HomeNDC LookupIngredientsDoxepin Hydrochloride › 00378-8123-45
Zonalon doxepin hydrochloride 50 mg/g Cream — NDC 00378-8123-45 package photo

Zonalon doxepin hydrochloride 50 mg/g Cream

by Mylan Pharmaceuticals Inc. · 1 TUBE in 1 CARTON (0378-8123-45) / 45 g in 1 TUBE
NDC 00378-8123-45
🏷️ FDA NDC (as labeled) 0378-8123-45 billing pads the labeler segment with a zero
This package
Contains45 g in 1 tube Medicaid pays$15.08 / unit · 12 mo Per package$678.63 / 45 g · Medicaid Pack sizes2 compare ↓
Also priced by: Part D plans $19.44/unit — full pricing hub ↓
Also comes in: 30 g 00378-8123-30
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →
⚠️
Other active recalls for Doxepin Hydrochloride (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Jul 25, 2025 — CGMP Deviations: Presence of Nitrosamine Drug Substance Related Impurity above the proposed interim limit. (Alembic Pharmaceuticals Limited) · FDA recall D-0566-2025
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 0378-8123-45
Product NDC 0378-8123
11-digit billing NDC 00378812345
NCPDP billing unit GM — per gram (weight)
RxCUI 1000091, 1000095
UNII 3U9A0FE9N5
Application # NDA020126
SPL Set ID 5f302247-525e-4acc-852b-00eb1d79af4b
Established class (EPC) Tricyclic Antidepressant
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2018-11-14
Route TOPICAL
Dosage form CREAM
Substance DOXEPIN HYDROCHLORIDE
GPI-14 90220015103710
GPI class Zonalon
GCN Seq No 021715
GCN 21210
HICL code 001650
Ingredient (HICL) Doxepin Hcl
HIC1 code L
Therapeutic class — broad (HIC1) Skin/Subcutaneous Tissue
HIC2 code L3
Therapeutic class — intermediate (HIC2) Protectives
HIC3 code L3P
Therapeutic class — specific (HIC3) Antipruritics,Topical
AHFS code 28:16.04.28
AHFS class Tricyclics, Other Norepi-Ru Inhibitors
FDB label name ZONALON 5% CREAM
FDB brand name Zonalon
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 0378-8123-45 — a 4-4-2 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 labeler segment → 00378-8123-45. 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 Tricyclic Antidepressant class.

Pharmacologic class Tricyclic Antidepressant
Drug family (ATC) Other antipruritics, Non-selective monoamine reuptake 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.

🏭 Manufacturer & labeler

LabelerMylan Pharmaceuticals Inc.
Application holderMYLAN PHARMACEUTICALS INC
FDA applicationNDA020126 (NDA)
Labeler code00378
First marketedNov 2018
Product typeHuman Prescription Drug
Portfolio473 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.

🩺 Clinical

Label name ZONALON 5% CREAM Ingredient Doxepin Hcl
📖 What it is MedlinePlus · NLM

Doxepin topical is used to relieve itching of the skin caused by eczema. Doxepin is in a class of medications called topical antipruritics. It may work by blocking histamine, a substance in the body that causes certain symptoms, such as itching.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • You're right that doxepin is also used as an antidepressant in pill form, but this cream version is completely different — it's applied to the skin specifically to relieve moderate...
  • What exactly is this cream for? My doctor said it's for itching but it's usually an antidepressant — that seems strange.
  • That's one of the most important things to know about this cream. Doxepin is absorbed through your skin into your bloodstream, and it can reach levels high enough to cause real dro...
  • Why does the cream make me so sleepy? I didn't expect that from something I'm putting on my skin.
📖 Read our full Doxepin Topical guide →
1
Nutrient depletion considerations

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

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.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII LKG8494WBH
    Benzyl alcohol is a clear liquid used as a preservative and solvent in medicines. It helps prevent bacterial and fungal growth and dissolves other ingredients to create uniform liquid formulations.
  • UNII 936JST6JCN
    Cetyl alcohol is a waxy, fatty substance derived from plant or animal sources. It acts as an emulsifier and thickener in medicines, helping blend oil and water components and giving products a smooth, creamy texture.
  • UNII 0RE8K4LNJS
    Isopropyl myristate is an oily liquid made from coconut or palm oil. It's used in medicines as an emollient and penetration enhancer to help the medicine absorb through skin or improve spreadability in topical products.
  • UNII YTQ40QRP5W
    PEG-10 Glyceryl Stearate is a synthetic compound made by combining polyethylene glycol with a fatty acid derivative. In medicines, it acts as an emulsifier and surfactant, helping blend oil and water-based ingredients together and improving how the product spreads or absorbs.
  • UNII YD01N1999R
    A waxy substance made from polyethylene glycol and stearic acid. It helps mix oil and water-based ingredients together and serves as an emulsifier and solubilizer in liquid and semi-solid medicines.
  • UNII 4T6H12BN9U
    Petrolatum is a purified mineral oil-based jelly derived from petroleum. In medicines, it acts as an emollient, lubricant, and moisture barrier to soften skin, reduce friction, and help prevent water loss from formulations.
  • UNII 506T60A25R
    Sorbitol is a natural sugar alcohol derived from glucose. It serves as a sweetener, humectant, and bulking agent in medications to improve taste and help maintain moisture in the product.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

9 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

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.

💲 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 gPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $15.08 $678.63 / 45 g
Medicare drug plans payPart D · Q2 2026 $19.44 $874.84 / 45 g
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
doxepin hydrochloride 50 mg/g 00093-9609-95 Teva 1 tube $6.579 AB Availability likely
Doxepin Hydrochloride 50 mg/g 00378-8117-45 Mylan 1 tube $6.579 AB Availability likely
Doxepin Hydrochloride 50 mg/g 69238-1733-06 Amneal 1 tube $6.579 AB Availability likely
Zonalon 50 mg/gthis 00378-8123-45 Mylan 1 tube AB FDA listed
Prudoxin 50 mg/g 00378-8130-45 Mylan 1 tube AB FDA listed
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
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

🏛️
2018
On the market since
Nov 2018
📍
2026
Currently FDA-listed
8 years listed
🔓
·
Generic versions listed
see equivalents
Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

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.

🗺️ 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 00378-8123-45, 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.
📅 Q2 2025 – Q4 2025 · 2 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
17
Units reimbursed last 4 qtrs
765
Gross reimbursed last 4 qtrs
$11.5K
Avg / prescription
$678.63
Avg / unit
$15.0806
Latest quarter Q4 2025
17Rx
Fee-for-service vs managed care
100% FFS
Fee-for-service · 17 Rx Managed care · 0 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: 765 units · 3.9 per 100k residents 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: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported 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
3.93.9
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 New York 3.9 /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.
1 tube00378-8123-30 58 Rx · $34,953
Drug total (last 4 qtrs): 75 Rx · 2,505 units · $46,490 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
00378-8123-30 1 TUBE in 1 CARTON (0378-8123-30) / 30 g in 1 TUBE 2018-11-26 Active
00378-8123-45 You're viewing this 1 TUBE in 1 CARTON (0378-8123-45) / 45 g in 1 TUBE 2018-11-14 Active

Pack size FAQ

What quantity is in NDC 00378-8123-45?
NDC 00378-8123-45 is listed by the FDA — 1 tube in 1 carton / 45 g in 1 tube.
What NDC number is used to bill for this package of Zonalon doxepin hydrochloride 50 mg/g Cream?
Bill NDC 00378-8123-45 — the 11-digit billing format is 00378812345. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 About this NDC listing & data coverage

Finished prescription product
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 ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
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

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
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 FDA registers it as 0378-8123-45, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00378-8123-45, written without dashes as 00378812345. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00378-8123-45, the first segment (00378) is the labeler code FDA assigned to Mylan Pharmaceuticals Inc.; the middle segment (8123) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (45) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Mylan Pharmaceuticals Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 1 tube (00378-8123-30). 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?
Mylan Pharmaceuticals 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage 34 words

INDICATIONS AND USAGE Zonalon ® Cream is indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus. (See DOSAGE AND ADMINISTRATION .)

⏱️ Dosage and Administration 213 words

DOSAGE AND ADMINISTRATION A thin film of Zonalon ® Cream should be applied four times each day with at least a 3 to 4 hour interval between applications. There are no data to establish the safety and effectiveness of Zonalon ® Cream when used for greater than 8 days. Chronic use beyond eight days may result in higher systemic levels and should be avoided.

Use of Zonalon ® Cream for longer than 8 days may result in an increased likelihood of contact sensitization. The risk for sedation may increase with greater body surface area application of Zonalon ® Cream (See WARNINGS section). Clinical experience has shown that drowsiness is significantly more common in patients applying Zonalon ® Cream to over 10% of body surface area; therefore, patients with greater than 10% of body surface area (see WARNINGS section) affected should be particularly cautioned concerning possible drowsiness and other systemic adverse effects of doxepin.

If excessive drowsiness occurs, it may be necessary to do one or more of the following: reduce the body surface area treated, reduce the number of applications per day, reduce the amount of cream applied, or discontinue the drug. Occlusive dressings may increase the absorption of most topical drugs; therefore, occlusive dressings should not be utilized with Zonalon ® Cream.

Contraindications 61 words

CONTRAINDICATIONS Because doxepin HCl has an anticholinergic effect and because significant plasma levels of doxepin are detectable after topical Zonalon ® Cream application, the use of Zonalon ® Cream is contraindicated in patients with untreated narrow angle glaucoma or a tendency to urinary retention. Zonalon ® Cream is contraindicated in individuals who have shown previous sensitivity to any of its components.

⚠️ Warnings 124 words

WARNINGS Drowsiness occurs in over 20% of patients treated with Zonalon ® Cream, especially in patients receiving treatment to greater than 10% of their body surface area. Patients should be warned about the possibility of sedation and cautioned against driving a motor vehicle or operating hazardous machinery while being treated with Zonalon ® Cream. The sedating effects of alcoholic beverages, antihistamines, and other CNS depressants may be potentiated when Zonalon ® Cream is used.

If excessive drowsiness occurs it may be necessary to reduce the frequency of applications, the amount of cream applied, and/or the percentage of body surface area treated, or discontinue the drug. However, the efficacy with reduced frequency of applications has not been established. Keep this product away from the eyes.

🤒 Adverse Reactions ~2 min read

ADVERSE REACTIONS Controlled Clinical Trials Systemic Adverse Effects In controlled clinical trials of patients treated with Zonalon ® Cream, the most common systemic adverse event reported was drowsiness. Drowsiness occurred in 71 of 330 (22%) of patients treated with Zonalon ® Cream compared to 7 of 334 (2%) of patients treated with vehicle cream. Drowsiness resulted in the premature discontinuation of the drug in approximately 5% of patients treated with Zonalon ® Cream in controlled clinical trials.

Local Site Adverse Effects In controlled clinical trials of patients treated with Zonalon ® Cream, the most common local site adverse event reported was burning and/or stinging at the site of application. These occurred in 76 of 330 (23%) of patients treated with Zonalon ® Cream compared to 54 of 334 (16%) of patients treated with vehicle cream. Most of these reactions were categorized as "mild"; however, approximately 25% of patients who reported burning and/or stinging reported the reaction as "severe".

Four patients treated with Zonalon ® Cream withdrew from the study because of the burning and/or stinging. The table below presents the adverse events reported at an incidence of ≥ 1% in either Zonalon ® or vehicle cream treatment groups during the trials: Adverse Event Zonalon ® N=330 Vehicle N=334 Burning/Stinging 76 (23.0%) 54 (16.2%) Drowsiness 71 (21.5%) 7 (2.1%) Dry Mouth Includes reports of "dry lips", "dry throat", and "thirst" 32 (9.7%) 4 (1.2%) Pruritus Includes reports of "pruritus exacerbated" 13 (3.9%) 20 (6.0%) Fatigue/Tiredness 10 (3.0%) 5 (1.5%) Exacerbated Eczema 10 (3.0%) 8 (2.4%) Other Application Site Reaction Includes report of "increased irritation at application site" 10 (3.0%) 16 (4.8%) Dizziness Includes reports of "lightheadedness" and "dizziness/vertigo" 7 (2.1%) 3 (0.9%) Mental/Emotional Changes 6 (1.8%) 1 (0.3%) Taste Perversion Includes reports of "bitter taste" and "metallic taste in mouth" 5 (1.5%) 1 (0.3%) Edema 4 (1.2%) 1 (0.3%) Headache 3 (0.9%) 14 (4.2%) Adverse events occurring in 0.5% to < 1.0% of Zonalon ® Cream treated patients in the controlled clinical trials included: nervousness/anxiety, tongue numbness, fever, and nausea.

Post-Marketing Experience Twenty-six cases of allergic contact dermatitis have been reported in patients using Zonalon ® Cream, twenty of which were documented by positive patch test to doxepin 5% cream.

🔄 Drug Interactions ~3 min read

Drug Interactions Studies have not been performed examining drug interactions with Zonalon ® Cream. However, since plasma levels of doxepin following topical application of Zonalon ® Cream can reach levels obtained with oral doxepin HCl therapy, the following drug interactions are possible following topical Zonalon ® Cream application: Drugs Metabolized by P450 2D6 The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7-10% of Caucasians are so-called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available.

Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers.

An individual who is stable on a given dosage regimen of a TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.

The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6. MAO Inhibitors Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors.

Therefore, MAO inhibitors should be discontinued at least two weeks prior to the cautious initiation of therapy with Zonalon ® Cream. The exact length of time may vary and is dependent upon the particular MAO inhibitor being used, the length of time it has been administered, and the dosage involved. Cimetidine Serious anticholinergic symptoms (i.e., severe dry mouth, urinary retention and blurred vision) have been associated with elevations in the serum levels of tricyclic antidepressants when cimetidine therapy is initiated.

Additionally, higher than expected tricyclic antidepressant levels have been observed when they are begun in patients already taking cimetidine. Alcohol Alcohol ingestion may exacerbate the potential sedative effects of Zonalon ® Cream. This is especially important in patients who may use alcohol excessively.

Tolazamide A case of severe hypoglycemia has been reported in a type II diabetic patient maintained on tolazamide (1 gm/day) 11 days after the addition of oral doxepin (75 mg/day).

🤰 Pregnancy 118 words

Pregnancy Reproduction studies have been performed in which doxepin was orally administered to rats and rabbits at doses up to 0.6 and 1.2 times, respectively, the estimated exposure to doxepin that results from use of 16 grams of Zonalon ® Cream per day (four applications of four grams of cream per day; dose multiples reflect comparisons made following normalization of the data on the basis of body surface area estimates) and have revealed no evidence of harm to rat or rabbit fetuses due to doxepin. There are, however, no adequate and well-controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

🧒 Pediatric Use 81 words

Pediatric Use The use of Zonalon ® Cream in pediatric patients is not recommended. Safe conditions for use of Zonalon ® Cream in children have not been established. One case has been reported of a 2.5-year-old child who developed somnolence, grand mal seizure, respiratory depression, ECG abnormalities, and coma after treatment with Zonalon ® Cream.

A total of 27 grams had been applied over three days for eczema. He was treated with supportive care, activated charcoal, and systemic alkalization and recovered.

🧓 Geriatric Use 179 words

Geriatric Use Clinical studies of Zonalon ® Cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

The extent of renal excretion of doxepin has not been determined. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selections. Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should be observed closely for confusion and oversedation when started on Zonalon ® Cream.

(See WARNINGS .) An 80-year-old male nursing home patient developed probable systemic anticholinergic toxicity which included urinary retention and delirium after Zonalon ® Cream had been applied to his arms, legs and back three times daily for two days.

🆘 Overdosage ~2 min read

OVERDOSAGE Deaths may occur from overdosage with this class of drugs. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible.

Manifestations Should overdosage with topical application of Zonalon ® Cream occur, the signs and symptoms may include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the symptoms listed under ADVERSE REACTIONS .

General Recommendations General Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line and initiate gastric decontamination. A minimum of six hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is strongly advised.

If signs of toxicity occur at any time during this period, extended monitoring is recommended. There are case reports of patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of significant poisoning prior to death and most received inadequate gastrointestinal decontamination. Monitoring of plasma drug levels should not guide management of the patient.

Cardiovascular A maximal limb-lead QRS duration of ≥ 0.10 seconds may be the best indication of the severity of the overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used.

Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. A pH >7.60 or a pCO 2 < 20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin.

Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide). In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning.

CNS In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines, or if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a poison control center.

Pediatric Management The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treaatment.

🧬 Clinical Pharmacology 181 words

CLINICAL PHARMACOLOGY Although doxepin HCl does have H 1 and H 2 histamine receptor blocking actions, the exact mechanism by which doxepin exerts its antipruritic effect is unknown. Zonalon ® Cream can produce drowsiness which may reduce awareness, including awareness of pruritic symptoms. In 19 pruritic eczema patients treated with Zonalon ® Cream, plasma doxepin concentrations ranged from nondetectable to 47 ng/mL from percutaneous absorption.

Plasma levels from topical application of Zonalon ® Cream can result in CNS and other systemic side effects. Once absorbed into the systemic circulation, doxepin undergoes hepatic metabolism that results in conversion to pharmacologically-active desmethyldoxepin. Further glucuronidation results in urinary excretion of the parent drug and its metabolites.

Desmethyldoxepin has a half-life that ranges from 28 to 52 hours and is not affected by multiple dosing. Plasma levels of both doxepin and desmethyldoxepin are highly variable and are poorly correlated with dosage. Wide distribution occurs in body tissues including lungs, heart, brain, and liver.

Renal disease, genetic factors, age, and other medications affect the metabolism and subsequent elimination of doxepin. (See PRECAUTIONS - Drug Interactions .)

📦 How Supplied / Storage and Handling 91 words

HOW SUPPLIED ZONALON ® Cream is available containing 50 mg of doxepin hydrochloride, USP equivalent to 44.3 mg of doxepin. ZONALON ® Cream, 5% is a soft white cream available as follows: NDC 0378-8123-30 carton containing one 30 g tube NDC 0378-8123-45 carton containing one 45 g tube Store below 27°C (80°F). Manufactured for: Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A. Manufactured by: DPT Laboratories, Ltd. San Antonio, TX 78215 U.S.A.

ZONALON is a registered trademark of Delcor Asset Corporation, a Mylan Company ©2017 Mylan Pharmaceuticals Inc. DPT:ZONA:R1 Revised: 6/2017 140900-0617

📋 Description 95 words

DESCRIPTION Zonalon ® (doxepin hydrochloride) Cream, 5% is a topical cream. Each gram contains: 50 mg of doxepin hydrochloride (equivalent to 44.3 mg of doxepin). Doxepin hydrochloride, USP is one of a class of agents known as dibenzoxepin tricyclic antidepressant compounds.

It is an isomeric mixture of N,N-dimethyldibenz[ b,e ]oxepin-Δ 11(6H),γ -propylamine hydrochloride. Doxepin hydrochloride has a molecular formula of C 19 H 21 NO•HCl and a molecular weight of 316. Zonalon ® Cream also contains sorbitol, cetyl alcohol, isopropyl myristate, glyceryl stearate, PEG-100 stearate, petrolatum, benzyl alcohol, titanium dioxide and purified water.

Structural Formula

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