of administering midodrine hydrochloride.
Stimulation of the α-adrenergic receptors of the bladder and the ureter increases the sphincter muscle tone. Desglymidodrine has no β-adrenergic effects.
6.2 Pharmacodynamic Properties
Administration of midodrine hydrochloride results in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension of various etiologies. Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10 mg dose of midodrine hydrochloride, with some effect persisting for 2 to 3 hours. Midodrine hydrochloride has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure.
6.3 Pharmacokinetic Properties
After oral administration, midodrine hydrochloride is rapidly absorbed. The peak plasma concentrations are reached after approximately 30 minutes, and the plasma concentration of the active metabolite, desglymidodrine, peaks after approximately 1 hour.
AUC and Cmax increase proportionally to the doses in a dosage range of 2.5 – 22.5 mg. Administration with food increases the AUC by approximately 25%, and the Cmax decreases by approximately 30%. The pharmacokinetics of desglymidodrine is not affected.
Neither midodrine nor desgylmidodrine are bound to plasma proteins to any significant extent (less than 30%).
Desglymidodrine diffuses poorly across the blood-brain barrier. Diffusion across the placenta has been reported. It is not known whether this drug is excreted in human milk.
Midodrine hydrochloride is partially hydrolysed before absorption (in the intestines), and partially after absorption (in plasma) by the separation of glycine, herewith generating the active metabolite, desglymidodrine. The elimination of desglymidodrine is primarily caused by an oxidative metabolism, followed by (partial) conjugation.
Midodrine (8%), desglymidodrine (40%), and their degradation products (55%) are excreted in the urine by more than 90% within 24 hours in conjugated or non-conjugated forms. The plasma elimination half-life for midodrine hydrochloride is approximately 30 minutes and is approximately 3 hours for desglymidodrine. Elimination of the active (-) enantiomer of desglymidodrine is slower than the elimination of the inactive (+) enantiomer.
7.1 Animal Toxicology or Pharmacology
Pharmacology safety studies and repeat-dose toxicity studies with animals did not show any indications of a safety risk for humans at therapeutic doses. Studies in the rat and rabbit show that at maternally toxic doses, midodrine is embryotoxic. There is no evidence of teratogenicity.
Midodrine is not genotoxic and after long term studies in rats (104 weeks) and mice (78 weeks), there was no evidence that midodrine was carcinogenic at dose of up to 10 mg/kg/day and up to 15 mg/kg/day, respectively, compared to a maximum patient daily dose of 30 mg (~0.5 mg/kg/day).
Midodrine hydrochloride is a vasopressor/antihypotensive. The chemical name for midodrine hydrochloride is Acetamide,2-amino-N--, monohydrochloride, (±)-. The molecular weight of midodrine hydrochloride is 290.7. Its structural formula and molecular formula are:
9.1 List of Excipients
Microcrystalline cellulose, pregelatinised starch, colloidal silicon dioxide, talc & magnesium stearate.
As on the pack
9.4 Packaging Information
For 5 mg: Bottle pack of 30 Tablets
For 10mg: Bottle pack of 30 Tablets
9.5 Storage and Handling Instructions
Store below 30°C.
Keep out of reach of children.
10.1 What CIPMIDO Tablets are and What they are used for?
CIPMIDO Tablet is a prescription medicine used in treatment of symptomatic orthostatic hypotension.
CIPMIDO Tablets contain midodrine hydrochloride. This belongs to a group of medicines called adrenergic and dopaminergic agents. Midodrine hydrochloride raises your blood pressure and is used to treat certain forms of low blood pressure in adults when other treatments have not worked.
10.2 What You Need to Know Before You Take CIPMIDO Tablets?
Before taking this medicine
You should not use CIPMIDO Tablets if
- you are allergic to midodrine hydrochloride or any of the other ingredients of CIPMIDO Tablets
- you have high blood pressure
- you have certain forms of cardiovascular disease (such as angina) or have suffered a heart attack
- you have a slow pulse
- you have difficulty urinating
- you have increased pressure in the eye (glaucoma)
- you have poor vision as a result of diabetes
- you have an over-active thyroid gland
- you have tumour near the kidney causing hormonal disorders (also known as pheochromocytoma)
- you have severe or acute kidney disease or problems
- you have an enlarged prostate.
Warnings and precautions
Talk to your doctor or pharmacist before taking this medicine if you have the condition of high blood pressure when you lie down. If you suffer from high blood pressure when you lie down, then:
Regular monitoring of your blood pressure when you are lying down and when you are standing up will be required. This is required to see if you are at risk of your blood pressure rising when you lie down, for example, at night. If your blood pressure does go up when you lie down and reducing the dose of midodrine hydrochloride does not correct this problem, then treatment with this medicine must be stopped.
It is important that you do not take this medicine late in the evening. You should take your last daily dose at least 4 hours before bedtime. This is because midodrine hydrochloride can cause high blood pressure if you are lying down for any period of time. By keeping your head elevated at night, the potential risk of your blood pressure rising when you lie down is reduced.
You should be monitored by your doctor for possible secondary effects of high blood pressure.
Also talk to your doctor if you:
• have a serious disorder of the nervous system (autonomic nervous system disorders), since taking this medicine may lead to a further drop in blood pressure when you stand up. If this occurs, further treatment with this medicine should be stopped.
• have or had heart disease, either where your heart cannot pump the blood around your body as well as it should (a condition called heart failure) or irregular heart rate, or if you had any blocked or leaking blood vessels including those of heart or brain.
• suffer from problems with your circulation, especially if you have symptoms such as pain or cramps in the stomach after eating, or pain or cramps in the legs after walking.
• are taking medication which reduces heart rate, such as digitalis preparations. Taking midodrine hydrochloride may further reduce your heart rate and your doctor may want to monitor your heart rate more closely if you take these medications together.
• suffer from a disease of the prostate, as you may find passing urine is difficult when taking this medicine.
You should have your kidney function and blood pressure checked by your doctor before you start using this medicine. During treatment with this medicine, your blood pressure will be checked regularly, and if necessary, your dose adjusted.
It is important that you immediately report symptoms related to high blood pressure, such as chest pain, palpitations, shortness of breath, headache and blurred vision. Your doctor will then decide whether to adjust dosage or stop your treatment with Midodrine hydrochloride.
If any of the warnings apply to you, or have had them in the past, talk to your doctor.
Other medicines and Midodrine hydrochloride Tablets
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. In particular, tell your doctor or pharmacist if you are taking any of the following:
• Reserpine and guanethidine (medicines used to reduce high blood pressure, antihistamines (used to treat allergies), hormones for the thyroid (used when the thyroid is not working properly), tricyclic antidepressants and MAO-inhibitors (both used to treat depression), nasal/sinus congestion relievers (vasoconstriction medicines that narrow blood vessels), or sympathomimetic agents (medicines that have a stimulating effect on certain parts of the nervous system) because concomitant use with this medicine may cause a large increase in blood pressure.
• Prazosin and phentolamine (medicines used to treat heart disease) because the effect of this medicine is blocked by these drugs.
• Digitalis preparations (medicines used to treat heart disease) because concomitant use with this medicine may lead to reduced heart rate.
• Steroids (for example, fludrocortisone acetate, an anti-inflammatory medicine) because this medicine may increase its effect.
• Medicine(s) which directly or indirectly reduce your heart rate because if this medicine is combined with Midodrine hydrochloride, it may further reduce your heart rate. It is advisable that your doctor closely monitors you.
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist before taking Midodrine hydrochloride.
Using this medicine while pregnant is not recommended. Tell your doctor if you are pregnant, or want to be, while you are being treated with this medicine.
Do not use this medicine if you are breast-feeding. Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breast-feeding.
Children and adolescents
Do not give this medicine to children and adolescents under the age 18 because the safety and efficacy of midodrine hydrochloride in this age group has not been established.
Effects on ability to drive and use machines
This medicine should not affect your ability to drive or use machines. However, if you feel dizzy or light-headed, do not drive or use any tools or machines and ask your doctor for advice.
10.3 How to Use CIPMIDO Tablets?
Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. This medicine may be taken with or without food.
How much you should take
Your doctor will decide your dose and tell you how long you should take this medicine. The treatment is usually long-term.
The recommended starting dose is normally one tablet of 2.5 mg three times a day. Your doctor may increase this dose weekly up to four 2.5 mg tablets (10 mg) three times daily. Most people do not need more than 30mg a day. The recommended total daily dose should be spread evenly into three doses per day in divided doses.
Timing of the evening dose
Avoid taking this medicine in the late evening. You should take the last dose at least 4 hours before your bedtime. Raising the position of your head at night reduces the potential risk of high blood pressure when you lie down. More information can be found in the section “Warnings and precautions”. If you feel that the effect of this medicine is too strong, or too weak, talk to your doctor or pharmacist.
If you take more CIPMIDO Tablets than you should
If you have taken more tablets than you should
• Contact your doctor or pharmacist immediately or go to the nearest hospital casualty department straight away.
• Take this leaflet and/or the pack with you so that this medicine can be identified.
• The following effects may happen: high blood pressure (hypertension) e.g. palpitations, shortness of breath, chest pain, headache and blurred vision, low heart rate (bradycardia), urgent desire to empty the bladder, difficulty urinating, hair standing up (goosebumps) or feelings of coldness.
If you forget to take CIPMIDO Tablets
If you forget to take a dose, take your next dose as usual and then keep taking your medicine as your doctor has told you. Do not take a double dose to make up for a forgotten dose, because this will increase the risk of high blood pressure when you lie down.
If you stop taking CIPMIDO Tablets
There will be no sudden drop in your blood pressure. Do not stop taking these tablets without asking your doctor first. Always talk to your doctor if you are considering stopping taking this medicine. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
10.4 Possible Side Effects of Midodrine hydrochloride tablets:
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat after taking these tablets.
Midodrine hydrochloride can lead to following side effects:
Very common (may affect more than 1 in 10 people):
• goosebumps, itching of the scalp and pain when urinating.
Common (may affect more than 1 in 100 but less than 1 in 10 people):
• increased blood pressure when lying down, headache, nausea (feeling sick), tingling and itching, flushing, rash, chills, heartburn, inflammation of the lining inside the mouth, difficulty urinating.
Uncommon (may affect more than 1 in 1,000 but less than 1 in 100 people):
• sleep disturbances (including difficulty sleeping), restlessness, agitation and irritability, slowed heart rate, urge to urinate.
Rare (may affect more than 1 in 10,000 but less than 1 in 1,000 people):
• palpitations, rapid heartbeat, abnormal liver function including an increase in the number of liver enzymes.
Not known (frequency cannot be estimated from the available data):
• abdominal pain, being sick (vomiting), diarrhoea, anxiety, feelings of confusion.
Consult your doctor if you experience any of these side effects. This is not a complete list of side effects and others may occur. Call your Doctor/Physician for medical advice about side effects.
Reporting of suspected adverse reactions:
If you get any side effects, talk to your doctor, pharmacist, or nurse or write to email@example.com. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the National Pharmacovigilance Program of India by calling on 1800 180 3024 or you can report to Cipla Ltd. on 1800 267 7779. By reporting side-effects, you can help provide more information on the safety of this product.
10.5 General Instructions:
Patients should be told that certain agents in over-the-counter products, such as cold remedies and diet aids, can elevate blood pressure, and therefore, should be used cautiously with Midodrine hydrochloride, as they may enhance or potentiate the pressor effects of Midodrine hydrochloride (see Drug Interactions). Patients should also be made aware of the possibility of supine hypertension. They should be told to avoid taking their dose if they are to be supine for any length of time, i.e., they should take their last daily dose of Midodrine hydrochloride 3 to 4 hours before bedtime to minimize nighttime supine hypertension.
Mfd. By Optimus Pharma Private Limited,
Plot No.73/B,73/B/2, EPIP, Pashamylaram (V),
Patancheru (M), Sangareddy (Dist.) – 502307,
Telangana State, India.
Registered Office: Cipla Ltd.
Cipla House, Peninsula Business Park,
Ganpatrao Kadam Marg
Mumbai – 400 013, India