Gabirol may be available in the countries listed below.
Rimantadine hydrochloride (a derivative of Rimantadine) is reported as an ingredient of Gabirol in the following countries:
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Cefaclen may be available in the countries listed below.
Cefalexin is reported as an ingredient of Cefaclen in the following countries:
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Cefpodoxim AL may be available in the countries listed below.
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Topiramato Novafarm Manipulaciones Generales may be available in the countries listed below.
Topiramate is reported as an ingredient of Topiramato Novafarm Manipulaciones Generales in the following countries:
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Cyclomed may be available in the countries listed below.
Aciclovir is reported as an ingredient of Cyclomed in the following countries:
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Bromhexin Sopharma may be available in the countries listed below.
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Oculac may be available in the countries listed below.
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Substitol retard may be available in the countries listed below.
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Relieving minor vaginal irritation and itching. It may also be used to cleanse and deodorize the vaginal area.
Betadine Douche is an antiseptic combination. It works by killing sensitive bacteria.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Betadine Douche. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
Some MEDICINES MAY INTERACT with Betadine Douche. However, no specific interactions are known at this time.
This may not be a complete list of all interactions that may occur. Ask your health care provider if Betadine Douche may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.
Use Betadine Douche as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Betadine Douche.
All medicines may cause side effects, but many people have no, or minor, side effects. When used in small doses, no COMMON side effects have been reported with this product. Seek medical attention right away if any of these SEVERE side effects occur:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chills; excessive vaginal dryness; fever; severe stomach pain; unusual vaginal discharge; vaginal pain, soreness, swelling, redness, or irritation.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
See also: Betadine side effects (in more detail)
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Betadine Douche may be harmful if swallowed.
Store Betadine Douche at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Keep Betadine Douche out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Betadine Douche. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.
Painsik may be available in the countries listed below.
Ketoprofen is reported as an ingredient of Painsik in the following countries:
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Nimopidina DOC may be available in the countries listed below.
Nimodipine is reported as an ingredient of Nimopidina DOC in the following countries:
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Mirtabene may be available in the countries listed below.
Mirtazapine is reported as an ingredient of Mirtabene in the following countries:
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Formigran may be available in the countries listed below.
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Ketamina Klonal may be available in the countries listed below.
Ketamine hydrochloride (a derivative of Ketamine) is reported as an ingredient of Ketamina Klonal in the following countries:
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Mebeverin Solvay may be available in the countries listed below.
Mebeverine hydrochloride (a derivative of Mebeverine) is reported as an ingredient of Mebeverin Solvay in the following countries:
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Mucotron may be available in the countries listed below.
Carbocisteine is reported as an ingredient of Mucotron in the following countries:
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Farsorbid may be available in the countries listed below.
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Normitab may be available in the countries listed below.
Atenolol is reported as an ingredient of Normitab in the following countries:
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Mucodyne Paediatric may be available in the countries listed below.
Carbocisteine is reported as an ingredient of Mucodyne Paediatric in the following countries:
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Phenxycap may be available in the countries listed below.
Glucosamine sulfate (a derivative of Glucosamine) is reported as an ingredient of Phenxycap in the following countries:
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Gloriamin may be available in the countries listed below.
Glutamine is reported as an ingredient of Gloriamin in the following countries:
Sodium Gualenate is reported as an ingredient of Gloriamin in the following countries:
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Cétrimide may be available in the countries listed below.
Cétrimide (DCF) is also known as Cetrimide (Rec.INN)
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Glossary
| DCF | Dénomination Commune Française |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Pediphen may be available in the countries listed below.
Diphenhydramine hydrochloride (a derivative of Diphenhydramine) is reported as an ingredient of Pediphen in the following countries:
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Betahistine EG may be available in the countries listed below.
Betahistine dihydrochloride (a derivative of Betahistine) is reported as an ingredient of Betahistine EG in the following countries:
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Lovastatina Normon may be available in the countries listed below.
Lovastatin is reported as an ingredient of Lovastatina Normon in the following countries:
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Ophthaline may be available in the countries listed below.
Zinc Sulfate monohydrate (a derivative of Zinc Sulfate) is reported as an ingredient of Ophthaline in the following countries:
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Mesalazine Disphar may be available in the countries listed below.
Mesalazine is reported as an ingredient of Mesalazine Disphar in the following countries:
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Irinotecan Accord may be available in the countries listed below.
Irinotecan hydrochloride trihydrate (a derivative of Irinotecan) is reported as an ingredient of Irinotecan Accord in the following countries:
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Adursal may be available in the countries listed below.
Ursodeoxycholic Acid is reported as an ingredient of Adursal in the following countries:
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Lopemid may be available in the countries listed below.
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MS Direct may be available in the countries listed below.
Morphine sulphate pentahydrate (a derivative of Morphine) is reported as an ingredient of MS Direct in the following countries:
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Istopril may be available in the countries listed below.
Enalapril maleate (a derivative of Enalapril) is reported as an ingredient of Istopril in the following countries:
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Ulcotenal may be available in the countries listed below.
Pantoprazole sodium (a derivative of Pantoprazole) is reported as an ingredient of Ulcotenal in the following countries:
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Soldesam may be available in the countries listed below.
Dexamethasone 21-(disodium phosphate) (a derivative of Dexamethasone) is reported as an ingredient of Soldesam in the following countries:
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Acliz may be available in the countries listed below.
Meclozine dihydrochloride (a derivative of Meclozine) is reported as an ingredient of Acliz in the following countries:
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Seratil may be available in the countries listed below.
Prochlorperazine maleate (a derivative of Prochlorperazine) is reported as an ingredient of Seratil in the following countries:
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Dexiven may be available in the countries listed below.
Calcitriol is reported as an ingredient of Dexiven in the following countries:
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Acrinol may be available in the countries listed below.
Ethacridine lactate (a derivative of Ethacridine) is reported as an ingredient of Acrinol in the following countries:
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Moexipril Hydrochloride (BANM, USAN) is known as Moexipril in the US.
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| BANM | British Approved Name (Modified) |
| USAN | United States Adopted Name |
Toposide may be available in the countries listed below.
Etoposide is reported as an ingredient of Toposide in the following countries:
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Toledomin may be available in the countries listed below.
Milnacipran hydrochloride (a derivative of Milnacipran) is reported as an ingredient of Toledomin in the following countries:
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Aterostat may be available in the countries listed below.
Simvastatin is reported as an ingredient of Aterostat in the following countries:
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Méclocycline may be available in the countries listed below.
Méclocycline (DCF) is also known as Meclocycline (Rec.INN)
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Glossary
| DCF | Dénomination Commune Française |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Eltair may be available in the countries listed below.
Budesonide is reported as an ingredient of Eltair in the following countries:
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In some countries, this medicine may only be approved for veterinary use.
Rec.INN
0001649-18-9
C19-H22-F-N3-O
327
Sedative agent
Neuroleptic
Agent for premedication
1-Butanone, 1-(4-fluorophenyl)-4-[4-(2-pyridinyl)-1-piperazinyl]-
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Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Generic Name: proparacaine (Ophthalmic route)
proe-PAR-a-kane
In the U.S.
Available Dosage Forms:
Therapeutic Class: Anesthetic, Local
Chemical Class: Amino Ester
Proparacaine eye drops are used to numb the eye before surgery, certain tests, or procedures. The eye drops are used to prevent pain during the procedure.
Proparacaine belongs to the group of medicines called local anesthetics. It works by blocking the pain signals at the nerve endings in the eye.
This medicine is to be administered only by or under the direct supervision of an eye doctor.
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Although appropriate studies on the relationship of age to the effects of proparacaine eye drops have not been performed in the pediatric population, no pediatric-specific problems have been documented to date.
No information is available on the relationship of age to the effects of proparacaine eye drops in geriatric patients.
| Pregnancy Category | Explanation | |
|---|---|---|
| All Trimesters | C | Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women. |
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain proparacaine. It may not be specific to Ophthetic. Please read with care.
A nurse or other trained health professional will give you this medicine. The eye drops are placed directly in the eye.
Your doctor will check your progress closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it.
It is very important to protect your eye from injury while it is still numb. Do not touch or rub the eye. Do not use additional eye drops in the eye until your doctor tells you to. Protect your eye from dust particles, sand, or anything that might cause irritation.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor or nurse immediately if any of the following side effects occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
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Forpar may be available in the countries listed below.
Cefepime is reported as an ingredient of Forpar in the following countries:
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Ceftriaxona Generis may be available in the countries listed below.
Ceftriaxone is reported as an ingredient of Ceftriaxona Generis in the following countries:
Ceftriaxone disodium salt (a derivative of Ceftriaxone) is reported as an ingredient of Ceftriaxona Generis in the following countries:
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Mirtazapine Actavis may be available in the countries listed below.
Mirtazapine is reported as an ingredient of Mirtazapine Actavis in the following countries:
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Aristocor may be available in the countries listed below.
Flecainide acetate (a derivative of Flecainide) is reported as an ingredient of Aristocor in the following countries:
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Rimoveron may be available in the countries listed below.
Rifampicin is reported as an ingredient of Rimoveron in the following countries:
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Mereprine may be available in the countries listed below.
Doxylamine succinate (a derivative of Doxylamine) is reported as an ingredient of Mereprine in the following countries:
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Manufactured by: Allergan Pharmaceuticals Ireland
a subsidiary of: Allergan, Inc. 2525 Dupont Dr., Irvine, CA 92612
Distant Spread of Toxin Effect
Postmarketing reports indicate that the effects of BOTOX® Cosmetic and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, cases of spread of effect have occurred at doses comparable to those used to treat cervical dystonia and at lower doses.
BOTOX® Cosmetic (onabotulinumtoxinA) for injection, is a sterile, vacuum-dried purified botulinum toxin type A, produced from fermentation of Hall strain Clostridium botulinum type A grown in a medium containing casein hydrolysate, glucose, and yeast extract, intended for intramuscular use. It is purified from the culture solution by dialysis and a series of acid precipitations to a complex consisting of the neurotoxin, and several accessory proteins. The complex is dissolved in sterile sodium chloride solution containing Albumin Human and is sterile filtered (0.2 microns) prior to filling and vacuum-drying.
The primary release procedure for BOTOX® Cosmetic uses a cell-based potency assay to determine the potency relative to a reference standard. The assay is specific to Allergan's products BOTOX® and BOTOX® Cosmetic. One Unit of BOTOX® Cosmetic corresponds to the calculated median intraperitoneal lethal dose (LD50) in mice. Due to specific details of this assay such as the vehicle, dilution scheme and laboratory protocols, Units of biological activity of BOTOX® Cosmetic cannot be compared to nor converted into Units of any other botulinum toxin or any toxin assessed with any other specific assay method. The specific activity of BOTOX® Cosmetic is approximately 20 Units/nanogram of neurotoxin protein complex.
Each vial of BOTOX® Cosmetic contains either 100 Units of Clostridium botulinum type A neurotoxin complex, 0.5 mg of Albumin Human, and 0.9 mg of sodium chloride or 50 Units of Clostridium botulinum type A neurotoxin complex, 0.25 mg of Albumin Human, and 0.45 mg of sodium chloride in a sterile, vacuum-dried form without a preservative.
BOTOX® Cosmetic blocks neuromuscular transmission by binding to acceptor sites on motor nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings. When injected intramuscularly at therapeutic doses, BOTOX® Cosmetic produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity. In addition, the muscle may atrophy, axonal sprouting may occur, and extrajunctional acetylcholine receptors may develop. There is evidence that reinnervation of the muscle may occur, thus slowly reversing muscle denervation produced by BOTOX® Cosmetic.
Using currently available analytical technology, it is not possible to detect BOTOX® Cosmetic in the peripheral blood following intramuscular injection at the recommended doses.
Two phase 3 randomized, multi-center, double-blind, placebo-controlled studies of identical design were conducted to evaluate BOTOX® Cosmetic for use in the temporary improvement of the appearance of moderate to severe glabellar facial lines. The studies enrolled healthy adults (ages 18 to 75) with glabellar lines of at least moderate severity at maximum frown. Patients were excluded if they had ptosis, deep dermal scarring, or an inability to substantially lessen glabellar lines even by physically spreading them apart. Subjects received a single treatment with BOTOX® Cosmetic (N=405, combined studies) or placebo (N=132, combined studies). Injection volume was 0.1 mL/injection site, for a dose/injection site in the active treatment groups of 4 Units. Subjects were injected intramuscularly in five sites, 1 in the procerus muscle and 2 in each corrugator supercilii muscle, for a total dose in the active treatment groups of 20 Units.
The co-primary efficacy endpoints were the investigator's rating of glabellar line severity at maximum frown and the subject's global assessment of change in appearance of glabellar lines, both at Day 30 post-injection. For the investigator rating, using a 4-point grading scale (0=none, 3=severe) a responder was defined as having a severity grade of 0 or 1. For the subject's global assessment of change, the ratings were from +4 (complete improvement) to -4 (very marked worsening). A responder was defined as having a grade of at least +2 (moderate improvement). After completion of the randomized studies, subjects were offered participation in an open label, repeat treatment study to assess the safety of repeated treatment sessions.
The combined results of these two efficacy trials are presented here. The mean age was 46 years, with 32 patients (6%) ≥ 65 years of age. Most of the subjects (82%) were women, and Caucasian (84%). At baseline, 210 patients (39%) had glabellar line severity scores at rest of moderate or severe.
In these studies, the severity of glabellar lines was reduced for up to 120 days in the BOTOX® Cosmetic group compared to the placebo group as measured both by investigator rating of glabellar line severity at maximum frown (Table 1), and by subject's global assessment of change in appearance of glabellar lines (Table 2).
a 95% confidence intervals are shown in parenthesis | |||
b Day 30: Co-Primary Efficacy Time point, P<0.001 | |||
| Day | BOTOX® Cosmetic | Placebo | Differencea |
| 7 | 74% 299/405 | 6% 8/132 | 68% (62, 74) |
| 30b | 80% 325/405 | 3% 4/132 | 77% (72, 82) |
| 60 | 70% 283/403 | 2% 2/130 | 69% (64, 74) |
| 90 | 48% 192/403 | 2% 3/128 | 45% (40, 51) |
| 120 | 25% 102/403 | 2% 2/128 | 24% (19, 29) |
a 95% confidence intervals are shown in parenthesis | |||
b Day 30: Co-Primary Efficacy Time point, P<0.001 | |||
| Day | BOTOX® Cosmetic | Placebo | Differencea |
| 7 | 82% 334/405 | 9% 12/132 | 73% (68, 80) |
| 30b | 89% 362/405 | 7% 9/132 | 83% (77, 88) |
| 60 | 82% 330/403 | 4% 5/130 | 78% (73, 83) |
| 90 | 63% 254/403 | 3% 4/128 | 60% (54, 66) |
| 120 | 39% 157/403 | 1% 1/128 | 38% (33, 43) |
In the subset of patients with resting severity scores of moderate or severe, the investigator assessment of a resting severity of mild or none at day 30 was also achieved by more BOTOX® Cosmetic treated patients (74%, 119/161) than placebo treated patients (20%, 10/49).
Analysis of the limited number of patients 65 years or older suggested a lower treatment-associated response compared to patients less than 65 years of age (Table 3).
a 95% confidence intervals are shown in parenthesis | ||||
| Assessment | Age Group | BOTOX® Cosmetic N=405 | Placebo N=132 | Differencea |
| Investigators (maximal frown) | < 65 | 83% 316/382 | 2% 2/123 | 81% (77, 86) |
| Subjects | < 65 | 91% 346/382 | 7% 8/123 | 84% (79, 90) |
| Investigators (maximal frown) | ≥ 65 | 39% 9/23 | 22% 2/9 | 17% (-17, 51) |
| Subjects | ≥ 65 | 70% 16/23 | 11% 1/9 | 58% (31, 86) |
Exploratory analyses by gender suggested that responder rates in the BOTOX® Cosmetic treated group were higher for women than for men for both the investigator assessment (day 30; 85% of 334 women, 59% of 71 men) and the Subject Assessment (day 30; 93% of women, 72% of men). In the limited number of non-Caucasian patients (n=64 in the BOTOX® Cosmetic treated group) the responder rates were similar to those observed in the Caucasian patients.
BOTOX® Cosmetic is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients ≤ 65 years of age.
BOTOX® Cosmetic is contraindicated in the presence of infection at the proposed injection site(s) and in individuals with known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.
BOTOX® and BOTOX® Cosmetic contain the same active ingredient in the same formulation. Therefore, adverse events observed with the use of BOTOX® also have the potential to be associated with the use of BOTOX® Cosmetic.
The recommended dosage and frequency of administration for BOTOX® Cosmetic should not be exceeded. Risks resulting from administration at higher dosages are not known.
The potency Units of BOTOX® Cosmetic are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of BOTOX® Cosmetic cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method (see DESCRIPTION).
Postmarketing safety data from BOTOX® Cosmetic and other approved botulinum toxins suggest that botulinum toxin effects may, in some cases, be observed beyond the site of local injection. The symptoms are consistent with the mechanism of action of botulinum toxin and may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death related to spread of toxin effects. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, and particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, symptoms consistent with spread of toxin effect have been reported at doses comparable to or lower than doses used to treat cervical dystonia.
No definitive serious adverse event reports of distant spread of toxin effect associated with dermatologic use of BOTOX®/BOTOX® Cosmetic at the labeled dose of 20 Units (for glabellar lines) or 100 Units (for severe primary axillary hyperhidrosis) have been reported.
No definitive serious adverse event reports of distant spread of toxin effect associated with BOTOX® for blepharospasm at the recommended dose (30 Units and below) or for strabismus at the labeled doses have been reported.
Care should be taken when injecting in or near vulnerable anatomic structures. Serious adverse events including fatal outcomes have been reported in patients who had received BOTOX® injected directly into salivary glands, the oro-lingual-pharyngeal region, esophagus and stomach. Some patients had pre-existing dysphagia or significant debility. (Safety and effectiveness have not been established for indications pertaining to these injection sites.) Pneumothorax associated with injection procedure has been reported following the administration of BOTOX® near the thorax. Caution is warranted when injecting in proximity to the lung, particularly the apices.
Serious and/or immediate hypersensitivity reactions have been reported. These reactions include anaphylaxis, urticaria, soft tissue edema, and dyspnea. If such a reaction occurs, further injection of BOTOX® Cosmetic should be discontinued and appropriate medical therapy immediately instituted. One fatal case of anaphylaxis has been reported in which lidocaine was used as the diluent, and consequently the causal agent cannot be reliably determined.
Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of BOTOX® Cosmetic (see ADVERSE REACTIONS).
Treatment with BOTOX® and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant effects occur, additional respiratory muscles may be involved (see WARNINGS).
Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised.
Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been postmarketing reports of serious breathing difficulties, including respiratory failure, in cervical dystonia patients.
Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech, or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin (see WARNINGS, ADVERSE REACTIONS, CLINICAL PHARMACOLOGY).
There have been reports following administration of BOTOX® of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular disease.
This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
The safe and effective use of BOTOX® Cosmetic depends upon proper storage of the product, selection of the correct dose, and proper reconstitution and administration techniques. Physicians administering BOTOX® Cosmetic must understand the relevant neuromuscular and/or orbital anatomy of the area involved, as well as any alterations to the anatomy due to prior surgical procedures (see WARNINGS).
Caution should be used when BOTOX® Cosmetic treatment is used in the presence of inflammation at the proposed injection site(s) or when excessive weakness or atrophy is present in the target muscle(s).
Reduced blinking from BOTOX® Cosmetic injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect and corneal ulceration, especially in patients with VII nerve disorders. In the use of BOTOX® for the treatment of blepharospasm, one case of corneal perforation in an aphakic eye requiring corneal grafting has occurred because of this effect. Careful testing of corneal sensation in eyes previously operated upon, avoidance of injection into the lower lid area to avoid ectropion, and vigorous treatment of any epithelial defect should be employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other means.
Inducing paralysis in one or more extraocular muscles may produce spatial disorientation, double vision or past pointing. Covering the affected eye may alleviate these symptoms.
Caution should be used when BOTOX® Cosmetic treatment is used in patients who have an inflammatory skin problem at the injection site, marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin or the inability to substantially lessen glabellar lines by physically spreading them apart as these patients were excluded from the Phase 3 safety and efficacy trials.
Needle-related pain and/or anxiety may result in vasovagal responses (including e.g., syncope, hypotension), which may require appropriate medical therapy.
Injection intervals of BOTOX® Cosmetic should be no more frequent than every three months and should be performed using the lowest effective dose (see ADVERSE REACTIONS, IMMUNOGENICITY).
The physician should provide a copy of the FDA-Approved Patient Medication Guide and review the contents with the patient. Patients should be advised to inform their doctor or pharmacist if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing), or if any existing symptom worsens.
Patients should be counseled that if loss of strength, muscle weakness, or impaired vision occur, they should avoid driving a car or engaging in other potentially hazardous activities.
Co-administration of BOTOX® Cosmetic and aminoglycosides1 or other agents interfering with neuromuscular transmission (e.g., curare-like nondepolarizing blockers, lincosamides, polymyxins, quinidine, magnesium sulfate, anticholinesterases, succinylcholine chloride) should only be performed with caution as the effect of the toxin may be potentiated.
The effect of administering different botulinum neurotoxin serotypes at the same time or within several months of each other is unknown. Excessive neuromuscular weakness may be exacerbated by administration of another botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin.
Administration of BOTOX® Cosmetic is not recommended during pregnancy. There are no adequate and well-controlled studies of BOTOX® Cosmetic in pregnant women. When pregnant mice and rats were injected intramuscularly during the period of organogenesis, the developmental NOEL (No Observed Effect Level) of BOTOX® Cosmetic was 4 Units/kg. Higher doses (8 Units/kg or 16 Units/kg) were associated with reductions in fetal body weights and/or delayed ossification.
In a range finding study in rabbits, daily injection of 0.125 Units/kg/day (days 6 to 18 of gestation) and 2 Units/kg (days 6 and 13 of gestation) produced severe maternal toxicity, abortions and/or fetal malformations. Higher doses resulted in death of the dams. The rabbit appears to be a very sensitive species to BOTOX® Cosmetic.
If the patient becomes pregnant after the administration of this drug, the patient should be apprised of the potential risks, including abortion or fetal malformations that have been observed in rabbits.
Long term studies in animals have not been performed to evaluate carcinogenic potential of BOTOX® Cosmetic.
The reproductive NOEL following intramuscular injection of 0, 4, 8, and 16 Units/kg was 4 Units/kg in male rats and 8 Units/kg in female rats. Higher doses were associated with dose-dependent reductions in fertility in male rats (where limb weakness resulted in the inability to mate), and testicular atrophy or an altered estrous cycle in female rats. There were no adverse effects on the viability of the embryos.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BOTOX® Cosmetic is administered to a nursing woman.
Use of BOTOX® Cosmetic is not recommended in children.
The two clinical studies of BOTOX® Cosmetic did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, the responder rates appeared to be higher for patients younger than age 65 than for patients 65 years or older (see CLINICAL STUDIES).
There were too few patients (N=3) over the age of 75 to allow any meaningful comparisons.
BOTOX® and BOTOX® Cosmetic contain the same active ingredient in the same formulation. Therefore adverse events observed with the use of BOTOX® also have the potential to be associated with the use of BOTOX® Cosmetic.
The most serious adverse events reported after treatment with botulinum toxin include spontaneous reports of death, sometimes associated with anaphylaxis, dysphagia, pneumonia, and/or other significant debility.
There have also been reports of adverse events involving the cardiovascular system, including arrhythmia and myocardial infarction, some with fatal outcomes. Some of these patients had risk factors including pre-existing cardiovascular disease (see WARNINGS).
New onset or recurrent seizures have also been reported, typically in patients who are predisposed to experiencing these events. The exact relationship of these events to the botulinum toxin injection has not been established. Additionally, a report of acute angle closure glaucoma one day after receiving an injection of botulinum toxin for blepharospasm was received, with recovery four months later after laser iridotomy and trabeculectomy. Focal facial paralysis, syncope and exacerbation of myasthenia gravis have also been reported after treatment of blepharospasm.
In general, adverse events occur within the first week following injection of BOTOX® Cosmetic and while generally transient may have a duration of several months or longer. Localized pain, infection, inflammation, tenderness, swelling, erythema and/or bleeding/bruising may be associated with the injection. Local weakness of the injected muscle(s) represents the expected pharmacological action of botulinum toxin. However, weakness of adjacent muscles may also occur due to spread of toxin.
In clinical trials of BOTOX® Cosmetic the most frequently reported adverse events following injection of BOTOX® Cosmetic were headache*, respiratory infection*, flu syndrome*, blepharoptosis and nausea.
Less frequently occurring (<3%) adverse reactions included pain in the face, erythema at the injection site*, paresthesia* and muscle weakness. While local weakness of the injected muscle(s) is representative of the expected pharmacological action of botulinum toxin, weakness of adjacent muscles may occur as a result of the spread of toxin. These events are thought to be associated with the injection and occurred within the first week. The events were generally transient but may last several months or longer.
(* incidence not different from Placebo)
The data described in Table 4 reflect exposure to BOTOX® Cosmetic in 405 subjects aged 18 to 75 who were evaluated in the randomized, placebo-controlled clinical studies to assess the use of BOTOX® Cosmetic in the improvement of the appearance of glabellar lines (see CLINICAL STUDIES). Adverse events of any cause were reported for 44% of the BOTOX® Cosmetic treated subjects and 42% of the placebo treated subjects. The incidence of blepharoptosis was higher in the BOTOX® Cosmetic treated arm than in placebo (3% vs. 0).
In the open-label, repeat injection study, blepharoptosis was reported for 2% (8/373) of subjects in the first treatment cycle and 1% (4/343) of subjects in the second treatment cycle. Adverse events of any type were reported for 49% (183/373) of subjects overall. The most frequently reported of these adverse events in the open-label study included respiratory infection, headache, flu syndrome, blepharoptosis, pain and nausea.
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 be predictive of rates observed in practice.
| Percent of Patients Reporting Adverse Events | ||
| Adverse Events by Body System | BOTOX® Cosmetic (N=405) % | Placebo (N=130) % |
| Overall | 44 | 42 |
| Body as a Whole | ||
| Pain in Face | 2 | 1 |
| Skin and Appendages | ||
| Skin Tightness | 1 | 0 |
| Digestive System | ||
| Nausea | 3 | 2 |
| Dyspepsia | 1 | 0 |
| Tooth Disorder | 1 | 0 |
| Special Senses | ||
| Blepharoptosis | 3 | 0 |
| Musculoskeletal System | ||
| Muscle Weakness | 2 | 0 |
| Cardiovascular | ||
| Hypertension | 1 | 0 |
Treatment with BOTOX® Cosmetic may result in the formation of neutralizing antibodies that may reduce the effectiveness of subsequent treatments with BOTOX® Cosmetic by inactivating the biological activity of the toxin. The rate of formation of neutralizing antibodies in patients receiving BOTOX® Cosmetic has not been well studied.
The critical factors for neutralizing antibody formation have not been well characterized. The results from some studies suggest that botulinum toxin injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. The potential for antibody formation may be minimized by injecting the lowest effective dose given at the longest feasible intervals between injections.
Transient ptosis, the most frequently reported complication, has been reported in the literature in approximately 5% of patients. There has been a single report of diplopia, which resolved completely in three weeks.
The following other adverse reactions have been identified since the drug has been marketed: abdominal pain; blurred vision; brachial plexopathy; decreased hearing; diarrhea; ear noise; erythema multiforme; fever; focal facial paralysis; glaucoma; localized numbness; loss of appetite; malaise; myalgia; myasthenia gravis; pruritus; psoriasiform eruption; retinal vein occlusion; sweating; syncope; vertigo with nystagmus; and vomiting.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to botulinum toxin.
Adverse events following use of BOTOX® Cosmetic should be reported to the Pharmacovigilance Department, Allergan Inc. (1-800-433-8871). Adverse events may also be reported to the U.S. Department of Health and Human Services (DHHS) Adverse Event Reporting System. Report forms and reporting requirement information can be obtained from Adverse Event Reporting System (AERS) through a toll free number 1-800-822-7967.
Excessive doses of BOTOX® Cosmetic may be expected to produce neuromuscular weakness with a variety of symptoms.
Symptoms of overdose are likely not to be present immediately following injection. Should accidental injection or oral ingestion occur or overdose be suspected, the person should be medically supervised for several weeks for signs and symptoms of systemic muscular weakness which could be local, or distant from the site of injection (see BOXED WARNING and WARNINGS). These patients should be considered for further medical evaluation and appropriate medical therapy immediately instituted, which may include hospitalization.
If the musculature of the oropharynx and esophagus are affected, aspiration may occur which may lead to development of aspiration pneumonia. If the respiratory muscles become paralyzed or sufficiently weakened, intubation and assisted respiration may be necessary until recovery takes place. Supportive care could involve the need for a tracheostomy and/or prolonged mechanical ventilation, in addition to other general supportive care.
In the event of overdose, antitoxin raised against botulinum toxin is available from the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. However, the antitoxin will not reverse any botulinum toxin-induced effects already apparent by the time of antitoxin administration. In the event of suspected or actual cases of botulinum toxin poisoning, please contact your local or state Health Department to process a request for antitoxin through the CDC. If you do not receive a response within 30 minutes, please contact the CDC directly at 1-770-488-7100. More information can be obtained at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm.
BOTOX® Cosmetic is to be reconstituted only with 0.9% sterile, non-preserved saline prior to intramuscular injection. Per the dilution table below, draw up the required amount of 0.9% sterile non-preserved sodium chloride solution into a syringe to obtain a reconstituted solution at a concentration of 4 Units/0.1 mL and a total treatment dose of 20 Units in 0.5 mL. The duration of activity of BOTOX® Cosmetic for glabellar lines is approximately 3-4 months. The safety and effectiveness of more frequent dosing with BOTOX® Cosmetic has not been clinically evaluated and is not recommended.
| Diluent Added to 100 Unit Vial (0.9% Sodium Chloride Injection Only) | Resulting Dose Units per 0.1 mL | Diluent Added to 50 Unit Vial (0.9% Sodium Chloride Injection Only) | Resulting Dose Units per 0.1 mL |
| 2.5 mL | 4 Units | 1.25 mL | 4 Units |
Reconstituted BOTOX® Cosmetic should be clear, colorless, and free of particulate matter.
BOTOX® Cosmetic is supplied as a single use vial. The product and diluent do not contain a preservative. Once opened and reconstituted it should be stored in a refrigerator (2° to 8°C) and used within 24 hours. Discard any remaining solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not freeze reconstituted BOTOX® Cosmetic.
Using a 21-gauge needle and an appropriately sized syringe draw up a total of 2.5 mL/100 Unit vial or 1.25 mL/50 Unit vial of 0.9% sterile saline without a preservative. Insert the needle at a 45° angle and slowly inject into the BOTOX® Cosmetic vial. Discard the vial if a vacuum does not pull the diluent into the vial. Gently rotate the vial and record the date and time of reconstitution on the space on the label.
Draw at least 0.5 mL of the properly reconstituted toxin into the sterile syringe, preferably a tuberculin syringe and expel any air bubbles in the syringe barrel. Remove the needle used to reconstitute the product and attach a 30-33 gauge needle. Confirm the patency of the needle.
Glabellar facial lines arise from the activity of the corrugator and orbicularis oculi muscles. These muscles move the brow medially, and the procerus and depressor supercilii pull the brow inferiorly. This creates a frown or “furrowed brow”. The location, size, and use of the muscles vary markedly among individuals. Lines induced by facial expression occur perpendicular to the direction of action of contracting facial muscles. An effective dose for facial lines is determined by gross observation of the patient's ability to activate the superficial muscles injected.
In order to reduce the complication of ptosis the following steps should be taken:
Using a 30-33 gauge needle, inject a dose of 0.1 mL into each of 5 sites, 2 in each corrugator muscle and 1 in the procerus muscle for a total dose of 20 Units. Typically the initial doses of reconstituted BOTOX® Cosmetic induce chemical denervation of the injected muscles one to two days after injection, increasing in intensity during the first week.
BOTOX® Cosmetic is supplied in a single use vial in the following sizes:
50 Units: NDC 0023-3919-50
100 Units: NDC 0023-9232-01
Vials of BOTOX® Cosmetic have a holographic film on the vial label that contains the name “Allergan” within horizontal lines of rainbow color. In order to see the hologram, rotate the vial back and forth between your fingers under a desk lamp or fluorescent light source. (Note: the holographic film on the label is absent in the date/batch area.) If you do not see the lines of rainbow color or the name “Allergan,” do not use the product and contact Allergan for additional information at 1-800-890-4345 from 7:00 AM to 3:00 PM Pacific Time.
Rx Only
Single use vial.
Unopened vials of BOTOX® Cosmetic should be stored in a refrigerator (2° to 8°C) for up to 36 months for the 50 Units and 100 Units vials.
Administer BOTOX® Cosmetic within 24 hours of reconstitution; during this period reconstituted BOTOX® Cosmetic should be stored in a refrigerator (2° to 8°C). Reconstituted BOTOX® Cosmetic should be clear, colorless and free of particulate matter.
Do not use after the expiration date on the vial. All vials, including expired vials, or equipment used with the drug should be disposed of carefully as is done with all medical waste.
Revised: 11/2011
© 2011 Allergan, Inc.
® marks owned by Allergan, Inc.
Manufactured by: Allergan Pharmaceuticals Ireland
a subsidiary of: Allergan, Inc., 2525 Dupont Dr., Irvine, CA 92612
71823US15C
BOTOX®
BOTOX® Cosmetic
(Boe-tox)
(onabotulinumtoxinA)
for Injection
Read the Medication Guide that comes with BOTOX or Botox Cosmetic before you start using it and each time it is given to you. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. You should share this information with your family members and caregivers.
What is the most important information I should know about BOTOX and Botox Cosmetic?
BOTOX and Botox Cosmetic may cause serious side effects that can be life threatening, including:
These problems can happen hours, days, to weeks after an injection of BOTOX or Botox Cosmetic. Call your doctor or get medical help right away if you have any of these problems after treatment with BOTOX or Botox Cosmetic:
