No human overdosage data are available for REZIRA Oral Solution.
HydrocodoneOverdosage with hydrocodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.
PseudoephedrineOverdosage with sympathomimetics, such as pseudoephedrine, may give rise to giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty in micturition, muscle weakness and tenseness, anxiety, restlessness, and insomnia. Many patients can present a toxic psychosis with delusion and hallucinations. Some may develop cardiac arrhythmias, circulatory collapse, convulsion, coma, and respiratory failure.
Treatment of overdosage consists of discontinuation of REZIRA Oral Solution together with institution of appropriate therapy. Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride is a specific antidote for respiratory depression which may result from overdosage or unusual sensitivity to opioids including hydrocodone. Therefore, an appropriate dose of naloxone hydrochloride should be administered, preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. For further information, see full prescribing information for naloxone hydrochloride. An antagonist should not be administered in the absence of clinically significant respiratory depression. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Gastric emptying may be useful in removing unabsorbed drug.
REZIRA Oral Solution is contraindicated in:
Use of hydrocodone bitartrate, a semisynthetic opioid, may result in the following:
Use of pseudoephedrine, a sympathomimetic amine, may result in the following:
The most common adverse reactions are central nervous system and cardiovascular reactions and include the following: Sedation, drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, dizziness, psychic dependence, mood changes, nervousness, sleeplessness, tremor or arrhythmia.
Other adverse reactions include:
Gastrointestinal System: Nausea and vomiting (more frequent in ambulatory than in recumbent patients), constipation.
Genitourinary System: Ureteral spasm, spasm of vesicle sphincters, urinary retention.
Cardiovascular System: Fast, slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitation, shock-like state, syncope.
Dermatological System: Skin rash, pruritus.
REZIRA® Oral Solution (hydrocodone bitartrate and pseudoephedrine hydrochloride) is indicated for:
Relief of cough and nasal congestion associated with common cold.
Important Limitations Of UseNot indicated for pediatric patients under 18 years of age.
Systemic exposure (in terms of peak plasma concentrations and area under plasma concentration versus time curve) of hydrocodone bitartrate and pseudoephedrine hydrochloride after single-dose administration of 5 mg hydrocodone and 60 mg pseudoephedrine are equivalent to respective reference solutions of 5 mL hydrocodone bitartrate (5 mg/5 mL) and 5 mL pseudoephedrine hydrochloride (60 mg/5 mL).
Hydrocodone had a mean (SD) peak plasma concentration of 10.6 (2.63) ng/mL at 1.4 (0.55) hours. The mean plasma half-life of hydrocodone is approximately 4.9 hours. Pseudoephedrine had a mean (SD) peak plasma concentration of 212 (46.2) ng/mL at 1.8 (0.56) hours. The mean plasma half-life of pseudoephedrine is approximately 5.6 hours.
Pregnancy Category C.
There are no adequate and well controlled studies of REZIRA Oral Solution in pregnant women. Reproductive toxicity studies have not been conducted with REZIRA Oral Solution; however, studies are available with an individual active ingredient or related active ingredient. Hydrocodone was teratogenic in hamsters. Codeine, an opiate related to hydrocodone, increased resorptions and decreased fetal weight in rats. Because animal reproduction studies are not always predictive of human response, REZIRA Oral Solution should be used during pregnancy only if the benefit justifies the potential risk to the fetus.
HydrocodoneHydrocodone has been shown to be teratogenic in hamsters when given in a dose approximately 35 times the maximum recommended human daily dose (MRHDD) (on a mg/m² basis at a single subcutaneous dose of 102 mg/kg on gestation day 8). Reproductive toxicology studies were also conducted with codeine, an opiate related to hydrocodone. In a study in which pregnant rats were dosed throughout organogenesis, a dose of codeine approximately 50 times the MRHDD of hydrocodone (on a mg/m² basis at an oral dose of 120 mg/kg/day of codeine) increased resorptions and decreased fetal weight; however, these effects occurred in the presence of maternal toxicity. In studies in which rabbits and mice were dosed throughout organogenesis, doses of codeine up to approximately 25 and 120 times, respectively, the MRHDD of hydrocodone (on a mg/m² basis at oral doses of 30 and 600 mg/kg/day, respectively), produced no adverse developmental effects.
Nonteratogenic EffectsBabies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose.
REZIRA is a clear, colorless to light yellow, grape-flavored liquid.
Each 5 mL of REZIRA Oral Solution contains: hydrocodone bitartrate, USP, 5 mg; and pseudoephedrine hydrochloride, USP, 60 mg.
Storage And HandlingREZIRA Oral Solution is supplied as a clear, colorless to light yellow, grape-flavored solution containing 5 mg hydrocodone bitartrate and 60 mg pseudoephedrine hydrochloride in each 5 mL. It is available in:
White HDPE bottles of one pint (480 mL): NDC 63717-875-16
Store solution at 20° to 25°C (68° to 77°F).
Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure.
Manufactured for: Hawthorn Pharmaceuticals, Inc., Morristown, NJ 07960. Revised: Jan: 2017
Included as part of the PRECAUTIONS section.
PRECAUTIONS Risks From Concomitant Use With Benzodiazepines Or Other CNS DepressantsConcomitant use of opioids, including REZIRA, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.
Advise both patients and caregivers about the risks of respiratory depression and sedation if REZIRA is used with benzodiazepines, alcohol, or other CNS depressants.
Respiratory DepressionHydrocodone bitartrate, one of the active ingredients of REZIRA Oral Solution, produces dose-related respiratory depression by directly acting on brain stem respiratory centers. Overdose of hydrocodone bitartrate in adults has been associated with fatal respiratory depression, and the use of hydrocodone bitartrate in children less than 6 years of age has been associated with fatal respiratory depression. Exercise caution when administrating REZIRA Oral Solution because of the potential for respiratory depression. If respiratory depression occurs, discontinue REZIRA Oral Solution and use naloxone hydrochloride when indicated to antagonize the effect and other supportive measures as necessary.
Drug DependenceHydrocodone can produce drug dependence of the morphine type and therefore, has the potential for being abused. Psychic dependence, physical dependence, and tolerance may develop upon repeated administration of REZIRA Oral Solution. Prescribe and administer REZIRA with the same degree of caution appropriate to the use of other opioid drugs.
Head Injury And Increased Intracranial PressureThe respiratory depression effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a pre-existing increase in intracranial pressure. Furthermore, opioids produce adverse reactions which may obscure the clinical course of patients with head injuries. The use of REZIRA Oral Solution should be avoided in these patients.
Activities Requiring Mental AlertnessHydrocodone bitartrate, one of the active ingredients in REZIRA Oral Solution, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of REZIRA Oral Solution. Concurrent use of REZIRA Oral Solution with alcohol or other central nervous system depressants should be avoided because additional impairment of central nervous system performance may occur.
Acute Abdominal ConditionsREZIRA Oral Solution should be used with caution in patients with acute abdominal conditions since the administration of hydrocodone may obscure the diagnosis or clinical course of patients with acute abdominal conditions. The concurrent use of other anticholinergics with hydrocodone may produce paralytic ileus.
Co-administration With AnticholinergicsThe concurrent use of anticholinergics with hydrocodone may produce paralytic ileus. Exercise caution when using REZIRA Oral Solution in patients taking anticholinergic medications.
Co-administration With MAOIs Or Tricyclic AntidepressantsREZIRA Oral Solution should not be used in patients receiving MAOI therapy or within 14 days of stopping such therapy as an increase in blood pressure or hypertensive crisis, may occur. In addition, the use of MAOIs or tricyclic antidepressants with hydrocodone bitartrate, one of the active ingredients in REZIRA Oral Solution, may increase the effect of either the antidepressant or hydrocodone.
Cardiovascular And Central Nervous System EffectsThe pseudoephedrine hydrochloride contained in REZIRA Oral Solution can produce cardiovascular and central nervous system effects in some patients such as insomnia, dizziness, weakness, tremor, or arrhythmias. In addition, central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension has been reported. Therefore, REZIRA Oral Solution should be used with caution in patients with cardiovascular disorders, and should not be used in patients with severe hypertension or coronary artery disease.
DosingPatients should be advised to measure REZIRA Oral Solution with an accurate milliliter measuring device. Patients should be informed that a household teaspoon is not an accurate measuring device and could lead to overdosage, which can result in serious adverse reactions. Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.
Coexisting ConditionsREZIRA Oral Solution should be used with caution in patients with diabetes, thyroid disease, Addison's disease, prostatic hypertrophy or urethral stricture, and asthma.
Renal ImpairmentREZIRA Oral Solution should be used with caution in patients with severe renal impairment.
Hepatic ImpairmentREZIRA Oral Solution should be used with caution in patients with severe hepatic impairment.
Patient Counseling Information OverdosagePatients should be advised not to increase the dose or dosing frequency of REZIRA Oral Solution because serious adverse events such as respiratory depression may occur with overdosage.
DosingPatients should be advised to measure REZIRA Oral Solution with an accurate milliliter measuring device. Patients should be informed that a household teaspoon is not an accurate measuring device and could lead to overdosage, especially when half a teaspoon is measured. Patients should be advised to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose.
Interactions With Benzodiazepines And Other Central Nervous System DepressantsInform patients and caregivers that potentially fatal additive effects may occur if REZIRA Oral Solution is used with benzodiazepines or other CNS depressants, including alcohol. Because of this risk, patients should avoid concomitant use of REZIRA Oral Solution with benzodiazepines or other CNS depressants, including alcohol.
Activities Requiring Mental AlertnessPatients should be advised to avoid engaging in hazardous tasks that require mental alertness and motor coordination such as operating machinery or driving a motor vehicle as REZIRA Oral Solution may produce marked drowsiness.
Drug DependencePatients should be cautioned that REZIRA Oral Solution contains hydrocodone bitartrate and can produce drug dependence.
MAOIsPatients should be informed that due to its pseudoephedrine component, they should not use REZIRA Oral Solution with a MAOI or within 14 days of stopping the use of an MAOI.
Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of FertilityCarcinogenicity, mutagenicity, and reproductive studies have not been conducted with REZIRA Oral Solution; however, published information is available for the individual active ingredients or related active ingredients.
HydrocodoneCarcinogenicity studies were conducted with codeine, an opiate related to hydrocodone. In 2 year studies in F344/N rats and B6C3F1 mice, codeine showed no evidence of tumorigenicity at dietary doses up to 70 and 400 mg/kg/day, respectively (approximately 30 and 80 times, respectively, the MRHDD of hydrocodone on a mg/m² basis).
PseudoephedrineTwo-year feeding studies in rats and mice demonstrated no evidence of carcinogenic potential with ephedrine sulfate, a structurally related drug with pharmacological properties similar to pseudoephedrine, at dietary doses up to 10 and 27 mg/kg, respectively (approximately 0.3 and 0.5 times, respectively, the MRHDD of pseudoephedrine hydrochloride on a mg/m² basis).
Use In Specific Populations Pregnancy Teratogenic EffectsPregnancy Category C.
There are no adequate and well controlled studies of REZIRA Oral Solution in pregnant women. Reproductive toxicity studies have not been conducted with REZIRA Oral Solution; however, studies are available with an individual active ingredient or related active ingredient. Hydrocodone was teratogenic in hamsters. Codeine, an opiate related to hydrocodone, increased resorptions and decreased fetal weight in rats. Because animal reproduction studies are not always predictive of human response, REZIRA Oral Solution should be used during pregnancy only if the benefit justifies the potential risk to the fetus.
HydrocodoneHydrocodone has been shown to be teratogenic in hamsters when given in a dose approximately 35 times the maximum recommended human daily dose (MRHDD) (on a mg/m² basis at a single subcutaneous dose of 102 mg/kg on gestation day 8). Reproductive toxicology studies were also conducted with codeine, an opiate related to hydrocodone. In a study in which pregnant rats were dosed throughout organogenesis, a dose of codeine approximately 50 times the MRHDD of hydrocodone (on a mg/m² basis at an oral dose of 120 mg/kg/day of codeine) increased resorptions and decreased fetal weight; however, these effects occurred in the presence of maternal toxicity. In studies in which rabbits and mice were dosed throughout organogenesis, doses of codeine up to approximately 25 and 120 times, respectively, the MRHDD of hydrocodone (on a mg/m² basis at oral doses of 30 and 600 mg/kg/day, respectively), produced no adverse developmental effects.
Nonteratogenic EffectsBabies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose.
Labor And DeliveryAs with all opioids, administration of REZIRA Oral Solution to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.
Nursing MothersCaution should be exercised when REZIRA is administered to nursing mothers. Hydrocodone and pseudoephedrine are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from REZIRA Oral Solution, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric UseSafety and effectiveness of REZIRA Oral Solution in pediatric patients under 18 years of age have not been established. The use of hydrocodone in children less than 6 years of age has been associated with fatal respiratory depression.
Geriatric UseClinical studies have not been conducted with REZIRA Oral Solution. Other reported clinical experience with the individual active ingredients of REZIRA Oral Solution has not identified differences in responses between the elderly and patients younger than 65 years of age. In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The pseudoephedrine contained in REZIRA Oral Solution is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Renal ImpairmentREZIRA Oral Solution should be given with caution in patients with severe impairment of renal function. Pseudoephedrine is primarily excreted unchanged in the urine as unchanged drug with the remainder apparently being metabolized in the liver. Therefore, pseudoephedrine may accumulate in patients with renal impairment.
Hepatic ImpairmentREZIRA Oral Solution should be given with caution in patients with severe impairment of hepatic function.
Administer REZIRA Oral Solution by the oral route only. Measure REZIRA Oral Solution with an accurate milliliter measuring device. Do not use a household teaspoon to measure the dose.
Adults 18 years Of Age And Older5 mL every 4 to 6 hours as needed, not to exceed 4 doses (20 mL) in 24 hours.
Use of hydrocodone bitartrate, a semisynthetic opioid, may result in the following:
Use of pseudoephedrine, a sympathomimetic amine, may result in the following:
The most common adverse reactions are central nervous system and cardiovascular reactions and include the following: Sedation, drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, dizziness, psychic dependence, mood changes, nervousness, sleeplessness, tremor or arrhythmia.
Other adverse reactions include:
Gastrointestinal System: Nausea and vomiting (more frequent in ambulatory than in recumbent patients), constipation.
Genitourinary System: Ureteral spasm, spasm of vesicle sphincters, urinary retention.
Cardiovascular System: Fast, slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitation, shock-like state, syncope.
Dermatological System: Skin rash, pruritus.
DRUG INTERACTIONSNo specific interaction studies have been conducted with REZIRA Oral Solution.
Benzodiazepines, Opioids, Antihistamines, Antipsychotics, Anti-anxiety Agents, Or Other CNS Depressants (Including Alcohol)The use of benzodiazepines, opioids, antihistamines, antipsychotics, anti-anxiety agents, or other CNS depressants (including alcohol) concomitantly with REZIRA Oral Solution may cause an additive CNS depressant effect, profound sedation, respiratory depression, coma, and death and should be avoided.
Monoamine Oxidase Inhibitors And Tricyclic AntidepressantsDo not prescribe REZIRA Oral Solution if the patient is taking a prescription MAOI (i.e., certain drugs used for depression, psychiatric or emotional conditions, or Parkinson's disease), or for 2 weeks after stopping a MAOI drug. The use of MAOIs or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone. An increase in blood pressure or hypertensive crisis may also occur when pseudoephedrine containing preparations are used with MAOIs.
Anticholinergic DrugsHydrocodone should be administered cautiously to persons receiving anticholinergic drugs in order to avoid paralytic ileus and excessive anticholinergic effects.
Drug Abuse And Dependence Controlled SubstanceREZIRA Oral Solution is a Schedule II controlled prescription containing hydrocodone bitartrate and should be prescribed and administered with caution.
AbuseHydrocodone can produce drug dependence of the morphine type and therefore, has the potential for being abused. Psychic dependence, physical dependence, and tolerance may develop upon repeated administration of REZIRA Oral Solution, and it should be prescribed and administered with the same degree of caution appropriate to the use of other opioid drugs.
DependencePsychic dependence, physical dependence, and tolerance may develop upon repeated administration of opioids; therefore, REZIRA Oral Solution should be prescribed and administered with caution.
Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued oral opioid use, although some mild degree of physical dependence may develop after a few days of opioid therapy.
