Micropam

Patient Information Leaflet: Information for the User

MICROPAM 5 mg/2.5 ml rectal solution, 10 mg/2.5 ml rectal solution

Diazepam
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What MICROPAM is and what it is used for
2. What you need to know before using MICROPAM
3. How to use MICROPAM
4. Possible side effects
5. How to store MICROPAM
6. Contents of the pack and other information

1. What MICROPAM is and what it is used for

MICROPAM contains the active substance diazepam, which belongs to a group of medicines called benzodiazepines.
This medicine is indicated:

• as an anticonvulsant for the treatment of seizures, including febrile seizures in children, characterized by rapid and involuntary muscle contractions;
• as a sedative prior to diagnostic procedures and interventions.

2. What you should know before using MICROPAM

Do not use MICROPAM

• if you are allergic to diazepam, to other similar medicines (benzodiazepines), or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer from myasthenia gravis, a disease causing muscle weakness and fatigue;
• if you have severe breathing problems (severe respiratory insufficiency);
• if you have severe liver problems (severe hepatic insufficiency);
• if you have breathing difficulties during sleep (sleep apnoea syndrome);
• if you are pregnant or breastfeeding (See section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before using MICROPAM.
Avoid using this medicine if you have an addiction to alcohol or to medicines that depress the central nervous system, as concomitant use could enhance the clinical effects of diazepam and increase the risk of serious breathing and heart problems (respiratory and cardiovascular depression) (See section “Other medicines and MICROPAM”).
Use this medicine with caution and always under medical supervision in the following cases:

• if you are elderly or debilitated (see section 3 “How to use MICROPAM – Use in the elderly”). Your doctor may decide to reduce the dose;
• if you are elderly, as you may be at increased risk of falls and hip fractures;
• if you have reduced blood flow to the brain (arteriosclerosis). Your doctor may decide to adjust the dose;
• if you have heart or lung problems (cardiorespiratory insufficiency, chronic respiratory insufficiency). Your doctor may decide to reduce the dose;
• if you have previously abused alcohol or drugs;
• if you suffer from liver problems, especially chronic hepatopathy. In this case, your doctor will reduce the dose;
• if you suffer from kidney problems (renal insufficiency);
• if you suffer from depression or anxiety associated with depression. Benzodiazepines should not be used alone to treat depression or anxiety related to depression, as suicidal thoughts may occur in such patients.

This medicine is not indicated:

• if you suffer from liver problems (severe, acute or chronic hepatic insufficiency, see section “Do not use MICROPAM”);
• as first-line treatment for mental illnesses (psychotic disorders).

The use of this medicine may cause a slight drop in blood pressure or breathing difficulties (transient respiratory impairment). Therefore, emergency measures to support respiration and circulation should be readily available.
Tolerance: After repeated use of this medicine for several weeks, its effectiveness may decrease (tolerance). If after a few weeks you feel the medicine is not working as well as it did at the beginning of treatment, consult your doctor.
Dependence: When taking this medicine, there is a risk of dependence, meaning the need to continue using the medicine. The risk increases with dose and duration of treatment. The risk is higher if you have previously abused drugs or alcohol. If you develop dependence, consult your doctor. You must avoid stopping treatment abruptly, as withdrawal symptoms may occur (see also section: “If you stop taking MICROPAM”).
Withdrawal: When you stop taking MICROPAM, you may experience withdrawal symptoms or a syndrome consisting of a worsening of the symptoms that led to treatment (see section “If you stop taking MICROPAM”). To minimize these symptoms, it is recommended to gradually reduce the dose. Withdrawal effects may also occur even if your doctor switches you from this medicine to another similar one.
Sudden discontinuation of treatment may cause epileptic seizures or convulsions if:

• you have previously suffered from convulsive seizures or suffer from epilepsy;
• you have previously abused alcohol or drugs.

Amnesia: This medicine may cause memory problems (anterograde amnesia – memory loss), especially when high doses are used. These effects generally appear several hours after administration; therefore, to reduce this risk, ensure uninterrupted sleep of 7–8 hours. These effects may be associated with inappropriate behaviour.
Behavioural reactions: If you experience behavioural disturbances such as: restlessness, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, psychosis (a psychiatric disorder indicating severe disturbance of the individual’s mental balance), or changes in behaviour, consult your doctor and stop taking the medicine immediately (see section 4. Possible side effects). Such reactions are more frequent in children and the elderly.
If you take this medicine for prolonged periods, regular blood tests and liver function checks are recommended.
Duration of treatment: Treatment duration should be as short as possible (see section “How to use MICROPAM”). Your doctor should monitor you after 4 weeks of treatment and periodically thereafter to assess your health status. The recommended duration is 8 to 12 weeks, including the tapering period. Your doctor may decide to extend treatment only after appropriate evaluations.
Your doctor will inform you about the limited duration of treatment and the need for gradual dose reduction.
Upon stopping treatment, you may experience a return of your original symptoms (rebound symptoms), possibly accompanied by other reactions such as mood changes, anxiety, sleep disturbances, and restlessness. Symptoms may reappear especially between doses, particularly if high doses are used.
If this occurs, inform your doctor. In case of prolonged treatment, your doctor should perform liver checks and blood tests.
Children
MICROPAM should be used in children only when absolutely necessary, and treatment duration should be as short as possible. If repeated administration is required in a child, breathing should be monitored by the doctor.
As safety and efficacy have not been established in children under 6 months of age, MICROPAM should be used with extreme caution in children under 6 months and only if no alternative therapeutic options are available.
Children under three months of age should only be treated with MICROPAM in a hospital setting (see section “How to use MICROPAM”).
Other medicines and MICROPAM
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Pay special attention and inform your doctor if you are taking the following medicines, as their concomitant use with MICROPAM may enhance the effects of MICROPAM and increase the risk of serious breathing and heart problems (respiratory and cardiovascular depression):

• antipsychotics (neuroleptics) and antidepressants (fluoxetine), used to treat mental disorders;
• anxiolytics/sedatives, used to treat anxiety;
• hypnotics, medicines used to promote sleep;
• anticonvulsants, such as valproic acid, used for epilepsy;
• sedating antihistamines, used to treat allergies;
• anaesthetics for general anaesthesia, such as ketamine, used during surgical procedures;
• some strong painkillers (narcotic analgesics, such as opioids) which may cause increased feelings of well-being when taken with MICROPAM. This may increase your desire to continue taking these medicines (dependence).

Concomitant use of MICROPAM and opioids (strong analgesics, medicines for opioid dependence substitution therapy, and some cough medicines) increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. Therefore, concomitant use should only be considered when other treatment options are not feasible.
However, if your doctor prescribes MICROPAM together with opioids, the dose and duration of concomitant treatment must be limited by the doctor.
Inform your doctor about all opioid medicines you are taking and follow the doctor’s dosage recommendations carefully. It may be helpful to inform family or friends to watch for the symptoms listed above.
Contact your doctor if you experience such symptoms.
Inform your doctor if you are taking any of the following medicines:

• theophylline, used for asthma;
• muscle relaxants used to relax muscles before surgery (such as suxamethonium, tubocurarine);
• corticosteroids, used to treat inflammation and allergies;
• cimetidine, omeprazole, esomeprazole used to treat stomach lesions (ulcers);
• isoniazid, used to treat tuberculosis;
• disulfiram, used in the treatment of alcoholism;
• oral contraceptives, used to prevent pregnancy;
• cisapride, used for stomach and intestinal problems; levodopa, used to treat Parkinson’s disease.

During treatment with this medicine, avoid taking:

• phenobarbital and carbamazepine, used to treat seizures;
• clozapine, phenytoin, used to treat certain mental disorders;
• rifampicin, an antibiotic;
• antiviral agents (atazanavir, ritonavir, delavirdine, efavirenz, indinavir, nelfinavir, saquinavir) used to treat viral infections;
• azoles (fluconazole, itraconazole, ketoconazole, voriconazole), used to treat fungal infections;
• fluvoxamine, used to treat depression;
• oxazepam and temazepam, used to treat anxiety.

MICROPAM with food, drinks and alcohol
During treatment with this medicine, avoid consuming grapefruit juice.
Avoid alcohol consumption during treatment with this medicine, as it may increase the sedative effect of the medicine. This negatively affects your ability to drive vehicles and operate machinery.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Do not use this medicine during pregnancy, except in cases of absolute necessity (serious indications) and under direct medical supervision.
If, due to serious health reasons, your doctor considers it necessary for you to take MICROPAM during the last trimester of pregnancy or during labour, your baby may experience low body temperature, loss of muscle tone, irregular heart rate, poor sucking, and breathing difficulties.
If MICROPAM has been taken regularly during the late stages of pregnancy, your baby may develop physical dependence and withdrawal symptoms.
Consult your doctor or pharmacist before using any medicine.
Breastfeeding
Do not use this medicine if you are breastfeeding, as diazepam passes into breast milk.
Fertility
If you are planning a pregnancy and are being treated with this medicine, inform your doctor, as treatment with MICROPAM must be discontinued.
Driving and using machines
The use of MICROPAM may significantly impair your ability to drive vehicles and operate machinery, as it may affect your motor skills and cause symptoms such as: tremor, drowsiness, memory loss (amnesia), impaired concentration, and fatigue (see section “Possible side effects”). These effects may occur immediately after starting treatment and may persist for several days after stopping treatment. If this happens, avoid driving or operating machinery.
MICROPAM contains benzyl alcohol, benzoic acid, sodium benzoate and propylene glycol
This medicine contains 37.5 mg of benzyl alcohol per single-dose container, equivalent to 15 mg/ml. Benzyl alcohol has been associated with a risk of serious adverse reactions, including breathing problems (gasping syndrome), in young children.
Do not use for more than one week in young children (under 3 years of age) unless otherwise recommended by a doctor or pharmacist. Consult your doctor or pharmacist if you have liver or kidney disease, are pregnant, or are breastfeeding. Benzyl alcohol may cause mild local irritation.
This medicine contains 1000 mg of propylene glycol per single-dose container, equivalent to 400 mg/ml.
If the child is under 5 years of age, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol. If you are pregnant or breastfeeding, do not take this medicine unless otherwise recommended by your doctor. Your doctor may perform additional monitoring during treatment. If you suffer from liver or kidney disease, do not take this medicine unless otherwise recommended by your doctor. Your doctor may perform additional monitoring during treatment.
This medicine contains 2.5 mg of benzoic acid and 122.5 mg of sodium benzoate per single-dose container, equivalent to 1 mg/ml and 49 mg/ml, respectively. Benzoic acid and sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks of age) (see section “Pregnancy and breastfeeding”). Benzoic acid and sodium benzoate may cause local irritation.

3. How to use MICROPAM

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
This medicine must be administered rectally (rectal route). Do not stop treatment without first consulting your doctor (see the section "If you stop treatment with MICROPAM" and the section "Warnings and precautions").

Use in adults: The recommended dose is 10 mg, which may be repeated if necessary.

Use in children
This medicine should be used in children only after careful medical evaluation of the actual need; therefore, the use of MICROPAM should be limited to the previously described therapeutic indications. The duration of treatment should be as short as possible.
Children under 3 years of age: The recommended dose is 5 mg.
Children over 3 years of age: The recommended dose is 10 mg.
In case of repeated administration in children, the doctor will monitor respiratory function.
In children under one year of age, the doctor may decide to prescribe diazepam to prevent seizures caused by febrile conditions. The usual dose is 0.5–1 mg/kg.
Children under three months of age should only be treated with diazepam in a hospital setting.
In children under 6 months of age, Micropam must be used with extreme caution and only if no alternative therapeutic options are available (see section "Warnings and precautions").

Instructions for use:

• Place the child with their abdomen on your knees, buttocks raised.
• Remove the closure cap from the single-dose container and lubricate the nozzle.
• Insert the nozzle into the anus. In children under 3 years of age, it is recommended to insert the nozzle halfway along its length; in children over 3 years of age and in adults, insert the nozzle fully.
• Important: To empty the single-dose container, the nozzle must be tilted downward relative to the ampoule of the container.
• When the single-dose container is empty, withdraw the nozzle while continuing to apply pressure to the ampoule of the container.
• Keep the child in the same position and press their buttocks together for several minutes to prevent leakage of liquid.

Duration of treatment
The duration of treatment should be as short as possible and under direct medical supervision. In general, treatment should not last longer than 8–12 weeks, including the period of discontinuation (see section "Warnings and precautions – Duration of treatment"). Extension of therapy should not occur without reassessment by the doctor.

Use in elderly and debilitated patients
In elderly patients and those with lung, kidney, or liver problems (chronic pulmonary insufficiency, chronic renal and hepatic dysfunction), a reduced dose should be administered.
Doses used in elderly patients should not exceed half of the normally recommended doses. If you have kidney problems, your doctor will assess your condition. Generally, in cases of reduced kidney function, your doctor will evaluate whether a dose adjustment is necessary.

If you use more MICROPAM than you should
If you (or someone else) have used an excessive dose of MICROPAM, or if you think a child may have taken this medicine, contact your doctor immediately or go to the nearest hospital emergency department.
In case of overdose, consider the possibility that other substances may have been taken, especially in cases of attempted suicide. Symptoms of overdose are more pronounced if you have used drugs or consumed alcoholic beverages.

Symptoms
An overdose may cause marked depression of the central nervous system, with symptoms such as loss of sensory and intellectual abilities (obnubilation), mental confusion, and excessive drowsiness (lethargy).
In more severe cases, muscle problems (ataxia, hypotonia), low blood pressure (hypotension), breathing difficulties (respiratory depression), coma, and death may occur.

Treatment
Treatment of overdose includes:

• Induction of vomiting within one hour after taking the medicine, if consciousness is preserved;
• Gastric lavage with protection of the airways if consciousness is impaired;
• Administration of activated charcoal;
• Administration of an antidote (flumazenil).

Take this leaflet and the medicine container with you to the hospital or to the doctor so they know which medicine has been taken.

If you forget to use MICROPAM
If you forget to take a dose, take it as soon as you remember, unless it is almost time for the next dose. Do not take a double dose to make up for the missed dose.

If you stop treatment with MICROPAM
Do not stop treatment with MICROPAM suddenly or without prior agreement with your doctor, as withdrawal symptoms may occur.
If your doctor decides to discontinue treatment, they will gradually reduce your dose to minimize withdrawal symptoms such as headache (cephalalgia), muscle pain, severe anxiety, tension, restlessness, confusion, and irritability.
In severe cases of withdrawal, derealization (feeling that things are not real), depersonalization (feeling of detachment from the surrounding environment), intolerance to sound (hyperacusis), numbness and tingling in hands and feet, sensitivity to light, noise, and physical contact, hallucinations (seeing or hearing things that do not exist), or epileptic seizures may occur (see section "Warnings and precautions").
Treatment must be discontinued gradually; otherwise, the symptoms for which you were being treated may reappear more intensely than before (rebound insomnia and anxiety). The risk of developing these symptoms is greater when stopping MICROPAM abruptly. You may also experience mood changes, anxiety, restlessness, and sleep disturbances (see section "Warnings and precautions").

If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Contact your doctor immediately if you experience:

• depression and mental disorders such as restlessness, agitation, irritability, aggression, delirium, rage, nightmares, hallucinations (seeing and hearing things that do not exist), psychosis (a serious mental condition in which a person loses touch with reality and the ability to think and judge clearly), changes in behaviour. If any of these side effects occur, treatment must be stopped. These reactions are more frequent in children and elderly patients.

In addition, you may experience the following side effects, which usually disappear during continued treatment:
Very common (may affect more than 1 in 10 people)

• drowsiness.

Common (may affect up to 1 in 10 people)

• confusion;
• difficulty controlling movements (ataxia), impaired motor function, tremor;
• fatigue, withdrawal symptoms (anxiety, panic, palpitations, sweating, tremor, gastrointestinal disorders, irritability, aggression, disturbed sensory perception, muscle spasms, general malaise, loss of appetite, paranoid psychosis, delirium, and epileptic seizures) (see section “Warnings and precautions”).

Uncommon (may affect up to 1 in 100 people)

• memory loss (anterograde amnesia) (see section “Warnings and precautions”), difficulty concentrating, balance disorders, dizziness, headache (cephalalgia), slurred speech;
• difficulty breathing (respiratory depression);
• stomach and intestinal problems (nausea, vomiting, constipation, diarrhoea), increased salivation;
• allergic skin reactions (itching, erythema, rash);
• a disease causing muscle weakness and fatigue (myasthenia).

Rare (may affect up to 1 in 1,000 people)

• psychiatric and paradoxical reactions such as excitement, restlessness, agitation, irritability, aggression, delirium, anger, hallucinations, psychosis, memory loss, nightmares, inappropriate behaviour, and other adverse effects on behaviour (see section “Warnings and precautions”);
• emotional blunting, reduced alertness, and depression;
• unconsciousness, insomnia, speech disorder (dysarthria);
• reduced heart rate (bradycardia), heart problems (heart failure), including cardiac arrest;
• low blood pressure (hypotension), fainting associated with loss of consciousness (syncope);
• respiratory arrest, increased mucus secretion (increased bronchial secretion) (see section “Warnings and precautions”);
• dry mouth, increased appetite;
• yellowing of the skin and whites of the eyes (jaundice), changes in results of certain blood tests (increased ALT, AST, alkaline phosphatase);
• reduced urine output (urinary retention), difficulty holding urine (incontinence);
• breast enlargement in men (gynaecomastia), impotence, increased or decreased sexual desire (libido).

Very rare (may affect up to 1 in 10,000 people)

• reduced number of white blood cells (leucopenia);
• severe allergic reaction (anaphylaxis);
• changes in results of certain blood tests (increased transaminases).

Frequency not known (cannot be estimated from the available data):
transient vision problems such as blurred vision, double vision (diplopia), rhythmic, involuntary, oscillating eye movements (nystagmus).
Drowsiness, blunting of emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia, or double vision may occur mainly at the beginning of therapy.
Confusional states may occur in elderly patients at high doses.
The risk of falls and fractures is increased in patients taking sedatives concomitantly (including alcoholic beverages) and in elderly patients.
Increased salivary and bronchial secretion has been reported, particularly in children.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MICROPAM

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
After opening the aluminium sheet, the medicine must be used immediately.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What MICROPAM contains
MICROPAM 5 mg/2.5 ml rectal solution

• The active substance is diazepam. 2.5 ml of solution contain 5 mg of diazepam.
• The other components are: benzoic acid, purified water, benzyl alcohol, ethanol, propylene glycol, sodium benzoate.

MICROPAM 10 mg/2.5 ml rectal solution

• The active substance is diazepam. 2.5 ml of solution contain 10 mg of diazepam.
• The other components are: benzoic acid, purified water, benzyl alcohol, ethanol, propylene glycol, sodium benzoate.

Description of the appearance of MICROPAM and contents of the pack
One pack contains 4 single-dose containers, yellow, individually packaged in laminated aluminium sachets.
Marketing Authorisation Holder
Aurobindo Pharma (Italia) s.r.l., Via San Giuseppe 102, 21047 Saronno (VA).
Manufacturer
Pinewood Laboratories Ltd, Ballymacarbry, Clonmel, Co. Tipperary (Ireland)