Modalim Tablets 100mg

M

1. Name Of The Medicinal Product

Modalim Tablets 100 mg

2. Qualitative And Quantitative Composition

Each tablet contains 100mg ciprofibrate as the active ingredient.

For excipients, see 6.1

3. Pharmaceutical Form

Tablet.

4. Clinical Particulars 4.1 Therapeutic Indications

Modalim tablets are recommended for the treatment of primary dyslipoproteinaemias, including types IIa, IIb, III and IV (hypercholesterolaemia, hypertriglyceridaemia and combined forms) - refractory to appropriate dietary treatment.

Dietary measures should be continued during therapy.

4.2 Posology And Method Of Administration

Adults

The recommended dosage is one tablet (100mg ciprofibrate) per day. This dose should not be exceeded (see Precautions).

Elderly Patients

As for adults, but see Precautions and Warnings.

Use in Case of Impaired Renal Function

In moderate renal impairment it is recommended that dosage be reduced to one tablet every other day. Patients should be carefully monitored. Modalim should not be used in severe renal impairment.

Use in Children

Not recommended since safety and efficacy in children has not been established.

Modalim tablets are for oral administration only.

4.3 Contraindications

Severe hepatic impairment.

Severe renal impairment.

Pregnancy and lactation.

Concurrent use with another fibrate.

Hypersensitivity to the active substance or to any component of the product.

4.4 Special Warnings And Precautions For Use

4.4.1 Special warnings

Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.

-Myalgia/myopathy:

- Patients should be advised to report unexplained muscle pain, tenderness or weakness immediately.

CPK levels should be assessed immediately in patients reporting these symptoms. Treatment should be discontinued if CPK levels are greater than ten times the upper limit of the normal range, if levels rise progressively or if there is other evidence of myopathy.

- Doses of 200mg Modalim per day or greater have been associated with a high risk of rhabdomyolysis. Therefore the daily dose should not exceed 100mg.

- Impaired renal function and any situation of hypoalbuminaemia such as nephrotic syndrome, high alcohol intake or hypothyroidism may increase the risk of myopathy.

- As with other fibrates, the risk of rhabdomyolysis and myoglobinuria may be increased if ciprofibrate is used in combination with other fibrates or HMG CoA reductase inhibitors (see section 4.3 Contraindications and section 4.5 Interaction with other Medicinal Products and Other Forms of Interaction).

Use with caution in patients with impaired hepatic function.

Periodic hepatic function tests are recommended. Modalim treatment should be discontinued if significant transaminases abnormalities persist or if cholestatic liver injury is evidenced.

Secondary causes of dyslipidaemia, such as hypothyroidism, should be excluded or corrected prior to commencing any lipid lowering drug treatment.

4.4.2 Special precautions for use

Association with oral anticoagulant therapy: concomitant oral anticoagulant therapy should be given at reduced dosage and adjusted according to INR (see section 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction).

If after a period of administration lasting several months, a satisfactory reduction in serum lipid concentrations has not been obtained, additional or different therapeutic measures must be considered.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

•Contra-indicated combination

Other fibrates: As with other fibrates, the risk of rhabdomyolysis and myoglobinuria may be increased if ciprofibrate is used in combination with other fibrates (see section 4.3 Contra-indications and section 4.4.1 Special warnings).

•Not recommended combinations

HMG CoA reductase inhibitors: As with other fibrates, the risk of myopathy, rhabdomyolysis and myoglobinuria may be increased if ciprofibrate is used in combination with HMG CoA reductase inhibitors (see section 4.4.1 Special warnings). The benefits of combined use should be carefully weighed against the risks. Physicians contemplating concomitant therapy with HMG CoA reductase inhibitors should consult the SPC of the relevant HMG CoA reductase inhibitor as some higher doses are contraindicated / not recommended with fibrates.

•Combination requiring caution

Oral anticoagulant therapy: Ciprofibrate is highly protein bound and therefore likely to displace other drugs from plasma protein binding sites. Ciprofibrate has been shown to potentiate the effect of warfarin, indicating that concomitant oral anticoagulant therapy should be given at reduced dosage and adjusted according to INR (see section 4.4.2 Special precautions for use).

•Combination to be taken into account

Oral hypoglycaemics: A possible interaction should be considered.

Oestrogens: Oestrogens can raise lipid levels. Although a pharmacodynamic interaction may be suggested, no clinical data are currently available.

4.6 Pregnancy And Lactation

There is no evidence that ciprofibrate is teratogenic but signs of embryotoxicity were observed at high doses in animals. Ciprofibrate is excreted in the breast milk of lactating rats. There are no data on the use of the drug in human pregnancy or lactation. Therefore the use of ciprofibrate is contraindicated during pregnancy and in nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

Dizziness, drowsiness, and tiredness have only rarely been reported in association with ciprofibrate. Patients should be warned that if they are affected they should not drive or operate machinery.

4.8 Undesirable Effects

Cutaneous disorders:

Cutaneous reactions mainly allergic have been reported: rashes, urticaria and pruritus, and very rarely photosensitivity.

As with other drugs in this class, a low occurrence of alopecia has been reported.

Muscular disorders:

As with other fibrates, elevation of serum creatine phosphokinase (CPK), myalgia and myopathy including myositis and rare cases of rhabdomyolysis have been reported. In the majority of cases muscle toxicity is reversible when treatment is withdrawn (see section 4.4 Special Warnings and Special Warnings for Use).

Neurological disorders:

Occasional reports of headache, vertigo.

Dizziness, drowsiness have only rarely been reported in association with ciprofibrate.

As with other drugs of this class, a low occurrence of impotence has been reported.

Gastro-intestinal disorders:

There have been occasional reports of gastrointestinal symptoms including nausea, vomiting, diarrhoea, dyspepsia, and abdominal pain. Generally, these side effects were mild to moderate in nature and occurred early on, becoming less frequent as treatment progressed.

Hepato-biliary disorders:

As with other fibrates, abnormal liver function tests have been observed occasionally. Very rare cases of cholestasis or cytolysis have been reported (see section 4.4 Special Warnings and Special Precautions for Use). Exceptional cases with chronic evolution have been observed.

Pulmonary disorders:

Isolated cases of pneumonitis or pulmonary fibrosis have been reported.

General disorders:

Tiredness has only rarely been reported in association with ciprofibrate.

4.9 Overdose

Overdosage with ciprofibrate has been rarely reported. Associated adverse events reflect those seen in routine use. There are no specific antidotes to ciprofibrate. Treatment of overdosage should be symptomatic. Gastric lavage and appropriate supportive care may be instituted if necessary. Ciprofibrate is non-dialysable.

5. Pharmacological Properties 5.1 Pharmacodynamic Properties

ATC Code: C10A B08

Pharmacotherapeutic group: Serum lipid reducing agents - fibrates.

Ciprofibrate is a new derivative of phenoxyisobutyric acid which has a marked hypolipidaemic action. It reduces both LDL and VLDL and hence the levels of triglyceride and cholesterol associated with these lipoprotein fractions. It also increases levels of HDL cholesterol.

Ciprofibrate is effective in the treatment of hyperlipidaemia associated with high plasma concentrations of LDL and VLDL (types IIa, IIb, III and IV according to the Fredrickson Classification). In clinical studies ciprofibrate has been shown to be effective in complementing the dietary treatment of such conditions.

5.2 Pharmacokinetic Properties

Ciprofibrate is readily absorbed in man, with maximum plasma concentrations occurring mainly between one and four hours following an oral dose. Following a single dose of 100mg, in volunteers, maximum plasma concentration of ciprofibrate was between 21 and 36?g/ml. In patients on chronic therapy, maximum levels from 53 to 165?g/ml have been measured.

Terminal elimination half-life in patients on long term therapy varies from 38 to 86 hours. The elimination half-life in subjects with moderate renal insufficiency was slightly increased compared with normal subjects (116.7h compared with 81.1h). In subjects with severe renal impairment, a significant increase was noted (171.9h).

Approximately 30-75% of a single dose administered to volunteers was excreted in the urine in 72 hours, either as unchanged ciprofibrate (20-25% of the total excreted) or as a conjugate. Subjects with moderate renal impairment excreted on average 7.0% of a single dose as unchanged ciprofibrate over 96 hours, compared with 6.9% in normal subjects. In subjects with severe insufficiency this was reduced to 4.7%.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Maize starch, Lactose monohydrate, Microcrystalline cellulose, Hypromellose, Powdered vegetable stearine, Sodium laurilsulfate.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

5 years when packed in blister strips

6.4 Special Precautions For Storage

There are no special storage precautions.

6.5 Nature And Contents Of Container

Clear PVC / Aluminium blister strips in packs of 28 tablets.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

sanofi-aventis

One Onslow Street

Guildford

Surrey GU1 4YS

8. Marketing Authorisation Number(S)

PL 11723/0050

9. Date Of First Authorisation/Renewal Of The Authorisation

13 June 2002

10. Date Of Revision Of The Text

October 2006

11. Legal Category

POM

Modalim Tablets 100mg

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