Nuedexta - patient leaflet, side effects, dosage

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND

healthcare professionals who are expected to prescribe Nuedexta are provided with the following items:

• Summary of Product Characteristics (SmPC)
• Educational material for Healthcare Professionals (HCPs)
• Patient alert cards

The educational material for HCPs should assist them in the collection and assessment of relevant patient’s details on pre-existing co-morbidities and concomitant medications prior to initiating Nuedexta therapy. Furthermore, educational material for HCPs should provide information on the following safety concerns and on the actions needed to reduce the risks:

• Off-label use

Allergic reactions

Cardiac effects (QT prolongation) including pre-existing cardiovascular conditions and clinically significant electrolyte imbalances

Drug-drug interactions including involvement of CYP2D6 substrates and inhibitors

Serotonin syndrome

Co-administration of a strong CYP3A4 inhibitor

Drug misuse and abuse

The patient alert card should be provided to all patients with instructions to carry it on them at all times. The card should contain details to alert any HCP treating the patient that they are being treated with Nuedexta and of the potential for interaction once a patient is on treatment with Nuedexta and another treatment is added.

BOTTLE CARTON (60 hard capsules) – NUEDEXTA 15 mg/9 mg capsules

1. NAME OF THE MEDICINAL PRODUCT

NUEDEXTA 15 mg/9 mg hard capsules dextromethorphan / quinidine

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Jenson Pharmaceutical Services Limited Carradine House, 237 Regents Park Road N3 3LF London

United Kingdom

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/13/833/001

BOTTLE LABEL (60 hard capsules) – NUEDEXTA 15 mg/9 mg capsules

1. NAME OF THE MEDICINAL PRODUCT

NUEDEXTA 15 mg/9 mg hard capsules dextromethorphan / quinidine

EXP

9. SPECIAL STORAGE CONDITIONS

Jenson Pharmaceutical Services Limited Carradine House, 237 Regents Park Road N3 3LF London

United Kingdom

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/13/833/001

BOTTLE CARTON (60 hard capsules) – NUEDEXTA 23 mg/9 mg capsules

1. NAME OF THE MEDICINAL PRODUCT

NUEDEXTA 23 mg/9 mg hard capsules dextromethorphan / quinidine

EXP

9. SPECIAL STORAGE CONDITIONS

Jenson Pharmaceutical Services Limited Carradine House, 237 Regents Park Road N3 3LF London

United Kingdom

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/13/833/003

BOTTLE LABEL (60 hard capsules) – NUEDEXTA 23 mg/9 mg capsules 1. NAME OF THE MEDICINAL PRODUCT

NUEDEXTA 23 mg/9 mg hard capsules dextromethorphan / quinidine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Jenson Pharmaceutical Services Limited Carradine House, 237 Regents Park Road N3 3LF London

United Kingdom

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/13/833/003

OUTER CARTON – NUEDEXTA 15 mg/9 mg capsules: PACK OF 13 CAPSULES

1. NAME OF THE MEDICINAL PRODUCT

NUEDEXTA 15 mg/9 mg hard capsules dextromethorphan / quinidine

• 7. OTHER SPECIAL WARNING(S), IF NECESSARY

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Jenson Pharmaceutical Services Limited Carradine House, 237 Regents Park Road N3 3LF London

United Kingdom

BLISTER SLEEVE (13 hard capsules) – NUEDEXTA 15 mg/9 mg capsules 1. NAME OF THE MEDICINAL PRODUCT

NUEDEXTA 15 mg/9 mg hard capsules dextromethorphan / quinidine

Day 9

Day 10

Package leaflet: information for the user

NUEDEXTA 15 mg/9 mg hard capsules

NUEDEXTA 23 mg/9 mg hard capsules dextromethorphan / quinidine

Read all of this leaflet carefully before you start taking 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 signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not

listed in this leaflet.

What is in this leaflet

What NUEDEXTA is and what it is used for

What you need to know before you take NUEDEXTA

How to take NUEDEXTA

Possible side effects

How to store NUEDEXTA

Contents of the pack and other information

What NUEDEXTA is and what it is used for

NUEDEXTA is a combination of two active substances:

Dextromethorphan acts on the brain.

Quinidine increases the amount of dextromethorphan in your body, by blocking the breakdown

of dextromethorphan by the liver.

NUEDEXTA is used for

if you take a medicine called thioridazine, which is used for mental illness but can also affect

the heart.

• if you are taking, or have taken during the last two weeks, certain medicines for depression

called monoamine oxidase inhibitors (MAOIs), such as phenelzine and moclobemide.

Please ask your doctor if you are not sure, if any of the above applies to you.

Warnings and precautions

Talk to your doctor before and after taking NUEDEXTA if:

you or a family member currently have or have ever had any heart disease or problems. This medicine may cause changes in heart rhythm. If you have certain heart problems or are currently taking certain other medicines, NUEDEXTA may not be appropriate for you, or your doctor may want to monitor your heart activity when you start NUEDEXTA.

you experience symptoms such as palpitations or fainting, which may be a sign of heart problems.

you develop symptoms of an allergic reaction such as swelling of the throat or tongue, difficulty breathing, dizziness, fever, rash, or hives after taking this medicine.

you experience symptoms such as bruising, bleeding under the skin, nosebleeds and/or bleeding gums, as this may be a sign of low levels of blood cells called platelets (thrombocytopenia).

you experience symptoms, such as yellowing of the skin or eyes, dark urine, nausea or vomiting, loss of appetite, abdominal pain, and fever, as this may be a sign of drug-induced

hepatitis (liver inflammation).

you have a condition called myasthenia gravis (an autoimmune neuro causes muscle weakness and fatigability).

you have problems with your liver or kidney. Depending on the severity of your problems, your doctor may carefully consider whether this medicine is suitable for you and monitor you more closely for potential side effects.

you have a tendency to have falls. This medicine may cause dizziness and your doctor might need to discuss appropriate precautions to reduce the r falls.

you have had at any time a serious condition called rotonin syndrome”, which can be caused by certain medicines e.g. antidepressants. Sympt of serotonin syndrome include agitation,

high blood pressure, restlessness, muscle spasms and twitching, high body temperature, excessive sweating, shivering, and tremor.

you have a history of drug abuse. Your doctor will monitor you closely for signs of NUEDEXTA misuse or abuse.

Stop taking NUEDEXTA and seek medical attention immediately if any of the above symptoms occur.

Children and adolescents

NUEDEXTA should not be used in children and adolescents below the age of 18 years.

NUEDEXTA

pharmacist if you are taking, have recently taken or might take any other

It is very important to tell your doctor if you are taking any of the medicines listed below, as these medicines should never be taken while you are taking NUEDEXTA:

• medicines containing quinidine, quinine, or mefloquine. These are medicines used to treat

malaria or heart rhythm problems,

• thioridazine, a medicine used in the treatment of schizophrenia and psychosis, that may affect

the heart,

• certain medicines for depression, called monoamine oxidase inhibitors (MAOIs- for example

phenelzine and moklobemide). Do not take NUEDEXTA if you have taken these antidepressants during the last two weeks and allow at least 14 days after stopping NUEDEXTA before starting an MAOI.

Please tell your doctor if you are taking any of the following medicines, as your doctor will closely monitor you for side effects. :

• medicines used to treat fungal infections, such as ketoconazole, itraconazole, fluconazole

medicines used to treat HIV infection and AIDS, such as atazanavir, indinavir, nelfinavir, ritonavir, saquinavir, amprenavir, fosamprenavir

medicines used to treat bacterial infections, including tuberculosis, containing clarithromycin, telithromycin, erythromycin and rifampicin

medicines used to treat various heart conditions, such as diltiazem, verapamil, digoxin,

flecainide and beta-blockers (such as metoprolol)

medicines used to prevent nausea and vomiting during chemotherapy and after surgery, such as aprepitant

certain medicines used to treat depression, including nortriptyline, desipramine, paroxetine

imipramine and amitriptyline, nefazodone

Your doctor will closely monitor you for side effects and/or may need to adjust the dose of the other medicine or NUEDEXTA.

NUEDEXTA with food, drink and alcohol

You should not drink grapefruit juice or eat grapefruits while you are taking NUEDEXTA as this can increase the likelihood of serious side effects.

Take care if you consume alcohol while effects such as dizziness and sleepiness.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, or if

ption, ask your doctor for advice before taking this medicine.

As NUEDEXTA may cause harm to your unborn baby, its use is not recommended when you are pregnant or if you are a women of childbearing potential not using contraception. Your doctor will discuss with you the risks and benefits of using this medicine in these situations.

It is not known whether the active substances of NUEDEXTA are expressed into human milk. Your doctor will decide if you should take this medicine while breast-feeding.

Driving and using machines

NUEDEXTA may cause dizziness. If this happens to you, do not drive or use machines.

NUEDEXTA contains lactose

If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take NUEDEXTA

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Start of treatment (first 4 weeks):

Your doctor will start your treatment with NUEDEXTA 15 mg/9 mg capsules which should be taken by you as follows:

• For the first seven days of treatment: one capsule per day, taken in the morning.
• From the eighth day of treatment onwards: two capsules per day, one in the morning and one in

the evening, 12 hours apart.

After 4 weeks:

Your doctor will assess you carefully. Depending on your response to the treatment, your doctor may either decide:

• to continue the treatment with NUEDEXTA 15 mg/9 mg capsules, or
• to give you a higher dose and to prescribe NUEDEXTA 23 mg/9 mg capsules to you.

Regardless of which strength of NUEDEXTA has been prescribed to you:

• continue the treatment with: two capsules per day (one capsule every 12 hours).

Use in older persons

No special dose adjustment of NUEDEXTA is required in older patients.

How to take NUEDEXTA

The capsule should be taken orally (by mouth) either with or without food at about the same time each day. When taking two capsules within 24 hours, you should leave about 12 hours between doses.

If you take more NUEDEXTA than you should

If you have taken more capsules than you should, speak to your doctor immediately.

Adverse reactions observed with this medicine may occur more often or may worsen and your doctor may perform some test and monitor you more closely.

Symptoms of dextromethorphan overdose include nausea, vomiting, stupor, coma, respiratory depression, seizures, increased heart rate, hyperexcitability, and toxic psychosis. Other effects include loss of coordinated movement (ataxia), involuntary eye movements (nystagmus), over contraction of the muscles (dystonia), blurred vision, and changes in muscle reflexes. Dextromethorphan may increase the risk of serotonin syndrome (see Warnings and precautions and Possible side effects).

Symptoms of quinidine overdose include irregular heartbeat and low blood pressure, and may also include vomiting, diarrhoea, ringing in the ears, high-frequency hearing loss, vertigo, blurred vision, double vision, increased sensitivity of the eyes to light, headache, confusion, and delirium (characterised by loss of attention, poor memory, disorientation, impaired speech).

e NUEDEXTA

1 or more capsules, you must not take a double dose to make up for the missed doses. Take your next dose at the usual time and make sure that approximately 12 hours passes between two doses.

If you stop taking NUEDEXTA

Do not stop taking this medicine without speaking to your doctor first, even if you begin to feel better. Stopping treatment may cause your symptoms to return.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most side effects are mild to moderate. However, some side effects may be serious and require treatment.

Tell your doctor immediately if you experience severe symptoms including agitation, high blood pressure, restlessness, muscle spasms and twitching, high body temperature, excessive sweating, shivering, and tremor. These may be a sign of a serious condition called “serotonin syndrome”.

Tell your doctor immediately if you notice any of the following:

• excessive muscle stiffness (spasticity)
• excessively slow or shallow breathing (respiratory depression) and/or turning blue.

The most commonly reported side effects are gastrointestinal disorders (such as diarrhoea, nausea), nervous system disorders (such as dizziness, headache, somnolence) and fatigue.

If any of the above occur, stop taking the capsules and tell your doctor immediately

A list of all other side effects is provided below:

Common side effects

(may affect up to 1 in 10 people)

diarrhoea, nausea

dizziness, headache, drowsiness fatigue

Uncommon side effects

(may affect up to 1 in 100 people)

decreased appetite

anxiety

distorted sense of taste (dysgeusia), sleepiness (hy

(syncope), fall

travel or motion sickness, ringing in the ears (tinnitus)

heart problems, such as slow, fast or irregular heart beat, or altered results during an

electrocardiogram (ECG – QT prolongation)

abdominal pain, constipation, dry mouth, wind (flatulence), stomach discomfort, vomiting increased liver enzymes (GGT, AST, ALT) rash

muscle spasms

weakness (asthenia), irritability

Rare

(may affect up to 1 in

loss of appetite (anorexia)

teeth grinding (bruxism), confusion, depressed mood, depression, disorientation (e.g. difficulty sensing time, direction, and recognition of people and places), early morning awakening, reduced emotional expressiveness (flat affect), hallucination, impulsive behaviour, indifference, insomnia, restlessness, disturbed sleep

• balance disorder, abnormal coordination, speech difficulties (dysarthria), movement

dysfunction, pins and needles / tingling or numbness (paraesthesia), loss of feeling or function in the lower limbs (paraparesis), sedation

• double vision, blurred vision
• heart attack (myocardial infarction), heart palpitations
• nose bleeds, throat pain, excessively slow or shallow breathing (respiratory depression), runny

nose, yawning

• abnormal faeces, indigestion, inflammation of the lining of the stomach (gastritis), numbness

and abnormal sensation in the mouth, rectal pain, dry tongue

• gall stones, increased bilirubin levels in the blood, abnormal liver function test
• redness of the skin (erythema), excessive sweating (hyperhidrosis), loss of sensation or

numbness of the face, night sweats

• musculoskeletal stiffness, muscle pain (myalgia), neck pain, pain in the limbs
• abnormally frequent daytime urination
• sexual dysfunction
• chest discomfort, chest pain, chills, feeling hot, gait disturbance (difficulty walking), flu-like

illness, fever, decreased oxygen levels in the blood

• bone fractures (skeletal injury)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store NUEDEXTA

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

Do not use this medicine after the expiry date which is stated on the bottle, blister EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What NUEDEXTA contains

The active substances are:

Each NUEDEXTA 15 mg/9 mg capsule contains dextromethorphan hydrobromide monohydrate, equivalent to 15.41 mg dextromethorphan and quinidine sulfate dihydrate, equivalent to 8.69 mg quinidine.

Each NUEDEXTA 23 mg/9 mg capsule contains dextromethorphan hydrobromide monohydrate, equivalent to 23.11 mg dextromethorphan and quinidine sulfate dihydrate, equivalent to 8.69 mg quinidine.

The other ingredients are croscarmellose sodium, cellulose microcrystalline, silica colloidal, lactose monohydrate, magnesium stearate and gelatin, titanium dioxide (E171), red iron oxide (E172), printing ink (shellac glaze, propylene glycol, titanium dioxide (E171)).

What NUEDEXTA looks like and contents of the pack

Each bottle consists of high density polyethylene (HDPE) with a child resistant polypropylene cap and contains 60 hard capsules. Each bottle will be contained within a carton.

Only for NUEDEXTA 15 mg/9 mg: Blister packs consist of a PVC based clear film with aluminium foil seal and contains 13 hard capsules. Each blister is packed in a sleeve. This pack is intended to be used for the first 10 days of treatment.

Description:

• NUEDEXTA 15 mg/9 mg is a brick red gelatin capsule, size 1, with “DMQ / 20–10” printed in white ink on the capsule.
• NUEDEXTA 23 mg/9 mg is a brick red gelatin capsule, size 1, with “DMQ / 30–10” printed in white ink on the capsule and three white bands around the circumference.