Tribenzor (olmesartan medoxomil, amlodipine, hydrochlorothiazide)

Tribenzor (olmesartan medoxomil, amlodipine, hydrochlorothiazide) Tablets is a combination of an angiotensin receptor blocker, a calcium channel blocker, and a diuretic used to treat high blood pressure.

WARNING

FETAL TOXICITY

• When pregnancy is detected, discontinue Tribenzor as soon as possible.
• Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Common side effects of Tribenzor include:

• dizziness,
• lightheadedness,
• tiredness,
• headache,
• diarrhea,
• muscle spasms or twitching,
• cold symptoms (stuffy or runny nose, sneezing, sore throat),
• flushing (warmth, redness, or tingly feeling),
• swelling of the hands or feet,
• nausea,
• upper respiratory tract infection,
• urinary tract infection, and
• swelling of the joints.

Tell your doctor if you have serious side effects of Tribenzor including:

• fainting,
• severe tiredness,
• big toe/joint pain,
• swelling hands/ankles/feet,
• symptoms of a high potassium blood level (such as muscle weakness, slow/irregular heartbeat),
• unusual change in the amount of urine (not including the normal increase in urine when you first start this drug), and
• severe or persistent diarrhea.

Dose once daily. Dosage may be increased in 2 week intervals, as needed. The maximum recommended dose of Tribenzor is 40/10/25 mg.

Dose selection should be individualized based on previous therapy.

Dosage Forms And Strengths

Tribenzor tablets are available in the following strength combinations:

Drug Interactions With Olmesartan Medoxomil

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)

• In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including olmesartan medoxomil, may result in deterioration of renal function, including possible acute renal failure.
• These effects are usually reversible. Monitor renal function periodically in patients receiving olmesartan medoxomil and NSAID therapy.
• The antihypertensive effect of angiotensin II receptor antagonists, including olmesartan medoxomil may be attenuated by NSAIDs including selective COX-2 inhibitors.

Dual Blockade Of The Renin-Angiotensin System (RAS)

• Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
• Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy.
• In general, avoid combined use of RAS inhibitors.
• Closely monitor blood pressure, renal function and electrolytes in patients on Tribenzor and other agents that affect the RAS.
• Do not co-administer aliskiren with Tribenzor in patients with diabetes [See CONTRAINDICATIONS]. Avoid use of aliskiren with Tribenzor in patients with renal impairment (GFR <60 ml/min).

Use With Colesevelam Hydrochloride

• Concurrent administration of bile acid sequestering agent colesevelam hydrochloride reduces the systemic exposure and peak plasma concentration of olmesartan.
• Administration of olmesartan at least 4 hours prior to colesevelam hydrochloride decreased the drug interaction effect.
• Consider administering olmesartan at least 4 hours before the colesevelam hydrochloride dose.

Lithium

• Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of olmesartan or thiazide diuretics.
• Monitor lithium levels in patients receiving Tribenzor and lithium.

Drug Interactions With Amlodipine

Simvastatin

• Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.

Immunosuppressants

• Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate.

CYP3A Inhibitors

• Co-administration of amlodipine with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction.
• Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment.

CYP3A Inducers

• No information is available on the quantitative effects of CYP3A inducers on amlodipine.
• Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.

Drug Interactions With Hydrochlorothiazide

• When administered concurrently the following drugs may interact with thiazide diuretics:
• Antidiabetic Drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.
• Cholestyramine and Colestipol Resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single dose of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.
• Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia.
• Non-steroidal Anti-inflammatory Drugs: In some patients the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when hydrochlorothiazide tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patients should be observed closely to determine if the desired effect of the diuretic is obtained.

• Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.
• Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.
• Potential neonatal adverse effects include
  • skull hypoplasia,
  • anuria,
  • hypotension,
  • renal failure, and
  • death.
• When pregnancy is detected, discontinue Tribenzor as soon as possible.
• These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy.
• Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
• Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
• In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.
• Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Tribenzor, unless it is considered lifesaving for the mother.
• Fetal testing may be appropriate, based on the week of pregnancy.
• Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Tribenzor for hypotension, oliguria, and hyperkalemia.
• It is not known whether amlodipine or olmesartan are excreted in human milk, but thiazides appear in human milk and olmesartan is secreted at low concentration in the milk of lactating rats.
• Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.