Taxotere

Generic Name: Docetaxel
Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: [2aR - [2aα,4β,4aβ,6β,9α(αR*,βS*),11α,12α,12aα,12bα]] - 12b - (acetyloxy) - 12 - (benzoyloxy) - 2a,3,4,4a,5,6,9,10,11,12,12a,12b - dodecahydro - 4,6,11 - trihydroxy - 4a,8,13,13 - tetramethyl - 5 - oxo - 7,11 - methano - 1H - cyclodeca[3,4]benz[1,2 - b]oxet - 9 - yl ester β-[[(1,1-dimethylethoxy)carbonyl]amino]-α-hydroxybenzenepropanoic acid
Molecular Formula: C₄₃H₅₃NO₁₄
CAS Number: 114977-28-5

• Treatment-related Mortality


• 
  

  Incidence of treatment-related mortality increased in patients with abnormal hepatic function, patients receiving higher doses, and patients with non-small cell lung carcinoma previously treated with platinum-based chemotherapy who received docetaxel monotherapy at a dose of 100 mg/m².^a Approximately half of deaths reported in breast cancer patients occurred during the first cycle; most deaths were due to sepsis.¹

  
  

• Hepatic Impairment


• 
  

  Docetaxel should not be administered to patients with serum total bilirubin >ULN, or patients with serum AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN.¹ These patients are at increased risk for grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death.¹ Increased risk for grade 4 febrile neutropenia, but not toxic death, in patients with isolated elevations of AST or ALT >1.5 times ULN.¹

  
  


• 
  

  Obtain and review bilirubin, AST, ALT, and alkaline phosphatase values prior to each cycle.¹

  
  

• Hematologic Monitoring


• 
  

  Docetaxel should not be administered to patients with neutrophil counts <1500/mm³.¹

  
  


• 
  

  Monitor blood cell counts frequently.¹

  
  

• Hypersensitivity


• 
  

  Severe hypersensitivity reactions (hypotension and/or bronchospasm, generalized rash/erythema) reported in patients who received the recommended 3-day dexamethasone premedication.¹ Hypersensitivity reactions requiring discontinuance reported in patients who did not receive dexamethasone premedication.¹ Hypersensitivity reactions resolved following discontinuance of the infusion and appropriate treatment.¹

  
  


• 
  

  Do not administer to patients with a history of severe hypersensitivity reactions to docetaxel or polysorbate 80.¹

  
  

• Fluid Retention


• 
  

  Severe fluid retention (poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, pronounced abdominal distention, ascites) reported in patients despite receiving the 3-day dexamethasone premedication.¹

  
  

• Experience of Supervising Clinician


• 
  

  Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy.¹ Adequate diagnostic and treatment facilities should be readily available to manage complications.¹

  
  

Introduction

Semisynthetic taxoid; an antineoplastic agent.^{1 2 3 4 5 6 7 8}

Uses for Taxotere

Breast Cancer

Treatment of locally advanced or metastatic breast cancer after failure of prior chemotherapy.^{a 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 40 54 b}

Non-small Cell Lung Carcinoma

Monotherapy of locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy.^{a 54 59 60 61 b}

In combination with cisplatin for treatment of unresectable locally advanced or metastatic non-small cell lung cancer in patients who have not previously received chemotherapy for this condition;^a also used in combination with carboplatin.^b

Taxotere Dosage and Administration

General

• 
  

  All patients should be premedicated before docetaxel administration to prevent severe hypersensitivity reactions and to reduce the incidence and severity of fluid retention.¹

  
  


• 
  

  Oral dexamethasone 8 mg twice daily for 3 days, starting 1 day prior to docetaxel administration, can be given.^a

  
  


• 
  

  Consult specialized references for procedures for proper handling and disposal of antineoplastics.^a

  
  

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.¹

Handle cautiously (by trained nonpregnant personnel); use protective equipment (e.g., gloves) and wash hands after removal of the gloves.¹

Immediately treat accidental contact with skin by thoroughly washing with soap and water; immediately treat accidental contact with mucous membranes by thoroughly washing with water.¹

Administer through polyethylene-lined administration sets.^{1 36} Use of inline filters is neither required nor recommended.³⁷

Dilution

Docetaxel for injection concentrate requires 2 dilutions prior to administration.¹

Remove vials from refrigerator and allow to stand at room temperature for approximately 5 minutes. Add the contents of the diluent vial to the vial of docetaxel for injection concentrate, to give a solution containing docetaxel 10 mg/mL.¹

Mix this solution by repeated inversions for at least 45 seconds; do not shake.^a If foaming occurs, allow solution to stand for a few minutes to allow foam to dissipate; all foam does not have to dissipate to continue preparation.^a

Withdraw the appropriate dose with a calibrated syringe and inject into 250 mL of either 0.9% sodium chloride injection or 5% dextrose injection to produce a final docetaxel concentration of 0.3–0.74 mg/mL.^a

If doses larger than 200 mg of docetaxel are required, increase volume of IV solution accordingly so that a docetaxel concentration of 0.74 mg/mL is not exceeded.^a

Rate of Administration

Administer over 1 hour.¹

Dosage

Adults

Breast Cancer

IV

60–100 mg/m² in repeated 3-week cycles.¹

Dosage adjustment during treatment may be necessary.¹ In patients initially dosed at 100 mg/m² who experience febrile neutropenia, neutrophil count <500/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or peripheral neuropathy, reduce dose by 25% (e.g., from 100 to 75 mg/m²) for subsequent courses of therapy.^{1 37} If the patient continues to experience these reactions, reduce dosage from 75 to 55 mg/m² or discontinue.¹ Discontinue entirely if >grade 3 peripheral neuropathy develops.^a

Higher doses may be tolerated by patients who are dosed initially at 60 mg/m² and who do not experience febrile neutropenia, neutrophil count <500/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or peripheral neuropathy.¹

Non-small Cell Lung Carcinoma

IV

Treatment after failure of platinum-based chemotherapy: 75 mg/m² in repeated 3-week cycles.^a Higher doses (i.e., 100 mg/m²) associated with increased hematologic toxicity, infection, and treatment-related mortality.^a

Chemotherapy-naive patients: 75 mg/m² immediately followed by cisplatin in repeated 3-week cycles.^a

Dosage adjustment during treatment may be necessary.^a In patients who are dosed initially at 75 mg/m² after failure of platinum-based chemotherapy who experience febrile neutropenia, neutrophil count <500/mm³ for more than 1 week, severe or cumulative cutaneous reactions, or other grade 3/4 nonhematologic toxicities, withhold until toxicity resolves and then resume at 55 mg/m².^a Discontinue entirely if >grade 3 peripheral neuropathy develops.^a

In chemotherapy-naive patients who are dosed initially at 75 mg/m² in conjunction with cisplatin whose nadir platelet count during the previous course is <25,000/mm³, or who experience febrile neutropenia or serious nonhematologic toxicities, reduce dose to 65 mg/m² for subsequent cycles.^a In patients who need further dose reduction, a dose of 50 mg/m² is recommended.^a

Prescribing Limits

Adults

Breast Cancer

IV

100 mg/m².¹

Special Populations

Hepatic Impairment

Not recommended in patients with hepatic impairment.¹ (See Hepatic Impairment under Boxed Warning.)

Renal Impairment

Dosage adjustment does not appear to be necessary.³⁷

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.^a

Cautions for Taxotere

Contraindications

• 
  

  Known hypersensitivity to docetaxel, polysorbate 80, or any other ingredient in the formulation.¹

  
  


• 
  

  Baseline neutrophil count <1500/mm³.¹

  
  

Warnings/Precautions

Warnings

Adequate Patient Evaluation and Monitoring

Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic therapy.¹

Patients must have recovered from acute toxicities (e.g., neutrophils recovered to >1500/mm³, platelets to >100,000/mm³) of previous cytotoxic therapy before each cycle.¹

Prior to and during therapy, assess serum bilirubin, AST and/or ALT, and alkaline phosphatase concentrations.¹ Frequent monitoring of blood cell counts also recommended.¹

Hematologic Effects

Frequency and severity of hematologic toxicity, febrile reactions and infections, and rates of septic death increase with dose and presence of hepatic dysfunction.^{1 7 22}

Neutropenia (i.e., neutrophils <2000/mm³) occurs in essentially all patients receiving doses of 60–100 mg/m² and is dose related; grade 4 neutropenia (<500/mm³) reported in >75% of patients.¹ Neutrophil nadir at day 7–8;^{1 8 13 14 19 20} the median duration of grade 4 neutropenia is about 7 days.^{1 5 7 13}

Cardiovascular Toxicity

Severe fluid retention reported despite 3 days of dexamethasone premedication.^{1 3} (See Fluid Retention in Boxed Warning.)

Peripheral edema usually begins in lower extremities and appears to be completely (although sometimes slowly) reversible;^{1 3 a} generally responds to standard measures, including sodium restriction and oral diuretics.^{1 3 13 25}

Patients should be premedicated with oral corticosteroids to reduce the incidence and severity of fluid retention.¹ (See General under Dosage and Administration.)

Monitor patients with preexisting effusions beginning with the first dose.¹

Fetal/Neonatal Morbidity and Mortality

Embryotoxic and fetotoxic in animals.¹ If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard or potential risk of losing pregnancy.^a (See Pregnancy under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Severe reactions, characterized by hypotension and/or bronchospasm or generalized rash/erythema, reported in some patients despite receiving recommended 3 days of dexamethasone premedication.¹ Hypersensitivity reactions requiring discontinuance reported in patients who did not receive corticosteroid premedication.^a

Patients should be premedicated with oral corticosteroids to reduce the severity of hypersensitivity reactions.¹ (See General under Dosage and Administration.)

Closely observe for hypersensitivity reactions, especially during the first and second infusions.¹

Reactions may occur within a few minutes following initiation of the infusion.^{1 9 25} Interruption of therapy generally is not needed for mild reactions (e.g., flushing, localized skin reactions);^{1 13 15 18 19 20 23} consider decreasing the infusion rate until symptoms resolve.³⁷

Discontinue immediately and treat if severe reaction occurs.¹

Do not administer to any patient who experienced a severe hypersensitivity reaction during a previous course.¹

Dermatologic Effects

Localized erythema of the extremities with edema followed by desquamation reported.¹

Adjust dosage if severe skin toxicity occurs.¹ (See Dosage under Dosage and Administration.)

Major Toxicities

Nervous System Effects

Severe neurosensory symptoms (paresthesia, dysesthesia, pain) reported.¹ Reduce dosage if occurs (see Dosage under Dosage and Administration); if symptoms persist, discontinue docetaxel.¹ Discontinue docetaxel in patients who develop >grade 3 peripheral neuropathy.^a

Asthenia reported; symptoms of fatigue and weakness may last a few days to several weeks and may be associated with deterioration of performance status in patients with progressive disease.¹

General Precautions

Patients who respond to docetaxel may not experience an improvement and/or may experience worsening in performance status.¹ The relationship between changes in performance status, response to therapy, and treatment-related adverse effects not established.¹

Prescribing and Dispensing Precautions

Ensure accuracy of prescription; similarity of spelling of Taxotere (docetaxel) and Taxol (paclitaxel) may result in errors.⁶²

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Discontinue nursing because of potential risk to nursing infants.¹

Pediatric Use

Safety and efficacy in pediatric patients <16 years of age not established.^{1 37}

Geriatric Use

Geriatric patients ≥65 years of age receiving docetaxel with cisplatin experienced a higher incidence of diarrhea, infections, peripheral edema, and stomatitis than younger adults.^a

Hepatic Impairment

Increased incidence of treatment-related mortality in patients with abnormal liver function.¹ (See Hepatic Impairment in Boxed Warning.)

Common Adverse Effects

Alopecia, myelosuppression (neutropenia, leukopenia, anemia), fluid retention, neurosensory effects, nausea, diarrhea, stomatitis.¹

Interactions for Taxotere

Appears to be metabolized by CYP3A4.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A.¹

Specific Drugs

Drug	Interaction
Cisplatin	Pharmacokinetic interaction unlikelya
Cyclosporine	Possible interactiona
Dexamethasone	No effect on docetaxel protein binding1
Erythromycin	Possible increased plasma docetaxel concentrationsa
Ketoconazole	Possible increased plasma docetaxel concentrationsa
Nifedipine	Possible increased plasma docetaxel concentrationsa

Taxotere Pharmacokinetics

Distribution

Extent

Not known whether docetaxel is distributed into milk.¹

Plasma Protein Binding

94–97%.¹

Elimination

Metabolism

Metabolized by CYP3A4 isoenzyme.¹

Elimination Route

Eliminated in feces (75%) and in urine (6%), mainly as metabolites; <8% recovered in feces as unchanged drug within 48 hours.¹

Half-life

Half-lives for the α, β, and γ phases are about 4 minutes, 36 minutes, and 11.1 hours, respectively.¹

Special Populations

Clearance reduced and systemic exposure increased in patients with mild to moderate hepatic impairment (serum AST and/or ALT >1.5 times ULN concurrent with alkaline phosphatase >2.5 times ULN).¹ Wide interindividual variation; insufficient data for dosage recommendation.¹

Stability

Storage

Parenteral

For Injection Concentrate

2–25°C in the original package to protect from bright light.¹ Freezing does not adversely affect the product.¹

Polysorbate 80 (in docetaxel injection) can cause leaching of diethylhexyl phthalate (DEHP) from PVC containers or administration sets.³⁶ Do not permit contact of undiluted docetaxel for injection concentrate with plasticized PVC equipment or devices.^{1 36} Stored diluted docetaxel solutions in glass or polypropylene containers or in plastic (polypropylene or polyolefin) bags and administer through polyethylene-lined administration sets.^{1 36}

Docetaxel solutions that have been diluted to 10 mg/mL (initial dilution) may be stored at room temperature or in the refrigerator for up to 8 hours.¹

Docetaxel solutions that have been diluted to 0.3–0.74 mg/mL (final dilution for infusion) should be used within 4 hours (including the 1 hour for administration).¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^{a HID}

Compatible
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility

Y-site CompatibilityHID

Compatible
Acyclovir sodium
Amifostine
Amikacin sulfate
Aminophylline
Ampicillin sodium
Ampicillin sodium–sulbactam sodium
Aztreonam
Bumetanide
Buprenorphine HCl
Butorphanol tartrate
Calcium gluconate
Cefazolin sodium
Cefepime HCl
Cefotaxime sodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Chlorpromazine HCl
Cimetidine HCl
Ciprofloxacin
Clindamycin phosphate
Co-trimoxazole
Dexamethasone sodium phosphate
Diphenhydramine HCl
Dobutamine HCl
Dopamine HCl
Doxycycline hyclate
Droperidol
Enalaprilat
Famotidine
Fluconazole
Furosemide
Ganciclovir sodium
Gemcitabine HCl
Gentamicin sulfate
Granisetron HCl
Haloperidol lactate
Heparin sodium
Hydrocortisone sodium phosphate
Hydrocortisone sodium succinate
Hydromorphone HCl
Hydroxyzine HCl
Imipenem–cilastatin sodium
Leucovorin calcium
Lorazepam
Magnesium sulfate
Mannitol
Meperidine HCl
Meropenem
Mesna
Metoclopramide HCl
Metronidazole
Morphine sulfate
Ofloxacin
Ondansetron HCl
Oxaliplatin
Palonosetron HCI
Pemetrexed disodium
Piperacillin sodium–tazobactam sodium
Potassium chloride
Prochlorperazine edisylate
Promethazine HCl
Ranitidine HCl
Ringer’s injection, lactated
Sodium bicarbonate
Ticarcillin disodium–clavulanate potassium
Tobramycin sulfate
Vancomycin HCl
Zidovudine
Incompatible
Amphotericin B
Doxorubicin HCl liposome injection
Methylprednisolone sodium succinate
Nalbuphine HCl

ActionsActions

• 
  

  A semisynthetic taxoid produced from the needles of the European yew (Taxus baccata) tree.^{1 2 3 4 5 6} Structurally and pharmacologically similar to paclitaxel.^{2 4 5 7 8}

  
  


• 
  

  Disrupts the microtubular network in cells that is essential for mitotic and interphase cellular function.¹

  
  

Advice to Patients

• 
  

  Importance of recognizing and reporting adverse effects including myelosuppressive effects, infectious complications, and cutaneous reactions.¹

  
  


• 
  

  Importance of reading the patient information leaflet.¹

  
  


• 
  

  Probable alopecia.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to fetus.¹

  
  


• 
  

  Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illness.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Docetaxel

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection concentrate, for IV infusion	40 mg (of anhydrous docetaxel) per mL (20 or 80 mg)	Taxotere (with bacteriostatic water for injection containing alcohol 13% w/w diluent)	Aventis

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

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2. Bissery MC, Nohynek G, Sanderink G-J et al. Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: preclinical experience. Anti-Cancer Drugs. 1995; 6:339-68. [PubMed 7670132]

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32. Lemenager M, Genouville C, Bessa EH et al. Docetaxel-induced alopecia can be prevented. Lancet. 1995; 346:371-2. [IDIS 351261] [PubMed 7623542]

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45. Miller VA, Rigas JR, Francis PA et al. Phase II trial of a 75-mg/m² dose of docetaxel with prednisone premedication for patients with advanced non-small cell lung cancer. Cancer. 1995; 75:968-72. [IDIS 342401] [PubMed 7842417]

46. Kunitoh H, Watanabe K, Onoshi T et al. Phase II trial of docetaxel in previously untreated advanced non-small-cell lung cancer: a Japanese cooperative study. J Clin Oncol. 1996; 14:1649-55. [IDIS 366407] [PubMed 8622084]

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48. Fossella FV, Lee JS, Berille J et al. Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. Semin Oncol. 1995; 22(2 Suppl 4):22-9. [PubMed 7740327]

49. Saarinen A, Jekunen A, Halme M et al. A phase II trial of docetaxel in advanced non-small cell lung cancer. Anti-Cancer Drugs. 1996; 7:890-2. [PubMed 8991195]

50. Cerny T, Kaplan S, Pavlidis N et al. Docetaxel (Taxotere^TM) is active in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG). Br J Cancer. 1994; 70:384-7. [PubMed 7914429]

51. Zalcberg J, Millward M, Bishop J et al. Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer. J Clin Oncol. 1998; 16:1948-53. [IDIS 406137] [PubMed 9586914]

52. Non-small cell lung cancer. From PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Aug.

53. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ. 1995; 311:899-909. [PubMed 7580546]

54. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. [PubMed 10994034]

55. Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer. Adopted on May 16, 1997 by the American Society of Clinical Oncology. J Clin Oncol. 1997; 15:2996-3018. [IDIS 391214] [PubMed 9256144]

56. Weick JK, Crowley J, Natale RB et al. A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1991; 9:1157-62. [PubMed 1646292]

57. Ramanathan RK, Belani CP. Chemotherapy for advanced non-small cell lung cancer: past, present, and future. Semin Oncol. 1997; 24:440-54. [PubMed 9280224]

58. Georgoulias V, Androulakis N, Dimopoulos AM et al. First-line treatment of advanced non-small-cell lung cancer with docetaxel and cisplatin: a multicenter phase II study. Ann Oncol. 1998; 9:331-4. [PubMed 9602269]

59. Shepherd FA, Dancey J, Ramlau R et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000; 18:2095-103. [IDIS 455768] [PubMed 10811675]

60. Fossella FV, DeVore R, Kerr RN et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol. 2000; 18:2354-62. [IDIS 449176] [PubMed 10856094]

61. Anon. FDA approves new indication for Taxotere. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1999 Dec 23.

62. FDA advise-ERR: medication errors associated with Taxotere and Taxol. Rockville, MD: US Food and Drug Administration; 2001 Feb 7.

a. Aventis. Taxotere (docetaxel) for injection concentrate prescribing information. Bridgewater, NJ; 2003 Apr.

b. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. [PubMed 10994034]

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:555-62.

More Taxotere resources

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• Taxotere Consumer Overview


• Taxotere Prescribing Information (FDA)


• Taxotere Advanced Consumer (Micromedex) - Includes Dosage Information


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Albuterol

Generic Name: Albuterol sulfate

Dosage Form: tablet

Albuterol Description

Albuterol tablets contain Albuterol sulfate, USP, the racemic form of Albuterol and a relatively selective beta2-adrenergic bronchodilator. Albuterol sulfate has the chemical name α1-[(tert-Butylamino)methyl]-4-hydroxy-m-xylene-α,α'-diol sulfate (2:1) (salt) and the following structural formula:

Albuterol sulfate has a molecular weight of 576.71, and the molecular formula is (C13H21NO3)2•H2SO4. Albuterol sulfate is a white or practically white powder, freely soluble in water and slightly soluble in ethanol.

The World Health Organization recommended name for Albuterol base is salbutamol.

Each Albuterol tablet for oral administration contains 2 or 4 mg of Albuterol as 2.4 or 4.8 mg of Albuterol sulfate, respectively. Each tablet also contains the following inactive ingredients: lactose (hydrous), magnesium stearate, pregelatinized (corn) starch and sodium lauryl sulfate.

Albuterol - Clinical Pharmacology

In vitro studies and in vivo pharmacologic studies have demonstrated that Albuterol has a preferential effect on beta2-adrenergic receptors compared with isoproterenol. While it is recognized that beta2-adrenergic receptors are the predominant receptors in bronchial smooth muscle, data indicate that there is a population of beta2-receptors in the human heart existing in a concentration between 10% and 50%. The precise function of these receptors has not been established (see WARNINGS).

The pharmacologic effects of beta-adrenergic agonist drugs, including Albuterol, are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'- adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Albuterol has been shown in most controlled clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects.

Albuterol is longer acting than isoproterenol in most patients by any route of administration because it is not a substrate for the cellular uptake processes for catecholamines nor for catechol-O-methyl transferase.

Preclinical

Intravenous studies in rats with Albuterol sulfate have demonstrated that Albuterol crosses the blood brain barrier and reaches brain concentrations amounting to approximately 5% of the plasma concentrations. In structures outside the 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.

Pharmacokinetics

Albuterol is rapidly absorbed after oral administration of one 4 mg Albuterol tablet in normal volunteers. Maximum plasma concentrations of about 18 ng/mL of Albuterol are achieved within 2 hours, and the drug is eliminated with a half-life of about 5 hours.

In other studies, the analysis of urine samples of patients given 8 mg of tritiated Albuterol orally showed that 76% of the dose was excreted over 3 days, with the majority of the dose being excreted within the first 24 hours. Sixty percent of this radioactivity was shown to be the metabolite. Feces collected over this period contained 4% of the administered dose.

Clinical Trials

In controlled clinical trials in patients with asthma, the onset of improvement in pulmonary function, as measured by maximum midexpiratory flow rate (MMEF), was within 30 minutes after a dose of Albuterol tablets, with peak improvement occurring between 2 and 3 hours. In controlled clinical trials in which measurements were conducted for 6 hours, clinically significant improvement (defined as maintaining a 15% or more increase in forced expiratory volume in 1 second [FEV1] and a 20% or more increase in MMEF over baseline values) was observed in 60% of patients at 4 hours and in 40% at 6 hours. In other single-dose, controlled clinical trials, clinically significant improvement was observed in at least 40% of the patients at 8 hours. No decrease in the effectiveness of Albuterol tablets was reported in patients who received long-term treatment with the drug in uncontrolled studies for periods up to 6 months.

Indications and Usage for Albuterol

Albuterol tablets are indicated for the relief of bronchospasm in adults and children 6 years of age and older with reversible obstructive airway disease.

Contraindications

Albuterol tablets are contraindicated in patients with a history of hypersensitivity to Albuterol, or any of its components.

Warnings

Paradoxical Bronchospasm

Albuterol tablets can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, Albuterol tablets should be discontinued immediately and alternative therapy instituted.

Cardiovascular Effects

Albuterol tablets, like all other beta-adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of Albuterol tablets at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, Albuterol tablets, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Deterioration of Asthma

Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of Albuterol tablets than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.

Use of Anti-Inflammatory Agents

The use of beta-adrenergic agonist bronchodilators alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids.

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions may occur after administration of Albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema. Albuterol, like other beta-adrenergic agonists, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes.

Rarely, erythema multiforme and Stevens-Johnson syndrome have been associated with the administration of oral Albuterol sulfate in children.

Precautions

General

Albuterol, as with all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension; 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 use of any beta-adrenergic bronchodilator.

Large doses of intravenous Albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, Albuterol 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.

Information for Patients

The action of Albuterol tablets may last up to 8 hours or longer. Albuterol tablets should not be taken more frequently than recommended. Do not increase the dose or frequency of Albuterol tablets without consulting your physician. If you find that treatment with Albuterol tablets becomes less effective for symptomatic relief, your symptoms get worse, and/or you need to take the product more frequently than usual, you should seek medical attention immediately. While you are taking Albuterol tablets, other asthma medications and inhaled drugs should be taken only as directed by your physician. Common adverse effects include palpitations, chest pain, rapid heart rate, and tremor or nervousness. If you are pregnant or nursing, contact your physician about use of Albuterol tablets. Effective and safe use of Albuterol tablets includes an understanding of the way that it should be administered.

Drug Interactions

The concomitant use of Albuterol tablets and other oral sympathomimetic agents is not recommended since such combined use may lead to deleterious cardiovascular effects. This recommendation does not preclude the judicious use of an aerosol bronchodilator of the adrenergic stimulant type in patients receiving Albuterol tablets. Such concomitant use, however, should be individualized and not given on a routine basis. If regular coadministration is required, then alternative therapy should be considered.

Monamine Oxidase Inhibitors or Tricyclic Antidepressants

Albuterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of Albuterol on the vascular system may be potentiated.

Beta-Blockers

Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-agonists, such as Albuterol tablets, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

Diuretics

The ECG changes and/or hypokalemia that may result from the administration of nonpotassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with nonpotassium-sparing diuretics.

Digoxin

Mean decreases of 16% to 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of Albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving Albuterol and digoxin on a chronic basis is unclear. Nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and Albuterol.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2- year study in Sprague-Dawley rats, Albuterol sulfate caused a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary doses of 2, 10, and 50 mg/kg (approximately 1/2, 3, and 15 times, respectively, the maximum recommended daily oral dose for adults on a mg/m2 basis, or, 2/5, 2 and 10 times, respectively, the maximum recommended daily oral dose for children on a mg/m2 basis). In another study this effect was blocked by the coadministration of propranolol, a non-selective beta-adrenergic antagonist.

In an 18-month study in CD-1 mice Albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 500 mg/kg, (approximately 65 times the maximum recommended daily oral dose for adults on a mg/m2 basis, or, approximately 50 times the maximum recommended daily oral dose for children on a mg/m2 basis). In a 22-month study in the Golden hamster, Albuterol sulfate showed no evidence of tumorigenicity at dietary doses of up to 50 mg/kg, (approximately 8 times the maximum recommended daily oral dose for adults on a mg/m2 basis, or, approximately 7 times the maximum recommended daily oral dose for children on a mg/m2 basis).

Albuterol sulfate was not mutagenic in the Ames test with or without metabolic activation using tester strains S. typhimurium TA1537, TA1538, and TA98 or E. Coli WP2, WP2uvrA, and WP67. No forward mutation was seen in yeast strain S. cerevisiae S9 nor any mitotic gene conversion in yeast strain S. cerevisiae JD1 with or without metabolic activation. Fluctuation assays in S. typhimurium TA98 and E. Coli WP2, both with metabolic activation, were negative. Albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay at intraperitoneal doses of up to 200 mg/kg.

Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses up to 50 mg/kg (approximately 15 times the maximum recommended daily oral dose for adults on a mg/m2 basis).

Pregnancy

Teratogenic Effects. Pregnancy Category C

Albuterol has been shown to be teratogenic in mice. A study in CD-1 mice at subcutaneous (sc) doses of 0.025, 0.25, and 2.5 mg/kg (approximately 3/1000, 3/100, and 3/10 times, respectively, the maximum recommended daily oral dose for adults on a mg/m2 basis), showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg. The drug did not induce cleft palate formation at the lowest dose, 0.025 mg/kg. Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated with 2.5 mg/kg of isoproterenol (positive control) subcutaneously (approximately 3/10 times the maximum recommended daily oral dose for adults on a mg/m2 basis).

A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when Albuterol was administered orally at a 50 mg/kg dose (approximately 25 times the maximum recommended daily oral dose for adults on a mg/m2 basis).

There are no adequate and well-controlled studies in pregnant women. Albuterol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been rarely reported in the offspring of patients being treated with Albuterol. Some of the mothers were taking multiple medications during their pregnancies. No consistent pattern of defects can be discerned, and a relationship between Albuterol use and congenital anomalies has not been established.

Use in Labor and Delivery

Because of the potential for beta-agonist interference with uterine contractility, use of Albuterol tablets for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Tocolysis

Albuterol has not been approved for the management of preterm labor. The benefit/risk ratio when Albuterol 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 Albuterol.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown for Albuterol in some animal studies, 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.

Pediatric Use

Safety and effectiveness in children below 6 years of age have not been established.

Adverse Reactions

In clinical trials, the most frequent adverse reactions to Albuterol tablets were:

Percent Incidence of Adverse Reactions

Reaction	Percent Incidence
Central nervous system
Nervousness	20%
Tremor	20%
Headache	7%
Sleeplessness	2%
Weakness	2%
Dizziness	2%
Drowsiness	<1%
Restlessness	<1%
Irritability	<1%
Cardiovascular
Tachycardia	5%
Palpitations	5%
Chest discomfort	<1%
Flushing	<1%
Musculoskeletal
Muscle cramps	3%
Gastrointestinal
Nausea	2%
Genitourinary
Difficulty in micturition	<1%

Rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema have been reported after the use of Albuterol.

In addition, Albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vomiting, vertigo, central nervous system stimulation, unusual taste, and drying or irritation of the oropharynx.

The reactions are generally transient in nature, and it is usually not necessary to discontinue treatment with Albuterol tablets. In selected cases, however, dosage may be reduced temporarily; after the reaction has subsided, dosage should be increased in small increments to the optimal dosage.

Overdosage

The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the symptoms listed under ADVERSE REACTIONS, e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness. Hypokalemia may also occur. As with all sympathomimetic medications, cardiac arrest and even death may be associated with abuse of Albuterol tablets. Treatment consists of discontinuation of Albuterol tablets together with appropriate symptomatic therapy.The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Albuterol tablets. The oral median lethal dose of Albuterol sulfate in mice is greater than 2000 mg/kg (approximately 250 times the maximum recommended daily oral dose for adults on a mg/m2 basis, or, approximately 200 times the maximum recommended daily oral dose for children on a mg/m2 basis). In mature rats, the subcutaneous (sc) median lethal dose of Albuterol sulfate is approximately 450 mg/kg (approximately 110 times the maximum recommended daily oral dose for adults on a mg/m2 basis, or, approximately 90 times the maximum recommended daily oral dose for children on a mg/m2 basis). In small young rats, the subcutaneous median lethal dose is approximately 2000 mg/kg (approximately 500 times the maximum recommended daily oral dose for adults on a mg/m2 basis, or, approximately 400 times the maximum recommended daily oral dose for children on a mg/m2 basis).

Albuterol Dosage and Administration

The following dosages of Albuterol tablets are expressed in terms of Albuterol base.

Usual Dosage

Adults and Children Over 12 Years of Age

The usual starting dosage for adults and children 12 years and older is 2 or 4 mg three or four times a day.

Children 6 to 12 Years of Age

The usual starting dosage for children 6 to 12 years of age is 2 mg three or four times a day.

Dosage Adjustment

Adults and Children Over 12 Years of Age

For adults and children 12 years and older, a dosage above 4 mg four times a day should be used only when the patient fails to respond. If a favorable response does not occur with the 4 mg initial dosage, it should be cautiously increased stepwise up to a maximum of 8 mg four times a day as tolerated.

Children 6 to 12 Years of Age Who Fail to Respond to the Initial Starting Dosage of 2 mg Four Times a Day

For children from 6 to 12 years of age who fail to respond to the initial starting dosage of 2 mg four times a day, the dosage may be cautiously increased stepwise, but not to exceed 24 mg/day (given in divided doses).

Elderly Patients and Those Sensitive to Beta-adrenergic Stimulators

An initial dosage of 2 mg three or four times a day is recommended for elderly patients and for those with a history of unusual sensitivity to beta-adrenergic stimulators. If adequate bronchodilation is not obtained, dosage may be increased gradually to as much as 8 mg three or four times a day.

The total daily dose should not exceed 32 mg in adults and children 12 years and older.

How is Albuterol Supplied

Albuterol Tablets, USP, contain Albuterol sulfate equivalent to 2 mg or 4 mg of Albuterol.

The tablets containing Albuterol sulfate equivalent to 2 mg of Albuterol are white, scored, round tablets debossed with M255 on the scored side. They are available as follows:

NDC 0378-0255-01

bottles of 100 tablets

NDC 0378-0255-05

bottles of 500 tablets

The tablets containing Albuterol sulfate equivalent to 4 mg of Albuterol are white, scored, round tablets debossed with M572 on the scored side. They are available as follows:

NDC 0378-0572-01

bottles of 100 tablets

NDC 0378-0572-05

bottles of 500 tablets

Store at 20° to 25°C (68° to 77°F). [See USP for Controlled Room Temperature.]

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505

REVISED MARCH 2006

ALB:R14

 

PRINCIPAL DISPLAY PANEL - 2 mg

NDC 0378-0255-01

Albuterol

TABLETS, USP

2 mg*

100 TABLETS (Rx only)

*Each tablet contains:

Albuterol sulfate, USP

2.4 mg equivalent to

Albuterol 2 mg.

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication out

of the reach of children.

Store at 20° to 25°C (68° to 77°F).

[See USP for Controlled Room

Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying

prescribing information.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505

RM0255A8

 

PRINCIPAL DISPLAY PANEL - 4 mg

NDC 0378-0572-01

Albuterol

TABLETS, USP

4 mg*

100 TABLETS (Rx only)

*Each tablet contains:

Albuterol sulfate, USP

4.8 mg equivalent to

Albuterol 4 mg.

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication out

of the reach of children.

Store at 20° to 25°C (68° to 77°F).

[See USP for Controlled Room

Temperature.]

Protect from light.

Usual Adult Dosage: See accompanying

prescribing information.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505

RM0572A7

Albuterol  Albuterol sulfate  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0378-0255 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Albuterol SULFATE (Albuterol) Albuterol 2 mg

Inactive Ingredients Ingredient Name Strength LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   STARCH, CORN   SODIUM LAURYL SULFATE

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 6mm Flavor Imprint Code M;255 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0378-0255-01 100 TABLET In 1 BOTTLE, PLASTIC None 2 0378-0255-05 500 TABLET In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA072894	05/04/2011

Albuterol  Albuterol sulfate  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0378-0572 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Albuterol SULFATE (Albuterol) Albuterol 4 mg

Inactive Ingredients Ingredient Name Strength LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   STARCH, CORN   SODIUM LAURYL SULFATE

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 9mm Flavor Imprint Code M;572 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0378-0572-01 100 TABLET In 1 BOTTLE, PLASTIC None 2 0378-0572-05 500 TABLET In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA072894	05/04/2011

Labeler - Mylan Pharmaceuticals Inc. (059295980)

Revised: 01/2010Mylan Pharmaceuticals Inc.

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• Albuterol Side Effects (in more detail)
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• Albuterol Monograph (AHFS DI)


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Theophylline

Pronunciation: thee-OF-i-lin
Generic Name: Theophylline
Brand Name: Quibron-T

Theophylline is used for:

Preventing and treating symptoms and blockage of airway due to asthma or other lung diseases (eg, emphysema, bronchitis). It may also be used for other conditions as determined by your doctor.

Theophylline is a xanthine derivative. It works by relaxing the muscle around the airways in the lungs, which allows them to widen and makes breathing easier. It also improves contraction of the diaphragm (the major breathing muscle) and decreases the response of the airways to irritants.

Do NOT use Theophylline if:

• you are allergic to any ingredient in Theophylline, similar medicines (eg, aminophylline), or xanthines (eg, caffeine, chocolate)


• you are using large amounts of other products that contain xanthine (such as chocolate or caffeinated drinks)


• you are taking dipyridamole intravenously (IV), febuxostat, halothane, or St. John's wort

Contact your doctor or health care provider right away if any of these apply to you.

Before using Theophylline:

Some medical conditions may interact with Theophylline. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of heart problems (eg, congestive heart failure, cor pulmonale), an irregular heartbeat, liver problems (eg, cirrhosis, hepatitis), viral infection, thyroid problems, increased acid levels in the body, brain or nerve problems, or seizures (eg, epilepsy)


• if you are in shock or have a fever, an ulcer, a severe infection, cystic fibrosis, or fluid in the lungs (pulmonary edema)


• if you smoke, are stopping or starting smoking, or are exposed to the smoke from cigarettes or marijuana


• if you are in the last 3 months of pregnancy

Some MEDICINES MAY INTERACT with Theophylline. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Aminoglutethimide, barbiturates (eg, phenobarbital), carbamazepine, hydantoins (eg, phenytoin), isoproterenol, moricizine, rifampin, St. John's wort, or sulfinpyrazone because they may decrease Theophylline's effectiveness


• Allopurinol, beta-blockers (eg, propranolol), cimetidine, disulfiram, enoxacin, estrogen, febuxostat, fluvoxamine, interferon alpha, macrolide antibiotics (eg, clarithromycin, erythromycin), methotrexate, mexiletine, oral contraceptives (birth control pills), pentoxifylline, propafenone, quinolone antibiotics (eg, ciprofloxacin), tacrine, thiabendazole, ticlopidine, troleandomycin, verapamil, viloxazine, or zileuton because they may increase the risk of Theophylline's side effects


• Ephedrine because the risk of side effects, such as nausea, nervousness, and trouble sleeping, may be increased


• Halothane because the risk of side effects such as irregular heartbeat may be increased


• Ketamine because the risk of seizures may be increased


• Adenosine, benzodiazepines (eg, diazepam, flurazepam, lorazepam, midazolam), dipyridamole IV, lithium, or nondepolarizing muscle relaxants (eg, pancuronium) because their effectiveness may be decreased by Theophylline

This may not be a complete list of all interactions that may occur. Ask your health care provider if Theophylline 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.

How to use Theophylline:

Use Theophylline as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Some foods may change the effectiveness or increase the side effects of Theophylline. Talk to your doctor about how you should take Theophylline with regard to food. Do not suddenly change your diet or eating habits without first checking with your doctor.


• Take Theophylline at evenly spaced times throughout the day. Taking Theophylline at the same time each day will help you remember to take it. Contact your doctor with any questions or concerns about the best way to take Theophylline.


• If you miss a dose of Theophylline, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Theophylline.

Important safety information:

• Drinking alcohol may increase the risk of side effects of Theophylline. Talk to your doctor before drinking alcohol while you are taking Theophylline.


• Tell your doctor or dentist that you take Theophylline before you receive any medical or dental care, emergency care, or surgery.


• Do not take more than the recommended dose or use more often than prescribed without checking with your doctor. If your symptoms become worse, contact your doctor.


• Carry an ID card at all times that says you take Theophylline.


• Avoid large amounts of food or drink that have caffeine (eg, coffee, tea, cocoa, cola, chocolate).


• Notify your doctor if you develop a new illness, especially if it is accompanied by fever; if a chronic illness becomes worse; or if you start or stop smoking cigarettes or marijuana.


• Tell your doctor if another doctor prescribes a new medicine or tells you to stop using a medicine that you have already been taking. Tell your doctor if you start or stop any medicine, either prescription or over the counter.


• Theophylline will not stop an asthma attack once one has started. Be sure to always carry appropriate rescue medicine (eg, bronchodilator inhaler) with you in case of an asthma attack.


• If you have more than one doctor, be sure to tell each of your doctors that you are taking Theophylline.


• Diabetes patients - Theophylline may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Theophylline may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Theophylline.


• Lab tests, including blood theophylline levels, may be performed while you use Theophylline. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Theophylline with caution in the ELDERLY; they may be more sensitive to its effects.


• Caution is advised when using Theophylline in CHILDREN, especially children younger than 1 year old; they may be more sensitive to its effects. Children may be more likely to experience mild, temporary behavior changes.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Theophylline while you are pregnant. Theophylline is found in breast milk. If you are or will be breast-feeding while you use Theophylline, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Theophylline:

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:

Irritability; mild, temporary caffeine-like effects (eg, headache, nausea, diarrhea, trouble sleeping); mild, temporary changes in behavior; restlessness; temporary increased urination.

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); confusion; dizziness; fast breathing; fast or irregular heartbeat; heart rhythm problems; seizures; severe or persistent nausea, diarrhea, or headache; sleeplessness; tremors; vomiting.

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: Theophylline side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include agitation; chest pain; confusion; decreased urination; fast or irregular heartbeat; headache; increased thirst; irritability; loss of appetite; muscle pain or tenderness; nausea; nervousness; persistent increased urination; restlessness; seizures; severe or persistent diarrhea; stomach pain; tremors or twitching; vomiting, especially of blood.

Proper storage of Theophylline:

Store Theophylline 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. Do not refrigerate. Keep Theophylline out of the reach of children and away from pets.

General information:

• If you have any questions about Theophylline, please talk with your doctor, pharmacist, or other health care provider.


• Theophylline is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Theophylline. 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.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Theophylline resources

• Theophylline Side Effects (in more detail)
• Theophylline Use in Pregnancy & Breastfeeding
• Drug Images
• Theophylline Drug Interactions
• Theophylline Support Group
• 5 Reviews for Theophylline - Add your own review/rating

• Theophylline Professional Patient Advice (Wolters Kluwer)


• Theophylline Prescribing Information (FDA)


• theophylline Advanced Consumer (Micromedex) - Includes Dosage Information


• theophylline Concise Consumer Information (Cerner Multum)


• Elixophyllin Prescribing Information (FDA)


• Quibron-T Prescribing Information (FDA)


• Theo-24 Prescribing Information (FDA)


• Theolair tablets Prescribing Information (FDA)


• Theophyllines Monograph (AHFS DI)


• Uniphyl Prescribing Information (FDA)

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