Sunday, May 30, 2010

Bacitracin and polymyxin B

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:

Betadine® may be confused with Betagan®, betaine

U.S. BRAND NAMES — AK-Poly-Bac™ ; Polysporin® [OTC]

PHARMACOLOGIC CATEGORY
Antibiotic, Ophthalmic
Antibiotic, Topical

DOSING: ADULTS
Ophthalmic infection: Ophthalmic (ointment): Instill 1/2" ribbon in the affected eye(s) every 3-4 hours for acute infections or 2-3 times/day for mild-to-moderate infections for 7-10 days.

Superficial dermal infection: Topical ointment/powder: Apply to affected area 1-4 times/day; may cover with sterile bandage if needed.

DOSING: PEDIATRIC — Refer to adult dosing.

(For additional information see "Bacitracin and polymyxin B: Pediatric drug information")

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Ointment, ophthalmic: Bacitracin 500 units and polymyxin B 10,000 units per g (3.5 g)
AK-Poly-Bac™ : Bacitracin 500 units and polymyxin 10,000 units per g (3.5 g)

Ointment, topical: Bacitracin 500 units and polymyxin B 10,000 units per g in white petrolatum (15 g, 30 g)
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (0.9 g, 15 g, 30 g)

Powder, topical:
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (10 g)

DOSAGE FORMS: CONCISE
Ointment, ophthalmic: Bacitracin 500 units and polymyxin B 10,000 units per g (3.5 g)
AK-Poly-Bac™ : Bacitracin 500 units and polymyxin 10,000 units per g (3.5 g)

Ointment, topical: Bacitracin 500 units and polymyxin B 10,000 units per g in white petrolatum (15 g, 30 g)
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (0.9 g, 15 g, 30 g)

Powder, topical:
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (10 g)

GENERIC EQUIVALENT AVAILABLE — Yes

USE — Treatment of superficial infections caused by susceptible organisms

ADVERSE REACTIONS SIGNIFICANT — 1% to 10%: Local: Rash, itching, burning, anaphylactoid reactions, swelling, conjunctival erythema

CONTRAINDICATIONS — Hypersensitivity to bacitracin, polymyxin B, or any component of the formulation

DRUG INTERACTIONS
Capreomycin: May enhance the neuromuscular-blocking effect of Polymyxin B. Risk C: Monitor therapy

Colistimethate: Polymyxin B may enhance the neuromuscular-blocking effect of Colistimethate. Risk C: Monitor therapy

Neuromuscular-Blocking Agents: Polymyxin B may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk D: Consider therapy modification

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted with this combination; therefore, Bacitracin and Polymyxin B is considered pregnancy category C. See individual agents.

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — It is not known if bacitracin or polymyxin B is found in breast milk. The manufacturer recommends that caution be exercised when administering Bacitracin and Polymyxin B to nursing women. See individual agents.

PRICING — (data from drugstore.com)
Ointment (Bacitracin-Polymyxin B)
500-10000 units/g (3.5): $17.99

CANADIAN BRAND NAMES — LID-Pack®; Optimyxin®

INTERNATIONAL BRAND NAMES — Glubacida (MX); Miratracina (CO); Nebacetina (MX); Neobacitracine (BE); Neospor & iacute;n Dermico (MX); Polisulfade (PT); Polixin Ungena (MX); Polyfax (MY); Polysporin Ophthalmic (ZA); Tribiot (MX)

MECHANISM OF ACTION — See individual agents.

PHARMACODYNAMICS / KINETICS — See individual agents.

Bacitracin and polymyxin B

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:

Betadine® may be confused with Betagan®, betaine

U.S. BRAND NAMES — AK-Poly-Bac™ ; Polysporin® [OTC]

PHARMACOLOGIC CATEGORY
Antibiotic, Ophthalmic
Antibiotic, Topical

DOSING: ADULTS
Ophthalmic infection: Ophthalmic (ointment): Instill 1/2" ribbon in the affected eye(s) every 3-4 hours for acute infections or 2-3 times/day for mild-to-moderate infections for 7-10 days.

Superficial dermal infection: Topical ointment/powder: Apply to affected area 1-4 times/day; may cover with sterile bandage if needed.

DOSING: PEDIATRIC — Refer to adult dosing.

(For additional information see "Bacitracin and polymyxin B: Pediatric drug information")

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Ointment, ophthalmic: Bacitracin 500 units and polymyxin B 10,000 units per g (3.5 g)
AK-Poly-Bac™ : Bacitracin 500 units and polymyxin 10,000 units per g (3.5 g)

Ointment, topical: Bacitracin 500 units and polymyxin B 10,000 units per g in white petrolatum (15 g, 30 g)
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (0.9 g, 15 g, 30 g)

Powder, topical:
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (10 g)

DOSAGE FORMS: CONCISE
Ointment, ophthalmic: Bacitracin 500 units and polymyxin B 10,000 units per g (3.5 g)
AK-Poly-Bac™ : Bacitracin 500 units and polymyxin 10,000 units per g (3.5 g)

Ointment, topical: Bacitracin 500 units and polymyxin B 10,000 units per g in white petrolatum (15 g, 30 g)
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (0.9 g, 15 g, 30 g)

Powder, topical:
Polysporin®: Bacitracin 500 units and polymyxin B 10,000 units per g (10 g)

GENERIC EQUIVALENT AVAILABLE — Yes

USE — Treatment of superficial infections caused by susceptible organisms

ADVERSE REACTIONS SIGNIFICANT — 1% to 10%: Local: Rash, itching, burning, anaphylactoid reactions, swelling, conjunctival erythema

CONTRAINDICATIONS — Hypersensitivity to bacitracin, polymyxin B, or any component of the formulation

DRUG INTERACTIONS
Capreomycin: May enhance the neuromuscular-blocking effect of Polymyxin B. Risk C: Monitor therapy

Colistimethate: Polymyxin B may enhance the neuromuscular-blocking effect of Colistimethate. Risk C: Monitor therapy

Neuromuscular-Blocking Agents: Polymyxin B may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk D: Consider therapy modification

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted with this combination; therefore, Bacitracin and Polymyxin B is considered pregnancy category C. See individual agents.

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — It is not known if bacitracin or polymyxin B is found in breast milk. The manufacturer recommends that caution be exercised when administering Bacitracin and Polymyxin B to nursing women. See individual agents.

PRICING — (data from drugstore.com)
Ointment (Bacitracin-Polymyxin B)
500-10000 units/g (3.5): $17.99

CANADIAN BRAND NAMES — LID-Pack®; Optimyxin®

INTERNATIONAL BRAND NAMES — Glubacida (MX); Miratracina (CO); Nebacetina (MX); Neobacitracine (BE); Neospor & iacute;n Dermico (MX); Polisulfade (PT); Polixin Ungena (MX); Polyfax (MY); Polysporin Ophthalmic (ZA); Tribiot (MX)

MECHANISM OF ACTION — See individual agents.

PHARMACODYNAMICS / KINETICS — See individual agents.

Bacitracin

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Bacitracin may be confused with Bactrim®, Bactroban®

U.S. BRAND NAMES — Baci-Rx; Baciguent® [OTC]; BaciiM®

PHARMACOLOGIC CATEGORY
Antibiotic, Miscellaneous
Antibiotic, Ophthalmic
Antibiotic, Topical

DOSING: ADULTS — Do not administer I.V.:

Antibiotic-associated colitis: Oral: 25,000 units 4 times/day for 7-10 days

VRE eradication (unlabeled use): Oral: 25,000 units 4 times/day for 7-10 days

Superficial dermal infection: Topical: Apply 1-5 times/day.

Ophthalmic infection: Ophthalmic (ointment): Instill 1/4" to 1/2" ribbon every 3-4 hours into conjunctival sac for acute infections, or 2-3 times/day for mild-to-moderate infections for 7-10 days.

Local irrigation: Solution: 50-100 units/mL in normal saline, lactated Ringer's, or sterile water for irrigation; soak sponges in solution for topical compresses 1-5 times/day or as needed during surgical procedures.

DOSING: PEDIATRIC — Do not administer I.V.

(For additional information see "Bacitracin: Pediatric drug information")

Treatment of infection:
Infants: I.M.:
≤ 2.5 kg: 900 units/kg/day in 2-3 divided doses
>2.5 kg: 1000 units/kg/day in 2-3 divided doses
Children: I.M.: 800-1200 units/kg/day divided every 8 hours

Superficial dermal infection: Topical: Refer to adult dosing.

Ophthalmic infection: Ophthalmic (ointment): Refer to adult dosing.

Local irrigation: Solution: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution: 50,000 units
BaciiM®: 50,000 units

Ointment, ophthalmic: 500 units/g (3.5 g)

Ointment, topical: 500 units/g (0.9 g, 15 g, 30 g, 120 g, 454 g)
Baciguent®: 500 units/g (15 g, 30 g)

Powder, for prescription compounding [micronized]:
Baci-Rx: 5 million units

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 50,000 units
BaciiM®: 50,000 units

Ointment, ophthalmic: 500 units/g (3.5 g)

Ointment, topical: 500 units/g (0.9 g, 15 g, 30 g, 120 g, 454 g)
Baciguent® [OTC]: 500 units/g (15 g, 30 g)

Powder, for prescription compounding [micronized]:
Baci-Rx: 5 million units

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — For I.M. administration only, do not administer I.V. Confirm any orders for parenteral use. pH of urine should be kept >6 by using sodium bicarbonate. Bacitracin sterile powder should be dissolved in 0.9% sodium chloride injection containing 2% procaine hydrochloride. Do not use diluents containing parabens.

USE — Treatment of susceptible bacterial infections mainly; has activity against gram-positive bacilli; due to toxicity risks, systemic and irrigant uses of bacitracin should be limited to situations where less toxic alternatives would not be effective

USE - UNLABELED / INVESTIGATIONAL — Oral administration: Successful in antibiotic-associated colitis; has been used for enteric eradication of vancomycin-resistant enterococci (VRE)

ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Cardiovascular: Hypotension, edema of the face/lips, chest tightness
Central nervous system: Pain
Dermatologic: Rash, itching
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, rectal itching
Hematologic: Blood dyscrasias
Miscellaneous: Diaphoresis

<1%: Rare cases of anaphylaxis have been reported in association with topical and intraoperative exposures.

CONTRAINDICATIONS — Hypersensitivity to bacitracin or any component of the formulation; I.M. use is contraindicated in patients with renal impairment

WARNINGS / PRECAUTIONS
Boxed warnings: Renal failure: See "Concerns related to adverse effects" below.

Concerns related to adverse effects: Renal failure: [U.S. Boxed Warning]: I.M. use may cause renal failure due to tubular and glomerular necrosis; monitor renal function daily. Avoid concurrent use with other nephrotoxic drugs; discontinue use if toxicity occurs. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment..

Other warnings/precautions: Appropriate administration: Do not administer intravenously because severe thrombophlebitis occurs.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY IMPLICATIONS — It is unknown if bacitracin crosses the placenta. The minimal absorption after topical use should limit the amount of medication available for transfer to the fetus.

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — It is unknown if bacitracin is distributed in human milk. The minimal absorption after topical use should limit the amount of medication available for transfer.

PRICING — (data from drugstore.com)
Ointment (Bacitracin)
500 units/g (3.5): $15.99
500 units/g (28.4): $12.99

MONITORING PARAMETERS — I.M.: Urinalysis, renal function tests

CANADIAN BRAND NAMES — Baciguent®; Baciject®

INTERNATIONAL BRAND NAMES — Glubacida (MX); Nebacetina (MX); Neosporin Dermico (MX); Polixin Ungena (MX); Tribiot (MX)

MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by preventing transfer of mucopeptides into the growing cell wall

PHARMACODYNAMICS / KINETICS
Duration: 6-8 hours

Absorption: Poor from mucous membranes and intact or denuded skin; rapidly following I.M. administration; not absorbed by bladder irrigation, but absorption can occur from peritoneal or mediastinal lavage

Distribution: CSF: Nil even with inflammation

Protein binding, plasma: Minimal

Time to peak, serum: I.M.: 1-2 hours

Excretion: Urine (10% to 40%) within 24 hours

PATIENT INFORMATION

(For additional information see "Bacitracin: Patient drug information")
Ophthalmic: Tilt head back, place medication in conjunctival sac and close eyes; apply light finger pressure on lacrimal sac for 1 minute following instillation. Ophthalmic ointment may cause blurred vision; do not share eye medications with others.

Topical: Do not be use for longer than 1 week unless directed by prescriber.

Bacitracin

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Bacitracin may be confused with Bactrim®, Bactroban®

U.S. BRAND NAMES — Baci-Rx; Baciguent® [OTC]; BaciiM®

PHARMACOLOGIC CATEGORY
Antibiotic, Miscellaneous
Antibiotic, Ophthalmic
Antibiotic, Topical

DOSING: ADULTS — Do not administer I.V.:

Antibiotic-associated colitis: Oral: 25,000 units 4 times/day for 7-10 days

VRE eradication (unlabeled use): Oral: 25,000 units 4 times/day for 7-10 days

Superficial dermal infection: Topical: Apply 1-5 times/day.

Ophthalmic infection: Ophthalmic (ointment): Instill 1/4" to 1/2" ribbon every 3-4 hours into conjunctival sac for acute infections, or 2-3 times/day for mild-to-moderate infections for 7-10 days.

Local irrigation: Solution: 50-100 units/mL in normal saline, lactated Ringer's, or sterile water for irrigation; soak sponges in solution for topical compresses 1-5 times/day or as needed during surgical procedures.

DOSING: PEDIATRIC — Do not administer I.V.

(For additional information see "Bacitracin: Pediatric drug information")

Treatment of infection:
Infants: I.M.:
≤ 2.5 kg: 900 units/kg/day in 2-3 divided doses
>2.5 kg: 1000 units/kg/day in 2-3 divided doses
Children: I.M.: 800-1200 units/kg/day divided every 8 hours

Superficial dermal infection: Topical: Refer to adult dosing.

Ophthalmic infection: Ophthalmic (ointment): Refer to adult dosing.

Local irrigation: Solution: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution: 50,000 units
BaciiM®: 50,000 units

Ointment, ophthalmic: 500 units/g (3.5 g)

Ointment, topical: 500 units/g (0.9 g, 15 g, 30 g, 120 g, 454 g)
Baciguent®: 500 units/g (15 g, 30 g)

Powder, for prescription compounding [micronized]:
Baci-Rx: 5 million units

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution: 50,000 units
BaciiM®: 50,000 units

Ointment, ophthalmic: 500 units/g (3.5 g)

Ointment, topical: 500 units/g (0.9 g, 15 g, 30 g, 120 g, 454 g)
Baciguent® [OTC]: 500 units/g (15 g, 30 g)

Powder, for prescription compounding [micronized]:
Baci-Rx: 5 million units

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — For I.M. administration only, do not administer I.V. Confirm any orders for parenteral use. pH of urine should be kept >6 by using sodium bicarbonate. Bacitracin sterile powder should be dissolved in 0.9% sodium chloride injection containing 2% procaine hydrochloride. Do not use diluents containing parabens.

USE — Treatment of susceptible bacterial infections mainly; has activity against gram-positive bacilli; due to toxicity risks, systemic and irrigant uses of bacitracin should be limited to situations where less toxic alternatives would not be effective

USE - UNLABELED / INVESTIGATIONAL — Oral administration: Successful in antibiotic-associated colitis; has been used for enteric eradication of vancomycin-resistant enterococci (VRE)

ADVERSE REACTIONS SIGNIFICANT
1% to 10%:
Cardiovascular: Hypotension, edema of the face/lips, chest tightness
Central nervous system: Pain
Dermatologic: Rash, itching
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, rectal itching
Hematologic: Blood dyscrasias
Miscellaneous: Diaphoresis

<1%: Rare cases of anaphylaxis have been reported in association with topical and intraoperative exposures.

CONTRAINDICATIONS — Hypersensitivity to bacitracin or any component of the formulation; I.M. use is contraindicated in patients with renal impairment

WARNINGS / PRECAUTIONS
Boxed warnings: Renal failure: See "Concerns related to adverse effects" below.

Concerns related to adverse effects: Renal failure: [U.S. Boxed Warning]: I.M. use may cause renal failure due to tubular and glomerular necrosis; monitor renal function daily. Avoid concurrent use with other nephrotoxic drugs; discontinue use if toxicity occurs. Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment..

Other warnings/precautions: Appropriate administration: Do not administer intravenously because severe thrombophlebitis occurs.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY IMPLICATIONS — It is unknown if bacitracin crosses the placenta. The minimal absorption after topical use should limit the amount of medication available for transfer to the fetus.

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — It is unknown if bacitracin is distributed in human milk. The minimal absorption after topical use should limit the amount of medication available for transfer.

PRICING — (data from drugstore.com)
Ointment (Bacitracin)
500 units/g (3.5): $15.99
500 units/g (28.4): $12.99

MONITORING PARAMETERS — I.M.: Urinalysis, renal function tests

CANADIAN BRAND NAMES — Baciguent®; Baciject®

INTERNATIONAL BRAND NAMES — Glubacida (MX); Nebacetina (MX); Neosporin Dermico (MX); Polixin Ungena (MX); Tribiot (MX)

MECHANISM OF ACTION — Inhibits bacterial cell wall synthesis by preventing transfer of mucopeptides into the growing cell wall

PHARMACODYNAMICS / KINETICS
Duration: 6-8 hours

Absorption: Poor from mucous membranes and intact or denuded skin; rapidly following I.M. administration; not absorbed by bladder irrigation, but absorption can occur from peritoneal or mediastinal lavage

Distribution: CSF: Nil even with inflammation

Protein binding, plasma: Minimal

Time to peak, serum: I.M.: 1-2 hours

Excretion: Urine (10% to 40%) within 24 hours

PATIENT INFORMATION

(For additional information see "Bacitracin: Patient drug information")
Ophthalmic: Tilt head back, place medication in conjunctival sac and close eyes; apply light finger pressure on lacrimal sac for 1 minute following instillation. Ophthalmic ointment may cause blurred vision; do not share eye medications with others.

Topical: Do not be use for longer than 1 week unless directed by prescriber.

Thursday, May 27, 2010

Alitretinoin

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Panretin® may be confused with pancreatin

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

U.S. BRAND NAMES — Panretin®

PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Retinoic Acid Derivative

DOSING: ADULTS
Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.

T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Gel:
Panretin®: 0.1% (60 g)

DOSAGE FORMS: CONCISE
Gel:
Panretin®: 0.1% (60 g)

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Do not use occlusive dressings.

USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma

USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas

ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Pain (0% to 34%)
Dermatologic: Rash (25% to 77%), pruritus (8% to 11%)
Neuromuscular & skeletal: Paresthesia (3% to 22%)

5% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)

CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy

WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.

Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.

Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.

Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.

CANADIAN BRAND NAMES — Panretin®

INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, NL, NO, PT, RU, SE, TR)

MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma

PHARMACODYNAMICS / KINETICS — Absorption: Not extensive

PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products

Alitretinoin

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Panretin® may be confused with pancreatin

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

U.S. BRAND NAMES — Panretin®

PHARMACOLOGIC CATEGORY
Antineoplastic Agent, Miscellaneous
Retinoic Acid Derivative

DOSING: ADULTS
Kaposi's sarcoma: Topical: Apply gel twice daily to cutaneous lesions.

T-cell lymphomas (unlabeled use): Topical: Apply gel twice daily to cutaneous lesions.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Gel:
Panretin®: 0.1% (60 g)

DOSAGE FORMS: CONCISE
Gel:
Panretin®: 0.1% (60 g)

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Do not use occlusive dressings.

USE — Orphan drug: Topical treatment of cutaneous lesions in AIDS-related Kaposi's sarcoma

USE - UNLABELED / INVESTIGATIONAL — Cutaneous T-cell lymphomas

ADVERSE REACTIONS SIGNIFICANT
>10%:
Central nervous system: Pain (0% to 34%)
Dermatologic: Rash (25% to 77%), pruritus (8% to 11%)
Neuromuscular & skeletal: Paresthesia (3% to 22%)

5% to 10%:
Cardiovascular: Edema (3% to 8%)
Dermatologic: Exfoliative dermatitis (3% to 9%), skin disorder (0% to 8%)

CONTRAINDICATIONS — Hypersensitivity to alitretinoin, other retinoids, or any component of the formulation; pregnancy

WARNINGS / PRECAUTIONS
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.

Concerns related to adverse effects: Photosensitivity: May be photosensitizing (based on experience with other retinoids); minimize sun or other UV exposure of treated areas.

Concurrent drug therapy issues: Products containing DEET: Do not use concurrently with topical products containing DEET.

Special populations: Elderly: Safety has not been established in the elderly. Pediatrics: Safety has not been established in children. Pregnancy: May cause fetal harm if absorbed by a woman who is pregnant.

DRUG INTERACTIONS — There are no known significant interactions.

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — Potentially teratogenic and/or embryotoxic; limb, craniofacial, or skeletal defects have been observed in animal models. If used during pregnancy or if the patient becomes pregnant while using alitretinoin, the woman should be advised of potential harm to the fetus. Women of childbearing potential should avoid becoming pregnant.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — Excretion in human breast milk is unknown; women are advised to discontinue breast-feeding prior to using this medication.

CANADIAN BRAND NAMES — Panretin®

INTERNATIONAL BRAND NAMES — Panretin (AR, AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HN, IE, IT, NL, NO, PT, RU, SE, TR)

MECHANISM OF ACTION — Binds to retinoid receptors to inhibit growth of Kaposi's sarcoma

PHARMACODYNAMICS / KINETICS — Absorption: Not extensive

PATIENT INFORMATION — For external use only; avoid UV light exposure (sun or sunlamps) of treated areas; avoid DEET-containing products

Aliskiren and hydrochlorothiazide

U.S. BRAND NAMES — Tekturna HCT®

PHARMACOLOGIC CATEGORY
Diuretic, Thiazide
Renin Inhibitor

DOSING: ADULTS — Hypertension: Oral: One tablet daily; dosage must be individualized (see below). May be substituted for previously titrated dosages of the individual components. Titrate at 2- to 4-week intervals as necessary.

Patients not controlled with single-agent therapy: Initiate by adding the lowest available dose of the alternative component (aliskiren 150 mg or hydrochlorothiazide 12.5 mg); titrate to effect (maximum daily aliskiren dose: 300 mg; maximum daily hydrochlorothiazide dose: 25 mg)

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT — Not recommended in patients with Clcr <30 mL/minute

DOSING: HEPATIC IMPAIRMENT — Dosage adjustment not required.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:
Tekturna HCT®:
150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg
150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg
300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg
300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg

DOSAGE FORMS: CONCISE
Tablet:
Tekturna HCT®: 150/12.5: Aliskiren 150 mg and hydrochlorothiazide 12.5 mg; 150/25: Aliskiren 150 mg and hydrochlorothiazide 25 mg; 300/12.5: Aliskiren 300 mg and hydrochlorothiazide 12.5 mg; 300/25: Aliskiren 300 mg and hydrochlorothiazide 25 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Administer with or without meals.

USE — Treatment of hypertension (not recommended for initial treatment)

ADVERSE REACTIONS SIGNIFICANT — Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent.

>10%: Renal: BUN increased (12%)

1% to 10%:
Central nervous system: Dizziness (2%), vertigo (1%)
Endocrine & metabolic: Hypokalemia (2%), uric acid level increased (2%)
Gastrointestinal: Diarrhea (2%)
Hepatic: ALT increased (1%)
Neuromuscular & skeletal: Arthralgia (1%), weakness (1%)
Respiratory: Cough (1%)
Miscellaneous: Flu-like syndrome (2%)

<1% (Limited to important or life-threatening): Hematocrit decreased, hemoglobin decreased, hyperkalemia

Note: Angioedema and periorbital edema have been reported with aliskiren. Severe dermatologic reactions and pancreatitis have been reported with hydrochlorothiazide.

CONTRAINDICATIONS — Hypersensitivity to hydrochlorothiazide, thiazides, or sulfonamide-derived drugs; anuria

WARNINGS / PRECAUTIONS
Boxed warnings: Pregnancy: See "Special populations" below.

Concerns related to adverse effects: Angioedema: Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use caution in any patient with a history of angioedema (of any etiology) as angioedema has been observed (rarely) with aliskiren use. Discontinue immediately following any signs and symptoms of angioedema. Electrolyte disturbances: Hyperkalemia may occur with renin inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia. Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma. Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume- or salt-depleted patients. Photosensitivity: Due to the hydrochlorothiazide component photosensitization may occur. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure); deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.

Disease-related concerns: Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. Hepatic impairment: Use caution in patients with hepatic impairment. Avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Hypovolemia: Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Renal artery stenosis: There has been no experience in treating patients with renal artery stenosis; use aliskiren with caution in patients with unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in patients with renal impairment; not recommended in patients with severe renal impairment (Clcr <30 mL/minute). Avoid hydrochlorothiazide in severe renal disease (ineffective); may precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Systemic lupus erythematosus (SLE): Hydrochlorothiazide can cause SLE exacerbation or activation.

Concurrent drug therapy: High potential for interactions: use caution in patients taking strong inhibitors of P-glycoprotein (eg, cyclosporine); concomitant therapy with cyclosporine is not recommended.

Special populations: Pediatrics: Safety and efficacy have not been established in children. Pregnancy: [U.S. Boxed Warning]: Based on human data, drugs that act on the angiotensin system can cause injury and death to the developing fetus when used in the second and third trimesters. Aliskiren should be discontinued as soon as possible once pregnancy is detected.

METABOLISM / TRANSPORT EFFECTS — See individual agents.

DRUG INTERACTIONS
ACE Inhibitors: Thiazide Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Thiazide Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Allopurinol: Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Analgesics (Opioid): May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

Atorvastatin: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy

Barbiturates: May enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased. Risk D: Consider therapy modification

Calcitriol: Thiazide Diuretics may enhance the hypercalcemic effect of Calcitriol. Risk C: Monitor therapy

Calcium Salts: Thiazide Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

CycloSPORINE: May increase the serum concentration of Aliskiren. Risk X: Avoid combination

Dofetilide: Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide. Risk X: Avoid combination

Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Ketoconazole: May increase the serum concentration of Aliskiren. Risk C: Monitor therapy

Lithium: Thiazide Diuretics may decrease the excretion of Lithium. Risk D: Consider therapy modification

MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — D (show table)

PREGNANCY IMPLICATIONS — See individual agents.

LACTATION — Excretion in breast milk unknown/not recommended

BREAST-FEEDING CONSIDERATIONS — See individual agents.

DIETARY CONSIDERATIONS — Take with or without meals; a high-fat meal reduces aliskiren absorption substantially.

PRICING — (data from drugstore.com)
Tablets (Tekturna HCT)
300-25 mg (30): $102.72

MONITORING PARAMETERS — Blood pressure; serum electrolytes, BUN, serum creatinine; fluid status

MECHANISM OF ACTION — Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Hydrochlorothiazide inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions.

PHARMACODYNAMICS / KINETICS — See individual agents.