T
tacrine hydrochloride
(tak’-reen hye-droe-klor’-ide)
Brand Name(s): Cognex
Clinical Pharmacology:Mechanism of Action: An agent that inhibits the enzyme acetylcholinesterase, thus increasing the concentration of acetylcholine at cholinergic synapses and enhancing cholinergic function in the CNS. Therapeutic Effect: Slows the progression of Alzheimer’s disease.
Pharmacokinetics: Rapidly absorbed following PO administration. Protein binding: 55%. Extensively metabolized in liver. Negligible amounts excreted in urine. Half-life: 2–4 hr.
Available Forms:
Indications and Dosages:Alzheimer’s disease: PO Initially, 10 mg 4 times a day for 6 wk, followed by 20 mg 4 times a day for 6 wk, 30 mg 4 times a day for 12 wk, then 40 mg 4 times a day if needed.
Dosage in hepatic impairment: For patients with ALT greater than 3–5 times normal, decrease the dose by 40 mg/day and resume the normal dose when ALT returns to normal. For patients with ALT greater than 5 times normal, stop treatment and resume it when ALT returns to normal.
Contraindications: Known hypersensitivity to tacrine, patients previously treated with tacrine who developed jaundice
Side Effects
Fatigue, chest pain, dyspepsia, anorexia, abdominal pain, flatulence, constipation, confusion, agitation, rash, depression, ataxia, insomnia, rhinitis, myalgia
Serious ReactionsSpecial Considerations
• Transaminase elevation is the most common reason for withdrawal of drug (8%); monitor ALT qwk for first 18 wk, then decrease to q3 mo; when dose is increased, monitor qwk for 6 wk
• If elevations occur, modify dose as follows: ALT ≤ 3 times upper limit normal (ULN), continue current dose; ALT >3 to ≤5 times ULN, reduce dose by 40 mg qd and resume dose titration when within normal limits; ALT >5 times ULN, stop treatment; rechallenge may be tried if ALT is <10 times ULN
Patient/Family Education
Monitoring Parameters
• AST (SGOT) and ALT (SGPT) levels every other week for the first 4 months, then every other month thereafter
Geriatric side effects at a glance:
Use with caution in older patients with: None
U.S. Regulatory Considerations
Other Uses in Geriatric Patient: None
Side Effects:
Geriatric Considerations – Summary: Tacrine, like newer cholinesterase inhibitors, is modestly effective for treatment of cognitive decline associated with Alzheimer’s disease. It is rarely used because of significant hepatotoxicity.tacrolimus
Brand Name(s): Prograf, Protopic
Clinical Pharmacology:Mechanism of Action: An immunologic agent that inhibits T-lymphocyte activation by binding to intracellular proteins, forming a complex, and inhibiting phosphatase activity. Therapeutic Effect: Suppresses the immunologically mediated inflammatory response; prevents organ transplant rejection.
Pharmacokinetics: Variably absorbed after PO administration (food reduces absorption). Protein binding: 75%–97%. Extensively metabolized in the liver. Excreted in urine. Not removed by hemodialysis. Half-life: 11.7 hr.
Available Forms:
Indications and Dosages:Prevention of liver transplant rejection: PO 0.1–0.15 mg/kg/day in 2 divided doses 12 hr apart. IV 0.03–0.15 mg/kg/day as a continuous infusion.
Prevention of kidney transplant rejection: PO 0.2 mg/kg/day in 2 divided doses 12 hr apart IV 0.03–0.15 mg/kg/day as continuous infusion.
Atopic dermatitis: Topical Apply 0.03% ointment to affected area twice a day. 0.1% ointment may be used in adults and the elderly. Continue until 1 wk after symptoms have cleared.
Unlabeled Uses: Prevention of organ rejection in patients receiving allogeneic bone marrow, heart, pancreas, pancreatic island cell, or small-bowel transplant, treatment of autoimmune disease, severe recalcitrant psoriasis
Contraindications: Concurrent use with cyclosporine (increases the risk of nephrotoxicity), hypersensitivity to HCO-60 polyoxyl 60 hydrogenated castor oil (used in solution for injection)
Side Effects
Headache, tremor, insomnia, paresthesia, diarrhea, nausea, constipation, vomiting, abdominal pain, hypertension
Serious Reactions
• Nephrotoxicity (characterized by increased serum creatinine level and decreased urine output), neurotoxicity (including tremor, headache, and mental status changes), and pleural effusion are common adverse reactions.
Patient/Family Education
• Notify the physician if chest pain, dizziness, headache, decreased urination, rash, respiratory infection, or unusual bleeding or bruising occurs
Monitoring Parameters
• Whole blood tacrolimus concentrations as measured by ELISA may be helpful in assessing rejection and toxicity, median trough concentrations measured after the second week of therapy ranged from 9.8 to 19.4 mg/ml
• CBC weekly during the first month of therapy, twice monthly during the second and third months of treatment, then monthly for the rest of the first year; liver function test results
Geriatric side effects at a glance:
U.S. Regulatory Considerations
tadalafil
Brand Name(s): Cialis
Clinical Pharmacology:Mechanism of Action: An erectile dysfunction agent that inhibits phosphodiesterase type 5, the enzyme responsible for degrading cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the penis, resulting in smooth muscle relaxation and increased blood flow. Therapeutic Effect: Facilitates an erection.
Available Forms:
Indications and Dosages:Erectile dysfunction: PO 10 mg 30 min before sexual activity. Dose may be increased to 20 mg or decreased to 5 mg, based on patient tolerance. Maximum dosing frequency is once daily.
Dosage in renal impairment: For patients with a creatinine clearance of 31–50 ml/min, the starting dose is 5 mg before sexual activity once a day and the maximum dose is 10 mg no more frequently than once q48h. For patients with a creatinine clearance of less than 31 ml/min, the starting dose is 5 mg before sexual activity once a day.
Dosage in mild or moderate hepatic impairment: Patients with Child-Pugh Class A or B hepatic impairment should take no more than 10 mg once a day.
Contraindications: Concurrent use of alpha-adrenergic blockers (other than the minimum dose tamsulosin), concurrent use of sodium nitroprusside or nitrates in any form, severe hepatic impairment
Side Effects
Serious Reactions
• Prolonged erections (lasting over 4 hr) and priapism (painful erections lasting over 6 hr) occur rarely.
Patient/Family Education
Monitoring Parameters
Geriatric side effects at a glance:
U.S. Regulatory Considerations
tamoxifen citrate
Brand Name(s): Nolvadex
Clinical Pharmacology:Mechanism of Action: A nonsteroidal antiestrogen that competes with estradiol for estrogen-receptor binding sites in the breasts, uterus, and vagina. Therapeutic Effect: Inhibits DNA synthesis and estrogen response.
Pharmacokinetics: Well absorbed from the GI tract. Metabolized in the liver. Primarily eliminated in feces by biliary system. Half-life: 7 days.
Available Forms:
Indications and Dosages:Adjunctive treatment of breast cancer: PO 20–40 mg/day. Give doses greater than 20 mg/day in divided doses.
Unlabeled Uses: Treatment of mastalgia, gynecomastia, pancreatic carcinoma, ovulation induction
Contraindications: Concomitant coumarin-type therapy when used in the treatment of breast cancer in high-risk women, history of deep vein thrombosis or pulmonary embolism in high-risk women
Side Effects
Serious Reactions
• Retinopathy, corneal opacity, and decreased visual acuity have been noted in patients receiving extremely high dosages (240–320 mg/day) for longer than 17 mo.
Special Considerations
• Treatment duration >5 yr may provide no further benefit and increase risk of endometrial cancer for some women; reevaluate the need for continued therapy
Patient/Family Education
• Notify the physician if leg cramps, weakness, weight gain, or vaginal bleeding, itching, or discharge occurs
• May initially cause an increase in bone and tumor pain, which appears to indicate a good tumor response to tamoxifen
Monitoring Parameters
• Assess the patient for signs and symptoms of hypercalcemia, including constipation, deep bone or flank pain, excessive thirst, hypotonicity of muscles, increased urine output, nausea and vomiting, and renal calculi
Geriatric side effects at a glance:
U.S. Regulatory Considerations
tamsulosin hydrochloride
(tam-soo-lo’-sin hye-droe-klor’-ide)
Brand Name(s): Flomax
Clinical Pharmacology:Mechanism of Action: An alpha1-antagonist that targets receptors around bladder neck and prostate capsule. Therapeutic Effect: Relaxes smooth muscle and improves urinary flow and symptoms of prostatic hyperplasia.
Pharmacokinetics: Well absorbed and widely distributed. Protein binding: 94%-99%. Metabolized in the liver. Primarily excreted in urine. Unknown if removed by hemodialysis. Half-life: 9–13 hr.
Available Forms:
Indications and Dosages:Benign prostatic hyperplasia: PO 0.4 mg once a day, approximately 30 min after same meal each day. May increase dosage to 0.8 mg if inadequate response in 2–4 wk.
Contraindications: Concurrent use of sildenafil, tadalafil, or vardenafil
Side Effects
Serious Reactions
Patient/Family Education
• Consider administration of first dose at bedtime; caution following first 12 hr after initiation or reinitiation of therapy for “first dose phenomenon”
Monitoring Parameters
Geriatric side effects at a glance:
Use with caution in older patients with: Congestive heart failure, patients taking medications for impotence (e.g., vardenafil, sildenafil, or tadalafil)
U.S. Regulatory Considerations
Other Uses in Geriatric Patient: Symptoms related to benign prostatic hypertrophy
Side Effects:
Geriatric Considerations – Summary: Alpha-adrendergic blockers are modestly effective alone, and in combination with 5-alpha reductase inhibitors (e.g., finasteride) in the treatment of urinary obstructive symptoms related to benign prostatic hyperplasia. Tamsulosin is a “uroselective” alpha-blocker which appears to cause less orthostatic hypotension than nonselective alpha-blockers such as terazosin, prazosin, and doxazosin.1 McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349:2387-2398.
2 Lowe FC. Role of the newer alpha1-adrenergic-receptor antagonists in the treatment of benign prostatic hyperplasia-related lower urinary tract symptoms. Clin Ther. 2004;26:1701-1713.
3 Alfuzosin (Uroxatral)—another alpha1-blocker for benign prostatic hyperplasia. Med Lett Drugs Ther. 2004;46:1-2.
tazarotene
Brand Name(s): Avage, Tazorac
Clinical Pharmacology:Mechanism of Action: Modulates differentiation and proliferation of epithelial tissue, binds selectively to retinoic acid receptors. Therapeutic Effect: Restores normal differentiation of the epidermis and promotes reduction of epidermal inflammation.
Pharmacokinetics: Minimal systemic absorption occurs through the skin. Binding to plasma proteins is greater than 99%. Metabolism is in the skin and liver. Elimination occurs through the fecal and renal pathways. Half-life: 18 hr.
Available Forms:
Indications and Dosages:Psoriasis: Topical Thin film applied once daily in the evening; cover only the lesions, and area should be dry before application
Acne vulgaris: Topical Thin film applied to affected areas once daily in the evening, after face is gently cleansed and dried.
Fine facial wrinkles, facial mottled hyperpigmentation (liver spots), hypopigmentation associated with photoaging: Topical Thin film applied to affected areas once daily in the evening, after face is gently cleansed and dried.
Contraindications: Hypersensitivity to tazarotene, benzyl alcohol, or any one of its components.
Side Effects
Desquamination, burning or stinging, dry skin, itching, erythema, worsening of psoriasis, irritation, skin pain, pruritis, xerosis, photosensitivity
Special Considerations
• Attractive alternative to oral retinoid therapy in psoriasis (e.g., etretinate), primarily due to less toxicity. Structural changes to the basic retinoid structure (e.g., conformational rigidity) are claimed to enhance therapeutic efficacy and reduce the local toxicity associated with topical tretinoin (retinoic acid). However, place in therapy should await direct comparisons vs standard regimens in terms of efficacy, toxicity, and cost
Patient/Family Education
• Burning or stinging after application, dryness, itching, peeling, or redness of the skin may occur during tazarotene therapy
Monitoring Parameters
Geriatric side effects at a glance:
U.S. Regulatory Considerations
tegaserod maleate
Brand Name(s): Zelnorm
Clinical Pharmacology:Mechanism of Action: An anti-irritable bowel syndrome (IBS) agent that binds to 5-HT4 receptors in the GI tract. Therapeutic Effect: Triggers a peristaltic reflex in the gut, increasing bowel motility.
Pharmacokinetics: Rapidly absorbed. Widely distributed. Protein binding: 98%. Metabolized by hydrolysis in the stomach and by oxidation and conjugation of the primary metabolite. Primarily excreted in feces. Half-life: 11 hr.
Available Forms:
Indications and Dosages:
Contraindications: Abdominal adhesions, diarrhea, history of bowel obstruction, moderate to severe hepatic impairment, severe renal impairment, suspected sphincter of Oddi dysfunction, symptomatic gallbladder disease
Side Effects
Serious Reactions
• Ischemic colitis, mesenteric ischemia, gangrenous bowel, rectal bleeding, syncope, hypotension, hypovolemia, electrolyte disorders, suspected sphincter of Oddi spasm, bile duct stone, cholecystitis with elevated transaminases, and hypersensitivity reaction including rash, urticaria, pruritus, and serious allergic type I reactions have been reported.
Patient/Family Education
Monitoring Parameters
Geriatric side effects at a glance:
U.S. Regulatory Considerations
telithromycin
Brand Name(s): Ketek, Ketek Pak
Clinical Pharmacology:Mechanism of Action: A ketolide that blocks protein synthesis by binding to ribosomal receptor sites on the bacterial cell wall. Therapeutic Effect: Bactericidal.
Pharmacokinetics: Protein binding: 60%-70%. More of drug is concentrated in WBCs than in plasma, and drug is eliminated more slowly from WBCs than from plasma. Partially metabolized by the liver. Minimally excreted in feces and urine. Half-life: 10 hr.
Available Forms:
Indications and Dosages:
Unlabeled Uses: Treatment of tonsillitis and pharyngitis due to Streptococcus pyogenes
Contraindications: Hypersensitivity to macrolide antibacterials, concurrent use of cisapride or pimozide
Side Effects
Serious Reactions
Patient/Family Education
• Do not take if you or a close relative has a rare heart condition called prolongation of the QT interval. Notify provider if you faint while on this medication
• Telithromycin may produce difficulty focusing that may last several hours after the first or second dose
Monitoring Parameters
Geriatric side effects at a glance:
U.S. Regulatory Considerations
Brand Name(s): Micardis
Clinical Pharmacology:
