Lanthanum

The effect of hepatic impairment on Fosrenol pharmacokinetics has not been assessed. Due to its mechanism of action and the lack of liver metabolism doses in hepatic impairment should not be modified, but patients should be monitored carefully.

The bioavailability of oral ciprofloxacin was decreased by approximately 50% when taken with lanthanum in a single dose study in healthy volunteers. It is recommended that oral floxacin formulations are taken at least 2 hours before or 4 hours after lanthanum.

Phosphate binders (including lanthanum) have been shown to reduce the absorption of levothyroxine. Consequently, thyroid hormone replacement therapy should not be taken within 2 hours of dosing with lanthanum and closer monitoring of TSH levels is recommended in patients receiving both medicinal products.

Interactions with drugs such as tetracycline and doxycycline are theoretically possible and if these compounds are to be co-administered, it is recommended that they are not to be taken within 2 hours of dosing with lanthanum.

Lanthanum is not metabolised by liver enzymes, but it is most likely excreted in the bile. Conditions resulting in a marked reduction of bile flow may be associated with incrementally slower elimination of lanthanum, which may result in higher plasma levels and increased tissue deposition of lanthanum. As the liver is the principal organ of elimination of absorbed lanthanum monitoring of liver function tests is recommended.

Exercise caution in all patients predisposed to gastrointestinal obstruction, ileus, subileus and perforation; for example those with altered gastrointestinal anatomy (e.g., diverticular disease, peritonitis, history of gastrointestinal surgery, gastrointestinal cancer and gastrointestinal ulceration), hypomotility disorders (e.g., constipation, diabetic gastroparesis) and when used with medications known to potentiate these effects.

There are no adequate data from the use of lanthanum in pregnant women.

One study in rats showed reproductive foetotoxicity (delayed eye opening and sexual maturation) and reduced pup weights at high doses. The potential risk for humans is unknown. Lanthanum is not recommended for use during pregnancy.

It is unknown whether lanthanum is excreted in human breast milk. The excretion of lanthanum in milk has not been studied in animals. Caution should be used in taking a decision whether to continue/discontinue breast feeding or to continue/discontinue therapy with lanthanum, taking into account the potential benefit of breast feeding to the child and the potential benefit of lanthanum therapy to the nursing mother.

Fertility

There are no fertility data available on lanthanum carbonate in humans. In rat toxicology studies, lanthanum carbonate had no adverse effects on fertility.

Lanthanum may induce dizziness and vertigo, which may impair the ability to drive and use machinery.

The most commonly reported adverse drug reactions, with the exception of headache and allergic skin reactions, are gastrointestinal in nature; these are minimised by taking lanthanum with food and generally abated with time with continued dosing.

The following convention was used for frequency of adverse drug reactions: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000), not known (cannot be estimated from the available data).

^* In a clinical trial in healthy subjects, the incidence of gastrointestinal adverse events was higher after administration of the oral powder formulation of lanthanum (13 subjects, 18.3%) than after chewable tablets (4 subjects, 6.6%).

Post-marketing experience

During post-approval use of lanthanum, cases of allergic skin reactions (including skin rashes, urticaria and pruritus) have been reported which show a close temporal relationship to lanthanum carbonate therapy. In clinical trials, allergic skin reactions were seen in both lanthanum and placebo/active comparator groups at a frequency of very common (≥1/10).

Although there have been a number of additional isolated reactions reported, none of these reactions are considered unexpected in this patient population.

Transient QT changes have been observed but these were not associated with an increase of cardiac adverse events.

Paediatric population

Frequency, type and severity of adverse reactions in children have not been fully established. In particular, uncertainty exists on the accumulation in bone and risk of growth retardation with treatment in children.