DINIKET

Package leaflet: Information for the patient

Diniket 1mg/ml concentrate for solution for infusion

Isosorbide dinitrate
Please read all of 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 nurse.
• If you get any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What Diniket is and what it is used for

Diniket contains the active substance isosorbide dinitrate and belongs to a group of medicines called organic nitrates.
Organic nitrates work by dilating both venous and peripheral arterial blood vessels, thereby reducing the workload of the heart. They also act by dilating the blood vessels of the heart, thus increasing blood supply to the area in need.
Diniket is used to treat acute heart failure (a sudden heart problem that impairs blood circulation) and severe angina pectoris that does not respond to oral therapy. Angina usually manifests as a pressing, constricting pain in the chest, neck and/or left arm, caused by reduced blood flow to the heart walls.

2. What you need to know before using Diniket

Do not use Diniket

• if you are allergic to isosorbide dinitrate, to other nitrates, or to any of the other ingredients of this medicine (listed in section 6)
• if you have acute circulatory failure (shock, collapse)
• if you have very low blood pressure (systolic pressure < 90 mmHg)
• if you have reduced blood volume (hypovolemia)
• if you have conditions associated with increased pressure in the head (increased intracranial pressure)
• if you have suffered head trauma or cerebral hemorrhage
• if you have had severe impairment of heart function (cardiogenic shock)
• if your blood pressure drops significantly during a heart attack
• if you have narrowing of the heart valves (aortic or mitral valve stenosis) or a muscular heart disorder known as obstructive hypertrophic cardiomyopathy
• if you have inflammation of the pericardium, the sac surrounding the heart (constrictive pericarditis)
• if you have fluid accumulation in the pericardium that prevents the heart from functioning properly (cardiac tamponade)
• if you have fluid accumulation in the lungs (toxic pulmonary edema)
• if you suffer from severe anemia (reduction in red blood cells in the blood)
• if you have a disease of the eye causing increased intraocular pressure called closed-angle glaucoma
• if you are pregnant
• if you are breastfeeding
• in children
• if you are taking a medicine for erectile dysfunction belonging to the class of phosphodiesterase inhibitors such as sildenafil, tadalafil, or vardenafil (see section “Warnings and Precautions” and “Other medicines and Diniket”)
• if you are taking medicines used for pulmonary hypertension (such as riociguat, a soluble guanylate cyclase stimulator). See section “Other medicines and Diniket”.

If you are in any of the above situations, consult your doctor.
Warnings and precautions
Talk to your doctor or nurse before using Diniket.
Particular caution is required in the following conditions:

• If you have a heart condition with severe impairment of the heart's pumping function (heart attack with left ventricular failure)
• If you suffer from orthostatic syndrome, a condition causing low blood pressure upon standing
• If you suffer from severe liver insufficiency
• If your blood oxygenation is insufficient (hypoxemia) due to lung disease or reduced blood supply to the heart (ischemic heart failure).

If you are on maintenance treatment with isosorbide dinitrate, you must not use phosphodiesterase inhibitors such as sildenafil, vardenafil, or tadalafil for the treatment of erectile dysfunction.
Additionally, you must not stop treatment with isosorbide dinitrate to take phosphodiesterase inhibitors, due to the risk of angina attacks (episodes accompanied by chest tightness and pain) (see also sections "Do not use Diniket" and "Other medicines and Diniket").
You must not use Diniket if you have taken phosphodiesterase inhibitors (used to treat erectile dysfunction, e.g., sildenafil, vardenafil, tadalafil) within the last 24 hours (48 hours for tadalafil).
Other medicines and Diniket
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
While being treated with Diniket, do not take:

• phosphodiesterase inhibitors such as sildenafil, tadalafil, or vardenafil used for erectile dysfunction. Using Diniket with these medicines could cause blood pressure to drop to dangerously low levels.

Inform your doctor if you are taking:

• medicines used to lower blood pressure (e.g., beta-blockers, calcium antagonists, vasodilators, ACE inhibitors, monoamine oxidase inhibitors), as they could cause a further drop in blood pressure.
• medicines used to treat depression (tricyclic antidepressants) or other mental illnesses (neuroleptics). These may also cause a further drop in blood pressure.
• medicines used to treat migraine (dihydroergotamine). If taken together, excessive increase in blood pressure may occur.
• medicines containing sapropterin (used, for example, to treat a disease called phenylketonuria).
• medicines containing riociguat (used, for example, to treat pulmonary hypertension). If taken concomitantly with isosorbide dinitrate, they could cause a drop in blood pressure.
• phosphodiesterase inhibitors such as sildenafil, vardenafil, or tadalafil for erectile dysfunction. You must not take acute treatment with isosorbide dinitrate within 24 hours after taking sildenafil or vardenafil, or within 48 hours after taking tadalafil.

If any of these situations apply to you, discuss them with your doctor or nurse.
Diniket with food, drinks, and alcohol
Alcohol can enhance the blood pressure-lowering effect. Avoid consuming alcohol during treatment with Diniket.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, ask your doctor or nurse for advice before taking this medicine. Your doctor will decide whether you should take this medicine.
Pregnancy
During pregnancy, Diniket will be administered by your doctor only if strictly necessary and under continuous medical supervision.
Breastfeeding
Since the active ingredient of Diniket is excreted in breast milk and could cause problems in the newborn, inform your doctor if you are breastfeeding.
Fertility
There are no available data on the effect of isosorbide dinitrate on male fertility.
Driving and using machines
Diniket may affect your reaction ability to the extent that your ability to drive vehicles or operate machinery may be impaired. This effect is enhanced by alcohol (see section “Diniket with food, drinks, and alcohol”). Do not drive or operate machinery until you know how this medicine affects your ability to perform these activities.
Diniket contains sodium
This medicine contains 3.54 mg of sodium per ml or 35.4 mg of sodium (main component of table salt) per 10 ml vial. This corresponds to 1.8% of the maximum recommended daily dietary intake of sodium for an adult.

3. How to use Diniket

Diniket will be administered to you only in a hospital setting and under close medical supervision. Your doctor will decide the most appropriate dose for you. If you have any doubts, consult your doctor or nurse.
Diniket is a concentrate for intravenous infusion, which may be diluted before use (with saline solution, 5–30% glucose solution, Ringer's solution, or solutions containing albumin) or administered undiluted via an infusion pump.

Adults and elderly
The recommended dose ranges from 2 mg to 10 mg/hour.
During treatment, you will be monitored for several important parameters such as: heart rate (pulse), blood pressure, electrocardiogram (ECG), and urine output. This monitoring ensures that the medicine is working properly and that the dose you are receiving is appropriate for you.

Use in children
This medicine is not suitable for children. If you have further questions about the use of this medicine, consult your doctor or nurse.

If you receive more Diniket than you should
Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive too much or too little.
Possible symptoms of an overdose of Diniket include: a sharp drop in blood pressure, pallor, sweating, weak pulse, rapid heartbeat, dizziness when standing, headache, weakness, nausea, vomiting, and diarrhea.
An increase in pressure within the skull (intracranial pressure) may also occur, leading to symptoms of brain distress.
Cases of increased intracranial pressure, hemoglobin alteration (methemoglobinemia), and bluish discoloration of the lips, nails, and skin (cyanosis) have also been reported, resulting in rapid breathing (tachypnea), anxiety, loss of consciousness, and cardiac arrest. If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common: may affect more than 1 in 10 people

• headache

Common: may affect from 1 to 10 in 100 people

• confusion, dizziness, drowsiness
• increased heart rate
• sudden drop in blood pressure when standing up from a sitting or lying position (orthostatic hypotension)
• feeling weak (asthenia)

Uncommon: may affect from 1 to 10 in 1,000 people

• worsening of angina symptoms (e.g. chest pain)
• circulatory collapse sometimes with slowed heart rate and fainting (syncope)
• nausea
• vomiting
• allergic skin reactions (e.g. rash), redness

Very rare: may affect less than 1 in 10,000 people

• heartburn (pyrosis)
• sudden allergic reaction with possible swelling of arms, legs, ankles, lips, tongue and/or throat, and difficulty swallowing or breathing (angioedema)
• widespread rash with blisters and peeling of the skin, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome)

Not known: frequency cannot be estimated from the available data

• decrease in blood pressure (hypotension)
• erythema, superficial thickening of the skin with peeling (exfoliative dermatitis)

During treatment with Diniket, a decrease in oxygen levels in the blood (hypoxaemia) may occur.
Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national adverse reaction reporting system.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Diniket

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp".
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions when contained in the closed vial.
Once the vial has been opened, the medicine must be used immediately.
For the diluted solution: the medicine solution must be stored in the refrigerator and used within 24 hours.
Do not dispose of any medicine via wastewater or household waste. This will help protect the environment.

6. Package contents and other information

What Diniket contains

• The active substance is isosorbide dinitrate. One vial contains 10 mg of isosorbide dinitrate in 10 ml of sterile solution.
• The other components are sodium chloride, water for injections, hydrochloric acid, and sodium hydroxide for pH adjustment.

Description of the appearance of Diniket and package contents
Diniket is a concentrate for solution for infusion. It is a clear, colourless, and odourless solution.
Diniket 1 mg/ml is supplied in 10 ml glass vials.
Each pack contains 10 vials of 10 ml each.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Merus Labs Luxco II S.à.R.L.
26-28, rue Edward Steichen
L-2540 Luxembourg (Luxembourg)

Manufacturer
Aesica Pharmaceuticals GmbH
Alfred Nobel Strasse 10
D-40789, Monheim
Germany

The following information is intended exclusively for physicians or healthcare professionals:
Diniket may be administered only to hospitalised patients under continuous cardiovascular monitoring, either diluted in continuous drop-by-drop infusion using an automatic drop-counting device, or undiluted using an infusion pump.
Diniket must be diluted under aseptic conditions immediately after opening. The diluted solution must be used immediately.
Diniket is compatible with commonly used hospital infusion solutions such as 0.9% sodium chloride solution, 5–30% glucose solutions, Ringer's solution, and solutions containing albumin.
Since Diniket is supersaturated with the active substance, crystalline deposits may be observed if Diniket is used in undiluted form. If such crystals are observed, the solution should preferably not be used.
The recommended dosage of isosorbide dinitrate ranges between 2 and 10 mg/hour. This dosage must always be adjusted to the individual patient. The contents of the vials must be added to the infusion solution immediately before use; opened vials must be used immediately.

During infusion, the following parameters must be monitored:

• Arterial pressure, ensuring systolic values do not fall below 90 mmHg;
• Electrocardiogram, recorded including chest leads;
• Heart rate;
• Urine output (preferably monitored via indwelling catheter).

In practice, proceed as follows:

• Determine, based on the patient's clinical condition, the dosage in mg/hour to be administered.
• Determine the duration of administration at the chosen mg/hour dosage.
• Horizontally, at the chosen mg/hour dosage, identify in the table the administration duration equal to or immediately longer than the desired duration.
• Read in the corresponding column the number of Diniket vials (and corresponding volume in parentheses) to be used.
• Remove from an infusion bottle a volume of solution equal to that of the Diniket vials to be added.
• Add to the infusion bottle the required number of Diniket vials.
• Start the intravenous infusion, adjusting the infusion rate according to the corresponding drop rate in drops/minute (Table 1) or in ml/hour (Table 2).

Table 1: Drop rate per minute / infusion time for 250 ml

Table 2: Infusion rates in ml per hour/infusion time for 250 ml

Example: - desired dosage: 5 mg/hour

• administration duration: 7 hours (total dose of 35 mg)
• vials of Diniket required = 4, equal to 40 ml, to be replaced with an equal volume in the 250 ml bottle
• administer at an infusion rate of 31.3 ml/hour or 10-11 drops/minute.

Incompatibilities
Materials made of polyethylene (PE), polypropylene (PP), or polytetrafluoroethylene (PTFE) have been shown to be suitable for the infusion of Diniket. However, it has been observed that infusion materials made of polyvinyl chloride (PVC) or polyurethane (PU) cause a loss of the active substance due to an absorption process. If PVC and/or PU tubing is used, the patient's response to isosorbide dinitrate should be monitored, as dose adjustments may be necessary.
Diniket does not contain polyethylene glycol, ethanol, or potassium ions.
This medicinal product must not be mixed with other medicinal products.