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%)
