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telmisartan/amlodipine (Twynsta)

 

Classes: ARB/CCB Combos; Calcium Channel Blockers, Dihydropyridine; Antianginal Agents

Dosing and uses of Twynsta (telmisartan/amlodipine)

 

Adult dosage forms and strengths

telmisartan/amlodipine

tablet

  • 40mg/10mg
  • 40mg/5mg
  • 80mg/10mg
  • 80mg/5mg

 

Hypertension

Initiate with 40 mg/5 mg or 80 mg/5 mg PO qDay, Or

Substitute for individually titrated components

May increase dose after at least 2 weeks, not to exceed 80 mg/10 mg qDay

Dosage range: Telmisartan 20-80 mg/amlodipine 2.5-10 mg PO qDay

Hepatic impairment or elderly: Initiate with decreased dose containing 2.5 mg amlodipine

May be adminsitered concomitantly with other antihypertensive agents

 

Renal Impairment

Mild to moderate impairment: Dose adjustment not recommended

 

Hepatic Impairment

Severe impairment: Titrate slowly; dose adjustment not recommended

 

Pediatric dosage forms and strengths

Safety & efficacy not established

 

Geriatric dosage forms and strengths

Not recommended as initial therapy for patients >75 years of age

 

Twynsta (telmisartan/amlodipine) adverse (side) effects

>10%

Peripheral edema (1-11%)

 

1-10%

Dizziness (3%)

Orthostatic hypotension (6%)

Syncope (2%)

Back pain (2%)

 

Postmarketing Reports

Most common reported include headache, asthenia, coughing, nausea, fatigue, hypoglycemia (in patients with diabetes), and angioedema (with fatal outcome), upper respiratory tract infection; gynecomastia, jaundice and hepatic enzyme elevations, extrapyramidal disorder

 

Warnings

Black box warnings

Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

 

Contraindications

Hypersensitivity

Do not coadminister with aliskiren in patients with diabetes mellitus

 

Cautions

Discontinue immediately with pregnancy; increased fetal/neonatal morbidity and mortality (see Black box warnings)

May cause hypotension, particularly if volume or salt depleted (correct before initiating)

Symptomatic hypotension with or without syncope may occur

Titrate slowly in patients with hepatic or severe renal impairment

May increase serum creatinine or BUN in patients w/ renal artery stenosis

Monitor for hyperkalemia

Use caution in heart failure, severe aortic stenosis (amlodipine), hepatic impairment, renal artery stenosis, or hypertrophic cardiomyopathy

Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy

Monitor for worsening heart failure; may lead to oliguria or progressive azotemia

Initiating calcium channel blockers in patients with severe obstructive coronary artery disease may precipitate MI or increase angina

 

Pregnancy and lactation

Pregnancy category: C (1st trimester); D (2nd & 3rd trimesters)

Discontinue as soon as possible, drugs that act directly on renin-angiotensin system known to cause injury or death to developing fetus

Reports of hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death

Oligohydramnios reported, presumably resulting from decreased fetal renal function

Oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development

Lactation: Discontinue drug or do not breast feed

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Twynsta (telmisartan/amlodipine)

Mechanism of action

Telmisartan is a vasoconstrictor angiotensin II receptor blocker (ARB); prevents angiotensin II from binding to its receptor, which in turn blocks the vasoconstriction and aldosterone secreting effects of angiotensin II.

Amlodipine is a dihydropyridine calcium channel blocker (CCB); acts in vascular smooth muscle to produce peripheral aterial vasodilation, which in turn reduces peripheral vascular resistance and blood pressure

 

Pharmacokinetics

Telmisartan

  • Half-Life: 24 hr
  • Onset: 1-2 hr
  • Bioavailability: 42-58%; dose-dependent
  • Vd: 500 L
  • Peak Plasma Time: 0.5-1 hr
  • Protein Bound: >99.5%
  • Metabolism: Liver to inactive metabolite (not metabolized via CYP)
  • Clearance: 800 mL/min
  • Excretion: Feces (97%)

Amlodipine

  • Half-Life: 30-50 hr
  • Bioavailability: 64-90%
  • Vd: 21 L/kg
  • Peak Plasma Time: 6-12 hr
  • Protein Bound: 93-98%
  • Metabolism: Liver (>90%); P450 CYP3A4
  • Clearance: 25 L/hr
  • Excretion: Urine (70%)