PRAVASTATIN SODIUM (Page 7 of 8)

14.6 Pediatric Clinical Study

A double-blind, placebo-controlled study in 214 patients (100 boys and 114 girls) with heterozygous familial hypercholesterolemia (HeFH), aged 8 to 18 years was conducted for 2 years. The children (aged 8-13 years) were randomized to placebo (N=63) or 20 mg of pravastatin daily (N=65) and the adolescents (aged 14-18 years) were randomized to placebo (N=45) or 40 mg of pravastatin daily (N=41). Inclusion in the study required an LDL-C level >95^th percentile for age and sex and one parent with either a clinical or molecular diagnosis of familial hypercholesterolemia. The mean baseline LDL-C value was 239 mg/dL and 237 mg/dL in the pravastatin (range: 151-405 mg/dL) and placebo (range: 154-375 mg/dL) groups, respectively.

Pravastatin significantly decreased plasma levels of LDL-C, Total-C, and ApoB in both children and adolescents (see Table 10). The effect of pravastatin treatment in the 2 age groups was similar.

Table 10: Lipid-Lowering Effects of Pravastatin in Pediatric Patients with Heterozygous Familial Hypercholesterolemia: Least-Squares Mean % Change from Baseline at Month 24 (Last Observation Carried Forward: Intent-to-Treat)*

* The above least-squares mean values were calculated based on log-transformed lipid values. † Significant at p≤0.0001 when compared with placebo.
	Pravastatin 20 mg(Aged 8-13 years) N=65	Pravastatin 40 mg(Aged 14-18 years)	Combined Pravastatin (Aged 8-18 years) N=106	Combined Placebo (Aged 8-18 years) N=108	95% CI of the Difference Between Combined Pravastatin and Placebo
LDL-C	−26.04	−21.07	−24.07	−1.52	(−26.74, −18.86)
TC	−20.75	−13.08	−17.72	−0.65	(−20.40, −13.83)
HDL-C	1.04	13.71	5.97	3.13	(−1.71, −7.43)
TG	−9.58	−0.30	−5.88	−3.27	(−13.95, 10.01)
ApoB (N)	−23.16(61)†	−18.08(39)	−21.11(100)	−0.97(106)	(−24.29, −16.18)

The mean achieved LDL-C was 186 mg/dL (range: 67-363 mg/dL) in the pravastatin group compared to 236 mg/dL (range: 105-438 mg/dL) in the placebo group.

The safety and efficacy of pravastatin doses above 40 mg daily have not been studied in children. The long-term efficacy of pravastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.

15 REFERENCES

1. Fredrickson DS, Levy RI, Lees RS. Fat transport in lipoproteins — An integrated approach to mechanisms and disorders. N Engl J Med. 1967;276: 34-44, 94-103, 148-156, 215-225, 273-281.
2. Manson JM, Freyssinges C, Ducrocq MB, Stephenson WP. Postmarketing surveillance of lovastatin and simvastatin exposure during pregnancy. Reprod Toxicol. 1996;10(6):439-446.
3. Shepherd J, Cobbe SM, Ford I, et al, for the West of Scotland Coronary Prevention Study Group (WOS). Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301-1307.
4. The Long-term Intervention with Pravastatin in Ischemic Disease Group (LIPID). Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357.
5. Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol and Recurrent Events Trial Investigators (CARE). The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001-1009.
6. Pitt B, Mancini GBJ, Ellis SG, et al, for the PLAC I Investigators. Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): Reduction in atherosclerosis progression and clinical events. J Am Coll Cardiol. 1995;26:1133-1139.
7. Jukema JW, Bruschke AVG, van Boven AJ, et al, for the Regression Growth Evaluation Statin Study Group (REGRESS). Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic man with normal to moderately elevated serum cholesterol levels. Circ. 1995;91:2528-2540.
8. Crouse JR, Byington RP, Bond MG, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries: Design features of a clinical trial with carotid atherosclerosis outcome (PLAC II). Control Clin Trials. 1992;13:495-506.
9. Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circ. 1995;92:1758-1764.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Pravastatin Sodium Tablets, USP are supplied as:

10 mg tablets: White to off-white, rounded, rectangular-shaped, biconvex tablets debossed with “B 10” on one side and plain on other side. They are suppliedin bottles of 30’s Count (NDC 70377-045-11), 90’s Count (NDC 70377-045-12) and 1000’s Count (NDC 70377-045-14). Bottles contain a desiccant canister.

20 mg tablets: White to off-white, rounded, rectangular-shaped, biconvex tablets debossed with “B 20” on one side and plain on other side. They are suppliedin bottles of 30’s Count (NDC 70377-046-11), 90’s Count (NDC 70377-046-12) and 1000’s Count (NDC 70377-046-14). Bottles contain a desiccant canister.

40 mg tablets: White to off-white, rounded, rectangular-shaped, biconvex tablets debossed with “B 40” on one side and plain on other side. They are supplied in bottles of 30’s Count (NDC 70377-047-11), 90’s Count (NDC 70377-047-12) and 1000’s Count (NDC 70377-047-14). Bottles contain a desiccant canister.

80 mg tablets: White to off-white, oval-shaped, biconvex tablets, debossed with “B 80” on one side and plain on other side. They are suppliedin bottles of 30’s Count (NDC 70377-048-11), 90’s Count (NDC 70377-048-12) and 500’s Count (NDC 70377-048-13). Bottles contain a desiccant canister.

16.2 Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light.

17 PATIENT COUNSELING INFORMATION

Muscle Pain

Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever or if these muscle signs or symptoms persist after discontinuing Pravastatin Sodium [see Warnings and Precautions (5.1) ].

Liver Enzymes

It is recommended that liver enzyme tests be performed before the initiation of Pravastatin Sodium, and thereafter when clinically indicated. All patients treated with Pravastatin Sodium should be advised to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.3) ].

Embryofetal Toxicity

Advise females of reproductive potential of the risk to a fetus, to use effective contraception during treatment, and to inform their healthcare provider of a known or suspected pregnancy [see Contraindications (4.3), Use in Specific Populations (8.1,8.3)].

Lactation

Advise women not to breastfeed during treatment with Pravastatin Sodium [see Contraindications (4.4), Use in Specific Populations (8.2)].

Manufactured by:

Appco Pharma LLC
Piscataway, NJ 08854

Manufactured for:

Biocon Pharma Inc.,
485 US Highway 1 S
Suite B305, IselinNJ 08830-3009

USA

Revised: 10/2020