Norco Side Effects Center

SIDE EFFECTS

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

The most frequently reported adverse reactions are light-headedness, dizziness, sedation, nausea and vomiting. Other adverse reactions include:

Central Nervous System – Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychological dependence, mood changes.

Gastrointestinal System – Constipation.

Genitourinary System – Ureteral spasm, spasm of vesical sphincters, and urinary retention.

Special Senses – Cases of hearing impairment or permanent loss have been reported predominantly in patients with chronic overdose.

Dermatological – Skin rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, allergic reactions

Hematological – Thrombocytopenia, agranulocytosis.

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

DRUG INTERACTIONS

Inhibitors Of CYP3A4 And CYP2D6

The concomitant use of NORCO and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma concentration of the hydrocodone from NORCO Tablets, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of NORCO and both CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of NORCO is achieved [see WARNINGS].

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the NORCO plasma concentration will decrease [see CLINICAL PHARMACOLOGY], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to NORCO.

If concomitant use is necessary, consider dosage reduction of NORCO until stable drug effects are achieved. Follow patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the NORCO dosage until stable drug effects are achieved. Follow for signs or symptoms of opioid withdrawal.

Inducers Of CYP3A4

The concomitant use of NORCO and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of NORCO [see CLINICAL PHARMACOLOGY], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to NORCO [see WARNINGS].

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the NORCO 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.

If concomitant use is necessary, consider increasing the NORCO dosage until stable drug effects are achieved. Follow the patient for signs and symptoms of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider NORCO dosage reduction and follow for signs of respiratory depression.

Benzodiazepines And Other 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 WARNINGS].

Examples

Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.

Serotonergic Drugs

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as 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), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome [see PRECAUTIONS; Information For Patients].

If concomitant use is warranted, carefully follow the patient, particularly during treatment initiation and dose adjustment. Discontinue NORCO if serotonin syndrome is suspected.

Monoamine Oxidase Inhibitors (MAOIs)

The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, or linezolid, may manifest as serotonin syndrome, or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS].

The use of NORCO is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

Mixed Agonist/Antagonist And Partial Agonist Opioid Analgesics

The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may reduce the analgesic effect of NORCO and/or precipitate withdrawal symptoms.

Advise patient to avoid concomitant use of these drugs.

Muscle Relaxants

Clinical Impact

NORCO 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 decrease the dosage of NORCO and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS].

Examples

cyclobenzaprine, metaxalone

Diuretics

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.

If concomitant use is warranted, follow patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs

The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

If concomitant use is warranted, follow patients for signs and symptoms of urinary retention or reduced gastric motility when NORCO Tablets are used concomitantly with anticholinergic drugs.

Drug Abuse And Dependence

Controlled Substance

NORCO contains hydrocodone, a Schedule II controlled substance.

Abuse

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

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 suffering from 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.

NORCO, 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 NORCO

NORCO is for oral use only. NORCO poses a risk of overdose and death. The risk is increased with concurrent abuse of NORCO with alcohol and other central nervous system depressants.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

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 NORCO in a patient physically dependent on opioids. Rapid tapering of NORCO 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 NORCO, gradually taper the dosage using a patient specific plan that considers the following: the dose of NORCO 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].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS; Pregnancy].

Read the entire FDA prescribing information for Norco (Hydrocodone Bitartrate and Acetaminophen)