Lenalidomide

Class: Biologic Response Modifiers
Chemical Name: 2,6-Piperidinedione, 3-(4-amino-1-3-dihydro-1-oxo-2H-isoindol-2yl)-; 3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl) piperidine-2,6-dione
Molecular Formula: C₁₃H₁₃N₃O₃
CAS Number: CAS-191732-72-6
Brands: Revlimid

Special Alerts:

[Posted 04/08/2011] ISSUE: FDA is informing the public that we are aware of results from clinical trials conducted inside and outside the United States that found that patients treated with lenalidomide (Revlimid) may be at an increased risk of developing new types of cancer compared to patients who did not take the drug. FDA is currently reviewing all available information on this potential risk and will communicate any new recommendations once it has completed its review.

BACKGROUND: Lenalidomide is used to treat a type of blood disorder known as myelodysplastic syndrome. Lenalidomide is also used along with other drugs to treat people with the cancer known as multiple myeloma.

RECOMMENDATION: At this time, there is no recommendation to delay, modify or restrict the use of lenalidomide for patients being treated according to the FDA-approved indications. FDA is currently reviewing all available information on this potential risks and will communicate any new recommendations once it has completed its review. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for lenalidomide to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of lenalidomide and consists of the following: medication guide, elements to assure safe use, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center ().

• Teratogenic Effects


• 
  

  Potential risk of teratogenicity and fetotoxicity due to structural similarity to thalidomide, a known human teratogen that can cause severe, life-threatening birth defects if administered during pregnancy.^{1 7} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  

• Teratogenicity Precautions


• 
  

  Contraindicated in pregnant women; use in women of childbearing potential only when alternative treatments are not available and adequate precautions taken to prevent fetal exposure.¹ (See Contraindications and also Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  Pregnancy must be excluded with 2 confirmed negative pregnancy tests (sensitivity to detect human serum chorionic gonadotropin [HCG] concentrations of ≥50 million IU/mL); one test within 10–14 days and another ≤24 hours prior to treatment initiation.^{1 j} Repeat pregnancy tests throughout therapy (i.e., once weekly during first month, then monthly or every 2 weeks in women with regular or irregular menstrual cycles, respectively).^{1 7 j}

  
  


• 
  

  Pregnancy must be prevented (even in females with a history of infertility) by simultaneous use of 2 forms of reliable contraception for ≥4 weeks prior to, throughout, and for 4 weeks after completion of therapy.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Mandatory contraception not required for females who have undergone hysterectomy or bilateral oophorectomy, are postmenopausal and have had no menses for ≥24 consecutive months, or practice continuous abstinence from heterosexual contact.¹

  
  


• 
  

  Sexually mature males (including successfully vasectomized men) must completely avoid unprotected sexual contact with women of childbearing potential (i.e., use latex condom throughout and for ≥4 weeks after lenalidomide therapy) because it is unknown if drug distributes into semen.^{1 7}

  
  


• 
  

  Provide pregnancy tests and counseling if a patient misses her period or has abnormalities in menstrual bleeding.¹

  
  


• 
  

  If pregnancy occurs, immediately discontinue treatment.¹ Refer patient to obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling.¹ Report any suspected fetal exposure to FDA MedWatch Program at 1-800-FDA-1088 and to manufacturer at 1-888-423-5436.¹

  
  

• Restricted Distribution Program


• 
  

  Available only through restricted distribution program, the RevAssist program, designed because of potential teratogenicity and to help ensure that fetal exposure does not occur.¹ (See Restricted Distribution Program under Dosage and Administration.)

  
  


• 
  

  Limits access to lenalidomide to prescribing clinicians, pharmacies, and patients who are registered in program and mandates compliance with registration, education, and safety requirements.^{1 7 j}

  
  


• 
  

  Registered prescribing clinicians must understand risks of teratogenicity if used during pregnancy and must not provide a prescription until a documented negative pregnancy test available.¹

  
  


• 
  

  Patient or parent/legal guardian (for minors 12–18 years of age) must be capable of understanding and complying with patient registration, education, patient survey, and safety requirements, including mandatory contraceptive measures and pregnancy testing.^{1 7}

  
  


• 
  

  Provide oral and written warnings of risk of possible contraceptive failure, hazards of using drug during pregnancy, exposing fetus to drug, and possibility of drug in semen.^{1 7}

  
  


• 
  

  Patient or parent/legal guardian must provide written acknowledgement of understanding of these warnings and need for mandatory contraceptive measures.^{1 7}

  
  

• Hematologic Toxicity


• 
  

  Risk of severe thrombocytopenia and neutropenia.^{1 7} (See Hematologic Effects under Cautions.)

  
  


• 
  

  Grade 3 or 4 neutropenia and/or thrombocytopenia reported in 80% of patients with myelodysplastic syndromes (MDS) with deletion 5q abnormality.¹ Dosage delay or reduction required in 80% of such patients; a second dosage delay or reduction required in 34% of patients.¹

  
  


• 
  

  Monitor CBCs weekly for the first 8 weeks of therapy for MDS and at least monthly thereafter.¹ Dosage interruption and/or reduction and supportive therapy (e.g., blood products) and/or hematopoietic agents (colony-stimulating factors) may be required.¹ (See Dosage Modification for Toxicity in Patients with MDS under Dosage and Administration.)

  
  

• Thromboembolic Effects


• 
  

  Increased risk of venous thromboembolism (e.g., DVT, PE) in patients with multiple myeloma when used in combination with dexamethasone.^{1 7 c h k} (See Thromboembolic Effects under Cautions.)

  
  


• 
  

  Monitor for signs and symptoms of thromboembolism.^{1 7}

  
  

Introduction

Biologic response modifier; thalidomide analog with immunomodulatory, antineoplastic, and antiangiogenic activity.^{1 a b c d e i}

Uses for Lenalidomide

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Myelodysplastic Syndrome (MDS)

Treatment of RBC transfusion-dependent anemia associated with low- or intermediate-1-risk MDS in patients with a cytogenetic deletion abnormality involving the long arm of chromosome 5 (deletion 5q abnormality), with or without additional cytogenetic abnormalities^{1 3 5 7 i} (designated an orphan drug by FDA for this use).⁶

Multiple Myeloma

Treatment of multiple myeloma (in combination with dexamethasone) in patients who have received at least one prior therapy^{1 7} (designated an orphan drug by FDA for this use).⁶

Combination therapy with dexamethasone substantially more effective than dexamethasone monotherapy in achieving overall, complete, and partial response in patients who have received at least one prior therapy.¹

Lenalidomide Dosage and Administration

General

• 
  

  Adjust dosage carefully according to individual response and laboratory parameters (e.g., blood cell counts).^{1 7}

  
  


• 
  

  Carefully monitor CBCs (including differential and platelets) during therapy.¹ (See Hematologic Effects under Cautions.)

  
  

Administration

Restricted Distribution Program

Distribution of lenalidomide is restricted because it is an analog of thalidomide (a known teratogen that can cause severe birth defects).¹ (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Must be obtained through a restricted distribution program (RevAssist) to ensure that fetal exposure to lenalidomide does not occur.^{1 c j} The program requires registration of clinicians, pharmacies, and patients; all must agree to accept specific responsibilities (e.g., mandatory contraceptive measures, pregnancy testing) designed to minimize pregnancy exposures in order to prescribe, dispense, or use lenalidomide.^{1 7 j}

RevAssist program ensures appropriately timed and properly documented pregnancy testing and counseling of patients before, during, and following lenalidomide therapy.¹

Prior to initiation of therapy, females must certify that they are not pregnant or not of childbearing potential (i.e., have undergone hysterectomy or bilateral oophorectomy, postmenopausal [no menses for ≥24 consecutive months]).¹

Pharmacists registered with the restricted distribution program must offer counseling, provide educational materials (e.g., patient information guide), and confirm negative pregnancy test results (in women of childbearing potential) each time drug is dispensed.^{1 c j}

To facilitate pregnancy testing and counseling in accordance with RevAssist program, prescribe and dispense ≤28-day supply of drug.^{1 7 c j} Patients and prescribers must participate in monthly telephone surveys to receive authorization for each prescription written.^{1 c j}

For additional details on program requirements, contact Celgene at 888-423-5436 or see RevAssist website at .^{1 7 j}

Oral Administration

Administer orally with water once daily.^{1 7}

Swallow capsules whole; do not break, chew, or open capsules.^{1 7}

Administer as a single 25-mg capsule for treatment of multiple myeloma.¹ Effects of substituting lower-strength capsules to achieve a 25-mg dose not known.¹

If a dose is missed, take as soon as remembered; if a dose is missed for an entire day, skip dose and resume regular dosing schedule the following day.⁷ Do not double a dose.⁷

Manufacturer makes no specific recommendations regarding administration with meals; food may decrease peak plasma concentrations.¹ (See Food under Pharmacokinetics.)

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Adults

Myelodysplastic Syndrome

Oral

Initially, 10 mg once daily.¹ Continue or adjust initial dosage based on clinical response and laboratory parameters (e.g., blood cell counts).^{1 7}

If thrombocytopenia and/or neutropenia occur, reduce dosage or interrupt therapy based on degree of myelosuppression.¹ (See Dosage Modification for Toxicity in Patients with MDS under Dosage and Administration.)

Dosage Modification for Toxicity in Patients with MDS

Oral

Table 1. Dosage Adjustment for Thrombocytopenia Occurring ≤4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage	Platelet Count (per mm3)	Dosage Adjustment
10 mg	Baseline count ≥100,000 and then decreases to <50,000	Discontinue therapy.1 When count returns to ≥50,000/mm3, resume therapy at 5 mg daily.1
10 mg	Baseline count <100,000 and then decreases to 50% of baseline	Discontinue therapy.1 When count returns to ≥50,000/mm3 (for baseline ≥60,000/mm3) or ≥30,000/mm3 (for baseline <60,000/mm3), resume therapy at 5 mg daily.1
5 mg	<30,000 or <50,000 (with platelet transfusions)	Discontinue therapy.1 When count returns to ≥30,000/mm3 (without hemostatic failure), resume therapy at 5 mg every other day.1

Table 2. Dosage Adjustment for Thrombocytopenia Occurring >4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage	Platelet Count (per mm3)	Dosage Adjustment
10 mg	<30,000 or <50,000 (with platelet transfusions)	Discontinue therapy.1 When count returns to ≥30,000/mm3 (without hemostatic failure), resume therapy at 5 mg daily.1
5 mg	<30,000 or <50,000 (with platelet transfusions)	Discontinue therapy. When count returns to ≥30,000/mm3 (without hemostatic failure), resume therapy at 5 mg every other day.1

Table 3. Dosage Adjustment for Neutropenia Occurring ≤4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage	ANC (per mm3)	Dosage Adjustment
10 mg	Baseline ≥1000 and then decreases to <750	Discontinue therapy.1 When ANC returns to ≥1000/mm3, resume therapy at 5 mg daily. 1
10 mg	Baseline ANC <1000 and then decreases to <500	Discontinue therapy.1 When ANC returns to ≥500/mm3, resume therapy at 5 mg daily. 1
5 mg	If ANC decreases to <500 for ≥7 days or decreases to <500 associated with fever (≥38.5°C)	Discontinue therapy.1 When ANC returns to ≥500/mm3, resume therapy at 5 mg every other day. 1

Table 4. Dosage Adjustment for Neutropenia Occurring >4 Weeks After Initiation of Therapy

Lenalidomide Daily Dosage	ANC (per mm3)	Dosage Adjustment
10 mg	If ANC decreases to <500 for ≥7 days or decreases to <500 associated with fever (≥38.5°C)	Discontinue therapy.1 When ANC returns to ≥500/mm3, resume therapy at 5 mg daily. 1
5 mg	If ANC decreases to <500 for ≥7 days or decreases to <500 associated with fever (≥38.5°C)	Discontinue therapy.1 When ANC returns to ≥500/mm3, resume therapy at 5 mg every other day. 1

Multiple Myeloma

Oral

Initially, 25 mg once daily given on days 1–21 of each 28-day cycle.^{1 d e} Administer with oral dexamethasone 40 mg daily on days 1–4, 9–12, and 17–20 of each 28-day cycle for the first 4 cycles of therapy, then reduce to 40 mg daily on days 1–4 of subsequent cycles.^{1 d e}

Continue or adjust initial dosage based on clinical response and laboratory parameters (e.g., blood cell counts).^{1 7} (See Dosage Modification for Toxicity in Patients with Multiple Myeloma Under Dosage and Administration.)

Dosage Modification for Toxicity in Patients with Multiple Myeloma

Hematologic Toxicity.

Oral

Continue at reduced dosage for remainder (up to 21 days) of treatment cycle.

Table 5. Dosage Adjustment for Thrombocytopenia During Therapy

Platelet Count (per mm3)	Dosage Adjustment
<30,000	Discontinue therapy and monitor CBCs weekly.1 When count returns to ≥30,000/mm3, reduce dosage to 15 mg daily.
For each subsequent decrease to <30,000	Discontinue therapy.1 When count returns to ≥30,000, resume at a dosage 5 mg less than previous dose; do not administer <5 mg daily.

Continue at reduced dosage for remainder (up to 21 days) of a 28-day treatment cycle.

Table 6. Dosage Adjustment for Neutropenia During Therapy

ANC (per mm3)	Dosage Adjustment
<1000	Discontinue therapy, add a granulocyte colony-stimulating factor (G-CSF), and monitor CBCs weekly.1
≥1000 (following discontinuation of therapy ) and no other toxicity present	Resume at 25 mg daily.1
≥1000 (following discontinuation of therapy) and other toxicity present	Reduce dosage to 15 mg daily.1
For each subsequent decrease to <1000	Discontinue therapy.1 When count returns to ≥1000/mm3, resume at a dosage 5 mg less than previous dose; do not administer <5 mg daily.1

Other Grade 3/4 Toxicities.

If patient experiences other grade 3 or 4 nonhematologic toxicities, interrupt therapy and resume at next lower dosage level when toxicity resolves or decreases to ≤grade 2 (i.e., reduce to 15 mg; if necessary, further reduce dosage 5 mg less than previous dose [not <5 mg daily given on days 1–21 of each 28-day cycle]).^{1 8}

Prescribing Limits

Adults

Multiple Myeloma

Oral

Minimum 5 mg daily given on days 1–21 of each 28-day cycle.¹

Special Populations

Renal Impairment

Myelodysplastic Syndrome

Oral

Dosage for Treatment of MDS in Adults with Renal Impairment8f

Clcr (mL/min)	Dosage
≥50	10 mg once daily
30–49	5 mg once daily
<30 (not requiring dialysis)	5 mg every 48 hours
End stage renal disease (requiring dialysis)	5 mg 3 times a week following each dialysis

Multiple Myeloma

Oral

Dosage may be increased to 15 mg once daily after 2 cycles in patients who have not responded to therapy.

Based on dosing for 21 days of a 28-day cycle.

Dosage for Multiple Myeloma in Adults with Renal Impairment8f

Clcr (mL/min)	Dosage
≥50	25 mg once daily
30–49	10 mg once daily,
<30 (not requiring dialysis)	15 mg every 48 hours
End stage renal disease (requiring dialysis)	15 mg 3 times a week following each dialysis

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function; reduced dosages may be required.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Lenalidomide

Contraindications

• 
  

  Pregnancy.^{1 7} (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  Females of childbearing potential, unless they comply with all special conditions required by manufacturer and RevAssist program.¹ (See Boxed Warning and see Restricted Distribution Program under Dosage and Administration.)

  
  


• 
  

  Known hypersensitivity to lenalidomide or any ingredient in the formulation.^{1 7}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.^{1 7} Teratogenic effects of lenalidomide not fully established, but considered a potential teratogen due to structural similarity to thalidomide, a known human teratogen associated with severe birth defects and fetal death.^{1 7 g} (See Boxed Warning.)

Contraindicated in female patients who are or may become pregnant unless alternative therapies not available and adequate precautions taken to avoid pregnancy.¹

Women of childbearing potential must use 2 forms of effective contraception ≥4 weeks prior to, throughout, and for 4 weeks following completion of therapy.^{1 7} Use a highly effective birth control method (e.g., intrauterine device [IUD]; oral, injectable, or implanted hormonal contraceptive; tubal ligation; vasectomized partner) and an effective barrier method (e.g., latex condom, diaphragm, cervical cap).¹ If either IUD or hormonal contraceptive use contraindicated, may use another highly effective method or 2 simultaneous effective barrier methods.¹

If clinician not available, information about emergency contraception (including information regarding clinicians who provide emergency contraceptive services) can be obtained by calling 1-888-668-2528.¹

Not known whether lenalidomide is present in semen; sexually mature males (including those who have undergone successful vasectomy) receiving lenalidomide must use a latex condom each time they have sexual contact with a woman of childbearing potential during therapy and for 4 weeks following completion of therapy.^{1 7}

Hematologic Effects

Risk of severe (grade 3 or 4) neutropenia and/or thrombocytopenia.^{1 3 7 a i}

Grade 3/4 hematologic toxicities reported in about 80% of patients with MDS associated with deletion 5q abnormality.¹ Generally occurs during initial weeks (approximately 6 weeks for neutropenia and 4 weeks for thrombocytopenia) of treatment and reverses with dosage reduction or discontinuance.^{1 3 5}

Higher frequency of grade 3/4 hematologic toxicities reported in patients with multiple myeloma receiving combination therapy with dexamethasone compared with those receiving dexamethasone alone.¹

Carefully monitor hematologic status during therapy.¹ Obtain baseline CBCs.^j In patients with MDS, perform weekly CBCs during first 8 weeks of therapy, and at least monthly thereafter.¹ In patients with multiple myeloma, perform CBCs every 2 weeks for the first 12 weeks of therapy, and at least monthly thereafter.¹

If hematologic toxicity occurs, interrupt therapy and/or reduce dosage according to degree of myelosuppression.¹ (See Dosage Modification for Toxicity in Patients with MDS and also Dosage Modification for Toxicity in Patients with Multiple Myeloma under Dosage and Administration.) Initiate supportive therapy with blood product transfusions or growth factors (e.g., G-CSF) if indicated.^{1 5}

Thromboembolic Events

Risk of venous thromboembolism (e.g., DVT, PE) in patients with multiple myeloma, especially when used in combination therapy with dexamethasone.^{1 7 c h k}

Monitor for signs and symptoms of thromboembolism (e.g., shortness of breath, chest pain, arm or leg swelling).¹ Carefully assess preexisting risk factors (e.g., age, recent surgery, trauma, immobility) and consider prophylactic antiplatelet or anticoagulation treatment. ^{1 c d h k} Based on limited data, some experts recommend prophylaxis in all patients receiving lenalidomide for multiple myeloma.^{c k}

Specific Populations

Pregnancy

Category X.¹ (See Contraindications and also Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether lenalidomide is distributed into milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 7}

Geriatric Use

No substantial differences in efficacy relative to younger adults; however, increased incidence of serious adverse effects reported in patients >65 years of age compared with younger patients.^{1 8}

Principally eliminated by kidneys.¹ Assess renal function and select dosage carefully due to greater frequency of decreased renal function in geriatric patients.¹ (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Substantially eliminated by kidneys; possible increased toxicity in patients with renal impairment.¹

Monitor renal function; adjust dosage if necessary based on degree of renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

MDS: Thrombocytopenia,^{1 3 5 b i} neutropenia,^{1 3 5 b c i} diarrhea,^{1 3 7 i} pruritus,^{1 3 7 i} rash,^{1 7 i} fatigue,^{1 3 7 i} constipation,^{1 i} nausea,^{1 i} nasopharyngitis,¹ arthralgia,¹ back pain,¹ fever,¹ peripheral edema,^{1 i} cough,¹ dizziness,¹ headache,¹ muscle cramps,¹ dyspnea,¹ pharyngitis,¹ asthenia,¹ epistaxis,¹ upper respiratory tract infection,¹ dry skin,¹ abdominal pain,¹ anemia,¹ pneumonia,¹ hypokalemia,¹ limb pain,¹ urinary tract infection,¹ anorexia,¹ edema,^{1 3} insomnia,¹ vomiting.¹

Multiple myeloma: Constipation,^{1 d} fatigue,^{1 d} insomnia,¹ muscle cramps,¹ diarrhea,¹ neutropenia,¹ anemia,¹ asthenia,¹ fever,¹ nausea,¹ headache,¹ peripheral edema,¹ dizziness,¹ dyspnea,¹ tremor,¹ weight loss,¹ thrombocytopenia,¹ rash,^{1 d} back pain,¹ hyperglycemia,¹ muscle weakness,¹ blurred vision,¹ cough,¹ dyspepsia,¹ anorexia,¹ upper respiratory tract infection,¹ dysgeusia,¹ paresthesia,¹ hypokalemia,¹ pneumonia,¹ arthralgia,¹ vomiting.¹

Interactions for Lenalidomide

Not metabolized by CYP isoenzymes.¹ Does not inhibit or induce CYP isoenzymes.¹

Specific Drugs

Drug	Interaction	Comments
Digoxin	Increased peak plasma digoxin concentrations1	Monitor plasma digoxin concentrations1
Warfarin	No pharmacokinetic interaction observed with single dose of warfarin1

Lenalidomide Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration.^{1 f}

In healthy patients, peak plasma concentrations attained within approximately 0.625–1.5 hours following oral administration.^{1 c f}

In patients with multiple myeloma, peak plasma concentrations attained within 0.5–4 hours following oral administration.¹ AUC is 57% higher than in healthy male volunteers.¹

Food

Food decreases peak plasma concentrations by 36%,¹ but does not alter extent of absorption.^{1 f}

Special Populations

In multiple myeloma patients with mild renal impairment, AUC increased by 56% compared with those with normal renal function.¹

Distribution

Extent

Not known whether distributed into human milk.¹

Not known whether crosses placenta in humans; embryocidal effects observed in rabbits.^{1 l}

Not known whether distributed into semen.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Plasma Protein Binding

Approximately 30–40%.^{1 f}

Elimination

Metabolism

Metabolic fate not known.¹ In vitro studies indicate that lenalidomide does not undergo metabolism via CYP isoenzymes.¹

Elimination Route

Primarily excreted in urine (67%) as unchanged drug via glomerular filtration and tubular secretion.^{1 f}

Partially (about 30%) removed by hemodialysis.^f

Half-life

Approximately 3–4 hours.^{1 c f}

No evidence of drug accumulation with multiple dosing.^{1 f}

Special Populations

In patients with renal impairment (Cl_cr <50 mL/minute), clearance reduced, systemic exposure increased, and half-life prolonged.^f

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).^{1 7}

Actions

• 
  

  A thalidomide analog; similar in structure, but functionally distinct.^{b c h} Exhibits more potent immunomodulating effects^{a c d} and lack of CNS effects compared with thalidomide.^{3 b} Insufficient information regarding teratogenic potential of lenalidomide.¹

  
  


• 
  

  Exact mechanism of action not fully elucidated.^{1 a b} Affects a broad range of ligand-induced responses, including angiogenesis, inflammation, immune response, and cell adhesion.^{1 3 c}

  
  


• 
  

  Antiangiogenic effects include inhibition of vascular endothelial growth factor (VEGF), an angiogenic cytokine secreted by bone marrow stromal cells and myeloma cells.^c

  
  


• 
  

  Enhances cell-mediated immunity by inhibiting secretion of proinflammatory cytokines (e.g., tumor necrosis factor [TNF; TNF-α]), and stimulating interleukin-2, interferon gamma, cytolytic T-cell and natural killer (NK) cell responses.^{1 3 a c i}

  
  


• 
  

  Interferes with growth signaling between myeloma cells and bone marrow stromal cells by modulating expression of cell surface adhesion molecules.^c

  
  


• 
  

  Exhibits direct antitumor effects by inducing cell cycle arrest and apoptosis in certain myeloma cell lines.^{1 8 a b c}

  
  


• 
  

  Improves erythropoiesis in patients with low- or intermediate-1-risk MDS associated with a deletion 5q abnormality alone or with additional chromosomal abnormalities.^{1 i} May have direct antiproliferative activity against deletion 5q cell lines.^{3 5 b}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of comprehensive counseling (i.e., orally and in writing) on benefits and risks (i.e., severe, potentially life-threatening birth defects) of drug.¹ (See Boxed Warning.)

  
  


• 
  

  Importance of taking lenalidomide only as prescribed, and in compliance with requirements of RevAssist program.¹ (See Restricted Distribution Program under Dosage and Administration.)

  
  


• 
  

  Importance of providing patients with a copy of manufacturer’s patient information (medication guide) each time drug is dispensed.^{1 7 c j}

  
  


• 
  

  Importance of warning women of childbearing potential not to take drug if pregnant, breast-feeding, or able to get pregnant (e.g., not using required methods of birth control).¹

  
  


• 
  

  Necessity of advising any woman of childbearing potential to avoid pregnancy by using mandatory contraceptive measures, unless she abstains from heterosexual contact.¹ (See Boxed Warning and see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  Importance of mandatory pregnancy testing prior to and during therapy.¹

  
  


• 
  

  Importance of immediately discontinuing therapy if pregnancy suspected.¹

  
  


• 
  

  Importance of women of childbearing potential informing clinicians of pregnancy, suspected pregnancy, missed menstrual period, unusual menstrual bleeding, or cessation of using contraceptive measures.¹

  
  


• 
  

  Importance of informing patient how to obtain information about emergency contraception (including information regarding clinicians who provide emergency contraceptive services) if clinician not available.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  Importance of informing sexually mature male patients (including those who have undergone a vasectomy) of necessity of using a latex condom when engaging in sexual contact with a woman of childbearing potential or a pregnant woman.^{1 7} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  Importance of male patients informing clinicians of unprotected heterosexual sexual contact during therapy and for first 4 weeks after drug discontinuance.¹ Importance of male patients informing clinician of suspected pregnancy of their sexual partner.¹

  
  


• 
  

  Importance of informing patients not to share drug with anyone else (even if the other individual has similar symptoms) and of not donating blood or semen while receiving drug and for 4 weeks afterward.^{1 7 j}

  
  


• 
  

  Importance of advising patients to swallow capsules whole with water, and not to break, chew, or open capsules.^{1 7}

  
  


• 
  

  Importance of taking a missed dose as soon as possible, and not doubling the next dose.⁷

  
  


• 
  

  Risk of hematologic toxicities; importance of periodic monitoring of blood cell counts during treatment.¹

  
  


• 
  

  Risk of venous thromboembolic events; importance of advising patients to immediately inform clinician if they develop symptoms of shortness of breath, chest pain, or swelling of the arms or legs.^{1 7 c}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{1 7}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{1 7} (See Cautions.)

  
  

Preparations

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

Distribution of lenalidomide is restricted.¹ (See Restricted Distribution Program under Dosage and Administration.)

Lenalidomide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	5 mg	Revlimid	Celgene
		10 mg	Revlimid	Celgene
		15 mg	Revlimid	Celgene
		25 mg	Revlimid	Celgene

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 ac

Acetaminophen, caffeine, and magnesium salicylate

Generic Name: acetaminophen, caffeine, and magnesium salicylate (ah seet oh MIN oh fen, KAF een, mag NEEZ ee um sa LIS il ate)

Brand Names: KneeRelief

What is acetaminophen, caffeine, and magnesium salicylate?

Acetaminophen is a pain reliever and a fever reducer.

Caffeine is used in this product to increase the pain relieving effects of acetaminophen.

Magnesium salicylate is used to reduce pain, inflammation, and fever.

The combination of acetaminophen, caffeine, and magnesium salicylate is used to treat pain and swelling from conditions such as muscle aches, arthritis, and joint soreness.

Acetaminophen, caffeine, and magnesium salicylate may also be used for purposes not listed in this medication guide.

What is the most important information I should know about acetaminophen, caffeine, and magnesium salicylate?

Magnesium salicylate should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Salicylates can cause a serious and sometimes fatal condition called Reye's syndrome in children. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen. Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Ask a doctor or pharmacist before using any other pain, cold, allergy, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

Stop taking this medication and call your doctor if you have a fever lasting longer than 3 days, or pain lasting longer than 10 days.

What should I discuss with my healthcare provider before taking acetaminophen, caffeine, and magnesium salicylate?

You should not use this medication if you are allergic to acetaminophen, caffeine, or magnesium salicylate. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  a stomach ulcer or bleeding;

  
  


• liver disease;


• kidney disease;


• 
  

  gout;

  
  


• 
  

  a bleeding or blood clotting disorder, such as hemophilia;

  
  


• 
  

  heart disease or congestive heart failure; or

  
  


• 
  

  high blood pressure (hypertension).

  
  

FDA pregnancy category C. It is not known whether acetaminophen, caffeine, and magnesium salicylate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Acetaminophen, caffeine, and magnesium salicylate can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Magnesium salicylate should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Salicylates can cause a serious and sometimes fatal condition called Reye's syndrome in children.

How should I take acetaminophen, caffeine, and magnesium salicylate?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts, or use it for longer than recommended.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.

Stop taking this medication and call your doctor if you have a fever lasting longer than 3 days, or pain lasting longer than 10 days.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using acetaminophen, caffeine, and magnesium salicylate. If you need surgery, tell the surgeon ahead of time that you are using acetaminophen, caffeine, and magnesium salicylate. You may need to stop using the medicine for a short time. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since this medication is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of acetaminophen can damage your liver or cause death.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms also may include ringing in your ears, headache, confusion, agitation, restless feeling, insomnia, hallucinations, low fever, loss of appetite, seizures, or coma.

What should I avoid while taking acetaminophen, caffeine, and magnesium salicylate?

Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Ask a doctor or pharmacist before using any other pain, cold, allergy, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

Many medicines available over the counter also contain caffeine, salicylates, or similar medicines (such as aspirin, ibuprofen, ketoprofen, or naproxen). Ask your doctor before taking any other medication for pain, arthritis, fever, or swelling.

Acetaminophen, caffeine, and magnesium salicylate side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop taking this medicine and call your doctor at once if you have a serious side effect such as: Stop using this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  black, bloody, or tarry stools;

  
  


• 
  

  coughing up blood or vomit that looks like coffee grounds;

  
  


• 
  

  nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  
  


• 
  

  easy bruising or bleeding;

  
  


• 
  

  agitation, confusion, or hallucinations; or

  
  


• 
  

  seizure (convulsions).

  
  

Less serious side effects may include:

• 
  

  mild nausea, vomiting, indigestion, or upset stomach;

  
  


• 
  

  ringing in your ears; or

  
  


• 
  

  trouble sleeping (insomnia).

  
  

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.

What other drugs will affect acetaminophen, caffeine, and magnesium salicylate?

Ask a doctor or pharmacist if it is safe for you to use acetaminophen, caffeine, and magnesium salicylate if you are also using any of the following drugs:

• 
  

  a blood thinner such as warfarin (Coumadin, Jantoven), heparin, enoxaparin (Lovenox), dalteparin (Fragmin), or tinzaparin (Innohep);

  
  


• 
  

  choline and magnesium salicylate (Trilisate, Tricosal), or salsalate (Disalcid);

  
  


• 
  

  salicylates such as aspirin, Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others;

  
  


• 
  

  medication used to prevent blood clots, such as alteplase (Activase), dipyridamole (Persantine), ticlopidine (Ticlid), and urokinase (Abbokinase); or

  
  


• 
  

  aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others.

  
  

This list is not complete and other drugs may interact with acetaminophen, caffeine, and magnesium salicylate. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More acetaminophen, caffeine, and magnesium salicylate resources

• Acetaminophen, caffeine, and magnesium salicylate Drug Interactions
• Acetaminophen, caffeine, and magnesium salicylate Support Group
• 2 Reviews for Acetaminophen, caffeine, and magnesium salicylate - Add your own review/rating

Compare acetaminophen, caffeine, and magnesium salicylate with other medications

• Muscle Pain

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen, caffeine, and magnesium salicylate.

Luveris

Pronunciation: LOO-troe-pin AL-fa
Generic Name: Lutropin Alfa
Brand Name: Luveris

Luveris is used for:

Stimulating ovulation in certain women who want to become pregnant.

Luveris is a fertility medicine. It works like human pituitary luteinizing hormone to stimulate certain cells to produce estradiol, which helps cause ovulation.

Do NOT use Luveris if:

• you are allergic to any ingredient in Luveris


• you have a history of certain problems with your ovaries (eg, primary ovarian failure, growths in the ovary, unusual growth of the ovary)


• you have uncontrolled thyroid problems, uncontrolled adrenal gland problems, growths in the brain (eg, pituitary tumor), or uterine bleeding of unknown cause


• you have certain tumors of the reproductive tract or organs or certain estrogen-dependent tumors


• you are pregnant

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

Before using Luveris:

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

• if you are 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 thyroid problems, adrenal gland problems, unusual vaginal bleeding, ovarian hyperstimulation syndrome, or tumors

Some MEDICINES MAY INTERACT with Luveris. However, no specific interactions with Luveris are known at this time.

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

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

• Luveris is usually given in combination with another medicine called follitropin alfa.


• Luveris comes with an additional patient leaflet. Read it carefully and reread it each time you get Luveris refilled.


• Luveris is usually administered as an injection at your doctor's office, hospital, or clinic. If you are using Luveris at home, carefully follow the injection procedures taught to you by your health care provider.


• If Luveris contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.


• Wash your hands with soap and water before mixing.


• When drawing a dose into the syringe, be sure to follow the procedure demonstrated to you to prevent contamination of the vial, syringe, or medicine. Never touch the rubber stopper of the vial or the needle of the syringe with your fingers.


• Carefully check that you have drawn the correct dose before administration.


• Gently rotate the vial between your fingers to mix Luveris. Do not shake.


• Use Luveris immediately after mixing. Discard any unused medicine.


• Use Luveris regularly to receive the most benefit from it.


• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor or pharmacist to explain local regulations for proper disposal.


• If you miss a dose of Luveris, contact your doctor immediately.

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

Important safety information:

• Because of the risk of severe side effects, such as ovarian hyperstimulation syndrome, a health care provider will monitor you for at least 2 weeks after you use Luveris.


• Luveris may cause a pregnancy with multiple fetuses (eg, twins, triplets). Talk with your doctor to discuss your chances of multiple births.


• LAB TESTS and medical tests, including a physical examination, blood hormone levels, ovarian ultrasounds, and liver function tests, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


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


• Luveris is not recommended for use in CHILDREN. Safety and effectiveness have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Do not use Luveris if you are pregnant. If you suspect that you could be pregnant, contact your doctor immediately. It is unknown if Luveris is excreted in breast milk. If you are or will be breast-feeding while you are using Luveris, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Luveris:

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:

Constipation; diarrhea; gas; headache; nausea; pain, redness, or swelling at the injection site; tiredness.

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); breast pain; decrease in the amount of urine produced; pain, tenderness, redness, or swelling of the leg; severe pelvic pain; severe or persistent nausea, vomiting, or diarrhea; shortness of breath; stomach pain or swelling; unexplained weight gain.

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: Luveris 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.

Proper storage of Luveris:

Luveris is usually handled and stored by a health care provider. If you are using Luveris at home, store Luveris as directed by your pharmacist or health care provider. Keep Luveris out of the reach of children and away from pets.

General information:

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


• Luveris 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 Luveris. 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 Luveris resources

• Luveris Side Effects (in more detail)
• Luveris Use in Pregnancy & Breastfeeding
• Luveris Support Group
• 0 Reviews for Luveris - Add your own review/rating

• Luveris Prescribing Information (FDA)


• Luveris Consumer Overview


• Luveris Monograph (AHFS DI)


• Luveris Advanced Consumer (Micromedex) - Includes Dosage Information


• Lutropin Alfa Professional Patient Advice (Wolters Kluwer)

Compare Luveris with other medications

• Follicle Stimulation

Wellbutrin

Pronunciation: bue-PROE-pee-on
Generic Name: Bupropion
Brand Name: Wellbutrin

Antidepressants may increase the risk of suicidal thoughts or actions in children, teenagers, and young adults. However, depression and certain other mental problems may also increase the risk of suicide. Talk with the patient's doctor to be sure that the benefits of using Wellbutrin outweigh the risks.

Wellbutrin contains the same ingredient that is in Zyban, a medicine used to help certain patients stop smoking. Some patients using bupropion to help them stop smoking have also developed depression and certain other mental or mood problems, including suicidal thoughts or actions.

Family and caregivers must closely watch patients who take Wellbutrin. It is important to keep in close contact with the patient's doctor. Contact the doctor at once if new, worsened, or sudden symptoms such as agitation, hostility, depressed mood, or any unusual change in mood or behavior occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur. Discuss any questions with the patient's doctor.

Wellbutrin is used for:

Treating depression. It may also be used for other conditions as determined by your doctor.

Wellbutrin is an antidepressant. It works in the brain to treat depression. Exactly how it works is not known.

Do NOT use Wellbutrin if:

• you are allergic to any ingredient in Wellbutrin


• you are taking any other medicine that contains bupropion


• you have a history of an eating disorder (eg, anorexia, bulimia) or seizures (eg, epilepsy)


• you are suddenly stopping the use of alcohol or sedatives (eg, benzodiazepines) after long-term use


• you are taking or have taken linezolid, methylene blue, or a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the last 14 days

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

Video: Treatment for Depression

Treatments for depression are getting better everyday and there are things you can start doing right away.

Before using Wellbutrin:

Some medical conditions may interact with Wellbutrin. 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 or a family member has a history of bipolar disorder (manic depression), other mental or mood problems (eg, depression), suicidal thoughts or attempts, or alcohol or substance abuse


• if you have diabetes, kidney problems, liver problems (eg, cirrhosis), high blood pressure, heart problems (eg, congestive heart failure), or a recent heart attack


• if you have a history of seizures, a head injury, or a tumor in the brain or spinal cord


• if you are taking nonprescription weight loss medicines or stimulants

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

• Amantadine, other antidepressants (eg, amitriptyline, fluvoxamine), antipsychotics (eg, haloperidol, risperidone), clopidogrel, corticosteroids (eg, prednisone), cyclophosphamide, HIV protease inhibitors (eg, nelfinavir), insulin, levodopa, linezolid, MAOIs (eg, phenelzine), methylene blue, nicotine patches, oral hypoglycemics (eg, glipizide), orphenadrine, sympathomimetics (eg, pseudoephedrine), theophylline, thiotepa, tiagabine, or ticlopidine because they may increase the risk of Wellbutrin's side effects


• Carbamazepine, efavirenz, phenobarbital, phenytoin, rifampin, or ritonavir because they may decrease Wellbutrin's effectiveness


• Antiarrhythmics (eg, flecainide, propafenone), beta-blockers (eg, metoprolol), phenothiazines (eg, thioridazine), selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine), or tricyclic antidepressants (eg, nortriptyline) because the risk of their side effects may be increased by Wellbutrin


• Tamoxifen because its effectiveness may be decreased by Wellbutrin, which may lead to an increased risk of breast cancer recurrence in women with a history of breast cancer

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

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

• Wellbutrin comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Wellbutrin refilled.


• Take Wellbutrin by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• Several weeks may pass before your symptoms improve. Do not stop taking Wellbutrin without checking with your doctor.


• Take your doses at the same times each day, at least 6 hours apart unless directed otherwise by your doctor. This may help to decrease the risk of seizures with Wellbutrin.


• Continue to take Wellbutrin even if you feel well. Do not miss any doses.


• If you miss a dose of Wellbutrin, skip the missed dose and go back to your regular dosing schedule. Do not take more than 1 dose within 6 hours. Do not take 2 doses at once.

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

Important safety information:

• Wellbutrin may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Wellbutrin with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Check with your doctor before you drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are taking Wellbutrin; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Wellbutrin may increase your risk of seizures. Your risk may be greater if you also have certain medical conditions, use certain medicines, or if you use a lot of alcohol. Talk to your doctor to see if you may have a greater risk of seizures while taking Wellbutrin.


• If you already drink alcohol or use sedatives, do not suddenly stop them without first checking with your doctor. Suddenly stopping them may increase your seizure risk.


• Do not take decongestants (eg, pseudoephedrine), stimulants, or diet pills while you are taking Wellbutrin without first checking with your doctor. They may increase your risk of seizures.


• The risk of seizures may be greater if you take Wellbutrin in high doses or for a long time. Do NOT take more than the recommended dose, change your dose, or use Wellbutrin for longer than prescribed without checking with your doctor.


• Children, teenagers, and young adults who take Wellbutrin may be at increased risk of suicidal thoughts or actions. Watch all patients who take Wellbutrin closely. Contact the doctor at once if new, worsened, or sudden symptoms such as depressed mood; anxious, restless, or irritable behavior; panic attacks; or any unusual change in mood or behavior occur. Contact the doctor right away if any signs of suicidal thoughts or actions occur.


• If you have trouble sleeping, you may be taking your dose too close to bedtime. Talk with your doctor about changing your dosing schedule.


• Wellbutrin contains the same ingredients as Zyban, a medicine used to help stop smoking, and Aplenzin, another medicine used to treat depression. Do not take Wellbutrin if you are also taking Zyban or Aplenzin. Discuss any questions or concerns with your doctor.


• Wellbutrin may interfere with certain lab tests, including urine screenings for amphetamines. Be sure your doctor and lab personnel know you are taking Wellbutrin.


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


• Wellbutrin should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Wellbutrin while you are pregnant. Wellbutrin is found in breast milk. Do not breast-feed while taking Wellbutrin.

Possible side effects of Wellbutrin:

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:

Changes in appetite; constipation; dizziness; drowsiness; dry mouth; headache; increased sweating; nausea; nervousness; restlessness; taste changes; trouble sleeping; vomiting; weight changes.

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, unusual hoarseness); blurred vision or other vision changes; changes in sexual desire or ability; chest pain; confusion; dark urine; delusions; fainting; fast or irregular heartbeat; fever, chills, or sore throat; hallucinations; hearing problems; menstrual changes; new or worsening mental or mood changes (eg, concentration problems, depression, panic attacks, aggressiveness, agitation, anxiety, impulsiveness, irritability, hostility, exaggerated feeling of well-being, inability to sit still); pale stools; red, swollen, blistered, or peeling skin; seizures; severe headache or dizziness; severe or persistent joint or muscle pain; severe or persistent nausea, vomiting, or stomach pain; severe or persistent nervousness, restlessness, or trouble sleeping; shortness of breath; suicidal thoughts or attempts; tremor; unusual swelling; yellowing of the skin or eyes.

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: Wellbutrin 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 chest pain; fainting; fast, slow, or irregular heartbeat; fever; hallucinations; loss of consciousness; rigid or painful muscles; seizures; severe dizziness; slow or difficult breathing.

Proper storage of Wellbutrin:

Store Wellbutrin at room temperature, between 59 and 77 degrees F (15 and 25 degrees C), in a tight, light-resistant container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Wellbutrin out of the reach of children and away from pets.

General information:

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


• Wellbutrin 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 Wellbutrin. 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 Wellbutrin resources

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

• Wellbutrin Advanced Consumer (Micromedex) - Includes Dosage Information


• Wellbutrin Prescribing Information (FDA)


• Wellbutrin Consumer Overview


• Aplenzin Consumer Overview


• Aplenzin Prescribing Information (FDA)


• Budeprion XL Prescribing Information (FDA)


• Bupropion Professional Patient Advice (Wolters Kluwer)


• Bupropion Prescribing Information (FDA)


• Bupropion Hydrochloride Monograph (AHFS DI)


• Wellbutrin SR Prescribing Information (FDA)


• Wellbutrin XL Prescribing Information (FDA)


• Zyban Prescribing Information (FDA)


• Zyban Consumer Overview

Compare Wellbutrin with other medications

• Depression

Lincomycin

Dosage Form: FOR ANIMAL USE ONLY
Lincomycin 300 INJECTION

Lincomycin Injectable brand of Lincomycin hydrochloride injectable

For Intramuscular Use in Swine Only

Lincomycin Injectable contains Lincomycin hydrochloride, an antibiotic produced byStreptomyces lincolnensis var. lincolnensis, which is chemically distinct from all other clinically available antibiotics and is isolated as a white crystalline solid.

INDICATIONS FOR SWINE

Lincomycin injectable is indicated for the treatment of infectious forms of arthritis caused by organisms sensitive to its activity. This included most of the organisms responsible for the various infectious arthritides in swine, such as  staphylococci, streptococci,  Erysipelothrix  and  Mycoplasma spp.  It is also indicated for the treatment of mycoplasma pneumonia.

Contraindications

As with all drugs, the use of Lincomycin Inectable is contraindicated in animals previously found to be hypersensitive to the drug.

Warning

Swine intended for human consumption should not be slaughtered within 48 hours of latest treatment.  Not for human use.

CAUTION

If no improvement is noted within 48 hours, consult a veterinarian.

Adverse Reactions

The intramuscular administration to swine may cause a transient diarrhea or loose stools. Although this effect has rarely been reported, one must be alert to the possibility that it may occur. Should this occur, it is important that the necessary steps be taken to prevent the effects of dehydration.

Lincomycin Dosage and Administration

For arthritis or mycoplasma pneumonia-5 mg per pound of body weight intramuscularly once daily for three to seven days as needed. When using Lincomycin Injectable containing 25 mg/mL,

1 mL/5 lb. body weight will provide 5 mg/lb. When using Lincomycin Injectable containing 100 mg/mL, 1 mL/20 lb body weight will provide 5 mg/lb. When using Lincomycin Injectable containing 300 mg/mL, 1 mL/60 lb. body weight will provide 5 mg/lb.

For optimal results, initiate treatment as soon as possible. As with any multi-dose vial, practice aseptic techniques in withdrawing each does. Adequately clean and disinfect the vial closure prior to entry with a sterile needle and syringe. No vial closure should be entered more than 20 times.

How is Lincomycin Supplied

Lincomycin Injectable is available in three concentrations: 300 mg/mL, 100 mg/mL and 25 mg/mL.

300 mg/mL: For use in swine weighing 300 pounds or more. Each mL contains Lincomycin hydrochloride equivalent to Lincomycin, 300 mg; also Benzyl Alcohol, 9.45 mg added as preservative. Supplied in 100 mL vials.

100 mg/mL: Each mL contains Lincomycin hydrochloride equivalent to Lincomycin , 100 mg; also Benzyl Alcohol, 9.45 mg added as preservative. Supplied in 100 mL vials.

25 mg/mL: Special baby pig concentration. Each mL contains Lincomycin hydrochloride equivalent to Lincomycin, 25 mg; also Benzyl Alcohol, 9.45 mg added as preservative. Supplied in 100 mL vials.

Indicated for the treatment of arthritis caused by susceptible organisms and for mycoplasma pneumonia.

Warning: Not for human use. Keep out of reach of children. Swine intended for human consumption shold not be slaughtered within 48 hours of latest treatment.

Lincomycin 300 INJECTION

300 mg/mL

STERILE Lincomycin HYDROCHLORIDE INJECTION


SWINE ANTIBIOTIC

For intramuslcular Use in Swine Over 300 lbs.

Restricted Drug - Use Only As Directed

(California). For Use in Animals Only.

Dosage: Usual daily dose for arthritis or mycoplasma pneumonia - 5 mg per pound of body weight (1 mL per each 60 pounds of body weight) intramuscularly for three to seven days. See package insert for complete product information.

Contains per mL: Lincomycin Hydrochloride equivalent to Lincomycin 300 mg; also Benzyl Alcohol, 9.45 mg added as preservative.

ANADA #: 200-315, Approved by F.D.A.

Store at controlled room temperature:

20o to 25oC (68oto 77oF) [see USP].

TAKE TIME OBSERVE LABEL DIRECTIONS

Lincomycin   Lincomycin  injection

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58005-636 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Lincomycin HYDROCHLORIDE (Lincomycin) Lincomycin HYDROCHLORIDE 300 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 58005-636-04 100 mL In 1 VIAL None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANADA	ANADA200-315	01/21/2004

Labeler - Sparhawk Laboratories, Inc. (958829558)

Revised: 05/2010Sparhawk Laboratories, Inc.