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Dear Readers! I started this blog when my daughter was in the NICU. She had ventriculitis. Her CSF report grew E.coli. But, she was injected Teicoplanin directly into her brain. The doctors made two errors here:

Teicoplanin is for gram-positive bacteria only. It does not treat E.coli.
Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

My daughter bled into the brain. She lived for another two years and ultimately died.

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Zopiclone - For the short-term treatment of insomnia

Zopiclone reduces sleep latency, decreases the number of nocturnal awakenings, and increases the duration of sleep. It is marketed as a sleeping pill and is not available in the United States.

It is indicated for the short-term and symptomatic relief of insomnia.

Zopiclone dose in Adults

Note: Treatment should generally not exceed 7 - 10 consecutive days.

Dose in the treatment of Insomnia:

Initial: 3.75 mg orally once a day at bedtime.
The dose may be increased to 5 mg and then to 7.5 mg once a day if necessary.
The maximum dose is 7.5 mg/day.

Patients with chronic respiratory insufficiency:

Initial: 3.75 mg orally once a day at bedtime.
The dose may be increased as tolerated up to 7.5 mg once a day with caution.
It should be avoided in patients with severe respiratory insufficiency.

Debilitated patients:

Initial: 3.75 mg orally once a day at bedtime.
The dose may be increased up to 5 mg daily if necessary to a maximum of 5 mg/day.
Dosage adjustment for concomitant therapy:
- Potent CYP3A4 inhibitors:
  - Initial zopiclone dose: 3.75 mg once a day at bedtime.
  - The dose may be increased to 5 mg once a day with caution.

Zopiclone dose in Children

Not recommended for use in Children.

Pregnancy Risk factor: D

Avoid it during pregnancy.
It can cause congenital malformations in the first trimester, and neonatal CNS depression during the final weeks of pregnancy.

Use of Zopiclone while breastfeeding

It is excreted in breastmilk at levels of 50% of plasma levels.
Avoid it while breastfeeding.

Zopiclone Dose in Liver disease:

Initial 3.75 mg once a day at bedtime.
The dose may be increased up to 5 mg once a day with caution.

Zopiclone dose in liver disease:

Hepatic impairment mild-to-moderate:
- 3.75 mg daily at bedtime
- You can increase the daily dose up to 5 mg.
Severe hepatic impairment
- Contraindicated.

Side effects of Zopiclone (Frequency not defined).

Some incidences tend to be higher in geriatric patients.

Cardiovascular:
- Palpitations
Central Nervous System:
- Aggressiveness Behavior
- Anxiety
- Bitter Taste
- Confusion
- Daytime Sedation
- Depression
- Dizziness
- Drowsiness
- Dysgeusia
- Euphoria
- Hypotonia
- Intoxicated Feeling
- Memory Impairment
- Nervousness
- Speech Disturbance
Dermatological:
- Diaphoresis
Gastrointestinal:
- Anorexia
- Constipation
- Coated Tongue
- Halitosis
- Increased Appetite
- Sialorrhea
- Xerostomia
Neuromuscular & Skeletal:
- Asthenia
- Tremor

Contraindication to Zopiclone Include:

Allergy to zopiclone and any component of the formulation
Grave respiratory impairment.
Sleep apnea Syndrome
Myasthenia gravis
Severe hepatic impairment.

Warnings and Precautions

Abnormal behavior/thinking:
- Patients might experience daytime anxiety or restlessness.
- Patients may experience abnormal thinking and behavior changes, including aggression, hallucinations and agitation, decreased inhibition, bizarre behavior and aggression.
Anterograde amnesia
- Patients taking zopiclone may experience anterograde amnesia.
Depression in the CNS:
- CNS depression can occur, which may lead to mental and physical impairments.
- The drug may cause persistent side effects in patients who are taking CNS depressants with them, not getting enough sleep at night, or on drugs that increase their levels.
- Patients are advised to wait at least 12 hours after taking the drug before engaging any activities that could require mental alertness.
Hypersensitivity
- It has been associated with allergic reactions, including angioedema and signs anaphylactics.
Paradoxical reactions
- It can sometimes lead to aggressive or hyperactive behavior, especially among young children and people with preexisting mental disorders.
Activities that are sleep-related:
- It has been reported that there is an increased risk of sleep-related hazardous activities like cooking, driving, and making calls while you sleep.
- Patients who have sleep disorders such as sleep apnea or restless legs syndrome and people with a family history of sleepwalking could be at greater risk for dangerous sleep-related activities.
Depression
- Patients with depression should use it with caution.
- It has been reported that it can lead to depression and even suicide attempts.
- Patients may take excessive amounts of the drug. Therefore, it should be prescribed in smaller amounts and for a shorter time.
Use of drugs:
- Patients who have a history or potential for addiction to drugs, alcohol, or personality disorders should be cautious about taking the drug.
- Long-term use may lead to tolerance, psychological dependence, or physical dependence.
- The risk of developing dependence is higher when the dose and duration are longer.
Hepatic impairment
- Patients with mild or moderate hepatic dysfunction should use it with caution. The dose should also be adjusted.
- It should not be used in severe liver disease.
Renal impairment
- The manufacturer suggests reducing the dosage and using the drug with caution in patients with kidney disease.
Respiratory disease
- Patients suffering from chronic respiratory disease should be cautious.
- It should not be used in severe cases of respiratory failure.

Zopiclone (United States: Not available): Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Bromopride	May enhance the CNS depressant effect of CNS Depressants.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Dapsone (Topical)	May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents.
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Local Anesthetics	Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased.
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Melatonin	May enhance the sedative effect of Hypnotics (Nonbenzodiazepine).
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Nitric Oxide	May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Piribedil	CNS Depressants may enhance the CNS depressant effect of Piribedil.
Pramipexole	CNS Depressants may enhance the sedative effect of Pramipexole.
Prilocaine	Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents.
ROPINIRole	CNS Depressants may enhance the sedative effect of ROPINIRole.
Rotigotine	CNS Depressants may enhance the sedative effect of Rotigotine.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Sodium Nitrite	Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Risk Factor D (Consider therapy modification)
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
CYP3A4 Inhibitors (Moderate)	May increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of Zopiclone. Management: The initial starting adult dose of zopiclone should not exceed 3.75 mg if combined with a strong CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Droperidol	May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Pitolisant	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Zolpidem	CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.
Risk Factor X (Avoid combination)
Alcohol (Ethyl)	May enhance the adverse/toxic effect of Zopiclone. Specifically, taking alcohol with zopiclone may increase the risk of complex sleep-related behaviors (eg, sleep-driving, eating food, making phone calls, leaving the house, etc.) Alcohol (Ethyl) may enhance the CNS depressant effect of Zopiclone.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Sodium Oxybate	Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Sodium Oxybate.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.

Monitor the patient for:

Confusion
Particularly in the elderly, excessive drowsiness
Respiratory depression
Patients suffering from hepatic or chronic respiratory problems should be closely monitored.

How to administer Zopiclone?

Administer immediately before bedtime.

Mechanism of action of Zopiclone:

It is similar in pharmacological characteristics to benzodiazepines.
It is a cyclopyrrolone-derived drug. It decreases sleep latency, reduces nocturnal awakenings and prolongs sleep.

The drug accounts for 45%.Protein-bound

It isMetabolizedThe liver is able to remove inactive metabolites via CYP3A4 or CYP2C8.

It has been abioavailability77% to 94% for the elderly.

Eliminating half-lifeThe duration of the drug is approximately 5 hours. It can be increased by up to 7 hours for the elderly and 12 hours for patients with liver disease.

It takes less than a minute to reach the peak serum concentration.Patients with hepatic impairment may experience delays of up to 2 hours. This is a difference of 3.5 hours.

It is mostly excreted in urine (75%) & feces (16%)

International Brands of Zopiclone: