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Bupropion hydrochloride 300 mg Tablet, Extended Release, 90-count — NDC 63304-724-90 (Billing 63304-0724-90)

by Sun Pharmaceutical Industries, Inc. · 90 TABLET, EXTENDED RELEASE in 1 BOTTLE

This is a package of 90 tablets of Bupropion hydrochloride 300 mg Tablet, Extended Release from Sun Pharmaceutical Industries, Inc., no longer marketed (first marketed Jan 2021), no longer in the FDA NDC Directory; retail pharmacies pay about $0.1034 per tablet (NADAC).

NDC 63304-0724-90
🏷️ FDA NDC (as labeled) 63304-724-90 billing pads the product segment with a zero
This package
Contains90-count Cost per ea$0.1034 NADAC Per package$9.31 / 90 tablets Pack sizes3 compare ↓
Also priced by: Medicaid pays $0.5168/unit — full pricing hub ↓
Product page 63304-0724-05 Also comes in: 30 tablets 63304-724-30 500 tablets 63304-724-05
Rx only Generic Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 9, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️
Other active recalls for Bupropion Hydrochloride (different manufacturers) — 3 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Sep 15, 2025 — Failed Tablet/Capsule Specifications (Graviti Pharmaceuticals Private Limited) · FDA recall D-0037-2026
Class II · Jun 24, 2024 — Failed Dissolution Specifications; the product is dissolving faster than the specified limits. (Amerisource Health Services LLC) · FDA recall D-0590-2024
Class II · Dec 29, 2023 — Presence of Foreign Tablets/Capsules (Rising Pharma Holding, Inc.) · FDA recall D-0222-2024
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Jan 2025. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 63304-724-90
Product NDC 63304-724
11-digit billing NDC 63304072490
NCPDP billing unit EA — each (per item)
RxCUI 993557
UNII ZG7E5POY8O
UPC 0363304724301
Application # ANDA203650
SPL Set ID fddb7191-c4f9-4e82-bd7d-259c3767710a
Established class (EPC) Aminoketone
Mechanism of action Dopamine Uptake Inhibitors; Norepinephrine Uptake Inhibitors
Physiologic effect Increased Dopamine Activity; Increased Norepinephrine Activity
DEA schedule Non-controlled
Marketing category ANDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Jan 2025)
Marketing start 2021-01-01
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance BUPROPION HYDROCHLORIDE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 58300040107530
GPI class buPROPion HCl ER (XL)
GCN Seq No 053007
GCN 20318
HICL code 001653
Ingredient (HICL) Bupropion Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H7
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 1)
HIC3 code H7D
Therapeutic class — specific (HIC3) Norepinephrine And Dopamine Reuptake Inhib (Ndris)
AHFS code 28:16.04.92
AHFS class Antidepressants, Miscellaneous
FDB label name BUPROPION HCL XL 300 MG TABLET
FDB brand name Bupropion Xl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 053007
  • GCN: 20318
  • GPI-14 (Medi-Span): 58300040107530
  • HICL (First Databank): 001653
  • AHFS class code: 28:16.04.92
  • RxCUI (RxNorm): 993557
Why two NDCs? The FDA registers this code as 63304-724-90 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 63304-0724-90. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Aminoketone class.

Pharmacologic class Aminoketone
Drug family (ATC) Centrally acting antiobesity products, Other antidepressants
How it works Norepinephrine Uptake Inhibitors, Dopamine Uptake Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name BUPROPION HCL XL 300 MG TABLET Ingredient Bupropion Hcl
📗 Our plain-language guide HelloPharmacist
  • Bupropion treats major depressive disorder. Some extended-release products, like Aplenzin and bupropion XL, can also prevent seasonal affective disorder, the depression that return...
  • Take it by mouth exactly as prescribed. XL tablets are taken once in the morning, with or without food, and must be swallowed whole. Your doctor will usually raise the dose gradual...
  • The most common ones are dry mouth, nausea, trouble sleeping, dizziness, headache, anxiety and tremor. Call your doctor right away if you have a seizure, new suicidal thoughts, sev...
  • It's best to limit or avoid alcohol. Rare neuropsychiatric events and lower alcohol tolerance have been reported. Never suddenly stop heavy drinking while on bupropion without talk...
📖 Read our full Bupropion guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
1
Nutrient depletion considerations

Bupropion may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Bupropion nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $0.103 $9.31 / 90 tablets
Medicaid paysCMS SDUD · 12 mo $0.5168 $46.51 / 90 tablets
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
NADAC price history (per ea) — tap or hover for the price & month
Dec 2021 May 2022 Nov 2022 Feb 2026 $0.199 $0.103
▼ Down 46% over the last 18 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startMarketing endStatus
63304-0724-05 63304-724-05 Main listing 500 TABLET, EXTENDED RELEASE in 1 BOTTLE $0.1034 / ea $51.68 2021-01-01 — Discontinued by firm
63304-0724-30 63304-724-30 30 TABLET, EXTENDED RELEASE in 1 BOTTLE $0.1034 / ea $3.10 2021-01-01 — Discontinued by firm
63304-0724-90 You're viewing this 90 TABLET, EXTENDED RELEASE in 1 BOTTLE $0.1034 / ea $9.30 2021-01-01 — Discontinued by firm

You're viewing one of 3 pack sizes for this product.

This pack effectively ties for the lowest per-ea cost of the 3 priced pack sizes ($0.1034 NADAC).

This pack accounts for about 10% of this product's recent Medicaid fills; most go to the 500 tablets pack. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 90-count package — 90 tablet, extended release in 1 bottle.
How does this package differ from NDC 63304-0724-30?
Both are Bupropion hydrochloride 300 mg Tablet, Extended Release — the drug itself is identical. This page's package is the 90-count one, while NDC 63304-0724-30 is the 30 tablets package.
What NDC number is used to bill for this package of Bupropion hydrochloride 300 mg Tablet, Extended Release?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Bupropion Hydrochloride XL 300 mg 00904-7469-04 Major 1 tablet $0.100 AB3 Availability likely save 3%
bupropion hydrochloride 300 mg 16571-0863-03 Rising 30 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride 300 mg 16729-0444-10 Accord 30 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride 300 mg 31722-0488-05 Camber 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride XL 300 mg 42806-0416-05 Epic 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride (XL) 300 mg 43598-0656-05 Dr 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride 300 mg 45963-0142-05 Actavis 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride (XL) 300 mg 50228-0145-05 ScieGen 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride 300 mg 50268-0134-13 AvPAK 1 tablet $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride 300 mg 60687-0793-21 American 1 tablet $0.100 AB3 Availability likely save 3%
Bupropion hydrochloride 300 mg 68001-0614-03 BluePoint 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride XL 300 mg 68180-0320-02 Lupin 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride 300 mg 69097-0072-12 Cipla 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride (XL) 300 mg 69097-0876-02 CIPLA 30 tablets $0.100 — Availability likely save 3%
Bupropion Hydrochloride XL 300 mg 69367-0289-05 Westminster 500 tablets $0.100 AB3 Discontinued save 3%
Bupropion hydrochloride 300 mg 70010-0785-03 Granules 30 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride XL 300 mg 82009-0052-05 Quallent 500 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride (XL) 300 mg 83301-0025-01 Mullan 30 tablets $0.100 AB3 Availability likely save 3%
Bupropion Hydrochloride XL 300 mg 42806-0349-05 Epic 500 tablets $0.101 AB3 Availability likely save 2%
Bupropion hydrochloride 300 mgthis 63304-0724-90 Sun 90 tablets $0.103 — Discontinued —
Bupropion Hydrochloride 300 mg 68001-0520-03 BluePoint 500 tablets $0.107 AB3 FDA listed +4%
Bupropion Hydrochloride (XL) 300 mg 24979-0102-02 Upsher-Smith 500 tablets $0.112 — Discontinued +8%
Bupropion Hydrochloride XL 300 mg 70436-0011-02 Slate 500 tablets $0.115 AB3 Availability likely +12%
Bupropion hydrochloride (XL) 300 mg 00527-2430-32 Lannett 30 tablets $0.144 AB3 FDA listed +40%
Wellbutrin Xl 300 mg 00187-0731-07 Bausch 7 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 00615-8505-05 NCS 15 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 50090-4749-00 A-S 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 50090-5245-00 A-S 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 50090-5334-00 A-S 30 tablets — — FDA listed —
Bupropion Hydrochloride XL 300 mg 50090-6961-00 A-S 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride XL 300 mg 50090-6962-00 A-S 90 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 50090-7334-00 A-S 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 50090-7335-00 A-S 90 tablets — AB3 FDA listed —
Bupropion Hydrochloride XL 300 mg 50090-7602-00 A-S 90 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 55700-0820-30 Quality 30 tablets — AB3 Discontinued —
Bupropion Hydrochloride (Xl) 300 mg 62135-0876-30 Chartwell 30 tablets — AB3 FDA listed —
bupropion 300 mg 63187-0521-30 Proficient 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 63187-0819-30 Proficient 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 63629-8475-01 Bryant 500 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 63629-8476-01 Bryant 30 tablets — AB3 FDA listed —
bupropion 300 mg 65841-0780-05 Zydus 500 tablets — AB3 FDA listed —
Bupropion hydrochloride 300 mg 67046-1497-03 Coupler 30 tablets — AB3 FDA listed —
Bupropion hydrochloride 300 mg 67046-1648-03 Coupler 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride XL 300 mg 68071-3928-09 NuCare 90 tablets — AB3 FDA listed —
bupropion 300 mg 68382-0354-05 Zydus 500 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 68788-7992-01 Preferred 100 tablets — AB3 FDA listed —
Bupropion hydrochloride 300 mg 68788-8815-01 Preferred 100 tablets — AB3 FDA listed —
Bupropion hydrochloride (XL) 300 mg 69680-0158-30 Vitruvias 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 70518-3790-00 REMEDYREPACK 30 tablets — AB3 Discontinued —
Bupropion Hydrochloride XL 300 mg 70518-4014-00 REMEDYREPACK 90 tablets — AB3 FDA listed —
bupropion hydrochloride 300 mg 70518-4343-00 REMEDYREPACK 30 tablets — AB3 FDA listed —
Bupropion hydrochloride 300 mg 70518-4415-00 REMEDYREPACK 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride XL 300 mg 70518-4446-00 REMEDYREPACK 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride XL 300 mg 70518-4551-00 REMEDYREPACK 90 tablets — AB3 Discontinued —
Bupropion Hydrochloride 300 mg 71205-0465-30 Proficient 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 71205-0968-30 Proficient 30 tablets — — FDA listed —
Bupropion Hydrochloride (XL) 300 mg 71335-1114-01 Bryant 30 tablets — — Discontinued —
Bupropion Hydrochloride 300 mg 71335-1214-01 Bryant 30 tablets — AB3 Discontinued —
Bupropion Hydrochloride (XL) 300 mg 71335-2312-01 Bryant 30 tablets — AB3 FDA listed —
Bupropion hydrochloride 300 mg 71335-2499-01 Bryant 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 72162-1278-09 Bryant 90 tablets — — Discontinued —
Bupropion Hydrochloride (XL) 300 mg 72162-1527-03 Bryant 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 72189-0124-30 DIRECT 30 tablets — AB3 FDA listed —
Bupropion HCL ER (XL) 300 mg 72189-0539-30 Direct_RX 30 tablets — AB3 FDA listed —
buPropion Hydrochloride XL 300 mg 72516-0036-03 Oryza 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 72789-0112-90 PD-Rx 90 tablets — — Discontinued —
Bupropion Hydrochloride (XL) 300 mg 76282-0481-05 Exelan 500 tablets — — FDA listed —
Bupropion Hydrochloride 300 mg 76420-0812-01 Asclemed 100 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 77771-0145-05 RADHA 500 tablets — AB3 FDA listed —
Bupropion Hydrochloride XL 300 mg 80425-0468-01 Advanced 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 80425-0539-01 Advanced 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 82804-0013-30 Proficient 30 tablets — — FDA listed —
Bupropion Hydrochloride 300 mg 85534-0006-01 HAWAII 100 tablets — AB3 FDA listed —
Bupropion hydrochloride 300 mg 87441-0014-01 Unit 30 tablets — AB3 FDA listed —
Bupropion Hydrochloride (XL) 300 mg 68788-4172-01 Preferred 100 tablets — AB3 FDA listed —
Bupropion Hydrochloride 300 mg 59651-0512-05 Aurobindo 500 tablets — AB3 FDA listed —
Bupropion hydrochloride 300 mg 70518-4739-00 REMEDYREPACK 90 tablets — AB3 FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2021
On the market since
Jan 2021
📍
2026
Currently FDA-listed
5 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerSun Pharmaceutical Industries, Inc.
Application holderSUN PHARMACEUTICAL INDUSTRIES LTD
FDA applicationANDA203650 (ANDA)
Labeler code63304
First marketedJan 2021
Product typeHuman Prescription Drug
Portfolio890 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 145 words ▾

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects aged 65 and older [see Warnings and Precautions (5.1)] . In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors.

Advise families and caregivers of the need for close observation and communication with the prescriber [see Warnings and Precautions (5.1)] . W ARN ING: SUICIDAL THOUGHTS AND BEHAVIORS S e e full prescribing information for complete boxed warning. Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.

(5.1) Monitor for worsening and emergence of suicidal thoughts and behaviors. (5.1)

🎯 Indications and Usage 205 words ▾

1 INDICATIONS AND USAGE Bupropion hydrochloride extended-release tablets, USP (XL) are aminoketone antidepressant, indicated for: treatment of major depressive disorder (MDD) (1.1) prevention of seasonal affective disorder (SAD) (1.2)

1.1Major Depressive Disorder (MDD) Bupropion hydrochloride extended-release tablets, USP (XL) are indicated for the treatment of major depressive disorder (MDD), as defined by the Diagnostic and Statistical Manual (DSM). The efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with MDD. The efficacy of the sustained-release formulation of bupropion in the maintenance treatment of MDD was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8-week study of acute treatment [see Clinical Studies (14.1)] .

1.2Seasonal Affective Disorder (SAD) Bupropion hydrochloride extended-release tablets, USP (XL) are indicated for the prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (SAD). The efficacy of bupropion hydrochloride extended-release tablets in the prevention of seasonal major depressive episodes was established in 3 placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal pattern as defined in the DSM [see Clinical Studies (14.2) ].

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION General Increase dose gradually to reduce seizure risk. (2.1, 5.3) Periodically reassess the dose and need for maintenance treatment. (2.2) Major Depressive Disorder Starting dose: 150 mg once daily.

Usual target dose: 300 mg once daily (2.2) After 4 days, may increase the dose to 300 mg once daily. (2.2) Seasonal Affective Disorder Initiate treatment in the autumn prior to onset of seasonal depressive symptoms. (2.3) Starting dose: 150 mg once daily.

Usual target dose: 300 mg once daily. (2.3) After one week, may increase the dose to 300 mg once daily. (2.3) Continue treatment through the winter season.

(2.3) Hepatic Impairment Moderate to severe hepatic impairment: 150 mg every other day (2.6) Mild hepatic impairment: Consider reducing the dose and/or frequency of dosing. (2.6, 8.7) Renal Impairment Consider reducing the dose and/or frequency of dosing. (2.7, 8.6)

2.1General Instructions for Use To minimize the risk of seizure, increase the dose gradually [see Warnings and Precautions (5.3) ]. Bupropion hydrochloride extended-release tablets (XL) should be swallowed whole and not crushed, divided, or chewed. Bupropion hydrochloride extended-release tablets (XL) should be administered in the morning and may be taken with or without food.

2.2Dosage for Major Depressive Disorder (MDD) The recommended starting dose for MDD is 150 mg once daily in the morning. After 4 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning. It is generally agreed that acute episodes of depression require several months or longer of antidepressant treatment beyond the response in the acute episode.

It is unknown whether the bupropion hydrochloride extended-release tablets (XL) dose needed for maintenance treatment is identical to the dose that provided an initial response. Periodically reassess the need for maintenance treatment and the appropriate dose for such treatment.

2.3Dosage for Seasonal Affective Disorder (SAD) The recommended starting dose for SAD is 150 mg once daily. After 7 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning. Doses above 300 mg of bupropion hydrochloride extended-release were not assessed in the SAD trials.

For the prevention of seasonal MDD episodes associated with SAD, initiate bupropion hydrochloride extended-release tablets (XL) in the autumn, prior to the onset of depressive symptoms. Continue treatment through the winter season. Taper and discontinue bupropion hydrochloride extended-release tablets (XL) in early spring.

For patients treated with 300 mg per day, decrease the dose to 150 mg once daily before discontinuing bupropion hydrochloride extended-release tablets (XL). Individualize the timing of initiation, and duration of treatment should be individualized, based on the patient’s historical pattern of seasonal MDD episodes.

2.4Switching Patients from Bupropion Hydrochloride Tablets or from Wellbutrin SR Sustained-Release Tablets When switching patients from bupropion hydrochloride Tablets to bupropion hydrochloride extended-release tablets (XL) or from Wellbutrin SR Sustained-Release Tablets to bupropion hydrochloride extended-release tablets (XL), give the same total daily dose when possible.

2.5To Discontinue Bupropion Hydrochloride Extended-Release Tablets (XL), Taper the Dose When discontinuing treatment in patients treated with bupropion hydrochloride extended-release tablets (XL) 300 mg once daily, decrease the dose to 150 mg once daily prior to discontinuation.

2.6Dosage Adjustment in Patients with Hepatic Impairment In patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose is 150 mg every other day . In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)] .

2.7Dose Adjustment in Patients with Renal… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 44 words ▾

3 DOSAGE FORMS AND STRENGTHS Bupropion Hydrochloride Extended-Release Tablets, USP (XL), 300 mg of bupropion hydrochloride, are white to pale yellow, round, film-coated tablets imprinted with ‘L1’ in black ink on one side and plain on the other side. Extended-release tablets: 300 mg (3)

⛔ Contraindications ~2 min read ▾

4 CONTRAINDICATIONS Bupropion hydrochloride extended-release tablets (XL) is contraindicated in patients with seizure disorder. • Bupropion hydrochloride extended-release tablets (XL) is contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with bupropion hydrochloride extended-release tablets (XL) [see Warnings and Precautions (5.3)]. • Bupropion hydrochloride extended-release tablets (XL) is contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions (5.3) and Drug Interactions (7.3)] . • The use of MAOIs (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride extended-release tablets (XL) or within 14 days of discontinuing treatment with bupropion hydrochloride extended-release tablets (XL) is contraindicated.

There is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (XL) is used concomitantly with MAOIs. The use of bupropion hydrochloride extended-release tablets (XL) within 14 days of discontinuing treatment with an MAOI is also contraindicated. Starting bupropion hydrochloride extended-release tablets (XL) in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated [see Dosage and Administration (2.9), Warnings and Precautions (5.4) and Drug Interactions (7.6)] . • Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients with known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release tablets (XL).

Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported [see Warnings and Precautions (5.8)] . Seizure disorder. (4, 5.3) Current or prior diagnosis of bulimia or anorexia nervosa.

(4, 5.3) Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs. (4, 5.3) Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with bupropion hydrochloride extended-release tablets (XL) or within 14 days of stopping treatment with bupropion hydrochloride extended-release tablets (XL). Do not use bupropion hydrochloride extended-release tablets (XL) within 14 days of stopping an MAOI intended to treat psychiatric disorders.

In addition, do not start bupropion hydrochloride extended-release tablets (XL) in a patient who is being treated with linezolid or intravenous methylene blue. (4, 7.6) Known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release tablets (XL) (4, 5.8)

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Neuropsychiatric Adverse Events During Smoking Cessation: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with bupropion hydrochloride extended-release tablets (XL) for the occurrence of such symptoms and instruct them to discontinue bupropion hydrochloride extended-release tablets (XL) and contact a healthcare provider if they experience such adverse events.

(5.2) Seizure Risk: The risk is dose-related. Can minimize risk by limiting daily dose to 450 mg and gradually increasing the dose. Discontinue if seizure occurs.

(4, 5.3, 7.3) Hypertension: bupropion hydrochloride extended-release tablets (XL) can increase blood pressure. Monitor blood pressure before initiating treatment and periodically during treatment. (5.4) Activation of Mania/Hypomania: Screen patients for bipolar disorder and monitor for these symptoms.

(5.5) Psychosis and Other Neuropsychiatric Reactions: Instruct patients to contact a healthcare professional if such reactions occur. (5.6) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. (5.7)

5.1Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

There has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (Selective Serotonin Reuptake Inhibitors [SSRIs] and others) show that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders.

Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients.

There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications.

These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1 . Table 1: Risk Differences in the Number of Suicidality Cases by Age Group in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Suicidal thoughts and behaviors in children, adolescents, and young adults [see Warnings and Precautions (5.1) ] Neuropsychiatric adverse events and suicide risk in smoking cessation treatment [see Warnings and Precautions (5.2) ] Seizure [see Warnings and Precautions (5.3) ] Hypertension [see Warnings and Precautions (5.4) ] Activation of mania or hypomania [see Warnings and Precautions (5.5) ] Psychosis and other neuropsychiatric events [see Warnings and Precautions (5.6) ] Angle-Closure Glaucoma [see Warnings and Precautions (5.7) ] Hypersensitivity reactions [see Warnings and Precautions (5.8) ] Most common adverse reactions are (incidence ≥ 5%; ≥ 2 times placebo rate): dry mouth, nausea, insomnia, dizziness, pharyngitis, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, tinnitus, myalgia, anorexia, urinary frequency, rash.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-406-7984 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. Commonly Observed Adverse Reactions in Controlled Clinical Trials of Sustained-Release Bup r opion Hydrochloride Adverse reactions that occurred in at least 5% of patients treated with bupropion HCl sustained-release (300 mg and 400 mg per day) and at a rate at least twice the placebo rate are listed below.

300 mg/day of bupropion HCl sustained-release: anorexia, dry mouth, rash, sweating, tinnitus, and tremor. 400 mg/day of bupropion HCl sustained-release: abdominal pain, agitation, anxiety, dizziness, dry mouth, insomnia, myalgia, nausea, palpitation, pharyngitis, sweating, tinnitus, and urinary frequency. Bupropion hydrochloride extended-release tablets (XL) have been demonstrated to have similar bioavailability both to the immediate-release and sustained-release formulations of bupropion.

The information included under this subsection and under subsection 6.2 is based primarily on data from controlled clinical trials with the sustained-release and extended-release formulations of bupropion hydrochloride. Major Depressive Disorder Adverse Reactions Leading to Discontinuation of Treatment with Bupropion HCl Immediate-Release, Bupropion HCl Sustained-Release, and Bupropion HCl Extended-Release in Major Depressive Disorder Trials In placebo-controlled clinical trials with bupropion HCl sustained-release, 4%, 9%, and 11% of the placebo, 300 mg/day and 400 mg/day groups, respectively, discontinued treatment because of adverse reactions.

The specific adverse reactions leading to discontinuation in at least 1% of the 300 mg/day or 400 mg/day groups and at a rate at least twice the placebo rate are listed in Table 2 . T able 2: Treatment Discontinuation Due to Adverse Reactions in Placebo-Controlled T r ials in MDD A dverse Reaction T erm Placebo ( n = 385) Bup r opion HCl Su stained-Release 300 mg/day ( n = 376) Bup r opion HCl Su stained-Release 400 mg/day ( n = 114) Rash 0% 2.4% 0.9% Nausea 0.3% 0.8% 1.8% Agitation 0.3% 0.3% 1.8% Migraine 0.3% 0% 1.8% In clinical trials with bupropion HCl immediate-release, 10% of patients and volunteers discontinued due to an adverse reaction.

Reactions resulting in discontinuation (in addition to those listed above for the sustained-release formulation), included vomiting, seizures, and sleep disturbances. Adverse Reactions Occurring at an Incidence of > 1% in Patients Treated with Bupropion HCl Immediate-Release or Bupropion HCl Sustained-Release in MDD Table 3 summarizes the adverse reactions that occurred in placebo-controlled trials in patients treated with bupropion HCl sustained-release… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS CYP2B6 inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical exposure, but should not exceed the maximum recommended dose. (7.1) Drugs metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide).

Consider dose reduction when using with bupropion. (7.2) Drugs that lower seizure threshold: Dose bupropion hydrochloride extended-release tablets (XL) with caution. (5.3, 7.3) Dopaminergic Drugs (levodopa and amantadine): CNS toxicity can occur when used concomitantly with bupropion hydrochloride extended-release tablets (XL).

(7.4) MAOIs: Increased risk of hypertensive reactions can occur when used concomitantly with bupropion hydrochloride extended-release tablets (XL). (7.6) Drug-laboratory test interactions: Bupropion hydrochloride extended-release tablets (XL) can cause false-positive urine test results for amphetamines. (7.7)

7.1Potential for Other Drugs to Affect Bupropion Hydrochloride Extended-Release Tablets (XL) Bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between bupropion hydrochloride extended-release tablets (XL) and drugs that are inhibitors or inducers of CYP2B6. Inhibitors of CYP2B6 T iclopidine and Clopidogrel: Concomitant treatment with these drugs can increase bupropion exposures but decrease hydroxybupropion exposure.

Based on clinical response, dosage adjustment of bupropion hydrochloride extended-release tablets (XL) may be necessary when coadministered with CYP2B6 inhibitors (e.g., ticlopidine or clopidogrel) [see Clinical Pharmacology (12.3)] . Inducers of CYP2B6 Ritonavir, Lopinavir, and Efavirenz: Concomitant treatment with these drugs can decrease bupropion and hydroxybupropion exposure. Dosage increase of bupropion hydrochloride extended-release tablets (XL) may be necessary when coadministered with ritonavir, lopinavir, or efavirenz but should not exceed the maximum recommended dose [see Clinical Pharmacology (12.3)] .

Carbamazepine, Phenobarbital, Phenytoin: While not systemically studied, these drugs may induce metabolism of bupropion and may decrease bupropion exposure [see Clinical Pharmacology (12.3)] . If bupropion is used concomitantly with a CYP inducer, it may be necessary to increase the dose of bupropion, but the maximum recommended dose should not be exceeded.

7.2Potential for Bupropion Hydrochloride Extended-Release Tablets (XL) to Affect Other Drugs Drugs Metabolized by CYP2D6 Bupropion and its metabolites (erythrohydrobupropion, threohydrobupropion, hydroxybupropion) are CYP2D6 inhibitors. Therefore, coadministration of bupropion hydrochloride extended-release tablets (XL) with drugs that are metabolized by CYP2D6 can increase the exposures of drugs that are substrates of CYP2D6. Such drugs include certain antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, and sertraline), antipsychotics (e.g., haloperidol, risperidone, and thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, and flecainide).

When used concomitantly with bupropion hydrochloride extended-release tablets (XL), it may be necessary to decrease the dose of these CYP2D6 substrates, particularly for drugs with a narrow therapeutic index. Drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), theoretically could have reduced efficacy when administered concomitantly with inhibitors of CYP2D6 such as bupropion. Patients treated concomitantly with bupropion hydrochloride extended-release tablets (XL)… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ . Risk Summary Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see Data).

There are risks to the mother associated with untreated depression (see Clinical Considerations). When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. When given to pregnant rabbits during organogenesis, non-dose-related increases in incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater.

Decreased fetal weights were seen at doses twice the MRHD and greater (see Animal Data) . The estimated background risk for major birth defects and miscarriage are unknown for the indicated population. All pregnancies have a background rate of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants.

Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. Data Human Data Data from the international bupropion Pregnancy Registry (675 first trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. The Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations.

No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database, which has a limited number of exposed cases with cardiovascular malformations, and a case-controlled study (6,853 infants with cardiovascular malformations and 5,753 with non-cardiovascular malformations) from the National Birth Defects Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester.

Study findings on bupropion exposure during the first trimester and risk left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO (n = 10; adjusted odds ratio (OR) = 2.6; 95% CI 1.2, 5.7), and the Slone Epidemiolog… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ . Risk Summary Data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see Data).

There are risks to the mother associated with untreated depression (see Clinical Considerations). When bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 10 times the maximum recommended human dose (MRHD) of 450 mg/day. When given to pregnant rabbits during organogenesis, non-dose-related increases in incidence of fetal malformations and skeletal variations were observed at doses approximately equal to the MRHD and greater.

Decreased fetal weights were seen at doses twice the MRHD and greater (see Animal Data) . The estimated background risk for major birth defects and miscarriage are unknown for the indicated population. All pregnancies have a background rate of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk A prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants.

Consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. Data Human Data Data from the international bupropion Pregnancy Registry (675 first trimester exposures) and a retrospective cohort study using the United Healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. The Registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations.

No increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. The prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international Pregnancy Registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). Data from the United Healthcare database, which has a limited number of exposed cases with cardiovascular malformations, and a case-controlled study (6,853 infants with cardiovascular malformations and 5,753 with non-cardiovascular malformations) from the National Birth Defects Prevention Study (NBDPS) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester.

Study findings on bupropion exposure during the first trimester and risk left ventricular outflow tract obstruction (LVOTO) are inconsistent and do not allow conclusions regarding possible association. The United Healthcare database lacked sufficient power to evaluate this association; the NBDPS found increased risk for LVOTO (n = 10; adjusted odds ratio (OR) = 2.6; 95% CI 1.2, 5.7), and the Slone Epidemiology case control study did not f… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 46 words ▾

8.4Pediatric Use Safety and effectiveness in the pediatric population have not been established. When considering the use of bupropion hydrochloride extended-release tablets (XL) in a child or adolescent, balance the potential risks with the clinical need [see Boxed Warning and Warnings and Precautions (5.1)] .

🆘 Overdosage 171 words ▾

10 OVERDOSAGE

10.1Human Overdose Experience Overdoses of up to 30 grams or more of bupropion have been reported. Seizure was reported in approximately one third of all cases. Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes such as conduction disturbances or arrhythmias, clonus, myoclonus, and hyperreflexia.

Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses. Although most patients recovered without sequelae, deaths associated with overdoses of bupropion alone have been reported in patients ingesting large doses of the drug. Multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest prior to death were reported in these patients.

10.2Overdosage Management Consult a Certified Poison Control Center for up-to-date guidance and advice. Call 1-800-222-1222 or refer to www.poison.org. There are no known antidotes for bupropion. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Consider the possibility of multiple drug overdose.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action of bupropion is unknown, as is the case with other antidepressants. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine and does not inhibit monoamine oxidase or the reuptake of serotonin.

12.3Pharmacokinetics Bupropion is a racemic mixture. The pharmacologic activity and pharmacokinetics of the individual enantiomers have not been studied. Following chronic dosing, the mean steady-state plasma concentration of bupropion was reached within 8 days.

The mean elimination half-life (±SD) of bupropion is 21 (±9) hours. In a study comparing 14-day dosing with bupropion hydrochloride extended-release tablets (XL), 300 mg once-daily to the immediate-release formulation of bupropion at 100 mg 3 times daily, equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the three metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion). Additionally, in a study comparing 14-day dosing with bupropion hydrochloride extended-release tablets (XL) 300 mg once daily to the sustained-release formulation of bupropion at 150 mg 2 times daily, equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the three metabolites.

Absorption Following single oral administration of bupropion hydrochloride extended-release tablets (XL) to healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5 hours. The presence of food did not affect the peak concentration or area under the curve of bupropion. Distribution I n vitro tests show that bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg/mL.

The extent of protein binding of the hydroxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that of bupropion. Met abolism Bupropion is extensively metabolized in humans. Three metabolites are active: hydroxybupropion, which is formed via hydroxylation of the tert- butyl group of bupropion, and the amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl group.

In vitro findings suggest that CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, while cytochrome P450 enzymes are not involved in the formation of threohydrobupropion. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of meta-chlorobenzoic acid, which is then excreted as the major urinary metabolite. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized.

However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is one half as potent as bupropion, while threohydrobupropion and erythrohydrobupropion are 5-fold less potent than bupropion. This may be of clinical importance, because the plasma concentrations of the metabolites are as high or higher than those of bupropion. At steady state, peak plasma concentration of hydroxybupropion occurred approximately 7 hours after administration of bupropion hydrochloride extended-release tablets (XL), and it was approximately 7 times the peak level of the parent drug.

The elimination half-life of hydroxybupropion is approximately 20 (±5) hours, and its AUC at steady state is about 13 times that of bupropion. The times to peak concentrations for the erythrohydrobupropion and threohydrobupropion metabolites are similar to that of hydroxybupropion. However, the elimination half-lives of erythrohydrobupropion and threohydrobupropion are longer, approximately 33 (±10) and 37 (±13) hours, respectively, and steady-state AUCs were 1.4 and 7 times that of bupropion, respectively.

Bupropion a… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 58 words ▾

12.1Mechanism of Action The mechanism of action of bupropion is unknown, as is the case with other antidepressants. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine and does not inhibit monoamine oxidase or the reuptake of serotonin.

📦 How Supplied / Storage and Handling 84 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Bupropion Hydrochloride Extended-Release Tablets, USP (XL), 300 mg of bupropion hydrochloride, are white to pale yellow, round, film-coated tablets imprinted with ‘L1’ in black ink on one side and plain on the other side and are supplied as follows: NDC 63304-724-30 Bottles of 30 with child-resistant closure NDC 63304-724-90 Bottles of 90 with child-resistant closure NDC 63304-724-05 Bottles of 500 Store at 20ºC to 25ºC (68ºF to 77ºF) [see USP Controlled Room Temperature]. Keep out of reach of children.

📋 Description 192 words ▾

11 DESCRIPTION Bupropion hydrochloride, an antidepressant of the aminoketone class, is chemically unrelated to tricyclic, tetracyclic, selective serotonin reuptake inhibitor, or other known antidepressant agents. Its structure closely resembles that of diethylpropion; it is related to phenylethylamines. It is designated as (±)-1-(3-chorophenyl)-2-[(1,1-dimethylethyl)amino]-1‑ propanone hydrochloride.

The molecular weight is 276.2. The molecular formula is C13H18ClNO·HCl. Bupropion hydrochloride, USP powder is white and soluble in water, in

0.1N hydrochloric acid, and in alcohol. It has a bitter taste and produces the sensation of local anesthesia on the oral mucosa. The structural formula is: Bupropion hydrochloride extended-release tablets, USP (XL) are supplied for oral administration as 300 mg white to pale yellow extended-release tablets.

Each extended-release tablet contains the labeled amount of bupropion hydrochloride, USP and the inactive ingredients: ethylcellulose, glyceryl behenate, hydroxypropyl cellulose, hypromellose, lactose monohydrate, methacrylic acid copolymer dispersion, polyethylene glycol, povidone, silicon dioxide, stearic acid, and triethyl citrate. The tablets are printed with edible black ink which contains ferrosoferric oxide, propylene glycol, and shellac glaze. The insoluble shell of the extended-release tablet may remain intact during gastrointestinal transit and is eliminated in the feces.

Meets USP dissolution Test 24. Bupropion Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Suicidal Thoughts and Behaviors Instruct patients, their families, and/or their caregivers to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down.

Advise families and caregivers of patients to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.

Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment Although bupropion hydrochloride extended-release tablets (XL) are not indicated for smoking cessation treatment, it contains the same active ingredient as Zyban ® which is approved for this use. Inform patients that some patients have experienced changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation and suicide when attempting to quit smoking while taking bupropion.

Instruct patients to discontinue bupropion hydrochloride extended-release tablets (XL) and contact a healthcare professional if they experience such symptoms [see Warnings and Precautions (5.2) and Adverse Reactions (6.2)]. Severe Allergic Reactions Educate patients on the symptoms of hypersensitivity and to discontinue bupropion hydrochloride extended-release tablets (XL) if they have a severe allergic reaction. Seizure Instruct patients to discontinue and not restart bupropion hydrochloride extended-release tablets (XL) if they experience a seizure while on treatment.

Advise patients that the excessive use or the abrupt discontinuation of alcohol, benzodiazepines, antiepileptic drugs, or sedatives/hypnotics can increase the risk of seizure. Advise patients to minimize or avoid the use of alcohol. A ngle - Closure Glaucoma Patients should be advised that taking bupropion hydrochloride extended-release tablets (XL) can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle-closure glaucoma.

Pre-existing glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle-closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible [see Warnings and Precautions (5.7)] .

Bupropion-Containing Products Educate patients that bupropion hydrochloride extended-release tablets (XL) contains the same active ingredient (bupropion) found in Zyban ® , which is used as an aid to smoking cessation treatment, and that bupropion hydrochloride extended-release tablets (XL) should not be used in combination with Zyban ® or any other medications that contain bupropion hydrochloride (such as Wellbutrin SR Sustained-Release Tablets, the sustained-release formulation, bupropion hydrochloride tablets, the immediate-release formulation, and Aplenzin ® , a bupropion hydrobromide formulation).

In addition, there are a number of generic bupropion hydrochloride products for the immediate, sustained, and extended-release formulations. P o tential for Cognitive and Motor Impairment Advise patients that any CNS-active drug like… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Bupropion Hydrochloride (bue proe’ pee on hye’ droe klor’ ide) Extended-Release Tablets, USP (XL) Rx Only IMPORTANT: Be sure to read the three sections of this Medication Guide. The first section is about the risk of suicidal thoughts and actions with antidepressant medicines; the second section is about the risk of changes in thinking and behavior, depression and suicidal thoughts or actions with medicines used to quit smoking; and the third section is entitled “What Other Important Information Should I Know About bupropion hydrochloride extended-release tablets (XL)?” A n tidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions This section of the Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines.

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions? 1 . Antidepressant medicines may increase the risk of suicidal thoughts or actions in some children, teenagers, or young adults within the first few months of treatment.

2 . Depression or other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions.

These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions. 3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member? • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

This is very important when an antidepressant medicine is started or when the dose is changed. • Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. • Keep all follow up visits with your healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms. C al l your healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying attempts to commit suicide new or worse depression new or worse anxiety feeling very agitated or restless panic attacks trouble sleeping (insomnia) new or worse irritability acting aggressive, being angry, or violent acting on dangerous impulses an extreme increase in activity and talking (mania) other unusual changes in behavior or mood What else do I need to know about antidepressant medicines? • Never stop an antidepressant medicine without first talking to a healthcare provider.

Stopping an antidepressant medicine suddenly can cause other symptoms. • A n tidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants. • A n tidepressant medicines have other side effects.

Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member. • A n tidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider.

Do not start new medicines without first checking with your healthcare provider. It is not known if bupropion hydrochloride extended-release tablets (XL) are safe and effective in children under the age of 18. Quitting Smoking, Quit-Smoking Medications, Changes in Thinking and Behavior, Depression, and Suicidal Thoughts or Actions This section of the Medication Guide is only about the risk of changes in thinking and behavior, depression and suicidal t… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Bupropion is a racemic mixture. The pharmacologic activity and pharmacokinetics of the individual enantiomers have not been studied. Following chronic dosing, the mean steady-state plasma concentration of bupropion was reached within 8 days.

The mean elimination half-life (±SD) of bupropion is 21 (±9) hours. In a study comparing 14-day dosing with bupropion hydrochloride extended-release tablets (XL), 300 mg once-daily to the immediate-release formulation of bupropion at 100 mg 3 times daily, equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the three metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion). Additionally, in a study comparing 14-day dosing with bupropion hydrochloride extended-release tablets (XL) 300 mg once daily to the sustained-release formulation of bupropion at 150 mg 2 times daily, equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the three metabolites.

Absorption Following single oral administration of bupropion hydrochloride extended-release tablets (XL) to healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5 hours. The presence of food did not affect the peak concentration or area under the curve of bupropion. Distribution I n vitro tests show that bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg/mL.

The extent of protein binding of the hydroxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that of bupropion. Met abolism Bupropion is extensively metabolized in humans. Three metabolites are active: hydroxybupropion, which is formed via hydroxylation of the tert- butyl group of bupropion, and the amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl group.

In vitro findings suggest that CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, while cytochrome P450 enzymes are not involved in the formation of threohydrobupropion. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of meta-chlorobenzoic acid, which is then excreted as the major urinary metabolite. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized.

However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is one half as potent as bupropion, while threohydrobupropion and erythrohydrobupropion are 5-fold less potent than bupropion. This may be of clinical importance, because the plasma concentrations of the metabolites are as high or higher than those of bupropion. At steady state, peak plasma concentration of hydroxybupropion occurred approximately 7 hours after administration of bupropion hydrochloride extended-release tablets (XL), and it was approximately 7 times the peak level of the parent drug.

The elimination half-life of hydroxybupropion is approximately 20 (±5) hours, and its AUC at steady state is about 13 times that of bupropion. The times to peak concentrations for the erythrohydrobupropion and threohydrobupropion metabolites are similar to that of hydroxybupropion. However, the elimination half-lives of erythrohydrobupropion and threohydrobupropion are longer, approximately 33 (±10) and 37 (±13) hours, respectively, and steady-state AUCs were 1.4 and 7 times that of bupropion, respectively.

Bupropion and its metabolites exhibit linear kinetics following chronic administration of 300 to 450 mg/day. E limination Following oral administration of 200 mg of 14C-bupropion in humans, 87% and 10% of the radioactive dose were recovered in the urine and feces, respectively. Only 0.5% of the oral dose was excreted as unchanged bupropion.

P opulation Subgroups Factors or conditions altering metabolic capacity (e.g… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Major Depressive Disorder The efficacy of bupropion in the treatment of major depressive disorder was established with the immediate-release formulation of bupropion hydrochloride in two 4-week, placebo-controlled trials in adult inpatients with MDD and in one 6-week, placebo-controlled trial in adult outpatients with MDD. In the first study, the bupropion dose range was 300 mg to 600 mg per day administered in 3 divided doses; 78% of patients were treated with doses of 300 mg to 450 mg per day. The trial demonstrated the efficacy of bupropion as measured by the Hamilton Depression Rating Scale (HAMD) total score, the HAMD depressed mood item (item 1), and the Clinical Global Impressions-Severity Scale (CGI-S).

The second study included 2 fixed doses of bupropion (300 mg and 450 mg per day) and placebo. This trial demonstrated the efficacy of bupropion for only the 450 mg dose. The efficacy results were significant for the HAMD total score and the CGI-S severity score, but not for HAMD item 1.

In the third study, outpatients were treated with bupropion 300 mg per day. This study demonstrated the efficacy of bupropion as measured by the HAMD total score, the HAMD item 1, the Montgomery-Asberg Depression Rating Scale (MADRS), the CGI-S score, and the CGI-Improvement Scale (CGI-I) score. A longer-term, placebo-controlled, randomized withdrawal trial demonstrated the efficacy of bupropion HCl sustained-release in the maintenance treatment of MDD.

The trial included adult outpatients meeting DSM-IV criteria for MDD, recurrent type, who had responded during an 8-week open-label trial of bupropion 300 mg per day. Responders were randomized to continuation of bupropion 300 mg per day or placebo for up to 44 weeks of observation for relapse. Response during the open-label phase was defined as a CGI-Improvement Scale score of 1 (very much improved) or 2 (much improved) for each of the final 3 weeks.

Relapse during the double-blind phase was defined as the investigator’s judgment that drug treatment was needed for worsening depressive symptoms. Patients in the bupropion group experienced significantly lower relapse rates over the subsequent 44 weeks compared to those in the placebo group. Although there are no independent trials demonstrating the efficacy of bupropion hydrochloride extended-release tablets (XL) in the acute treatment of MDD, studies have demonstrated similar bioavailability between the immediate-, sustained-, and extended-release formulations of bupropion HCl under steady-state conditions (i.e., the exposures [C max and AUC] for bupropion and its metabolites are similar among the 3 formulations).

14.2Seasonal Affective Disorder The efficacy of bupropion hydrochloride extended-release tablets (XL) in the prevention of seasonal major depressive episodes associated with SAD was established in 3 randomized, double-blind, placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal pattern (as defined by DSM-IV criteria). Bupropion treatment was initiated prior to the onset of symptoms in the autumn (September to November). Treatment was discontinued following a 2-week taper that began during the first week of spring (fourth week of March), resulting in a treatment duration of approximately 4 to 6 months for the majority of patients.

Patients were randomized to treatment with bupropion hydrochloride extended-release tablets (XL) or placebo. The initial bupropion dose was 150 mg once daily for 1 week, followed by up-titration to 300 mg once daily. Patients who were deemed by the investigator to be unlikely or unable to tolerate 300 mg once daily were allowed to remain on, or had their dose reduced to, 150 mg once daily.

The mean bupropion doses in the 3 trials ranged from 257 mg to 280 mg per day. Approximately 59% of patients continued in the study for 3 to 6 months; 26% continued for < 3 months, 15% continued for > 6 months. To enter the trials, patients must h… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence ~1 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Bupropion is not a controlled substance.

9.2Abuse Humans Controlled clinical studies of bupropion HCl immediate-release conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed patients demonstrated an increase in motor activity and agitation/excitement. In a population of individuals experienced with drugs of abuse, a single dose of 400 mg bupropion produced mild amphetamine-like activity as compared to placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI), and a score intermediate between placebo and amphetamine on the Liking Scale of the ARCI.

These scales measure general feelings of euphoria and drug desirability. Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. Nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers.

However, higher doses (that could not be tested because of the risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs. Bupropion hydrochloride extended-release tablets are intended for oral use only. The inhalation of crushed tablets or injection of dissolved bupropion has been reported.

Seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection. Animals Studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. In rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavioral response, and increase rates of responding in several schedule-controlled behavior paradigms.

In primate models assessing the positive reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. In rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

🧪 Nonclinical Toxicology 200 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Lifetime carcinogenicity studies were performed in rats and mice at doses up to 300 and 150 mg/kg/day bupropion hydrochloride, respectively. These doses are approximately 7 and 2 times the maximum recommended human dose (MRHD), respectively, on a mg/m 2 basis. In the rat study there was an increase in nodular proliferative lesions of the liver at doses of 100 to 300 mg/kg/day of bupropion hydrochloride (approximately 2 to 7 times the MRHD on a mg/m 2 basis); lower doses were not tested.

The question of whether or not such lesions may be precursors of neoplasms of the liver is currently unresolved. Similar liver lesions were not seen in the mouse study, and no increase in malignant tumors of the liver and other organs was seen in either study. Bupropion produced a positive response (2 to 3 times control mutation rate) in 2 of 5 strains in one Ames bacterial mutagenicity assay, but was negative in another.

Bupropion produced an increase in chromosomal aberrations in 1 of 3 in vivo rat bone marrow cytogenetic studies. A fertility study in rats at doses up to 300 mg/kg/day revealed no evidence of impaired fertility.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 197 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Lifetime carcinogenicity studies were performed in rats and mice at doses up to 300 and 150 mg/kg/day bupropion hydrochloride, respectively. These doses are approximately 7 and 2 times the maximum recommended human dose (MRHD), respectively, on a mg/m 2 basis. In the rat study there was an increase in nodular proliferative lesions of the liver at doses of 100 to 300 mg/kg/day of bupropion hydrochloride (approximately 2 to 7 times the MRHD on a mg/m 2 basis); lower doses were not tested.

The question of whether or not such lesions may be precursors of neoplasms of the liver is currently unresolved. Similar liver lesions were not seen in the mouse study, and no increase in malignant tumors of the liver and other organs was seen in either study. Bupropion produced a positive response (2 to 3 times control mutation rate) in 2 of 5 strains in one Ames bacterial mutagenicity assay, but was negative in another.

Bupropion produced an increase in chromosomal aberrations in 1 of 3 in vivo rat bone marrow cytogenetic studies. A fertility study in rats at doses up to 300 mg/kg/day revealed no evidence of impaired fertility.

📄 Package Label / Principal Display Panel 147 words ▾

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL ONCE-DAILY NDC 63304-724-30 buPROPion HYDROCHLORIDE Extended-Release Tablets, USP (XL) 300 mg WARNING: Do not use in combination with Zyban® or any other medicines that contain bupropion hydrochloride. PHARMACIST: PLEASE DISPENSE WITH ACCOMPANYING MEDICATION GUIDE Rx only Sun Pharma 30 Tablets Label Bupropion 300 mg 30s

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL ONCE-DAILY NDC 63304-724-90 buPROPion HYDROCHLORIDE Extended-Release Tablets, USP (XL) 300 mg WARNING: Do not use in combination with Zyban® or any other medicines that contain bupropion hydrochloride. PHARMACIST: PLEASE DISPENSE WITH ACCOMPANYING MEDICATION GUIDE Rx only Sun Pharma 90 Tablets Label Bupropion 300 mg 90s

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL ONCE-DAILY NDC 63304-724-05 buPROPion HYDROCHLORIDE Extended-Release Tablets, USP (XL) 300 mg WARNING: Do not use in combination with Zyban® or any other medicines that contain bupropion hydrochloride. PHARMACIST: PLEASE DISPENSE WITH ACCOMPANYING MEDICATION GUIDE Rx only Sun Pharma 500 Tablets Label Bupropion 300 mg 500s

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
36
Units reimbursed last 4 qtrs
1K
Gross reimbursed last 4 qtrs
$525.02
Avg / prescription
$14.58
Avg / unit
$0.5168
Latest quarter Q4 2025
0Rx
Medicaid pays / ea
$0.5168
gross reimbursed
vs
NADAC / ea
$0.1034
acquisition cost
=
Spread
+$0.4134
+400% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 36 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: 349 units · 5.0 per 100k residents MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: 667 units · 33.7 per 100k residents NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
5.033.7
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Nebraska 33.7 /100k
2 Massachusetts 5.0 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
500 tablets63304-0724-05 241 Rx · $3,097
30 tablets63304-0724-30 74 Rx · $976
90 tablets this page63304-0724-90 36 Rx · $525
Drug total (last 4 qtrs): 351 Rx · 10,641 units · $4,598 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) ✓ Available
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 30 tablets (63304-0724-30), 500 tablets (63304-0724-05). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Sun Pharmaceutical Industries, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 63304-0723-05 · Sun 63304-0734-10 · Sun →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.