Medzol

Medzol Uses, Dosage, Side Effects, Food Interaction and all others data.

Medzol binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites w/in the CNS, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to Cl ions, which results in hyperpolarisation (a less excitable state) and stabilisation. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors.

General effects

Medzol is a short-acting benzodiazepine central nervous system (CNS) depressant. Pharmacodynamic properties of midazolam and its metabolites, which are similar to those of other benzodiazepine drugs, include sedative, anxiolytic, amnestic, muscle relaxant, as well as hypnotic activities. Benzodiazepines enhance the inhibitory action of the amino acid neurotransmitter gamma-aminobutyric acid (GABA). Receptors for GABA are targeted by many important drugs that affect GABA function and are commonly used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, and aggressive behavior.

Sedation and memory

Trade Name Medzol
Availability Prescription only
Generic Midazolam
Midazolam Other Names Midazolam, Midazolamum
Related Drugs Valtoco, Nayzilam, Diastat, lorazepam, diazepam, topiramate, promethazine, Ativan, levetiracetam, Keppra
Type Injection
Formula C18H13ClFN3
Weight Average: 325.767
Monoisotopic: 325.078203343
Protein binding

Midazolam is approximately 97% bound to plasma protein, mainly albumin, in adults. The 1-hydroxy metabolite is approximately 89% bound to plasma protein.

Groups Approved, Illicit
Therapeutic Class Benzodiazepine hypnotics, Benzodiazepine sedatives
Manufacturer Themis Medicare Ltd
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Medzol
Medzol

Uses

  • Short-term management of insomnia
  • Conscious/Procedural sedation prior to or during diagnostic, therapeutic or endoscopic procedures such as dentistry, upper gastrointestinal endoscopy, bronchoscopy, cystoscopy, coronary angiography and cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations etc. and surgery performed under local anesthesia, either alone or in combination with other CNS depressants
  • Premedication
  • Induction of general anesthesia
  • Sedation in intensive care
  • Sedation in general anesthesia
  • Status epilepticus.

Medzol is also used to associated treatment for these conditions: Seizures, Epileptic, Refractory seizure disorders, Anaesthesia, Anxiolytic therapy therapy, Preoperative Sedation, Sedation for mechanically-ventilated patients, Preoperative amnesia

How Medzol works

The actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the central nervous system. Benzodiazepines increase the activity of GABA, thereby producing a sedating effect, relaxing skeletal muscles, and inducing sleep, anesthesia, and amnesia. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening. These receptors have been identified in different body tissues including the heart and skeletal muscle, although mainly appear to be present in the central nervous system.

Dosage

Medzol dosage

The duration of treatment with oral midazolam should not be more than of 2 weeks. In certain cases extension beyond the maximum treatment period may be necessary.Insomnia:

  • Adults: 7.5 mg to 15 mg daily (Oral)
  • Elderly: 7.5 mg daily(Oral)
  • Premedication: 7.5 mg to 15 mg, should be given 30-60 minutes before the procedure(Oral)

Endoscopic or Cardiovascular procedures:

  • Adult: initial dose is 2.5 mg (IV)
  • Elderly & debilitated patients: 1-1.5 mg (IV)
  • Induction of Anesthesia: Adult: 10-15 mg (IV) or 0.07-0.1 mg/Kg body weight, usually 5 mg (IM)
  • Children: 0.15-0.20 mg/Kg (IM)
  • Elderly & debilitated patients: 0.025-0.05 mg/Kg (IM)

Rectal administration in children: for preoperative sedation, rectal administration of the ampoule solution is 0.35-0.45 mg/Kg, 20-30 min before induction of general anesthesia

Side Effects

Drowsiness is the most common side effect. Less common side effects are CNS depression, ataxia, confusion, tiredness, muscle weakness, fatigue, headache, dizziness and double vision. These effects occur predominantly at the start of treatment and usually disappear with dose adjustment or continuation of therapy.

Toxicity

LD50=215 mg/kg, in rats.

Overdose

Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs. Serious cardiorespiratory adverse reactions have occurred, sometimes ending in death or permanent neurologic effects, after the administration of midazolam.

A note on cardiac and respiratory depression

After administration of midazolam, continuous monitoring of respiratory and cardiac function is recommended until the patient is in stable condition. Serious and life-threatening cardiorespiratory adverse reactions, including hypoventilation, airway obstruction, apnea, and hypotension have been reported with the use of midazolam. Patients should be monitored in a setting with immediate access to resuscitative drugs if they are required. Resuscitation equipment and personnel trained in their use and skilled in airway management should be available when midazolam is administered.

The usual recommended intramuscular pre-medicating doses of midazolam do not depress the ventilatory response to carbon dioxide stimulation to a clinically significant extent in adults. Intravenous induction doses of midazolam depress the ventilatory response to carbon dioxide stimulation for at least 15 minutes longer than the duration of ventilatory depression following administration of thiopental in adults. Impairment of ventilatory response to carbon dioxide is more severe in adult patients diagnosed with chronic obstructive pulmonary disease (COPD).

A note on dependence

When midazolam is used in long-term sedation in the ICU (intensive care unit) or other settings, physical dependence on midazolam may develop. The risk of dependence increases with dose and duration of treatment; this risk is also greater in patients with a medical history of substance abuse.

Special caution should be exercised when administering midazolam in the following populations

High-risk patients include adults over 60 years of age, chronically ill or debilitated patients, which may include patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function, pediatric patients (especially those with cardiovascular instability). These high-risk patients require lower dosages and should be monitored on a continuous basis for early signs of alterations of vital functions, so that appropriate management may be administered.

Mutagenesis

Medzol was negative for genotoxicity during in vitro and in vivo assays.

Impairment of Fertility

When midazolam (0, 1, 4, or 16 mg/kg) was given orally to male and female rats before and during mating and continuing in females throughout gestation and lactation, no adverse effects on male or female fertility were observed. Medzol plasma exposures (AUC) at the highest dose tested were approximately 6 times that in humans at the recomended human dose.

Precaution

CNS depressants, erythromycin, azole type animycotics and cimetidine may interfere the metabolism of Medzol. So caution should be taken during the concomitant treatment with these drugs along with Medzol. Long time use of Medzol may increase dependency. As Medzol is a strong sedative, it should not be taken before driving or other performance skilled tasks.

Interaction

CNS depressants, erythromycin, azole type animycotics and cimetidine may interact with Medzol.

Food Interaction

  • Avoid grapefruit products.

[Moderate] GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice.

The proposed mechanism is CYP450 3A4 enzyme inhibition.

In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines.

Tolerance may develop with chronic ethanol use.

The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition.

Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.



MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam.

Patients taking triazolam or alprazolam should be monitored for excessive sedation.

Alternatively, the patient could consume orange juice which does not interact with these drugs.

Patients should be advised to avoid alcohol during benzodiazepine therapy.

Volume of Distribution

Female gender, old age, and obesity may increase the volume of distribution. Medzol may also cross the placenta and has been detected in human milk and cerebrospinal fluid.

Intravenous administration

1.24 to 2.02 L/kg [pediatric patients (6 months to 12

Intramuscular administration

The mean apparent volume of distribution of midazolam after a single IM dose of 10 mg midazolam in healthy adults was 2117 (±845.1) mL/kg.

Elimination Route

Oral Absorption: Rapidly absorbed after oral administration. The absolute bioavailability, if given intramuscularly (IM), is greater than 90% . Due to first pass metabolism, only 40-50% of the administered oral dose reaches the circulation. The absolute bioavailability of the midazolam syrup in pediatric patients is about 36%.

Intramuscular Absorption: The mean peak concentration (Cmax) and time to peak (Tmax) following the IM dose was 90 ng/mL (20% CV) and 0.5 hour (50% CV).

Rectal administration: After rectal administration midazolam is absorbed rapidly. Maximum plasma concentration is reached within 30 minutes. The absolute bioavailability is approximately 50%.

Intranasal Administration: Medzol is absorbed rapidly after intranasal administration. Mean peak plasma concentrations are reached within 10.2 to 12.6 minutes. The bioavailability is between 55 and 57%.

Half Life

Intravenous: healthy adults = 1.8 to 6.4 hours (mean of 3 hours).

Intramuscular: Following IM administration of 10 mg midazolam, mean (±SD) elimination half-life was 4.2 (±1.87) hours.

Clearance

Intramuscular: apparent total body clearance, 367.3 (±73.5) mL/hr/kg. Intravenous: total clearance (Cl), 0.25 to 0.54 L/hr/kg

Elimination Route

The α-hydroxymidazolam glucuronide conjugate of midazolam is excreted in urine. No significant amount of parent drug or metabolites is found in urine before beta-glucuronidase and sulfatase deconjugation, suggesting that the urinary metabolites are excreted mainly as conjugates. The amount of midazolam excreted unchanged in the urine when given intravenously is less than 0.5%. 45% to 57% of the dose was excreted in the urine as 1-hydroxymethyl midazolam conjugate.

Plasma clearance of midazolam is higher in patients that remain in supine position, because of a 40-60 percent increase in hepatic blood flow during supination. Pregnancy may also increase the metabolism of midazolam.

Pregnancy & Breastfeeding use

Insufficient data are available on Medzol to assess its safety during pregnancy. But benzodiazepines adversely affect the human fetus. So their use should be avoided if there is safer alternative. Medzol is excreted through breast milk. Therefore, Medzol should not be used by the nursing mothers.

Contraindication

Known hypersensitivity to Medzol or other benzodiazepines, severe respiratory insufficiency, severe hepatic insufficiency, sleep apnea syndrome, myasthenia gravis, patients with a history of alcohol or drug abuse and children.

Special Warning

Protect from light and moisture, store in cool and dry place. Keep out of the reach of children.

Acute Overdose

Medzol should not be used more than the dosage guideline. Over dosage produces severe depression ranging from drowsiness to coma.

Innovators Monograph

You find simplified version here Medzol

Medzol contains Midazolam see full prescribing information from innovator Medzol Monograph, Medzol MSDS, Medzol FDA label

FAQ

What is Medzol used for?

Medzol is a benzodiazepine medication used for anesthesia, procedural sedation, trouble sleeping, and severe agitation. Medzol injection is used to produce sleepiness or drowsiness and relieve anxiety before surgery or certain procedures.

How safe is Medzol?

Medzol is an extremely useful and safe medication for both inpatients and outpatients.

How does Medzol work?

Medzol work by increasing the effect of a certain natural chemical (GABA) in the brain.

What are the common side effects of Medzol?

Common side effects of Medzol are Nausea, vomiting, dizziness, or drowsiness may occur. If any of these effects persist or worsen, notify the doctor or pharmacist promptly.

Is Medzol safe during pregnancy?

Medzol be avoided for use as general anesthesia and sedation during the third trimester of pregnancy for surgeries not related to delivery of the baby.

Is Medzol safe during breastfeeding?

The small amounts of Medzol excreted into breastmilk would not be expected to cause adverse effects in most breastfed infants. A safety scoring system finds Medzol acceptable to use during breastfeeding.

Can I drink alcohol with Medzol?

Do not drink alcohol while taking Medzol. This medication can increase the effects of alcohol. You may feel more drowsy, dizzy, or tired if you take midazolam with alcohol.

Can I drive after taking Medzol?

Avoid driving or hazardous activity until the effects of Medzol have worn off completely. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

How do I take Medzol?

Take this medication by mouth as directed by your doctor. It is usually given as a single dose before a procedure or anesthesia.

When should be taken of Medzol?

The total dose of Medzol, usually ranging from 0.3 to 0.5mg/kg should be administered 15 to 30 minutes before induction of anaesthesia.

How long does Medzol take to work?

The onset of action is about 2 minutes after the injection. Maximum effect is obtained in about 5 to 10 minutes. The IV injection of Medzol should be given slowly at a rate of approximately 1mg in 30 seconds.

What is the half life of Medzol?

The half-life, which is how long it takes for half the drug to leave the system, is 1.5 to 2.5 hours. This is actually very short compared to many other benzodiazepines.

How does Medzol cause death?

Medzol injection may cause serious or life-threatening breathing problems such as shallow, slowed, or temporarily stopped breathing that may lead to permanent brain injury or death.

Who should not take Medzol?

You should not use Medzol if you are allergic to it, or if you have: narrow-angle glaucoma; untreated or uncontrolled open-angle glaucoma; or an allergy to cherries.

Who should not take Medzol?

You should not use Medzol if you are allergic to it, or if you have: narrow-angle glaucoma; untreated or uncontrolled open-angle glaucoma; or an allergy to cherries.

What happens if I miss a dose?

In a medical setting you are not likely to miss a dose.

What happens if I overdose?

In a medical setting an overdose would be treated quickly.

What happen If I stop taking Medzol?

You should not stop this Medzol suddenly as there can be withdrawal symptoms like sweating, vomiting, shaking, abdominal/muscle cramps, seizures, mental/mood changes such as agitation/anxiety.

Can Medzol affects my heart ?

Under spinal anaesthesia, intravenous Medzol decreases blood pressure and heart rate (HR)'. However, the effects of Medzol on the cardiac autonomic nervous system, which has a vital role in neural control for maintaining cardio- vascular stability, have not been well studied.

Is Medzol bad for kidneys?

Medzol has delayed metabolism and elimination in renal impairment and should be avoided. Morphine and its derivatives accumulate in renal failure and shorter-acting opiates are preferable.

Can Medzol affects my liver?

Medzol therapy has not been associated with serum aminotransferase elevations and has not been linked to cases of clinically apparent liver injury.

*** Taking medicines without doctor's advice can cause long-term problems.
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