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Hysingla ER

  • Generic Name: hydrocodone bitartrate extended-release tablets
  • Brand Name: Hysingla ER
  • Drug Class: Opioid Analgesics

Hysingla ER(Hydrocodone Bitartrate Extended-release Tablets) side effects drug center

 

PROFESSIONAL

CONSUMER

SIDE EFFECTS

 

Hysingla ER Side Effects Center

What Is Hysingla ER?

Hysingla ER (hydrocodone bitartrate) extended-release is an opioid agonist used to manage pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

What Is Hysingla ER?

Common side effects of Hysingla ER include:

What Are Side Effects of Hysingla ER?

Dosage for Hysingla ER

The starting dose for patients who are not opioid tolerant is Hysingla ER 20 mg orally every 24 hours.

What Drugs, Substances, or Supplements Interact with Hysingla ER?

Hysingla ER may interact with macrolide antibiotics, azole-antifungals, protease inhibitors, CYP3A4 inducers, pentazocine, nalbuphine, butorphanol, buprenorphine, MAO inhibitors, anticholinergics, laxatives, other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol. Tell your doctor all medications and supplements you use.

Hysingla ER During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before taking Hysingla ER, as it may harm a fetus. This drug passes into breast milk and could have undesirable effects on a nursing infant.

Additional Information

Consult your doctor before breastfeeding. Withdrawal symptoms may occur if you suddenly stop taking this medication.

Our Hysingla ER (hydrocodone bitartrate) extended-release Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Hysingla ER Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Opioid medicine can slow or stop your breathing, and death may occur. A person caring for you should give naloxone and/or seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.

Stop using hydrocodone and call your doctor at once if you have:

  • noisy breathing, sighing, shallow breathing, breathing that stops during sleep;
  • a slow heart rate or weak pulse;
  • pain or burning when you urinate;
  • confusion, tremors, severe drowsiness;
  • a light-headed feeling, like you might pass out;
  • low cortisol levels--nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness; or
  • high levels of serotonin in the body--agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea.

Serious breathing problems may be more likely in older adults and in those who are debilitated or have wasting syndrome or chronic breathing disorders.

Common side effects may include:

  • constipation, nausea, vomiting;
  • dizziness, drowsiness, feeling tired;
  • headache; or
  • cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Hysingla ER (Hydrocodone Bitartrate Extended-release Tablets)

 

Hysingla ER Professional Information

SIDE EFFECTS

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-naïve 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-Naïve and Opioid-Experienced Patients

MedDRA Preferred Term Open-label Titration Period Double-blind Treatment Period
(N=905)
(%)		 Placebo
(N=292)
(%)		 HYSINGLA ER
(N=296)
(%)
Nausea 16 5 8
Constipation 9 2 3
Vomiting 7 3 6
Dizziness 7 2 3
Headache 7 2 2
Somnolence 5 1 1
Fatigue 4 1 1
Pruritus 3 <1 0
Tinnitus 2 1 2
Insomnia 2 2 3
Decreased appetite 1 1 2
Influenza 1 1 3

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 cough, nasal congestion, oropharyngeal pain

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].

DRUG INTERACTIONS

Table 3 includes clinically significant drug interactions with HYSINGLA ER.

Table 3: Clinically Significant Drug Interactions with HYSINGLA ER

Inhibitors of CYP3A4
Clinical Impact: The concomitant use of HYSINGLA ER and CYP3A4 inhibitors can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of HYSINGLA ER and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of HYSINGLA ER is achieved [see WARNINGS AND PRECAUTIONS]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease [see CLINICAL PHARMACOLOGY], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone.
Intervention: If concomitant use is necessary, consider dosage reduction of HYSINGLA ER until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the HYSINGLA ER dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
Examples Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir)
CYP3A4 Inducers
Clinical Impact: The concomitant use of HYSINGLA ER and CYP3A4 inducers can decrease the plasma concentration of hydrocodone [see CLINICAL PHARMACOLOGY], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone [see WARNINGS AND PRECAUTIONS]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase [see CLINICAL PHARMACOLOGY], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.
Intervention: If concomitant use is necessary, consider increasing the HYSINGLA ER dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider HYSINGLA ER dosage reduction and monitor for signs of respiratory depression.
Examples: Rifampin, carbamazepine, phenytoin
Benzodiazepines and Other Central Nervous System (CNS) Depressants
Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].
Examples Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.
Serotonergic Drugs
Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue HYSINGLA ER if serotonin syndrome is suspected.
Examples Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine Oxidase Inhibitors (MAOIs)
Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS AND PRECAUTIONS].
Intervention: The use of HYSINGLA ER is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Examples Phenelzine, tranylcypromine, linezolid
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
Clinical Impact: May reduce the analgesic effect of HYSINGLA ER and/or precipitate withdrawal symptoms.
Intervention: Avoid concomitant use.
Examples butorphanol, nalbuphine, pentazocine, buprenorphine
Muscle Relaxants
Clinical Impact: Hydrocodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and deg naloxone for the emergency treatment of opioid overdose [see DOSAGE AND ADMINISTRATION, Warnicrease the dosage of HYSINGLA ER and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribinngs and PRECAUTIONS].
Examples Cyclobenzaprine, metaxalone
Diuretics
Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs
Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when HYSINGLA ER is used concomitantly with anticholinergic drugs.
Strong Laxatives
Clinical Impact: Concomitant use of HYSINGLA ER with strong laxatives that rapidly increase gastrointestinal motility, may decrease hydrocodone absorption and result in decreased hydrocodone plasma levels.
Intervention: If HYSINGLA ER is used in these patients, closely monitor for the development of adverse events as well as changing analgesic requirements.
Examples lactulose

Drug Abuse And Dependence

Controlled Substance

HYSINGLA ER contains hydrocodone bitartrate, a Schedule II controlled substance.

Abuse

HYSINGLA ER contains hydrocodone, a substance with a high potential for abuse similar to other opioids, including fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. HYSINGLA ER can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS AND PRECAUTIONS].

The high drug content in the extended-release formulation adds to the risk of adverse outcomes from abuse and misuse.

All patients treated with opioids require careful monitoring for signs of abuse and addiction because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

"Drug-seeking" behavior is very common in persons with substance use disorders. Drug seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people with untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

HYSINGLA ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of HYSINGLA ER

HYSINGLA ER is for oral use only. Abuse of HYSINGLA ER poses a risk of overdose and death. Abuse may occur by taking intact tablets in quantities greater than prescribed or without legitimate purpose, by crushing and chewing or snorting the crushed formulation, or by injecting a solution made from the crushed formulation. The risk is increased with concurrent use of HYSINGLA ER with alcohol or other central nervous system depressants. Taking cut, broken, chewed, crushed, or dissolved HYSINGLA ER increases the risk of overdose and death.

With parenteral abuse, the inactive ingredients in HYSINGLA ER can result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury, embolism, and death. Parenteral drug abuse is commonly associated with transmission of infectious diseases, such as hepatitis and HIV.

Abuse Deterrence Studies

HYSINGLA ER is formulated with physicochemical properties intended to make the tablet more difficult to manipulate for misuse and abuse, and maintains some extended release characteristics even if the tablet is physically compromised. To evaluate the ability of these physicochemical properties to reduce the potential for abuse of HYSINGLA ER, a series of in vitro laboratory studies, pharmacokinetic studies and clinical abuse potential studies was conducted. A summary is provided at the end of this section.

In Vitro Testing

In vitro physical and chemical tablet manipulation studies were performed to evaluate the success of different extraction methods in defeating the extended-release formulation. Results support that HYSINGLA ER resists crushing, breaking, and dissolution using a variety of tools and solvents and retains some extended-release properties despite manipulation. When subjected to an aqueous environment, HYSINGLA ER gradually forms a viscous hydrogel (i.e., a gelatinous mass) that resists passage through a hypodermic needle.

Clinical Abuse Potential Studies

Studies in Non-dependent Opioid Abusers

Two randomized, double-blind, placebo and active-comparator studies in non-dependent opioid abusers were conducted to characterize the abuse potential of HYSINGLA ER following physical manipulation and administration via the intranasal and oral routes. For both studies, drug liking was measured on a bipolar drug liking scale of 0 to 100 where 50 represents a neutral response of neither liking nor disliking, 0 represents maximum disliking, and 100 represents maximum liking. Response to whether the subject would take the study drug again was measured on a unipolar scale of 0 to 100 where 0 represents the strongest negative response (“definitely would not take drug again”) and 100 represents the strongest positive response (“definitely would take drug again”).

Intranasal Abuse Potential Study

In the intranasal abuse potential study, 31 subjects were dosed and 25 subjects completed the study. Treatments studied included intranasally administered tampered HYSINGLA ER 60 mg tablets, powdered hydrocodone bitartrate 60 mg, and placebo. Incomplete dosing due to granules falling from the subjects’ nostrils occurred in 82% (n = 23) of subjects receiving tampered HYSINGLA ER compared to no subjects with powdered hydrocodone or placebo.

The intranasal administration of tampered HYSINGLA ER was associated with statistically significantly lower mean and median scores for drug liking and take drug again (P<0.001 for both), compared with powdered hydrocodone as summarized in Table 4.

Table 4. Summary of Maximum Scores (Emax) on Drug Liking and Take Drug Again VAS Following intranasal Administration of HYSINGLA ER and Hydrocodone Powder in Non-dependent Opioid Abusers

VAS Scale (100 point) HYSINGLA ER Manipulated Hydrocodone Powder
Intranasal (n=25)
Drug Liking*
  Mean (SE) 65.4 (3.7) 90.4 (2.6)
  Median (Range) 56 (50–100) 100 (51–100)
Take Drug Again**
  Mean (SE) 36.4 (8.2) 85.2 (5.0)
  Median (Range) 14 (0-100) 100 (1-100)
*Bipolar scale (0=maximum negative response, 50=neutral response, 100=maximum positive response)
** Unipolar scale (0=maximum negative response, 100=maximum positive response)

Figure 1 demonstrates a comparison of peak drug liking scores for tampered HYSINGLA ER compared with powdered hydrocodone in subjects (n = 25) who received both treatments intranasally. The Y-axis represents the percent of subjects attaining a percent reduction in peak drug liking scores for tampered HYSINGLA ER vs. hydrocodone powder greater than or equal to the value on the X-axis.

Approximately 80% (n = 20) of subjects had some reduction in drug liking with tampered HYSINGLA ER relative to hydrocodone powder. Sixty-eight percent (n = 17) of subjects had a reduction of at least 30% in drug liking with tampered HYSINGLA ER compared with hydrocodone powder, and approximately 64% (n = 16) of subjects had a reduction of at least 50% in drug liking with tampered HYSINGLA ER compared with hydrocodone powder. Approximately 20% (n = 5) of subjects had no reduction in liking with tampered HYSINGLA ER relative to hydrocodone powder.

Figure 1: Percent Reduction Profiles for Emax of Drug Liking VAS for Manipulated HYSINGLA ER vs. Hydrocodone Powder, N = 25 Following Intranasal Administration

ercent Reduction Profiles for Emax of Drug Liking VAS for Manipulated HYSINGLA ER vs. Hydrocodone Powder, N = 25 Following Intranasal Administration - Illustration

Oral Abuse Potential Study

In the oral abuse potential study, 40 subjects were dosed and 35 subjects completed the study. Treatments studied included oral administrations of chewed HYSINGLA ER 60 mg tablets, intact HYSINGLA ER 60 mg tablets, 60 mg aqueous hydrocodone bitartrate solution, and placebo.

The oral administration of chewed and intact HYSINGLA ER was associated with statistically lower mean and median scores on scales that measure drug liking and desire to take drug again (P<0.001), compared to hydrocodone solution as summarized in Table 5.

Table 5. Summary of Maximum Scores (Emax) on Drug Liking and Take Drug Again VAS Following Oral Administration of HYSINGLA ER and Hydrocodone Solution in Non-dependent Recreational Opioid Users

VAS Scale (100 point) HYSINGLA ER Hydrocodone Solution
Oral (n=35) Intact Chewed
Drug Liking*
  Mean (SE) 63.3 (2.7) 69.0 (3.0) 94.0 (1.7)
  Median (Range) 58 (50–100) 66 (50–100) 100 (51–100)
Take Drug Again**
  Mean (SE) 34.3 (6.1) 44.3 (6.9) 89.7 (3.6)
  Median (Range) 24 (0-100) 55 (0-100) 100 (1-100)
*Bipolar scale (0=maximum negative response, 50=neutral response, 100=maximum positive response)
** Unipolar scale (0=maximum negative response, 100=maximum positive response)

Figure 2 demonstrates a comparison of peak drug liking scores for chewed HYSINGLA ER compared with hydrocodone solution in subjects who received both treatments orally. The Y-axis represents the percent of subjects attaining a percent reduction in peak drug liking scores for chewed HYSINGLA ER vs. hydrocodone solution greater than or equal to the value on the X-axis.

Approximately 80% (n = 28) of subjects had some reduction in drug liking with chewed HYSINGLA ER relative to hydrocodone solution. Approximately 69% (n = 24) of subjects had a reduction of at least 30% in drug liking with chewed HYSINGLA ER compared with hydrocodone solution, and approximately 60% (n = 21) of subjects had a reduction of at least 50% in drug liking with chewed HYSINGLA ER compared with hydrocodone solution. Approximately 20% (n = 7) of subjects had no reduction in drug liking with chewed HYSINGLA ER relative to hydrocodone solution.

Figure 2. Percent Reduction Profiles for Emax of Drug Liking VAS for Chewed HYSINGLA ER vs. Hydrocodone Solution, N = 35 Following Oral Administration

Percent Reduction Profiles for Emax of Drug Liking VAS for Chewed HYSINGLA ER vs. Hydrocodone Solution, N = 35 Following Oral Administration - Illustration

The results of a similar analysis of drug liking for intact HYSINGLA ER relative to hydrocodone solution were comparable to the results of chewed HYSINGLA ER relative to hydrocodone solution. Approximately 83% (n = 29) of subjects had some reduction in drug liking with intact HYSINGLA ER relative to hydrocodone solution. Eighty-three percent (n = 29) of subjects had a reduction of at least 30% in peak drug liking scores with intact HYSINGLA ER compared to hydrocodone solution, and approximately 74% (n = 26) of subjects had a reduction of at least 50% in peak drug liking scores with intact HYSINGLA ER compared with hydrocodone solution. Approximately 17% (n = 6) had no reduction in drug liking with intact HYSINGLA ER relative to hydrocodone solution.

Summary

The in vitro data demonstrate that HYSINGLA ER has physical and chemical properties that are expected to deter intranasal and intravenous abuse. The data from the clinical abuse potential studies, along with support from the in vitro data, also indicate that HYSINGLA ER has physicochemical properties that are expected to reduce intranasal abuse and oral abuse when chewed. However, abuse of HYSINGLA ER by the intravenous, intranasal, and oral routes is still possible.

Additional data, including epidemiological data, when available, may provide further information on the impact of HYSINGLA ER on the abuse liability of the drug. Accordingly, this section may be updated in the future as appropriate.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Do not abruptly discontinue HYSINGLA ER in a patient physically dependent on opioids. Rapid tapering of HYSINGLA ER in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing HYSINGLA ER, gradually taper the dosage using a patient specific plan that considers the following: the dose of HYSINGLA ER the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use In Specific Populations].

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

&Copy; Hysingla ER Patient Information is supplied by Cerner Multum, Inc. and Hysingla ER Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.