VALIUM 10 mg / 2 ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Valium 10mg/2ml Injectable Solution

Diazepam

Read all of this leaflet carefully before you start using 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 pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Valium and what is it used for

Valium contains the active substance diazepam, which belongs to a group of medicines called benzodiazepines.

Diazepam has a calming effect, sedative, muscle relaxant, and anticonvulsant effects.

Doctors prescribe Valium to people who have moderate or severe agitation, anxiety, or mental tension. Benzodiazepines are only indicated for the treatment of intense disorders that limit activity or subject to significant stress.

Doctors also prescribe Valium as preoperative medication for basal sedation in patients with anxiety or tension, induction of anesthesia, and sedation prior to diagnostic, surgical, and endoscopic procedures (cardiac catheterization).

For patients with alcohol withdrawal syndrome for relief of excitement, panic, tremors, and hallucinations (delirium tremens).

For the acute treatment of status epilepticus (single or repeated epileptic seizures that persist for a sufficient time to potentially produce neurological damage), severe convulsions, tetanus (a disease that causes muscle spasms), in gynecology in pre-eclampsia or eclampsia (convulsions due to a sudden and unexpected increase in blood pressure before childbirth or during pregnancy) as a second line of treatment (if magnesium sulfate is not available or if seizures continue despite the administration of magnesium sulfate). The doctor will assess the possible risk to the fetus versus the therapeutic benefit for the mother.

Valium is also prescribed by doctors for the treatment of muscle spasms due to local trauma (injury, inflammation) and other conditions related to cerebral palsy (a group of disorders that affect a person's ability to move, balance, and posture), paraplegia (paralysis of the lower half of the body, affecting both legs), and the stiff person syndrome, including tetanus.

2. What you need to know before you start using Valium

Do not use Valium

• If you are allergic to diazepam or any of the other ingredients of this medicine (listed in section 6).
• If you are allergic (hypersensitive) to other medicines in the benzodiazepine group.
• If you have breathing difficulties related or not to sleepfor a long time.
• If you have a disease called "myasthenia gravis", which is characterized by muscle weakness and fatigue.
• If you have severe respiratory problems (severe respiratory failure).
• If you have severe liver problems (severe liver failure).
• If you are addicted to drugs or alcohol, you should not use Valium unless your doctor has formally indicated it.

This medicine is not recommended for the primary treatment of psychotic disorders (severe mental disorders that cause abnormal ideas and perceptions), nor should it be used as the only treatment in patients with depression, alone or associated with anxiety.

If you have any doubts about this, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Valium

• If you have any heart, liver, or kidney disease
• If you have breathing difficulties
• If you have severe muscle weakness
• If you have other diseases
• If you have allergies
• If you have a history of or problems with drug or central nervous system depressant dependence, including alcohol
• If you have other diseases

Your doctor will decide to use a lower dose of Valium or not to use it at all.

In patients with depression, Valium only acts on the anxious component, so it does not constitute a treatment for depression itself and may eventually unmask some signs of it (suicide risk).

If you are epileptic and are undergoing long-term treatment with Valium, it is not recommended to use the benzodiazepine antagonist Anexate (flumazenil) to reverse the effect of Valium, as seizures may appear.

Your doctor will pay special attention to the high risk associated if you are an elderly patient or are very debilitated.

Children

The duration of treatment should be as short as possible.

Elderly patients

If you are an elderly patient, your doctor will administer a lower dose. The pharmacological effects of benzodiazepines in elderly patients seem to be greater than in the younger population.

Other medicines and Valium

Use of Valium with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine. This is extremely important because when taking more than one medicine at the same time, its effect can be enhanced or weakened. For example, tranquilizers, sleep inducers, and similar medications act on the brain and nerves and can reinforce the effect of Valium.

Cimetidine, ketoconazole, fluconazole, voriconazole, fluvoxamine, fluoxetine, hormonal contraceptives, disulfiram, isoniazid, diltiazem, idelalisib, modafinil, armodafinil, esomeprazole, and omeprazole temporarily increase the sedative effect of Valium, increasing the risk of drowsiness. The same happens with grapefruit juice.

On the other hand, medications such as rifampicin and carbamazepine produce a decrease in the effects of Valium.

Also, the metabolism of phenytoin may be affected if it is being treated with Valium, so if you are using this medication, your doctor will adjust the doses of the same.

The sedative effect and cardiopulmonary depression can be increased when combining Valium with other central nervous system depressants, which can cause coma or death.

Xanthines such as theophylline and caffeine oppose the sedative effects of Valium.

Therefore, you should not use Valium with any other medication unless your doctor has allowed it.

If you need more information, consult your doctor or pharmacist.

Using Valium with food, drinks, and alcohol

Alcoholic beverages increase the sedative effects of Valium, so you should avoid using alcoholic beverages during treatment. If you need additional information, consult your doctor.

Do not take diazepam in combination with grapefruit juice, as it can increase the levels of diazepam in your body.

Risk of dependence

The use of benzodiazepines and benzodiazepine-like drugs can lead to physical and psychological dependence. This occurs mainly after uninterrupted use of the medication for a long time. To minimize the risk of dependence, the following precautions should be taken into account:

• The use of benzodiazepines will only be done under medical prescription (never because they have been effective in other patients), and never advise them to other people.
• Once dependence has developed, your doctor will give you instructions to follow and apply the corresponding treatment.
• Strictly follow your doctor's instructions.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

If, for strict medical necessity, Valium is administered before or during childbirth, the newborn may experience hypothermia (abnormally low body temperature), weakness, hypotension, and breathing difficulties. Similarly, cases of withdrawal syndrome have been reported in newborns.

Benzodiazepines pass into breast milk, so you should consult your doctor about the use or not of Valium while breastfeeding.

Driving and using machines

Do not drive or operate tools or machines because this medication can cause sedation, amnesia, difficulty concentrating, and muscle weakness, which can negatively affect the ability to drive vehicles or operate machinery. The doctor must decide when these activities can be resumed. This effect is increased if you have also consumed alcohol.

Valium contains ethanol, benzyl alcohol, benzoic acid, sodium benzoate, and propylene glycol

This medication contains 8.5% ethanol (alcohol), which corresponds to an amount of 170.5 mg per dose, equivalent to 4.3 ml of beer or 1.8 ml of wine.

This medication is harmful to people who suffer from alcoholism.

The alcohol content should be taken into account in the case of pregnant or breastfeeding women, children, and high-risk groups, such as patients with liver or epilepsy diseases.

This medication contains 31.4 mg of benzyl alcohol in each 2 ml ampoule, equivalent to 15.7 mg/1 ml.

Benzyl alcohol can cause allergic reactions.

Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol can accumulate in your body and cause adverse effects (metabolic acidosis).

Consult your doctor or pharmacist if you have liver or kidney disease. This is because large amounts of benzyl alcohol can accumulate in the body and cause adverse effects (metabolic acidosis).

Benzyl alcohol has been linked to the risk of serious adverse effects, including respiratory problems ("gasping syndrome") in children.

Do not administer this medication to your newborn (up to 4 weeks of age) unless your doctor has recommended it.

This medication should not be used for more than one week in children under 3 years of age unless your doctor or pharmacist indicates it.

This medication contains 5 mg of benzoic acid and 95 mg of sodium benzoate in each 2 ml ampoule.

Benzoic acid and sodium benzoate may increase the risk of jaundice (yellowish color of the skin and eyes) in newborns (up to 4 weeks of age).

This medication contains 828 mg of propylene glycol in each 2 ml ampoule, equivalent to 414 mg/1 ml.

If you are pregnant or breastfeeding, do not take this medication unless your doctor has recommended it. Your doctor may perform additional checks while you are taking this medication.

If you have liver or kidney failure, do not take this medication unless your doctor has recommended it. Your doctor may perform additional checks while you are taking this medication.

If the child is under 5 years of age, consult your doctor or pharmacist, especially if they have been given other medications that contain propylene glycol or alcohol.

3. How to use Valium

Follow your doctor's instructions for administering this medication exactly. If in doubt, consult your doctor or pharmacist again.

Valium is administered by deep intramuscular injection.

Valium can also be administered intravenously with the following electrolyte perfusion solutions: NaCl 0.9%, Dextrose 5.5%, or Dextrose 10%. The use of bags and perfusion equipment containing PVC should be avoided when administering the medication(see section 6).

If you think the effect of Valium is too strong or too weak, tell your doctor or pharmacist.

Your doctor will adjust the dose to each patient. The doses will be lower in elderly patients or in debilitated patients and in patients with chronic respiratory disorders.

Your doctor will indicate the duration of treatment with Valium, which will be as short as possible.

If you use more Valium than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91. 562.04.20, indicating the medication and the amount ingested.

If you stop treatment with Valium

After withdrawal of treatment, the previous symptoms may appear transiently (although more accentuated), it is recommended to gradually decrease the dose until the definitive suppression of treatment.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

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

If you think any of the side effects you are suffering from is serious or if you notice any side effect not mentioned in this leaflet, tell your doctor or pharmacist.

Most patients tolerate Valium well, but the most frequent side effects, which occur especially at the beginning of treatment, are fatigue, muscle weakness, and drowsiness.

Occasionally, other side effects have been described, such as confusion, decreased alertness, loss of sensitivity, dizziness, affective disorders, emotional and mood changes, constipation, depression, diplopia (double vision), ataxia (inability to coordinate voluntary muscle movements), difficulty articulating words, digestive changes, alteration of heart rhythm, headache, hypotension, circulatory changes, changes in libido (sexual appetite), nausea, dry mouth or hypersalivation (exaggerated salivary secretion), incontinence or urinary retention, skin rashes, stuttering, tremors, vertigo, and blurred vision. The most frequent skin reactions are rash (skin inflammation), urticaria (red patches), and pruritus (itching or uncomfortable skin irritation that causes the desire to scratch the affected area).

Very rarely, increased transaminases and alkaline phosphatase, jaundice, and cardiac arrest have been reported.

An increased risk of falls and fractures has been observed in elderly patients and in patients taking other sedative medications (including alcoholic beverages) at the same time.

Cardiac failure, respiratory depression, including respiratory failure, may occur.

It is known that when benzodiazepines are used, behavioral side effects such as restlessness, disorientation, agitation, irritability, delirium (incoherence of ideas), outbursts of rage, aggression, nervousness, hostility, anxiety, nightmares, abnormal dreams, hallucinations, psychosis (loss of contact with reality), hyperactivity, or inappropriate behavior can occur. These reactions are more frequent in the elderly and in children. If you experience these effects, you should stop treatment and contact your doctor immediately.

Furthermore, the use of benzodiazepines can lead to dependence, mainly when the medication is taken continuously for a long time. It is not recommended to abruptly stop the medication, always following the doctor's instructions.

Anterograde amnesia (difficulty remembering recent events) may appear at normal doses, the risk increases when the dose is increased. Amnestic effects may be associated with behavioral changes.

If you notice any other reaction not described in this leaflet, consult your doctor or pharmacist.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es/. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Valium

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Store in the outer packaging.

Do not store at a temperature above 30°C.

Do not use Valium if it is stored incorrectly, as the content may become cloudy or separate into phases.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need in the SIGRE collection point at the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

It has been shown that during use, it presents physical and chemical stability for 24 hours at room temperature.

From a microbiological point of view, the medication should be used immediately. Otherwise, the time it is stored and the conditions prior to its use will be the responsibility of the user.

Do not mix or dilute with other solutions or medications in the syringe or perfusion bottle.

6. Container Content and Additional Information

Valium Composition

• The active ingredient is diazepam. Each 2 ml ampoule contains 10 mg of diazepam.
• The other components are ethanol, benzyl alcohol, propylene glycol, sodium hydroxide, benzoic acid (E-210), sodium benzoate (E-211), and water for injection.

Product Appearance and Container Content

Valium is presented as an injectable solution in 2 ml ampoules. It is available in packs of 5 or 50 ampoules (clinical packaging).

Marketing Authorization Holder and Manufacturer

Holder:

Atnahs Pharma Netherlands B.V.

Copenhagen Towers

Ørestads Boulevard 108, 5.tv

DK-2300 København S

Denmark

Manufacturers:

Roche Farma, S.A.

C/ Eratóstenes, 19

Getafe

28906 Madrid

or

CENEXI SAS

Rue Marcel et Jacques Gaucher, 52

Fontenay Sous Bois F-94120 - France

Date of Last Revision of this Prospectus: May 2021

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

The dose should be individualized based on the needs of each individual and the smallest effective amount should be administered, especially in children, elderly patients, and debilitated individuals or those with liver disease or low serum albumin levels.

Moderate to Severe Anxiety States:The dose for adults is 2 to 10 mg intramuscularly or intravenously, repeated every 3-4 hours if necessary. The recommended dose in elderly patients and patients with renal and/or hepatic insufficiency is the smallest effective amount possible.

Patients with Alcohol Withdrawal:10 mg intramuscularly or intravenously. If necessary, 5-10 mg every 3-4 hours (Alternative regimen: 0.1-0.2 mg/kg intravenously every 8 hours, until symptoms cease). Then oral treatment.

As Premedication:10-20 mg intramuscularly, one hour before inducing anesthesia. Children: 0.1-0.2 mg/kg intramuscularly.

For Anesthetic Induction:0.2-0.5 mg/kg intravenously.

Pre-Intervention Sedation:10-20 mg intravenously (5 mg initially and 2.5 mg every 30 seconds until the eyelids drop to half-pupil). In obese patients, 30 mg intravenously; children: 0.1-0.2 mg/kg intravenously.

In Status Epilepticus:0.15-0.25 mg/kg intravenously, repeated at 10-15 minute intervals, if necessary, or by continuous infusion. (Maximum dose: 3 mg/kg in 24 hours).

Tetanus:0.1-0.3 mg/kg body weight should be administered intravenously at 1-4 hour intervals. Another possibility is continuous infusion or through a gastric tube (3-4 mg/kg body weight in 24 hours).

Preeclampsia and Eclampsia:In case of convulsion, or if there is a risk of convulsion, and magnesium sulfate is not available, administer 10-20 mg by intravenous injection. If additional doses are required, they can be administered, both by intravenous injection and by continuous intravenous infusion, up to a maximum of 100 mg in 24 hours. The dose of 100 mg is the total dose that can be administered in 24 hours, this dose should not be administered as a single intravenous injection but as a series of slow intravenous injections or as a continuous intravenous infusion. If epileptic seizures continue despite the administration of magnesium sulfate, Valium can be administered at a dose of 5-10 mg by intravenous injection.

In Muscle Spasms:5 to 10 mg intramuscularly or intravenously, repeatable if necessary every 3-4 hours.

Administration Method

Intramuscular injection should be deep.

Intravenous injection should always be administered very slowly (approximately 0.5-1 ml per minute) in large-caliber vessels. Excessively rapid administration can lead to apnea. It is advisable to have a respiratory assistance system available when using the intravenous route. Intra-arterial injection or extravasation should be avoided at all costs due to the possibility of vascular alterations.

Valium can be administered with the following electrolytic perfusion solutions: NaCl 0.9%, Dextrose 5.5%, or Dextrose 10%.

It has been shown that during use, it presents physical and chemical stability for 24 hours at room temperature.

From a microbiological point of view, the medication should be used immediately. Otherwise, the storage time and conditions prior to use will be the responsibility of the user.

It should not be mixed or diluted with other solutions or medications in the syringe or infusion bottle.

There is evidence that diazepam can be adsorbed by plastic perfusion bags and perfusion equipment containing PVC. This adsorption leads to a decrease in the concentration of diazepam by 50% or more, especially when prepared perfusion bags are stored for 24 hours or more in warm environmental conditions or when long perfusion tubes or low perfusion speeds are used. The use of bags and perfusion equipment containing PVC should be avoided when administering diazepam. Care should be taken when switching between PVC-containing bags and equipment and those that do not contain PVC.

In any case, after the cessation of acute symptoms, if continued treatment is necessary, it will be done orally.