Side Effects of Vicodin (hydrocodone/acetaminophen)

Vicodin (hydrocodone/acetaminophen) is a combination of a narcotic pain-reliever and a cough suppressant, similar to codeine, and a non-narcotic analgesic (pain reliever) and antipyretic (fever reducer) prescribed for moderate to moderately severe pain.

Hydrocodone blocks the receptors on nerve cells in the brain that give rise to the sensation of pain.

Acetaminophen works by elevating the threshold to pain, that is, in order for pain to be felt, greater stimulation of the nerves responsible for the sensation of pain is necessary. It reduces fever through its action on the temperature-regulating center of the brain. Frequently, hydrocodone and acetaminophen are combined to achieve pain relief, as in Vicodin and Lortab. 

Common side effects of Vicodin include

• lightheadedness,
• dizziness,
• sedation,
• nausea,
• vomiting,
• drowsiness,
• constipation, and
• spasm of the ureter, which can lead to difficulty urinating.

Serious side effects of Vicodin include impaired thinking and physical abilities required for driving or operating machinery and depressed breathing.

Hydrocodone may be habit-forming. Mental and physical dependence can occur but are unlikely when used for short-term pain relief. Acetaminophen can cause severe liver failure if excessive amounts are used and when combined with chronic alcohol use or other drugs that also impair liver function.

Drug interactions of Vicodin include other narcotics, antihistamines, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantly with Vicodin may exhibit an additive CNS depression.

When combined therapy is contemplated, the dose of one or both agents should be reduced.

The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.

There are no adequate studies of Vicodin in pregnant women. Vicodin is excreted in breast milk, and should be used cautiously by breastfeeding mothers.

Common side effects of hydrocodone/acetaminophen are:

• lightheadedness,
• dizziness,
• sedation,
• nausea, and
• vomiting.

Other important side effects include:

• drowsiness,
• constipation, and
• spasm of the ureter, which can lead to difficulty in urinating.

Hydrocodone can impair thinking and the physical abilities required for driving or operating machinery. Hydrocodone can depress breathing, and should be used with caution in elderly, debilitated patients and in patients with serious lung disease.

Hydrocodone may be habit-forming. Mental and physical dependence can occur but are unlikely when used for short-term pain relief.

Acetaminophen can cause severe liver failure if excessive amounts are used and when combined with chronic alcohol use or other drugs that also impair liver function.

The following adverse reactions have been identified during post approval use of hydrocodone and acetaminophen tablets. 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 predominately 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 hydrocodone bitartrate and acetaminophen tablets.
• Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids.

Inhibitors Of CYP3A4 And CYP2D6

• The concomitant use of hydrocodone bitartrate and acetaminophen tablets 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 hydrocodone bitartrate and acetaminophen tablets, resulting in increased or prolonged opioid effects.
• These effects could be more pronounced with concomitant use of hydrocodone bitartrate and acetaminophen tablets and both CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and acetaminophen tablets is achieved.
• After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone bitartrate and acetaminophen tablets.
• If concomitant use is necessary, consider dosage reduction of hydrocodone bitartrate and acetaminophen tablets 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 hydrocodone bitartrate and acetaminophen tablets dosage until stable drug effects are achieved. Follow for signs or symptoms of opioid withdrawal.

Inducers Of CYP3A4

• The concomitant use of hydrocodone bitartrate and acetaminophen tablets and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of hydrocodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone.
• After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase, 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 hydrocodone bitartrate and acetaminophen tablets dosage until stable drug effects are achieved.
• Follow the patient for signs and symptoms of opioid withdrawal.
• If a CYP3A4 inducer is discontinued, consider hydrocodone bitartrate and acetaminophen tablets dosage reduction and follow for signs of respiratory depression.

Benzodiazepines And Other CNS Depressants

• Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants, such as benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
• 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.

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), 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.
• If concomitant use is warranted, carefully follow the patient, particularly during treatment initiation and dose adjustment. Discontinue hydrocodone bitartrate and acetaminophen tablets 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).
• The use of hydrocodone bitartrate and acetaminophen tablets 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 hydrocodone bitartrate and acetaminophen tablets and/or precipitate withdrawal symptoms.
• Advise patient to avoid concomitant use of these drugs.

Muscle Relaxants

• Hydrocodone bitartrate and acetaminophen tablets may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
• If concomitant use is warranted, monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of hydrocodone bitartrate and acetaminophen tablets and/or the muscle relaxant as necessary.

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 hydrocodone bitartrate and acetaminophen tablets are used concomitantly with anticholinergic drugs.

Drug Abuse And Dependence

Controlled Substance

• Hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, a Schedule II controlled substance.

Abuse

• Hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, a substance with a high potential for abuse similar to other opioids, including fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol, can be abused and are subject to misuse, addiction, and criminal diversion.
• 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. Health care 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.
• Hydrocodone bitartrate and acetaminophen tablets, 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 HydrocodoneBitartrate and Acetaminophen Tablets

• Hydrocodone bitartrate and acetaminophen tablets are for oral use only. Hydrocodone bitartrate and acetaminophen tablets pose a risk of overdose and death. The risk is increased with concurrent abuse of hydrocodone bitartrate and acetaminophen tablets 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 results 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.
• Hydrocodone bitartrate and acetaminophen tablets should not be abruptly discontinued in a physically dependent patient. If hydrocodone bitartrate and acetaminophen tablets are abruptly discontinued in a physically dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome:
  • restlessness,
  • lacrimation,
  • rhinorrhea,
  • yawning,
  • perspiration,
  • chills,
  • myalgia, and
  • mydriasis.
• Other signs and symptoms also may develop, including:
  • irritability,
  • anxiety,
  • backache,
  • joint pain,
  • weakness,
  • abdominal cramps,
  • insomnia,
  • nausea,
  • anorexia,
  • vomiting,
  • diarrhea, or
  • increased blood pressure, respiratory rate, or heart rate.
• Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs.