Hydrocodone Bitartrate Extended-release Tablets

HYSINGLA ER (hydrocodone bitartrate) extended-release tablets are supplied in 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg and 120 mg film-coated tablets for oral administration. The tablet strengths describe the amount of hydrocodone per tablet as the bitartrate salt.

Hydrocodone bitartrate is an opioid agonist. Its chemical name is 4,5α-epoxy-3-methoxy-17methylmorphinan-6-one tartrate (1:1) hydrate (2:5). Its structural formula is:

Empirical formula: C18H21NO3 • C4H6O6 • 2½H2O; Molecular weight: 494.49.

Hydrocodone bitartrate exists as fine white crystals or a crystalline powder. It is affected by light. It is soluble in water, slightly soluble in alcohol, and insoluble in ether and chloroform.

The 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg and 120 mg tablets contain the following inactive ingredients: Butylated Hydroxytoluene (BHT, an additive in Polyethylene Oxide), Hydroxypropyl Cellulose, Macrogol/PEG 3350, Magnesium Stearate, Microcrystalline Cellulose, Polyethylene Oxide, Polysorbate 80, Polyvinyl Alcohol, Talc, Titanium Dioxide, and Black Ink.

The 20 mg tablets also contain Iron Oxide Yellow and FD&C Blue #2 Aluminum Lake/Indigo Carmine Aluminum Lake.

The 30 mg tablets also contain Iron Oxide Yellow.

The 40 mg tablets also contain Iron Oxide Yellow, Iron Oxide Red, and Iron Oxide Black.

The 60 mg tablets also contain Iron Oxide Yellow and Iron Oxide Red.

The 80 mg tablets also contain Iron Oxide Red.

The 100 mg tablets also contain FD&C Blue #2 Aluminum Lake.

Black Ink Contains: Shellac Glaze (in Ethanol), Isopropyl Alcohol, Iron Oxide Black, N-Butyl Alcohol, Propylene Glycol and Ammonium Hydroxide.

Dosage Forms And Strengths

• 20 mg film-coated extended-release tablets (round, green-colored, bi-convex tablets printed with “HYD 20”)
• 30 mg film-coated extended-release tablets (round, yellow-colored, bi-convex tablets printed with “HYD 30”)
• 40 mg film-coated extended-release tablets (round, grey-colored, bi-convex tablets printed with “HYD 40”)
• 60 mg film-coated extended-release tablets (round, beige-colored, bi-convex tablets printed with “HYD 60”)
• 80 mg film-coated extended-release tablets (round, pink-colored, bi-convex tablets printed with “HYD 80”)
• 100 mg film-coated extended-release tablets (round, blue-colored, bi-convex tablets printed with “HYD 100”)
• 120 mg film-coated extended-release tablets (round, white-colored, bi-convex tablets printed with “HYD 120”)

Storage And Handling

HYSINGLA ER (hydrocodone bitartrate) extended-release tablets 20 mg are round, green-colored, biconvex tablets printed with “HYD 20” and are supplied in child-resistant closure, opaque plastic bottles of 60 (NDC 59011-271-60).

HYSINGLA ER (hydrocodone bitartrate) extended-release tablets 30 mg are round, yellow-colored, biconvex tablets printed with “HYD 30” and are supplied in child-resistant closure, opaque plastic bottles of 60 (NDC 59011-272-60).

HYSINGLA ER (hydrocodone bitartrate )extended-release tablets 40 mg are round, grey-colored, biconvex tablets printed with “HYD 40” and are supplied in child-resistant closure, opaque plastic bottles of 60 (NDC 59011-273-60).

HYSINGLA ER (hydrocodone bitartrate) extended-release tablets 60 mg are round, beige-colored, biconvex tablets printed with “HYD 60” and are supplied in child-resistant closure, opaque plastic bottles of 60 (NDC 59011-274-60).

HYSINGLA ER (hydrocodone bitartrate) extended-release tablets 80 mg are round, pink-colored, biconvex tablets printed with “HYD 80” and are supplied in child-resistant closure, opaque plastic bottles of 60 (NDC 59011-275-60).

HYSINGLA ER (hydrocodone bitartrate) extended-release tablets 100 mg are round, blue-colored, biconvex tablets printed with “HYD 100” and are supplied in child-resistant closure, opaque plastic bottles of 60 (NDC 59011-276-60).

HYSINGLA ER (hydrocodone bitartrate) extended-release tablets 120 mg are round, white-colored, biconvex tablets printed with “HYD 120” and are supplied in child-resistant closure, opaque plastic bottles of 60 (NDC 59011-277-60).

Store at 25°C (77°F); excursions permitted between 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

Dispense in tight, light-resistant container, as defined by the USP.

Manufactured by: Purdue Pharma L.P., Stamford, CT 06901-3431, www.purduepharma.com or call 1-888-726-7535. Revised: Dec 2016

Included as part of the PRECAUTIONS section.

HYSINGLATM™ ER
(hye-SING-luh)
(hydrocodone bitartrate) Extended-release Tablets

HYSINGLA ER is:

• A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain severe enough to require daily, around-the-clock, long-term treatment with an opioid, when other pain treatments such as non-opioid pain medicines or immediate-release opioid medicines do not treat your pain well enough or you cannot tolerate them.
• A long-acting (extended-release) opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.
• Not for use to treat pain that is not around-the-clock.

Important information about HYSINGLA ER:

• Get emergency help right away if you take too much HYSINGLA ER (overdose). When you first start taking HYSINGLA ER, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur.
• Taking HYSINGLA ER with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.
• Never give anyone else your HYSINGLA ER. They could die from taking it. Store HYSINGLA ER away from children and in a safe place to prevent stealing or abuse. Selling or giving away HYSINGLA ER is against the law.

Do not take HYSINGLA ER if you have:

• severe asthma, trouble breathing, or other lung problems.
• a bowel blockage or have narrowing of the stomach or intestines.

Before taking HYSINGLA ER, tell your healthcare provider if you have a history of:

• head injury, seizures
• liver, kidney, thyroid problems
• problems urinating
• pancreas or gallbladder problems
• heart rhythm problems (long QT syndrome)
• abuse of street or prescription drugs, alcohol addiction, or mental health problems

Tell your healthcare provider if you are:

• pregnant or planning to become pregnant. Prolonged use of HYSINGLA ER during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated.
• breastfeeding. Not recommended during treatment with HYSINGLA ER. It may harm your baby.
• taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking HYSINGLA ER with certain other medicines can cause serious side effects and could lead to death.

When taking HYSINGLA ER:

• Do not change your dose. Take HYSINGLA ER exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
• Take your prescribed dose every 24 hours, at the same time every day. Do not take more than your prescribed dose in 24 hours. If you miss a dose, take your next dose at your usual time the next day.
• Swallow HYSINGLA ER whole. Do not cut, break, chew, crush, dissolve, snort, or inject HYSINGLA ER because this may cause you to overdose and die.
• HYSINGLA ER should be taken 1 tablet at a time. Do not pre-soak, lick, or wet the tablet before placing it in your mouth to avoid choking on the tablet.

Call your healthcare provider if the dose you are taking does not control your pain.

• Do not stop taking HYSINGLA ER without talking to your healthcare provider.
• After you stop taking HYSINGLA ER, flush any unused tablets down the toilet.

While taking HYSINGLA ER, DO NOT:

• Drive or operate heavy machinery until you know how HYSINGLA ER affects you. HYSINGLA ER can make you sleepy, dizzy, or lightheaded.
• Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with HYSINGLA ER may cause you to overdose and die.

The possible side effects of HYSINGLA ER are:

• constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

• trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.

These are not all the possible side effects of HYSINGLA ER. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov.

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

• Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS]
• Life-Threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS]
• Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS]
• Interactions with Benzodiazepine or Other CNS Depressants [see WARNINGS AND PRECAUTIONS]
• Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]
• Severe Hypotension [see WARNINGS AND PRECAUTIONS]
• Gastrointestinal Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Withdrawal [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

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

A total of 1,827 patients were treated with HYSINGLA ER in controlled and open-label chronic pain clinical trials. Five hundred patients were treated for 6 months and 364 patients were treated for 12 months. The clinical trial population consisted of opioid-na�ve and opioid-experienced patients with persistent moderate to severe chronic pain.

The common adverse reactions ( ≥ 2%) reported by patients in clinical trials comparing HYSINGLA ER (20-120 mg/day) with placebo are shown in Table 2 below:

Table 2: Adverse Reactions Reported in ≥ 2% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Na�ve and Opioid-Experienced Patients

The adverse reactions seen in controlled and open-label chronic pain studies are presented below in the following manner: most common ( ≥ 5%), common ( ≥ 1% to < 5%), and less common ( < 1%).

The most common adverse reactions ( ≥ 5%) reported by patients treated with HYSINGLA ER in the chronic pain clinical trials were constipation, nausea, vomiting, fatigue, upper respiratory tract infection, dizziness, headache, somnolence.

The common ( ≥ 1% to < 5%) adverse events reported by patients treated with HYSINGLA ER in the chronic pain clinical trials organized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class were:

Ear and labyrinth disorders: tinnitus

Gastrointestinal disorders abdominal pain, abdominal pain upper, diarrhea, dry mouth, dyspepsia, gastroesophageal reflux disease

General disorders and administration site conditions: chest pain, chills, edema peripheral, pain, pyrexia

Infections and infestations: bronchitis, gastroenteritis, gastroenteritis viral, influenza, nasopharyngitis, sinusitis, urinary tract infection

Injury, poisoning and procedural complications: fall, muscle strain

Metabolism and nutrition disorders: decreased appetite

Musculoskeletal and connective tissue disorders: arthralgia, back pain, muscle spasms, musculoskeletal pain, myalgia, pain in extremity

Nervous system disorders: lethargy, migraine, sedation

Psychiatric disorders: anxiety, depression, insomnia

Respiratory, thoracic and mediastinal disorders: cough, nasal congestion, oropharyngeal pain

Skin and subcutaneous tissue disorders: hyperhidrosis, pruritus, rash

Vascular disorders: hot flush, hypertension

Other less common adverse reactions that were seen in < 1% of the patients in the HYSINGLA ER chronic pain clinical trials include the following in alphabetical order: abdominal discomfort, abdominal distention, agitation, asthenia, choking, confusional state, depressed mood, drug hypersensitivity, drug withdrawal syndrome, dysphagia, dyspnea, esophageal obstruction, flushing, hypogonadism, hypotension, hypoxia, irritability, libido decreased, malaise, mental impairment, mood altered, muscle twitching, edema, orthostatic hypotension, palpitations, presyncope, retching, syncope, thinking abnormal, thirst, tremor, and urinary retention.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of hydrocodone. 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.

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in HYSINGLA ER.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Hysingla ER (Hydrocodone Bitartrate Extended-release Tablets)

• Pain Management
• Pain Management Medication Types
• Pain Management: Musculoskeletal Pain