Canfora New.Fa.Dem. may be available in the countries listed below.
Camphor D-Camphor (a derivative of Camphor) is reported as an ingredient of Canfora New.Fa.Dem. in the following countries:
International Drug Name Search
Generic Name: levobunolol ophthalmic (lee voe BYOO noe lole)
Brand names: Akbeta, Betagan, Levobunolol, Betagan C-Cap
Levobunolol is a beta-blocker that reduces pressure inside the eye.
Levobunolol ophthalmic may also be used for other purposes not listed in this medication guide.
Before using this medication, tell your doctor if you have breathing problems such as bronchitis or emphysema, a history of heart disease or congestive heart failure, diabetes, history of stroke, blood clot, or circulation problems, a thyroid disorder, or a muscle disorder such as myasthenia gravis.
Levobunolol ophthalmic is sometimes given together with other eye medications. Do not use any other eye medication unless your doctor has prescribed it for you. If you use another eye medication, use it at least 10 minutes before or after using levobunolol ophthalmic. Do not use the medications at the same time.
asthma, or severe chronic obstructive pulmonary disease (COPD);
slow heartbeats; or
a heart condition called "AV block."
If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:
breathing problems such as bronchitis or emphysema;
a history of heart disease or congestive heart failure;
diabetes;
history of stroke, blood clot, or circulation problems;
a thyroid disorder; or
a muscle disorder such as myasthenia gravis.
Use levobunolol ophthalmic exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on your prescription label.
To apply the eye drops:
Tilt your head back slightly and pull down your lower eyelid. Hold the dropper above the eye with the dropper tip down. Look up and away from the dropper as you squeeze out a drop, then close your eye.
Gently press your finger to the inside corner of the eye (near your nose) for about 1 minute to keep the liquid from draining into your tear duct. If you use more than one drop in the same eye, wait about 5 minutes before putting in the next drop.
Do not allow the dropper tip to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.
Do not use the eye drops if the liquid has changed colors or has particles in it. Call your doctor for a new prescription.
Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and use the medicine at the next regularly scheduled time. Do not use extra medicine to make up the missed dose.
Overdose symptoms may include slow heart rate, feeling short of breath, swelling, rapid weight gain, or fainting.
Levobunolol ophthalmic is sometimes given together with other eye medications. Do not use any other eye medication unless your doctor has prescribed it for you. If you use another eye medication, use it at least 10 minutes before or after using levobunolol ophthalmic. Do not use the medications at the same time.
severe swelling, itching, burning, redness, pain, or discomfort in or around your eye;
drainage, crusting, or oozing of your eyes or eyelids;
bronchospasm (wheezing, chest tightness, trouble breathing);
slow heart rate, weak pulse, fainting, slow breathing (breathing may stop);
feeling short of breath, even with mild exertion;
swelling, rapid weight gain; or
severe blistering, peeling, and red skin rash.
Less serious side effects may include:
mild burning, stinging, itching, or discomfort of your eyes;
blurred vision;
mildly swollen or puffy eyes;
headache, dizziness, spinning sensation;
depression, confusion, tired feeling;
muscle weakness;
mild skin rash or itching; or
nausea, diarrhea.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Usual Adult Dose for Intraocular Hypertension:
levobunolol 0.5% solution: 1 to 2 drops to affected eye(s) once a day
or
levobunolol 0.25% solution: 1 to 2 drops to affected eye(s) twice a day
Usual Adult Dose for Glaucoma (Open Angle):
levobunolol 0.5% solution: 1 to 2 drops to affected eye(s) once a day
or
levobunolol 0.25% solution: 1 to 2 drops to affected eye(s) twice a day
Before using levobunolol ophthalmic, tell your doctor if you are using any of the following drugs:
digoxin (digitalis, Lanoxin);
reserpine;
insulin or diabetes medications you take by mouth;
any other beta-blocker such as atenolol (Tenormin), bisoprolol (Zebeta), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), timolol (Blocadren), and others;
a calcium channel blocker such as amlodipine (Norvasc), diltiazem (Tiazac, Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia, Adalat), verapamil (Calan, Covera, Isoptin, Verelan); or
medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), haloperidol (Haldol), mesoridazine (Serentil), or thioridazine (Mellaril).
This list is not complete and there may be other drugs that can interact with levobunolol ophthalmic. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
See also: levobunolol side effects (in more detail)
Generic Name: prenatal multivitamins (PRE nay tal VYE ta mins)
Brand Names: Advance Care Plus, Bright Beginnings, Cenogen Ultra, CitraNatal 90 DHA, CitraNatal Assure, CitraNatal DHA, CitraNatal Rx, Complete Natal, Complete-RF, CompleteNate, Concept DHA, Concept OB, Dualvit OB, Duet, Duet Chewable, Duet DHA, Duet DHA EC, Edge OB, Folbecal, Foltabs, Foltabs 90 plus DHA, Foltabs plus DHA, Gesticare, Gesticare DHA, Icar Prenatal, Icare Prenatal Rx, Inatal Advance, Inatal Ultra, Lactocal-F, Marnatal-F Plus, Maternity, Maxinate, Mission Prenatal, Mission Prenatal HP, Multinatal Plus, Nata 29 OB, Nata 29 Prenatal, Natachew, Natafort, Natelle, Natelle C, Natelle Plus with DHA, Natelle Prefer, Natelle-ez, Neevo, Neevo DHA, Nestabs CBF, Novanatal, NovaStart, O-Cal Prenatal, OB Complete, OB Complete with DHA, OB Natal One, Ob-20, OptiNate, Pre-H-Cal, Precare, Precare Conceive, Precare Premier, PreferaOB, Premesis Rx, PrenaCare, PrenaFirst, PrenaPlus, Prenatabs CBF, Prenatabs FA, Prenatabs OBN, Prenatabs Rx, Prenatal 1 Plus 1, Prenatal 19, Prenatal AD, Prenatal Elite, Prenatal H, Prenatal Low Iron, Prenatal Multivitamins, Prenatal Plus, Prenatal Plus Iron, Prenatal S, Prenatal-U, Prenate Advanced Formula, Prenate DHA, Prenate Elite, Prenate Elite Plus Iron, Prenavite FC, Prenavite PC, PreNexa, Previte Rx, PrimaCare, PrimaCare Advantage, PrimaCare One, Pruet DHA, Pruet DHA EC, RE OB 90 Plus DHA, RE OB Plus DHA, Renate, Renate DHA, Renate DHA Extra, RightStep, Se-Care, Se-Care Conceive, Se-Natal 90, Se-Natal One, Select-OB, Select-OB+DHA, Strongstart, Stuart Prenatal with Beta Carotene, Tandem DHA, Tandem OB, Tri Rx, TriAdvance, TriCare, Trinatal Rx, Trinate, UltimateCare Advance, UltimateCare One, Ultra-Natal, Verotin-BY, Verotin-GR, Vinatal 600, Vinatal Forte, Vinate 90, Vinate Advanced (New Formula), Vinate AZ, Vinate AZ Extra, Vinate C, Vinate Calcium, Vinate Care, Vinate Good Start, Vinate GT, Vinate IC, Vinate II (New Formula), Vinate III, Vinate M, Vinate One, Vinate PN Care, Vinate Ultra, Vitafol PN, Vitafol-OB, Vitafol-OB+DHA, Vitaphil, Vitaphil Aide, Vitaphil Plus DHA, Vitaphil Plus DHA 90, Vitaspire, Viva DHA, Vynatal F.A.
Prenatal vitamins are a combination of many different vitamins that are normally found in foods and other natural sources.
Prenatal vitamins are used to provide the additional vitamins needed during pregnancy. Minerals may also be contained in prenatal multivitamins.
Prenatal vitamins may also be used for other purposes not listed in this medication guide.
There are many brands and forms of prenatal vitamin available and not all brands are listed on this leaflet.
Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.
Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.
Before taking prenatal vitamins, tell your doctor about all of your medical conditions.
Use this medication as directed on the label, or as your doctor has prescribed. Do not use the medication in larger amounts or for longer than recommended.
Many multivitamin products also contain minerals such as calcium, iron, magnesium, potassium, and zinc. Minerals (especially taken in large doses) can cause side effects such as tooth staining, increased urination, stomach bleeding, uneven heart rate, confusion, and muscle weakness or limp feeling. Read the label of any multivitamin product you take to make sure you are aware of what it contains.
Swallow the regular tablet or capsule whole. Do not break, chew, crush, or open it.
The chewable tablet must be chewed or allowed to dissolve in your mouth before swallowing. You may also allow the chewable tablet to dissolve in drinking water, fruit juice, or infant formula (but not milk or other dairy products). Drink this mixture right away.
It is important to take prenatal vitamins regularly to get the most benefit.
Store prenatal vitamins in their original container. Storing vitamins in a glass container can ruin the medication.
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.
Overdose symptoms may include stomach pain, vomiting, diarrhea, constipation, loss of appetite, hair loss, peeling skin, tingly feeling in or around your mouth, changes in menstrual periods, weight loss, severe headache, muscle or joint pain, severe back pain, blood in your urine, pale skin, and easy bruising or bleeding.
Avoid the regular use of salt substitutes in your diet if your multivitamin contains potassium. If you are on a low-salt diet, ask your doctor before taking a vitamin or mineral supplement.
When taken as directed, prenatal vitamins are not expected to cause serious side effects. Less serious side effects may include:
upset stomach;
headache; or
unusual or unpleasant taste in your mouth.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Vitamin and mineral supplements can interact with certain medications, or affect how medications work in your body. Before taking a prenatal vitamin, tell your doctor if you also use:
diuretics (water pills);
heart or blood pressure medications;
tretinoin (Vesanoid);
isotretinoin (Accutane, Amnesteen, Clavaris, Sotret);
trimethoprim and sulfamethoxazole (Cotrim, Bactrim, Gantanol, Gantrisin, Septra, TMP/SMX); or
an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), diclofenac (Cataflam, Voltaren), etodolac (Lodine), indomethacin (Indocin), ketoprofen (Orudis), and others.
This list is not complete and there may be other medications that can interact with or be affected by prenatal vitamins. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
Azulavine may be available in the countries listed below.
Sodium Gualenate is reported as an ingredient of Azulavine in the following countries:
International Drug Name Search
Aciclovir Edigen may be available in the countries listed below.
Aciclovir is reported as an ingredient of Aciclovir Edigen in the following countries:
International Drug Name Search
If Navelbine accidentally leaks into surrounding tissue, the skin and/or muscle may be severely damaged. Notify your doctor immediately if you feel pain or irritation at the injection site. Fatalities have occurred when medicines similar to vinorelbine were injected into the spine. This drug is for intravenous (IV; into a vein) use only.
Navelbine can cause blood disorders (eg, granulocytopenia) than can decrease your ability to fight infection. Notify your doctor immediately if you develop signs of infection, such as persistent sore throat or fever.
Treating cancer.
Navelbine is an antineoplastic. It works by targeting cancer cells and interfering with their reproduction.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Navelbine. 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 Navelbine. Tell your health care provider if you are taking any other medicines, especially any of the following:
This may not be a complete list of all interactions that may occur. Ask your health care provider if Navelbine 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 Navelbine 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 Navelbine.
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:
Diarrhea; hair loss; nausea; vomiting; weakness.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; constipation; cough; numbness or tingling of your fingers or toes; pain, redness, or swelling at the injection site; shortness of breath; stomach pain; unusual bleeding or bruising.
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: Navelbine 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.
Navelbine is usually handled and stored by a health care provider. If you are using Navelbine at home, store Navelbine as directed by your pharmacist or health care provider. Keep Navelbine out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Navelbine. 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.
Treating and preventing infection due to minor cuts, scrapes, and burns.
Lanabiotic Ointment is an antibiotic combination. It works by killing sensitive bacteria on the skin or in wounds.
Contact your doctor or health care provider right away if any of these apply to you.
Some medical conditions may interact with Lanabiotic Ointment. 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 Lanabiotic Ointment. Because little, if any, of Lanabiotic Ointment is absorbed into the blood, the risk of it interacting with another medicine is low.
Ask your health care provider if Lanabiotic Ointment 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 Lanabiotic Ointment 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 Lanabiotic Ointment.
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); skin irritation, pain, burning, cracking, redness, or peeling not present before using Lanabiotic Ointment; worsening or recurrence of wound symptoms.
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.
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.
Store Lanabiotic Ointment at room temperature, between 59 and 86 degrees F (15 and 30 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Lanabiotic Ointment out of the reach of children and away from pets.
This information is a summary only. It does not contain all information about Lanabiotic Ointment. 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.
Alco may be available in the countries listed below.
Pseudoephedrine hydrochloride (a derivative of Pseudoephedrine) is reported as an ingredient of Alco in the following countries:
International Drug Name Search
Levalbuterol Inhalation Solution USP, Concentrate 1.25 mg (0.25%)*
*Potency expressed as Levalbuterol
PRESCRIBING INFORMATION
Rx Only
Levalbuterol Inhalation Solution, USP is a sterile, clear, colorless, preservative-free solution of the hydrochloride salt of Levalbuterol, the (R)-enantiomer of the drug substance racemic albuterol. Levalbuterol HCl is a relatively selective beta2-adrenergic receptor agonist (see CLINICAL PHARMACOLOGY). The chemical name for Levalbuterol HCl is (R)-α1-[[(1,1-dimethylethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol hydrochloride, and its established chemical structure is as follows:
The molecular weight of Levalbuterol HCl is 275.8, and its molecular formula is C13H21NO3·HCl. It is a white to off-white, crystalline solid, with a melting point of approximately 187°C and solubility of approximately 180 mg/mL in water.
Levalbuterol HCl is the USAN modified name for (R)-albuterol HCl in the United States.
Levalbuterol Inhalation Solution, USP, Concentrate is supplied in 0.5 mL individually-wrapped unit-dose vials and should be diluted with sterile normal saline before administration by nebulization. Each 0.5 mL unit-dose vial contains 1.25 mg/0.5 mL (0.25%) of Levalbuterol HCl, USP (as 1.44 mg of Levalbuterol HCl), sodium chloride, USP to adjust tonicity and sulfuric acid NF to adjust the pH to 4.0 (3.3 to 4.5).
Activation of beta2-adrenergic receptors on airway smooth muscle leads to the activation of adenylcyclase and to an increase in the intracellular concentration of cyclic-3′, 5′-adenosine monophosphate (cyclic AMP). This increase in cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Levalbuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Levalbuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway.
While it is recognized that beta2-adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there is a population of beta2-receptors in the human heart that comprise between 10% and 50% of cardiac beta-adrenergic receptors. The precise function of these receptors has not been established (see WARNINGS). However, all beta-adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes.
Results from an in vitro study of binding to human beta-adrenergic receptors demonstrated that Levalbuterol has approximately 2-fold greater binding affinity than racemic albuterol and approximately 100-fold greater binding affinity than (S)-albuterol. In guinea pig airways, Levalbuterol HCl and racemic albuterol decreased the response to spasmogens (e.g., acetylcholine and histamine), whereas (S)-albuterol was ineffective. These results suggest that the bronchodilatory effects of racemic albuterol are attributable to the (R)-enantiomer.
Intravenous studies in rats with racemic albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5.0% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain.
Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown.
The inhalation pharmacokinetics of Levalbuterol Inhalation Solution, USP were investigated in a randomized cross-over study in 30 healthy adults following administration of a single dose of 1.25 mg and a cumulative dose of 5 mg of Levalbuterol Inhalation Solution, USP and a single dose of 2.5 mg and a cumulative dose of 10 mg of racemic albuterol sulfate inhalation solution by nebulization using a PARI LC Jet™ nebulizer with a Dura-Neb® 2000 compressor.
Following administration of a single 1.25 mg dose of Levalbuterol Inhalation Solution, USP exposure to (R)-albuterol (AUC of 3.3 ng•hr/mL) was approximately 2-fold higher than following administration of a single 2.5 mg dose of racemic albuterol inhalation solution (AUC of 1.7 ng•hr/mL) (see Table 1.0). Following administration of a cumulative 5 mg dose of Levalbuterol Inhalation Solution, USP (1.25 mg given every 30 minutes for a total of four doses) or a cumulative 10 mg dose of racemic albuterol inhalation solution (2.5 mg given every 30 minutes for a total of four doses), Cmax and AUC of (R)-albuterol were comparable (see Table 1.0).
| ||||
| Single Dose | Cumulative Dose | |||
| Levalbuterol Inhalation Solution, USP 1.25 mg | Racemic albuterol sulfate 2.5 mg | Levalbuterol Inhalation Solution, USP 5 mg | Racemic albuterol sulfate 10 mg | |
| Cmax (ng/mL) (R)-albuterol | 1.1 (0.45) | 0.8 (0.41)* | 4.5 (2.20) | 4.2 (1.51)* |
| Tmax (h)† (R)-albuterol | 0.2 (0.17, 0.37) | 0.2 (0.17, 1.50) | 0.2 (-0.18‡, 1.25) | 0.2 (-0.28‡ , 1.00) |
| AUC (ng●h/mL) (R)-albuterol | 3.3 (1.58) | 1.7 (0.99)* | 17.4 (8.56) | 16.0 (7.12)* |
| T½ (h) (R)-albuterol | 3.3 (2.48) | 1.5 (0.61) | 4.0 (1.05) | 4.1 (0.97) |
The pharmacokinetic parameters of (R)- and (S)-albuterol in children with asthma were obtained using population pharmacokinetic analysis. These data are presented in Table 2.0. For comparison, adult data obtained by conventional pharmacokinetic analysis from a different study are also presented in Table 2.0.
In children, AUC and Cmax of (R)-albuterol following administration of 0.63 mg Levalbuterol Inhalation Solution, USP were comparable to those following administration of 1.25 mg racemic albuterol sulfate inhalation solution.
When the same dose of 0.63 mg of Levalbuterol HCl, USP was given to children and adults, the predicted Cmax of (R)-albuterol in children was similar to that in adults (0.52 vs. 0.56 ng/mL), while predicted AUC in children (2.55 ng•hr/mL) was about 1.5-fold higher than that in adults (1.65 ng•hr/mL). These data support lower doses for children 6-11 years old compared with the adult doses (see DOSAGE AND ADMINISTRATION).
| ||||||
| Treatment | Children 6-11 years | Adults ≥ 12 years | ||||
| Levalbuterol Inhalation Solution, USP 0.31 mg | Levalbuterol Inhalation Solution, USP 0.63 mg | Racemic albuterol 1.25 mg | Racemic albuterol 2.5 mg | Levalbuterol Inhalation Solution, USP 0.63 mg | Levalbuterol Inhalation Solution, USP 1.25 mg | |
| AUC0-∞ (ng●hr/mL)* | 1.36 | 2.55 | 2.65 | 5.02 | 1.65† | 3.3‡ |
| Cmax (ng/mL)§ | 0.303 | 0.521 | 0.553 | 1.08 | 0.56† | 1.1‡ |
Information available in the published literature suggests that the primary enzyme responsible for the metabolism of albuterol enantiomers in humans is SULT1A3 (sulfotransferase). When racemic albuterol was administered either intravenously or via inhalation after oral charcoal administration, there was a 3- to 4-fold difference in the area under the concentration-time curves between the (R)- and (S)-albuterol enantiomers, with (S)-albuterol concentrations being consistently higher. However, without charcoal pretreatment, after either oral or inhalation administration the differences were 8- to 24-fold, suggesting that (R)-albuterol is preferentially metabolized in the gastrointestinal tract, presumably by SULT1A3.
The primary route of elimination of albuterol enantiomers is through renal excretion (80% to 100%) of either the parent compound or the primary metabolite. Less than 20% of the drug is detected in the feces. Following intravenous administration of racemic albuterol, between 25% and 46% of the (R)-albuterol fraction of the dose was excreted as unchanged (R)-albuterol in the urine.
The effect of hepatic impairment on the pharmacokinetics of Levalbuterol Inhalation Solution, USP has not been evaluated.
The effect of renal impairment on the pharmacokinetics of racemic albuterol was evaluated in 5 subjects with creatinine clearance of 7 to 53 mL/min, and the results were compared with those from healthy volunteers. Renal disease had no effect on the half-life, but there was a 67% decline in racemic albuterol clearance. Caution should be used when administering high doses of Levalbuterol Inhalation Solution, USP to patients with renal impairment.
In a randomized, double-blind, placebo-controlled, cross-over study, 20 adults with mild-to-moderate asthma received single doses of Levalbuterol Inhalation Solution, USP (0.31, 0.63, and 1.25 mg) and racemic albuterol sulfate inhalation solution (2.5 mg). All doses of active treatment produced a significantly greater degree of bronchodilation (as measured by percent change from pre-dose mean FEV1) than placebo, and there were no significant differences between any of the active treatment arms. The bronchodilator responses to 1.25 mg of Levalbuterol Inhalation Solution, USP and 2.5 mg of racemic albuterol sulfate inhalation solution were clinically comparable over the 6-hour evaluation period, except for a slightly longer duration of action (>15% increase FEV1 from baseline) after administration of 1.25 mg of Levalbuterol Inhalation Solution, USP. Systemic beta-adrenergic adverse effects were observed with all active doses and were generally dose-related for (R)-albuterol. Levalbuterol Inhalation Solution, USP at a dose of 1.25 mg produced a slightly higher rate of systemic beta-adrenergic adverse effects than the 2.5 mg dose of racemic albuterol sulfate inhalation solution.
In a randomized, double-blind, placebo-controlled, cross-over study, 12 adults with mild-to-moderate asthma were challenged with inhaled methacholine chloride 20 and 180 minutes following administration of a single dose of 2.5 mg of racemic albuterol sulfate, 1.25 mg of Levalbuterol HCl, 1.25 mg of (S)-albuterol, or placebo using a PARI LC Jet™ nebulizer. Racemic albuterol sulfate, Levalbuterol HCl, and (S)-albuterol had a protective effect against methacholine-induced bronchoconstriction 20 minutes after administration, although the effect of (S)-albuterol was minimal. At 180 minutes after administration, the bronchoprotective effect of 1.25 mg of Levalbuterol HCl was comparable to that of 2.5 mg of racemic albuterol sulfate. At 180 minutes after administration, 1.25 mg of (S)-albuterol had no bronchoprotective effect.
In a clinical study in adults with mild-to-moderate asthma, comparable efficacy (as measured by change from baseline FEV1) and safety (as measured by heart rate, blood pressure, ECG, serum potassium, and tremor) were demonstrated after a cumulative dose of 5 mg of Levalbuterol Inhalation Solution, USP (four consecutive doses of 1.25 mg administered every 30 minutes) and 10 mg of racemic albuterol sulfate inhalation solution (four consecutive doses of 2.5 mg administered every 30 minutes).
The safety and efficacy of Levalbuterol Inhalation Solution, USP were evaluated in a 4-week, multicenter, randomized, double-blind, placebo-controlled, parallel group study in 362 adult and adolescent patients 12 years of age and older, with mild-to-moderate asthma (mean baseline FEV1 60% of predicted). Approximately half of the patients were also receiving inhaled corticosteroids. Patients were randomized to receive Levalbuterol HCl 0.63 mg, Levalbuterol HCl 1.25 mg, racemic albuterol sulfate 1.25 mg, racemic albuterol sulfate 2.5 mg, or placebo three times a day administered via a PARI LC Plus™ nebulizer and a Dura-Neb® portable compressor. Racemic albuterol delivered by a chlorofluorocarbon (CFC) metered dose inhaler (MDI) was used on an as-needed basis as the rescue medication.
Efficacy, as measured by the mean percent change from baseline FEV1, was demonstrated for all active treatment regimens compared with placebo on day 1 and day 29. On both day 1 (see Figure 1.0) and day 29 (see Figure 2.0), 1.25 mg of Levalbuterol HCl demonstrated the largest mean percent change from baseline FEV1 compared with the other active treatments. A dose of 0.63 mg of Levalbuterol HCl and 2.5 mg of racemic albuterol sulfate produced a clinically comparable mean percent change from baseline FEV1 on both day 1 and day 29.
Figure 1.0: Mean Percent Change from Baseline FEV1 and Day 1, Adults and Adolescents ≥12 years old
Figure 2.0: Mean Percent Change from Baseline FEV1 on Day 29, Adults and Adolescents ≥12 years old
The mean time to onset of a 15% increase in FEV1 over baseline for Levalbuterol at doses of 0.63 mg and 1.25 mg was approximately 17 minutes and 10 minutes, respectively, and the mean time to peak effect for both doses was approximately 1.5 hours after 4 weeks of treatment. The mean duration of effect, as measured by a >15% increase from baseline FEV1, was approximately 5 hours after administration of 0.63 mg of Levalbuterol and approximately 6 hours after administration of 1.25 mg of Levalbuterol after 4 weeks of treatment. In some patients, the duration of effect was as long as 8 hours.
A multi-center, randomized, double-blind, placebo- and active-controlled study was conducted in children with mild-to-moderate asthma (mean baseline FEV1 73% of predicted) (n =316). Following a 1-week placebo run-in, subjects were randomized to Levalbuterol HCl (0.31 or 0.63 mg), racemic albuterol (1.25 or 2.5 mg), or placebo, which were delivered three times a day for 3 weeks using a PARI LC Plus™ nebulizer and a Dura-Neb® 3000 compressor.
Efficacy, as measured by mean peak percent change from baseline FEV1, was demonstrated for all active treatment regimens compared with placebo on day 1 and day 21. Time profile FEV1 curves for day 1 and day 21 are shown in Figure 3.0 and Figure 4.0, respectively. The onset of effect (time to a 15% increase in FEV1 over test day baseline) and duration of effect (maintenance of a >15% increase in FEV1 over test day baseline) of Levalbuterol were clinically comparable to those of racemic albuterol.
Figure 3.0: Mean Percent Change from Baseline FEV1 on Day 1, Children 6-11 Years of Age
Figure 4.0: Mean Percent Change from Baseline FEV1 on Day 21, Children 6-11 Years of Age
Levalbuterol Inhalation Solution, USP is indicated for the treatment or prevention of bronchospasm in adults, adolescents, and children 6 years of age and older with reversible obstructive airway disease.
Levalbuterol Inhalation Solution, USP is contraindicated in patients with a history of hypersensitivity to Levalbuterol HCl or racemic albuterol.
Levalbuterol HCl, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmias; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines. Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after the use of any beta-adrenergic bronchodilator.
Large doses of intravenous racemic albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-adrenergic agonist medications, Levalbuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation.
See illustrated Patient’s Instructions for Use.
The action of Levalbuterol Inhalation Solution, USP may last up to 8 hours. Levalbuterol Inhalation Solution, USP should not be used more frequently than recommended. Do not increase the dose or frequency of dosing of Levalbuterol Inhalation Solution, USP without consulting your physician. If you find that treatment with Levalbuterol Inhalation Solution, USP becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to use the product more frequently than usual, you should seek medical attention immediately. While you are taking Levalbuterol Inhalation Solution, USP, other inhaled drugs and asthma medications should be taken only as directed by your physician. Common adverse effects include palpitations, chest pain, rapid heart rate, headache, dizziness, and tremor or nervousness. If you are pregnant or nursing, contact your physician about the use of Levalbuterol Inhalation Solution, USP.
Effective and safe use of Levalbuterol Inhalation Solution, USP requires consideration of the following information in addition to that provided under Patient’s Instructions for Use:
Levalbuterol Inhalation Solution, USP single-use low-density polyethylene (LDPE) vials should be protected from light and excessive heat. Store in the protective foil pouch between 20°C and 25°C (68°F and 77°F) [see USP Controlled Room Temperature]. Do not use after the expiration date stamped on the container. Open the foil pouch just prior to administration. Once the foil pouch is opened, the contents of the vial should be used immediately. Discard any vial if the solution is not colorless. Levalbuterol Inhalation Solution, USP, Concentrate should be diluted with sterile normal saline before administration by nebulization.
The drug compatibility (physical and chemical), efficacy, and safety of Levalbuterol Inhalation Solution, USP when mixed with other drugs in a nebulizer have not been established.
Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should be used with caution with Levalbuterol. If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.
No carcinogenesis or impairment of fertility studies have been carried out with Levalbuterol HCl alone. However, racemic albuterol sulfate has been evaluated for its carcinogenic potential and ability to impair fertility.
In a 2-year study in Sprague-Dawley rats, racemic albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at and above dietary doses of 2 mg/kg (approximately 2 times the maximum recommended daily inhalation dose of Levalbuterol HCl for adults and children on a mg/m2 basis). In another study, this effect was blocked by the coadministration of propranolol, a nonselective beta-adrenergic antagonist. In an 18-month study in CD-1 mice, racemic albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 500 mg/kg (approximately 260 times the maximum recommended daily inhalation dose of Levalbuterol HCl for adults and children on a mg/m2 basis). In a 22-month study in the Golden hamster, racemic albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 50 mg/kg (approximately 35 times the maximum recommended daily inhalation dose of Levalbuterol HCl for adults and children on a mg/m2 basis).
Levalbuterol HCl was not mutagenic in the Ames test or the CHO/HPRT Mammalian Forward Gene Mutation Assay. Although Levalbuterol HCl has not been tested for clastogenicity, racemic albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay. Reproduction studies in rats using racemic albuterol sulfate demonstrated no evidence of impaired fertility at oral doses up to 50 mg/kg (approximately 55 times the maximum recommended daily inhalation dose of Levalbuterol HCl for adults on a mg/m2 basis).
A reproduction study in New Zealand White rabbits demonstrated that Levalbuterol HCl was not teratogenic when administered orally at doses up to 25 mg/kg (approximately 110 times the maximum recommended daily inhalation dose of Levalbuterol HCl for adults on a mg/m2 basis). However, racemic albuterol sulfate has been shown to be teratogenic in mice and rabbits. A study in CD-1 mice given racemic albuterol sulfate subcutaneously showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg (less than the maximum recommended daily inhalation dose of Levalbuterol HCl for adults on a mg/m2 basis) and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg (approximately equal to the maximum recommended daily inhalation dose of Levalbuterol HCl for adults on a mg/m2 basis). The drug did not induce cleft palate formation when administered subcutaneously at a dose of 0.025 mg/kg (less than the maximum recommended daily inhalation dose of Levalbuterol HCl for adults on a mg/m2 basis). Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated subcutaneously with 2.5 mg/kg of isoproterenol (positive control).
A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when racemic albuterol sulfate was administered orally at a dose of 50 mg/kg (approximately 110 times the maximum recommended daily inhalation dose of Levalbuterol HCl for adults on a mg/m2 basis).
A study in which pregnant rats were dosed with radiolabeled racemic albuterol sulfate demonstrated that drug-related material is transferred from the maternal circulation to the fetus.
There are no adequate and well-controlled studies of Levalbuterol Inhalation Solution, USP in pregnant women. Because animal reproduction studies are not always predictive of human response, Levalbuterol Inhalation Solution, USP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
During marketing experience of racemic albuterol, various congenital anomalies, including cleft palate and limb defects, have been rarely reported in the offspring of patients being treated with racemic albuterol. Some of the mothers were taking multiple medications during their pregnancies. No consistent pattern of defects can be discerned, and a relationship between racemic albuterol use and congenital anomalies has not been established.
Because of the potential for beta-adrenergic agonists to interfere with uterine contractility, the use of Levalbuterol Inhalation Solution, USP for the treatment of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.
Levalbuterol HCl has not been approved for the management of preterm labor. The benefit:risk ratio when Levalbuterol HCl is administered for tocolysis has not been established. Serious adverse reactions, including maternal pulmonary edema, have been reported during or following treatment of premature labor with beta2-agonists, including racemic albuterol.
Plasma levels of Levalbuterol after inhalation of therapeutic doses are very low in humans, but it is not known whether Levalbuterol is excreted in human milk.
Because of the potential for tumorigenicity shown for racemic albuterol in animal studies and the lack of experience with the use of Levalbuterol Inhalation Solution, USP by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Caution should be exercised when Levalbuterol Inhalation Solution, USP is administered to a nursing woman.
The safety and efficacy of Levalbuterol Inhalation Solution, USP have been established in pediatric patients 6 years of age and older in one adequate and well-controlled clinical trial (see CLINICAL PHARMACOLOGY; Pharmacodynamics and Clinical Trials). Use of Levalbuterol HCl in children is also supported by evidence from adequate and well-controlled studies of Levalbuterol Inhalation Solution, USP in adults, considering that the pathophysiology and the drug’s exposure level and effects in pediatric and adult patients are substantially similar. Safety and effectiveness of Levalbuterol Inhalation Solution, USP in pediatric patients below the age of 6 years have not been established.
Data on the use of Levalbuterol Inhalation Solution, USP in patients 65 years of age and older are very limited. A very small number of patients 65 years of age and older were treated with Levalbuterol Inhalation Solution, USP in a 4-week clinical study (see CLINICAL PHARMACOLOGY; Clinical Trials) (n=2 for 0.63 mg and n=3 for 1.25 mg). In these patients, bronchodilation was observed after the first dose on day 1 and after 4 weeks of treatment. There are insufficient data to determine if the safety and efficacy of Levalbuterol Inhalation Solution, USP are different in patients < 65 years of age and patients 65 years of age and older. In general, patients 65 years of age and older should be started at a dose of 0.63 mg of Levalbuterol Inhalation Solution, USP. If clinically warranted due to insufficient bronchodilator response, the dose of Levalbuterol Inhalation Solution, USP may be increased in elderly patients as tolerated, in conjunction with frequent clinical and laboratory monitoring, to the maximum recommended daily dose (see DOSAGE AND ADMINISTRATION).
Adverse events reported in ≥ 2% of patients receiving Levalbuterol Inhalation Solution, USP or racemic albuterol and more frequently than in patients receiving placebo in a 4-week, controlled clinical trial are listed in Table 3.0.
| Body System Preferred Term | Percent of Patients | |||
| Placebo (n=75) | Levalbuterol Inhalation Solution,USP 1.25 mg (n=73) | Levalbuterol Inhalation Solution, USP 0.63 mg (n=72) | Racemic Albuterol 2.5 mg (n=74) | |
| Body as a Whole | ||||
| Allergic reaction | 1.3 | 0 | 0 | 2.7 |
| Flu syndrome | 0 | 1.4 | 4.2 | 2.7 |
| Accidental injury | 0 | 2.7 | 0 | 0 |
| Pain | 1.3 | 1.4 | 2.8 | 2.7 |
| Back pain | 0 | 0 | 0 | 2.7 |
| Cardiovascular | ||||
| Tachychardia | 0 | 2.7 | 2.8 | 2.7 |
| Migraine | 0 | 2.7 | 0 | 0 |
| Digestive System | ||||
| Dyspepsia | 1.3 | 2.7 | 1.4 | 1.4 |
| Musculoskeletal System | ||||
| Leg cramps | 1.3 | 2.7 | 0 | 1.4 |
| Central Nervous System | ||||
| Dizziness | 1.3 | 2.7 | 1.4 | 0 |
| Hypertonia | 0 | 0 | 0 | 2.7 |
| Nervousness | 0 | 9.6 | 2.8 | 8.1 |
| Tremor | 0 | 6.8 | 0 | 2.7 |
| Anxiety | 0 | 2.7 | 0 | 0 |
| Respiratory System | ||||
| Cough increased | 2.7 | 4.1 | 1.4 | 2.7 |
| Infection viral | 9.3 | 12.3 | 6.9 | 12.2 |
| Rhinitis | 2.7 | 2.7 | 11.1 | 6.8 |
| Sinusitis | 2.7 | 1.4 | 4.2 | 2.7 |
| Turbinate edema | 0 | 1.4 | 2.8 | 0 |
The incidence of certain systemic beta-adrenergic adverse effects (e.g., tremor, nervousness) was slightly less in the Levalbuterol HCl 0.63 mg group compared with the other active treatment groups. The clinical significance of these small differences is unknown.
Changes in heart rate 15 minutes after drug administration and in plasma glucose and potassium 1 hour after drug administration on day 1 and day 29 were clinically comparable in the Levalbuterol Inhalation Solution, USP 1.25 mg and the racemic albuterol 2.5 mg groups (see Table 4.0). Changes in heart rate and plasma glucose were slightly less in the Levalbuterol Inhalation Solution, USP 0.63 mg group compared with the other acti
