Midazolam Injection USP 10mg/10ml Taj Pharma

  1. NAME OF THE MEDICINAL PRODUCT

Midazolam Injection USP 2mg/2ml Taj Pharma
Midazolam Injection USP 5mg/ml Taj Pharma
Midazolam Injection USP 5mg/5ml Taj Pharma
Midazolam Injection USP 10mg/2ml Taj Pharma
Midazolam Injection USP 10mg/10ml Taj Pharma
Midazolam Injection USP 50mg/10ml Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION 

    a) Each ml solution contains:
    Midazolam USP………………………1mg
    b) Each ml solution contains:
    Midazolam USP………………………5mg

    c) Each ml solution contains:
    Midazolam USP………………………1mg

    d) Each ml solution contains:
    Midazolam USP………………………5mg

    e) Each ml solution contains:
    Midazolam USP………………………1mg

    f) Each ml solution contains:
    Midazolam USP………………………5mg

Excipient(s) with known effect

Each 1ml contains 1.97 mg of Sodium

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Solution for Injection/ Infusion

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

As intravenous sedative cover before and during minor medical, dental and surgical procedures such as gastroscopy, endoscopy, cystoscopy, bronchoscopy and cardiac catheterisation.

For sedation by continuous infusion in patients in intensive care.

As an intramuscular premedication for patients with physical status ASA I-IV who are to undergo surgical procedures.

As an alternative intravenous agent for the induction of anaesthesia in high risk and elderly patients, especially where cardiovascular stability is of particular importance. Induction is more reliable when heavy opiate premedication has been administered or when midazolam is given with a narcotic analgesic such as fentanyl.

4.2 Posology and method of administration

Posology

Intravenous sedation : One or more intravenous administrations over a single operating session.

In most circumstances, the 2mg/ml formulation is more convenient for titration purposes.

Adults: An assessment should be made of the degree of sedation necessary for the planned procedure.

The dose should be titrated against the response of the patient. The desired titration end point will depend upon the procedure. Full sedation will be evident by drowsiness, slurred speech but response to commands will be maintained.

As a guide, it is recommended that 0.4ml of Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma 5mg/ml solution (equivalent to 2mg midazolam) be administered intravenously over 30 seconds. If after 2 minutes, sedation is not adequate, incremental doses of 0.1ml to 0.2ml of Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma 5mg/ml solution (0.5 to 1mg midazolam) should be given.

Usual dose range 2.5mg – 7.5mg total dose (equivalent to around 0.07mg/kg body weight).

Dosages greater than 5.0mg are not usually necessary.

Elderly people: OLDER PATIENTS ARE MORE SENSITIVE TO THE EFFECTS OF BENZODIAZEPINES. IN THESE PATIENTS DOSES GREATER THAN 3.5MG ARE NOT USUALLY NECESSARY AND LOW DOSES AS LITTLE AS 1MG – 2MG (0.2 – 0.4ML) MAY BE ADEQUATE. THE INITIAL DOSE SHOULD NOT EXCEED 1 – 1.5MG (0.2 – 0.3ML).

Paediatric population: Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection has not been evaluated for use as an intravenous sedative in children.

Sedation by continuous infusion in intensive care : For sedation in the intensive care unit, dosages vary considerably and the dosage of Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection should be individualised and titrated to the desired state of sedation according to the clinical need, physical status, age and concomitant medication.

Patients receiving Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection for sedation by continuous infusion in the intensive care situation should receive ventilatory support.

Safety of continuous infusion of midazolam injection for periods of over fourteen days in duration has not been established in clinical trials.

Adults and children : Loading dose : For patients already sedated, a loading dose of midazolam is not required. To induce sedation, a loading dose of 0.03 – 0.3mg/kg is recommended, depending on the level of sedation required. This should be administered over a five minute period.

Maintenance dose : The dosage varies considerably. A dose between 0.03 – 0.2mg/kg per hour is recommended, commencing at the lower end of the range.

The dosage should be reduced or the loading dose should even be omitted in hypovolaemic, vasoconstricted and hypothermic patients.

Combination therapy

Intravenous bolus sedation : Where analgesia is provided by a narcotic analgesic the latter should be administered first, the dose of midazolam should be carefully titrated and low doses 1 – 2mg (0.2 – 0.4ml) may be adequate. In the elderly, smaller doses as little as 0.5 – 1mg (0.1 – 0.2ml) may be adequate.

Sedation by continuous infusion in intensive care : Where analgesia is provided by narcotic analgesics, the rate of infusion of Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection should be titrated carefully to the sedative needs of the patient.

Intravenous induction of anaesthesia : One or more bolus intravenous injections over a single anaesthetic session.

Adults : The dose should be titrated against the individual response of the patient. Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection should be given by slow intravenous injection until there is a loss of eyelid reflex, response to commands and voluntary movements.

In anticipating the required dose of midazolam, both the premedication already given and the age of the patient are important. Young, fit unpremedicated patients may require at least 0.3mg/kg body-weight, whereas patients premedicated with an opiate usually require only 0.2mg/kg body-weight.

Older people : OLDER PATIENTS ARE MORE SENSITIVE TO THE EFFECTS OF BENZODIAZEPINES. INDUCTION MAY BE ADEQUATE WITH 0.1MG/KG BODY-WEIGHT IN PREMEDICATED PATIENTS AND 0.2MG/KG BODY-WEIGHT IN UNPREMEDICATED PATIENTS.

Paediatric population : Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection has been shown to be an effective agent for induction of anaesthesia in children over 7 years of age, at a dose of 0.15mg/kg body-weight.

Intramuscular premedication : Adults : A single intramuscular injection of 0.07 – 0.1mg/kg body-weight, administered 30 – 60 minutes pre-operatively, has been shown to be adequate in most cases. The usual dose is about 5mg.

Atropine or hyoscine hydrobromide may be given concomitantly, bearing in mind that hyoscine hydrobromide will enhance and prolong the sedative and amnesic effects of midazolam.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection can be combined with atropine or hyoscine hydrobromide in the same syringe to be given as a single intramuscular injection.

Elderly people : OLDER PATIENTS ARE MORE SENSITIVE TO THE EFFECTS OF BENZODIAZEPINES AND IN THESE PATIENTS A LOWER DOSE OF 2.5MG MAY BE ADEQUATE.

Paediatric population: Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection has not been evaluated for use as an intramuscular premedicant in children.

Use in Special Populations:

Renal Impairment:

In patients with renal impairment (creatinine clearance <10ml/min) the pharmacokinetics of unbound midazolam following a single IV dose is similar to that reported in healthy volunteers. However, after prolonged infusion in intensive care unit (ICU) patients, the mean duration of the sedative effect in the renal failure population was considerably increased most likely due to accumulation of α-hydroxymidazolam glucuronide.

There is no specific data in patients with severe renal impairment (creatinine clearance below 30 ml/min) receiving midazolam for induction of anaesthesia.

Hepatic Impairment

Hepatic impairment reduces the clearance of i.v. midazolam with a subsequent increase in terminal half-life. Therefore, the clinical effects may be stronger and prolonged. The required dose of midazolam may be reduced and proper monitoring of vital signs should be established. (See section 4.4).

Paediatric population

See above and section 4.4

Method of administration

Intravenous injection or by intravenous infusion

For the administration of Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection, the patient should be placed in a supine position and remain there throughout the procedure. Resuscitation facilities should always be available and a second person fully trained in the use of such equipment should always be present. It is recommended that patients should remain under medical supervision until at least 1 hour has elapsed from the time of injection. They should always be accompanied home by a responsible adult.

Patients who have received Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection alone for IV sedation prior to minor procedures should be warned not to drive or operate machinery for 12 hours. Where midazolam is used concurrently with other central nervous system depressants (e.g. potent analgesics) recovery may be prolonged. Patients should therefore be assessed carefully before being allowed to go home or resume normal activities.

4.3 Contraindications

  • Hypersensitivity to the active substance, benzodiazepines or to any excipient listed in section 6.1.
  • Use of this drug for conscious sedation in patients with severe respiratory failure, or acute respiratory depression

4.4 Special warnings and precautions for use

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma should be administered only by experienced physicians in a setting fully equipped for the monitoring and support of respiratory and cardiovascular function and by persons specifically trained in the recognition and management of expected adverse events including respiratory and cardiac resuscitation.

Severe cardiorespiratory adverse events have been reported. These have included respiratory depression, apnoea, respiratory arrest and/or cardiac arrest. Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered (see section 4.8).

Special caution is required for the indication of conscious sedation in patients with impaired respiratory function.

Paediatric population

In this population, midazolam is indicated for sedation in ICU only. Paediatric patients less than 6 months of age are particularly vulnerable to airway obstruction and hypoventilation, therefore titration with small increments to clinical effect and careful respiratory rate and oxygen saturation monitoring are essential (see also section ‘Preterm infants’ below).

When midazolam is used for premedication, adequate observation of the patient after administration is mandatory as inter-individual sensitivity varies and symptoms of overdose may occur.

Special caution should be exercised when administering midazolam to high-risk patients:

− adults over 60 years of age

− chronically ill or debilitated patients, e.g.

− patients with chronic respiratory insufficiency

− patients with chronic renal failure, impaired hepatic function or with impaired cardiac function

− pediatric patients specially those with cardiovascular instability.

These high-risk patients require lower dosages (see section 4.2) and should be continuously monitored for early signs of alterations of vital functions.

As with any substance with CNS depressant and/or muscle-relaxant properties, particular care should be taken when administering midazolam to a patient with myasthenia gravis.

Tolerance

Some loss of efficacy has been reported when midazolam was used as long-term sedation in intensive care units (ICU).

Dependence

When midazolam is used in long-term sedation in ICU, it should be borne in mind that physical dependence on midazolam may develop. The risk of dependence increases with dose and duration of treatment it is also greater in patients with a medical history of alcohol and/or drug abuse (see section 4.8).

Withdrawal symptoms

During prolonged treatment with midazolam in ICU, physical dependence may develop. Therefore, abrupt termination of the treatment will be accompanied by withdrawal symptoms. The following symptoms may occur: headaches, muscle pain, anxiety, tension, restlessness, confusion, irritability, rebound insomnia, mood changes, hallucinations and convulsions. Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, it is recommended to decrease doses gradually.

Amnesia

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma causes anterograde amnesia (frequently this effect is very desirable in situations such as before and during surgical and diagnostic procedures), the duration of which is directly related to the administered dose. Prolonged amnesia can present problems in outpatients, who are scheduled for discharge following intervention. After receiving midazolam parenterally, patients should be discharged from hospital or consulting room only if accompanied by an attendant.

Paradoxical reactions

Paradoxical reactions such as agitation, involuntary movements (including tonic/clonic convulsions and muscle tremor), hyperactivity, hostility, rage reaction, aggressiveness, paroxysmal excitement and assault, have been reported to occur with midazolam. These reactions may occur with high doses and/or when the injection is given rapidly. The highest incidence to such reactions has been reported among children and the elderly.

Altered elimination of midazolam

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma elimination may be altered in patients receiving compounds that inhibit or induce CYP3A4 and the dose of midazolam may need to be adjusted accordingly (see section 4.5).

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma elimination may also be delayed in patients with liver dysfunction, low cardiac output and in neonates (see section 5.2).

Preterm infants and neonates

Due to an increased risk of apnoea, extreme caution is advised when sedating preterm and former preterm non intubated patients. Careful monitoring of respiratory rate and oxygen saturation is required.

Rapid injection should be avoided in the neonatal population.

Neonates have reduced and/or immature organ function and are also vulnerable to profound and/or prolonged respiratory effects of midazolam.

Adverse haemodynamic events have been reported in paediatric patients with cardiovascular instability; rapid intravenous administration should be avoided in this population.

Concomitant use of alcohol / CNS depressants

The concomitant use of midazolam with alcohol or/and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of midazolam possibly including severe sedation or clinically relevant respiratory depression (see section 4.5).

Risk from concomitant use of opioids

Concomitant use of midazolam and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as midazolam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe midazolam concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2).

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers (where applicable) to be aware of these symptoms (see section 4.5).

Medical history of alcohol or drug abuse

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma as other benzodiazepines should be avoided in patients with a medical history of alcohol or drug abuse.

Discharging criteria

After receiving midazolam, patients should be discharged from hospital or consulting room only when recommended by treating physician and if accompanied by an attendant. It is recommended that the patient is accompanied when returning home after discharge.

This medicinal product contains less than 1 mmol sodium (23 mg) per ampoule, i.e. essentially ‘sodium- free’

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacokinetic Interactions

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma is metabolised by CYP3A4. Inhibitors and inducers of CYP3A4 have the potential to respectively increase and decrease the plasma concentrations and, subsequently, the effects of midazolam thus requiring dose adjustments accordingly.

Pharmacokinetic interactions with CYP3A4 inhibitors or inducers are more pronounced for oral as compared to i.v midazolam, in particular since CYP3A4 also exists in the upper gastro-intestinal tract. This is because for the oral route both systemic clearance and availability will be altered while for the parenteral route only the change in the systemic clearance becomes effective.

After a single dose of i.v midazolam the maximal clinical effect of CYP3A4 inhibition will be minor, but the duration of effect may be prolonged. However after prolonged dosing midazolam, both the magnitude and duration of effect will be increased in the presence of CYP3A4 inhibition.

There are no available studies on CYP3A4 modulation on the pharmacokinetics of midazolam after rectal and intramuscular administration. It is expected that these interactions will be less pronounced for the rectal than for the oral route because the gastro-intestinal tract is by-passed whereas after i.m administration the effects of CYP3A4 modulation should not substantially differ from those seen with i.v midazolam.

It is therefore recommended to carefully monitor the clinical effects and vital signs during the use of midazolam, taking into account that they may be stronger and longer after co-administration of a CYP3A4 inhibitor, be it given only once. Notably, administration of high doses or long-term infusions of midazolam to patients receiving strong CYP3A4 inhibitors, e.g. during intensive care, may result in long-lasting hypnotic effects, delayed recovery and respiratory depression, thus requiring dose adjustments.

With respect to induction, it should be considered that the inducing process needs several days to reach its maximum effect and also several days to dissipate. Contrary to a treatment of several days with an inducer, a short-term treatment is expected to result in less apparent DDI with midazolam. However, for strong inducers a relevant induction even after short-term treatment cannot be excluded.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma is not known to change the pharmacokinetics of other drugs.

Drugs that inhibit CYP3A4

Azole antifungals

  • Ketoconazole increased the plasma concentrations of intravenous midazolam by 5-fold while the terminal half-life increased by about 3-fold. If parenteral midazolam is coadministered with the strong CYP3A4 inhibitor ketoconazole, it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Staggered dosing and dosage adjustment should be considered, especially if more than a single i.v. dose of midazolam is administered.
  • Voriconazole increased the exposure of intravenous midazolam by 3-fold whereas its elimination half-life increased by about 3-fold.
  • Fluconazole and itraconazole both increased the plasma concentrations of intravenous midazolam by 2 – 3-fold associated with an increase in terminal half-life by 2.4-fold for itraconazole and 1.5-fold for fluconazole, respectively.
  • Posaconazole increased the plasma concentrations of intravenous midazolam by about 2-fold.
  • It should be kept in mind that if midazolam is given orally, its exposure will drastically be higher than the above-mentioned ones, notably with ketoconazole, itraconazole, voriconazole.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma ampoules are not indicated for oral administration.

Macrolide antibiotics

  • Erythromycin increases the plasma concentrations of intravenous midazolam by about 1.6 – 2-fold associated with an increase of the terminal half-life of midazolam by 1.5 – 1.8-fold.
  • Clarithromycin increased the plasma concentrations of midazolam by up to 2.5-fold associated with an increase in terminal half-life by 1.5 – 2-fold.

Additional information from oral midazolam

  • Roxithromycin: There is no information on roxithromycin with i.v midazolam but the mild effect on the terminal half-life of oral midazolam increase of 30%, indicates that the effects on i.v midazolam may be minor.
  • Quinupristin/ dalfopristin and telithomycin may increase plasma concentration of midazolam

HIV Protease inhibitors

  • Saquinavir and other HIV protease inhibitors: Co-administration with protease inhibitors may cause a large increase in the concentration of midazolam. Upon coadministration with ritonavir-boosted lopinavir, the plasma concentrations of intravenous midazolam increased by 5.4-fold, associated with a similar increase in terminal half-life. If parenteral midazolam is co-administered with HIV protease inhibitors, treatment setting should follow the description in the above section for azole antifungals, ketoconazole.

Additional information from oral midazolam

Based on data for other CYP3A4 inhibitors, plasma concentrations of midazolam are expected to be significantly higher when midazolam is given orally. Therefore protease inhibitors should not be co-administered with orally administered midazolam

Calcium-channel blockers

  • Diltiazem: A single dose of diltiazem increased the plasma concentrations of intravenous midazolam by about 25% and the terminal half-life was prolonged by 43%.

Additional information from oral midazolam

  • Verapamil/diltiazem increased the plasma concentrations of oral midazolam by 3- and 4-fold, respectively. The terminal half-life of midazolam was increased by 41% and 49% respectively

Various drugs/Herbs

  • Atorvastatin showed a 1.4-fold increase in plasma concentrations of IV midazolam compared to control group.

Additional information from oral midazolam

  • Nefazodone increased the plasma concentrations of oral midazolam by 4.6-fold with an increase of its terminal half-life by 1.6-fold.
  • Aprepitant dose dependently increased the plasma concentrations of oral midazolam by 3.3-fold after 80 mg/day associated with an increase in terminal half-life by ca. 2-fold. therefore increasing the risk of prolonged sedation.

Drugs that induce CYP3A4

  • Rifampicin decreased the plasma concentrations of intravenous midazolam by about 60% after 7 days of rifampicin 600mg o.d. The terminal half-life decreased by about 50-60%.

Additional information from oral midazolam

  • Rifampicin decreased the plasma concentrations of oral midazolam by 96% in healthy subjects and its psychomotor effects were almost totally lost.
  • Carbamazepine / phenytoin: Repeat dosages of carbamezepine or phenytoin resulted in a decrease in plasma concentrations of oral midazolam by up to 90% and a shortening of the terminal half-life by 60%.
  • Efavirenz: The 5-fold increase in the ratio of the CYP3A4 generated metabolite α-hydroxymidazolam to midazolam confirms its CYP3A4-inducing effect.

Herbs and food

  • St. John’s Wort decreased plasma concentrations of midazolam by about 20 – 40 % associated with a decrease in terminal half life of about 15 – 17%. Depending on the specific St John’s Wort extract, the CYP3A4-inducing effect may vary.

Pharmacodynamic Drug-Drug Interactions (DDI)

Sedative and hypnotics

The co-administration of midazolam with other sedative/hypnotic agents and CNS depressants, including alcohol, is likely to result in enhanced sedation and respiratory depression.

Examples include opiate derivatives (be they used as analgesics, antitussives or substitutive treatments), antipsychotics, other benzodiazepines used as anxiolytics or hypnotics, barbiturates, propofol, ketamine, etomidate; sedative antidepressants, non recent H1-antihistamines, sodiumoxybate, and centrally acting antihypertensive drugs.

Opioids

The concomitant use of sedative medicines such as benzodiazepines or related drugs such as midazolam with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited (see section 4.4).

Alcohol

Alcohol may markedly enhance the sedative effect of midazolam, so concurrent intake should be strongly avoided (see section 4.4).

Muscle relaxants

Increased sedative effect with baclofen and tizanidine.

Inhalation anaesthetics

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma decreases the minimum alveolar concentration (MAC) of inhalational anaesthetics.

Antihypertensives, vasodilators & diuretics:

Enhanced hypotensive effect with ACE-inhibitors, alpha-blockers, angiotensin-II receptor antagonists, calcium channel blockers, adrenergic neurone blockers, beta-blockers, moxonidine, nitrates, hydralazine, minoxidil, sodium nitroprusside and diuretics.

Anti-epileptics

Carbamazepine reduces the plasma concentrations of midazolam. Benzodiazepines may alter ie. Either increase or decrease the plasma concentrations of phenytoin.

Others

Nilotinib and Nabilone may increase plasma concentration of midazolam.

4.6 Fertility, pregnancy and lactation

Pregnancy

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma should not be used during pregnancy unless clearly necessary. It is preferable to avoid using it for caesarean.

Insufficient data are available on midazolam to assess its safety during pregnancy. Animal studies do not indicate a teratogenic effect, but foetotoxicity was observed as with other benzodiazepines. No data on exposed pregnancies are available for the first two trimesters of pregnancy.

The administration of high doses of midazolam in the last trimester of pregnancy, during labour or when used as an induction agent of anaesthesia for caesarean section has been reported to produce maternal or foetal adverse effects (inhalation risk in mother, irregularities in the foetal heart rate, hypotonia, poor sucking, hypothermia and respiratory depression in the neonate).

Moreover, infants born from mothers who received benzodiazepines chronically during the latter stage of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the post-natal period.

The risk for neonate should be taken into account in case of administration of midazolam for any surgery near the term.

Breast-feeding

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma passes in low quantities into breast milk. Nursing mothers should be advised to discontinue breast-feeding for 24 hours following administration of midazolam.

4.7 Effects on ability to drive and use machines

Sedation, amnesia, impaired attention and impaired muscular function may adversely affect the ability to drive or use machines.

Prior to receiving midazolam, the patient should be warned not to drive a vehicle or operate a machine until completely recovered. The physician should decide when these activities may be resumed. It is recommended that the patient is accompanied when returning home after discharge.

Where midazolam is used concurrently with other central nervous system depressants (e.g. potent analgesics) recovery may be prolonged. Patients should therefore be assessed carefully before being allowed to go home or resume normal activities.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

  • The medicine is likely to affect your ability to drive
  • Do not drive until you know how the medicine affects you
  • It is an offence to drive while under the influence of this medicine
  • However, you would not be committing an offence (called ‘statutory defence’) if:

o The medicine has been prescribed to treat a medical or dental problem and o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and

o It was not affecting your ability to drive safely

4.8 Undesirable effects

The following undesirable effects have been reported to occur when midazolam is injected:

Frequency categories are as follows:

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)

Not known (cannot be estimated from the available data)

SOC Frequency Adverse event
Immune system disorders Not known Hypersensitivity, anaphylactic shock, angioedema
Psychiatric disorders Not known Confusional state, euphoric mood, hallucination

Agitation*, hostility*, rage*, hyperactivity, aggressiveness*, excitement*, Assault*

Physical drug dependence and withdrawal syndrome, Abuse

Nervous system disorders Not known Sedation (prolonged and postoperative), alertness decreased, somnolence, headache, dizziness, ataxia, anterograde amnesia**, the duration of which is directly related to the administered dose

Convulsions local have been reported in premature infants and neonates

Involuntary movements (including tonic/clonic movements and muscle tremor)*, psychomotor hyperactivity*

Drug withdrawal convulsions

Cardiac disorders Not known Cardiac arrest, bradycardia, cardiovascular disorder, Hypotension, vasodilation
Respiratory, thoracic and mediastinal disorders Not known Respiratory depression, apnoea, respiratory arrest, dyspnea, laryngospasm, hiccups, bronchospasm
Gastrointestinal disorders Not known Nausea, vomiting, constipation, dry mouth
Skin and subcutaneous tissue disorders Not known Rash, urticaria, pruritus, skin reactions,
General disorders and administration site conditions Not known Fatigue, injection site erythema, injection site pain, thrombophlebitis, thrombosis
Injury, poisoning and procedural complications Not known Falls, fractures***

* Such paradoxical drug reactions have been reported particularly among children and the elderly (see section 4.4).

** Anterograde amnesia may still be present at the end of the procedure and in isolated cases prolonged amnesia has been reported (see section 4.4).

*** The risk of falls and fractures is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.

Dependence: Use of midazolam even in therapeutic doses may lead to the development of physical dependence. After prolonged i.v administration, discontinuation, especially abrupt discontinuation of the product, may be accompanied by withdrawal symptoms including withdrawal convulsions (see section 4.4). Cases of abuse have been reported.

Severe cardio-respiratory adverse events have occurred. Life-threatening incidents are more likely to occur in adults over 60 years of age and those with pre-existing respiratory insufficiency or impaired cardiac function, particularly when the injection is given too rapidly or when a high dosage is administered (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important.

4.9 Overdose

Symptoms

Like other benzodiazepines, midazolam commonly causes drowsiness, ataxia, dysarthria and nystagmus. Overdose of midazolam is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and in rare cases to coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.

Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.

Management Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.

If taken orally further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure.

If CNS depression is severe consider the use of flumazenil, a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug.

The correct information for using Flumazenil can also be obtained from the UK National Poison Information Service by calling on the following telephone number.

Tel: 0844-892-0111 (directs caller to relevant local centre.)

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group:

Hypnotics and sedatives (benzodiazepine derivatives).

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma is a derivative of the imidazobenzodiazepine group. The free base is a lipophilic substance with low solubility in water.

The basic nitrogen in position 2 of the imidazobenzodiazepine ring system enables the active ingredient of midazolam to form water-soluble salts with acids. These produce a stable and well tolerated injection solution.

Mechanism of action

The pharmacological action of midazolam is characterised by short duration because of rapid metabolic transformation. Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma has a sedative and sleep-inducing effect of pronounced intensity. It also exerts an anxiolytic, an anticonvulsant and a muscle-relaxant effect.

After i.m. or i.v. administration anterograde amnesia of short duration occurs (the patient does not remember events that occurred during the maximal activity of the compound).

5.2 Pharmacokinetic properties

Absorption after i.m. injection

Absorption of midazolam from the muscle tissue is rapid and complete. Maximum plasma concentrations are reached within 30 minutes. The absolute bioavailability after i.m. injection is over 90%.

Distribution

When midazolam is injected i.v., the plasma concentration-time curve shows one or two distinct phases of distribution. The volume of distribution at steady state is 0.7 – 1.2 l/kg. 96 – 98% of midazolam is bound to plasma proteins. The major fraction of plasma protein binding is due to albumin. There is a slow and insignificant passage of midazolam into the cerebrospinal fluid. In humans, midazolam has been shown to cross the placenta slowly and to enter foetal circulation. Small quantities of midazolam are found in human milk.

Biotransformation

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma is almost entirely eliminated by biotransformation. The fraction of the dose extracted by the liver has been estimated to be 30 – 60%. Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma is hydroxylated by the cytochrome P4503A4 isozyme and the major urinary and plasma metabolite is alpha-hydroxymidazolam. Plasma concentrations of alpha-hydroxymidazolam are 12% of those of the parent compound. Alpha-hydroxymidazolam is pharmacologically active, but contributes only minimally (about 10%) to the effects of intravenous midazolam.

Elimination

In healthy volunteers, the elimination half-life of midazolam is between 1.5 – 2.5 hours. Plasma clearance is in the range of 300 – 500ml/min. Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma is excreted mainly by renal route (60 – 80% of the injected dose) and recovered as glucuroconjugated alpha-hydroxymidazolam. Less than 1% of the dose is recovered in urine as unchanged drug. The elimination half-life of alpha-hydroxy-midazolam is shorter than 1 hour. When midazolam is given by i.v. infusion, its elimination kinetics do not differ from those following bolus injection.

Pharmacokinetics in special populations

Elderly

In adults over 60 years of age, the elimination half-life may be prolonged up to four times.

Children

The elimination half-life after i.v. administration is shorter in children 3 – 10 years old (1 – 1.5 hours) as compared with that in adults. The difference is consistent with an increased metabolic clearance in children.

Neonates

In neonates the elimination half-life is on average 6 – 12 hours, probably due to liver immaturity and the clearance is reduced (see section 4.4).

Obese

The mean half-life is greater in obese than in non-obese patients (5.9 vs 2.3 hours). This is due to an increase of approximately 50% in the volume of distribution corrected for total body weight. The clearance is not significantly different in obese and non-obese patients.

Patients with hepatic impairment

The elimination half-life in cirrhotic patients may be longer and the clearance smaller as compared to those in healthy volunteers (see section 4.4).

Patients with renal impairment

The elimination half-life in patients with chronic renal failure is similar to that in healthy volunteers.

Critically ill patients

The elimination half-life of midazolam is prolonged up to six times in the critically ill.

Patients with cardiac insufficiency

The elimination half-life is longer in patients with congestive heart failure compared with that in healthy subjects (see section 4.4).

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride, Hydrochloric acid, Sodium hydroxide, Water for injections

6.2 Incompatibilities

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection is stable, both physically and chemically, for up to 1 hour at room temperature when mixed in the same syringe with Atropine Sulphate Injection BP or Hyoscine Hydrobromide Injection 0.4mg/ml. There is no evidence of the adsorption of midazolam onto the plastic of infusion apparatus or syringes.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection when mixed with 500ml infusion fluids containing dextrose 4% with sodium chloride 0.18%, dextrose 5% or sodium chloride 0.9% is chemically and physically stable for up to 24 hours at 25°C and up to 72 hours at 2 to 8°C. However, for pharmaceutical microbiological reasons, the product should be used immediately after dilution. When aseptically prepared, the diluted solution may be kept for not more than 24 hours if stored under refrigeration at a temperature between 2-8°C.

Admixture with Hartmann’s solution is not recommended, as the potency of midazolam decreases.

6.3 Shelf life

Unopened: 3 years.

After reconstitution: not applicable

After first opening: not applicable

6.4 Special precautions for storage

Protect from light.

Store below 25°C.

6.5 Nature and contents of container

Clear One Point Cut (OPC) 2ml & 10ml glass ampoules, glass type I, Ph. Eur.

Pack sizes: 5 x 2ml ampoules; 10 x 2ml ampoules.

5 x 10ml ampoules; 10 x 10ml ampoules

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

If only part used, discard the remaining solution.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

MIDAZOLAM INJECTION USP
2MG/2ML / 5MG/ML / 5MG/5ML / 10MG/2ML / 10MG/10ML / 50MG/10ML
TAJ PHARMA

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or nurse.
  • If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

This product will be referred to as Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection from here on.

WHAT IS IN THIS LEAFLET:

  1. What Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection is and what it is used for
  2. What you need to know before you are given Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection
  3. How you will be given Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection
  4. Possible side effects
  5. How to store Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection
  6. Contents of the pack and other information1. WHAT MIDAZOLAM INJECTION IS AND WHAT IT IS USED FOR

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma injection contains Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma. Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma belongs to a group of medicines called benzodiazepines which can cause sedation (sleepiness) and relieve anxiety.

It is used:

  • to sedate patients during minor surgical and dental operations, and medical procedures such as passing a tube into the stomach or bladder
  • to sedate patients in intensive care unit
  • as an anaesthetic in high risk and elderly patients
  • by injection into a muscle to provide pre medication for some patients prior to surgery.
  1. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN MIDAZOLAM INJECTION

You must not be given Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection if

  • youare allergic to Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma or any other benzodiazepines or to any of the other ingredients of this medicine (listed in section 6).
  • You have severe breathing problems and you are going to have Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection for conscious sedation.

You must not be given midazolam injection if any of the above apply to you. If you are not sure, talk to your doctor or nurse before you are given this medicine.

Children

If your child is going to be given this medicine:

  • It is particularly important to tell your doctor or nurse if your child has cardiovascular disease (heart problems). Your child will be carefully monitored and the dose will be adjusted specially
  • Children must be carefully monitored. For infants and babies under 6 months of age this will include monitoring of breathing and oxygen levels.

Warnings and precautions:

Talk to your doctor or nurse before you are given Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection.

Adults

Before Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection is given, let your doctor or nurse know if:

  • you are over 60 years of age
  • you suffer from a lung or breathing disorder
  • you have a problem with your kidneys or liver
  • have a long-term illness or debilitated (have an illness that makes you feel very weak, run down and short of energy)
  • you have ever been diagnosed as suffering from a personality disorder
  • you regularly drink large amounts of alcohol or you have had problems with alcohol use in the past
  • you regularly take recreational drugs or you have had problems with drug use in the past
  • you are pregnant or think you may be pregnant (see “Pregnancy and breast-feeding”)
  • you suffer from a condition called myasthenia gravis (which causes severe weakness of the muscles)
  • you suffer from heart disease or you have an abnormally low volume of blood in the circulation (for example, due to haemorrhage, dehydration or severe burns)
  • you are taking any medicine from the group of medicines known as opioids: taking these medicines with Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection may result in sedation, difficulties in breathing (respiratory depression), coma and may be fatal. Even if opioids are prescribed, your doctor may need to change the dose, the duration of treatment or monitor you regularly.

If any of the above applies to you, or if you are not sure, talk to your doctor or nurse before you are given this medicine.

Other medicines and Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection:

Tell your doctor or nurse if you are using, have recently used or might use any other medicines.

This is extremely important because some medicines can strengthen or weaken the effects of others.

In particular, tell your doctor or nurse if you are taking any of the medicine following:

  • strong pain relievers, such as codeine or pethidine
  • diltiazem, nifedipine or verapamil (used for angina or high blood pressure, verapamil may also be used to control irregular heartbeats)
  • medicines to treat high blood pressure like minoxidil, moxonidine, sodium nitroprusside, hydralazine, calcium channel blockers, beta blockers, alpha blockers and ACE inhibitors
  • medicines known as water pills or diuretics
  • the anti-fungal medicines ketoconazole, voriconazole, fluconazole, posaconazole or itraconazole
  • erythromycin, roxithromycin, clarithromycin, quinupristin/dalfopristin and telithomycin (macrolide antibiotics)
  • any other benzodiazepine drugs, such as diazepam or temazepam
  • hypnotics (medicines that make you sleep)
  • sedatives (medicines that make you feel calm or sleepy)
  • antidepressants (medicines for treatment of depression)
  • medicines for epilepsy (fits) such as phenytoin and carbamazepine
  • antihistamines (used to treat allergies)
  • medicines used in HIV infections called protease inhibitors (such as saquinavir) and efavirenz
  • atorvastatin (used to treat high cholesterol levels in blood)
  • rifampicin (used to treat mycobacterial infections such as tuberculosis)
  • herbal medicine St John’s Wort
  • ciclosporin used to suppress the immune system
  • medicines used to treat cancer such as nilotinib
  • medicines effective against vomiting and nausea, such as nabilone.

If you are already taking one of these medicines, speak to your doctor before you receive Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection.

Concomitant use of Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection and opioids (strong pain killers, medicines for substitution therapy and some cough medicines) increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible.

However if your doctor does prescribe Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection together with opioids the dose and duration of concomitant treatment should be limited by your doctor.

Operations

If you are going to have an inhaled anaesthetic (one that you breath in) for an operation or for dental treatment, it is important to tell your doctor or dentist that you have been given this medicine.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection with alcohol

Do not drink alcohol if you have been given midazolam injection. This is because alcohol can increase the sedative effect of midazolam injection and may cause problems with your breathing.

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 for advice before taking this medicine.

If you have passed through prolonged treatment during last phase of pregnancy with this medicine, your baby may develop physical dependence and risk of withdrawal symptoms after birth.

Breast- feeding

Do not breast-feed for 24 hours after being given midazolam injection. This is because midazolam may pass into your breast milk.

Driving and using machines:

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection will affect your ability to drive and operate machinery. You should speak to your doctor for advice on when you will be able to drive, operate machines or resume normal activities.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma injection may make you sleepy, forgetful or affect your concentration and co-ordination. This may affect your performance at skilled tasks such as driving or using machines.

You should always be taken home by a responsible adult after your treatment, if you have received midazolam injection. The medicine can affect your ability to drive as it may make you sleepy or dizzy.

  • do not drive after receiving this medicine until you know how it affects you
  • it is an offence to drive if this medicine affects your ability to drive
  • however, you would not be committing an offence if:
    • the medicine has been prescribed to treat a medical or dental problem and
    • you have been given according to the instructions given by the prescriber or in the information provided with the medicine and
    • it was not affecting your ability to drive safely.

Talk to your doctor or nurse if you are not sure whether it is safe for you to drive after receiving this medicine.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection contains Sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

  1. HOW YOU WILL BE GIVEN MIDAZOLAM INJECTION

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection will be given only by experienced doctors and trained people in a setting fully equipped for life support and who will recognize and be able to treat known side effects if they happen.

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection may be administered by intravenous injection (injection into a vein) or by intravenous infusion (given by a drip into a vein).

Your doctor will give this medicine to you and decide on the dose to be given based on the particular procedure they are doing, the degree of sleep (sedation) required, your weight, your response to the medication.

You should always be taken home by a responsible adult after your treatment.

Use in Children

  • In infants and babies under 6 months of age Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection is only recommended for sedation in intensive care units. The dose will be given gradually into a vein.
  • Children 12 years and under will usually be given Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection into a vein. When Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma injection is used for premedication (to cause relaxation, calm and drowsiness before an anesthetic) it may be given into the back passage (rectum).

If you think you have beengiven more Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection than you should have.

This is unlikely as your injection will be administered by a doctor or nurse. If you are concerned about the dose, discuss it with your doctor.

If you are accidentally given too much midazolam injection you may feel drowsy, lose your co-ordination (ataxia) and reflexes, have problems with your speech (dysarthria), have involuntary eye movements (nystagmus), develop low blood pressure (hypotension), stop breathing (apnoea) and suffer cardiorespiratory depression (slowed or stopped breathing and heart beat) and coma.

If you stop using Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma injection:

  • if you are given midazolam injection for a long time you may:
    • become tolerant to it. The medicine becomes less effective and does not work as well for you
    • become dependent upon this medicine and get withdrawal symptoms (see below).

Your doctor will reduce your dose gradually to avoid these effects happening to you.

Withdrawal symptoms:

Benzodiazepine medicines, like midazolam injection, may make you dependent if used for a long time. This means that if you stop treatment suddenly, or lower the dose too quickly, you may get withdrawal symptoms. The symptoms can include: headache; muscle pain; feeling very worried (anxious), tense, restless, confused or bad-tempered (irritable); problems with sleeping (insomnia); mood changes; hallucinations (seeing and possibly hearing things that are not there); fits (convulsions).

If you have any further questions on the use of this product ask your doctor or pharmacist.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side-effects, although not everyone gets them.

Serious side effects

Stop having midazolam injection and see your doctor straight away if you notice any of the following side effects. They can be life threatening and you may need urgent medical treatment:

  • anaphylactic shock (a life threatening allergic reaction). Signs may include a sudden rash, itching or lumpy rash (hives) and swelling of the face, lips, tongue or other parts of the body. You may have shortness of breath, wheezing or troubled breathing
  • heart attack (cardiac arrest). Signs may include chest pain which may spread to your neck and shoulders and down your left arm
  • general allergic reactions (skin reactions, heart and blood system reactions, wheezing)
  • breathing problems or complications (sometimes causing the breathing to stop)
  • choking and sudden blockage of the airway (laryngospasm).

Life threatening side effects are more likely to occur in adults over 60 years of age and those who already have breathing difficulties or heart problems, particularly if the injection is given too fast or at a high dose.

Other possible side effects:

The following side effects have been reported since the marketing of midazolam injection

Not known (frequency cannot be estimated from the available data):

  • confusion
  • hallucinations (seeing and possibly hearing things that are not really there)
  • reduced alertness
  • dizziness or fainting
  • fits (convulsion) due to withdrawal of drug
  • agitation, restlessness, hostility, rage or aggressionon and excitement particularly in children and older patients
  • Hiccup
  • dry mouth
  • potential drug dependence and withdrawal syndrome
  • low blood pressure
  • redness of face and neck (flushing)
  • feeling of sick or being sick
  • constipation
  • Injection site problems (Injection site redness, swelling of the skin, pain at the injection site)
  • difficulty coordinating muscles
  • involuntary movements
  • euphoria (an excessive feeling of happiness or excitement)
  • drowsiness and prolonged sedation
  • headache
  • fits (convulsion) in premature infants and new-born babies
  • temporary memory loss – how long this occurs depends on how much midazolam was given to you. You may experience this temporary memory loss after your treatment. In isolated cases temporary memory loss had been prolonged (lasted for a long time)
  • hives (lumpy rash)
  • abuse of Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma
  • slow heart rate
  • inflammation of veins, clotting in blood vessels (thrombophlebitis and thrombosis)
  • dry mouth
  • tiredness (fatigue)
  • muscle spasms and muscle tremors (shaking of muscles that you cannot control)
  • Falls and fractures

Older people:

  • Older patients taking benzodiazepine medicines have a higher risk of falling and breaking bones.
  • Potential drug dependence, abuse and withdrawal. If you have received Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma injection for a long time, you may find yourself becoming addicted and experience withdrawal symptoms once discontinued. If you have symptoms of agitation, anxiety and restlessness, speak to your doctor or nurse.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE MIDAZOLAM INJECTION

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and ampoule label after “Exp”. The expiry date refers to the last day of that month.

Keep the ampoules (small bottles) in the outer carton in order to protect from light.

Do not store above 25°C.

Do not use the ampoule if it is damaged or the contents are discoloured.

If only part used, discard the remaining solution.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection contains

a) Each ml solution contains:
Midazolam USP………………………1mg

b) Each ml solution contains:
Midazolam USP………………………5mg

c) Each ml solution contains:
Midazolam USP………………………1mg

d) Each ml solution contains:
Midazolam USP………………………5mg

e) Each ml solution contains:
Midazolam USP………………………1mg

f) Each ml solution contains:
Midazolam USP………………………5mg

The other ingredients are sodium chloride, hydrochloric acid, sodium hydroxide and water for injections.

What Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection looks like and contents of pack

Midazolam Injection USP 2mg/2ml / 5mg/ml / 5mg/5ml / 10mg/2ml / 10mg/10ml / 50mg/10ml Taj Pharma Injection 5mg in 1ml is a clear, colourless or slightly yellow, sterile solution contained in clear glass ampoules (small bottles). Each 1ml of this solution contains 5mg of midazolam.

The injection is available in packs of 10 ampoules containing 2ml or 10ml of solution.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com