Lexiva

Generic Name: Fosamprenavir Calcium
Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: C-[(3S)-tetrahydro-3-furanyl] ester [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-1-(phenylmethyl)-2-(phosphonooxy)propyl] carbamic acid disodium salt
Molecular Formula: C₂₅H₃₄N₃Na₂O₉PS
CAS Number: 226700-80-7

Introduction

Antiretroviral; HIV protease inhibitor (PI).¹

Uses for Lexiva

Treatment of HIV Infection

Treatment of HIV infection in conjunction with other antiretrovirals.¹

Usually used in PI-based regimens that include a PI and 2 nucleoside reverse transcriptase inhibitors (NRTIs).^{1 3 4}

For initial treatment in HIV-infected adults and adolescents who are treatment-naive, some experts state that ritonavir-boosted fosamprenavir (given once or twice daily) is an alternative (not a preferred) PI for use in PI-based regimens in conjunction with 2 NRTIs.³ These experts state that fosamprenavir (without low-dose ritonavir) should be used with caution in PI-based regimens since such regimens may be associated with virologic failure and result in resistance mutations conferring resistance to other PIs (e.g., darunavir).³

When a PI-based regimen is used in children, some experts state that ritonavir-boosted fosamprenavir (given twice daily) in conjunction with 2 NRTIs is an alternative (not a preferred) regimen for initial treatment in treatment-naive children ≥6 years of age.⁴ These experts state that fosamprenavir (without low-dose ritonavir) in conjunction with 2 NRTIs can be considered for initial treatment in treatment-naive children ≥2 years of age in special circumstances when preferred or alternative PI-based regimens cannot be used.⁴

When selecting fosamprenavir for use in multiple-drug regimens, consider that data are insufficient to date to determine whether a regimen that includes ritonavir-boosted fosamprenavir is as effective as a regimen that includes the fixed-combination of lopinavir and ritonavir in adults who previously received PIs and that once-daily ritonavir-boosted fosamprenavir is not recommended in PI-experienced adults or in any pediatric patient.¹

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with a risk for transmission of the virus.¹¹ Used in conjunction with other antiretrovirals.¹¹

Postexposure prophylaxis of HIV infection† in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.¹⁰ Used in conjunction with other antiretrovirals.¹⁰

Lexiva Dosage and Administration

Administration

Oral Administration

Tablets

Administer orally without regard to meals.¹

Suspension

Administer with food in children.¹ Administer on an empty stomach in adults.¹

If vomiting occurs soon after a dose (within 30 minutes), repeat dose.¹

Shake well prior to each dose.¹

The taste can be improved by refrigerating the suspension.¹

Dosage

Available as fosamprenavir calcium; dosage expressed in terms of fosamprenavir.¹

Must be given in conjunction with other antiretrovirals.¹ If used with both ritonavir and efavirenz, dosage adjustment may be needed depending on frequency of administration.¹ (See Specific Drugs under Interactions.)

Pediatric Patients

Oral suspension is the preferred dosage form for young children because of suitability for providing the calculated dosage.¹

Children ≥2 years of age: Dosage is based on weight.¹ Do not exceed adult dosage.¹

Once-daily regimen (with or without low-dose ritonavir) is not recommended in pediatric patients.¹

Treatment of HIV Infection

Treatment-naive Pediatric Patients

Oral

Children 2–5 years of age (oral suspension): 30 mg/kg twice daily (without ritonavir).¹

Children ≥6 years of age (oral suspension): 30 mg/kg twice daily (without ritonavir).¹ If ritonavir-boosted regimen used, 18 mg/kg twice daily boosted with low-dose ritonavir (3 mg/kg twice daily).¹

Children weighing ≥39 kg (tablets): 700 mg twice daily boosted with low-dose ritonavir (100 mg twice daily).^{1 4}

Children weighing ≥47 kg (tablets): 1.4 g twice daily (without ritonavir).^{1 4}

Treatment-experienced Pediatric Patients

Oral

Children 2–5 years of age: Data are insufficient for dosage recommendations.¹

Children ≥6 years of age (oral suspension): 18 mg/kg twice daily boosted with low-dose ritonavir (3 mg/kg twice daily).¹

Children weighing ≥39 kg (tablets): 700 mg twice daily boosted with low-dose ritonavir (100 mg twice daily).^{1 4}

Adults

Treatment of HIV Infection

Treatment-naive Adults

Oral

1.4 g twice daily (without ritonavir).¹

1.4 g once daily boosted with low-dose ritonavir (100 or 200 mg once daily) or 700 mg twice daily boosted with low-dose ritonavir (100 mg twice daily).¹

PI-experienced Adults

Oral

700 mg twice daily boosted with low-dose ritonavir (100 mg twice daily).¹ A once-daily regimen of ritonavir-boosted fosamprenavir not recommended in treatment-experienced patients.¹

Postexposure Prophylaxis of HIV†

Occupational Exposure†

Oral

1.4 g twice daily (without ritonavir).¹¹ Alternatively, 1.4 g once daily with low-dose ritonavir (200 mg once daily) or 700 mg twice daily with low-dose ritonavir (100 mg twice daily).¹¹

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.¹¹

Nonoccupational Exposure†

Oral

1.4 g twice daily (without ritonavir).¹⁰

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.¹⁰

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Maximum 1.4 g twice daily (without ritonavir) or 700 mg twice daily boosted with ritonavir (100 mg twice daily).¹ Do not exceed adult dosage.¹

Adults

Treatment of HIV Infection

Treatment-naive Adults

Oral

Maximum 1.4 g once daily boosted with ritonavir (200 mg once daily) or 700 mg twice daily boosted with ritonavir (100 mg twice daily).¹ Higher than recommended dosages of fosamprenavir and/or ritonavir associated with increased serum transaminase concentrations; higher dosages not recommended.¹

PI-experienced Adults

Oral

Maximum 700 mg twice daily boosted with ritonavir (100 mg twice daily).¹ Higher than recommended dosages of fosamprenavir and/or ritonavir associated with increased serum transaminase concentrations; higher dosages not recommended.¹

Special Populations

Hepatic Impairment

Mild hepatic impairment (Child-Pugh score 5–6): Use with caution.¹ If fosamprenavir (without ritonavir) is used, treatment-naive adults should receive fosamprenavir 700 mg twice daily.¹ If ritonavir-boosted fosamprenavir is used, treatment-naive and treatment-experienced adults should receive fosamprenavir 700 mg twice daily with low-dose ritonavir (100 mg once daily).¹

Moderate hepatic impairment (Child-Pugh score 7–9): Use with caution.¹ If fosamprenavir (without ritonavir) is used, treatment-naive adults should receive fosamprenavir 700 mg twice daily.¹ If ritonavir-boosted fosamprenavir is used, treatment-naive and treatment-experienced adults should receive fosamprenavir 450 mg twice daily with low-dose ritonavir (100 mg once daily).¹

Severe hepatic impairment (Child-Pugh score 10–15): Use with caution.¹ If fosamprenavir (without ritonavir) is used, treatment-naive adults should receive fosamprenavir 350 mg twice daily.¹ If ritonavir-boosted fosamprenavir is used, treatment-naive and treatment-experienced adults should receive fosamprenavir 300 mg twice daily with low-dose ritonavir (100 mg once daily).¹

Renal Impairment

Dosage adjustment not necessary.³

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Cautions for Lexiva

Contraindications

• 
  

  Known hypersensitivity to fosamprenavir, amprenavir (no longer commercially available in the US), or any ingredient in the formulation.¹

  
  


• 
  

  Concomitant use with drugs highly dependent on CYP3A4 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (i.e., rifampin, ergot alkaloids, cisapride, St. John’s wort, lovastatin, simvastatin, pimozide, delavirdine, midazolam, triazolam).¹ (See Specific Drugs under Interactions.)

  
  


• 
  

  Concomitant use of a ritonavir-boosted fosamprenavir regimen and flecainide or propafenone.¹ (See Antiarrhythmic Agents under Interactions.)

  
  

Warnings/Precautions

Sensitivity Reactions

Dermatologic and Hypersensitivity Reactions

Rash (usually maculopapular and of mild to moderate intensity, with or without pruritus) reported.¹ Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, reported rarely.¹

Discontinue if severe or life-threatening rash or moderate rash accompanied by systemic symptoms occurs.¹

Sulfonamide Sensitivity

Because fosamprenavir contains a sulfonamide moiety, use with caution in patients with known sulfonamide allergy.¹

Potential for cross-sensitivity between sulfonamide drugs and fosamprenavir unknown.¹

Interactions

When a ritonavir-boosted fosamprenavir regimen is used, the usual cautions, precautions, and contrainfdications associated with ritonavir should be considered.¹

Serious and/or life-threatening drug interactions or loss of virologic effect can occur with some drugs.¹ (See Contraindications and Specific Drugs under Interactions.)

Hepatic Effects

Patients with coexisting hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or marked elevations in transaminase concentrations prior to fosamprenavir therapy may be at increased risk for developing transaminase elevations.¹

Perform appropriate laboratory tests to evaluate hepatic function prior to initiating fosamprenavir therapy and monitor patients closely during treatment.¹ (See Hepatic Impairment under Cautions.)

Use of fosamprenavir with ritonavir at higher than recommended dosages may result in elevated transaminase concentrations.¹

Hyperglycemic and Diabetogenic Effects

Hyperglycemia (potentially persistent), new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred.¹

Monitor blood glucose and initiate or adjust dosage of insulin or oral hypoglycemic agents as needed.¹

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]);¹ this may necessitate further evaluation and treatment.¹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance.¹ Evaluate patients for physical signs of fat redistribution.¹⁹

Lipid Effects

Increases in triglyceride and cholesterol concentrations have occurred with ritonavir-boosted fosamprenavir.^{1 19 21} HIV infection itself is associated with lipid disorders.¹⁹

Determine serum triglyceride and cholesterol concentrations prior to initiating fosamprenavir and periodically monitor during therapy; manage lipid disorders as clinically appropriate.^{1 19} (See HMG-CoA Reductase Inhibitors under Interactions.)

Hematologic Effects

Neutropenia has been reported with fosamprenavir;¹ acute hemolytic anemia has been reported in at least one patient who received amprenavir (no longer commercially available in the US).¹

Hemophilia A and B

Spontaneous bleeding reported with PIs;¹ causal relationship not established.¹

Use with caution in patients with hemophilia A or B.^{1 3} Increased hemostatic therapy (e.g., antihemophilic factor) may be needed.¹

Nephrolithiasis

Nephrolithiasis reported in postmarketing surveillance.^{1 19} If signs or symptoms of nephrolithiasis occur, consider temporarily interrupting or discontinuing fosamprenavir.^{1 19}

HIV Resistance

Possible amprenavir resistance in patients treated with fosamprenavir.¹ The possible effect of fosamprenavir therapy on subsequent therapy with other PIs unknown.¹

Cardiovascular Effects

Postmarketing reports of myocardial infarction in patients receiving fosamprenavir.¹ Possible association between cumulative exposure to fosamprenavir/amprenavir and increased risk of myocardial infarction.¹⁹ Higher relative risk of myocardial infarction reported with PIs compared with other antiretroviral drug classes, possibly due to ability of PIs to elevate serum lipid concentrations.^{19 20} HIV infection itself is associated with ischemic heart disease.¹⁹

Monitor modifiable risk factors for cardiovascular disease (e.g., hypertension, diabetes, smoking) and manage as clinically appropriate.¹⁹ Individualize treatment, carefully considering risks and benefits of continued treatment.¹⁹

Specific Populations

Pregnancy

Category C.¹

Antiretroviral Pregnancy Registry at 800-258-4263.¹

Some experts state safety and pharmacokinetic data insufficient to recommend routine use of fosamprenavir in pregnant women, but ritonavir-boosted fosamprenavir may be considered if other antiretroviral agents are not tolerated.¹²

Lactation

Distributed into milk in rats;¹ not known whether distributed into human milk.¹

Instruct HIV-infected women not to breast-feed^{1 12} because of risk of HIV transmission and risk of adverse effects in the infant.^{1 2}

Pediatric Use

Safety and efficacy not established in children <2 years of age.¹

Once-daily regimen not recommended in pediatric patients.¹

Adverse effects in children 2–18 years of age similar to those reported in adults; vomiting reported more frequently in pediatric patients than in adults.¹

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently from younger adults.¹

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Hepatic Impairment

Clearance decreased.¹

Use with caution; assess hepatic function prior to and periodically during therapy.¹

Dosage adjustments necessary in patients with hepatic impairment (Child-Pugh score 5–15).¹ (See Hepatic Impairment under Dosage and Administration.)

Increased risk for further elevations in hepatic enzyme concentrations in patients with chronic HBV or HCV infection and those with marked increases in AST or ALT concentrations prior to fosamprenavir therapy.¹

Common Adverse Effects

Diarrhea, nausea, vomiting, headache, rash.¹

Interactions for Lexiva

Amprenavir (active metabolite of fosamprenavir) is metabolized by CYP3A4.¹

Amprenavir inhibits CYP3A4 and also may induce CYP3A4.¹

Amprenavir does not inhibit CYP2D6, 1A2, 2C9, 2C19, or P2E1¹ or uridine glucuronosyltransferase (UDPGT).¹

Some interaction studies have been performed using fosamprenavir.¹ These studies may not predict magnitude of interaction with ritonavir-boosted fosamprenavir.¹

Since fosamprenavir is metabolized to amprenavir, interactions reported with amprenavir (no longer commercially available in the US) also apply to fosamprenavir.¹

When fosamprenavir is used with low-dose ritonavir, consider interactions reported with low-dose ritonavir.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors or substrates of CYP3A4 with possible alteration in metabolism of amprenavir and/or the other drug.¹

Specific Drugs

Drug	Interaction	Comments
Abacavir	Studies using amprenavir indicate pharmacokinetic interaction unlikely1 In vitro evidence of synergistic antiretroviral effects1
Alfuzosin	Potential for increased alfuzosin concentrations that could result in hypotension1	Concomitant use with fosamprenavir (with or without low-dose ritonavir) is contraindicated1
Antacids	Decreased amprenavir concentrations and AUC1	Not considered clinically important; manufacturer states there are no restrictions for concomitant use of fosamprenavir and antacids2
Antiarrhythmic agents (amiodarone, flecainide, systemic lidocaine, propafenone, quinidine)	Possible increased antiarrhythmic agent concentrations1 Potential for serious or life-threatening effects (e.g., cardiac arrhythmias) if ritonavir-boosted fosamprenavir used in patients receiving flecainide or propafenone1 Potential for serious or life-threatening effects (e.g., cardiac arrhythmias) if fosamprenavir used in conjunction with amiodarone, systemic lidocaine, or quinidine1	In patients receiving ritonavir-boosted fosamprenavir, concomitant use with flecainide or propafenone contraindicated1 Caution if fosamprenavir used concomitantly with amiodarone, systemic lidocaine, or quinidine; antiarrhythmic concentration monitoring recommended1
Anticoagulants, oral	Warfarin concentrations may be affected1	Monitor INR1
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Fosamprenavir: Possible decreased amprenavir concentrations when used with carbamazepine, phenobarbital, or phenytoin;1 possible decreased antiretroviral efficacy1 Ritonavir-boosted fosamprenavir and phenytoin: Increased concentrations of amprenavir and decreased concentrations of phenytoin1	Fosamprenavir (without low-dose ritonavir): Use concomitantly with caution1 Ritonavir-boosted fosamprenavir: Monitor phenytoin concentrations; increase phenytoin dosage if indicated; no dosage adjustment recommended for ritonavir-boosted fosamprenavir 1
Antidepressants, tricyclics	Possible increased concentrations of tricyclic antidepressants (amitriptyline, imipramine) 1	Monitor tricyclic antidepressant concentrations1
Antifungals, azoles (itraconazole, ketoconazole, voriconazole)	Itraconazole: Possible increased antifungal and amprenavir concentrations1 3 Ketoconazole: Possible increased ketoconazole concentrations with fosamprenavir (with or without low-dose ritonavir)1 3 Voriconazole: Although specific data not available on interaction with ritonavir-boosted fosamprenavir, studies using low-dose ritonavir and voriconazole indicate decreased voriconazole concentrations;3 9 in addition, fosamprenavir (without ritonavir) possibly may result in increased concentrations of both drugs3	Itraconazole: In patients receiving fosamprenavir (with or without ritonavir), consider monitoring itraconazole concentrations to guide dosage adjustments; in those receiving fosamprenavir (without ritonavir), may need to reduce antifungal dosage in those receiving >400 mg of itraconazole daily;1 3 in those receiving ritonavir-boosted fosamprenavir, itraconazole dosage >200 mg daily not recommended unless plasma concentrations are monitored1 3 Ketoconazole: In patients receiving fosamprenavir (without ritonavir), may need to reduce antifungal dosage in those receiving >400 mg of ketoconazole daily;1 in those receiving ritonavir-boosted fosamprenavir, use caution and ketoconazole dosage >200 mg daily not recommended1 Voriconazole: Concomitant ritonavir-boosted fosamprenavir not recommended unless potential benefits outweigh risks; consider monitoring voriconazole plasma concentrations;3 9 if fosamprenavir (without ritonavir) is used, monitor frequently for toxicity3 9
Antimycobacterials (rifabutin, rifampin, rifapentine)	Rifabutin: 150 mg every other day with ritonavir-boosted fosamprenavir results in increased amprenavir concentrations and increased rifabutin metabolite concentrations compared with rifabutin 300 mg daily alone1 Rifampin: Studies using amprenavir indicate decreased amprenavir concentrations;1 possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1	Rifabutin: If fosamprenavir (without ritonavir) used with rifabutin, reduce rifabutin dosage by at least 50%1 (150 mg once daily or 300 mg 3 times weekly has been suggested);3 if ritonavir-boosted fosamprenavir used with rifabutin, reduce rifabutin dosage by at least 75% (maximum dosage of 150 mg once every other day or 3 times weekly);1 3 monitor for neutropenia by performing CBCs weekly and as clinically indicated1 Rifampin: Concomitant use contraindicated1 Rifapentine: Concomitant use not recommended3
Atazanavir	Decreased atazanavir concentrations; no change in amprenavir concentrations1	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 3
Benzodiazepines (alprazolam, clorazepate, diazepam, flurazepam, midazolam, triazolam)	Midazolam or triazolam: Possible increased concentrations of midazolam or triazolam; potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1 Other benzodiazepines: Possible increased concentrations of alprazolam, clorazepate, diazepam, flurazepam1	Midazolam or triazolam: Manufacturer of fosamprenavir states that concomitant use is contraindicated;1 some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation3 Other benzodiazepines: Clinical importance of pharmacokinetic interaction unknown; a decrease in benzodiazepine dosage may be needed1
Bosentan	Increased bosentan concentrations1	In patients already receiving fosamprenavir (with or without low-dose ritonavir) for ≥10 days, initiate bosentan using a dosage of 62.5 mg once daily or every other day based on individual tolerability1 3 In patients already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating fosamprenavir (with or without low-dose ritonavir); after ≥10 days of fosamprenavir, resume bosentan using a dosage of 62.5 mg once daily or every other day based on individual tolerability1 3
Calcium-channel blocking agents (diltiazem, felodipine, nifedipine, nicardipine, nimodipine, verapamil, amlodipine, nisoldipine, isradipine)	Possible increased concentrations of calcium-channel blocking agent1	Use concomitantly with caution; clinical monitoring recommended1
Cisapride	Possible increased cisapride concentrations; potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1	Concomitant use contraindicated1
Clarithromycin	Studies using amprenavir indicate increased amprenavir concentrations and AUC1	Not considered clinically important;2 dosage adjustment not needed3
Colchicine	Increased colchicine concentrations1	Patients with renal or hepatic impairment: Avoid concomitant use of colchicine and ritonavir-boosted fosamprenavir1 Colchicine for treatment of gout flares: In those receiving ritonavir-boosted fosamprenavir, use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later and repeat dose no earlier than 3 days later; in those receiving fosamprenavir (without ritonavir), use initial colchicine dose of 1.2 mg and repeat dose no earlier than 3 days later1 Colchicine for prophylaxis of gout flares: In those receiving ritonavir-boosted fosamprenavir, decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 once daily;1 in those receiving fosamprenavir (without ritonavir), decrease colchicine dosage to 0.3 mg twice daily or 0.6 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once daily in those originally receiving 0.6 mg once daily1 Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving ritonavir-boosted fosamprenavir, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily);1 in those receiving fosamprenavir (without ritonavir), use maximum colchicine dosage of 1.2 mg daily (may be given as 0.6 mg twice daily)1
Corticosteroids (dexamethasone, fluticasone)	Fluticasone nasal spray/oral inhalation: Increased fluticasone concentrations with fosamprenavir (with or without low-dose ritonavir) resulting in decreased cortisol concentrations1 Dexamethasone: Possible decreased amprenavir concentrations; possible decreased antiretroviral efficacy1	Fluticasone nasal spray/oral inhalation: Consider alternative in patients receiving fosamprenavir (without ritonavir), especially when long-term corticosteroid therapy is anticipated; concomitant use with ritonavir-boosted fosamprenavir not recommended unless potential benefits outweigh risk of systemic corticosteroid adverse effects1 Dexamethasone: Use concomitantly with caution1
Darunavir	Data not available regarding concomitant use of darunavir and fosamprenavir (with or without low-dose ritonavir)3
Delavirdine	Studies using amprenavir indicate possible increased amprenavir concentrations and AUC and possible decreased delavirdine plasma concentrations and AUC;1 possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1 In vitro evidence of synergistic antiretroviral effects1	Concomitant use contraindicated1
Didanosine	In vitro evidence of synergistic antiretroviral effects1
Efavirenz	Substantially decreased amprenavir concentrations if used with fosamprenavir;1 additional pharmacokinetic interactions if ritonavir-boosted fosamprenavir used1 In vitro evidence of synergistic antiretroviral effects1	If fosamprenavir used with efavirenz, boosting with ritonavir required 1 2 3 When efavirenz used with ritonavir-boosted fosamprenavir, fosamprenavir 1.4 g once daily with ritonavir 300 mg once daily or fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily recommended1 3
Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)	Possible increased concentrations of ergot alkaloids and potential for serious and/or life-threatening effects such as ergot toxicity (peripheral vasospasm and ischemia of the extremities and other tissues)1	Concomitant use contraindicated1 If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving fosamprenavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible12
Estrogens or Progestins	Hormonal contraceptive containing ethinyl estradiol 35 mcg with norethindrone 0.5 mg per tablet: Decreased ethinyl estradiol and norethindrone concentrations with ritonavir-boosted fosamprenavir; clinically important increase in serum transaminase concentrations1 Hormonal contraceptives: Possible loss of virologic response if used with fosamprenavir (without ritonavir)1 Hormone replacement therapy: Possible increase in serum transaminase concentrations with ritonavir-boosted fosamprenavir1	Hormonal contraceptives: Concomitant use not recommended;3 use alternative nonhormonal (e.g., barrier) contraceptives1 3
Etravirine	Fosamprenavir or ritonavir-boosted fosamprenavir: Substantially increased amprenavir concentrations17	Do not administer concomitantly;3 17 appropriate dosages for concomitant use with respect to safety and efficacy not established3 17
Histamine H2-receptor antagonists (cimetidine, famotidine, nizatidine, ranitidine)	Decreased amprenavir plasma concentrations and AUC;1 possible decreased antiretroviral efficacy1	Use concomitantly with caution;1 administer at different times;3 consider using ritonavir-boosted fosamprenavir3
HMG-CoA reductase inhibitors (statins)	Possible decreased clearance and increased concentrations of some HMG-CoA reductase inhibitors (e.g., atorvastatin, rosuvastatin) with potential for increased risk of myopathy (including rhabdomyolysis)1	Lovastatin or simvastatin: Concomitant use with fosamprenavir contraindicated1 Atorvastatin or rosuvastatin: Use lowest possible dosage of the HMG-CoA reductase inhibitor with careful monitoring1 Consider using HMG-CoA reductase inhibitors with low potential for interaction (e.g., fluvastatin, pravastatin)1
Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)	Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1	Monitor concentrations of the immunosuppressive agent1
Indinavir	Studies using amprenavir indicate possible increased amprenavir plasma concentrations and AUC and decreased indinavir concentrations;1 concomitant use of ritonavir-boosted fosamprenavir not evaluated1 In vitro evidence of additive antiretroviral effects1	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 3
Lamivudine	Studies using amprenavir indicate no evidence of pharmacokinetic interaction1 In vitro evidence of synergistic antiretroviral effects1
Lopinavir	Fosamprenavir: Decreased amprenavir concentrations; no change in lopinavir concentrations 1 Ritonavir-boosted fosamprenavir: Decreased amprenavir concentrations; altered lopinavir concentrations1 Increased incidence of adverse effects reported1 In vitro evidence of additive antiretroviral effects1	Appropriate dosages for concomitant use with respect to safety and efficacy not established;1 3 concomitant use not recommended3
Maraviroc	Possible increased concentrations of maraviroc3	Recommended dosage of maraviroc is 150 mg twice daily3
Methadone	Decreased methadone concentrations1	Not considered clinically important; monitor for symptoms of opiate withdrawal and adjust methadone dosage if needed1 3
Nelfinavir	Studies using amprenavir indicate possible alterations in amprenavir and nelfinavir pharmacokinetics;1 concomitant use of ritonavir-boosted fosamprenavir and nelfinavir not evaluated1 In vitro evidence of additive antiretroviral effects1	Appropriate dosages for concomitant use with respect to safety and efficacy not established1
Nevirapine	Decreased amprenavir concentrations and increased nevirapine concentrations with fosamprenavir (without ritonavir); clinically important interaction unlikely with ritonavir-boosted fosamprenavir1 In vitro evidence of additive antiretroviral effects1	Concomitant use of fosamprenavir (without ritonavir) with nevirapine not recommended1 Dosage adjustment not needed when ritonavir-boosted fosamprenavir is given twice daily with nevirapine; concomitant use with ritonavir-boosted fosamprenavir given once daily not studied1
Paroxetine	Decreased paroxetine concentrations with ritonavir-boosted fosamprenavir1	Monitor closely for antidepressant response;3 adjust paroxetine dosage based on clinical effects1 3
Pimozide	Possible increased pimozide concentrations;1 potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1	Concomitant use contraindicated1
Proton-pump inhibitors (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)	Esomeprazole: When used with fosamprenavir (without ritonavir), no change in amprenavir concentrations or AUC, and increased esomeprazole AUC;1 when used with ritonavir-boosted fosamprenavir, clinically important pharmacokinetic interaction unlikely1	Can be administered at the same time as proton-pump inhibitors with no change in plasma amprenavir concentrations1
Ritonavir	Increased plasma concentrations and AUC of amprenavir1 3 Concomitant low-dose ritonavir used to therapeutic advantage (ritonavir-boosted fosamprenavir);1 increased potential for drug interactions since ritonavir is a potent inhibitor of CYP3A4 and also inhibits CYP2D61 In vitro evidence of additive antiretroviral effects1	When ritonavir-boosted fosamprenavir is used in a once-daily regimen, recommended dosage is fosamprenavir 1.4 g once daily with ritonavir 100 or 200 mg once daily; when used in a twice-daily regimen, recommended dosage is fosamprenavir 700 mg twice with ritonavir 100 mg twice daily1 3 Once-daily regimen of ritonavir-boosted fosamprenavir not recommended in PI-experienced patients1
St. John’s wort (Hypericum perforatum)	Possible decreased amprenavir concentrations;1 possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1	Concomitant use contraindicated1
Saquinavir	Decreased amprenavir concentrations1 In vitro evidence of synergistic antiretroviral effects1	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 3
Sildenafil	Possible increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1	Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with fosamprenavir (with or without low-dose ritonavir) is contraindicated;1 3 fosamprenavir manufacturer states that a safe and effective dose for concomitant use not established1 Sildenafil for treatment of erectile dysfunction: If used concomitantly with fosamprenavir (with or without low-dose ritonavir), use reduced sildenafil dosage (25 mg repeated no more frequently than once every 48 hours) and monitor closely for adverse sildenafil effects1 3
Stavudine	In vitro evidence of synergistic antiretroviral effects1
Tadalafil	Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1 3	If tadalafil (Adcirca) is initiated for treatment of PAH in patients already receiving fosamprenavir (with or without low-dose ritonavir) for ≥1 week, use an initial tadalafil dosage of 20 mg once daily and increase dosage to 40 mg once daily based on individual tolerability1 Avoid use of tadalafil (Adcirca) for treatment of PAH during initiation of fosamprenavir (with or

Clobetasol Lotion

Dosage Form: lotion
Clobetasol Propionate Lotion, 0.05%

Rx Only

For dermatologic use only

Not for ophthalmic, oral or intravaginal use

DESCRIPTION

Clobetasol Propionate Lotion, 0.05% contains clobetasol propionate, a synthetic fluorinated corticosteroid, for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. Clobetasol propionate is 21-chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3, 20-dione 17-propionate, with the molecular formula C25H32ClFO5, a molecular weight of 466.97 (CAS Registry Number 25122-46-7).

The following is the chemical structure:

Clobetasol propionate

Clobetasol propionate is a white to practically-white crystalline powder insoluble in water.

Each gram of Clobetasol Propionate Lotion, 0.05% contains 0.5 mg of clobetasol propionate, in a vehicle base composed of carbomer 940, hypromellose, mineral oil, polyoxyethylene glycol 300 isostearate, polysorbate 80, propylene glycol, purified water, and sodium hydroxide.

CLINICAL PHARMACOLOGY

Like other topical corticosteroids, clobetasol propionate lotion, 0.05% has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids in general is unclear. However, corticosteroids are thought to act by induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and occlusion. For example, occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and other disease processes in the skin may increase percutaneous absorption.

There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Due to the fact that circulating levels are usually below the level of detection, the use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

Clobetasol propionate lotion, 0.05% is in the super-high range of potency as compared with other topical corticosteroids in vasoconstrictor studies.

In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, clobetasol propionate lotion, 0.05% demonstrated rates of suppression that were numerically higher than those of a clobetasol propionate 0.05% cream, (See PRECAUTIONS).

CLINICAL STUDIES

The efficacy of clobetasol propionate lotion, 0.05% in psoriasis and atopic dermatitis has been demonstrated in two adequate and well-controlled clinical trials. The first study was conducted in patients with moderate to severe plaque psoriasis. Patients were treated twice daily for 4 weeks with either clobetasol propionate lotion, 0.05% or vehicle lotion. Study results demonstrated that the efficacy of clobetasol propionate lotion, 0.05% in treating moderate to severe plaque psoriasis was superior to that of vehicle.

At the end of treatment (4 weeks), 30 of 82 patients (36.6%) treated with clobetasol propionate lotion, 0.05% compared with 0 of 29 (0%) treated with vehicle achieved success. Success was defined as a score of none or very mild (no or very slight clinical signs or symptoms of erythema, plaque elevation, or scaling) on the Global Severity scale of psoriasis.

The second study was conducted in patients with moderate to severe atopic dermatitis. Patients were treated twice daily for 2 weeks with either clobetasol propionate lotion, 0.05% or vehicle lotion. Study results demonstrated that the efficacy of clobetasol propionate lotion, 0.05% in treating moderate to severe atopic dermatitis was superior to that of vehicle.

At the end of treatment (2 weeks), 41 of 96 of patients (42.7%) treated with clobetasol propionate lotion, 0.05% compared with 4 of 33 (12.1%) treated with vehicle achieved success. Success was defined as a score of none or very mild (no or very slight clinical signs or symptoms of erythema, induration/papulation, oozing/crusting, or pruritus) on the Global Severity scale of atopic dermatitis.

INDICATIONS AND USAGE

Clobetasol Propionate Lotion, 0.05% is a super-high potent corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses only in patients 18 years of age or older (see PRECAUTIONS). Treatment should be limited to 2 consecutive weeks. The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week.

For the treatment of moderate to severe plaque psoriasis, localized lesions (less than 10% body surface area) that have not sufficiently improved after the initial 2-week treatment with clobetasol propionate lotion, 0.05% may be treated for up to 2 additional weeks. Any additional benefits of extending treatment should be weighed against the risk of HPA axis suppression before prescribing for more than 2 weeks.

Patients should be instructed to use clobetasol propionate lotion, 0.05% for the minimum amount of time necessary to achieve the desired results (see PRECAUTIONS).

Use in patients younger than 18 years of age is not recommended due to numerically high rates of HPA axis suppression (see PRECAUTIONS: Pediatric Use).

CONTRAINDICATIONS

Clobetasol Propionate Lotion, 0.05% is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.

PRECAUTIONS

General

Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested.

Systemic absorption of topical corticosteroids has caused reversible adrenal suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.

Conditions which increase systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of adrenal suppression (see laboratory tests below). If adrenal suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.

The effect of clobetasol propionate lotion, 0.05% on HPA axis function was compared to clobetasol propionate cream 0.05% in adults in two studies, one for psoriasis and one for atopic dermatitis. In total, 8 of 10 evaluable patients with moderate to severe plaque psoriasis experienced adrenal suppression following 4 weeks of clobetasol propionate lotion, 0.05% therapy (treatment beyond 4 consecutive weeks is not recommended in moderate to severe plaque psoriasis). In follow-up testing, 1 of 2 patients remained suppressed after 8 days. In this comparative study, for clobetasol propionate cream, 0.05% there were 3 of 10 evaluable patients with HPA axis suppression. Furthermore, 5 of 9 evaluable patients with moderate to severe atopic dermatitis experienced adrenal suppression following 2 weeks of clobetasol propionate lotion, 0.05% therapy (treatment beyond 2 consecutive weeks is not recommended in moderate to severe atopic dermatitis). Of the 3 patients that had follow-up testing, one patient failed to recover adrenal function 7 days post-treatment. For patients treated with clobetasol propionate cream, 0.05%, 4 of 9 evaluable patients experienced adrenal suppression following 2 weeks of treatment. Of the 2 patients that had follow-up testing, both recovered adrenal function 7 days post-treatment. The proportion of subjects suppressed may be underestimated because the adrenal glands were stimulated weekly with cosyntropin in these studies.

The potential increase in systemic exposure does not correlate with any proven benefit, but may lead to an increased potential for hypothalamic-pituitary-adrenal (HPA) axis suppression.  Patients with acute illness or injury may have increased morbidity and mortality with intermittent HPA axis suppression. Patients should be instructed to use clobetasol propionate lotion, 0.05% for the minimum amount of time necessary to achieve the desired results (See INDICATIONS AND USAGE).

If irritation develops, clobetasol propionate lotion, 0.05% should be discontinued and appropriate alternative therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation, as with most topical products not containing corticosteroids.

In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of clobetasol propionate lotion, 0.05% should be discontinued until the infection has been adequately controlled.

Clobetasol propionate lotion, 0.05% should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.

Information for Patients

Patients using topical corticosteroids should receive the following information and instructions:

• This medication is to be used as directed by the physician and should not be used longer than the prescribed time period.


• This medication should not be used for any disorder other than that for which it was prescribed.


• The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.


• Patients should wash their hands after applying the medication.


• Patients should report any signs of local or systemic adverse reactions to the physician.


• Patients should inform their physicians that they are using clobetasol propionate lotion, 0.05% if surgery is contemplated.


• This medication is for external use only. It should not be used on the face, underarms or groin area, and avoid contact with the eyes and lips.


• As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.


• Patients should be informed to not use more than 50 g (50 mL or 1.75 fl. oz.) per week of clobetasol propionate lotion, 0.05%.

Laboratory Tests

The following tests may be helpful in evaluating patients for HPA axis suppression:

―    Cosyntropin stimulation test

―    AM plasma cortisol test

―    Urinary free cortisol test

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.

Clobetasol propionate was non-mutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test.

Studies in the rat following subcutaneous administration at dosage levels up to 50 μg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

Pregnancy

Teratogenic Effects

Pregnancy category C.

Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals.

Clobetasol propionate is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent.

Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 1.4 and 0.04 times, respectively, the human topical dose of clobetasol propionate lotion, 0.05%. Abnormalities seen included cleft palate and skeletal abnormalities.

In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 μg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of clobetasol propionate lotion, 0.05%. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.

A teratogenicity study in rats using the dermal route resulted in dose related maternal toxicity and fetal effects from 0.05 to 0.5 mg/kg/day of clobetasol propionate. These doses are approximately 0.14 to 1.4 times, respectively, the human topical dose of clobetasol propionate lotion, 0.05%. Abnormalities seen included low fetal weights, umbilical herniation, cleft palate, reduced skeletal ossification, and other skeletal abnormalities.

There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobetasol propionate lotion, 0.05% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Because many drugs are excreted in human milk, caution should be exercised when clobetasol propionate lotion, 0.05% is administered to a nursing woman.

Pediatric Use

Use of Clobetasol Propionate Lotion, 0.05% in pediatric patients is not recommended due to the potential for HPA axis suppression (see PRECAUTIONS: General).

The HPA axis suppression potential of clobetasol propionate lotion, 0.05% has been studied in adolescents (12 to 17 years of age) with moderate to severe atopic dermatitis covering a minimum of 20% of the total body surface area. In total 14 patients were evaluated for HPA axis function. Patients were treated twice daily for 2 weeks with clobetasol propionate lotion, 0.05%. After 2 weeks of treatment, 9 out of 14 of the patients experienced adrenal suppression. One out of 4 patients treated with clobetasol propionate lotion, 0.05% who were retested remained suppressed two weeks post-treatment. In comparison, 2 of 10 of the patients treated with clobetasol propionate cream, 0.05% demonstrated HPA axis suppression. One patient who was retested recovered.

None of the patients who developed HPA axis suppression had concomitant clinical signs of adrenal suppression and none of them was discontinued from the study for reasons related to the safety or tolerability of clobetasol propionate lotion, 0.05%. However, patients with acute illness or injury may have increased morbidity and mortality with intermittent HPA axis suppression.

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of glucocorticosteroid insufficiency during and/or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Geriatric Use

Clinical studies of clobetasol propionate lotion, 0.05% did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

In controlled clinical trials with clobetasol propionate lotion, 0.05%, the following adverse reactions have been reported: burning/stinging, skin dryness, irritation, erythema, folliculitis, pruritus, skin atrophy, and telangiectasia.

The pooled incidence of local adverse reactions in trials for psoriasis and atopic dermatitis with clobetasol propionate lotion, 0.05% at 1.0% or greater was:

Adverse Reaction	Incidence
Skin Atrophy	4.2%
Telangiectasia	3.2%
Discomfort Skin	1.3%
Skin Dry	1.0%

Other local adverse events occurred at rates less than 1.0%. Similar rates of local adverse reactions were reported in the comparator (clobetasol propionate cream, 0.05%). Most local adverse events were rated as mild to moderate and they are not affected by age, race or gender.

The following additional local adverse reactions have been reported with topical corticosteroids. They may occur more frequently with the use of occlusive dressings and higher potency corticosteroids including clobetasol propionate. These reactions are listed in an approximate decreasing order of occurrence: irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria.

OVERDOSAGE

Topically applied clobetasol propionate lotion, 0.05% can be absorbed in sufficient amount to produce systemic effects (See PRECAUTIONS).

DOSAGE AND ADMINISTRATION

Clobetasol Propionate Lotion, 0.05% should be applied to the affected skin areas twice daily and rubbed in gently and completely. (See INDICATIONS AND USAGE).

Clobetasol Propionate Lotion, 0.05% contains a super-high potent topical corticosteroid; therefore treatment should be limited to:

―   2 consecutive weeks for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses,

―   and up to 2 additional weeks in very localized lesions of moderate to severe plaque psoriasis (no more than 10 % body surface area) that have not sufficiently improved after the initial 2 weeks of treatment with clobetasol

    propionate lotion, 0.05%.

The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis.

Therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

Use in patients younger than 18 years is not recommended because of numerically high rates of HPA axis suppression (See PRECAUTIONS: Pediatric Use).

Unless directed by physician, Clobetasol Propionate Lotion, 0.05% should not be used with occlusive dressings.

HOW SUPPLIED

Clobetasol Propionate Lotion, 0.05% is supplied in the following sizes:

1 fl. oz. (30 mL) high density polyethylene bottles.

2 fl. oz. (59 mL) high density polyethylene bottles.

4 fl. oz. (118 mL) high density polyethylene bottles.

Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature]

Manufactured by:

Actavis Mid Atlantic LLC

1877 Kawai Road

Lincolnton, NC 28092 USA

FORM NO. 0404

Rev. 09/08

VC3210

Patient Information

Clobetasol Propionate Lotion, 0.05%

For External Use Only

Not for Ophthalmic (Eye) Use

Read the Patient Information that comes with Clobetasol Propionate Lotion before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is Clobetasol Propionate Lotion?

Clobetasol Propionate Lotion is a medicine called a topical (skin use only) corticosteroid. It is used for a short time to reduce the inflammation and itching of:

• Moderate to severe skin conditions (atopic dermatitis and other skin problems)


• Moderate to severe plaque psoriasis.

Clobetasol Propionate Lotion is a super-high potent (very strong) topical corticosteroid. It is very important that you use Clobetasol Propionate Lotion only as directed, in order to avoid serious side effects.

Who should not use Clobetasol Propionate Lotion?

Do not use Clobetasol Propionate Lotion if you are allergic to any of its ingredients, or to any other corticosteroid. The active ingredient is clobetasol propionate. See the end of this leaflet for the complete list of other ingredients in Clobetasol Propionate Lotion. Ask your doctor or pharmacist if you need a list of other corticosteroids.

Clobetasol Propionate Lotion is not recommended for use on anyone younger than 18 years of age. Clobetasol Propionate Lotion has not been studied in children under 12 years old. Children have smaller body sizes and have a higher chance of side effects.

What should I tell my doctor before using Clobetasol Propionate Lotion?

Tell your doctor:

• if you are pregnant, think you are pregnant, or plan to be pregnant. Talk with your doctor before using Clobetasol Propionate Lotion or if you are already using Clobetasol Propionate Lotion, as it is not known if Clobetasol Propionate Lotion can harm your unborn child.


• if you are breastfeeding. It is not known if Clobetasol Propionate Lotion passes into your milk.


• if you think you have a skin infection. You may need another medicine to treat the skin infection before you use Clobetasol Propionate Lotion.

Tell your doctor about all the other medicines and skin products you use, including prescription and non-prescription medicines, cosmetics, vitamins, and herbal supplements. Some medicines can cause serious side effects if used while you are using Clobetasol Propionate Lotion.

How should I use Clobetasol Propionate Lotion?

• Use Clobetasol Propionate Lotion exactly as directed by your doctor. Clobetasol Propionate Lotion is for skin use only.


• Apply Clobetasol Propionate Lotion twice a day, once in the morning and once at night, or as directed by your doctor. Use only enough to cover the affected areas. Do not apply Clobetasol Propionate Lotion to your face, neck, groin or armpits. Do not get Clobetasol Propionate Lotion on your lips or in or near your eyes.


• Make sure your skin is clean and dry before applying Clobetasol Propionate Lotion.


• Turn the bottle of Clobetasol Propionate Lotion upside down. Pour a small amount, less than 1 teaspoonful of Clobetasol Propionate Lotion onto your fingertips, or directly on your affected skin area. Gently, rub the Clobetasol Propionate Lotion into your affected skin area, until the lotion disappears.


• Wash your hands after using Clobetasol Propionate Lotion.


• If you forget to apply Clobetasol Propionate Lotion at the scheduled time, use it as soon as you remember. Then go back to your regular schedule. If it is about time for your next dose, apply just that 1 dose, and continue with your normal application schedule. Do not try to make up for the missed dose. If you miss several doses, tell your doctor.


• Throw away unused Clobetasol Propionate Lotion.

What should I avoid while using Clobetasol Propionate Lotion?

Do not do the following while using Clobetasol Propionate Lotion:

• Do not get Clobetasol Propionate Lotion on your face, lips, or in or near your eyes because this might cause irritation. If you do, use a lot of water to rinse the Clobetasol Propionate Lotion off your face, lips, or out of your eyes. If your eyes keep stinging after rinsing them well with water, call your doctor right away.

• Do not apply Clobetasol Propionate Lotion to your groin or armpits.


• Do not bandage or cover your treated areas unless your doctor tells you to do so.


• Do not wear tight fitting clothes over your treated skin areas.


• Do not use Clobetasol Propionate Lotion any longer than 2 weeks (14 days) for moderate to severe conditions (atopic dermatitis and other skin problems).


• Do not use Clobetasol Propionate Lotion any longer than an extra 2 weeks (4 weeks total) for psoriasis on a small area of your body (less than 10 percent of your body surface area) that is not much better after the first 2 weeks of treatment.


• Do not use more than 50 grams (50 mL or 1.75 fluid ounces) of Clobetasol Propionate  Lotion a week. Clobetasol Propionate Lotion comes in 3 different size bottles, a 1-ounce, a 2-ounce, and a 4-ounce bottle.

What are the possible side effects of Clobetasol Propionate Lotion?

Clobetasol Propionate Lotion can pass through your skin. Too much Clobetasol Propionate Lotion passing through your skin can shut down your adrenal glands. This usually happens if you use too much Clobetasol Propionate Lotion, or you use it for too long. If this happens, your adrenal glands may not start working immediately once you stop using Clobetasol Propionate Lotion. Shutting down of the adrenal glands can cause nausea, vomiting, fever, low blood pressure, heart attack, and even death because your body cannot respond to any stress or illness.

Your doctor may do special blood and urine tests to check your adrenal gland function while you are using Clobetasol Propionate Lotion.

Other possible side effects with Clobetasol Propionate Lotion include mild burning, stinging, itching, redness, irritation, and dry skin. Also, thinning of the skin, widening of small blood vessels in the skin, and skin discomfort at the site of application may happen. Sometimes your condition will get worse with use of Clobetasol Propionate Lotion.

If you are ill or injured, or going to have surgery, tell your doctor that you are using Clobetasol Propionate Lotion.

Tell your doctor if you:

• are going to have surgery.


• get sick or don’t feel right. Call your doctor right away.

• have irritation of the treated skin area that does not go away.


• have any unusual effects that you do not understand.


• have affected areas that do not seem to be getting better after 2 weeks of using Clobetasol Propionate Lotion.

These are not all the possible side effects of Clobetasol Propionate Lotion. For more information, ask your doctor or pharmacist.

General information about the safe and effective use of Clobetasol Propionate Lotion.

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Clobetasol Propionate Lotion for a condition for which it was not prescribed. Do not give Clobetasol Propionate Lotion to other people, even if they have the same symptoms you have. It may harm them. Keep Clobetasol Propionate Lotion and all medicines out of reach of children.

This leaflet summarizes the most important information about Clobetasol Propionate Lotion. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Clobetasol Propionate Lotion that is written for health professionals.

What are the ingredients of Clobetasol Propionate Lotion?

Active Ingredient: clobetasol propionate

Inactive Ingredients: carbomer 940, hypromellose, mineral oil, polyoxyethylene glycol 300 isostearate, polysorbate 80, propylene glycol, purified water, and sodium hydroxide.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Manufactured by:

Actavis Mid Atlantic LLC

1877 Kawai Road

Lincolnton, NC 28092 USA

FORM NO. 0404

Rev. 09/08

VC3210

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

CLOBETASOL PROPIONATE  clobetasol propionate  lotion

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0472-0404 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CLOBETASOL PROPIONATE (CLOBETASOL) CLOBETASOL PROPIONATE 0.05 mL  in 100 mL

Inactive Ingredients Ingredient Name Strength CARBOMER HOMOPOLYMER TYPE C   HYPROMELLOSES   MINERAL OIL   POLYSORBATE 80   PROPYLENE GLYCOL   WATER   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0472-0404-91 1 BOTTLE In 1 CARTON contains a BOTTLE 1 30 mL In 1 BOTTLE This package is contained within the CARTON (0472-0404-91) 2 0472-0404-92 1 BOTTLE In 1 CARTON contains a BOTTLE 2 59 mL In 1 BOTTLE This package is contained within the CARTON (0472-0404-92) 3 0472-0404-94 1 BOTTLE In 1 CARTON contains a BOTTLE 3 118 mL In 1 BOTTLE This package is contained within the CARTON (0472-0404-94)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA078223	01/03/2012

Labeler - Actavis Mid Atlantic LLC (809515898)

Registrant - Actavis Mid Atlantic LLC (809515898)

Establishment
Name	Address	ID/FEI	Operations
Actavis Mid Atlantic LLC		809515898	MANUFACTURE

Revised: 09/2008Actavis Mid Atlantic LLC

Hemorrhoidal HC cream, ointment, suppository

Generic Name: hydrocortisone rectal (cream, ointment, suppository) (hye dro KORT i zone REK tal)

Brand Names: Anucort-HC, Anumed-HC, Anusol-HC, Cortizone-10 Anal Itch Cream, Hemorrhoidal HC, Hemril-30, Hemril-HC Uniserts, Preparation H Hydrocortisone, Procto-Kit 1%, Procto-Kit 2.5%, Procto-Pak 1%, Proctocort, Proctocream-HC, Proctosert HC, Proctosol-HC, Proctozone HC, Proctozone-H, Recort Plus, Rectasol-HC, Tucks HC

What is hydrocortisone rectal?

Hydrocortisone is a steroid medicine that reduces inflammation in the body.

The information in this medication guide is specific to hydrocortisone rectal cream, ointment, or suppository.

Hydrocortisone rectal is used to treat itching or swelling caused by hemorrhoids or other inflammatory conditions of the rectum or anus.

Hydrocortisone rectal is also used together with other medications to treat ulcerative colitis, proctitis, and other inflammatory conditions of the lower intestines and rectal area.

Hydrocortisone rectal may also be used for purposes not listed in this medication guide.

What is the most important information I should know about hydrocortisone rectal?

The information in this medication guide is specific to hydrocortisone rectal cream, ointment, or suppository.

Do not take hydrocortisone rectal by mouth. It is for use only in your rectum.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions. You may need to use this medication for up to 8 weeks.

Call your doctor at once if you have any bleeding from your rectum, feeling short of breath (even with mild exertion), swelling of your ankles or feet, or rapid weight gain.

There may be other drugs that can interact with hydrocortisone rectal. 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.

Call your doctor if your symptoms do not improve or if they get worse after using this medicine for a few days.

What should I discuss with my health care provider before using hydrocortisone rectal?

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

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  congestive heart failure;

  
  


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  a history of tuberculosis;

  
  


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  stomach ulcer or diverticulitis;

  
  


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  a colostomy or ileostomy;

  
  


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  fever or any type of infection;

  
  


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  kidney disease;

  
  


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  high blood pressure; or

  
  


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  myasthenia gravis.

  
  

Also tell your doctor if you have diabetes. Steroid medicines may increase the glucose (sugar) levels in your blood or urine. You may also need to adjust the dose of your diabetes medications.

FDA pregnancy category C. It is not known whether hydrocortisone rectal will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether hydrocortisone passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use hydrocortisone rectal?

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Do not take hydrocortisone rectal by mouth. It is for use only in your rectum.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions. You may need to use this medication for up to 8 weeks.

Wash your hands before and after using this medicine.

Try to empty your bowel and bladder just before using hydrocortisone rectal.

Remove the outer wrapper from the suppository before inserting it. Avoid handling the suppository too long or it will melt in your hands. The rectal suppository can stain clothing or other fabrics it comes into contact with.

For best results from the suppository, lie down after inserting it and hold in the suppository. The suppository will melt quickly once inserted and you should feel little or no discomfort while holding it in.

For best results from the cream, use only the applicator provided with the medication. Otherwise, follow the directions provided with your rectal cream.

Avoid using the bathroom for one to three hours after inserting the cream or suppository.

Apply the ointment to the rectum and surrounding skin of the rectal area as directed on the package label.

Call your doctor if your symptoms do not improve or if they get worse after using this medicine for a few days.

Store the rectal cream at room temperature away from moisture and heat. Store the rectal suppositories at cool room temperature away from moisture and heat. Do not refrigerate or freeze them.

What happens if I miss a dose?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use 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 hydrocortisone rectal is not expected to produce life-threatening symptoms. However, long-term use of high steroid doses can lead to symptoms such as thinning skin, easy bruising, changes in the shape or location of body fat (especially in your face, neck, back, and waist), increased acne or facial hair, menstrual problems, impotence, or loss of interest in sex.

What should I avoid while using hydrocortisone rectal ?

Avoid getting a vaccine during your treatment with hydrocortisone rectal. Vaccines may not work as well while you are using a steroid medicine.

Hydrocortisone rectal side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

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  feeling short of breath, even with mild exertion;

  
  


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  swelling of your ankles or feet;

  
  


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  muscle weakness;

  
  


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  rapid weight gain, especially in your face and midsection;

  
  


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  severe rectal pain or burning;

  
  


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  bleeding from your rectum;

  
  


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  severe stomach pain;

  
  


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  sudden and severe headache or pain behind your eyes; or

  
  


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  seizure (convulsions).

  
  

Less serious side effects may include:

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  mild rectal pain or burning;

  
  


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  acne;

  
  


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  changes in your menstrual periods;

  
  


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  increased sweating; or

  
  


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  increased facial or body hair growth.

  
  

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 hydrocortisone rectal ?

Before using hydrocortisone rectal, tell your doctor if you also use insulin or take oral diabetes medication.

There may be other drugs that can interact with hydrocortisone rectal. 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 Hemorrhoidal HC resources

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

Compare Hemorrhoidal HC with other medications

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Where can I get more information?

• Your pharmacist can provide more information about hydrocortisone rectal cream, ointment, or suppository.

See also: Hemorrhoidal HC side effects (in more detail)