Metadol-D (Knight Therapeutics): Uses, Side Effects and Dosage

Serious Warnings and Precautions

What is METADOL-D used for?

METADOL-D is used in adults to treat opioid addiction through maintenance and detoxification treatment. It is used in combination with social and medical services. Only a qualified healthcare professional can prescribe METADOL-D.

METADOL-D is NOT used “as needed” to treat pain that you only have once in a while.

How does METADOL-D work?

METADOL-D belongs to the class of medicines known as opioids, which also includes codeine, fentanyl, hydromorphone and morphine.

METADOL-D acts by suppressing the symptoms of opioid withdrawal without producing a “high”, while the long-acting nature of the drug allows for once-a-day maintenance dosing.

What are the ingredients in METADOL-D?

Medicinal ingredient: methadone hydrochloride

Non-medicinal ingredients:

• METADOL-D oral solution contains: citric acid, dextrose, glycerin, methylparaben, polyethylene glycol, sodium benzoate, sodium cyclamate and water.
• METADOL-D oral concentrate contains: citric acid, dextrose, glycerin, propylene glycol, sodium benzoate, sodium cyclamate and water.

METADOL-D comes in the following dosage forms:

METADOL-D Oral Solution: 1mg/mL

METADOL-D Oral Concentrate: 10mg/mL

Do not use METADOL-D if:

• your healthcare professional did not prescribe it for you
• you are allergic to methadone hydrochloride, other opioids, or any of the other ingredients in METADOL-D
• you have severe asthma, trouble breathing, or any other breathing problems
• you have a heart problem that causes the right side of the heart to fail (cor pulmonale)
• you have bowel blockage or narrowing of the stomach or intestines
• you have a condition where the bowel does not work properly (ileus) or have severe pain in your abdomen
• you have or may have a condition that needs abdominal surgery such as appendicitis or pancreatitis
• you have a severe diarrhea caused by antibiotics or food poisoning
• you have a head injury or increased pressure in your skull
• you have central nervous system (CNS) depression

• you suffer from alcoholism or alcohol withdrawal

• you suffer from seizures
• you are taking or have taken in the last 14 days a certain type of antidepressant called monoamine oxidase inhibitors (MAOIs)

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take METADOL-D. Talk about any health conditions or problems you may have, including if you:

• have a history of abusing illicit drugs, prescription drugs or alcohol
• are drinking or planning to drink alcoholic beverages or take medications that contain alcohol
• have severe kidney problems or lung disease
• have liver problems
• have heart problems
• have low blood pressure or a low blood volume

• are at risk of developing an irregular heart rhythm (prolonged QT interval) that may be associated with:

  • having a heart disease where the heart muscle becomes thick (cardiac hypertrophy)
  • taking diuretics
  • having low potassium or magnesium levels in your blood
• suffer from chronic or severe constipation
• suffer from migraines
• have difficulty urinating
• have or have a history of problems with your mood (such as depression or anxiety) or other mental health problems
• have problems with your thyroid, adrenal or prostate gland
• have a sleep disorder which causes pauses in breathing or shallow breathing while sleeping (sleep apnea)
• are pregnant or are planning to breastfeed
• are 65 years of age or older

Other warnings you should know about:

Opioid dependence and addiction: There are important differences between physical dependence and addiction. It is important that you talk to your healthcare professional if you have questions or concerns about abuse, addiction or physical dependence.

Pregnancy, nursing, labour and delivery: Opioids can be transferred to your baby through breast milk, or while still in the womb. METADOL-D can then cause life-threatening breathing problems in your unborn baby or nursing infant.

Driving and using machines: Before you do tasks which may require special attention, you should wait until you know how you react to METADOL-D. METADOL-D can cause:

• drowsiness
• dizziness or
• light headedness

This can usually occur after you take your first dose and when your dose is increased.

Disorder of the adrenal gland: You may develop a disorder of the adrenal gland called adrenal insufficiency. This means that your adrenal gland is not making enough of certain hormones. You may experience symptoms such as:

• nausea, vomiting
• feeling tired, weak or dizzy
• decreased appetite

You may be more likely to have problems with your adrenal gland if you have been taking opioids for longer than one month. Your healthcare professional may do tests, give you another medication, and slowly take you off METADOL-D.

Serotonin toxicity (also known as serotonin syndrome): METADOL-D can cause serotonin toxicity, a rare but potentially life-threatening condition. It can cause serious changes in how your brain, muscles and digestive system work. You may develop serotonin toxicity if you take METADOL-D with certain anti-depressants or migraine medications.

Serotonin toxicity symptoms include:

• fever, sweating, shivering, diarrhea, nausea, vomiting;
• muscle shakes, jerks, twitches or stiffness, overactive reflexes, loss of coordination;
• fast heartbeat, changes in blood pressure;
• confusion, agitation, restlessness, hallucinations, mood changes, unconsciousness, and coma.

Sexual Function/Reproduction: Long term use of opioids may lead to a decrease in sex hormone levels. It may also lead to low libido (desire to have sex), erectile dysfunction or being infertile.

Sleep Apnea: Opioids can cause a problem called sleep apnea (stopping breathing from time to time while sleeping). Tell your healthcare professional if you have a history of sleep apnea or if anyone notices that you stop breathing from time to time while sleeping.

Testing and check-ups: Your healthcare professional will regularly monitor your health. This includes monitoring for signs of:

• misuse and abuse
• sleep apnea (a sleep disorder which causes pauses in breathing or shallow breathing while sleeping)
• respiratory depression and sedation (e.g., slow, shallow, or weak breathing)
• low blood pressure
• problems with your heart rhythm.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may also interact with METADOL-D:

• anticonvulsants used to treat seizures (e.g., phenytoin, carbamazepine, phenobarbital)
• anticoagulants used to thin the blood and prevent blood clots (e.g., warfarin and other coumarins)
• antiretrovirals used to treat viral infections (e.g., nevirapine, efavirenz, ritonavir, lopinavir, zidovudine, didanosine, stavudine)
• antifungals used to treat fungal infections (e.g., ketoconazole, voriconazole)
• antibiotics used to treat bacterial infections (e.g., erythromycin, rifampin)
• medicines used to treat migraines (e.g., triptans)
• antiarrhythmics used to treat an abnormal heart rhythm
• calcium channel blockers used to lower blood pressure
• medicines used to regulate salt and water balances in the body (e.g., diuretics, mineralocorticoid hormones, laxatives)

How to take METADOL-D:

• Take METADOL-D exactly as your healthcare professional tells you to. DO NOT increase, decrease, or stop taking your dose without talking to your healthcare professional. Talk to your healthcare professional if you are not sure.
• METADOL-D must be taken orally, by mouth. Do NOT take METADOL-D any other way.
• METADOL-D will be given to you in either grape Kool-Aid®, orange Tang®, Allen’s® apple juice, tangerine-grapefruit or lemonade Crystal Light®. Any remaining solution should be refrigerated (2^oC to 8^oC) for not more than 14 days or 7 days if diluted in Allen’s® Apple Juice.
• Your dose should be taken all at once, and preferably at the same time every day.

Usual dose:

Your dose is personalized for you. Your healthcare professional will determine the best dose for you based on your symptoms and what METADOL-D is used for. During treatment, your healthcare professional may adjust your dose based on your response to the treatment

Stopping your Medication:

If you have been taking METADOL-D for more than a few days, you should not stop taking it all of a sudden.

Your healthcare professional will monitor and guide you on how to slowly stop taking METADOL-D. You should do it slowly to avoid uncomfortable symptoms such as having:

• body aches
• diarrhea
• goosebumps
• loss of appetite
• nausea
• feeling nervous or restless
• runny nose
• sneezing
• tremors or shivering
• stomach cramps
• rapid heart rate (tachycardia)
• having trouble with sleeping
• an unusual increase in sweating
• heart palpitations
• an unexplained fever
• weakness
• yawning

By reducing or stopping your opioid treatment, your body will become less used to opioids. If you start treatment again, you will need to start at the lowest dose. You may overdose if you restart at the last dose you took before you slowly stopped taking METADOL-D.

Refilling your prescription for METADOL-D:

A new written prescription is required from your healthcare professional each time you need more METADOL-D. Therefore, it is important that you contact your healthcare professional before your current supply runs out.

Only obtain prescriptions for this medicine from the healthcare professional in charge of your treatment. Do not seek prescriptions from other healthcare professional unless you switch to another healthcare professional for your pain management.

Occasionally, the brand of methadone prescribed or dispensed by your healthcare professional may change. Should you experience any side effects, discuss with your healthcare professional.

Overdose:

Signs of overdose with METADOL-D may include:

• unusually slow or weak breathing;
• dizziness;
• confusion;
• extreme drowsiness;
• muscle weakness;
• cold and clammy skin;
• slow heart rate;
• shrinking or widening of pupils.

Missed Dose:

It is important that you do not miss any doses. If you miss a dose, take your next dose at your usual time. You should always try to get back on track with your regular dosing schedule. Do not take two doses at the same time. If you miss several doses in a row, talk to your healthcare professional before restarting your medication.

What are possible side effects from using METADOL-D?

These are not all the possible side effects you may have when taking METADOL-D. If you experience any side effects not listed here, tell your healthcare professional.

Side effects with METADOL-D may include:

• Drowsiness
• Insomnia
• Dizziness
• Fainting
• Lightheadedness
• Nausea, vomiting, poor appetite
• Dry mouth
• Headache
• Problems with vision
• Weakness, uncoordinated muscle movement
• Itching
• Sweating, facial flushing
• Constipation. Talk with your healthcare professional about ways to prevent constipation when you start using METADOL-D.
• Low sex drive, impotence (erectile dysfunction), infertility

Serious side effects and what to do about them

Serotonin toxicity (also known as Serotonin syndrome): a reaction which may cause

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If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, tell your healthcare professional.

Reporting Side Effects

Storage:

Your healthcare professional will store this product.

For take home doses:

• Refrigerate (2^oC to 8^oC) METADOL-D diluted with Allen’s® Apple Juice for not more than 7 days, or 14 days if diluted with any other juice. • Keep unused or expired METADOL-D in a secure place to prevent theft, misuse or accidental exposure. It should be kept under lock, out of sight and reach of children and pets.
• Never take medicine in front of small children as they will want to copy you. Accidental ingestion by a child is dangerous and may result in death. If a child accidentally takes METADOL-D, get emergency help right away.
• METADOL-D should never be thrown into household trash, where children and pets may find it. It should be returned to a pharmacy for proper disposal.

If you want more information about METADOL-D:

• Talk to your healthcare professional.
• Find the full product monograph that is prepared for healthcare professionals and includes this Patient Medication Information by visiting the Health Canada website: (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html); the manufacturer’s website (https://knighttx.com), by emailing medinfo@knighttx.com or by calling 1-844-483-5636.