Nisoldipine

Nisoldipine is an oral calcium channel blocker (CCB) of the dihydropyridine (DHP) class that is used to treat high blood pressure. Other calcium channel blockers in the DHP class include nifedipine (Procardia, Adalat), amlodipine (Norvasc), felodipine (Plendil), nicardipine (Cardene), and isradipine (Dynacirc). Calcium channel blockers prevent calcium from entering certain types of muscle cells. Since the muscle cells need calcium to contract, CCBs prevent the cells from contracting, that is, they cause the muscle cells to relax. Nisoldipine selectively relaxes the muscles of small arteries causing the arteries to dilate but has little or no effect on muscles of veins or the heart. Dilation of arteries reduces blood pressure. Nisoldipine was approved by the FDA in February of 1995.

The recommended dose is 17 to 34 mg or 20 to 40 mg daily depending on the formulation that is used. Doses may be increased at one week intervals. Tablets should be swallowed whole and taken on an empty stomach. Individuals with poor liver function require lower doses of nisoldipine.

Cimetidine (Tagamet) or any drug that reduces the activity of liver enzymes that break down nisoldipine can increase blood levels of nisoldipine, possibly causing more side effects. Examples of drugs that may reduce break down of nisoldipine include ketoconazole, itraconazole (Sporanox), and erythromycin.

Nisoldipine is a prescription medication used to treat high blood pressure. Nisoldipine belongs to a group of drugs called calcium channel blockers, which relax blood vessels, making it easier for the heart to pump blood.

This medication comes in an extended release tablet form and is taken once a day and should be taken without food.

Common side effects of nisoldipine include swelling, headache, and nausea. Nisoldipine can cause dizziness. Do not drive or operate heavy machinery until you know how nisoldipine affects you.

Before taking nisoldipine, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• have a known hypersensitivity to nisoldipine or to any of its ingredients
• have a known hypersensitivity to aspirin
• have a known hypersensitivity to the inactive ingredient FD&C Yellow No. 5 (tartrazine)
• have liver problems
• have kidney problems
• have heart problems
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

• Store at room temperature between 15 – 30°C (59 – 86°F).
• Dispense in tight, light-resistant containers.
• Protect from light and moisture.
• Keep this and all medicines out of the reach of children.

Calcium-channel blocking agent; dihydropyridine derivative.1 2 3 4 5 6 8 9 10 11 12 42 45

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 11 12 500

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).500 501 502 503 504 515

Calcium-channel blockers may be preferred in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease)45 523 and in geriatric patients, including those with isolated systolic hypertension.502 510

Black hypertensive patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).500 501 504 However, diminished response to these other drug classes is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

Should not be used for acute management of hypertensive crises†.46

In addition to the use of nisoldipine, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet .

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well .

Remember that nisoldipine will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease .

Take nisoldipine exactly as directed even if you feel well. Do not take more of nisoldipine and do not take it more often than your doctor ordered. nisoldipine works best if there is a constant amount in the blood. To keep blood levels constant, take nisoldipine at the same time each day and do not miss any doses.

Swallow the extended release tablet whole. Do not break, crush, or chew it. It is best to take nisoldipine on an empty stomach .

Dosing

The dose of nisoldipine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of nisoldipine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended release tablets):
  • For high blood pressure:
    • Adults—10 to 20 milligrams (mg) once a day. Your doctor may increase your dose if needed.
    • Children—Use and dose must be determined by your doctor .

Missed Dose

If you miss a dose of nisoldipine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloating or swelling of face, arms, hands, lower legs, or feet
• rapid weight gain
• tingling of hands or feet
• unusual weight gain or loss

• Chest pain
• dizziness, lightheadedness, or fainting
• fast, irregular, pounding, or racing heartbeat or pulse
• feeling of warmth or heat
• flushing or redness of skin, especially on face and neck
• headache
• rash
• sweating

• Chest tightness
• shortness of breath
• swelling of the arms, face, legs, lips, tongue, or throat

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Body aches or pain
• congestion
• cough
• dryness or soreness of throat
• fever
• heartbeat sensations
• hoarseness
• pain or tenderness around eyes and cheekbones
• runny nose
• stuffy nose
• tender, swollen glands in neck
• trouble in swallowing
• voice changes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If you have an allergy to nisoldipine or any other part of nisoldipine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are taking phenytoin.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take nisoldipine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use nisoldipine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take on an empty stomach. Take 1 hour before or 2 hours after meals.
• Swallow whole. Do not chew, break, or crush.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Sular: 8.5 mg

Sular: 17 mg [contains tartrazine (fd&c yellow #5)]

Sular: 34 mg

Generic: 8.5 mg, 17 mg, 20 mg, 25.5 mg, 30 mg, 34 mg, 40 mg

Dosage adjustments are not needed in patients with mild to moderate renal function impairment.

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Consider therapy modification

Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Nisoldipine. Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Nisoldipine. Avoid combination

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Nisoldipine. Avoid combination

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Grapefruit Juice: May increase the serum concentration of Nisoldipine. Avoid combination

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Adverse events were not observed in animal reproduction studies when using doses that were not maternally toxic. Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are preferred (ACOG, 2013).

Slow release (old formulation);
Initial dose: 10 mg orally once a day
Maintenance dose: 10 to 60 mg orally once a day

Controlled release (new formulation):
Initial dose: 8.5 mg orally once a day
Maintenance dose: 8.5 to 34 mg orally once a day

Blood pressure should be monitored closely during any dosage adjustment.

Data not available

Administration with a high fat meal can lead to excessive peak drug concentration and should be avoided.

Grapefruit products should be avoided before and after dosing.

Tablets should be swallowed whole, not bitten, divided, or crushed.

This product contains tartrazine, FD&C Yellow No 5, which may cause an allergic reaction, particularly in patients with aspirin hypersensitivity.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Data not available

Slow release (old formulation):
Blood pressure response increases over the 10 to 60 mg daily dose range but adverse event rates also increase. Doses beyond 60 mg once daily are not recommended.

Controlled release (new formulation):
Blood pressure response increases over the 8.5 to 34 mg daily dose range but adverse event rates also increase. Doses beyond 34 mg once daily are not recommended.

Nisoldipine should be taken on an empty stomach, one hour before or two hours after a meal.

Periodic monitoring of blood pressure has been recommended particularly during any dosage adjustment.