Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide (Page 2 of 8)
5.5 Patients with Hepatic Impairment
Amlodipine.Amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t1/2 ) is 56 hours in patients with severely impaired hepatic function, titrate slowly when administering to patients with severe hepatic impairment.
5.6 Electrolyte and Metabolic Imbalances
Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets contain hydrochlorothiazide which can cause hypokalemia, hyponatremia and hypomagnesemia. Hypomagnesemia can result in hypokalemia which may be difficult to treat despite potassium repletion. Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets also contains olmesartan, a drug that affects the RAS. Drugs that inhibit the RAS can also cause hyperkalemia.
Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.
Hyperuricemia may occur or frank gout may be precipitated in patients receiving thiazide therapy.
Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels.
5.7 Postsympathectomy Patients
The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.
5.8 Systemic Lupus Erythematosus
Hydrochlorothiazide. Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
5.9 Acute Myopia and Secondary Angle-Closure Glaucoma
Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
5. 10 Sprue-like Enteropathy
Olmesartan medoxomil. Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with olmesartan, exclude other etiologies. Consider discontinuation of olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets in cases where no other etiology is identified.
6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets
In the controlled trial of olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets, patients were randomized to olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets 40/10/25 mg, olmesartan medoxomil/amlodipine 40/10 mg, olmesartan medoxomil/hydrochlorothiazide 40/25 mg, or amlodipine/hydrochlorothiazide 10/25 mg. Subjects who received triple combination therapy were treated between two and four weeks with one of the three dual combination therapies. Safety data from this study were obtained in 574 patients with hypertension who received olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets for 8 weeks.
The frequency of adverse reactions was similar between men and women, patients < 65 years of age and patients ≥ 65 years of age, patients with and without diabetes, and Black and non-Black patients. Discontinuations because of adverse events occurred in 4% of patients treated with olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets 40/10/25 mg compared to 1% of patients treated with olmesartan medoxomil/amlodipine 40/10 mg, 2% of patients treated with olmesartan medoxomil/hydrochlorothiazide 40/25 mg, and 2% of patients treated with amlodipine/hydrochlorothiazide 10/25 mg. The most common reason for discontinuation with olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets was dizziness (1%).
Dizziness was one of the most frequently reported adverse reactions with incidence of 1.4% to 3.6% in subjects continuing on dual combination therapy compared to 5.8% to 8.9% in subjects who switched to olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets.
The other most frequent adverse reactions that occurred in at least 2% of subjects are presented in the table below:
Adverse Reaction | OM 40/AML10/HCTZ 25 mg(N = 574)n (%) | OM 40/AML10 mg(N = 596)n (%) | OM 40/HCTZ 25mg(N = 580)n (%) | AML10/HCTZ 25 mg(N = 552)n (%) |
Edema peripheral | 44 (7.7) | 42 (7) | 6 (1) | 46 (8.3) |
Headache | 37 (6.4) | 42 (7) | 38 (6.6) | 33 (6) |
Fatigue | 24 (4.2) | 34 (5.7) | 31 (5.3) | 36 (6.5) |
Nasopharyngitis | 20 (3.5) | 11 (1.8) | 20 (3.4) | 16 (2.9) |
Muscle spasms | 18 (3.1) | 12 (2) | 14 (2.4) | 13 (2.4) |
Nausea | 17 (3) | 12 (2) | 22 (3.8) | 12 (2.2) |
Upper respiratory tract infection | 16 (2.8) | 26 (4.4) | 18 (3.1) | 14 (2.5) |
Diarrhea | 15 (2.6) | 14 (2.3) | 12 (2.1) | 9 (1.6) |
Urinary tract infection | 14 (2.4) | 8 (1.3) | 6 (1) | 7 (1.3) |
Joint swelling | 12 (2.1) | 17 (2.9) | 2 (0.3) | 16 (2.9) |
Syncope was reported by 1% of olmesartan medoxomil, amlodipine and hydrochlorothiazide tablets subjects compared to 0.5% or less for the other treatment groups.
Olmesartan medoxomil
Olmesartan medoxomil has been evaluated for safety in more than 3825 patients/subjects, including more than 3275 patients treated for hypertension in controlled trials. This experience included about 900 patients treated for at least 6 months and more than 525 treated for at least 1 year. Treatment with olmesartan medoxomil was well tolerated, with an incidence of adverse reactions similar to that seen with placebo. Adverse reactions were generally mild, transient, and without relationship to the dose of olmesartan medoxomil.
Amlodipine
Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials.
The following adverse reactions occurred in < 1% but > 0.1% of patients in controlled clinical trials under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert physicians to a possible relationship:
Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, hypotension, peripheral ischemia, syncope, tachycardia, postural dizziness, postural hypotension, vasculitis
Central and Peripheral Nervous System : hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo
Gastrointestinal : anorexia, constipation, dyspepsia*, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia
General : allergic reaction, asthenia*, back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease
Musculoskeletal System : arthralgia, arthrosis, muscle cramps*, myalgia
Psychiatric : sexual dysfunction (male* and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization
Respiratory : dyspnea*, epistaxis
Skin and Appendages : angioedema, erythema multiforme, pruritus*, rash*, rash erythematous, rash maculopapular
Special Senses : abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus
Urinary System : micturition frequency, micturition disorder, nocturia
Autonomic Nervous System: dry mouth, sweating increased
Metabolic and Nutritional: hyperglycemia, thirst
Hemopoietic: leukopenia, purpura, thrombocytopenia
* = events that occurred in less than 1% in placebo-controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies.
The following adverse reactions occurred in < 0.1% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia.
Hydrochlorothiazide
Other adverse reactions that have been reported with hydrochlorothiazide, without regard to causality, are listed below:
Body as a Whole: weakness
Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation
Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia
Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions
Metabolic: hyperglycemia, glycosuria, hyperuricemia
Musculoskeletal: muscle spasm
Nervous System/Psychiatric: restlessness
Renal: renal failure, renal dysfunction, interstitial nephritis
Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis
Special Senses: transient blurred vision, xanthopsia
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.
https://medlibrary.org/lib/rx/meds/olmesartan-medoxomil-amlodipine-and-hydrochlorothiazide-3/page/2/