Zubsolv
- Generic Name: buprenorphine and naloxone sublingual tablets
- Brand Name: Zubsolv
- Drug Class: Opioid Antagonists
Zubsolv (Buprenorphine and Naloxone Sublingual Tablets) side effects drug center
- Related Drugs
- headache,
- nausea,
- vomiting,
- increased sweating,
- constipation,
- insomnia,
- weakness,
- chills,
- infection,
- abdominal pain,
- back pain,
- diarrhea,
- runny or stuffy nose,
- pain and swelling of the lower limbs,
- fever,
- flu symptoms,
- indigestion,
- anxiety,
- depression,
- dizziness,
- nervousness,
- drowsiness,
- increased cough,
- sore throat, and
- watery eyes.
- weak or shallow breathing, breathing that stops during sleep;
- a light-headed feeling, like you might pass out;
- confusion, loss of coordination, extreme weakness;
- blurred vision, slurred speech;
- liver problems--upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
- high levels of serotonin in the body--agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea;
- low cortisol levels--nausea, vomiting, loss of appetite, dizziness, worsening tiredness or weakness; or
- opioid withdrawal symptoms--shivering, goose bumps, increased sweating, feeling hot or cold, runny nose, watery eyes, diarrhea, muscle pain.
- dizziness, drowsiness, blurred vision, feeling drunk, trouble concentrating;
- withdrawal symptoms;
- tongue pain, redness or numbness inside your mouth;
- nausea, vomiting, constipation;
- headache, back pain;
- fast or pounding heartbeats, increased sweating; or
- sleep problems (insomnia).
- Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS]
- Respiratory and CNS Depression [see WARNINGS AND PRECAUTIONS]
- Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS]
- Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]
- Opioid Withdrawal [see WARNINGS AND PRECAUTIONS]
- Hepatitis, Hepatic Events [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
- Elevation of Cerebrospinal Fluid Pressure [see WARNINGS AND PRECAUTIONS]
- Elevation of Intracholedochal Pressure [see WARNINGS AND PRECAUTIONS]
What Is Zubsolv?
Zubsolv (buprenorphine and naloxone) Sublingual Tablets is a partial opioid agonist used along with counseling and psychosocial support for maintenance treatment of opioid dependence.
What Are Side Effects of Zubsolv?
Common side effects of Zubsolv include:
Dosage for Zubsolv
The recommended target dosage of Zubsolv sublingual tablet is 11.4 mg/2.8 mg buprenorphine/naloxone/day (two 5.7/1.4 mg tablets) as a single daily dose.
What Drugs, Substances, or Supplements Interact with Zubsolv?
Zubsolv may interact with azole antifungals, antibiotics HIV protease inhibitors, efavirenz, phenobarbital, carbamazepine, phenytoin, rifampicin, benzodiazepines or other CNS depressants. Tell your doctor all medications and supplements you use.
Zubsolv During Pregnancy and Breastfeeding
During pregnancy, Zubsolv should be used only if prescribed. Use of this drug during pregnancy may result in breathing problems in a newborn. The medications in Zubsolv pass into breast milk. It is unknown if this drug may harm a nursing infant. Consult your doctor before breastfeeding. Withdrawal symptoms may occur if you suddenly stop taking this medication.
Additional Information
Our Zubsolv (buprenorphine and naloxone) Sublingual Tablets Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
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 seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.
Call your doctor at once or seek emergency medical attention if you have:
Serious breathing problems may be more likely in older adults and those who are debilitated or have wasting syndrome or chronic breathing disorders.
Common side effects may include:
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 Zubsolv (Buprenorphine and Naloxone Sublingual Tablets)
SIDE EFFECTS
The following serious adverse reactions are described elsewhere in the labeling:
Clinical Trials 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.
ZUBSOLV for use as initial treatment was evaluated in two clinical trials that had identical, blinded, two-day induction phases, comparing ZUBSOLV to generic buprenorphine. On the first day, subjects received an initial dose of ZUBSOLV 1.4 mg/0.36 mg or generic buprenorphine 2 mg, followed by ZUBSOLV 4.2 mg/1.08 mg or generic buprenorphine 6 mg 1.5 hours later. In total, safety data were available for 538 opioid-dependent subjects exposed to ZUBSOLV (buprenorphine/naloxone) sublingual tablets when used for initial treatment.
Table 1: Adverse Reactions in ≥ 5% of Patients During the Induction Phase by System Organ Class and Preferred Term (Safety Population)
| System Organ Class Preferred Term | ZUBSOLV (N=538) |
Generic BUP (N=530) |
Overall (N=1068) |
| N (%) | |||
| Patients with any Adverse Reactions | 139 (26%) | 136 (26%) | 275 (26%) |
| Gastrointestinal Disorders | 64 (12%) | 60 (11%) | 124 (12%) |
| Nausea | 29 (5%) | 36 (7%) | 65 (6%) |
| Vomiting | 25 (5%) | 26 (5%) | 51 (5%) |
| Nervous System Disorders | 48 (9%) | 44 (8%) | 92 (9%) |
| Headache | 36 (7%) | 35 (7%) | 71 (7%) |
| BUP = buprenorphine ZUBSOLV = buprenorphine/naloxone |
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The safety of buprenorphine/naloxone for longer-term use (up to 16 weeks of treatment) was evaluated in previous studies in 497 opioid-dependent subjects. The prospective evaluation of buprenorphine/naloxone was supported by clinical trials using buprenorphine tablets without naloxone and other trials using buprenorphine sublingual solutions. In total, safety data were available from 3214 opioid-dependent subjects exposed to buprenorphine at doses in the range used in treatment of opioid addiction. See Table 2.
Table 2: Adverse Events > 5% by Body System and Treatment Group in a 4-week Study
| Body System / Adverse Event (COSTART Terminology) | N (%) | N (%) |
| Buprenorphine/ naloxone 16/4 mg/day N=107 |
Placebo N=107 |
|
| Body as a Whole | ||
| Asthenia | 7 (7%) | 7 (7%) |
| Chills | 8 (8%) | 8 (8%) |
| Headache | 39 (37%) | 24 (22%) |
| Infection | 6 (6%) | 7 (7%) |
| Pain | 24 (22%) | 20 (19%) |
| Pain Abdomen | 12 (11%) | 7 (7%) |
| Pain Back | 4 (4%) | 12 (11%) |
| Withdrawal Syndrome | 27 (25%) | 40 (37%) |
| Cardiovascular System | ||
| Vasodilation | 10 (9%) | 7 (7%) |
| Digestive System | ||
| Constipation | 13 (12%) | 3 (3%) |
| Diarrhea | 4 (4%) | 16 (15%) |
| Nausea | 16 (15%) | 12 (11%) |
| Vomiting | 8 (8%) | 5 (5%) |
| Nervous System | ||
| Insomnia | 15 (14%) | 17 (16%) |
| Respiratory System | ||
| Rhinitis | 5 (5%) | 14 (13%) |
| Skin and Appendages | ||
| Sweating | 15 (14%) | 11 (10%) |
The adverse event profile of buprenorphine was also characterized in the dose-controlled study of buprenorphine solution, over a range of doses in four months of treatment. Table 3 shows adverse events reported by at least 5% of subjects in any dose group in the dose-controlled study.
Table 3: Adverse Events (≥ 5%) by Body System and Treatment Group in a 16-week Study
| Body System /Adverse Event (COSTART Terminology) | Buprenorphine dose* | ||||
| Very Low* (N=184) N (%) |
Low* (N=180) N (%) |
Moderate* (N=186) N (%) |
High* (N=181) N (%) |
Total* (N=731) N (%) |
|
| Body as a Whole | |||||
| Abscess | 9 (5%) | 2 (1%) | 3 (2%) | 2 (1%) | 16 (2%) |
| Asthenia | 26 (14%) | 28 (16%) | 26 (14%) | 24 (13%) | 104 (14%) |
| Chills | 11 (6%) | 12 (7%) | 9 (5%) | 10 (6%) | 42 (6%) |
| Fever | 7 (4%) | 2 (1%) | 2 (1%) | 10 (6%) | 21 (3%) |
| Flu Syndrome. | 4 (2%) | 13 (7%) | 19 (10%) | 8 (4%) | 44 (6%) |
| Headache | 51 (28%) | 62 (34%) | 54 (29%) | 53 (29%) | 220 (30%) |
| Infection | 32 (17%) | 39 (22%) | 38 (20%) | 40 (22%) | 149 (20%) |
| Injury Accidental | 5 (3%) | 10 (6%) | 5 (3%) | 5 (3%) | 25 (3%) |
| Pain | 47 (26%) | 37 (21%) | 49 (26%) | 44 (24%) | 177 (24%) |
| Pain Back | 18 (10%) | 29 (16%) | 28 (15%) | 27 (15%) | 102 (14%) |
| Withdrawal Syndrome | 45 (24%) | 40 (22%) | 41 (22%) | 36 (20%) | 162 (22%) |
| Digestive System | |||||
| Constipation | 10 (5%) | 23 (13%) | 23 (12%) | 26 (14%) | 82 (11%) |
| Diarrhea | 19 (10%) | 8 (4%) | 9 (5%) | 4 (2%) | 40 (5%) |
| Dyspepsia | 6 (3%) | 10 (6%) | 4 (2%) | 4 (2%) | 24 (3%) |
| Nausea | 12 (7%) | 22 (12%) | 23 (12%) | 18 (10%) | 75 (10%) |
| Vomiting | 8 (4%) | 6 (3%) | 10 (5%) | 14 (8%) | 38 (5%) |
| Nervous System | |||||
| Anxiety | 22 (12%) | 24 (13%) | 20 (11%) | 25 (14%) | 91 (12%) |
| Depression | 24 (13%) | 16 (9%) | 25 (13%) | 18 (10%) | 83 (11%) |
| Dizziness | 4 (2%) | 9 (5%) | 7 (4%) | 11 (6%) | 31 (4%) |
| Insomnia | 42 (23%) | 50 (28%) | 43 (23%) | 51 (28%) | 186 (25%) |
| Nervousness | 12 (7%) | 11 (6%) | 10 (5%) | 13 (7%) | 46 (6%) |
| Somnolence | 5 (3%) | 13 (7%) | 9 (5%) | 11 (6%) | 38 (5%) |
| Respiratory System | |||||
| Cough Increase | 5 (3%) | 11 (6%) | 6 (3%) | 4 (2%) | 26 (4%) |
| Pharyngitis | 6 (3%) | 7 (4%) | 6 (3%) | 9 (5%) | 28 (4%) |
| Rhinitis | 27 (15%) | 16 (9%) | 15 (8%) | 21 (12%) | 79 (11%) |
| Skin and Appendages | |||||
| Sweat | 23 (13%) | 21 (12%) | 20 (11%) | 23 (13%) | 87 (12%) |
| Special Senses | |||||
| Runny Eyes | 13 (7%) | 9 (5%) | 6 (3%) | 6 (3%) | 34 (5%) |
| *Sublingual solution. Doses in this table cannot necessarily be delivered in tablet form, but for comparison purposes: "Very low" dose (1 mg solution) would be less than a tablet dose of 2 mg "Low" dose (4 mg solution) approximates a 6 mg tablet dose "Moderate" dose (8 mg solution) approximates a 12 mg tablet dose "High" dose (16 mg solution) approximates a 24 mg tablet dose |
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Post-marketing Experience
The following adverse reactions have been identified during post-approval use of buprenorphine and naloxone sublingual tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate a causal relationship to drug exposure. The most frequently reported post-marketing adverse event not observed in clinical trials was peripheral edema.
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 ZUBSOLV.
Androgen Deficiency
Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].
Local Reactions
Glossodynia, glossitis, oral mucosal erythema, oral hypoesthesia, and stomatitis
DRUG INTERACTIONS
Table 4 includes clinically significant drug interactions with ZUBSOLV.
Table 4: Clinically Significant Drug Interactions
| Benzodiazepines and other Central Nervous System (CNS) Depressants | |
| Clinical Impact: | Due to additive pharmacologic effects, the concomitant use of benzodiazepines and other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. |
| Intervention: | Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate. Before co-prescribing benzodiazepines for anxiety or insomnia, ensure that patients are appropriately diagnosed and consider alternative medications and non-pharmacologic treatments [see WARNINGS AND PRECAUTIONS]. If concomitant use is warranted, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, as is recommended for all patients in treatment for opioid use disorder [see WARNINGS AND PRECAUTIONS]. |
| Examples: | Alcohol, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids. |
| Inhibitors of CYP3A4 | |
| Clinical Impact: | The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of ZUBSOLV is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see CLINICAL PHARMACOLOGY], potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine. |
| Intervention: | If concomitant use is necessary, consider dosage reduction of ZUBSOLV 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 ZUBSOLV 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 buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see CLINICAL PHARMACOLOGY], potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see CLINICAL PHARMACOLOGY], which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression. |
| Intervention: | If concomitant use is necessary, consider increasing the ZUBSOLV dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider ZUBSOLV dosage reduction and monitor for signs of respiratory depression. |
| Examples: | Rifampin, carbamazepine, phenytoin. |
| Antiretrovirals: Non-Nucleoside Reverse Transcriptase inhibitors (NNRTIs) | |
| Clinical Impact: | Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. Efavirenz, nevirapine, and etravirine are known CYP3A inducers, whereas delavirdine is a CYP3A inhibitor. Significant pharmacokinetic interactions between NNRTIs (e.g., efavirenz and delavirdine) and buprenorphine have been shown in clinical studies, but these pharmacokinetic interactions did not result in any significant pharmacodynamic effects. |
| Intervention: | Patients who are on chronic ZUBSOLV treatment should have their dose monitored if NNRTIs are added to their treatment regimen. |
| Examples: | Efavirenz, nevirapine, etravirine, delavirdine. |
| Antiretrovirals: Protease Inhibitors (PIs) | |
| Clinical Impact: | Studies have shown some antiretroviral protease inhibitors (PIs) with CYP3A4 inhibitory activity (nelfinavir, lopinavir/ritonavir, ritonavir) have little effect on buprenorphine pharmacokinetic and no significant pharmacodynamic effects. Other PIs with CYP3A4 inhibitory activity (atazanavir and atazanavir/ritonavir) resulted in elevated levels of buprenorphine and norbuprenorphine, and patients in one study reported increased sedation. Symptoms of opioid excess have been found in post-marketing reports of patients receiving buprenorphine and atazanavir with and without ritonavir concomitantly. |
| Intervention: | Monitor patients taking ZUBSOLV and atazanavir with and without ritonavir, and reduce dose of ZUBSOLV if warranted. |
| Examples: | Atazanavir, ritonavir. |
| Antiretrovirals: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) | |
| Clinical Impact: | Nucleoside reverse transcriptase inhibitors (NRTIs) do not appear to induce or inhibit the P450 enzyme pathway, thus no interactions with buprenorphine are expected. |
| Intervention: | None. |
| 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 ZUBSOLV 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 effect 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 ZUBSOLV is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. |
| Examples: | Phenelzine, tranylcypromine, linezolid. |
| Muscle Relaxants | |
| Clinical Impact: | Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. |
| Intervention: | Monitor patients receiving muscle relaxants and ZUBSOLV for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of ZUBSOLV and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, strongly consider prescribing naloxone for the emergency treatment of opioid overdose [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS]. |
| 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 the 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 ZUBSOLV is used concomitantly with anticholinergic drugs. |
Read the entire FDA prescribing information for Zubsolv (Buprenorphine and Naloxone Sublingual Tablets)
© Zubsolv Patient Information is supplied by Cerner Multum, Inc. and Zubsolv Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
