Chemical formula: C₁₇H₁₈N₂O₆ Molecular mass: 346.335 g/mol PubChem compound: 4485
Nifedipine interacts in the following cases:
Nifedipine may increase the blood pressure lowering effect of PDE 5 inhibitors.
Nifedipine may increase the blood pressure lowering effect of α-adrenergic blocking agents.
Upon co-administration of weak to moderate inhibitors of the cytochrome P450 3A4 system the blood pressure should be monitored and, if necessary, a reduction in the nifedipine dose considered.
Nifedipine may increase the blood pressure lowering effect of diuretics.
Nifedipine may increase the blood pressure lowering effect of β-blockers. When nifedipine is administered simultaneously with β-receptor blockers, the patient should be carefully monitored, since deterioration of heart failure is also known to develop in isolated cases. Nifedipine may be used in combination with beta-blocking drugs and other antihypertensive agents but the possibility of an additive effect resulting in postural hypotension should be borne in mind. Nifedipine will not prevent possible rebound effects after cessation of other antihypertensive therapy.
Nifedipine may increase the blood pressure lowering effect of other calcium antagonists.
Nifedipine may increase the blood pressure lowering effect of ACE-inhibitors.
Nifedipine may increase the blood pressure lowering effect of angiotensin II receptor-antagonists.
A formal interaction study investigating the potential of a drug interaction between nifedipine and certain azole anti-mycotics has not yet been performed. Drugs of this class are known to inhibit the cytochrome P450 3A4 system. When administered orally together with nifedipine, a substantial increase in systemic bioavailability of nifedipine due to a decreased first pass metabolism cannot be excluded
No interaction studies have been carried out between nifedipine and macrolide antibiotics. Certain macrolide antibiotics are known to inhibit the cytochrome P450 3A4 mediated metabolism of other drugs. Therefore, the potential for an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
A clinical study investigating the potential of a drug interaction between nifedipine and certain anti-HIV protease inhibitors has not yet been performed. Drugs of this class are known to inhibit the cytochrome P450 3A4 system. In addition, drugs of this class have been shown to inhibit in vitro the cytochrome P450 3A4 mediated metabolism of nifedipine. When administered together with nifedipine, a substantial increase in plasma concentrations of nifedipine due to a decreased first pass metabolism and a decreased elimination cannot be excluded.
In single cases of in vitro fertilization calcium antagonists like nifedipine have been associated with reversible biochemical changes in the spermatozoa’s head section that may result in impaired sperm function. In those men who are repeatedly unsuccessful in fathering a child by in vitro fertilization, and where no other explanation can be found, calcium antagonists like nifedipine should be considered as possible causes.
No formal studies have been performed to investigate the potential interaction between nifedipine and carbamazepine or phenobarbitone. As both drugs have been shown to reduce the plasma concentrations of the structurally similar calcium channel blocker nimodipine due to enzyme induction, a decrease in nifedipine plasma concentrations and hence a decrease in efficacy cannot be excluded.
Due to its inhibition of cytochrome P450 3A4, cimetidine elevates the plasma concentrations of nifedipine and may potentiate the antihypertensive effect.
Simultaneous administration of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.
The simultaneous administration of nifedipine and digoxin may lead to reduced digoxin clearance and hence an increase in plasma concentrations of digoxin. The patient should therefore be checked for symptoms of digoxin overdosage as a precaution and, if necessary, the glycoside dose should be reduced taking account of the plasma concentration of digoxin.
Concomitant administration of nifedipine with fentanyl causes severe hypotension and the need for fluid administration has been observed in patients treated with nifedipine and fentanyl (for anesthesia).
A clinical study investigating the potential of a drug interaction between nifedipine and fluoxetine has not yet been performed. Fluoxetine has been shown to inhibit in vitro the cytochrome P450 3A4 mediated metabolism of nifedipine. Therefore an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
Nifedipine may increase the blood pressure lowering effect of α-methyldopa.
A clinical study investigating the potential of a drug interaction between nifedipine and nefazodone has not yet been performed. Nefazodone is known to inhibit the cytochrome P450 3A4 mediated metabolism of other drugs. Therefore an increase of nifedipine plasma concentrations upon co-administration of both drugs cannot be excluded.
Phenytoin induces the cytochrome P450 3A4 system. Upon co-administration with phenytoin, the bioavailability of nifedipine is reduced and thus its efficacy weakened. When both drugs are concomitantly administered, the clinical response to nifedipine should be monitored and, if necessary, an increase of the nifedipine dose considered. If the dose of nifedipine is increased during co-administration of both drugs, a reduction of the nifedipine dose should be considered when the treatment with phenytoin is discontinued.
When nifedipine and quinidine have been administered simultaneously, lowered plasma quinidine levels or, after discontinuation of nifedipine, a distinct increase in plasma concentrations of quinidine has been observed in individual cases. For this reason, when nifedipine is either additionally administered or discontinued, monitoring of the quinidine plasma concentration and, if necessary, adjustment of the quinidine dose are recommended. Some authors reported increased plasma concentrations of nifedipine upon coadministration of both drugs, while others did not observe an alteration in the pharmacokinetics of nifedipine. Therefore, the blood pressure should be carefully monitored, if quinidine is added to an existing therapy with nifedipine. If necessary, the dose of nifedipine should be decreased.
Simultaneous administration of quinupristin/dalfopristin and nifedipine may lead to increased plasma concentrations of nifedipine.
No formal studies have been performed to investigate the potential interaction between nifedipine and valproic acid. As valproic acid has been shown to increase the plasma concentrations of the structurally similar calcium channel blocker nimodipine due to enzyme inhibition, an increase in nifedipine plasma concentrations and hence an increase in efficacy cannot be excluded.
Tacrolimus has been shown to be metabolised via the cytochrome P450 3A4 system. Data recently published indicate that the dose of tacrolimus administered simultaneously with nifedipine may be reduced in individual cases. Upon co-administration of both drugs the tacrolimus plasma concentrations should be monitored and, if necessary, a reduction in the tacrolimus dose considered.
Diabetic patients taking nifedipine may require adjustment of their control.
Nifedipine should not be used during pregnancy unless the clinical condition of the woman requires treatment with nifedipine. Nifedipine should be reserved for women with severe hypertension who are unresponsive to standard therapy.
There are no adequate and well controlled studies in pregnant women.
The available information is inadequate to rule out adverse drug effects on the unborn and newborn child. Therefore any use in pregnancy requires a very careful individual risk benefit assessment and should only be considered if all other treatment options are either not indicated or have failed to be efficacious.
In animal studies nifedipine has been shown to produce embryotoxicity, fetotoxicity and teratogenicity.
From the clinical evidence available a specific prenatal risk has not been identified. Although an increase in perinatal asphyxia, caesarean delivery as well as prematurity and intrauterine growth retardation has been reported. It is unclear whether these reports are due to the underlying hypertension, its treatment or to a specific drug effect.
Acute pulmonary oedema has been observed when calcium channel blockers, among others nifedipine, have been used as a tocolytic agent during pregnancy, especially in cases of multiple pregnancy (twins or more), with the intravenous route and/or concomitant use of beta-2 agonists.
Nifedipine is excreted in the breast milk. The nifedipine concentration in the milk is almost comparable with mother serum concentration. For immediate release formulations, it is proposed to delay breastfeeding or milk expression for 3 to 4 hours after drug administration to decrease the nifedipine exposure to the infant.
In single cases of in vitro fertilization calcium antagonists like nifedipine have been associated with reversible biochemical changes in the spermatozoa’s head section that may result in impaired sperm function. In those men who are repeatedly unsuccessful in fathering a child by in vitro fertilization, and where no other explanation can be found, calcium antagonists like nifedipine should be considered as possible causes.
Reactions to the drug, which vary in intensity from individual to individual, can impair the ability to drive or to operate machinery. This applies particularly at the start of treatment, on changing the medication and in combination with alcohol.
Adverse drug reactions (ADRs) based on placebo-controlled studies with nifedipine sorted by CIOMS III categories of frequency (clinical trial data base: nifedipine n=2,661; placebo n=1,486; status: 22 Feb 2006 and the ACTION study: nifedipine n=3,825; placebo n=3,840) are listed below:
ADRs listed under “common” were observed with a frequency below 3% with the exception of oedema (9.9%) and headache (3.9%).
The frequencies of ADRs reported with nifedipine-containing products are summarised in the list below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and rare (≥1/10,000 to <1/1,000). The ADRs identified only during the ongoing postmarketing surveillance, and for which a frequency could not be estimated, are listed under “Not known”.
Not Known: Agranulocytosis, Leucopenia
Uncommon: Allergic reaction, Allergic oedema/angioedema (incl. larynx oedema*)
Rare: Pruritus, Urticaria, Rash
Not Known: Anaphylactic/Anaphlactic/anaphylactoid reaction
Uncommon: Anxiety reactions, Sleep disorders
Not Known: Hyperglycaemia
Common: Headache
Uncommon: Vertigo, Migraine, Dizziness, Tremor
Rare: Par-/Dysaesthesia
Not Known: Hypoaesthesia, Somnolence
Uncommon: Visual disturbances
Not Known: Eye pain
Uncommon: Tachycardia, Palpitations
Not Known: Chest pain (Angina pectoris)
Common: Oedema (incl. Peripheral oedema), Vasodilatation
Uncommon: Hypotension, Syncope
Uncommon: Nosebleed, Nasal congestion
Not Known: Dyspnoea, Pulmonary oedema**
Common: Constipation
Uncommon: Gastrointestinal and abdominal pain, Nausea, Dyspepsia, Flatulence, Dry mouth
Rare: Gingival hyperplasia
Not Known: Bezoar, Dysphagia, Intestinal obstruction, Intestinal ulcer, Vomiting, Gastroesophageal sphincter insufficiency
Uncommon: Transient increase in liver enzymes
Not Known: Jaundice
Uncommon: Erythema
Not Known: Toxic Epidermal Necrolysis, Photosensitivity allergic reaction, Palpable purpura
Uncommon: Muscle cramps, Joint swelling
Not Known: Arthralgia, Myalgia
Uncommon: Polyuria, Dysuria
Uncommon: Erectile dysfunction
Common: Feeling unwell
Uncommon: Unspecific pain, Chills
* = may result in life-threatening outcome
** = cases have been reported when used as tocolytic during pregnancy
In dialysis patients with malignant hypertension and hypovolaemia a distinct fall in blood pressure can occur as a result of vasodilation.
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