Pepcid

Generic Name: Famotidine
Class: Histamine H2-Antagonists
VA Class: GA301
Chemical Name: 3-[[[2-[(Aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]-N-(aminosulfonyl)propanimidamide
Molecular Formula: C₈H₁₅N₇O₂S₃
CAS Number: 76824-35-6

Introduction

Histamine H₂ receptor antagonist.^{1 3 4 6 23 46 48 114}

Uses for Pepcid

Duodenal Ulcer

Short-term treatment of active duodenal ulcer (endoscopically or radiographically confirmed).^{1 4 5 6 7 12 16 18 19 22 91 92 93 94 114 123 124 128 129 130 135}

Maintenance of healing and reduction in recurrence of duodenal ulcer.^{1 4 8 88 91 93 114}

Pathologic GI Hypersecretory Conditions

Treatment of Zollinger-Ellison syndrome, multiple endocrine adenomas.^{1 4 5 10 51 93 114 122 132}

Gastric Ulcer

Short-term treatment of active benign gastric ulcer.^{1 4 5 9 12 14 20 22 75 89 93 94 124 131 136 140}

Gastroesophageal Reflux (GERD)

Short-term treatment of symptomatic GERD.^{1 139 167 168 169 170 171 172 173 174 175}

Short-term treatment of esophagitis, including erosions or ulcers (endoscopically diagnosed) in patients with GERD.^{1 167 168 171}

Self-medication as initial therapy for less severe symptomatic GERD†.²⁶¹

Short-term self-medication for relief of heartburn symptoms in adults and adolescents ≥12 years of age.^{238 260}

Short-term self-medication for prevention of heartburn symptoms associated with acid indigestion and sour stomach brought on by ingestion of certain foods and beverages in adults and children ≥12 years of age.^{238 260}

Pepcid Dosage and Administration

Administration

Administered orally,¹ or by slow IV injection or intermittent IV infusion in hospitalized patients with pathological GI hypersecretory conditions or intractable duodenal ulcer, or when oral therapy is not feasible.²⁴⁰

Oral Administration

Administer with or without food; administration with food may slightly enhance bioavailabilty.^{1 3 47 114}

Antacids may be used as necessary for pain relief.^{1 4 6 7 16 18 19 49 94}

Tablet for self-medication should be administered with a glass of water.^{c d}

Chewable tablets (Pepcid AC Chewable, Pepcid Complete) for self-medication should be chewed thoroughly before swallowing.^{238 260}

For duodenal ulcer treatment, the advantage of administration once daily at bedtime (when convenience is important for compliance) over twice-daily administration has not been determined.^{4 7 16 18 93 130}

For gastric ulcer treatment in adults, administer once daily at bedtime.^{1 9 22 93 131 136}

For gastroesophageal reflux, once daily dosage not considered appropriate.²⁶¹

Oral Suspension

Add 46 mL of water to bottle containing 400 mg of famotidine for 40 mg/5mL suspension.^{1 3 14}

Shake oral suspension vigorously for 5–10 seconds after reconstitution and before each use.¹

Intermittent Direct IV Injection

Dilution

Dilute 20 mg to 5–10 mL with 0.9% sodium chloride injection or other compatible IV solution before direct IV injection.²⁴⁰

Rate of Administration

Inject over not less than 2 minutes (no faster than 10 mg/minute).²⁴⁰

Intermittent IV infusion

Dilution

Dilute 20 mg in at least 100 mL of 5% dextrose injection or other compatible IV solution.²⁴⁰

No additional dilution required for commercially available infusion solution (20 mg famotidine in 50 mL of 0.9% sodium chloride injection).²⁴⁰

Rate of Administration

Over 15–30 minutes.²⁴⁰

Dosage

Pediatric Patients

General Parenteral Dosage

May administer IV in hospitalized pediatric patients with pathologic hypersecretory conditions, intractable ulcer, or for short-term use when oral therapy is not feasible.^b

Safety and efficacy have not been established in children <1 year of age.^b

Treatment of Children 1–16 Years of Age

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240}

Intermittent Direct IV Injection

Initially, 0.25 mg/kg (15-minute infusion) every 12 hours (maximum 40 mg daily).²⁴⁰ Up to 0.5 mg/kg every 12 hours has provided gastric acid suppression.^b

Intermittent IV Infusion

Initially, 0.25 mg/kg (over not less than 2 minutes) every 12 hours (maximum 40 mg daily).²⁴⁰ Up to 0.5 mg/kg every 12 hours has provided gastric acid suppression^b

Gastroesophageal Reflux

Treatment of GERD in Infants <3 Months of Age

Oral

0.5 mg/kg once daily for up to 4 weeks.^a

Infants should also be receiving conservative measures (e.g., thickened feedings).^a

IV

Safety and efficacy not established.^b

Treatment of GERD in Infants 3 Months to <1 Year of Age

Oral

0.5 mg/kg twice daily for up to 4 weeks.^a

Infants should also be receiving conservative measures (e.g., thickened feedings).^a

IV

Safety and efficacy not established.^b

Treatment of GERD in Children 1–16 Years of Age

Oral

1 mg/kg daily in 2 divided doses (maximum 40 mg twice daily); up to 2 mg/kg daily has been used.^a

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240 b}

IV

Dosage not established.^b

Treatment of Esophagitis in Children 1- 16 Years of Age

Oral

1 mg/kg daily in 2 divided doses (maximum 40 mg twice daily); up to 2 mg/kg daily has been used.^a

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240 b}

IV

Dosage not established.^b

Self-medication for Heartburn in Adolescents ≥12 Years of Age

Oral

10-mg tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Chewable tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

20-mg tablets: 20 mg once or twice daily (maximum 40 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Fixed combination of famotidine, calcium carbonate, and magnesium hydroxide (Pepcid Complete): 1 tablet (10 mg of famotidine) once or twice daily (maximum 2 tablets in 24 hours continuously for 2 weeks).^e Do not swallow whole; chew completely before swallowing.^e

Self-medication for Prevention of Heartburn In Adolescents ≥12 Years of Age

Oral

10-mg tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 239 260 267 268 269}

10-mg chewable tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

20-mg tablets: 20 mg once or twice daily (10–60 minutes before ingestion of causative food or beverage); maximum 40 mg in 24 hours continuously for 2 weeks or as directed by clinician.^d

Duodenal Ulcer

Treatment of Duodenal Ulcer in Children 1–16 Years of Age

Oral

0.5 mg/kg once daily at bedtime or in 2 divided doses daily (maximum 40 mg daily);¹ up to 1 mg/kg daily has been used.^{1 240}

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.^{1 240}

Gastric Ulcer

Treatment of Gastric Ulcer in Children 1–16 Years of Age

Oral

0.5 mg/kg once daily at bedtime or in 2 divided doses daily (maximum 40 mg daily);¹ up to 1 mg/kg daily has been used.^{1 240}

Individualize duration and dosage based on clinical response and/or gastric or esophageal pH determination and endoscopy.¹

Adults

General Parenteral Dosage

May administer IV in hospitalized adults with pathologic hypersecretory conditions, intractable ulcer, or for short-term use when oral therapy is not feasible.^b

Dosage for parenteral administration in patients with GERD has not been established.^b

Intermittent Direct IV Injection

20 mg every 12 hours (maximum 40 mg daily).^{2 114 240}

Intermittent IV Infusion

20 mg every 12 hours (maximum 40 mg daily).^{2 114 240}

Gastroesophageal Reflux

Treatment of GERD

Oral

20 mg twice daily for up to 6 weeks.^{1 167 173 174}

40 mg once daily at bedtime also has been used, but is less effective^{1 139 167 168} and not considered appropriate therapy.²⁶¹

Treatment of Esophagitis

Oral

20 or 40 mg twice daily for up to 12 weeks.^{1 167 168 171}

Self-medication for Heartburn

Oral

10-mg tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Chewable tablets: 10 mg once or twice daily (maximum 20 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

Fixed combination of famotidine, calcium carbonate, and magnesium hydroxide (Pepcid Complete): 1 tablet (10 mg of famotidine) once or twice daily (maximum 2 tablets in 24 hours continuously for 2 weeks).^e Do not swallow whole; chew completely before swallowing.^e

20-mg tablets: 20 mg once or twice daily (maximum 40 mg in 24 hours continuously for 2 weeks) or as directed by clinician.^{238 239 260 267 268 269}

Self-medication for Prevention of Heartburn

Oral

10-mg tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 239 260 267 268 269}

Chewable tablets: 10 mg once or twice daily (15–60 minutes before ingestion of causative food or beverage); maximum 20 mg in 24 hours continuously for 2 weeks or as directed by clinician.^{238 260} Do not swallow whole; chew completely before swallowing.^{238 260}

20-mg tablets: 20 mg once or twice daily (10–60 minutes before ingestion of causative food or beverage); maximum 40 mg in 24 hours continuously for 2 weeks or as directed by clinician .^d

Duodenal Ulcer

Treatment of Active Duodenal Ulcer

Oral

40 mg once daily at bedtime, or 20 mg twice daily.^{1 2 4 7 16 18 19 22 92 114 129 130}

Healing may occur within 2 weeks in some, ^{1 4 6 16 18 19 22} and within 4 weeks in most patients;^{1 4 6 7 16 18 19 22 93 114 129} some patients may benefit from an additional 4 weeks of therapy.^{1 4 7 16 18 19 22 129}

Occasionally may be necessary to continue full-dose therapy for >6–8 weeks.^{1 114 116}

Safety and efficacy of continuing full-dose therapy for >8 weeks have not been established.^{1 4}

Maintenance of Healing of Duodenal Ulcer

Oral

20 mg once daily at bedtime.^{1 4 8 114}

Gastric Ulcer

Oral

40 mg daily at bedtime for up to 8 weeks.^{1 9 22 93 131 136}

Complete healing of gastric ulcers usually occurs within 8 weeks.^{9 22 131 136}

Safety and efficacy of therapy for >8 weeks have not been established.¹

Pathologic GI Hypersecretory Conditions

Zollinger-Ellison Syndrome

Oral

20 mg every 6 hours.^{1 4 114} Higher doses administered more frequently may be necessary; adjust dosage according to response and tolerance and continue as long as necessary.^{1 4 10 114 122 141}

20–160 mg every 6 hours generally has been necessary to maintain basal gastric acid secretion at <10 mEq/hour.^{1 10 51 114 123 141}

Up to 160 mg every 6 hours,¹ or 800 mg daily in divided doses, ^{2 3 4 10 122} has been used in severe disease.

Intermittent IV Infusion

20 mg every 12 hours.^b Higher initial dosage may be required;^{10 114 115 116 240} adjust to individual needs and continue as long as necessary.^{115 116 240 b}

Prescribing Limits

Pediatric Patients

General Parenteral Dosage

Treatment of children 1–16 Years of Age

Intermittent Direct IV Injection

Maximum 40 mg daily.²⁴⁰

Intermittent IV Infusion

Maximum 40 mg daily.²⁴⁰

Gastroesophageal Reflux

Treatment of GERD in Infants <1 Year of Age

Oral

Safety and efficacy for >4 weeks not established.^a

Treatment of GERD without Esophagitis in Children 1–16 Years of Age

Oral

Maximum 40 mg twice daily.^a

Treatment of Esophagitis (including Erosions, Ulcerations) in Children 1- 16 Years of Age

Oral

Maximum 40 mg twice daily.^a

Self-Medication For Heartburn in Adolescents ≥12 Years of Age

Oral

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 267 268 269}

Self-medication for Prevention of Heartburn in Adolescents ≥12 Years of Age

Oral

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 267 268 269}

Duodenal Ulcer

Treatment of Active Duodenal Ulcer in Children 1–16 Years of Age

Oral

Maximum 40 mg daily.¹

Gastric Ulcer

Treatment of Gastric Ulcer in Children 1–16 Years of Age

Oral

Maximum 40 mg daily.¹

Adults

General Parenteral Dosage

Intermittent Direct IV Injection

Maximum 40 mg daily.²⁴⁰

Intermittent IV Infusion

Maximum 40 mg daily.²⁴⁰

Gastroesophageal Reflux

Treatment of Symptomatic GERD

Oral

Safety and efficacy for >6 weeks not established.^{1 167 173 174}

Treatment of Esophagitis

Oral

Safety and efficacy for >12 weeks not established.^{1 167 168 171}

Self-medication for Heartburn

Oral

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 238 260 267 268 269}

Self-medication for Prevention of Heartburn

Maximum 20 or 40 mg in 24 hours continuously for 2 weeks.^{238 260 267 268 269}

Duodenal Ulcer

Treatment of Active Duodenal Ulcer

Oral

Safety for >8 weeks not established.^{1 4}

Gastric Ulcer

Short-term Treatment of Active Benign Gastric Ulcer

Oral

Safety and efficacy for >8 weeks not established.¹

Pathologic GI Hypersecretory Conditions (e.g., Zollinger-Ellison Syndrome)

Oral

Up to 160 mg every 6 hours,¹ or 800 mg daily in divided doses.^{2 3 4 10 122}

Special Populations

Renal Impairment

Pediatric Patients

Consider dosage adjustment in children with moderate or severe renal impairment.^{1 240}

Adults

In adults, modify dose and/or frequency of administration to the degree of renal impairment; adverse CNS effects have been reported.^{1 4 86 114}

Moderate (Cl_cr<50 mL/minute) or Severe (Cl_cr< 10 mL/minute)

Oral

Decrease to 50% of usual dosage.^{1 114 115}

Alternatively, increase dosing interval to 36–48 hours according to response.^{1 114 115}

IV

Decrease to 50% of usual dosage.^b

Alternatively, increase dosing interval to 36–48 hours according to response.^b

Cl_cr of 30–60 mL/minute per 1.48 m²

50% of usual adult dosage has been recommended.^{4 86}

Cl_cr < 30 mL/minute per 1.48 m²

25% of usual adult dosage has been recommended.^{4 86}

Cautions for Pepcid

Contraindications

• 
  

  Known hypersensitivity to famotidine, any ingredient in the formulation, or to other histamine H₂ antagonists (i.e., cimetidine, nizatidine, ranitidine).^{1 240}

  
  

Warnings/Precautions

General Precautions

Gastric Malignancy

Response to famotidine does not preclude presence of gastric malignancy.¹

Phenylketonuria

Pepcid AC chewable tablets contain aspartame (Nutrasweet), which is metabolized in the GI tract to provide 1.4 mg of phenylalanine per tablet.^c

Respiratory Effects

Administration of H₂-receptor antagonists has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).^{270 271}

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category B.^{1 3}

Self-medication in pregnant women: consult clinician before using.²³⁸

Lactation

Distributed into milk.¹ Discontinue nursing or the drug.¹

Self-medication in nursing women: consult clinician before using.²³⁸

Pediatric Use

Infants <1 year of age: Consider for GERD treatment only if other conservative measures (e.g., thickened feedings) are used concurrently and potential benefits outweigh risks.^{a b}

Safety and efficacy for self-medication not established in children <12 years of age; do not use unless directed by clinician.^{238 239 260}

Renal Impairment

Use with caution.^{1 3 114 240} Dosage adjustments necessary in patients with severe renal impairment.^{1 3 114 240} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Headache, dizziness, constipation, diarrhea.^{1 4 5 7 9 13 22 123 130}

Interactions for Pepcid

Does not appear to inhibit hepatic metabolism of drugs by hepatic CYP isoenzymes.^{1 3 4 21 39 40 41 42 45 46 93 114 118 125 127}

Antacids appear to cause slight but clinically unimportant decrease in bioavailability.^{1 3 47 114} May concomitantly administer with antacids.^{1 4 6 7 16 18 19 47 49 94}

Pepcid Pharmacokinetics

Absorption

Bioavailability

Oral: about 40–50%.^{1 3 4 11 46 85 114 118} Similar (50%) in children 11–15 years of age.¹

Tablets and oral suspension reportedly are bioequivalent.^{1 2 3 114}

Onset

Gastric acid inhibition within 1 hour after IV or oral administration.^{1 2 11 118} Peak inhibition within 0.5–3 hours following IV,^{1 11 114 118} 1–4 hours following oral^{1 10 11 46 51 114} administration.

Duration

Dose-dependent inhibition of gastric acid secretion.^{1 4 11 46 48 60 61 62 63 65 81 118}

Inhibition of basal and nocturnal secretion for 10–12 hours after single oral 20-^{1 2 11 61 62 63 81} or 40-mg^{1 2 46 61 62} dose.^{1 2 11 46 61 62 63 81 93 114 118}

Inhibition of food-stimulated secretion generally persists for 8–10 hours after morning administration, but may dissipate within 6–8 hours after a 20-mg oral dose in some patients.^{1 4 81}

Inhibition of nocturnal gastric acid secretion is 10–15 hours after single 10- or 20-mg IV dose.^{1 2 11}

Food

May slightly enhance bioavailability.^{1 3 47 114}

Distribution

Extent

Widely distributed, highest concentrations in the kidney, liver, pancreas, and submandibular gland.^{4 84}

Distributed into human milk.^{a b}

Does not cross the placenta in animal studies;² not known if famotidine crosses the placenta in humans.²

Plasma Protein Binding

15–20%.^{1 3 4 114 118}

Elimination

Metabolism

Metabolized in the liver¹¹⁵ to inactive famotidine S-oxide (S-famotidine).^{1 2 3 82 84 114}

Minimal first-pass metabolism.^{1 3 114 118}

Elimination Route

Excreted principally in urine;^{1 2 3 4 53 86 114 118} 25–30% excreted unchanged within 24 hours after oral administration,^{1 2 3 4 65 81 83 114} 65–80%^{1 2 3 4 85 86 114} after IV administration.^{1 2 3 4 83 85 86} Small fraction of orally administered dose is excreted in urine as famotidine S-oxide.^{4 83} Remainder of orally administered dose eliminated in feces.⁴

Interindividual variation in metabolism and excretion.^{4 83 118}

Half-life

2.5–4 hours (adults).^{1 2 4 11 65 81 83 85 86 93 118}

Special Populations

In patients with renal impairment, close correlation between Cl_cr and elimination half-life;^{a b} >20 hours when Cl_cr <10 mL/minute,^{1 3 4 86 114} 24 hours in anuric patients.¹

Does not appear to be removed by hemodialysis.⁴

Stability

Storage

Oral

Tablets

20 and 40 mg film-coated tablets: 25°C (may be exposed to 15–30°C) in tight, light-resistant containers.^{1 2 3 152}

Tablets for Self-medication

10 mg tablets, chewable tablets, film-coated tablets: 25–30°C.^{238 267 268}

10 mg chewable tablets in combination with calcium carbonate and magnesium hydroxide: 25–30°C.^e

20 mg film-coated tablets: 20–30°C.^d

Protect from moisture.^{238 267 268 d e}

For Suspension

Reconstituted suspension or dry powder: 25°C (may be exposed to 15–30°C) in tight containers.^a

Suspension may be refrigerated;¹¹⁵ protect from freezing.^{1 2 3}

Discard unused suspension after 30 days.^{1 2 3}

Parenteral

Injection

2–8°C;^{1 2} expiration date of 24 months following the date of manufacture when stored at this temperature.^{2 3} If freezing occurs, thaw at room temperature,^{1 3} or in warm water bath, or under running hot tap water;¹¹⁵ allow sufficient time for dissolution of all ingredients.^{1 3} Do not thaw by microwave because of potential hazard of rapidly increased temperature and vapor pressure in a closed system. Diluted solutions of famotidine not used immediately after preparation should be refrigerated and used within 48 hours.^{b 115}

Injection for IV infusion only

25°C.²⁴¹ Protect from excessive heat; brief exposure up to 35°C will not adversely affect the stability of the solution.²⁴⁰ Stable for 15 months when stored as recommended.²⁴¹

Compatibility

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

Parenteral

Solution Compatibility^HID

Compatible
Amino acids
Dextrose 5% in water
Fat emulsion 10%, IV
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Cefazolin sodium
Flumazenil
Vancomycin HCl

Y-Site CompatibilityHID

Compatible
Acyclovir sodium
Allopurinol sodium
Amifostine
Aminophylline
Amiodarone HCl
Ampicillin sodium
Ampicillin sodium–sulbactam sodium
Amsacrine
Anakinra
Atropine sulfate
Aztreonam
Bivalirudin
Bretylium tosylate
Calcium gluconate
Cefazolin sodium
Cefotaxime sodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Chlorpromazine HCl
Cisplatin
Cladribine
Cyclophosphamide
Cytarabine
Dexamethasone sodium phosphate
Dexmedetomidine HCl
Dextran 40
Digoxin
Diphenhydramine HCl
Dobutamine HCl
Docetaxel
Dopamine HCl
Doxorubicin HCl
Doxorubicin HCl liposome injection
Droperidol
Enalaprilat
Epinephrine HCl
Erythromycin lactobionate
Esmolol HCl
Etoposide phosphate
Fenoldopam mesylate
Filgrastim
Fluconazole
Fludarabine phosphate
Folic acid
Gemcitabine HCl
Gentamicin sulfate
Granisetron HCl
Haloperidol lactate
Heparin sodium
Hetastarch in lactated electrolyte injection (Hextend)
Hydrocortisone
Hydrocortisone sodium succinate
Hydromorphone HCl
Hydroxyzine HCl
Imipenem–cilastatin sodium
Inamrinone lactate
Isoproterenol HCl
Labetalol HCl
Lidocaine HCl
Linezolid
Lorazepam
Magnesium sulfate
Melphalan HCl
Meperidine HCl
Methotrexate sodium
Methylprednisolone sodium succinate
Metoclopramide HCl
Midazolam HCl
Morphine sulfate
Nafcillin sodium
Nicardipine HCl
Nitroglycerin
Norepinephrine bitartrate
Ondansetron HCl
Oxacillin sodium
Oxalipatin
Paclitaxel
Pemetrexed disodium
Perphenazine
Phenylephrine HCl

Neosporin Ointment

Pronunciation: BAS-i-TRAY-sin/NEE-oh-MYE-sin/POL-ee-MIX-in
Generic Name: Bacitracin/Neomycin/Polymyxin
Brand Name: Examples include Lanabiotic and Neosporin

Neosporin Ointment is used for:

Treating and preventing infection due to minor cuts, scrapes, and burns.

Neosporin Ointment is an antibiotic combination. It works by killing sensitive bacteria on the skin or in wounds.

Do NOT use Neosporin Ointment if:

• you are allergic to any ingredient in Neosporin Ointment

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

Before using Neosporin Ointment:

Some medical conditions may interact with Neosporin Ointment. 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 deep wounds, puncture wounds, animal bites, or serious burns

Some MEDICINES MAY INTERACT with Neosporin Ointment. Because little, if any, of Neosporin Ointment is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Neosporin Ointment may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Neosporin Ointment:

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

• Neosporin Ointment is for external use only. Do not use in or near the eyes, nose, or mouth. If you get Neosporin Ointment in your eyes, rinse immediately with cool tap water.


• Do not apply Neosporin Ointment over large areas of your body without first checking with your doctor.


• Wash your hands thoroughly before and after using Neosporin Ointment, unless your hands are part of the treated area.


• Wash and completely dry the affected area. Apply a small amount of Neosporin Ointment (about the size of the tip of the finger) to the affected area. Gently rub the medicine in until it is evenly distributed.


• The treated area may be covered with bandages.


• If you miss a dose of Neosporin Ointment and you are using it regularly, use it as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

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

Important safety information:

• If your symptoms do not get better within 1 week, if they clear up and then reappear, or if they get worse, check with your doctor.


• Do NOT take more than the recommended dose or use for longer than 1 week without checking with your doctor.


• If your doctor recommended that you use Neosporin Ointment for a certain period of time, it is important to use Neosporin Ointment for the full course of treatment, even if your symptoms improve within a few days.


• Neosporin Ointment should not be used in CHILDREN younger than 2 years old; safety and effectiveness in these 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 Neosporin Ointment while you are pregnant. It is not known if Neosporin Ointment is found in breast milk. If you are or will be breast-feeding while you use Neosporin Ointment, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Neosporin Ointment:

All medicines may cause side effects, but many people have no, or minor, side effects. When used in small doses, no COMMON side effects have been reported with this product. Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); skin irritation, pain, burning, cracking, redness, or peeling not present before using Neosporin Ointment; worsening or recurrence of wound symptoms.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Neosporin 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 Neosporin Ointment:

Store Neosporin Ointment at room temperature, between 59 and 86 degrees F (15 and 30 degrees C), in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Neosporin Ointment out of the reach of children and away from pets.

General information:

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


• Neosporin Ointment 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 Neosporin Ointment. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Neosporin resources

• Neosporin Side Effects (in more detail)
• Neosporin Use in Pregnancy & Breastfeeding
• Neosporin Drug Interactions
• Neosporin Support Group
• 1 Review for Neosporin - Add your own review/rating

Compare Neosporin with other medications

• Bacterial Skin Infection

Meropenem

Class: Carbapenems
Chemical Name: [4R-[3(3S*,5S*),4α,5β,6β(R)]]-3-[[5- [(Dimethylamino)carbonyl] - 3 - pyrrolidinyl]thio] - 6 - (1 - hydroxyethyl) - 4 - methyl - 7 - oxo - 1 - azabicyclo[3.2.0]hept - 2 - ene - 2 - carboxylic acid trihydrate
Molecular Formula: C₁₇H₂₅N₃O₅S•3H₂OC₁₇H₂₅N₃O₅S
CAS Number: 119478-56-7
Brands: Merrem

Introduction

Antibacterial; carbapenem β-lactam antibiotic.^{1 2 3}

Uses for Meropenem

Intra-abdominal Tract Infections

Treatment of intra-abdominal infections (complicated appendicitis, peritonitis) caused by susceptible viridans streptococci, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Bacteroides fragilis, B. thetaiotaomicron, or Peptostreptococcus.^{1 2 3 4 6 7 9 10 12 24 28 43}

Has a broad spectrum of antibacterial activity against both aerobes and anaerobes; may be used empirically to treat intra-abdominal infections before identification of the causative organism.^{1 2 6 7 10}

For immunosuppressed patients or those with severe intra-abdominal infections, IDSA recommends an initial empiric regimen with broad spectrum of activity such as meropenem or imipenem; a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone) in conjunction with metronidazole; ciprofloxacin in conjunction with metronidazole; piperacillin-tazobactam; or aztreonam in conjunction with metronidazole.²⁸ For mild to moderate community-acquired intra-abdominal infections, IDSA recommends an initial empiric regimen with narrower spectrum of activity such as ampicillin-sulbactam; cefazolin or cefuroxime in conjunction with metronidazole; ticarcillin-clavulanate; ertapenem; or a fluoroquinolone (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin) in conjunction with metronidazole.²⁸

For postoperative (nosocomial) intra-abdominal infections, IDSA recommends the empiric regimen be selected based on local nosocomial susceptibility patterns; these infections usually require treatment with multiple-drug regimens and often involve resistant organisms.²⁸

Meningitis

Treatment of bacterial meningitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), or Neisseria meningitidis in children ≥3 months of age.^{1 2 8 10} Also has been used for treatment of meningitis in adults†.^{29 46}

Efficacy for treatment of meningitis caused by highly penicillin- or cephalosporin-resistant S. pneumoniae has not been established.^{1 29 44 45}

Can be used as monotherapy for meningitis caused by susceptible bacteria.¹ Although not usually considered initial drug of choice,^{24 25 29 30} recommended as an alternative in children and adults for treatment of meningitis caused by S. pneumoniae or H. influenzae.^{24 25 29 30} Also may be useful for meningitis caused by susceptible gram-negative bacteria (e.g., Enterobacter†, Citrobacter†, Serratia marcescens†) resistant to usually recommended regimens.²⁹

Respiratory Tract Infections

Treatment of respiratory tract infections†, including community-acquired pneumonia (CAP) and nosocomial pneumonia.^{19 20 21 22 23 24 26 27}

ATS, IDSA, and others consider meropenem an alternative, not a drug of first choice, for empiric treatment of CAP† caused by S. pneumoniae.^{19 20 23 26} ATS and IDSA suggest the drug be reserved for when CAP may be caused by Ps. aeruginosa,^{20 23} Klebsiella,²³ or other gram-negative bacteria.²³ Also may be considered when anaerobes are known or suspected to be involved.¹⁹

A drug of choice for empiric treatment of nosocomial pneumonia†.^{24 26} ATS, IDSA, and others recommend an antipseudomonal cephalosporin (cefepime, ceftazidime), antipseudomonal penicillin (piperacillin-tazobactam, ticarcillin-clavulanate), or antipseudomonal carbapenem (imipenem or meropenem) for initial therapy of hospital-acquired pneumonia, ventilator-associated pneumonia, or health-care associated pneumonia because these drugs have broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria.^{24 26 27} In severely ill patients or in those with late-onset disease or risk factors for multidrug-resistant bacteria, initial regimen should also include an aminoglycoside (amikacin, gentamicin, tobramycin) or antipseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) to improve coverage against Pseudomonas.^{24 26} In hospitals where oxacillin-resistant (methicillin-resistant) Staphylococcus are common or if there are risk factors for these strains, the initial regimen also should include vancomycin or linezolid.^{24 26 27} In hospitals where multidrug-resistant Ps. aeruginosa are frequent causes of nosocomial pneumonia, an initial regimen of cefepime or a carbapenem (imipenem or meropenem) in conjunction with an aminoglycoside is recommended.^{26 54}

Septicemia

Treatment of septicemia† caused by susceptible bacteria.²⁴

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections caused by susceptible S. aureus (including β-lactamase-producing strains, but not oxacillin-resistant [methicillin-resistant] strains), S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), viridans streptococci, Enterococcus faecalis (not vancomycin-resistant strains), Ps. aeruginosa, E. coli, Proteus mirabilis, B. fragilis, or Peptostreptococcus.¹

Urinary Tract Infections

Treatment of complicated urinary tract infections† caused by susceptible bacteria.³⁸

Acinetobacter Infections

Treatment of infections caused by Acinetobacter†;²⁴ a drug of choice used with or without an aminoglycoside.²⁴

Anthrax

Recommended as one of several anti-infectives that can be included in multiple-drug regimens used for the treatment of anthrax†, including inhalational anthrax and anthrax meningitis.^{31 39}

Has in vitro activity against Bacillus anthracis; data not available regarding in vivo activity.⁴⁰

Bacillus Infections

Treatment of infections caused by Bacillus cereus†.²⁴ Vancomycin considered drug of choice; carbapenems (imipenem or meropenem) or clindamycin are alternatives.²⁴

Burkholderia Infections

Treatment of melioidosis† caused by Burkholderia pseudomallei.^{24 31 32 33 34} Severe illness requires an initial parenteral regimen of ceftazidime, imipenem, or meropenem (with or without concomitant co-trimoxazole or doxycycline), followed by a prolonged oral maintenance regimen of co-trimoxazole in conjunction with doxycycline or amoxicillin-clavulanate.^{31 34}

Treatment of glanders† caused by B. mallei.^{31 34} Experience is limited regarding treatment of human cases; optimum regimens not identified.^{31 34} Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy.²⁴ Others suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.³⁴

The US Army Medical Research Institute of Infectious Diseases (USAMRIID) and European Commission’s Task Force on Biological and Chemical Agent Threats (BICHAT) state that the same treatment regimens recommended for naturally occurring melioidosis or glanders should be used if these Burkholderia infections occur in the context of biologic warfare or bioterrorism.^{31 34} These experts suggest that postexposure prophylaxis with doxycycline or co-trimoxazole for ≥10 days can be attempted in such situations, but is of unproven benefit.^{31 34}

Campylobacter Infections

Treatment of systemic infections caused by Campylobacter fetus†;²⁴ a drug of choice.²⁴

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga canimorsus†.²⁴

Optimum regimens for treatment of Capnocytophaga infections not identified; some clinicians recommend use of penicillin G or, alternatively, a third generation cephalosporin (cefotaxime, ceftizoxime, ceftriaxone), a carbapenem (imipenem or meropenem), vancomycin, a fluoroquinolone, or clindamycin.²⁴

Clostridium Infections

Treatment of infections caused by Clostridium perfringens†; alternative to penicillin G for those with penicillin hypersensitivity or for polymicrobial infections.^{24 25}

Nocardia Infections

Treatment of infections caused by Nocardia†.^{24 25} Co-trimoxazole usually drug of first choice;²⁴ alternatives include sulfisoxazole, a tetracycline (e.g., doxycycline, minocycline), a carbapenem (imipenem or meropenem), amikacin, ceftriaxone, amoxicillin-clavulanate, cycloserine, or linezolid.^{24 25}

Rhodococcus Infections

Treatment of infections caused by Rhodococcus equi†.²⁴ Optimum regimens not identified; combination regimens usually recommended, including vancomycin given with a fluoroquinolone, rifampin, a carbapenem (imipenem or meropenem), or amikacin.²⁴

Empiric Therapy inFebrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients†.^{14 24} Used alone or in conjunction with other anti-infectives.^{14 24}

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.¹⁴ Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.¹⁴

Meropenem Dosage and Administration

Administration

Administer by IV injection or infusion.¹

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

IV Injection

Reconstitution

Reconstitute single-use vials containing 500 mg or 1 g with 10 or 20 mL, respectively, of sterile water for injection to provide a solution containing approximately 50 mg/mL.¹ The vial should be shaken until dissolution occurs and then allowed to stand until the solution is clear.¹

Rate of Administration

The appropriate dose of reconstituted solution should be injected over a period of 3–5 minutes.¹

IV Infusion

Reconstitution and Dilution

Reconstitute infusion vials containing 500 mg or 1 g with a compatible IV solution (e.g., 0.9% sodium chloride, 5% dextrose) to provide solutions containing approximately 2.5–50 mg/mL.¹ Alternatively, reconstitute vials containing 500 mg or 1 g with 10 or 20 mL, respectively, of sterile water for injection and then further dilute in a compatible IV.¹

Rate of Administration

Infuse IV over 15–30 minutes.¹

Dosage

Available as the trihydrate; dosage expressed in terms of anhydrous meropenem.¹³

To minimize risk of seizures, closely adhere to dosage recommendations, especially in patients with factors known to predispose to seizure activity; dosage adjustment recommended for patients with advanced age and/or renal impairment.¹

Anticonvulsant therapy should be continued in patients with existing seizure disorders.¹ (See CNS Effects under Cautions.)

Pediatric Patients

Intra-abdominal Infections

IV

Children ≥3 months of age weighing ≤50 kg: 20 mg/kg (up to 1 g) every 8 hours.^{1 2}

Children ≥3 months weighing >50 kg: 1 g every 8 hours.¹

Meningitis

IV

Children ≥3 months of age weighing ≤50 kg: 40 mg/kg (up to 2 g) every 8 hours.^{1 2}

Children ≥3 months weighing >50 kg: 2 g every 8 hours.¹

Skin and Skin Structure Infections

IV

Children ≥3 months of age weighing ≤50 kg: 10 mg/kg (up to 500 mg) every 8 hours.¹

Children ≥3 months weighing >50 kg: 500 mg every 8 hours.¹

Burkholderia Infections†

Initial Treatment of Severe Disease†

IV

Children ≥3 months of age weighing ≤40 kg: 10–20 mg/kg every 8 hours.³⁴

Children ≥3 months weighing >40 kg: use adult dosage.³⁴

Initial IV regimen continued for ≥14 days and until clinical improvement occurs.^{31 34} When appropriate, switch to a prolonged oral maintenance regimen (e.g., co-trimoxazole with doxycycline, amoxicillin-clavulanate).^{31 34} Lifelong follow-up recommended for all patients to identify relapse.³¹

Adults

Intra-abdominal Infections

IV

1 g every 8 hours.¹

Meningitis†

IV

6 g daily.²⁹ Dosage of 40 mg/kg every 8 hours (up to 6 g daily) has been used in conjunction with ceftriaxone or cefotaxime.⁴⁶

Respiratory Tract Infections†

Nosocomial Pneumonia†

IV

1 g every 8 hours.²⁷

Skin and Skin Structure Infections

IV

500 mg every 8 hours.¹

Burkholderia Infections†

Initial Treatment of Severe Disease†

IV

25 mg/kg IV every 8 hours (up to 6 g daily) recommended by USAMRIID and others; concomitant co-trimoxazole (8 mg/kg of trimethoprim daily given IV in 4 divided doses) also may be indicated.^{31 32 33} Other clinicians recommend 0.5–1 g every 8 hours with or without co-trimoxazole.³⁴

Initial IV regimen continued for ≥14 days and until clinical improvement occurs.^{31 34} When appropriate, switch to a prolonged oral maintenance regimen (e.g., co-trimoxazole with doxycycline, amoxicillin-clavulanate).^{31 34} Lifelong follow-up recommended for all patients to identify relapse.³¹

Prescribing Limits

Pediatric Patients

IV

2 g every 8 hours.¹

Special Populations

Hepatic Impairment

Dosage adjustments not required.¹

Renal Impairment

Dosage adjustments recommended in adults with Cl_cr ≤50 mL/minute.¹ Data insufficient to make dosage recommendations for pediatric patients with renal impairment.¹

Dosage for Adults with Renal Impairment1

Clcr (mL/min)	Daily Dosage
26–50	usual dose every 12 hours
10–25	50% of usual dose every 12 hours
<10	50% of usual dose once every 24 hours

Manufacturer states data insufficient to make dosage recommendations in patients undergoing hemodialysis or peritoneal dialysis.¹ Meropenem removed by hemodialysis; some clinicians suggest that supplemental doses be given after each hemodialysis session.^{47 48} Also removed by various forms of continuous renal replacement therapy, including continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous hemofiltration (CVVHF), and continuous ambulatory peritoneal dialysis (CAPD).^{49 50 51 52 53} To avoid inadequate concentrations in anuric patients undergoing these procedures, some clinicians suggest dosage adjustments are necessary and should be based on characteristics of the specific procedure (e.g., filter or membrane type, amount of filtrate produced, dialysate flow rate).^{49 50 51 52 53}

Geriatric Patients

No dosage adjustments except those related to renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Meropenem

Contraindications

• 
  

  Known hypersensitivity to meropenem, other carbapenems, or any ingredient in the formulation.¹

  
  


• 
  

  History of anaphylactic reaction to β-lactams.¹

  
  

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible organism.¹ Careful observation of the patient is essential.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives may permit overgrowth of clostridia.¹ Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.¹

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.^{1 56 57 58 59} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.^{1 56 57 58 59}

CNS Effects

Seizures and other CNS effects reported, especially in those with CNS disorders (e.g., brain lesions, history of seizures) or with bacterial meningitis and/or renal impairment.¹

Do not exceed recommended dosage, especially in those with known factors that predispose to seizures.¹ Anticonvulsant therapy should be continued in those with known seizure disorders.¹

If focal tremors, myoclonus, or seizures occur, evaluate the patient neurologically, initiate anticonvulsant therapy if necessary, and determine whether meropenem dosage should be decreased or the drug discontinued.¹

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity reactions (e.g., anaphylaxis) reported with β-lactams.¹

If hypersensitivity occurs, discontinue meropenem and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).¹

Cross-hypersensitivity

Partial cross-allergenicity among β-lactam antibiotics, including penicillins, cephalosporins, and other β-lactams.¹

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to meropenem, cephalosporins, penicillins, or other drugs.¹

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of meropenem and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

Laboratory Monitoring

Periodically assess organ system functions, including renal, hepatic, and hematopoietic, during prolonged therapy.¹

Sodium Content

Each g of meropenem contains 3.92 mEq (90.2 mg) of sodium as sodium carbonate.¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Not known whether distributed into milk.¹ Use with caution.¹

Pediatric Use

Safety and efficacy not established in children <3 months of age.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.¹ Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.¹

No dosage adjustments except those related to renal function.¹ (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Pharmacokinetics not affected by hepatic impairment; dosage adjustments not required.¹

Renal Impairment

Decreased clearance.¹ Dosage adjustments recommended in patients with Cl_cr ≤50 mL/minute.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, vomiting, constipation), local reactions (pain and inflammation at injection site, phlebitis/thrombophlebitis), headache, anemia, rash, pruritus, sepsis, apnea, shock, glossitis, oral candidiasis.¹

Interactions for Meropenem

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides	In vitro evidence of synergistic antibacterial effects against Ps. aeruginosa1
Probenecid	Decreased renal tubular secretion of meropenem; increased meropenem concentrations and AUC and prolonged half-life1	Concomitant use not recommended1
Valproic acid	Valproic serum concentrations may be decreased to subtherapeutic concentrations; possible increased risk of seizures1 35 36 37	Use concomitantly with caution36 55

Meropenem Pharmacokinetics

Distribution

Extent

Well distributed into body tissues and fluids, including bronchial mucosa, lung, bile, gynecologic tissue (endometrium, myometrium, ovary, cervix, fallopian tube), muscle, heart valves, skin, and interstitial and peritoneal fluid.¹

Distributed into CSF.¹

Plasma Protein Binding

Approximately 2%.¹

Elimination

Metabolism

Partially metabolized; at least 1 metabolite is microbiologically active.¹

Elimination Route

Eliminated in urine as unchanged drug.¹ 70% of an IV dose eliminated in urine as unchanged drug.¹

Half-life

Adults with normal renal function: approximately 1 hour.¹

Children 3 months to 2 years of age: approximately 1.5 hours.¹

Special Populations

Pharmacokinetics not affected by hepatic impairment.¹

Decreased clearance in patients with renal impairment.¹

Stability

Storage

Parenteral

Powder for Injection

20–25°C.¹ Do not freeze reconstituted or diluted solutions.¹

Solutions for IV injection containing approximately 50 mg/mL prepared using water for injection are stable for 2 hours at 15–25°C or 12 hours at 4°C.¹

Solutions for IV infusion containing 2.5–50 mg/mL prepared using 0.9% sodium chloride are stable for up to 2 hours at 15–25°C or 18 hours at 4°C; those prepared using 5% dextrose are stable for up to 1 hour at 15–25°C or 8 hours at 4°C.^{1 1}

ADD-Vantage vials reconstituted to a concentration of 5–20 mg/mL using 0.45% sodium chloride are stable for up to 6 hours at 15–25°C or 24 hours at 4°C.¹ ADD-Vantage vials reconstituted to a concentration of 1–20 mg/mL using 0.9% sodium chloride are stable for up to 4 hours at 15–25°C or 24 hours at 4°C;¹ those prepared using 5% dextrose injection are stable 1 hours at 15–25°C or 8 hours at 4°C; .¹

Compatibility

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

Parenteral

Solution Compatibility^HID

Incompatible (by conventional definition, but recommended for dilution with use in shorter periods of time)

Dextrose 5% with potassium chloride 0.15%

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% with sodium bicarbonate 0.02%

Dextrose 2.5% in sodium chloride 0.45%

Dextrose 5% in sodium chloride 0.2 or 0.9%

Dextrose 5 or 10% in water

Mannitol 2.5 or 10%

Normosol M with dextrose 5%

Ringer’s injection

Ringer’s injection, lactated

Sodium bicarbonate 5%

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Drug Compatibility

Admixture CompatibilityHID

Compatible
Aminophylline
Atropine sulfate
Cimetidine HCl
Dexamethasone sodium phosphate
Dobutamine HCl
Dopamine HCl
Enalaprilat
Fluconazole
Furosemide
Gentamicin sulfate
Heparin sodium
Magnesium sulfate
Metoclopramide HCl
Morphine sulfate
Norepinephrine bitartrate
Phenobarbital sodium
Ranitidine HCl
Vancomycin HCl
Incompatible
Amphotericin B
Metronidazole HCl
Multivitamins
Variable
Acyclovir sodium
Doxycycline hyclate
Ondansetron HCl
Zidovudine

Y-Site CompatibilityHID

Compatible
Aminophylline
Atenolol
Atropine sulfate
Cimetidine HCl
Dexamethasone sodium phosphate
Digoxin
Diphenhydramine HCl
Docetaxel
Enalaprilat
Fluconazole
Furosemide
Gentamicin sulfate
Heparin sodium
Linezolid
Metoclopramide HCl
Milrinone lactate
Morphine sulfate
Norepinephrine bitartrate
Phenobarbital sodium
Potassium chloride
Vancomycin HCl
Incompatible
Amphotericin B
Diazepam
Metronidazole HCl
Variable
Acyclovir sodium
Calcium gluconate
Doxycycline hyclate
Ondansetron HCl
Zidovudine

Actions and SpectrumActions

• 
  

  Synthetic carbapenem β-lactam antibiotic; structurally and pharmacologically related to imipenem and ertapenem.^{1 2 3}

  
  


• 
  

  Usually bactericidal in action.¹

  
  


• 
  

  Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.¹

  
  


• 
  

  Spectrum of activity includes many gram-positive and -negative aerobic bacteria and some gram-positive and -negative anaerobic bacteria.¹ Stable in the presence of a variety of β-lactamases (including penicillinases, cephalosporinases, and extended-spectrum β-lactamases).¹

  
  


• 
  

  Gram-positive aerobes: Active in vitro and in clinical infections against Streptococcus pneumoniae (penicillin-susceptible strains only) and viridans streptococci.¹ Also active in vitro against Staphylococcus aureus and S. epidermidis.¹ Oxacillin-resistant (methicillin-resistant) staphylococci are resistant.¹

  
  


• 
  

  Gram-negative aerobes: Active in vitro and in clinical infections against Escherichia coli, Haemophilus influenzae (including β-lactamase-producing strains), Klebsiella pneumoniae, Neisseria meningitidis and Pseudomonas aeruginosa.¹ Also active in vitro against Acinetobacter, Aeromonas hydrophila, Campylobacter jejuni, Citrobacter, Enterobacter, H. influenzae (ampicillin-resistant, non-β-lactamase-producing strains; BLNAR), Havnia alvei, K. oxytoca, Moraxella catarrhalis, Morganella morganii, Pasteurella multocida, Proteus mirabilis, P. vulgaris, Salmonella, Shigella, Serratia marcescens, and Yersinia enterocolitica.¹

  
  


• 
  

  Anaerobes: Active in vitro and in clinical infections against Bacteroides fragilis, B. thetaiotaomicron, and Peptostretptococcus.¹ Also active in vitro against B. distasonis, B. ovatus, B. uniformis, B. ureolyticus, B. vulgatus, Clostridium difficile, C. perfringens, Eubacterium lentum, Fusobacterium, Prevotella bivia, P. intermedia, P. melaninogenica, Porphyromonas asaccharolytica, and Propionibacterium acnes.¹

  
  

Advice to Patients

• 
  

  Advise patients that antibacterials (including meropenem) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹

  
  


• 
  

  Importance of completing full course of therapy, even if feeling better after a few days.¹

  
  


• 
  

  Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with meropenem or other antibacterials in the future.¹

  
  


• 
  

  Importance of informing clinicians of other medical conditions, including history of seizures.¹

  
  


• 
  

  Importance of discontinuing therapy and informing clinician if an allergic or hypersensitivity reaction occurs.¹

  
  


• 
  

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

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.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.

Meropenem (Trihydrate)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV use only	500 mg (of anhydrous meropenem)	Merrem I.V. (with sodium carbonate)	AstraZeneca
		1 g (of anhydrous meropenem)	Merrem I.V. (with sodium carbonate)	AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Merrem 1GM Solution (ASTRAZENECA): 1/$79.56 or 5/$386.17

Merrem 500MG Solution (ASTRAZENECA): 1/$39.99 or 10/$365.99

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.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. AstraZeneca Pharmaceuticals. Merrem IV (meropenem) for injection for intravenous use only prescribing information. Wilmington, DE; 2005 May.

2. Wiseman LR, Wagstaff AJ, Brogden RN et al. Meropenem: a review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs. 1995; 50:73-101. [PubMed 7588092]

3. Pryka RD, Haig GM. Meropenem: a new carbapenem antimicrobial. Ann Pharmacother. 1994; 28:1045-54. [IDIS 335809] [PubMed 7803882]

4. Condon RE, Walker AP, Sirinek KR et al. Meropenem versus tobramycin plus clindamycin for treatment of intraabdominal infections: results of a prospective, randomized, double-blind clinical trial. Clin Infect Dis. 1995; 21:544-50. [IDIS 354815] [PubMed 8527541]

5. Brismar B, Malmborg AS, Tunevall G et al. Meropenem versus imipenem/cilastatin in the treatment of intra-abdominal infections. J Antimicrob Chemother. 1995; 35:139-48. [IDIS 343753] [PubMed 7768761]

6. Geroulanos SJ and the Meropenem Study Group. Meropenem versus imipenem/cilastatin in intra-abdominal infections requiring surgery. J Antimicrob Chemother. 1995; 36(Suppl A):191-205. [IDIS 353291] [PubMed 8543495]

7. Huizinga WKJ, Warren BL, Baker LW et al. Antibiotic monotherapy with meropenem in the surgical management of intra-abdominal infections. J Antimicrob Chemother. 1995; 36(Suppl A):179-89. [IDIS 353290] [PubMed 8543493]

8. Klugman KP, Dagan R, and the Meropenem Meningitis Study Group. Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Antimicrob Agents Chemother. 1995; 39:1140-6. [IDIS 346314] [PubMed 7625802]

9. Anonymous. Meropenem—an advatageous antibiotic? Drug and Therapeutics Bulletin. 1996; 34:53-5.

10. Bradley JS, Faulkner KL, Klugman KP. Efficacy, safety and tolerability of meropenem as empiric antibiotic therapy in hospitalized pediatric patients. Pediatr Infect Dis J. 1996; 15:749-57. [IDIS 372345] [PubMed 8858694]

11. Fukasawa M, Sumita Y, Harabe ET et al. Stability of meropenem and effect of 1β- methyl substitution on its stability in the presence of renal dehydropeptidase I. Antimicrob Agents Chemother. 1992; 36:1577-9. [PubMed 1510457]

12. Briceland LL, Tobin EH. Focus on meropenem: a broad-spectrum parenteral carbapenem antimicrobial agent. Formulary. 1996; 31:759-74.

13. Zeneca Pharmaceuticals, Wilmington, DE: Personal communication.

14. Hughes WT, Armstrong D, Bodey GP et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002; 34:730-51. [IDIS 479956] [PubMed 11850858]

15. Pizzo PA. Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med. 1993; 328:1323-32. [IDIS 313154] [PubMed 8469254]

16. Ramphal R, Gucalp R, Rotstein C et al. Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient. Am J Med. 1996; 100(Suppl 6A):83S-89S. [IDIS 370422] [PubMed 8678102]

17. Viscoli C. The evolution of the empirical management of fever and neutropenia in cancer patients. J Antimicrob Chemother. 1998; 41(Suppl D):65-80. [IDIS 409104] [PubMed 9688453]

18. Rolston KV. Expanding the options for risk-based therapy in febrile neutropenia. Diagn Microbiol Infect Dis. 1998; 31:411-6. [PubMed 9635917]

19. Bartlett JG, Dowell SF, et al. Practice guidelines for the management of community-acquired pneumonia in adults. Clin Infect Dis. 2000; 31:347-82. [IDIS 454042] [PubMed 10987697]

20. American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001; 163:1730-54. [IDIS 466552] [PubMed 11401897]

21. Bartoloni A, Strohmeyer M, Corti G et al. Multicenter randomized trial comparing meropenem (1.5 g daily) and imipenem/cilastatin (2 g daily) in the hospital treatment of community-acquired pneumonia. Drugs Exp Clin Res. 1999; 25:243-52. [PubMed 10713862]

22. Alvarez Lerma F and the Serious Infection Study Group. Efficacy of meropenem as monotherapy in the treatment of ventilator-associated pneumonia. J Chemother. 2001; 13:70-81. [PubMed 11233804]

23. Mandell LA, Bartlett JG, Dowell SF et al. Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003; 37:1405-33. [IDIS 516151] [PubMed 14614663]

24. Anon. Choice of antibacterial drugs. Med Lett Treat Guid. 2004; 2:18-26.

25. Committee on Infectious Diseases, American Academy of Pediatrics. Red book: 2003 report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003.

26. Anon. Drugs for pneumonia. Med Lett Treat Guid. 2003; 1:83-8.

27. American Thoracic Society and the Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneum

Venlafaxine 75mg Tablets (Actavis UK Ltd)

1. Name Of The Medicinal Product

Venlafaxine 75mg Tablets

2. Qualitative And Quantitative Composition

Each Venlafaxine 75mg Tablet contains 75mg venlafaxine as venlafaxine hydrochloride

Excipients: Lactose monohydrate and Sunset Yellow (E110)

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Film coated tablets

Orange, 10 mm round biconvex, scored film-coated tablets. Marked V4

4. Clinical Particulars

4.1 Therapeutic Indications

Venlafaxine is indicated for the treatment of depressive illness including depression accompanied by anxiety.

Following an initial response Venlafaxine is indicated for the prevention of relapses of the initial episode of depression or for the prevention of the recurrence of new episodes

4.2 Posology And Method Of Administration

Treatment with Venlafaxine should not be started until 14 days after discontinuing a monoamine oxidase inhibitor (MAOI).

Depression:

The recommended dose is 75mg per day given in two divided doses (37.5mg twice daily). Most patients respond to this dose. It is recommended that venlafaxine tablets are taken with food. If, after an adequate trial and evaluation, further clinical improvement is required, the dose may be increased to 150mg per day given in two divided doses (75mg twice daily). There may be an increased risk of side effects at higher doses and dose increments should be made only after a clinical evaluation and after at least 3-4 weeks of therapy (see section 4.4). The lowest effective dose should be maintained.

In more severely depressed or hospitalised patients, and under close supervision of a physician, the daily dose may then be increased by up to 75mg every two or three days until the desired response is achieved. In those more severely depressed and hospitalised patients who require daily doses of 300 mg or more , treatment should be initiated under specialist supervision including shared care arrangements. The maximum recommended dose is 375 mg per day. The dose should then be gradually reduced to the minimal effective dose, consistent with patient response and tolerance.

A limited amount of venlafaxine should be provided to reduce the risk from overdose (see section 4.4).

Usually, the dosage for prevention of relapse or for prevention of recurrence of a new episode is similar to that used during the index episode. Patients should be re-assessed regularly in order to evaluate the benefit of long-term therapy.

Patients with Renal or Hepatic Impairment:

For patients with mild renal impairment (GFR>30ml/minute) or mild hepatic impairment , no change in dosage is necessary.

For patients with moderate renal impairment (GFR 10-30ml/minute) or moderate hepatic impairment , the dose should be reduced by 50%. This dose may be given once daily due to the longer half-lives of venlafaxine and O-desmethylvenlafaxine (ODV) in these patients.

Insufficient data are available to support the use of Venlafaxine in patients with severe renal impairment (GFR <10ml/minute) or severe hepatic impairment.

Elderly Patients:

No adjustment in the usual dosage is recommended for elderly patients. However, as with any therapy, caution should be exercised in treating the elderly (e.g. due to the possibility of renal impairment. See also dosage recommendations for renal impairment). The lowest effective dose should always be used and patients should be carefully monitored when an increase in the dose is required.

Children/Adolescents:

Controlled clinical studies in children and adolescents with Major Depressive Disorder failed to demonstrate efficacy and do not support the use of Venlafaxine in these patients (see sections 4.3 Contra-indications and 4.8 Undesirable Effects).

The efficacy and safety of Venlafaxine for other indications in children and adolescents under the age of 18 have not yet been established.

Maintenance/Continuation/Extended Treatment:

The physician should periodically re-evaluate the usefulness of long-term treatment with Venlafaxine for the individual patient. It is generally agreed that acute episodes of major depression require several months or longer of sustained therapy.

Venlafaxine has been shown to be efficacious during long-term (up to 12 months) treatment.

In clinical trials venlafaxine was demonstrated to be effective for preventing relapse, or recurrence of new episodes, in patients responding to venlafaxine treatment during the index episode.

Discontinuing Venlafaxine:

Discontinuation effects are well known to occur with the abrupt withdrawal of other antidepressants (see section 4.8 Undesirable Effects). Following treatment with daily doses of venlafaxine greater than 75mg for more than one week, it is recommended that when discontinuing treatment the dose should be gradually reduced over at least a further week. If high doses have been used for more than 6 weeks, tapering over at least a 2-week period is recommended.

4.3 Contraindications

• Hypersensitivity to venlafaxine or to any of the excipients.

• Concomitant use of venlafaxine with monoamine oxidase inhibitors (See Interactions with other Medicinal Products and Other Forms of Interactions).

• Venlafaxine should not be used in children and adolescents under the age of 18 years with Major Depressive Disorder (see section 4.4 Special warnings and Precautions for Use)

4.4 Special Warnings And Precautions For Use

•Suicide/suicidal thoughts or clinical worsening: depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events).

This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. Other psychiatric conditions for which venlafaxine is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be comorbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

• Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

• Activation of manic of hypomania has been reported rarely in patients who have received antidepressants, including venlafaxine. As with all antidepressants, Venlafaxine should be used with caution in patients with a history of mania.

• Venlafaxine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease.

Therefore, it should be used with caution in these patients. Clinically significant electrocardiogram findings were observed in 1% of venlafaxine-treated patients compared with 0.2% of placebo-treated patients. Clinically significant changes in PR, QRS or QTc intervals were rarely observed in patients treated with venlafaxine during clinical trials.

• Venlafaxine should be introduced with caution in patients with a history of seizure and should be discontinued in any patient developing a seizure.

• Dose-related increases in blood pressure have been reported particularly in patients receiving daily doses greater than 200mg. Measurement of blood pressure is therefore recommended for patients receiving venlafaxine. The presence of treated hypertension or elevated blood pressure at baseline did not seem to predispose patients to further increases during venlafaxine therapy.

• Due to the possibility of drug abuse with CNS-active drugs, physicians should evaluate patients for a history of drug abuse, and follow such patients closely.

Clinical studies have shown no evidence of drug-seeking behaviour, development of tolerance, or dose escalation over time among patients taking venlafaxine.

• Increases in heart rate can occur, particularly at high doses. In clinical trials the mean heart rate was increased by approximately 4 beats/minute in patients treated with venlafaxine. Caution should be exercised in patients whose underlying conditions might be compromised by increases in heart rate.

• Dosage should be reduced in patients with moderate to severe renal impairment or hepatic cirrhosis (see sections 4.2 and 4.5).

• Postural hypotension has been observed occasionally during venlafaxine treatment. Patients, especially the elderly, should be alerted to the possibility of dizziness or unsteadiness.

• Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.

• Mydriasis has been reported in association with venlafaxine; therefore patients with raised intra-ocular pressure or at a risk of narrow angle glaucoma should be monitored closely.

• There have been reports of cutaneous bleeding abnormalities, such as ecchymosis and purpura, with serotonin-reuptakeinhibitors (SSRIs). Other bleeding manifestations (e.g. gastrointestinal bleeding and mucous membrane bleeding) have been reported. Caution is advised in patients predisposed to bleeding due to factors such as age, underlying medical conditions or concomitant medications.

• Clinically relevant increases in serum cholesterol were recorded in 5.3% of venlafaxine-treated patients and 0.0% of placebo-treated patients treated for at least 3 months in placebo-controlled trials. Measurement of serum cholesterol levels should be considered during long-term treatment.

• The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established. Co-administration of venlafaxine and weight loss agents is not recommended. Venlafaxine is not indicated for weight loss alone or in combination with other products.

• As with SSRIs, venlafaxine should be used with caution in patients already receiving neuroleptics, since symptoms suggestive of Neuroleptic Malignant Syndrome cases have been reported with this combination.

• Use in children and adolescents under 18 years of age. Venlafaxine Tablets should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, longterm safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

• The colouring sunset yellow FCF (E110) may cause allergic reactions.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

MAOIs:

Adverse reactions, some serious, have been reported when venlafaxine therapy is initiated soon after discontinuation of an MAOI, and when an MAOI is initiated soon after discontinuation of venlafaxine. These reactions have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, and hyperthermia with features resembling neuroleptic malignant syndrome, seizures and death. Do not use Venlafaxine in combination with an MAOI, or within at least 14 days of discontinuing MAOI treatment. Allow at least 7 days after stopping Venlafaxine before starting an MAOI (see also Contra-indications).

Serotonergic drugs:

Based on the known mechanism of action of venlafaxine and the potential for serotonergic syndrome, caution is advised when venlafaxine is co-administered with drugs that may affect the serotonergic neurotransmitter systems (such as triptans, SSRIs or lithium).

Lithium:

Venlafaxine had no effect on the pharmacokinetics of lithium.

Imipramine/desipramine:

The metabolism of imipramine and its metabolite 2-OH-imipramine were unaffected by venlafaxine although the total renal clearance of 2-hydroxydesipramine was reduced and desipramine AUC and C_max were increased by approximately 35%.

Haloperidol:

In a pharmacokinetic study co-administration of venlafaxine with a single 2mg oral dose of haloperidol resulted in a 42% decrease in renal clearance, a 70% increase in AUC and an 88% increase in C_max for haloperidol. The elimination half-life remained unchanged.

Diazepam:

The pharmacokinetic profiles of venlafaxine and ODV were not significantly altered by the administration of diazepam. Venlafaxine has no effect on the pharmacokinetic profile of diazepam or on the psychomotor or psychometric effects induced by diazepam.

Clozapine:

Increased levels of clozapine, that were temporally associated with adverse events, including seizures, have been reported following the addition of venlafaxine.

Alcohol:

Venlafaxine has been shown not to increase the impairment of mental or motor skills caused by ethanol. However, as with all CNS-active drugs, patients should be advised to avoid alcohol consumption while taking Venlafaxine.

ECT:

There is little clinical experience of the concurrent use of venlafaxine with ECT. As prolonged seizure activity has been reported with concomitant SSRI antidepressants, caution is advised.

Drugs metabolised by Cytochrome P450 isoenzymes:

Venlafaxine is primarily metabolised to its equally active metabolite, ODV, by the cytochrome P450 enzyme CYP2D6. However, unlike many other antidepressants, no dosage adjustment is necessary when Venlafaxine is administered concomitantly with drugs which inhibit CYP2D6, or when used in patients who are poor CYP2D6 metabolisers, since the total concentration of active compound (venlafaxine and ODV) is not affected.

The major elimination pathways for venlafaxine are through CYP2D6 and CYP3A4.

Therefore, caution should be used with concomitant intake of drugs which inhibit both of these enzymes. Such interactions have not been studied to date.

Studies indicate that venlafaxine is a relatively weak inhibitor of CYP2D6.

Venlafaxine did not inhibit CYP1A2, CYP2C9 or CYP3A4. This was confirmed by in vivo studies with the following drugs: alprazolam (CYP3A4), caffeine (CYP1A2), carbamazepine (CYP3A4) and diazepam (CYP3A4 and CYP2C19).

Cimetidine:

Cimetidine inhibited the first-pass metabolism of venlafaxine but had no significant effect on the formation or elimination of ODV, which is present in much greater quantities in the systemic circulation. No dosage adjustment therefore seems necessary when Venlafaxine is co-administered with cimetidine. For elderly patients, or patients with hepatic dysfunction the interaction could potentially be more pronounced, and for such patients clinical monitoring is indicated when Venlafaxine is administered with cimetidine.

Warfarin:

Potentiation of anticoagulant effects including increases in PT or INR have been reported in patients taking warfarin following the addition of venlafaxine.

Indinavir:

A pharmacokinetic study with indinavir has shown a 28% decrease in AUC and a 36% decrease in C_max for indinavir. Indinavir did not affect the pharmacokinetics of venlafaxine and ODV. The clinical significance of this interaction is not known

4.6 Pregnancy And Lactation

There are no adequate data from the use of venlafaxine in pregnant women. Animal studies are insufficient with respect to effects on pregnancy. The potential risk for humans is unknown. Venlafaxine should not be used during pregnancy unless clearly necessary. If venlafaxine is used until or shortly before birth, discontinuation effects in the newborn should be considered.

Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated an association of PPHN to SNRI treatment, this potential risk cannot be ruled out with venlafaxine taking into account the related mechanism of action (inhibition of the re-uptake of serotonin).

There is evidence to suggest that venlafaxine and its metabolite, ODV, transfers into breast milk. Therefore a decision should be made whether or not to breast-feed or to discontinue venlafaxine.

4.7 Effects On Ability To Drive And Use Machines

Although venlafaxine has been shown not to affect psychomotor, cognitive, or complex behaviour performance in healthy volunteers, any psychoactive drug may impair judgement, thinking or motor skills. Therefore patients should be cautioned about their ability to drive or operate hazardous machinery.

4.8 Undesirable Effects

See also Special Warnings and Precautions for Use.

The most commonly observed adverse events associated with the use of venlafaxine in clinical trials, and which occurred more frequently than those which were associated with placebo were: nausea, insomnia, dry mouth, somnolence, dizziness, constipation, sweating, nervousness, asthenia and abnormal ejaculation/orgasm.

The occurrence of most of these adverse events was dose-related, and the majority of them decreased in intensity and frequency over time. They generally did not lead to cessation of treatment.

Adverse events observed with venlafaxine, from both spontaneous and clinical trials reports, are classified in body systems and listed below as very common (>1/10); common (<1/10 and >1/100); uncommon (<1/100 and >1/1000); rare (<1/1000); very rare >1/10,000):

Blood and lymphatic system disorders

Uncommon: ecchymosis, mucous membrane bleeding;

Rare: prolonged bleeding time, haemorrhage, thrombocytopenia;

Very rare: blood dyscrasias (including agranulocytosis, aplastic anaemia, neutropenia and pancytopenia).

Cardiovascular and vascular disorders (see Special Warnings and Precautions for Use)

Common: hypertension, palpitation, vasodilatation;

Uncommon: postural hypotension, syncope, arrhythmias (including tachycardia);

Very rare: Torsade de Pointes, QT prolongation, ventricular tachycardia, ventricular fibrillation.

Gastrointestinal disorders

Very common: constipation, nausea (see below);

Common: anorexia, diarrhoea, dyspepsia, vomiting;

Uncommon: bruxism;

Rare: gastrointestinal bleeding;

Very rare: pancreatitis.

General disorders

Very common: asthenia, headache;

Common: abdominal pain, chills, pyrexia;

Rare: anaphylaxis

Metabolic and nutritional disorders

Common: serum cholesterol increased (particularly with prolonged administration and possibly with higher doses (see Special Warnings and Precautions for Use),weight gain or loss;

Uncommon: hyponatraemia including SIADH (see Special Warnings and Precautions for Use), increased liver enzymes (see below);

Rare: hepatitis;

Very rare: prolactin increased.

Musculo-skeletal disorders

Common: arthralgia, myalgia;

Uncommon: muscle spasm;

Very rare: rhabdomyolysis.

Neurological disorders

Very common: dizziness, dry mouth, insomnia, nervousness, somnolence;

Common: abnormal dreams, agitation, anxiety, confusion, hypertonia, paraesthesia, tremor;

Uncommon: hallucinations, myoclonus;

Rare: ataxia and disorders of balance and co-ordination, speech disorders including dysarthria, extrapyramidal disorders including dyskinesia, dystonia, mania or hypomania (see Special Warnings and Precautions for Use), neuroleptic malignant syndrome-like effects, seizures (see Special Warnings and Precautions for Use), serotonergic syndrome;

Very rare:delirium.

Renal and urinary disorders

Common: urinary frequency;

Uncommon: urinary retention.

Reproductive and breast disorders

Very common: abnormal ejaculation/orgasm;

Common: decreased libido, impotence, menstrual cycle disorders;

Rare: galactorrhoea.

Respiratory system disorders

Common: dyspnoea, yawning;

Very rare: pulmonary eosinophilia.

Skin and subcutaneous tissue disorders

Very common: sweating (including night sweats);

Common: pruritus, rash;

Uncommon: angioedema, maculopapular eruptions, urticaria, photosensitivity reactions, alopecia;

Rare: erythema multiforme, Stevens Johnson syndrome.

Special senses

Common: abnormal vision/accommodation, mydriasis, tinnitus;

Uncommon: altered taste sensation.

Adverse events from paediatric clinical trials:

In paediatric MDD clinical trials the following adverse events were reported at a frequency of at least 2% of patients and occurred at a rate of at least twice that of placebo: abdominal pain, chest pain, tachycardia, anorexia, weight loss, constipation, dyspepsia, nausea, ecchymosis, epistaxis, mydriasis, myalgia, dizziness, emotional lability, tremor, hostility and suicidal ideation.

Special Notes:

Nausea is most common at the start of treatment with the incidence decreasing over the first few weeks. The nausea experienced with Venlafaxine is usually mild to moderate, and infrequently results in vomiting or withdrawal. The incidence increases with higher doses particularly when the dose is increased rapidly.

Reversible increases in liver enzymes are seen in a small number of patients treated with venlafaxine. These generally resolve on discontinuation of therapy.

Withdrawal reactions reported on abrupt cessation, dose reduction or tapering of venlafaxine include fatigue, somnolence, headache, nausea or vomiting, loss of appetite, dizziness, light-headedness, anorexia, dry mouth,diarrhoea, insomnia, nightmares, nervousness, agitation, anxiety, confusion, hypomania, weakness, decreased co-ordination, tinnitus, tremor, convulsions, paraesthesia, sweating and vertigo. The majority of symptoms experienced on withdrawal of Venlafaxine are non-serious and self-limiting (see also Posology and Administration).

Cases of suicidal ideation and suicidal behaviours have been reported during mirtazapine therapy or early after treatment discontinuation (see section 4.4).

4.9 Overdose

Electrocardiogram changes (e.g. prolongation of QT interval, bundle branch block, QRS prolongation), sinus and ventricular tachycardia, bradycardia and seizures, hypotension and changes in level of consciousness have been reported in association with overdosage of venlafaxine usually when in combination with alcohol and/or other CNS drugs

There have been reports of fatalities in patients taking overdoses of Venlafaxine, predominantly in combination with alcohol and/or other CNS drugs.

Management of Overdosage - Ensure an adequate airway, oxygenation and ventilation. Monitoring of cardiac rhythm and vital signs is recommended as are general supportive and symptomatic measures. Use of activated charcoal or gastric lavage should be considered. Induction of emesis is not recommended. No specific antidotes for venlafaxine are known.

The haemodialysis clearance of venlafaxine and its main active metabolite are low, therefore, they are not considered dialysable.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Other antidepressants, ATC code: N06AX16

Venlafaxine is a structurally novel antidepressant which is chemically unrelated to tricyclic, tetracyclic, or other available antidepressant agents. It is a racemate with two active enantiomers.

The mechanism of Venlafaxine's antidepressant action in humans is believed to be associated with its potentiation of neurotransmitter activity in the central nervous system. Preclinical studies have shown that venlafaxine and its major metabolite, Odesmethylvenlafaxine, are potent neuronal serotonin and noradrenaline re-uptake inhibitors (SNRI) and weak inhibitors of dopamine reuptake. In addition, venlafaxine and O-desmethylvenlafaxine reduce β-adrenergic responsiveness in animals after both acute (single dose) and chronic administration. Venlafaxine and its major metabolite appear to be equipotent with respect to their overall action on neurotransmitter reuptake.

Venlafaxine has virtually no affinity for rat brain muscarinic, histaminergic or adrenergic receptors in vitro. Pharmacologic activity at these receptors may be related to various side effects seen with other antidepressant drugs, such as anticholinergic, sedative and cardiovascular effects

5.2 Pharmacokinetic Properties

Venlafaxine is well absorbed and undergoes extensive first-pass metabolism. Mean peak plasma concentrations of venlafaxine range from approximately 33 to 172ng/ml after 25 to 150mg single doses, and are reached in approximately 2.4 hours.

Venlafaxine is extensively metabolised in the liver. O-desmethylvenlafaxine is the major active metabolite of venlafaxine. The mean disposition half-life of venlafaxine and O-desmethylvenlafaxine is approximately 5 and 11 hours, respectively. Mean peak O-desmethylvenlafaxine plasma concentrations range from approximately 61 to 325ng/ml and are reached in approximately 4.3 hours. Plasma concentrations of venlafaxine and O-desmethylvenlafaxine generally correlated well with dose levels.

Venlafaxine and O-desmethylvenlafaxine are 27% and 30% bound to plasma proteins respectively. O-desmethylvenlafaxine, other minor venlafaxine metabolites, and nonmetabolised venlafaxine are excreted primarily through the kidneys.

5.3 Preclinical Safety Data

None

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet Core:

Lactose monohydrate

Microcrystalline cellulose

Croscarmellose sodium

Povidone K30

Magnesium stearate

Tablet Coating:

Opadry 03B23319 Orange containing;

Hypromellose 6 cP

Titanium dioxide (E171)

Macrogol / PEG 400

Sunset yellow FCF lake (E110)

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

48 months

6.4 Special Precautions For Storage

No special precautions for storage

6.5 Nature And Contents Of Container

Al/PVC Blister

HDPE Container with LDPE screw Cap

14, 28, 30, 42, 56 tablets

* Not all pack sizes may be marketed

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Actavis Group PTC ehf,

Reykjavikurvegur 76-78,

220 Hafnarfjordur,

Iceland

8. Marketing Authorisation Number(S)

PL30306/0218

9. Date Of First Authorisation/Renewal Of The Authorisation

17/11/2008

10. Date Of Revision Of The Text

18.02.2011

11 DOSIMETRY

(IF APPLICABLE)

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS

(IF APPLICABLE)