Evzio

Side effects of Naloxone are:

• increase or decrease in blood pressure,
• abnormal heart rate and rhythm,
• troubled breathing,
• cardiac arrest,
• fluid retention in lungs, and
• diarrhea.

Naloxone is available as injection of 0.4 and 1 mg/ml, auto Injector of 0.4 mg/0.4 ml, and nasal spray of 2mg and 4mg.

Naloxone should be stored at room temperature 20 C to 25 C (68 F to 77 F).

Narcan and Evzio are the brand names available for naloxone in the US.

Narcan is available in generic form. You need a prescription from your doctor or other health care professional to obtain Narcan.

Common Side Effects of Naloxone

You should tell your doctor if any of the following side effects are severe or don't go away:

• Low or high blood pressure
• Racing heartbeat
• Nausea or vomiting
• Shaking, sweating, and/or other symptoms of withdrawal
• Shortness of breath

Serious Side Effects of Naloxone

You should stop using this medicine and call your doctor if you experience any of the following serious side effects:

• Irregular heartbeat or heart stopping
• Seizures

Evzio is part of the drug class:

• Antidotes

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of naloxone injection in children.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of naloxone injection in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving naloxone injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Morphine
• Morphine Sulfate Liposome
• Naldemedine
• Naloxegol
• Oxycodone
• Oxymorphone

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Clonidine
• Yohimbine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart disease or
• Kidney disease or
• Liver disease—Use with caution. May make these conditions worse.

This section provides information on the proper use of a number of products that contain naloxone. It may not be specific to Evzio. Please read with care.

A home health caregiver or a family member will give you or your child this medicine. It is given as a shot under your skin or into a muscle.

This medicine comes with patient instructions and a training device. Let your home health caregiver or family member read and follow the directions carefully. Ask your doctor if you have any questions.

To use:

• This medicine is available as an autoinjector and can only be used one time. It is available in 2 dosage strengths: 0.4 milligram (mg)/0.4 milliliter (mL) autoinjector or 2 mg/0.4mL autoinjector.
• It also contains printed instructions on the device label and a speaker that provides electronic instructions which guides the user through each step of the injection.
• Inject the medicine into the outer thighs, through clothing, if needed. If you are giving this medicine to a child younger than 1 year of age, you should pinch the thigh muscle while giving the medicine.
• Do not use the medicine if it is cloudy, discolored, or has large particles in it.
• Do not remove the red safety guard until you are ready to use it.
• After giving the first dose of Evzio® to the patient, get emergency medical help right away.
• Closely watch the patient for signs and symptoms of opioid emergency may return after several minutes.
• Give a new naloxone injection every 2 to 3 minutes if symptoms returned and monitor the patient until emergency help is received.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For opioid emergency:
    • Adults and children—0.4 or 2 milligrams (mg) injected under the skin or into a muscle.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

This medicine should be given immediately after a suspected or known overdose of an opioid or narcotic medicine. This is to prevent a serious condition called respiratory or central nervous system depression.

Severe opioid withdrawal symptoms may happen suddenly after receiving this medicine. These include body aches, a fever, sweating, runny nose, sneezing, goose bumps, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, stomach cramps, fast heartbeat, and increased blood pressure.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Risk of Recurrent Respiratory and Central Nervous System Depression

The duration of action of most opioids may exceed that of Evzio resulting in a return of respiratory and/or central nervous system depression after an initial improvement in symptoms. Therefore, it is necessary to seek emergency medical assistance immediately after delivering the first dose of Evzio. Keep the patient under continued surveillance, and administer additional doses of Evzio as necessary [see Dosage and Administration (2.2)]. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance.

Risk of Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists

Reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete. Larger or repeat doses of naloxone hydrochloride may be required to antagonize buprenorphine because the latter has a long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor [see Dosage and Administration (2.3)]. Buprenorphine antagonism is characterized by a gradual onset of the reversal effects and a decreased duration of action of the normally prolonged respiratory depression.

Precipitation of Severe Opioid Withdrawal

The use of Evzio in patients who are opioid dependent may precipitate an acute abstinence syndrome characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying and hyperactive reflexes. Monitor patients for the development of the signs and symptoms of opioid withdrawal.

Abrupt postoperative reversal of opioid depression after using naloxone hydrochloride may result in nausea, vomiting, sweating, tremulousness, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. These events have primarily occurred in patients who had pre-existing cardiovascular disorders or received other drugs that may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, after use of naloxone hydrochloride, monitor patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects for hypotension, ventricular tachycardia or fibrillation, and pulmonary edema in an appropriate healthcare setting. It has been suggested that the pathogenesis of pulmonary edema associated with the use of naloxone hydrochloride is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures.

The following serious adverse reactions are discussed elsewhere in the labeling:

• Precipitation of Severe Opioid Withdrawal [see Warnings and Precautions (5.3)]

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The following adverse reactions were observed in Evzio clinical studies. In two pharmacokinetic studies with a total of 54 healthy adult subjects exposed to 0.4 mg Evzio, 0.8 mg Evzio (two 0.4 mg Evzios) or 2 mg Evzio, adverse reactions occurring in more than one subject were dizziness and injection site erythema.

The following adverse reactions have been identified during post-approval use of naloxone hydrochloride in the post-operative setting. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in post-operative patients have resulted in significant reversal of analgesia and have caused agitation [see Warnings and Precautions (5.3)].

Other events that have been reported in post-marketing use of Evzio include agitation, disorientation, confusion, and anger.

Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome. Signs and symptoms have included: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal signs and symptoms also included: convulsions, excessive crying, hyperactive reflexes [see Warnings and Precautions (5.3)].

Evzio (naloxone hydrochloride injection, USP) is a pre-filled, single-use auto-injector. Evzio is not made with natural rubber latex. Chemically, naloxone hydrochloride is the hydrochloride salt of 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride with the following structure:

C19H21NO4• HCl

M.W. 363.84

Naloxone hydrochloride occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform.

Each 0.4 mL of Evzio contains 2 mg naloxone hydrochloride, 3.34 mg of sodium chloride, hydrochloric acid to adjust pH, and water for injection. The pH range is 3.0 to 4.5.