CIPMIDO Tablets (Midodrine hydrochloride)

Table of Content

Orthostatic hypotension is clinically defined as a sustained decrease in systolic blood pressure of 20 mmHg or a decrease in diastolic blood pressure of 10 mmHg within three minutes of standing up. Available estimates suggest about 5% of middle-aged patients (<50 years old) and 30% of elderly patients (>70 years) suffer from orthostatic hypotension (OH). Although incidence of OH increases with age, it can also occur secondary to neuropathy like in diabetes (about 10-20%) or central lesions like Parkinson’s disease (up to 35%). OH imposes significant burden on the healthcare system due to high risk of mortality, cardiovascular events, falls in elderly and higher hospitalization.

The pathological process of OH involves failure of counter-regulatory mechanisms such as baroreceptor reflex and sympathetic activation in postural regulation of blood pressure. In many patients, OH may be asymptomatic while being diagnosed only on systematic measurement of blood pressure in upright position by the physician. Symptomatic OH, on the other hand, presents most commonly, with dizziness, light-headedness, fatigue, blurred vision or even syncope or unusual symptoms such as pain in the neck and shoulders (the so-called ‘‘coat hanger pain’’). It therefore becomes imperative to search for OH systematically in high-risk patients.

In contrast to hypertension, which is most often asymptomatic but requires treatment to avoid long-term complications, management of OH is aimed at preventing falls and improving functional capacity of the patients. The management protocol for OH includes interruption of OH-precipitating drugs, non-pharmacologic measures such as intake of salt water, elastic stockings, etc and lastly pharmacologic treatment with vasopressors or corticosteroids (for volume expansion). The different drugs used in the management of OH include midodrine, pyridostigmine, droxidopa and fludrocortisone.

Midodrine has been approved by the USFDA in the treatment of symptomatic orthostatic hypotension. Midodrine is an oral pro-drug which undergoes hydrolysis to produce its active metabolite, desglymidodrine. It acts as an agonist selectively at the peripheral α1-adrenergic receptors which causes vasoconstriction of the arteriolar and venous systems resulting in increase in blood pressure. A range of placebo-controlled trials and systematic reviews have indicated the therapeutic efficacy in increasing standing and supine blood pressure as well as improving global symptom scores assessed by physicians and patients. Common side effects which may be observed with midodrine are supine hypertension, piloerection, and urinary retention.

To be sold by retail on the prescription of Cardiologist only.

1.    Generic Name

Midodrine Hydrochloride Tablets USP 2.5mg

2.    Black Box Warning

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.

3.    Qualitative and Quantitative Composition

Each uncoated tablet contains:

Midodrine Hydrochloride USP……….2.5 mg

Excipients …………………………….q.s

4.    Dosage Form and Strength

Dosage form: Solid dosage form; oral, uncoated tablets.

Strength: 2.5 mg

5.    Clinical Particulars

5.1 Therapeutic Indication

Midodrine is indicated in the treatment of symptomatic orthostatic hypotension.

5.2 Posology and Method of Administration

Posology

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. Higher dosages have not been studied. 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. It is essential to adjust individually the dosage to achieve a correct balance between the therapeutic effects and the possible risks. The last daily dose should be taken at least 4 hours before bedtime in order to prevent supine hypertension.

Midodrine tablets may be taken with food.

5.3 Contraindications

Midodrine 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 aneurism)
  • Hypertension
  • Serious obliterative blood vessel disease, cerebro-vascular occlusions and vessel spasms
  • Acute renal disease
  • Severe renal insufficiency (creatinine clearance of less than 30 ml/min.)
  • Serious prostate disorder (e.g. Hypertrophy of the prostate gland)
  • Urinary retention
  • Proliferative diabetic retinopathy
  • Pheochromocytoma
  • Hyperthyroidism
  • Narrow angle glaucoma
  • Hypersensitivity to the active substance or to any of the excipients (see section 8.1).

5.4 Special 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 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 hypertension during the night can be reduced by elevating the head. Patients should be monitored for possible secondary events on hypertension.

In patients suffering from serious disturbances of the autonomous nervous system, administration of midodrine may lead to a further reduction of blood pressure in the standing position. If this is the case, further treatment with midodrine 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 recommended in the case of patients with prostate disorders. Use of the drug may cause urinary retention.

Midodrine 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. Treatment with midodrine 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 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.

5.5 Drug Interactions

Potential Effect of Midodrine on Other Drugs

Midodrine is an inhibitor of Cytochrome P450 CYP2D6 and may therefore affect the metabolism of other drugs metabolised by this isoenzyme (e.g. perphenazine, amiodarone, metoclopramide). This may lead to increased systemic exposure and increased effects of these 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 (see section 5.2). However, decreased clearance of medicinal products metabolised by CYP2D6 (e.g. promethazine) has been reported.

Potential Effect of Other Drugs on Midodrine

No studies to evaluate the effect of other drugs on the pharmacokinetics of midodrine 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.

Alpha-adrenergic Antagonists

The effect of midodrine is blocked by a-adrenergic blockers such as prazosine and phentolamine. - Monitoring is recommended if midodrine is combined with other drugs that directly or indirectly reduce the heart rate.

Glycosides

Simultaneous use of digitalis preparations is not recommended, since the bradycardia which occurs as a result of the use of midodrine is then potentiated and heart block may occur.

Corticosteroid Preparations

Patients being treated with midodrine in combination with mineralocorticoids or glucocorticoids (e.g. fludrocortisone) maybe at increased risk of glaucoma/increased intraocular pressure, and should be carefully monitored. Midodrine 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 is combined with other drugs that directly or indirectly reduce the heart rate.

Falsely Elevated Plasma Metanephrine

Patients taking midodrine 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 patient staking midodrine require biochemical investigation for potential phaeochromocytomas and paragangliomas.

5.6 Use in Special Populations

Geriatric Patients

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 disease and severe renal insufficiency

Patients with Hepatic Impairment

No specific studies have been performed in this patient population, so experience is missing.

Pediatric Patients

The safety and efficacy of midodrine hydrochloride in children has not been established. No data are available.

Pregnant Women

There are no data on the use of midodrine in pregnant women. Studies in animals have shown reproductive toxicity at maternally toxic doses.  Midodrine is not recommended during pregnancy and in woman of childbearing potential not using contraception.

Lactating Women

It is unknown whether midodrine is excreted in the breast milk. A risk to the suckling child cannot be excluded. Midodrine should not be used during breast-feeding.

Fertility

Animal studies are insufficient with respect to the assessment of fertility.

5.7 Effects on Ability to Drive and Use Machines

Midodrine tablets have negligible influence on ability to drive or use machines. However, patients who experience dizziness or light-headedness while receiving midodrine tablets should refrain from driving or operating machinery.

5.8 Undesirable Effects

Summary of safety profile

The most frequently occurring events associated with treatment include piloerection, dysuria and pruritus of the scalp. Events of supine hypertension have been reported during treatment, the degree of which is dose dependent.

Tabulated list of adverse reactions

The following table presents the adverse drug reactions reported from clinical trials and from spontaneous reporting.

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).

Frequency

 

 

System Organ

Class

Very common

(≥1/10)

Common

(≥1/100, < 1/10)

Uncommon

(≥ 1/1000, < 1/100)

Rare (≥

1/10,000, <

1/1000)

Not known

Psychiatric disorders

 

 

Sleep disorders Insomnia

 

Anxiety

Confusional state

Nervous system disorders

 

Paraesthesia Paraesthesia of the scalp

Headache

Restlessness

Excitability

Irritability

 

 

Cardiac disorders

 

 

Reflex bradycardia

Tachycardia Palpitations

 

Vascular disorders

 

Supine hypertension (dose dependent effect)

 

 

 

Gastrointestinal disorders

 

Nausea

Heartburn

Dyspepsia

Stomatitis

 

 

Abdominal pain Vomiting 

Diarrhoea 

Hepatobiliary disorders

 

 

 

Abnormal hepatic function

Raised liver enzymes

 

Skin and subcutaneous tissue disorders

Piloerection

(goosebumps) Pruritus of the scalp

Pruritus Chills, flushing, skin rash

 

 

 

Renal and urinary disorders

Dysuria

Urinary retention

Urinary urgency

 

 

 

Reporting of Suspected Adverse Reactions

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 drugsafety@cipla.com. 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.

5.9 Overdose

Symptoms

Overdose symptoms are those seen as undesirable effects, in particular hypertension, piloerection (goosebumps), and sensation of coldness, bradycardia (reflex-bradycardia) and urinary retention.

Management

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 degradation product desglymidodrine is dialyzable.

6.    Pharmacological Properties

Pharmacotherapeutic category: cardiac stimulants (excl. cardiac glycosides), ATC-code: C01C A17.

6.1.              Mechanism of Action

Midodrine is the rapidly absorbed pro-drug of the pharmacologically active constituent desglymidodrine. Desglymidodrine is a sympathicomimetic with a direct and selective effect on the peripheral 1-adrenergic receptors. This α1-stimulative effect induces vasoconstriction of the venous system (reduction in the venous pool). The α-adrenergic effects of desglymidodrine are almost wholly attributable to the (-) enantiomer of desglymidodrine. After taking midodrine (as a racemic mixture present in the tablets) (+) desglymidodrine is also formed, 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.

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 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, with some effect persisting for 2 to 3 hours. Midodrine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure.

6.3 Pharmacokinetic Properties

Absorption

After oral administration, midodrine 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.

Distribution

Neither midodrine nor desgylmidodrine are bound to plasma proteins to any significant extent (less than 30%). Animal studies show that desglymidodrine is distributed in target organs and 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.

Biotransformation

Midodrine 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.

Excretion

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 form. The plasma elimination half-life for midodrine 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.    Nonclinical Properties

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).

8.    Description

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:

Midodrine hydrochloride, USP is an odorless, white, crystalline powder. It is soluble in water and sparingly soluble in methanol and has a pKa of 7.8 (0.3% aqueous solution) and a pH of 3.5 to 5.5 (5% aqueous solution). It has a melting range of 200°C to 203°C.

9. Pharmaceutical Particulars

9.1 List of Excipients

Microcrystalline Cellulose pH 102, Pregelatine Starch, Croscarmellose Sodium, Colloidal Silicone Dioxide, Magnesium Stearate.

9.2 Incompatibilities

Not applicable

9.3 Shelf-Life

Please see manufacturing date and expiry date printed on pack. Do not use the product after the expiry date which is stated on the packaging. The expiry date refers to the last day of that Month.

9.4 Packaging Information

20 Tablets are packed in one ALU – PVC blister along with pack insert.

9.5 Storage and Handling Instructions

Do not store above 30°C. Protect from light and moisture.

Keep out of reach and sight of Children.

10. Patient Counselling Information

10.1 What is Midodrine and What is it Used for

Midodrine works by constricting (narrowing) the blood vessels and increasing blood pressure.

Midodrine is used to treat low blood pressure (hypotension) that causes severe dizziness or a light-headed feeling, like you might pass out. Midodrine is for use only when low blood pressure affects daily life. Midodrine may not improve your ability to perform daily activities.

10.2 What You Need to Know Before You Take Midodrine

You should not use midodrine if you have severe heart disease, overactive thyroid, an adrenal gland tumor, kidney disease, if you are unable to urinate, or if your blood pressure is high even while lying down.

Midodrine can increase blood pressure even when you are at rest. This medicine should be used only if you have severely low blood pressure that affects your daily life. Midodrine may not improve your ability to perform daily activities.

Before taking this medicine

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

  • severe heart disease
  • kidney disease, or if you are unable to urinate
  • you have a slow pulse
  • pheochromocytoma (tumor of the adrenal gland)
  • overactive thyroid
  • high blood pressure even while lying down
  • you have increased pressure in the eye (glaucoma)
  • you have poor vision as a result of diabetes
  • you have an enlarged prostate

To make sure midodrine is safe for you, tell your Doctor/Physician if you have:

  • diabetes
  • glaucoma or a history of vision problems
  • liver disease
  • a history of kidney disease.

It is not known whether midodrine will harm an unborn baby. 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 in this age group has not been established.

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.

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 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 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 which regulate the function of body organs such as heart and stomach), 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 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.

If any of the warnings apply to you, or have had them in the past, talk to your doctor.

Other Medicines and Midodrine 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 it may further reduce your heart rate. It is advisable that your doctor closely monitors you.

10.3 How to Use Midodrine

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Midodrine is usually taken 3 times per day, with doses spaced at least 3 hours apart. Avoid taking this medicine in the late evening. You should take the last dose at least 4 hours before your bedtime.

You may take midodrine with or without food.

Take this medicine during your normal waking hours, when you are most likely to be upright and not lying down or napping. Ask your Doctor/Physician about how to take this medicine if you normally lie down during the day.

Midodrine can increase your blood pressure even while you are lying down or sleeping (when blood pressure is usually lowest). Long-term high blood pressure (hypertension) can lead to serious medical problems.

Follow your Doctor/Physician's instructions about the best way to position your body while you are laying down or sleeping. You may need to keep your head elevated to help prevent high blood pressure.

Your blood pressure will need to be checked before and during treatment with midodrine. Check your blood pressure while you are lying down and check it again with your head elevated.

Your kidney and liver function may also need to be checked.

Avoid taking a dose within less than 4 hours before your normal bedtime.

Ask a Doctor/Physician or pharmacist before using any over-the-counter diet pills, or cough/cold medicine that contains phenylephrine or pseudoephedrine. These medicines may raise your blood pressure.

10.4 Possible Side Effects

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.

Stop taking midodrine and call your Doctor/Physician at once if you have:

  • severely slowed heart rate--weak pulse, severe dizziness or light-headed feeling; or
  • dangerously high blood pressure--severe headache, pounding sensation in your ears ("hearing" your heartbeats), blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure.

Common side effects may include:

  • chills, goosebumps;
  • numbness, tingling, or itching (especially in your scalp);
  • headache, dizziness, tired feeling;
  • nausea; or
  • increased urination, painful or difficult urination, or sudden urge to urinate.

This is not a complete list of side effects and others may occur. Call your Doctor/Physician for medical advice about side effects.

If you get any side effects, talk to your doctor, pharmacist, or nurse or write to drugsafety@cipla.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.

11. Details of Manufacturer

Mfd. By BDR Pharmaceuticals Intl. Pvt. Ltd.,

At: Plot No. 16, Pharmacity,

Selaqui, Dehradun,

Uttarakhand – 248011.

Registered Office:

Cipla House, Peninsula Business Park,

Ganpatrao Kadam Marg

Lower Parel

Mumbai – 400 013, India

12. Details of Permission or Licence Number with Date

44/UA/LL/2009 dated 07/07/2009

13. Date of Revision

05/03/2021