Subutex 0.4mg Uses

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What is Subutex 0.4mg?

Subutex 0.4mg is an opioid medication, sometimes called a narcotic.

This medication guide provides information about the Subutex 0.4mg brand of Subutex 0.4mg injection. Subutex 0.4mg is another brand of Subutex 0.4mg injection that is used to treat moderate to severe pain.

Subutex 0.4mg is used to treat opioid addiction. Subutex 0.4mg is not for use as a pain medication.

Subutex 0.4mg is given to people who have started addiction treatment with an oral form of Subutex 0.4mg placed under the tongue or inside the cheek (such as Suboxone or Subutex 0.4mg).

Subutex 0.4mg is available only in a certified healthcare setting under a special program. You will not be able to give yourself this medicine.

Subutex 0.4mg may also be used for purposes not listed in this medication guide.

Subutex 0.4mg indications

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Subutex 0.4mg is indicated for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal Subutex 0.4mg-containing product (i.e., doses of no more than 8 mg per day of Subutex 0.4mg or Suboxone sublingual tablet equivalent or generic equivalent).

Subutex 0.4mg should be used as part of a complete treatment program to include counseling and psychosocial support.

Subutex 0.4mg is not appropriate for new entrants to treatment and patients who have not achieved and sustained prolonged clinical stability, while being maintained on Subutex 0.4mg 8 mg per day or less of a Subutex 0.4mg or Suboxone sublingual tablet equivalent or generic equivalent.

How should I use Subutex 0.4mg?

Use Subutex 0.4mg patch as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Ask your health care provider any questions you may have about how to use Subutex 0.4mg patch.

Uses of Subutex 0.4mg in details

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Use: Labeled Indications

Opioid use disorder:

Extended-release injection: Maintenance treatment of moderate to severe opioid use disorder in patients who have initiated treatment with 8 to 24 mg of a transmucosal Subutex 0.4mg-containing product, followed by dose adjustment for a minimum of 7 days.

Subdermal implant: Maintenance treatment of opioid use disorder in patients who have achieved and sustained prolonged clinical stability on low to moderate doses (≤8 mg/day) of a transmucosal Subutex 0.4mg-containing product for 3 months or longer with no need for supplemental dosing or adjustments

Sublingual tablet: Medically supervised withdrawal and maintenance treatment of opioid use disorder.

Limitations of use: Subutex 0.4mg should be used as part of a complete treatment program to include counseling and psychosocial support.

Pain management:

Buccal film, transdermal patch: Management of pain severe enough to require around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Immediate-release injection: Management of pain severe enough to require an opioid analgesic and for which treatments are inadequate

Limitations of use: Reserve Subutex 0.4mg for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products, immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Subutex 0.4mg buccal film and transdermal patch are not indicated as an as needed analgesic.

Off Label Uses

Opioid withdrawal in heroin-dependent hospitalized patients (immediate-release injection)

Data from a limited number of patients studied who received Subutex 0.4mg parenterally for opioid withdrawal during hospitalization for an acute medical problem suggests that Subutex 0.4mg is safe when used in this setting; Additional data may be necessary to further define the role of Subutex 0.4mg in the management of postoperative pain as a perineural adjunct.

Subutex 0.4mg description

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Subutex 0.4mg transdermal patch is available in three strengths: Subutex 0.4mg 5 mg contains 5 mg Subutex 0.4mg in a drug-containing matrix that releases a nominal 5 micrograms of Subutex 0.4mg per hour over 7 days.

Subutex 0.4mg 10 mg contains 10 mg Subutex 0.4mg in a drug-containing matrix that releases a nominal 10 micrograms of Subutex 0.4mg per hour over 7 days.

Subutex 0.4mg 20 mg contains 20 mg Subutex 0.4mg in a drug-containing matrix that releases a nominal 20 micrograms of Subutex 0.4mg per hour over 7 days.

Subutex 0.4mg is a rectangular or square, transdermal patch consisting of a protective liner and functional layers including a Subutex 0.4mg-containing adhesive matrix.

Excipients/Inactive Ingredients: Levulinic acid, oleyl oleate, povidone (PVP), polyacrylate (dry solids), polyethylene terephthalate (PET).

Subutex 0.4mg dosage

Dosage and Titration: The lowest Subutex 0.4mg 5 mg should be used as the initial dose in all patients.

During initiation, titration, and treatment with Subutex 0.4mg, patients may continue their existing NSAID or acetaminophen regimen as needed.

The dose of Subutex 0.4mg should not be increased at less than 3-day intervals when steady-state levels are attained. Changes in Subutex 0.4mg dosage may be individually titrated based on the need for supplemental PRN analgesia and the patient's analgesic response to Subutex 0.4mg.

To increase the dose, a larger patch should replace the patch that is currently being worn, or a combination of patches should be applied in different places to achieve the desired dose. It is recommended that no more than two patches be applied at the same time, regardless of patch strength.

Titration should continue every 3-7 days until adequate analgesia is achieved.

If adequate pain control cannot be achieved with Subutex 0.4mg, therapy should be discontinued and the patient converted to an appropriate analgesic regimen as determined by a physician.

Discontinuation: After removal of Subutex 0.4mg, plasma concentrations decrease gradually. This should be considered when therapy with Subutex 0.4mg is to be followed by other opioids. As a general rule, a subsequent opioid should not be administered within 24 hours after removal of Subutex 0.4mg.

Conversion From Opioids: Subutex 0.4mg can be used as an alternative to treatment with other opioids. Such patients should be started on the lowest available dose Subutex 0.4mg 5 mg and continue taking short-acting supplemental analgesics during titration, as required.

Children: The safety and efficacy of Subutex 0.4mg in patients under 18 years of age has not been established.

Renal Impairment: No special dose adjustment of Subutex 0.4mg is necessary in patients with renal impairment.

Hepatic Impairment: There is no need for dosage adjustment when using Subutex 0.4mg in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment may accumulate Subutex 0.4mg during Subutex 0.4mg treatment. Consideration of alternate therapy should be given, and Subutex 0.4mg should be used with caution, if at all, in such patients.

Elderly: No dosage adjustment of Subutex 0.4mg is required in elderly patients.

Administration: Subutex 0.4mg should be applied to non-irritated, intact skin of the upper outer arm, upper chest, upper back or the side of the chest. Subutex 0.4mg should be applied to a relatively hairless or nearly hairless skin site. If none are available, the hair at the site should be clipped with scissors, not shaven.

Application sites should be rotated whenever a patch is replaced or added. Application sites should be re-used at no less than 3-week intervals.

If the application site must be cleaned, it should be done with clear water only. Soaps, alcohol, oils, lotions, or abrasive devices should not be used. The skin must be dry before the transdermal patch is applied.

Subutex 0.4mg should be worn continuously for 7 days. Subutex 0.4mg should be pressed firmly in place at the application site, making sure contact is complete, especially around the edges. If the edges of the patch begin to peel off, the edges may be taped down with suitable skin tape. If a transdermal patch falls off, a new one should be applied. Bathing, showering, or swimming should not affect the patch. While wearing Subutex 0.4mg, patients should be advised to avoid exposing the Subutex 0.4mg site to direct external heat sources such as heating pads, electric blankets, heat lamps, etc., as an increase in absorption of Subutex 0.4mg may occur. The effects of the use of Subutex 0.4mg while in hot tubs and saunas have not been studied.

Patch Application: Applying the Patch: Step 1: Each patch is sealed in a pouch. Just before use, open the pouch by tearing where indicated. Take out the patch.

Step 2: The sticky side of the patch is covered with a silvery protective foil. Carefully peel off half the foil. Try not to touch the sticky part of the patch.

Step 3: Stick the patch onto the chosen area of the skin and remove the remaining foil.

Step 4: Press the patch against the skin with the palm of the hand and count slowly to 30. Make sure that the whole patch is in contact with the skin, especially at the edges.

Step 5: Find a calendar that will help to remember to change the patch every 7th day. Mark the day when the first patch was put on and make a note of the time of day.

Wearing the Patch: Subutex 0.4mg should be applied to non-irritated, intact skin of the upper outer arm, upper chest, upper back or the side of the chest. Application sites should be re-used at no less than 3-week (21 days) intervals.

If a transdermal patch falls off before it needs changing, a new patch should be applied.

Changing the Patch: Take the old patch off.

Fold it in half with the sticky side inwards. Put the used patch into its original pouch. Then put the pouch in the bin used for the household rubbish. Even used patches contain some active medicine that may harm children or animals, so make sure the used patches are always kept well away from them. Throw it away carefully, out of the reach and sight of children.

Stick a new patch on a different appropriate skin site. The patient should not apply a new patch to the same site for the following 3-4 weeks.

Mark the day and time of application on the calendar.

Remember to change the patch at the same time of day each time.

Subutex 0.4mg interactions

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What other drugs will affect Subutex 0.4mg?

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Drug interactions common to other potent opioid analgesics also may occur with Subutex 0.4mg (Subutex 0.4mg). Particular care should be taken when Subutex 0.4mg (Subutex 0.4mg) is used in combination with central nervous system depressant drugs. Although specific information is not presently available, caution should be exercised when Subutex 0.4mg (Subutex 0.4mg) is used in combination with MAO inhibitors. There have been reports of respiratory and cardiovascular collapse in patients who received therapeutic doses of diazepam and Subutex 0.4mg (Subutex 0.4mg). A suspected interaction between Subutex 0.4mg (Subutex 0.4mg) and phenprocoumon resulting in purpura has been reported.

CYP3A4 Inhibitors: Since the metabolism of Subutex 0.4mg is mediated by the CYP3A4 isozyme, coadministration of drugs that inhibit CYP3A4 activity may cause decreased clearance of Subutex 0.4mg. Thus patients coadministered with inhibitors of CYP3A4 such as macrolide antibiotics (e.g., erythromycin), azole antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritanovir) while receiving Subutex 0.4mg (Subutex 0.4mg) should be carefully monitored and dosage adjustment made if warranted.

CYP3A4 Inducers: Cytochrome P450 inducers, such as rifampin, carbamazepine, and phenytoin, induce metabolism and as such may cause increased clearance of Subutex 0.4mg. Caution is advised when administering Subutex 0.4mg (Subutex 0.4mg) to patients receiving these medications and if necessary dose adjustments should be considered

Subutex 0.4mg side effects

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What are the possible side effects of Subutex 0.4mg?

The following adverse reactions are discussed in more detail in other sections of 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.

The safety of Subutex 0.4mg was evaluated in 848 opioid-dependent subjects. In these studies, there was a total of 557 subjects who received at least 6 monthly SC injections of Subutex 0.4mg and 138 subjects who received 12 monthly SC injections. Adverse events led to premature discontinuation in 4% of the group receiving Subutex 0.4mg compared with 2% in the placebo group (13-0001, NCT02357901).

In the Phase 3 open-label study (13-0003, NCT02510014), adverse events leading to drug dose reductions were reported in 7.3% of subjects receiving Subutex 0.4mg.

Table 1. Total Subjects Exposed to Subutex 0.4mg
Study 13-0001 (NCT02357901)

Up to 6 Injections

Study 13-0003 (NCT02510014) Total Subjects Exposed To

Subutex 0.4mg

*Not included in total subjects exposed to Subutex 0.4mg

† FLEX = 300 mg initial dose with an option to receive either 100 mg or 300 mg for subsequent dosing per clinician's discretion

‡ = Not included in total unique subjects exposed to Subutex 0.4mg, already accounted for in Study 13-0001 section of table

Roll-Over

Up to 6 Injections

De-Novo

Up to 12 Injections

Subutex 0.4mg 300/100 mg Subutex 0.4mg 300/300 mg Placebo From Subutex 0.4mg 300/100 mg To

Subutex 0.4mg 300/Flex†

From Subutex 0.4mg 300/300 mg To

Subutex 0.4mg 300/Flex†

From Placebo

To

Subutex 0.4mg 300/Flex†

Subutex 0.4mg 300/Flex
N = 203 N = 201 N = 100* N = 112‡ N = 113‡ N= 32 N = 412 N = 848

Table 2 shows the non-injection site-related adverse reactions (ADRs) for the groups receiving Subutex 0.4mg 300/300 mg (6 doses of 300 mg SC injections) 300/100 mg (300 mg SC injections for the first two doses followed by 4 doses of 100 mg SC injections) and placebo (volume-matched ATRIGEL® delivery system subcutaneous injections) reported following administration in the 6 month, double-blind, placebo-controlled study. The systemic safety profile for Subutex 0.4mg, given by a healthcare provider in clinical trials, was consistent with the known safety profile of transmucosal Subutex 0.4mg. Common adverse reactions associated with Subutex 0.4mg included constipation, nausea, vomiting, abnormal liver enzymes, headache, sedation and somnolence. Dose dependent hepatic effects observed in the Phase 3, double-blind study (13-0001, NCT02357901) included the incidence of ALT more than 3 times the upper limit of normal (> 3 × ULN) in 12.4%, 5.4%, and 4.0% of the Subutex 0.4mg 300/300-mg, Subutex 0.4mg 300/100-mg, and placebo groups, respectively. The incidence of AST > 3 × ULN was 11.4%, 7.9%, and 1.0%, respectively. Adverse drug reactions [by MedDRA Preferred Terms (PT)] reported in at least 2% of subjects receiving Subutex 0.4mg are grouped by System Organ Class (SOC).

Table 2. Adverse Reactions for Phase 3 Double-Blind Study: ≥2% of Subjects Receiving Subutex 0.4mg
System Organ Class

Preferred Term

PLACEBO Subutex 0.4mg

300/100 mg

Subutex 0.4mg

300/300 mg

Count (%) Count (%) Count (%)

*There were no cases of serious liver injury attributed to study drug.

Total N = 100 N = 203 N = 201
Gastrointestinal disorders 12 (12%) 51 (25.1%) 45 (22.4%)
Constipation 0 19 (9.4) 16 (8)
Nausea 5 (5) 18 (8.9) 16 (8)
Vomiting 4 (4) 19 (9.4) 11 (5.5)
General disorders and administration site conditions 17 (17%) 40 (19.7%) 49 (24.4%)
Fatigue 3 (3) 8 (3.9) 12 (6)
Investigations* 2 (2%) 21 (10.3%) 19 (9.5%)
Alanine aminotransferase increased (ALT) 0 2 (1) 10 (5)
Aspartate aminotransferase increased (AST) 0 7 (3.4) 9 (4.5)
Blood creatine phosphokinase increased (CPK) 1 (1) 11 (5.4) 5 (2.5)
Gamma-glutamyl transferase increased (GGT) 1 (1) 6 (3) 8 (4)
Nervous system disorders 7 (7%) 35 (17.2%) 25 (12.4%)
Headache 6 (6) 19 (9.4) 17 (8.5)
Sedation 0 7 (3.4) 3 (1.5)
Dizziness 2 (2) 5 (2.5) 3 (1.5)
Somnolence 0 10 (4.9) 4 (2)

Table 3 shows the injection site-related adverse events reported by ≥2 subjects in the Phase 3 studies. Most injection site adverse drug reactions (ADRs) were of mild to moderate severity, with one report of severe injection site pruritus. None of the injection site reactions were serious. One reaction, an injection site ulcer, led to study treatment discontinuation.

Table 3. Injection Site Adverse Drug Reactions Reported by ≥2 Subjects in the Phase 3 Double-Blind Study

*Patients received SUBOXONE film for a run-in period before they switched to Subutex 0.4mg injection.

Preferred term, n (%) 13-0001 (Ph3DB) 13-0003 (Ph3OL) All

Phase 3*

Roll–over De-novo
Subutex 0.4mg

300/300

(N = 201)

Subutex 0.4mg 300/100

(N = 203)

Placebo

(N = 100)

Subutex 0.4mg 300 →

Subutex 0.4mg

300/Flex

(N = 113)

Subutex 0.4mg 100 →

Subutex 0.4mg

300/Flex

(N = 112)

Placebo →

Subutex 0.4mg 300/Flex

(N = 32)

Subutex 0.4mg 300/Flex

(N = 412)

Total

Subutex 0.4mg (N = 848)

Subjects with any injection site reactions 38 (18.9%) 28 (13.8%) 9 (9.0%) 6 (5.3%) 13 (11.6%) 2 (6.3%) 61 (14.8%) 140 (16.5%)
Injection site pain 12 (6.0%) 10 (4.9%) 3 (3.0%) 4 (3.5%) 2 (1.8%) 2 (6.3%) 33 (8.0%) 61 (7.2%)
Injection site pruritus 19 (9.5%) 13 (6.4%) 4 (4.0%) 2 (1.8%) 6 (5.4%) 1 (3.1%) 17 (4.1%) 56 (6.6%)
Injection site erythema 6 (3.0%) 9 (4.4%) 0 1 (0.9%) 4 (3.6%) 0 21 (5.1%) 40 (4.7%)
Injection site induration 2 (1.0%) 2 (1.0%) 0 0 1 (0.9%) 0 7 (1.7%) 12 (1.4%)
Injection site bruising 2 (1.0%) 2 (1.0%) 0 0 0 0 2 (0.5%) 6 (0.7%)
Injection site swelling 1 (0.5%) 2 (1.0%) 0 1 (0.9%) 1 (0.9%) 0 1 (0.2%) 6 (0.7%)
Injection site discomfort 1 (0.5%) 1 (0.5%) 0 0 0 0 3 (0.7%) 5 (0.6%)
Injection site reaction 1 (0.5%) 0 0 0 3 (2.7%) 0 1 (0.2%) 5 (0.6%)
Injection site cellulitis 0 1 (0.5%) 0 0 0 0 2 (0.5%) 3 (0.4%)
Injection site infection 1 (0.5%) 0 1 (1.0%) 0 0 0 2 (0.5%) 3 (0.4%)

Longer-term experience

In an interim analysis of the ongoing open-label long-term safety study (13-0003), safety was evaluated for up to 12 injections over the course of a year. Adverse events were reported for 432 of 669 subjects during the treatment period. The overall adverse event profile was similar to the double-blind trial described above.

Postmarketing Experience

The most frequently reported systemic postmarketing adverse event observed with Subutex 0.4mg sublingual tablets was drug misuse or abuse. The most frequently reported systemic postmarketing adverse event with Subutex 0.4mg/naloxone sublingual tablets and film was peripheral edema.

The following adverse reactions have been identified during post-approval use of Subutex 0.4mg. 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 Subutex 0.4mg.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids.

Subutex 0.4mg contraindications

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What is the most important information I should know about Subutex 0.4mg?

Using Subutex 0.4mg improperly will increase your risk of serious side effects or death. Even if you have used other narcotic medications, you may still have serious side effects from Subutex 0.4mg. Follow all dosing instructions carefully.

Like other narcotic medicines, Subutex 0.4mg can slow your breathing. Death may occur if breathing becomes too weak.

Never crush a tablet or other pill to mix into a liquid for injecting the drug into your vein. This practice has resulted in death with the misuse of Subutex 0.4mg and similar prescription drugs.

Wear a medical alert tag or carry an ID card stating that you take Subutex 0.4mg, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you are being treated for narcotic addiction.

Avoid drinking alcohol, which can increase some of the side effects of Subutex 0.4mg. Using too much of this medicine in addition to drinking alcohol can cause death.

Do not stop using Subutex 0.4mg suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using Subutex 0.4mg. You may need to use less and less before you stop the medication completely.

This medication may impair your thinking or reactions. Avoid driving or operating machinery until you know how Subutex 0.4mg will affect you.



Active ingredient matches for Subutex 0.4mg:

Buprenorphine in Germany, Switzerland.


List of Subutex 0.4mg substitutes (brand and generic names)

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Unit description / dosage (Manufacturer)Price, USD
Talgesic 0.6 mg Injection (Indus Pharma Pvt. Ltd.)$ 0.09
Injectable; Injection; Buprenorphine Hydrochloride 0.3 mg / ml
Tablet; Sublingual; Buprenorphine Hydrochloride 0.2 mg
Tablet; Sublingual; Buprenorphine Hydrochloride 0.4 mg
Temgesic 200 mcg x 50's
Temgesic 300 mcg/1 mL x 1 mL x 5's
Temgesic 0.2 mg x 10 x 5's
Temgesic 0.3 mg/1 mL x 1 mL x 5's$ 52.13
Temgesic 0.2 mg x 50's$ 57.35
Injectable; Injection; Buprenorphine Hydrochloride 0.3 mg / ml
Tablet; Sublingual; Buprenorphine Hydrochloride 0.2 mg
Tablet; Sublingual; Buprenorphine Hydrochloride 0.4 mg
Temgesic 200 mcg x 50's
Temgesic 300 mcg/1 mL x 1 mL x 5's
Temgesic 0.2 mg x 10 x 5's
Temgesic 0.3 mg/1 mL x 1 mL x 5's$ 52.13
Temgesic 0.2 mg x 50's$ 57.35
Injectable; Injection; Buprenorphine Hydrochloride 0.3 mg / ml
Tablet; Sublingual; Buprenorphine Hydrochloride 0.2 mg
Tablet; Sublingual; Buprenorphine Hydrochloride 0.4 mg
Temgesic 200 mcg x 50's
Temgesic 300 mcg/1 mL x 1 mL x 5's
Temgesic 0.2 mg x 10 x 5's
Temgesic 0.3 mg/1 mL x 1 mL x 5's$ 52.13
Temgesic 0.2 mg x 50's$ 57.35
Tablet, Film-Coated; Oral; Buprenorphine Hydrochloride
Tablet; Sublingual; Buprenorphine Hydrochloride 0.2 mg
Tablet; Sublingual; Buprenorphine Hydrochloride 0.4 mg
TIDIGESIC Injection / 0.3mg per ml / 1ml units (Sun Pharmaceutical Industries Ltd.)$ 0.14
TIDIGESIC Tablet Sub - lingual / 0.2mg / 10 units (Sun Pharmaceutical Industries Ltd.)$ 0.30
TIDIGESIC Injection / 0.3mg per ml / 2ml units (Sun Pharmaceutical Industries Ltd.)$ 0.18
Tidigesic 0.2mg SL-TAB / 10 (Sun Pharmaceutical Industries Ltd.)$ 0.30
Tidigesic 0.3mg/ml INJ / 1ml (Sun Pharmaceutical Industries Ltd.)$ 0.14
Tidigesic 0.3mg/ml INJ / 2ml (Sun Pharmaceutical Industries Ltd.)$ 0.18
0.2 mg x 10's (Sun Pharmaceutical Industries Ltd.)$ 0.30

References

  1. DailyMed. "BUPRENORPHINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
  2. PubChem. "buprenorphine". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
  3. DrugBank. "buprenorphine". http://www.drugbank.ca/drugs/DB00921 (accessed September 17, 2018).

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