Adalat CC

Name: Adalat CC

Proper Use of nifedipine

This section provides information on the proper use of a number of products that contain nifedipine. It may not be specific to Adalat CC. Please read with care.

In addition to the use of this medicine, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium (salt). 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 this medicine 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.

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

If you are taking the extended-release tablets, part of the tablet may pass into your stool after your body has absorbed the medicine. This is normal and nothing to worry about.

Dosing

The dose of this medicine 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 this medicine. 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 treatment of chest pain or high blood pressure:
    • For oral dosage form (capsules):
      • Adults—At first, 10 milligrams (mg) three times a day. Your doctor may increase your dose as needed.
      • Children—Use and dose must be determined by your doctor.
    • For oral dosage form (extended-release tablets):
      • Adults—At first, 30 or 60 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 90 mg once a day.
      • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, 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.

What do I need to tell my doctor BEFORE I take Adalat CC?

  • If you have an allergy to nifedipine or any other part of Adalat CC (nifedipine extended-release tablets).
  • 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 any of these drugs: Carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's wort.
  • If you have had a recent heart attack.
  • If you are breast-feeding or plan to breast-feed.
  • If you have a rare hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. Some products have lactose.

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 Adalat CC with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Adalat CC?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how Adalat CC affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • It is rare, but worse chest pain and heart attack can happen after this medicine is first started or after the dose is raised. The risk may be greater in people who have very bad heart blood vessel disease. Talk with the doctor.
  • Have your blood pressure checked often. Talk with your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Avoid grapefruit and grapefruit juice.
  • If you are taking Adalat CC and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • Very bad stomach and bowel problems like blockage and ulcers have happened with a long-acting form of this medicine. Sometimes, these problems have led to the need to go to the hospital. Talk with the doctor.
  • This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Adalat CC with your other drugs.
  • If you are 65 or older, use this medicine with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Adalat CC while you are pregnant.

Adalat CC - Clinical Pharmacology

Nifedipine is a calcium ion influx inhibitor (slow-channel blocker or calcium ion antagonist) which inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The contractile processes of vascular smooth muscle and cardiac muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Nifedipine selectively inhibits calcium ion influx across the cell membrane of vascular smooth muscle and cardiac muscle without altering serum calcium concentrations.

Mechanism of Action

The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. The increased peripheral vascular resistance, an underlying cause of hypertension, results from an increase in active tension in the vascular smooth muscle. Studies have demonstrated that the increase in active tension reflects an increase in cytosolic free calcium.

Nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. The binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. Stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. The reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure.

Pharmacokinetics and Metabolism

Nifedipine is completely absorbed after oral administration. The bioavailability of nifedipine as Adalat CC relative to immediate release nifedipine is in the range of 84%-89%. After ingestion of Adalat CC tablets under fasting conditions, plasma concentrations peak at about 2.5-5 hours with a second small peak or shoulder evident at approximately 6-12 hours post dose. The elimination half-life of nifedipine administered as Adalat CC is approximately 7 hours in contrast to the known 2 hour elimination half-life of nifedipine administered as an immediate release capsule.

When Adalat CC is administered as multiples of 30 mg tablets over a dose range of 30 mg to 90 mg, the area under the curve (AUC) is dose proportional; however, the peak plasma concentration for the 90 mg dose given as 3 x 30 mg is 29% greater than predicted from the 30 mg and 60 mg doses.

Two 30 mg Adalat CC tablets may be interchanged with a 60 mg Adalat CC tablet. Three 30 mg Adalat CC tablets, however, result in substantially higher Cmax values than those after a single 90 mg Adalat CC tablet. Three 30 mg tablets should, therefore, not be considered interchangeable with a 90 mg tablet.

Once daily dosing of Adalat CC under fasting conditions results in decreased fluctuations in the plasma concentration of nifedipine when compared to t.i.d. dosing with immediate release nifedipine capsules. The mean peak plasma concentration of nifedipine following a 90 mg Adalat CC tablet, administered under fasting conditions, is approximately 115 ng/mL. When Adalat CC is given immediately after a high fat meal in healthy volunteers, there is an average increase of 60% in the peak plasma nifedipine concentration, a prolongation in the time to peak concentration, but no significant change in the AUC. Plasma concentrations of nifedipine when Adalat CC is taken after a fatty meal result in slightly lower peaks compared to the same daily dose of the immediate release formulation administered in three divided doses. This may be, in part, because Adalat CC is less bioavailable than the immediate release formulation.

Nifedipine is extensively metabolized to highly water soluble, inactive metabolites accounting for 60% to 80% of the dose excreted in the urine. Only traces (less than 0.1% of the dose) of the unchanged form can be detected in the urine. The remainder is excreted in the feces in metabolized form, most likely as a result of biliary excretion.

Nifedipine is metabolized via the cytochrome P450 3A4 system. Drugs that are known to either inhibit or induce this enzyme system may alter the first pass or clearance of nifedipine.

No studies have been performed with Adalat CC in patients with renal failure; however, significant alterations in the pharmacokinetics of nifedipine immediate release capsules have not been reported in patients undergoing hemodialysis or chronic ambulatory peritoneal dialysis. Since the absorption of nifedipine from Adalat CC could be modified by renal disease, caution should be exercised in treating such patients.

Because nifedipine is metabolized via the cytochrome P450 3A4 system, its pharmacokinetics may be altered in patients with chronic liver disease. Adalat CC has not been studied in patients with hepatic disease; however, in patients with hepatic impairment (liver cirrhosis) nifedipine has a longer elimination half-life and higher bioavailability than in healthy volunteers.

The degree of protein binding of nifedipine is high (92%-98%). Protein binding may be greatly reduced in patients with renal or hepatic impairment.

After administration of Adalat CC to healthy elderly men and women (age > 60 years), the mean Cmax is 36% higher and the average plasma concentration is 70% greater than in younger patients.

In healthy subjects, the elimination half-life of a different sustained release nifedipine formulation was longer in elderly subjects (6.7 h) compared to young subjects (3.8 h) following oral administration. A decreased clearance was also observed in the elderly (348 mL/min) compared to young subjects (519 mL/min) following intravenous administration.

Co-administration of nifedipine with grapefruit juice results in up to a 2-fold increase in AUC and Cmax, due to inhibition of CYP3A related first-pass metabolism. Ingestion of grapefruit and grapefruit juice should be avoided while taking nifedipine.

Clinical Studies

Adalat CC produced dose-related decreases in systolic and diastolic blood pressure as demonstrated in two double-blind, randomized, placebo-controlled trials in which over 350 patients were treated with Adalat CC 30, 60 or 90 mg once daily for 6 weeks. In the first study, Adalat CC was given as monotherapy and in the second study, Adalat CC was added to a beta-blocker in patients not controlled on a beta-blocker alone. The mean trough (24 hours post-dose) blood pressure results from these studies are shown below:

MEAN REDUCTIONS IN TROUGH SUPINE BLOOD PRESSURE (mmHg)
SYSTOLIC/DIASTOLIC
* Placebo response subtracted.

STUDY 1

Adalat CC

N

MEAN TROUGH

DOSE

REDUCTION*

30 MG

60

5.3/2.9

60 MG

57

8.0/4.1

90 MG

55

12.5/8.1

 

 

 

STUDY 2

Adalat CC

N

MEAN TROUGH

DOSE

REDUCTION*

30 MG

58

7.6/3.8

60 MG

63

10.1/5.3

90 MG

62

10.2/5.8

The trough/peak ratios estimated from 24 hour blood pressure monitoring ranged from 41%-78% for diastolic and 46%-91% for systolic blood pressure.

Hemodynamics

Like other slow-channel blockers, nifedipine exerts a negative inotropic effect on isolated myocardial tissue. This is rarely, if ever, seen in intact animals or man, probably because of reflex responses to its vasodilating effects. In man, nifedipine decreases peripheral vascular resistance which leads to a fall in systolic and diastolic pressures, usually minimal in normotensive volunteers (less than 5-10 mm Hg systolic), but sometimes larger. With Adalat CC, these decreases in blood pressure are not accompanied by any significant change in heart rate. Hemodynamic studies of the immediate release nifedipine formulation in patients with normal ventricular function have generally found a small increase in cardiac index without major effects on ejection fraction, left ventricular end-diastolic pressure (LVEDP) or volume (LVEDV). In patients with impaired ventricular function, most acute studies have shown some increase in ejection fraction and reduction in left ventricular filling pressure.

Electrophysiologic Effects

Although, like other members of its class, nifedipine causes a slight depression of sinoatrial node function and atrioventricular conduction in isolated myocardial preparations, such effects have not been seen in studies in intact animals or in man. In formal electrophysiologic studies, predominantly in patients with normal conduction systems, nifedipine administered as the immediate release capsule has had no tendency to prolong atrioventricular conduction or sinus node recovery time, or to slow sinus rate.

Warnings

Excessive Hypotension

Although in most patients the hypotensive effect of nifedipine is modest and well tolerated, occasional patients have had excessive and poorly tolerated hypotension. These responses have usually occurred during initial titration or at the time of subsequent upward dosage adjustment, and may be more likely in patients using concomitant beta-blockers.

Severe hypotension and/or increased fluid volume requirements have been reported in patients who received immediate release capsules together with a beta-blocking agent and who underwent coronary artery bypass surgery using high dose fentanyl anesthesia. The interaction with high dose fentanyl appears to be due to the combination of nifedipine and a beta-blocker, but the possibility that it may occur with nifedipine alone, with low doses of fentanyl, in other surgical procedures, or with other narcotic analgesics cannot be ruled out. In nifedipine-treated patients where surgery using high dose fentanyl anesthesia is contemplated, the physician should be aware of these potential problems and, if the patient’s condition permits, sufficient time (at least 36 hours) should be allowed for nifedipine to be washed out of the body prior to surgery.

Increased Angina and/or Myocardial Infarction

Rarely, patients, particularly those who have severe obstructive coronary artery disease, have developed well-documented increased frequency, duration and/or severity of angina or acute myocardial infarction upon starting nifedipine or at the time of dosage increase. The mechanism of this effect is not established.

Beta-Blocker Withdrawal

 When discontinuing a beta-blocker it is important to taper its dose, if possible, rather than stopping abruptly before beginning nifedipine. Patients recently withdrawn from beta blockers may develop a withdrawal syndrome with increased angina, probably related to increased sensitivity to catecholamines. Initiation of nifedipine treatment will not prevent this occurrence and on occasion has been reported to increase it.

Congestive Heart Failure

Rarely, patients (usually while receiving a beta-blocker) have developed heart failure after beginning nifedipine. Patients with tight aortic stenosis may be at greater risk for such an event, as the unloading effect of nifedipine would be expected to be of less benefit to these patients, owing to their fixed impedance to flow across the aortic valve.

Adverse experiences

The incidence of adverse events during treatment with Adalat CC in doses up to 90 mg daily were derived from multi-center placebo-controlled clinical trials in 370 hypertensive patients. Atenolol 50 mg once daily was used concomitantly in 187 of the 370 patients on Adalat CC and in 64 of the 126 patients on placebo. All adverse events reported during Adalat CC therapy were tabulated independently of their causal relationship to medication.

The most common adverse event reported with Adalat CC was peripheral edema. This was dose related and the frequency was 18% on Adalat CC 30 mg daily, 22% on Adalat CC 60 mg daily and 29% on Adalat CC 90 mg daily versus 10% on placebo.

Other common adverse events reported in the above placebo-controlled trials include:

Adalat CC (%) PLACEBO (%)
(n=370) (n=126)
Adverse Event

Headache

19

13

Flushing/heat sensation

4

0

Dizziness

4

2

Fatigue/asthenia

4

4

Nausea

2

1

Constipation

1

0

Where the frequency of adverse events with Adalat CC and placebo is similar, causal relationship cannot be established.

The following adverse events were reported with an incidence of 3% or less in daily doses up to 90 mg:

Body as a Whole/Systemic: chest pain, leg pain

Central Nervous System: paresthesia, vertigo

Dermatologic: rash

Gastrointestinal: constipation

Musculoskeletal: leg cramps

Respiratory: epistaxis, rhinitis

Urogenital: impotence, urinary frequency

Other adverse events reported with an incidence of less than 1.0% were:

Body as a Whole/Systemic: allergic reaction, asthenia, cellulitis, substernal chest pain, chills, facial edema, lab test abnormal, malaise, neck pain, pelvic pain, pain, photosensitivity reaction

Cardiovascular: atrial fibrillation, bradycardia, cardiac arrest, extrasystole, hypotension, migraine, palpitations, phlebitis, postural hypotension, tachycardia, cutaneous angiectases

Central Nervous System: anxiety, confusion, decreased libido, depression, hypertonia, hypesthesia, insomnia, somnolence

Dermatologic: angioedema, petechial rash, pruritus, sweating

Gastrointestinal: abdominal pain, diarrhea, dry mouth, dysphagia, dyspepsia, eructation, esophagitis, flatulence, gastrointestinal disorder, gastrointestinal hemorrhage, GGT increased, gum disorder, gum hemorrhage, vomiting

Hematologic: eosinophilia, lymphadenopathy

Metabolic: gout, weight loss

Musculoskeletal: arthralgia, arthritis, joint disorder, myalgia, myasthenia

Respiratory: dyspnea, increased cough, rales, pharyngitis, stridor

Special Senses: abnormal vision, amblyopia, conjunctivitis, diplopia, eye disorder, eye hemorrhage, tinnitus

Urogenital/Reproductive: dysuria, kidney calculus, nocturia, breast engorgement, polyuria, urogenital disorder, erectile dysfunction (ED)

The following adverse events have been reported rarely in patients given nifedipine in coat core or other formulations: allergenic hepatitis, alopecia, anaphylactic reaction, anemia, arthritis with ANA (+), depression, erythromelalgia, exfoliative dermatitis, fever, gingival hyperplasia, gynecomastia, hyperglycemia, jaundice, leukopenia, mood changes, muscle cramps, nervousness, paranoid syndrome, purpura, shakiness, sleep disturbances, Stevens-Johnson syndrome, syncope, taste perversion, thrombocytopenia, toxic epidermal necrolysis, transient blindness at the peak of plasma level, tremor and urticaria.

How is Adalat CC Supplied

Adalat CC extended release tablets are supplied as 30 mg, 60 mg, and 90 mg round film coated tablets. The different strengths can be identified as follows:

Strength Color Markings

30 mg

Pink

30 on one side and Adalat CC on the other side

60 mg

Salmon

60 on one side and Adalat CC on the other side

90 mg

Dark Red

90 on one side and Adalat CC on the other side

Adalat® CC Tablets are supplied in:

Strength NDC Code

Bottles of 100

30 mg

52427-494-01

60 mg

52427-495-01

90 mg

52427-496-01

The tablets should be protected from light and moisture and stored below 86°F (30°C). Dispense in tight, light-resistant containers.

Manufactured for:

Almatica Pharma, Inc.

Pine Brook, NJ 07058 USA

Adalat is a registered trademark of Alvogen Group Holdings LLC

Rx Only

PI494-00 Rev. 05/2016 P

Principal Display Panel

NDC 52427-494-01

ADALAT© CC

(nifedipine)

Extended Release Tablets

30 mg

100 Tablets

Rx Only

Principle Display Panel

NDC 52427-495-01 

ADALAT© CC

(nifedipine)

Extended Release Tablets

60 mg

100 Tablets

Rx Only

Principle Display Panel

NDC 52427-496-01

ADALAT© CC

(nifedipine)

Extended Release Tablets

90 mg

100 Tablets

Rx Only

Adalat CC 
nifedipine tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52427-494
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NIFEDIPINE (NIFEDIPINE) NIFEDIPINE 30 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
CROSPOVIDONE (15 MPA.S AT 5%)  
FERRIC OXIDE RED  
HYDROXYPROPYL CELLULOSE (TYPE H)  
HYPROMELLOSES  
LACTOSE, UNSPECIFIED FORM  
MAGNESIUM STEARATE  
POLYETHYLENE GLYCOLS  
SILICON DIOXIDE  
STARCH, CORN  
TITANIUM DIOXIDE  
Product Characteristics
Color PINK Score no score
Shape ROUND Size 15mm
Flavor Imprint Code 30;ADALAT;CC
Contains     
Packaging
# Item Code Package Description
1 NDC:52427-494-01 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020198 02/01/2017
Adalat CC 
nifedipine tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52427-495
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NIFEDIPINE (NIFEDIPINE) NIFEDIPINE 60 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
CROSPOVIDONE (15 MPA.S AT 5%)  
FERRIC OXIDE RED  
HYDROXYPROPYL CELLULOSE (TYPE H)  
HYPROMELLOSES  
LACTOSE, UNSPECIFIED FORM  
MAGNESIUM STEARATE  
POLYETHYLENE GLYCOLS  
SILICON DIOXIDE  
STARCH, CORN  
TITANIUM DIOXIDE  
Product Characteristics
Color PINK (SALMON) Score no score
Shape ROUND Size 15mm
Flavor Imprint Code 60;ADALAT;CC
Contains     
Packaging
# Item Code Package Description
1 NDC:52427-495-01 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020198 02/01/2017
Adalat CC 
nifedipine tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52427-496
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NIFEDIPINE (NIFEDIPINE) NIFEDIPINE 90 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE  
CROSPOVIDONE (15 MPA.S AT 5%)  
FERRIC OXIDE RED  
HYDROXYPROPYL CELLULOSE (TYPE H)  
HYPROMELLOSES  
LACTOSE, UNSPECIFIED FORM  
MAGNESIUM STEARATE  
POLYETHYLENE GLYCOLS  
SILICON DIOXIDE  
STARCH, CORN  
TITANIUM DIOXIDE  
Product Characteristics
Color PINK Score no score
Shape ROUND Size 15mm
Flavor Imprint Code 90;ADALAT;CC
Contains     
Packaging
# Item Code Package Description
1 NDC:52427-496-01 100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020198 02/01/2017
Labeler - Almatica Pharma Inc. (962454505)
Revised: 12/2015   Almatica Pharma Inc.

What is the most important information i should know about nifedipine (procardia)?

You should not use nifedipine if you are allergic to it.

Before taking nifedipine, tell your doctor if you have kidney or liver disease, a blockage in your digestive tract (stomach or intestines), a history of stomach surgery, coronary artery disease, underactive thyroid, diabetes, or congestive heart failure.

If you need surgery, tell the surgeon ahead of time that you are using nifedipine. You may need to stop using the medicine for a short time.

Many drugs can interact with nifedipine. Tell your doctor about all other medications you use.

Do not stop taking nifedipine without first talking to your doctor, even if you feel fine. Stopping suddenly may make your condition worse. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Nifedipine Pregnancy Warnings

Animal studies have revealed evidence of embryotoxicity, placentotocity, fetotoxicity, and teratogenicity. There are no controlled data in human pregnancy. Cases of perinatal asphyxia, cesarean delivery, prematurity, and intrauterine growth retardation were reported. Calcium channel blockers (CCBs) have been associated with acute pulmonary edema, especially in patients receiving IV CCBs, those with multiple pregnancy, and/or with concomitant beta-2 agonist use. Reversible changes in sperm function have occurred with use of CCBs. AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. -Some experts recommend: Use is contraindicated. AU TGA pregnancy category: C US FDA pregnancy category: -Immediate-release capsules: C -Extended-release tablets: Not assigned. Risk Summary: This drug has been shown to be teratogenic in animal models. Comments: -If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. -Some experts recommend use after week 20 in patients only if all other treatment options are not indicated or have failed to be efficacious.

Nifedipine Levels and Effects while Breastfeeding

Summary of Use during Lactation

Because of the low levels of nifedipine in breastmilk, amounts ingested by the infant are small and no adverse effects have been reported among Because of the low levels of nifedipine in breastmilk, amounts ingested by the infant are small and no adverse effects have been reported among a limited number of infants exposed to nifedipine in breastmilk. Nifedipine is used to treat painful nipple vasospasm (e.g., Raynaud phenomenon) in nursing mothers.[1]

Drug Levels

Maternal Levels. A woman taking nifedipine10 mg four times daily was given a 20 mg test dose 10 days postpartum. One hour after this dose, peak milk levels of the drug and its pyridine metabolite were 43 and 15 mcg/L, respectively. By 4 hours after the dose, the levels of both drugs in breastmilk were less than 5 mcg/L.[2]

Another woman taking a doses of 10, 20 and 30 mg every 8 hours on different days shortly after delivering a premature infant had peak milk levels 1 hour after each dose. The half-life of the drug in milk varied with dosage: 1.4 hours with the 10 mg dose; 3.1 hours with the 20 mg dose; and 2.4 hours with the 30 mg dose. The average milk half-life of all doses was 3.3 hours. The highest milk level found was 53 mcg/L at 30 minutes after the 30 mg dose. Nifedipine had fallen to undetectable levels (<2 mcg/L) by 5.25 hours after the 10 mg dose. At 8 hours after the dose, nifedipine concentrations in milk were 3.2 mcg/L with the 20 mg dose and 4.9 mcg/L with the 30 mg dose. The total amounts in milk collected over 24 hours were 0.12 mcg with 10 mg every 8 hours, an average of 1.07 mcg with 20 mg every 8 hours, and an average of 1.71 mcg with 30 mg every 8 hours. Using the peak milk level data from the 30 mg every 8 hour dosage in this study, the authors estimated that an exclusively breastfed infant would receive an estimated maximum of 7.5 mcg/kg daily with this maternal dosage regimen.[3]

In 6 women taking a dose of 10 mg three times daily, milk levels ranged from <1 to 10.3 mcg/L at random times between 1 and 8 hours after a dose, with a median of 3.5 mcg/L.[4]

In a study of 21 women taking a median dosage of 40 mg daily, mostly as a sustained-release product, 13 donated milk samples at a median of 7 days postpartum (range 1 to 100 days). The infants would receive an average daily dosage of 0.1% of their mother's weight-adjusted dosage in breast milk.[5]

Effects in Breastfed Infants

No adverse reactions have been reported among infants exposed to nifedipine in breastmilk mostly at maternal dosages of 30 mg daily beginning shortly postpartum and continuing for up to 6 months in some.[2][5][6][7][8][9][10][11]

Effects on Lactation and Breastmilk

No direct effects are known. However, nifedipine has been used to decrease the pain of nipple vasospasm (or Raynaud phenomenon of the nipple), allowing mothers to continue nursing who might otherwise discontinue breastfeeding. The dosage of nifedipine reportedly used to treat the condition is 30 to 60 mg daily either as a single dose of a sustained-release product or 10 to 20 mg 3 times daily of an immediate-release product. Lower dosages can be tried if these doses are not tolerated.[1][6][7][8][9][12]

Nifedipine had no effect on milk composition (sodium, potassium, calcium, chloride, nitrogen, phosphorus and total lipids) in one woman.[3]

Alternate Drugs to Consider

Nitrendipine

References

1. Berens P, Eglash A, Malloy M et al. ABM Clinical Protocol #26: Persistent pain with breastfeeding. Breastfeed Med. 2016;11:46-53. PMID: 26881962

2. Penny WJ, Lewis MJ. Nifedipine is excreted in human milk. Eur J Clin Pharmacol. 1989;36(4):427-8. PMID: 2737237

3. Ehrenkranz RA, Ackerman BA, Hulse JD. Nifedipine transfer into human milk. J Pediatr. 1989;114(3):478-80. PMID: 2921695

4. Manninen AK, Juhakoski A. Nifedipine concentrations in maternal and umbilical serum, amniotic flud, breast milk and urine of mothers and offspring. Int J Clin Pharm Res. 1991;11:231-6. PMID: 1814844

5. Taddio A, Oskamp M, Ito S et al. Is nifedipine use during labour and breast-feeding safe for the neonate? Clin Invest Med. 1996;19(4 Suppl):S11. Abstract.

6. Lawlor-Smith LS, Lawlor-Smith CL. Raynaud's phenomenon of the nipple: a preventable cause of breastfeeding failure? Med J Aust. 1996;166:448. Letter. PMID: 9140358

7. Garrison CP. Nipple vasospasm, Raynaud's syndrome, and nifedipine. J Hum Lact. 2002;18(4):382-5. PMID: 12449056

8. Anderson JE, Held N, Wright K. Raynaud's phenomenon of the nipple: a treatable cause of painful breastfeeding. Pediatrics. 2004;113(4):e360-4. PMID: 15060268

9. Page SM, McKenna DS. Vasospasm of the nipple presenting as painful lactation. Obstet Gynecol. 2006;108 (3 part 2):806-8. PMID: 17018510

10. O'Sullivan S, Keith MP. Raynaud phenomenon of the nipple: a rare finding in rheumatology clinic. J Clin Rheumatol. 2011;17:371-2. PMID: 21946463

11. Wu M, Chason R, Wong M. Raynaud's phenomenon of the nipple. Obstet Gynecol. 2012;119 (2 Pt 2):447-9. PMID: 22270434

12. Barrett ME, Heller MM, Fullerton Stone H, Murase JE. Raynaud phenomenon of the nipple in breastfeeding mothers: An underdiagnosed cause of nipple pain. JAMA Dermatology. 2013;149:300-6. PMID: 23247299

(web3)